bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Just put it online’: the Taylor White project as a digitization case study
Authors: Zinger Emily
Published: May 2021

Creating access to digital surrogates of primary source materials has spurred the growth of history of science as a field. Enabling and supporting virtual access requires an understanding of the behind-the-scenes requirements of a digitization project. Using McGill's Taylor White Project as a case study, this article reveals how such a project is managed, to result in a unique digital collection that supports research in both the humanities and the sciences. The workflows described transformed a collection of 938 eighteenth-century natural history drawings from a relatively inaccessible archive to a searchable and browsable digital collection, complete with contextualizing interactive visualizations. Understanding this process reveals some of the ways in which digitized data can create new avenues for questioning and examining information.
Experiments confirm a dispersive phenotype associated with a natural gene drive system
Authors: Runge Jan-Niklas , Lindholm Anna K.
Published: May 2021

Meiotic drivers are genetic entities that increase their own probability of being transmitted to offspring, usually to the detriment of the rest of the organism, thus ‘selfishly’ increasing their fitness. In many meiotic drive systems, driver-carrying males are less successful in sperm competition, which occurs when females mate with multiple males in one oestrus cycle (polyandry). How do drivers respond to this selection? An observational study found that house mice carrying the
t
haplotype, a meiotic driver, are more likely to disperse from dense populations. This could help the
t
avoid detrimental sperm competition, because density is associated with the frequency of polyandry. However, no controlled experiments have been conducted to test these findings. Here, we confirm that carriers of the
t
haplotype are more dispersive, but we do not find this to depend on the local density.
t
-carriers with above-average body weight were particularly more likely to disperse than wild-type mice.
t
-carrying mice were also more explorative but not more active than wild-type mice. These results add experimental support to the previous observational finding that the
t
haplotype affects the dispersal phenotype in house mice, which supports the hypothesis that dispersal reduces the fitness costs of the
t
.
Three-dimensional magnetic reconnection in astrophysical plasmas
Authors: Li Ting , Priest Eric , Guo Ruilong
Published: May 2021

Magnetic reconnection is a fundamental process in laboratory, magnetospheric, solar and astrophysical plasmas, whereby magnetic energy is converted into heat, bulk kinetic energy and fast particle energy. Its nature in two dimensions is much better understood than that in three dimensions, where its character is completely different and has many diverse aspects that are currently being explored. Here, we focus on the magnetohydrodynamics of three-dimensional reconnection in the plasma environment of the Solar System, especially solar flares. The theory of reconnection at null points, separators and quasi-separators is described, together with accounts of numerical simulations and observations of these three types of reconnection. The distinction between separator and quasi-separator reconnection is a theoretical one that is unimportant for the observations of energy release. A new paradigm for solar flares, in which three-dimensional reconnection plays a central role, is proposed.
Myosin cross-bridge kinetics slow at longer muscle lengths during isometric contractions in intact soleus from mice
Authors: Fenwick Axel J. , Lin David C. , Tanner Bertrand C. W.
Published: May 2021

Muscle contraction results from force-generating cross-bridge interactions between myosin and actin. Cross-bridge cycling kinetics underlie fundamental contractile properties, such as active force production and energy utilization. Factors that influence cross-bridge kinetics at the molecular level propagate through the sarcomeres, cells and tissue to modulate whole-muscle function. Conversely, movement and changes in the muscle length can influence cross-bridge kinetics on the molecular level. Reduced, single-molecule and single-fibre experiments have shown that increasing the strain on cross-bridges may slow their cycling rate and prolong their attachment duration. However, whether these strain-dependent cycling mechanisms persist in the intact muscle tissue, which encompasses more complex organization and passive elements, remains unclear. To investigate this multi-scale relationship, we adapted traditional step-stretch protocols for use with mouse soleus muscle during isometric tetanic contractions, enabling novel estimates of length-dependent cross-bridge kinetics in the intact skeletal muscle. Compared to rates at the optimal muscle length (
L
o
), we found that cross-bridge detachment rates increased by approximately 20% at 90% of
L
o
(shorter) and decreased by approximately 20% at 110% of
L
o
(longer). These data indicate that cross-bridge kinetics vary with whole-muscle length during intact, isometric contraction, which could intrinsically modulate force generation and energetics, and suggests a multi-scale feedback pathway between whole-muscle function and cross-bridge activity.
A non-coding indel polymorphism in the
fruitless
gene of
Drosophila melanogaster
exhibits antagonistically pleiotropic fitness effects
Authors: Jardine Michael D. , Ruzicka Filip , Diffley Charlotte , Fowler Kevin , Reuter Max
Published: May 2021

The amount of genetic variation for fitness within populations tends to exceed that expected under mutation–selection–drift balance. Several mechanisms have been proposed to actively maintain polymorphism and account for this discrepancy, including antagonistic pleiotropy (AP), where allelic variants have opposing effects on different components of fitness. Here, we identify a non-coding indel polymorphism in the
fruitless
gene of
Drosophila melanogaster
and measure survival and reproductive components of fitness in males and females of replicate lines carrying each respective allele. Expressing the
fruitless
region in a hemizygous state reveals a pattern of AP, with one allele generating greater reproductive fitness and the other conferring greater survival to adulthood. Different fitness effects were observed in an alternative genetic background, which may reflect dominance reversal and/or epistasis. Our findings link sequence-level variation at a single locus with complex effects on a range of fitness components, thus helping to explain the maintenance of genetic variation for fitness. Transcription factors, such as
fruitless
, may be prime candidates for targets of balancing selection since they interact with multiple target loci and their associated phenotypic effects.
Birth timing generates reproductive trade-offs in a non-seasonal breeding primate
Authors: Dezeure Jules , Baniel Alice , Carter Alecia , Cowlishaw Guy , Godelle Bernard , Huchard Elise
Published: May 2021

