bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining the Educational Value of Student-Run Clinics for Health Care Students
Authors: Huang Kelly , Maleki Mona , Regehr Glenn , McEwen Heather
Published: January 2021

Purpose

Student-run clinics (SRCs) are increasingly recognized as an educational experience in many health professions’ curricula. Several benefits have been documented, including students with SRC experience using patient-centered approaches to care, showing interest in working with marginalized populations, and more fully appreciating the care provided by interprofessional teams. Yet, few studies have explored student experiences within SRCs or examined how these experiences affect and shape these documented attitudes. This study explored the experiences of students at an SRC and the effect of these experiences on their learnings.

Method

From November 2016 to July 2017, 23 students in the Community Health Initiative by University Students SRC at the University of British Columbia participated in 2 focus group interviews: the first after their first clinic day and the second on their final clinic day. Open- and closed-ended questions were used to explore participants’ learnings from the SRC. Using a grounded theory approach, the authors iteratively analyzed the transcribed interviews, adjusting questions for subsequent focus groups as new themes evolved. Three investigators each separately coded the data; the full team then collectively consolidated the themes and developed explanatory models for each theme.

Results

Two themes were identified from the focus group input: (1) through managing real, complex patients—in situations unlike those offered in classroom and case-based learning environments—students gained insights into the intricacies of incorporating the patient’s perspective into their definition and management of the patient’s problem, and (2) by working as a team instead of focusing on delineating scopes of practice, students gained a meaningful understanding of the roles of practitioners from other health professions.

Conclusions

This study provides insights into the unique opportunities SRCs offer health care students early in their training, enabling them to develop a richer understanding and appreciation of holistic and interprofessional approaches to patient care.
Blastocyst and cleavage stage embryo biopsy for preimplantation genetic testing of the sickle cell gene in carrier couples: the experience of an IVF clinic in a developing country: a retrospective study
Authors: Ashiru Oladapo A. , Ogbeche Rose O. , Oladimeji Moruf O. , Iloabachie Ebele C. , Umana Akemini E. , Osumah Jumoke G.
Published: January 2021

Introduction:

Embryo biopsy is a prerequisite for preimplantation genetic testing (PGT). Although cleavage stage biopsy is very common, trophectoderm biopsy at blastocyst stage has become increasingly popular in recent times. This study describes the clinical success of PGT cycles for sickle cell anemia using both cleavage and trophectoderm biopsy in a developing country.

Materials and Methods:

All patients undergoing in vitro fertilization and PGT for sickle cell anemia from April 2011 to February 2017. Embryos were biopsied either on day 3 (blastomere) or day 5/6 (trophectoderm). Laser pulses (ZILOS-tk Laser) perforating the zona pellucida were followed by either blastomere aspiration from a day 3 cleavage stage embryo or trophectoderm biospy from a day 5/6 blastocyst. Embryos were vitrified awaiting subsequent thaw and transfer. After excluding homozygous hemoglobin SS embryos, frequencies of positive human chorionic gonadotrophin, clinical pregnancy, implantation rate and live birth rate were recorded for day 3 cleavage stage embryos (group A) and day 5/6 blastocysts (group B).

Results:

Of the 34 patients undergoing in vitro fertilization PGT for sickle cell anemia, embryos from 18 underwent day 3 blastomere aspiration (group A) whereas embryos from 16 underwent day 5/6 trophectoderm biopsies (group B). The mean patient age was 34.4 years for group A and 34.1 years for group B. A total of 131 embryos were biopsied in group A and 106 in group B. Percentages of unaffected embryos (ie, HB AA and AS) in groups A and B were 40.4% and 68.0%, respectively. Positive human chorionic gonadotrophin rates were 7.7% and 60%, clinical pregnancy rates 7.7% and 20%, implantation rates 3.7% and 32.1%, and live birth rates 3.7% and 20%, respectively.

Conclusions:

In this developing country, the use of trophectoderm biopsy for interrogating embryos at risk for sickle cell anemia appeared superior to blastomere aspiration at the cleavage stage for the purpose of PGT.
Establishing the global working group on Reproductive and Developmental Environmental Health (RDEH): practicum of a global resource
Authors: Power Allison M. , Woodruff Tracey J. , Conry Jeanne A. , Giudice Linda C.
Published: January 2021

Advocacy, training, and research for the prevention of adverse health effects from environmental exposure are the major foci of the International Federation of Gynecology and Obstetrics (FIGO) Reproductive and Developmental Environmental Health (RDEH) Working Group. A critical need for a consistent global effort to address these threats to human reproductive and developmental health was identified after the publication of influential committee opinions (ACOG, Obstet Gynecol, 2013; FIGO, Int J Gynaecol Obstet, 2015) and the assembling of the FIGO 2015 Pre-Congress Workshop, “Summit on Shaping Our Planetary Legacy: Setting an Agenda for Environmental Reproductive Health.” RDEH’s goals are to convene experts of diverse backgrounds to generate evidence-based knowledge and propose solutions to the increasing threats of harmful environmental chemicals to global human reproduction and development by prevention of harm through education, research, and advocacy. This practicum is a guide for establishing a global task force, such as FIGO RDEH, for developing collaboration among experts across disciplines and time zones, and for building accessible and vital databases.
Sperm viral decontamination: a juncture between prevention and risk minimization in the ART laboratory
Authors: Huyser Carin , Richter Karin
Published: January 2021

The present report describes the transition of a technique designed for the removal of infectious pathogens from animal semen to a clinical application in human immunodeficiency virus-seropositive males requesting assisted reproductive technology treatment. The relevance and application of the decontamination technique in the present-day and emerging viral epidemics is questioned. The medical history and screening of a patient will verify the type and level of viral infection, and if viruses are attached and/or potentially internalized in the sperm cell of a carrier. The procedure will only be relevant as a risk-reduction method during assisted reproductive technology treatment if the viral infection/load is known, as applied to human immunodeficiency virus positive male patients at our Unit.
Pituitary adenylate cyclase-activating polypeptide/vasoactive intestinal peptide [Part 1]: biology, pharmacology, and new insights into their cellular basis of action/signaling which are providing new therapeutic targets
Authors: Moody Terry W. , Jensen Robert T.
Published: January 2021

Purpose of review

To discuss recent advances of vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase-activating polypeptide (PACAP) receptors in pharmacology, cell biology, and intracellular signaling in cancer.

Recent findings

Recent studies provide new insights into the pharmacology, cell biology of the VIP/PACAP system and show they play important roles in a number of human cancers, as well as in tumor growth/differentiation and are providing an increased understanding of their signaling cascade that is suggesting new treatment targets/approaches.

Recent insights from studies of VIP/PACAP and their receptors in both central nervous system disorders and inflammatory disorders suggest possible new treatment approaches. Elucidation of the exact roles of VIP/PACAP in these disorders and development of new therapeutic approaches involving these peptides have been limited by lack of specific pharmacological tools, and exact signaling mechanisms involved, mediating their effects. Reviewed here are recent insights from the elucidation of structural basis for VIP/PACAP receptor activation as well as the signaling cascades mediating their cellular effects (using results primarily from the study of their effects in cancer) that will likely lead to novel targets and treatment approaches in these diseases.
Diagnosis of Vascular Rupture Due to Arteriovenous Malformation Using Postmortem Angiography and 3-Dimensonal Printing
Authors: Mi Jingya , Dong Hewen , Wan Lei , Zou Donghua , Li Zhengdong , Tian Zhiling , Wang Zhuoqun , Liu Ningguo , Chen Yijiu
Published: January 2021

Postmortem computed tomography (PMCT), PMCT angiography, and 3-dimensonal (3D) printing technology are increasingly applied to forensic practice. Although their effectiveness is undeniably confirmed, their potential role in practice still needs to be further explored. Here, we report a typical case in which such 4 technologies were applied to a woman found dead with stomach content beneath the head on the pillow in her residence. At first, the cause of death was simply considered as hypertensive cerebral hemorrhage after preliminary examination. However, the initial judgment was questioned by her family for her devoid of hypertension history. As indicated by the targeted PMCT with cerebral angiography, the woman died of pathological cerebral hemorrhage due to arteriovenous malformation, which was still unconvincing enough for the family because in violent death, some cerebral hemorrhage could also be located in the same position. Finally, the family came to be convinced when the close connection between the deformed blood vessels and hematoma was perfectly demonstrated by the application of 3D printing technology. This study proved that it can be an efficient tool for identifying the cause of death when the integration is made of 3D printing technology and PMCT angiography, as a more intuitive evidence of forensic science.
Global gradients in intertidal species richness and functional groups
Authors: Thyrring Jakob , Peck Lloyd S.
Published: January 2021

Whether global latitudinal diversity gradients exist in rocky intertidal α-diversity and across functional groups remains unknown. Using literature data from 433 intertidal sites, we investigated α-diversity patterns across 155° of latitude, and whether local-scale or global-scale structuring processes control α-diversity. We, furthermore, investigated how the relative composition of functional groups (algae, grazers, predators and suspension-feeders) changes with latitude. α-diversity differed among hemispheres with a mid-latitudinal peak in the north, and a non-significant unimodal pattern in the south, but there was no support for a latitudinal diversity gradient. Although global-scale drivers had no discernible effect, the local-scale drivers significantly affected α-diversity, and our results reveal that latitudinal diversity gradients are outweighed by local-processes. In three functional groups: predators, grazers and suspension-feeders diversity declined with latitude, coinciding with an inverse gradient in algae. Overall, we propose more studies are needed on the magnitude and influence of physical and biotic drivers across multiple scales.
Detection of SARS-CoV-2 nucleocapsid antigen from serum can aid in timing of COVID-19 infection
Authors: Ahava MJ , Kurkela S , Kuivanen S , Lappalainen M , Jarva H , Jääskeläinen AJ
Published: January 2021