The evolutionary benefits of reproductive seasonality are often measured by a single-fitness component, namely offspring survival. Yet different fitness components may be maximized by different birth timings. This may generate fitness trade-offs that could be critical to understanding variation in reproductive timing across individuals, populations and species. Here, we use long-term demographic and behavioural data from wild chacma baboons (Papio ursinus) living in a seasonal environment to test the adaptive significance of seasonal variation in birth frequencies. We identify two distinct optimal birth timings in the annual cycle, located four-month apart, which maximize offspring survival or minimize maternal interbirth intervals (IBIs), by respectively matching the annual food peak with late or early weaning. Observed births are the most frequent between these optima, supporting an adaptive trade-off between current and future reproduction. Furthermore, infants born closer to the optimal timing favouring maternal IBIs (instead of offspring survival) throw more tantrums, a typical manifestation of mother–offspring conflict. Maternal trade-offs over birth timing, which extend into mother–offspring conflict after birth, may commonly occur in long-lived species where development from birth to independence spans multiple seasons. Our findings therefore open new avenues to understanding the evolution of breeding phenology in long-lived animals, including humans.
Out of the extratropics: the evolution of the latitudinal diversity gradient of Cenozoic marine plankton
Authors: Raja Nussaïbah B. , Kiessling Wolfgang
Published: May 2021

Many ecological and evolutionary hypotheses have been proposed to explain the latitudinal diversity gradient, i.e. the increase in species richness from the poles to the tropics. Among the evolutionary hypotheses, the ‘out of the tropics’ (OTT) hypothesis has received considerable attention. The OTT posits that the tropics are both a cradle and source of biodiversity for extratropical regions. To test the generality of the OTT hypothesis, we explored the spatial biodiversity dynamics of unicellular marine plankton over the Cenozoic era (the last 66 Myr). We find large-scale climatic changes during the Cenozoic shaped the diversification and dispersal of marine plankton. Origination was generally more likely in the extratropics and net dispersal was towards the tropics rather than in the opposite direction, especially during the warmer climates of the early Cenozoic. Although migration proportions varied among major plankton groups and climate phases, we provide evidence that the extratropics were a source of tropical microplankton biodiversity over the last 66 Myr.
A latitudinal gradient in thermal transgenerational plasticity and a test of theory
Authors: Munch Stephan B. , Lee Who Seung , Walsh Matthew , Hurst Thomas , Wasserman Ben A. , Mangel Marc , Salinas Santiago
Published: May 2021

Transgenerational plasticity (TGP) occurs when phenotypes are shaped by the environment in both the current and preceding generations. Transgenerational responses to rainfall, CO
2
and temperature suggest that TGP may play an important role in how species cope with climate change. However, little is known about how TGP will evolve as climate change continues. Here, we provide a quantitative test of the hypothesis that the predictability of the environment influences the magnitude of the transgenerational response. To do so, we take advantage of the latitudinal decrease in the predictability of temperatures in near shore waters along the US East Coast. Using sheepshead minnows (
Cyprinodon variegatus
) from South Carolina, Maryland, and Connecticut, we found the first evidence for a latitudinal gradient in thermal TGP. Moreover, the degree of TGP in these populations depends linearly on the decorrelation time for temperature, providing support for the hypothesis that thermal predictability drives the evolution of these traits.
Phylogenetic analysis of the salinipostin γ-butyrolactone gene cluster uncovers new potential for bacterial signalling-molecule diversity
Authors: Creamer Kaitlin E. , Kudo Yuta , Moore Bradley S. , Jensen Paul R.
Published: May 2021

Bacteria communicate by small-molecule chemicals that facilitate intra- and inter-species interactions. These extracellular signalling molecules mediate diverse processes including virulence, bioluminescence, biofilm formation, motility and specialized metabolism. The signalling molecules produced by members of the phylum Actinobacteria generally comprise γ-butyrolactones, γ-butenolides and furans. The best-known actinomycete γ-butyrolactone is A-factor, which triggers specialized metabolism and morphological differentiation in the genus

Streptomyces

. Salinipostins A–K are unique γ-butyrolactone molecules with rare phosphotriester moieties that were recently characterized from the marine actinomycete genus

Salinispora

. The production of these compounds has been linked to the nine-gene biosynthetic gene cluster (BGC) spt. Critical to salinipostin assembly is the γ-butyrolactone synthase encoded by spt9. Here, we report the surprising distribution of spt9 homologues across 12 bacterial phyla, the majority of which are not known to produce γ-butyrolactones. Further analyses uncovered a large group of spt-like gene clusters outside of the genus

Salinispora

, suggesting the production of new salinipostin-like diversity. These gene clusters show evidence of horizontal transfer and location-specific recombination among