SARS-CoV-2 RNA can be detected in respiratory samples for weeks or even months after onset of COVID-19 disease. Therefore, one of the diagnostic challenges of PCR positive cases is differentiating between acute COVID-19 disease and convalescent phase. Recently, the presence of SARS-CoV-2 nucleocapsid antigen in serum samples of COVID-19 patients was published [Le Hingrat et al. Detection of SARS-CoV-2 N-antigen in blood during acute COVID-19 provides a sensitive new marker and new testing alternatives, Clinical Microbiology and Infection, 2020].

Our study aimed to characterize the analytical specificity and sensitivity of an enzyme-linked immunosorbent assay (Salocor SARS-CoV-2 Antigen Quantitative Assay Kit© (Salofa Ltd, Salo, Finland)) for the detection of SARS-CoV-2 antigen in serum, and to characterize the kinetics of antigenemia. The evaluation material included a negative serum panel of 155 samples, and 126 serum samples from patients with PCR-confirmed COVID-19.

The specificity of the Salocor SARS-CoV-2 serum N antigen test was 98.0%. In comparison with simultaneous positive PCR from upper respiratory tract (URT) specimens, the test sensitivity was 91.7%. In a serum panel in which the earliest serum sample was collected two days before the collection of positive URT specimen, and the latest 48 days after (median 1 day post URT sample collection), the serum N antigen test sensitivity was 94% within 14 days post onset of symptoms. The antigenemia resolved approximately two weeks after the onset of disease and diagnostic PCR.

The combination of simultaneous SARS-CoV-2 antigen and antibody testing appeared to provide useful information for the timing of COVID-19. Our results suggest that SARS-CoV-2 N-antigenemia may be used as a diagnostic marker in acute COVID-19.
Individual prediction of trauma-focused psychotherapy response in youth with posttraumatic stress disorder using resting-state functional connectivity
Authors: Zhutovsky Paul , Zantvoord Jasper B. , Ensink Judith B.M. , Kelder Rosanne Op den , Lindauer Ramon J.L. , Wingen Guido A. van
Published: January 2021

Randomized controlled trials have shown efficacy of trauma-focused psychotherapies in youth with posttraumatic stress disorder (PTSD). However, response varies considerably among individuals. Currently, no biomarkers are available to assist clinicians in identifying youth who are most likely to benefit from treatment. In this study, we investigated whether resting-state functional magnetic resonance imaging (rs-fMRI) could distinguish between responders and non-responders on the group- and individual patient level.

Pre-treatment rs-fMRI was recorded in 40 youth (ages 8-17 years) with (partial) PTSD before trauma-focused psychotherapy. Change in symptom severity from pre- to post-treatment was assessed using the Clinician-Administered PTSD scale for Children and Adolescents to divide participants into responders (≥30% symptom reduction) and non-responders. Functional networks were identified using meta-independent component analysis. Group-differences within- and between-network connectivity between responders and non-responders were tested using permutation testing. Individual predictions were made using multivariate, cross-validated support vector machine classification.

A network centered on the bilateral superior temporal gyrus predicted treatment response for individual patients with 76.17% accuracy (pFWE = 0.018, 87.14% sensitivity, 65.20% specificity, area-under-receiver-operator-curve of 0.82). Functional connectivity between the frontoparietal and sensorimotor network was significantly stronger in non-responders (pFWE = 0.012) on the group-level. Within-network connectivity was not significantly different between groups.

This study provides proof-of-concept evidence for the feasibility to predict trauma-focused psychotherapy response in youth with PTSD at an individual-level. Future studies are required to test if larger cohorts could increase accuracy and to test further generalizability of the prediction models.
Heading for personalized rTMS in tinnitus: reliability of individualized stimulation protocols in behavioral and electrophysiological responses
Authors: Schoisswohl Stefan , Langguth Berthold , Hebel Tobias , Abdelnaim Mohamed A. , Volberg Gregor , Schecklmann Martin
Published: January 2021

Background

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation tool potentially modulating pathological brain activity. Its clinical effectiveness is hampered by varying results and characterized by inter-individual variability in treatment responses. RTMS individualization might constitute a useful strategy to overcome this variability. A precondition for this approach would be that repeatedly applied protocols result in reliable effects. The condition tinnitus provides the advantage of immediate behavioral consequences (tinnitus loudness changes) after interventions and thus offers an excellent model to exemplify TMS personalization.

Objective

The aim was to investigate the test-retest reliability of short rTMS stimulations in modifying tinnitus loudness and oscillatory brain activity as well as to examine the feasibility of rTMS individualization in tinnitus.

Methods

Three short verum (1Hz, 10Hz, 20Hz; 200 pulses) and one sham (0.1Hz; 20 pulses) rTMS protocol were administered on two different days in 22 tinnitus patients. Before and after each protocol, oscillatory brain activity was recorded with electroencephalography (EEG) together with behavioral tinnitus loudness ratings. RTMS individualization was executed by dint of behavioral and electrophysiological responses. Stimulation responders were identified via consistent sham-superior increases in tinnitus loudness (behavioral responders) and alpha power increases or gamma power decreases (alpha responders/ gamma responders) in accordance to the prevalent neurophysiological models for tinnitus.

Results

It was feasible to identify individualized rTMS protocols featuring reliable tinnitus loudness changes (55% behavioral responder), alpha increases (91% alpha responder) and gamma decreases (100% gamma responder) respectively. Alpha responses primary occurred over parieto-occipital areas, whereas gamma responses mainly appeared over frontal regions. Contrary, test-retest correlation analyses per protocol on a group-level were not significant neither for behavioral nor for electrophysiological effects. No associations between behavioral and EEG responses were given.

Conclusion

RTMS individualization via behavioral and electrophysiological data in tinnitus can be considered as a feasible approach to overcome low reliability on group-level. The present results open the discussion favoring personalization utilizing neurophysiological markers rather than behavioral responses. These insights are not only useful for the rTMS treatment of tinnitus but also for neuromodulation interventions in other pathologies as our results suggest that the individualization of stimulation protocols is feasible despite absent group-level reliability.
Aerosol tracer testing in Boeing 767 and 777 aircraft to simulate exposure potential of infectious aerosol such as SARS-CoV-2
Authors: Kinahan Sean M , Silcott David B , Silcott Blake E , Silcott Ryan M , Silcott Peter J , Silcott Braden J , Distelhorst Steven L , Herrera Vicki L , Rivera Danielle N , Crown Kevin K , Lucero Gabriel A , Santarpia Joshua L
Published: January 2021

The COVID-19 pandemic has reintroduced questions regarding the potential risk of SARS-CoV-2 exposure amongst passengers on an aircraft. Quantifying risk with computational fluid dynamics models or contact tracing methods alone is challenging, as experimental results for inflight biological aerosols is lacking. Using fluorescent aerosol tracers and real time optical sensors, coupled with DNA-tagged tracers for aerosol deposition, we executed ground and inflight testing on Boeing 767 and 777 airframes.

Analysis here represents tracer particles released from a simulated infected passenger, in multiple rows and seats, to determine the exposure risk via penetration into breathing zones in that row and numerous rows ahead and behind the index case. We completed over 65 releases of 180,000,000 fluorescent particles from the source, with 40+ Instantaneous Biological Analyzer and Collector sensors placed in passenger breathing zones for real-time measurement of simulated virus particle penetration.

Results from both airframes showed a minimum reduction of 99.54% of 1 µm aerosols from the index source to the breathing zone of a typical passenger seated directly next to the source. An average 99.97 to 99.98% reduction was measured for the breathing zones tested in the 767 and 777, respectively. Contamination of surfaces from aerosol sources was minimal, and DNA-tagged 3 µm tracer aerosol collection techniques agreed with fluorescent methodologies.
Human colorectal pre-cancer atlas identifies distinct molecular programs underlying two major subclasses of pre-malignant tumors
Authors: Chen Bob , McKinley Eliot T. , Simmons Alan J. , Ramirez-Solano Marisol A. , Zhu Xiangzhu , Southard-Smith Austin N. , Markham Nicholas O. , Sheng Quanhu , Drewes Julia L. , Xu Yanwen , Heiser Cody N. , Zhou Yuan , Revetta Frank , Berry Lynne , Zheng Wei , Washington M. Kay , Cai Qiuyin , Sears Cynthia L. , Goldenring James R. , Franklin Jeffrey L. , Vandekar Simon , Roland Joseph T. , Su Timothy , Huh Won Jae , Liu Qi , Coffey Robert J. , Shrubsole Martha J. , Lau Ken
Published: January 2021