Salinispora

strains. The results suggest that γ-butyrolactone production may be more widespread than previously recognized. The identification of new γ-butyrolactone BGCs is the first step towards understanding the regulatory roles of the encoded small molecules in Actinobacteria.
Evolution of COVID-19 symptoms during the first 9 months after illness onset
Authors: Wynberg Elke , van Willigen Hugo , Dijkstra Maartje , Boyd Anders , Kootstra Neeltje A. , van den Aardweg Joost G. , van Gils Marit J. , Matser Amy , de Wit Marije R. , Leenstra Tjalling , de Bree Godelieve , de Jong Menno D. , Prins Maria ,   the RECoVERED Study Group
Published: May 2021

Background

Few longitudinal data on COVID-19 symptoms across the full spectrum of disease severity are available. We evaluated symptom onset, severity and recovery up to nine months after illness onset.

Methods

The RECoVERED Study is a prospective cohort study based in Amsterdam, the Netherlands. Participants aged>18 years were recruited following SARS-CoV-2 diagnosis via the local Public Health Service and from hospitals. Standardised symptom questionnaires were completed at recruitment, at one week and month after recruitment, and monthly thereafter. Clinical severity was defined according to WHO criteria. Kaplan-Meier methods were used to compare time from illness onset to symptom recovery, by clinical severity. We examined determinants of time to recovery using multivariable Cox proportional hazards models.

Results

Between 11 May 2020 and 31 January 2021, 301 COVID-19 patients (167[55%] male) were recruited, of whom 99/301(32.9%) had mild, 140/301(46.5%) moderate, 30/301(10.0%) severe and 32/301(10.6%) critical disease. The proportion of symptomatic participants who reported at least one persistent symptom at 12 weeks after illness onset was greater in those with severe/critical disease (81.7%[95%CI=68.7-89.7%]) compared to those with mild or moderate disease (33.0%[95%CI=23.0-43.3%] and 63.8%[95%CI=54.8-71.5%]). Even at nine months after illness onset, almost half of all participants (42.1%[95%CI=35.6-48.5]) overall continued to report ≥1 symptom. Recovery was slower in participants with BMI≥30kg/m2 (HR 0.51[95%CI=0.30-0.87]) compared to those with BMI<25kg/m2, after adjusting for age, sex and number of comorbidities.

Conclusions

COVID-19 symptoms persisted for nine months after illness onset, even in those with mild disease. Obesity was the most important determinant of speed of recovery from symptoms.
SIR-based model with multiple imperfect vaccines
Authors: Aguilar-Canto Fernando Javier , de León Ugo Avila Ponce , Avila-Vales Eric
Published: May 2021

Since the introduction of vaccination in the current COVID-19 outbreak, many countries have approved and implemented vaccination campaigns to mitigate and ultimately curtail the pandemic. Several types of vaccines have been proposed and many of them have finally been approved and used in different countries. The different types of vaccines have different vaccine parameters, and therefore, this situation induces the necessity of modeling mathematically the scenario of multiple imperfect vaccines. In this paper, we introduce a SIR-based model considering different vaccines, and study the basic properties of the model, including the stability of the Disease-Free Equilibrium (DFE), which is locally asymptotically stable if the reproduction number is less than 1. A sequence of further results aims to enumerate the conditions where the reproduction number can be decreased (or increased). Two important mathematical propositions indicate that in general vaccination might not be enough to contain an outbreak and that the addition of new vaccines could be counterproductive if the leakiness parameter is greater than a threshold η. This model, despite its simplicity, was validated with data of the COVID-19 pandemic in five countries: Israel, Chile, Germany, Lithuania, and Czech Republic, observing that improvements for the vaccine campaigns can be suggested by the developed theory.
Comprehensive and Temporal Surveillance of SARS-CoV-2 in Urban Water Bodies: Early Signal of Second Wave Onset
Authors: Hemalatha Manupati , Tharak Athmakuri , Kopperi Harishankar , Kiran Uday , Gokulan C. G. , Mishra Rakesh K , Mohan S Venkata
Published: May 2021

The possible faecal-oral transmission of SARS-CoV-2 through domestic discharges has emerged as a serious public health concern. Based on persistence of the virus in environment, the wastewater-based epidemiology (WBE) enabled the surveillance of infection in a community. The water bodies connected to the anthropogenic activities have strong possibility of presence of the SARS-CoV-2 genetic material. In this work, we monitored urban, peri-urban and rural lakes in and around Hyderabad as a long-term surveillance study for presence of enteric virus SARS-CoV-2 gene fragments. The study time of seven months coincided with the first and second wave of COVID-19 infection. The study depicted differential viral RNA copies in the urban lake with high viral load observed during the peaks of wave I and wave II. Distinct variability in viral genes detection was observed amongst all five lakes which were in concordance with the human activity of the catchment area. The SARS-CoV-2 genes were not detected in peri-urban and rural lakes, whereas the urban lakes having direct functional attributes from domestic activity, in the community showed presence of viral load. The outcome of the study clearly shows that the urban water streams linked with domestic discharge will function as a proxy for wastewater epidemiological studies. The surge in viral gene load from February 2021 sample suggests the on shoot of the second wave of infection, which correlated well with the prevailing pandemic situation. Implementation of regular WBE based monitoring system for the water bodies/wastewater in the urban and semi-urban areas will help to understand the outbreak and spread of virus in the community.
Impact of vaccination on the COVID-19 pandemic: Evidence from U.S. states
Authors: Chen Xiao , Huang Hanwei , Ju Jiandong , Sun Ruoyan , Zhang Jialiang
Published: May 2021