Most colorectal cancers (CRCs) develop from either adenomas (ADs) or sessile serrated lesions (SSLs). The origins and molecular landscapes of these histologically distinct pre-cancerous polyps remain incompletely understood. Here, we present an atlas at single-cell resolution of sporadic conventional tubular/tubulovillous ADs, SSLs, hyperplastic polyps (HPs), microsatellite stable (MSS) and unstable (MSI-H) CRC, and normal colonic mucosa. Using single-cell transcriptomics and multiplex imaging, we studied 69 datasets from 33 participants. We also examined separate sets of 66 and 274 polyps for RNA and targeted gene sequencing, respectively. We performed multiplex imaging on a tissue microarray of 14 ADs and 15 CRCs, and we integrated pre-cancer polyp data with published single-cell and The Cancer Genome Atlas (TCGA) bulk CRC data to establish potential polyp-cancer relationships. Striking differences were observed between ADs and SSLs that extended to MSS and MSI-H CRCs, respectively, reflecting their distinct origins and trajectories. ADs arose from WNT pathway dysregulation in stem cells, which aberrantly expanded and expressed a Hippo and ASCL2 regenerative program. In marked contrast, SSLs were depleted of stem cell-like populations and instead exhibited a program of gastric metaplasia in the setting of elevated cytotoxic inflammation. Using subtype-specific gene regulatory networks and shared genetic variant analysis, we implicated serrated polyps, including some HPs conventionally considered benign, as arising from a metaplastic program in committed absorptive cells. ADs and SSLs displayed distinct patterns of immune cell infiltration that may influence their natural history. Our multi-omic atlas provides novel insights into the malignant potential of colorectal polyps and serves as a framework for precision surveillance and prevention of sporadic CRC.
Emergence and Evolution of a Prevalent New SARS-CoV-2 Variant in the United States
Authors: Pater Adrian A. , Bosmeny Michael S. , Barkau Christopher L. , Ovington Katy N. , Chilamkurthy Ramadevi , Parasrampuria Mansi , Eddington Seth B. , Yinusa Abadat O. , White Adam A. , Metz Paige E. , Sylvain Rourke J. , Hebert Madison M. , Benzinger Scott W. , Sinha Koushik , Gagnon Keith T.
Published: January 2021

Genomic surveillance can lead to early identification of novel viral variants and inform pandemic response. Using this approach, we identified a new variant of the SARS-CoV-2 virus that emerged in the United States (U.S.). The earliest sequenced genomes of this variant, referred to as 20C-US, can be traced to Texas in late May of 2020. This variant circulated in the U.S. uncharacterized for months and rose to recent prevalence during the third pandemic wave. It initially acquired five novel, relatively unique non-synonymous mutations. 20C-US is continuing to acquire multiple new mutations, including three independently occurring spike protein mutations. Monitoring the ongoing evolution of 20C-US, as well as other novel emerging variants, will be essential for understanding SARS-CoV-2 host adaptation and predicting pandemic outcomes.
The impact of the coronavirus disease 2019 (COVID-19) pandemic on university students’ dietary intake, physical activity, and sedentary behaviour
Authors: Bertrand Leandy , Shaw Keely A. , Ko Jongbum , Deprez Dalton , Chilibeck Philip D. , Zello Gordon A.
Published: January 2021

University students are a vulnerable group for poor dietary intake, insufficient physical activity and sedentary behaviour. The purpose of this study was to examine the impact of COVID-19 on university students’ dietary intake, physical activity and sedentary behaviour. Participants were students (n=125) from the Universities of Saskatchewan and Regina. An online questionnaire was administered retrospectively (for pre-pandemic) and prospectively (during the pandemic) to examine students’ dietary intake, physical activity and sedentary behaviour. Overall, nutrient and caloric intakes were significantly reduced (p<0.05) during the pandemic, and alcohol intake increased (p=0.03). Before the pandemic, 16% and 54% of the participants were meeting the Canadian 24-Hour Movement Guidelines for Adults (18–64 years) of 150 minutes of moderate-vigorous physical activity and 8 hours or less of sedentary activity respectively. Only 10% met the guidelines for physical activity while 30% met the guidelines for sedentary behaviour during the pandemic. The minutes per week spent engaging in moderate to vigorous physical activity during the pandemic decreased by approximately 20% (p<0.001). The hours spent in sedentary activities increased by 3 hours per day (p<0.001). Our findings confirm that during the pandemic, students’ inadequate dietary intake, high alcohol consumption, low physical activity and high sedentary behaviour were significantly compounded.

Novelty

During COVID-19, the nutrient and caloric intakes of university students decreased, and alcohol intake increased significantly.

University students’ physical activity levels decreased, and sedentary activity increased significantly during COVID-19.