Governments worldwide are implementing mass vaccination programs in an effort to end the novel coronavirus (COVID-19) pandemic. Although the approved vaccines exhibited high efficacies in randomized controlled trials1,2, their population effectiveness in the real world remains less clear, thus casting uncertainty over the prospects for herd immunity. In this study, we evaluated the effectiveness of the COVID-19 vaccination program and predicted the path to herd immunity in the U.S. Using data from 12 October 2020 to 7 March 2021, we estimated that vaccination reduced the total number of new cases by 4.4 million (from 33.0 to 28.6 million), prevented approximately 0.12 million hospitalizations (from 0.89 to 0.78 million), and decreased the population infection rate by 1.34 percentage points (from 10.10% to 8.76%). We then built a Susceptible-Infected-Recovered (SIR) model with vaccination to predict herd immunity. Our model predicts that if the average vaccination pace between January and early March 2021 (2.08 doses per 100 people per week) is maintained, the U.S. can achieve herd immunity by the last week of July 2021, with a cumulative vaccination coverage of 60.2%. Herd immunity could be achieved earlier with a faster vaccination pace, lower vaccine hesitancy, or higher vaccine effectiveness. These findings improve our understanding of the impact of COVID-19 vaccines and can inform future public health policies regarding vaccination, especially in countries with ongoing vaccination programs.
MASK MANDATES REDUCE COVID-19 MORTALITY: Analysis of 37 States and the District of Columbia, with a further analysis of the impact of demographic and medical factors on efficacy
Authors: Maloney Michael J.
Published: May 2021

As the number of COVID-19 deaths in the US increased, various policies were enacted to slow the spread of the pandemic. While the situation has improved in recent months, determining how best to combat the current pandemic is still essential. Failure to do so invites both further resurgences of the current pandemic, and more pandemics in the years to come. As a result of the widespread failure to contain the spread of COVID-19, enough deaths have occurred that the impact of policy on mortality may be statistically evaluated. This paper uses Optimal Discriminant Analysis (ODA) to evaluate the hypothesized ability of limited mask mandates (MM) to reduce the daily number of COVID-19 deaths in the states analyzed. The mandates were found to reduce mortality in half the states analyzed and did not result in increased mortality in any states. A full range of cofactors were analyzed to determine which, if any, influenced the efficacy of the mandates in the states in which mandates had an effect. Institutional Health Subindex of the Social Capital Index, state health score, population density, portion of the population with nongroup health insurance, state GDP, and the rate of pregnancy related diabetes were all correlated with increased mandate efficacy. In contrast, incarceration rate, overcrowded housing, severely overcrowded housing, portion of the population with military provided insurance, portion of the population uninsured, the portion of the population unable to see a doctor due to cost, and the portion of the population who were American Indian/Native Alaskan were all correlated with reduced mandate efficacy.
The Influence of Coronavirus Disease-2019 (COVID-19) On Parkinson’s Disease: An Updated Systematic Review
Authors: Jaiswal Vikash , Alquraish Danah , Sarfraz Zouina , Nagpal Shavy , Shrestha Prakriti Singh , Mukherjee Dattatreya , Guntipalli Prathima , Sarfraz Azza , Sánchez Velazco Diana F , Bhatnagar Arushee , Savani Saloni , Halilaj Elmjedina , Ruxmohan Samir , Cueva Wilson
Published: May 2021

Background

COVID-19 has affected global communities with multiple neurological complications in addition to other critical medical issues. COVID-19 binds to the host’s angiotensin-converting enzyme2 (ACE2) receptors, which are expressed in the neurons and glial cells, acting as an entry port to the central nervous system (CNS). ACE2 receptors are abundantly expressed on dopamine neurons, which may worsen the prognosis of motor symptoms in Parkinson’s disease (PD). SARS-CoV-2 may lead to an indirect response via immune-mediated cytokine storms and propagate through the CNS leading to damage. PD is also been associated with certain post-viral infections apart from COVID-19, such as HSV, Influenzavirus A, Measles virus, Cytomegalovirus, and Mumps.

Objective

In this systematic review, we aim to provide a thorough analysis of associations between COVID-19 and neurological outcomes for patients with PD.

Methods

Using PRISMA statement 2020, a systematic review was conducted to isolate confirmed COVID-19 patients and analyze the PD-associated neurological outcomes. A systematic literature search was conducted using the following databases: PubMed, Science Direct, Google Scholar, and Cochrane databases. The following keywords were used “COVID19, SARS-CoV-2, Parkinson’s disease, Pandemic, Mortality.” A modified Delphi process was employed to include the studies and ensure that the clinical outcome measures were addressed.

Results

Of the 355 records located during the initial round of screening, 16 were included in the final synthesis. Of PD patients who tested positive for SARS-CoV-2, worsening motor symptoms and other viral-associated symptoms were reported. These symptoms included bradykinesia, tremors, gait disturbances, delirium and dementia, and severe spasms of arms and legs. Encephalopathy was presented in two of the included studies. Increased mortality rates were identified for hospitalized patients due to COVID-19 and PD as compared to other patient groups, albeit with limited generalizability due to high bias of included studies.