During COVID-19 students did not engage in sufficient physical activity to offset the increased sedentary behaviour.
The Effect of Short Message Service (SMS)-Reminders on Child Health in Parents of Newborns: A Pilot Randomised Controlled Trial
Authors: Shah M , Ramsay J , Dymock M , Marsh J , Newall N , McCallum C , Davis J , Snelling T
Published: January 2021

Background

Incomplete vaccination in Australia is greatly due to vaccine hesitancy, which is driven by multiple factors. Studies analysing the effect of behavioural ‘nudges’ on vaccine uptake have shown promising results. Although there is some evidence for positively framed SMS vaccine messages, evidence is lacking for loss-based framed messages which may be highly effective but may paradoxically risk increasing vaccine hesitancy. This pilot study aimed to evaluate the effect of loss-based framed SMS messages on vaccine hesitancy.

Methods

This single-blinded randomised controlled trial enrolled pregnant women from antenatal clinics in King Edward Memorial Hospital, Perth, WA which delivers approximately 6000 higher-risk infants per year. Participants were randomised to receive either a loss-based framed SMS message warning of the risks of failure to vaccinate, or a sham SMS message unrelated to vaccination, and were asked to complete the short-scale vaccine hesitancy questionnaire before and after the intervention.

Discussion

The application of behavioural sciences through SMS-reminders has the potential to improve vaccination rates. There are difficulties in engaging with parents of newborns about vaccine hesitancy. Further research is warranted using other approaches to recruitment.

Highlights

Pilot randomised controlled trial on the use of SMS reminders to influence vaccine hesitancy

Application of behavioural economics, nudge techniques and mobile health

Vaccine hesitancy measured using the short-scale PACV questionnaire

There are difficulties in engaging with parents of newborns about vaccine hesitancy

Further research needed to optimise message framing, timing and reduce vaccine hesitancy

Trial Registration

The trial is registered with the Australia and New Zealand Clinical Trials Register (ACTRN12618001510235).
The SLIM1 transcription factor is required for arsenic resistance inArabidopsis thaliana
Authors: Jobe Timothy O. , Yu Qi , Hauser Felix , Xie Qingqing , Meng Yuan , Maassen Tim , Kopriva Stanislav , Schroeder Julian I.
Published: January 2021

The transcriptional regulators of arsenic-induced gene expression remain largely unknown. Sulfur assimilation is tightly linked with arsenic detoxification. Here we report that mutant alleles in the SLIM1 transcription factor are substantially more sensitive to arsenic than cadmium. Arsenic treatment caused high levels of oxidative stress in theslim1mutants, andslim1alleles were impaired in both thiol and sulfate accumulation. We further found enhanced arsenic accumulation in roots ofslim1mutants. Transcriptome analyses indicate an important role for SLIM1 in arsenic-induced tolerance mechanisms. The present study identifies the SLIM1 transcription factor as an essential component in arsenic tolerance and arsenic-induced gene expression. Our results suggest that the severe arsenic sensitivity of theslim1mutants is caused by altered redox status.
High rates of evolution preceded shifts to sex-biased gene expression inLeucadendron, the most sexually dimorphic angiosperms
Authors: Scharmann Mathias , Rebelo Anthony G , Pannell John R
Published: January 2021

The males and females of many dioecious plants differ in morphological (Dawson and Geber 1999; Barrett and Hough 2013; Tonnabel et al. 2017), physiological (Juvany and Munné-Bosch 2015), life-history (Delph 1999), and defence traits (Cornelissen and Stiling 2005). Ultimately, such sexual dimorphism must largely be due to differential gene expression between the sexes (Ellegren and Parsch 2007), but little is known about how sex-biased genes are recruited and how their expression evolves over time. We measured gene expression in leaves of males and females of ten species sampled across the South African Cape genusLeucadendron, which shows repeated changes in sexual dimorphism and includes the most extreme differences between males and females in flowering plants (Midgley 2010; Barrett and Hough 2013; Tonnabel et al. 2014). Even in the most dimorphic species in our sample, fewer than 2% of genes showed sex-biased gene expression (SBGE) in vegetative tissue, with surprisingly little correspondence between SBGE and vegetative dimorphism across species. The identity of sex-biased genes inLeucadendronwas highly species-specific, with a rapid turnover among species. In animals, sex-biased genes often evolve more quickly than unbiased genes in their sequences and expression levels (Ranz et al. 2003; Khaitovich et al. 2005; Ellegren and Parsch 2007; Voolstra et al. 2007; Harrison et al. 2015; Naqvi et al. 2019), consistent with hypotheses invoking rapid evolution due to sexual selection. Our phylogenetic analysis inLeucadendron, however, clearly indicates that sex-biased genes are recruited from a class of genes with ancestrally rapid rates of expression evolution, perhaps due to low evolutionary or pleiotropic constraints. Nevertheless, we also find evidence for adaptive evolution of expression levels once sex bias evolves. Thus, although the expression of sex-biased genes is ultimately responsive to selection, high rates of expression evolution might usually predate the evolution of sex bias.
Glacial connectivity and current population fragmentation in sky-islands explain the contemporary distribution of genomic variation in two narrow-endemic montane grasshoppers from a biodiversity hotspot
Authors: Tonzo Vanina , Ortego Joaquín
Published: January 2021

Aim

Cold-adapted biotas from mid-latitudes often show small population sizes, harbor low levels of local genetic diversity, and are highly vulnerable to extinction due to ongoing climate warming and the progressive shrink of montane and alpine ecosystems. In this study, we use a suite of analytical approaches to infer the demographic processes that have shaped contemporary patterns of genomic variation inOmocestus bolivariandO. femoralis, two narrow-endemic and red-listed Iberian grasshoppers forming highly fragmented populations in the sky island archipelago of the Baetic System.

Location

Southeastern Iberia.

Methods

We quantified genomic variation in the two focal taxa and coupled ecological niche models and a spatiotemporally explicit simulation approach based on coalescent theory to determine the relative statistical support of a suite of competing demographic scenarios representing contemporary population isolation (i.e., a predominant role of genetic drift)vs. historical connectivity and post-glacial colonization of sky islands (i.e., pulses of gene flow and genetic drift linked to Pleistocene glacial cycles).

Results

Inference of spatial patterns of genetic structure, environmental niche modelling, and statistical evaluation of alternative species-specific demographic models within an Approximate Bayesian Computation framework collectively supported genetic admixture during glacial periods and postglacial colonization of sky islands, rather than long-term population isolation, as the scenario best explaining the current distribution of genomic variation in the two focal taxa. Moreover, our analyses revealed that isolation in sky islands have also led to extraordinary genetic fragmentation and contributed to reduce local levels of genetic diversity.

Main conclusions

This study exemplifies the potential of integrating genomic and environmental niche modelling data across biological and spatial replicates to determine whether organisms with similar habitat requirements have experienced concerted/idiosyncratic responses to Quaternary climatic oscillations, which can ultimately help to reach more general conclusions about the vulnerability of mountain biodiversity hotspots to ongoing climate warming.
ARID1A-mutant and deficient bladder cancer is sensitive to EZH2 pharmacologic inhibition
Authors: Ferguson James E. , Rehman Hasibur , Chandrashekar Darshan S. , Chakravarthi Balabhadrapatruni V. S. K. , Nepal Saroj , Eich Marie-Lisa , Robinson Alyncia D. , Agarwal Sumit , Hodigere Balasubramanya Sai Akshaya , Naik Gurudatta , Manne Upender , Netto George J , Pan Chong-xian , Sonpavde Guru , Varambally Sooryanarayana
Published: January 2021

Metastatic urothelial carcinoma of the bladder is generally incurable by current systemic therapy. Molecular characterization of bladder cancer (BLCa) has revealed multiple candidate driver genes for BLCa tumorigenesis. Epigenetic/chromatin modifiers have been shown to be frequently mutated in BLCa, with ARID1A mutations highly prevalent in nearly 20% of early and late stage tumors. EZH2 is a histone methyltransferase that acts as an oncogene. The data herein show that ARID1A deficient tumors, but not ARID1A wild-type tumors are sensitive to EZH2 inhibition. Specifically, EZH2 inhibitor-treated ARID1A deficient bladder cancer cells show significantly reduced cell viability, colony formation, andin vivotumor growth relative to ARID1A-wild type bladder cancer cells. Thus, our study suggests that a specific subset of bladder cancer patients with ARID1A mutations can be therapeutically treated with pharmacologic inhibitors targeting EZH2.
A method for the efficient iron-labeling of patient-derived xenograft cells and cellular imaging validation
Authors: Knier Natasha N. , Dubois Veronica P. , Ronald John A. , Foster Paula J.
Published: January 2021

There is momentum towards implementing patient-derived xenograft models (PDX) in cancer research to reflect the histopathology, tumour behavior, and metastatic properties observed in the original tumour. These models are more predictive of clinical outcomes and are superior to cell lines for preclinical drug evaluation and therapeutic strategies. To study PDX cells preclinically, we used both bioluminescence imaging (BLI) to evaluate cell viability and magnetic particle imaging (MPI), an emerging imaging technology to allow for detection and quantification of iron nanoparticles. The goal of this study was to develop the first successful iron labeling method of breast cancer cells derived from patient brain metastases and validate this method with imaging during tumour development.