Conclusion

Patients with PD may experience substantial worsening of motor and non-motor symptoms due to COVID 19. Given the novelty of neurological-viral associations, clinical studies in the future ought to explore the disease severity and neurological outcomes in COVID-19 positive patients with PD as compared to non-PD patients, in addition to understanding the role of ACE2 in increased vulnerability to contracting the infection and as a treatment modality.
Plasmodium infection induces cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein
Authors: Lapidus Sarah , Liu Feimei , Casanovas-Massana Arnau , Dai Yile , Huck John D. , Lucas Carolina , Klein Jon , Filler Renata B. , Strine Madison S. , Sy Mouhamad , Deme Awa B. , Badiane Aida S. , Dieye Baba , Ndiaye Ibrahima Mbaye , Diedhiou Younous , Mbaye Amadou Moctar , Diagne Cheikh Tidiane , Vigan-Womas Inés , Mbengue Alassane , Sadio Bacary D. , Diagne Moussa M. , Moore Adam J. , Mangou Khadidiatou , Diallo Fatoumata , Sene Seynabou D. , Pouye Mariama N. , Faye Rokhaya , Diouf Babacar , Nery Nivison , Costa Federico , Reis Mitermayer , Muenker M. Catherine , Hodson Daniel Z. , Mbarga Yannick , Katz Ben Z. , Andrews Jason R. , Campbell Melissa , Srivathsan Ariktha , Kamath Kathy , Baum-Jones Elisabeth , Faye Ousmane , Sall Amadou Alpha , Vélez Juan Carlos Quintero , Cappello Michael , Wilson Michael , Ben-Mamoun Choukri , Somé Fabrice A. , Dabiré Roch K. , Moukoko Carole Else Eboumbou , Ouédraogo Jean Bosco , Boum Yap , Shon John , Ndiaye Daouda , Wisnewski Adam , Parikh Sunil , Iwasaki Akiko , Wilen Craig B. , Ko Albert I. , Ring Aaron M. , Bei Amy K.
Published: May 2021

Individuals with acute malaria infection generated high levels of antibodies that cross-react with the SARS-CoV-2 Spike protein. Cross-reactive antibodies specifically recognized the sialic acid moiety on N-linked glycans of the Spike protein and do not neutralize in vitro SARS-CoV-2. Sero-surveillance is critical for monitoring and projecting disease burden and risk during the pandemic; however, routine use of Spike protein-based assays may overestimate SARS-CoV-2 exposure and population-level immunity in malaria-endemic countries.
Deep learning generates custom-made logistic regression models for explaining how breast cancer subtypes are classified
Authors: Shibahara Takuma , Wada Chisa , Yamashita Yasuho , Fujita Kazuhiro , Sato Masamichi , Kuwata Junichi , Okamoto Atsushi , Ono Yoshimasa
Published: May 2021

Differentiating the intrinsic subtypes of breast cancer is crucial for deciding the best treatment strategy. Deep learning can predict the subtypes from genetic information more accurately than conventional statistical methods, but to date, deep learning has not been directly utilized to examine which genes are associated with which subtypes. To clarify the mechanisms embedded in the intrinsic subtypes, we developed an explainable deep learning model called a point-wise linear (PWL) model that generates a custom-made logistic regression for each patient. Logistic regression, which is familiar to both physicians and medical informatics researchers, allows us to analyze the importance of the feature variables, and the PWL model harnesses these practical abilities of logistic regression. In this study, we show that analyzing breast cancer subtypes is clinically beneficial for patients and one of the best ways to validate the capability of the PWL model. First, we trained the PWL model with RNA-seq data to predict PAM50 intrinsic subtypes and applied it to the 41/50 genes of PAM50 through the subtype prediction task. Second, we developed a deep enrichment analysis method to reveal the relationships between the PAM50 subtypes and the copy numbers of breast cancer. Our findings showed that the PWL model utilized genes relevant to the cell cycle-related pathways. These preliminary successes in breast cancer subtype analysis demonstrate the potential of our analysis strategy to clarify the mechanisms underlying breast cancer and improve overall clinical outcomes.
Intravital imaging of Candida albicans identifies differential in vitro and in vivo filamentation phenotypes for transcription factor deletion mutants
Authors: Wakade Rohan S. , Huang Manning , Mitchell Aaron P. , Wellington Melanie , Krysan Damian J.
Published: May 2021

Candida albicans is an important cause of human fungal infections. A widely studied virulence trait of C. albicans is its ability to undergo filamentation to hyphae and pseudohyphae. Although yeast, pseudohyphae and hyphae are present in pathological samples of infected mammalian tissue, it has been challenging to characterize the role of regulatory networks and specific genes during in vivo filamentation. In addition, the phenotypic heterogeneity of C. albicans clinical isolates is becoming increasingly recognized and correlating this heterogeneity with pathogenesis remains an important goal. Here, we describe the use of an intravital imaging approach to characterize C. albicans filamentation in a mammalian model of infection by taking advantage of the translucence of mouse pinna (ears). Using this model, we have found that the in vitro and in vivo filamentation phenotypes of different C. albicans isolates can vary significantly, particularly when in vivo filamentation is compared to solid agar-based assays. We also show that the well-characterized transcriptional regulators Efg1 and Brg1 appear to play important roles both in vivo and in vitro. In contrast, Ume6 is much more important in vitro than in vivo. Finally, strains that are dependent on Bcr1 for in vitro filamentation are able to form filaments in vivo. This intravital imaging approach provides a new approach to the systematic characterization of this important virulence trait during mammalian infection. Our initial studies provide support for the notion that the regulation and initiation of C. albicans filamentation in vivo is distinct from in vitro induction.

Importance

Candida albicans is one of the most common causes of fungal infections in humans. C. albicans undergoes a transition from a round yeast form to a filamentous form during infection which is critical for its ability to cause disease. Although this transition has been studied in the laboratory for years, methods to do so in an animal model of infection have been limited. We have developed a microscopy method to visualize fluorescently labeled C. albicans undergoing this transition in the subcutaneous tissue of mice. Our studies indicate that the regulation of C. albicans filamentation during infection is distinct from that observed in laboratory conditions.
Prevalence of Macroprolactin in Hyperprolactinemic patients receiving Anti-psychotics
Authors: Al Wasify Loai Ali Al Mortada , Al Maamary Shaikha Said , Al Tobi Mohammed Nasser Rashid
Published: May 2021

Background

Prolactin (PRL) hormone circulates in the blood in three forms, mono-prolactin which constitutes 85 % of prolactin in healthy and hyperprolactinemia conditions, a dimeric prolactin (big PRL) and polymeric PRL (big-big prolactin or Macroprolactin). Macroprolactin in normal conditions is not exceeding 2% of the total serum prolactin and had no biological activity. In some cases, of hyperprolactinemia the dominant form becomes MaPRL and exceeding the 2% percentage of total leading to misdiagnosis of hyperprolactinemia and un-necessary radiological investigations. The aim of this study is to detect the prevalence of MaPRL in Psychiatric patients with hyperprolactinemia due to anti-psychotic medications at Al Masarra hospital.

Material and methods

The study was conducted on 190 samples from patients with high prolactin in Al Masarra Hospital either inpatients or out-patient clinics either male or non-lactating not pregnant female. The measurement of Prolactin level was measured by the automated analyser COBAS e411, Roche Diagnostic. Macroprolactin was precipitated by using Polyethylene glycol (PEG).

Results

Prevalence of Macroprolactin was 10.5 % of hyperprolactinemic patients receiving antipsychotics. There was a statistically significant difference in gender between the symptomatic and asymptomatic group. There was no significant difference in medications used between the symptomatic and asymptomatic group and there was a statistically significant difference in total Prolactin & Macroprolactin between males and females.

Conclusions

Investigation for Macroprolactin should be done in every hyperprolactinemia patient who is receiving antipsychotics more especially the asymptomatic cases to avoid unnecessary radiological imaging and treatment.
Giving patients a voice within healthcare reform: the qualitative VOICE study
Authors: Hoffmann Kathryn , Rumpler Nicole , George Aaron , de Boeckxstaens Pauline
Published: May 2021

Background

Inclusion of patients in healthcare service and system planning is an increasingly important tool to improve healthcare systems worldwide. In 2012, a focused healthcare reform was initiated in Austria to strengthen the primary care sector.

Objectives

The aim of this study was to assess the perceptions, desires and needs of patients in terms of primary care as a necessary building block of the Austrian healthcare reform.

Methods

This study was designed as an exploratory qualitative study using semi-structured interviews between the years 2013 and 2018. Research questions focused on patients’ positive and negative experiences with regard to GP consultations and the overall primary care system, as well as desires for improvement. Qualitative content analysis by Mayring was used to analyze the material.

Results

Altogether, 41 interviews were conducted with seven main-categories identified. These categories include coordination and time management around consultation, human and professional aspects of consultation including coordination of care, access and availability including opening hours, infrastructure and hygiene of the waiting room, personnel, and overarching healthcare system factors.

Conclusion

This study demonstrates the importance of bringing the patients’ voice into ongoing healthcare reform. Without appreciating and responding to patients’ perceptions and needs, healthcare reform in Austria might be challenged to improve in areas such as time, coordination and navigation. Successful health care reform necessitates the inclusion of the patient voice.
Machine learning enabled subgroup analysis with real-world data to inform better clinical trial design
Authors: Xu Jie , Zhang Hao , Zhang Hansi , Bian Jiang , Wang Fei
Published: May 2021

Restrictive eligibility criteria for clinical trials may limit the generalizability of treatment effectiveness and safety to real-world patients. In this paper, we propose a machine learning approach to derive patient subgroups from real-world data (RWD), such that the patients within the same subgroup share similar clinical characteristics and safety outcomes. The effectiveness of our approach was validated on two existing clinical trials with the electronic health records (EHRs) from a large clinical research network. One is the donepezil trial for Alzheimer’s disease (AD), and the other is the Bevacizumab trial on colon cancer (CRC). The results show that our proposed algorithm can identify patient subgroups with coherent clinical manifestations and similar risk levels of encountering severe adverse events (SAEs). We further exemplify that potential rules for describing the patient subgroups with less SAEs can be derived to inform the design of clinical trial eligibility criteria.
COVID-19 Pandemic and Prevalence of Self-care Practices among the Future Physicians: A Bangladesh Study
Authors: Johora Fatema , Abbasy Asma Akter , Jeenia Fatiha Tasmin , Bhowmik Mithun Chandro , Aktar Mohsena , Choudhury Nargis Akhter , Moitra Priyanka , Ferdoush Jannatul
Published: May 2021

Background

Since December 2019, the novel coronavirus, SARS-CoV-2, has garnered global attention due to its rapid transmission, which has infected more than twenty nine million people worldwide. World is facing enormous stress and anxiety as there is no effective medicine or vaccine to treat or prevent COVID-19 till date. Experts are recommending self-care like social distancing, respiratory etiquette, hand washing, using face mask to prevent corona virus infection.

Materials and methods

This descriptive cross-sectional study was designed to assess the prevalence of self-care practice among the undergraduate medical students (4th year) of 14 medical colleges of Bangladesh during COVID-19 pandemic. A structured questionnaire survey linked in the google form was used as study instrument and was distributed among study population through email, messenger, whatsapp and other social media during the month of October 2020. Total 916 students were participated in the study.

Results

79.8% of students reported self-care practice in study period. 44.98% of students went outside once in a week. 90.5%, 70.96% and 52.62% of respondents always used face mask, followed 20 seconds hand washing principle and maintained social distancing. Face masks (97.8%), sanitizers (76.7%) and gloves (71.9%) are most common items purchased as protective mesures. Most of the students (76.9%) follow their hobbies as a coping strategy to overcome phychological stress, while 6% of students took professional help.

Conclusion

Suboptimal practice of self-care was found among the undergraduate medical students of Bangladesh.
Linking carbohydrate structure with function in the human gut microbiome using hybrid metagenome assemblies
Authors: Ravi Anuradha , Troncoso-Rey Perla , Ahn-Jarvis Jennifer , Corbin Kendall R. , Harris Suzanne , Harris Hannah , Aydin Alp , Kay Gemma L. , Viet Thanh Le , Gilroy Rachel , Pallen Mark J. , Page Andrew J. , O’Grady Justin , Warren Frederick J.
Published: May 2021

Background

Complex carbohydrates that escape digestion in the small intestine, are broken down in the large intestine by enzymes encoded by the gut microbiome. This is a symbiotic relationship between particular microbes and the host, resulting in metabolic products that influence host gut health and are exploited by other microbes. However, the role of carbohydrate structure in directing microbiota community composition and the succession of carbohydrate-degrading microbes is not fully understood. Here we take the approach of combining data from long and short read sequencing allowing recovery of large numbers of high quality genomes, from which we can predict carbohydrate degrading functions, and impact of carbohydrate on microbial communities.

Results

In this study we evaluate species-level compositional variation within a single microbiome in response to six structurally distinct carbohydrates in a controlled model gut using hybrid metagenome assemblies. We identified 509 high-quality metagenome-assembled genomes (MAGs) belonging to ten bacterial classes and 28 bacterial families. We found dynamic variations in the microbiome amongst carbohydrate treatments, and over time. Using these data, the MAGs were characterised as primary (0h to 6h) and secondary degraders (12h to 24h). Annotating the MAG’s with the Carbohydrate Active Enzyme (CAZyme) database we are able to identify species which are enriched through time and have the potential to actively degrade carbohydrate substrates.

Conclusions

Recent advances in sequencing technology allowed us to identify significant unexplored diversity amongst starch degrading species in the human gut microbiota including CAZyme profiles and complete MAGs. We have identified changes in microbial community composition in response to structurally distinct carbohydrate substrates, which can be directly related to the CAZyme complement of the enriched MAG’s. Through this approach, we have identified a number of species which have not previously been implicated in starch degradation, but which have the potential to play an important role.
LncRNA DLEU2 regulates Sirtuins and mitochondrial respiratory chain complex IV: a novel pathway in obesity and DOHaD
Authors: Zhang Jian , Kay Matthew Krivacka , Choudhury Mahua
Published: May 2021

Long noncoding RNAs (lncRNAs) are commonly dysregulated in cancer but are mostly unknown for roles in metabolic regulation. Sirtuins, an epigenetic modulator class, regulate metabolic pathways. However, how sirtuins are regulated via lncRNA is unknown. In our findings, DLEU2, a lncRNA involved in primarily blood cancers, and sirtuins were both significantly decreased in the livers of high-fat high-fructose diet (HFD-HF) fed male mouse offspring (F1) whose mothers (F0) were either fed chow diet or HFD-HF during reproductive and pregnancy windows. Confirming this connection, upon silencing DLEU2, transcription levels of SIRT1 through 6 and translational levels of SIRT1, 3, 5, and 6 were significantly downregulated. Knockdown of DLEU2 also significantly decreased the protein level of cytochrome-c oxidase (complex IV, MTCO1) without altering other mitochondrial complexes, leading to increased reactive oxygen species production. Interestingly, in F1 livers, the protein level of MTCO1 was also significantly decreased under an HFD-HF diet or even under chow diet if the mother was exposed to HFD-HF. Our findings therefore reveal for the first time that a lncRNA can regulate sirtuins and a specific mitochondrial complex, furthermore suggesting a potential role of DLEU2 in metabolic disorders over one or more generations.

HIGHLIGHTS

Maternal diet can modulate hepatic lncRNA DLEU2 and its downstream regulators in offspring

DLEU2 is required for specific sirtuin regulation and mitochondrial respiration chain complex IV expression

Offspring liver depleted of DLEU2 show decreased mitochondrial respiration chain complex IV and specific sirtuins at transcriptional and translational levels
Performance evaluation of RNA purification kits and blood collection tubes in the Extracellular RNA Quality Control (exRNAQC) study
Authors:   The exRNAQC Consortium, Anckaert Jasper , Avila Cobos Francisco , Decock Anneleen , Decruyenaere Philippe , Deleu Jill , De Preter Katleen , De Wever Olivier , De Wilde Jilke , Dhondt Bert , D’huyvetter Thibaut , Everaert Celine , Fierro Carolina , Helsmoortel Hetty Hilde , Hendrix An , Hulstaert Eva , Koster Jan , Kuersten Scott , Mercer Tim R , Mestdagh Pieter , Morlion Annelien , Nijs Nele , Nuytens Justine , Philippron Annouck , Piofczyk Thomas , Poma-Soto Franco , Schoofs Kathleen , Schroth Gary P. , Thas Olivier , Vanden Eynde Eveline , Vandesompele Jo , Van Maerken Tom , Van Paemel Ruben , Verniers Kimberly , Verwilt Jasper , Yigit Nurten
Published: May 2021

The use of blood-based extracellular RNA (cell-free RNA; exRNA) as clinical biomarker requires the implementation of a validated procedure for sample collection, processing, and profiling. So far, no study has systematically addressed the pre-analytical variables affecting transcriptome analysis of exRNAs. In the exRNAQC study, we evaluated ten blood collection tubes, three time intervals between blood draw and downstream processing, and eight RNA purification methods using the supplier-specified minimum and maximum biofluid input volumes. The impact of these pre-analytics on deep transcriptome profiling of both small and messenger RNA from healthy donors’ plasma or serum was assessed for each pre-analytical variable separately and for interactions between a selected set of pre-analytics, resulting in 456 extracellular transcriptomes. Making use of 189 synthetic spike-in RNAs, the processing and analysis workflow was controlled. When comparing blood collection tubes, so-called preservation tubes do not stabilize exRNA well, and result in variable RNA concentration and sensitivity (i.e., the number of detected RNAs) over time, as well as compromised reproducibility. We also document large differences in RNA purification kit performance in terms of sensitivity, reproducibility, and observed transcriptome complexity, and demonstrate interactions between specific blood collection tubes, purification kits and time intervals. Our results are summarized in 11 performance metrics that enable an informed selection of the most optimal sample processing workflow for a given experiment. In conclusion, we put forward robust quality control metrics for exRNA quantification methods with validated standard operating procedures (SOPs), representing paramount groundwork for future exRNA-based precision medicine applications.
Evaluating brain parcellations using the distance controlled boundary coefficient
Authors: Zhi Da , King Maedbh , Hernandez-Castillo Carlos R. , Diedrichsen Jörn
Published: May 2021

One important approach to human brain mapping is to define a set of distinct regions that can be linked to unique functions. Numerous brain parcellations have been proposed, using cytoarchitectonic, structural or functional Magnetic Resonance Imaging (fMRI) data. The intrinsic smoothness of brain data, however, poses a problem for current methods seeking to compare different parcellations. For example, criteria that simply compare within-parcel to between-parcel similarity provide even random parcellations with a high value. Furthermore, the evaluation is biased by the spatial scale of the parcellation. To address this problem, we propose the Distance Controlled Boundary Coefficient (DCBC), an unbiased criterion to evaluate discrete parcellations. We employ this new criterion to evaluate existing parcellations of the human neocortex in their power to predict functional boundaries for an fMRI data set with many different tasks, as well as for resting-state data. We find that common anatomical parcellations do not perform better than chance, suggesting that task-based functional boundaries do not align well with sulcal landmarks. Parcellations based on resting-state fMRI data perform well; in some cases, as well as a parcellation defined on the evaluation data itself. Finally, multi-modal parcellations that combine functional and anatomical criteria perform substantially worse than those based on functional data alone, indicating that functionally homogeneous regions often span major anatomical landmarks. Overall, the DCBC advances the field of functional brain mapping by providing an unbiased metric that compares the predictive ability of different brain parcellations to define brain regions that are functionally maximally distinct.
Museum of Spatial Transcriptomics
Authors: Moses Lambda , Pachter Lior
Published: May 2021

The function of many biological systems, such as embryos, liver lobules, intestinal villi, and tumors depends on the spatial organization of their cells. In the past decade high-throughput technologies have been developed to quantify gene expression in space, and computational methods have been developed that leverage spatial gene expression data to identify genes with spatial patterns and to delineate neighborhoods within tissues. To assess the ability and potential of spatial gene expression technologies to drive biological discovery, we present a curated database of literature on spatial transcriptomics dating back to 1987, along with a thorough analysis of trends in the field such as usage of experimental techniques, species, tissues studied and computational approaches used. Our analysis places current methods in historical context, and we derive insights about the field that can guide current research strategies. A companion supplement offers a more detailed look at the technologies and methods analyzed:https://pachterlab.github.io/LP_2021/.