Luciferase expressing human breast cancer PDX cells (F2-7) were successfully labeled after incubation with micron-sized iron oxide particles (MPIO; 25 μg Fe/mL). NOD/SCID/ILIIrg-/-(n=5) mice received injections of 1×106iron-labeled F2-7 cells into the fourth mammary fat pad (MFP). BLI was performed longitudinally to day 49 and MPI was performed up to day 28.In vivoBLI revealed that signal increased over time with tumour development. MPI revealed decreasing signal in the tumours and increasing signal in the liver region over time.

Here, we demonstrate the first application of MPI to monitor the growth of a PDX MFP tumour. To accomplish this, we also demonstrate the first successful labeling of PDX cells with iron oxide particles. Imaging of PDX cells provides a powerful system to better develop personalized therapies targeting breast cancer brain metastasis.
Taxonomy, distribution and host relationships of aphidiine wasps (Hymenoptera: Aphidiidae) parasitizing aphids (Hemiptera: Aphididae) in Australian grain production landscapes
Authors: Ward Samantha , Umina Paul A. , Polaszek Andrew , Hoffmann Ary A.
Published: January 2021

Aphid parasitoids (Hymenoptera; Aphidiidae) were surveyed within grain production landscapes in Victoria, Australia between 2017 and 2018, as well as more sporadically nationwide between 2016 and 2019. In addition, aphidiine records were collated from insect depositories around Australia and online databases. The 5551 specimens recorded constituted a total of 23 species and seven genera.Diaeretiella rapae(M’Intosh) was the most common species, representing more than 70% of all aphidiines recorded. This species also showed a greater northerly geographic range than other aphidiines. During sampling between 2017 and 2019, aphidiines were reared from mummies to ascertain host-parasitoid relationships.Diaeretiella rapaewas again the most commonly reared parasitoid, although aphidiine preference varied with aphid host and between states and territories. An illustrated dichotomous key to Australian aphidiines in grain production landscapes is provided for the 11 species sampled in our field surveys. This is the first comprehensive review of aphidiines sampled within Australia in over two decades. Knowledge about the diversity and distribution of these parasitoids is important for understanding their impact on current and future invasions of aphid species. In addition, understanding the interactions between grain aphids and their associated parasitoids will further support the inclusion of parasitoid wasps into integrated pest management (IPM) strategies.
Dimensionality reduction by UMAP reinforces sample heterogeneity analysis in bulk transcriptomic data
Authors: Yang Yang , Sun Hongjian , Zhang Yu , Zhang Tiefu , Gong Jialei , Wei Yunbo , Duan Yong-Gang , Shu Minglei , Yang Yuchen , Wu Di , Yu Di
Published: January 2021

Transcriptome profiling and differential gene expression constitute a ubiquitous tool in biomedical research and clinical application. Linear dimensionality reduction methods especially principal component analysis (PCA) are widely used in detecting sample-to-sample heterogeneity in bulk transcriptomic datasets so that appropriate analytic methods can be used to correct batch effects, remove outliers and distinguish subgroups. In response to the challenge in analysing transcriptomic datasets with large sample size such as single-cell RNA-sequencing (scRNA-seq), non-linear dimensionality reduction methods were developed. t-distributed stochastic neighbour embedding (t-SNE) and uniform manifold approximation and projection (UMAP) show the advantage of preserving local information among samples and enable effective identification of heterogeneity and efficient organisation of clusters in scRNA-seq analysis. However, the utility of t-SNE and UMAP in bulk transcriptomic analysis has not been carefully examined. Therefore, we compared major dimensionality reduction methods (linear: PCA; nonlinear: multidimensional scaling (MDS), t-SNE, and UMAP) in analysing 71 bulk transcriptomic datasets with large sample sizes. UMAP was found superior in preserving sample level neighbourhood information and maintaining clustering accuracy, thus conspicuously differentiating batch effects, identifying pre-defined biological groups and revealing in-depth clustering structures. We further verified that new clustering structures visualised by UMAP were associated with biological features and clinical meaning. Therefore, we recommend the adoption of UMAP in visualising and analysing of sizable bulk transcriptomic datasets.
An optimized stepwise algorithm combining rapid antigen and RT-qPCR for screening of COVID-19 patients
Authors: Halfon Philippe , Penaranda Guillaume , Khiri Hacène , Garcia Vincent , Drouet Hortense , Philibert Patrick , Psomas Christina , Delord Marion , Allemand-Sourrieu Julie , Retornaz Frédérique , Charpin Caroline , Gonzales Thomas , Pegliasco Hervé , Allardet-Servent Jérôme
Published: January 2021

Background

Diagnosing SARS CoV-2 infection with certainty is essential for appropriate case management. We investigated the combination of rapid antigen detection (RAD) and RT-qPCR assays in a stepwise procedure to optimize the detection of COVID-19.

Methods

From August 2020 to November 2020, 43,399 patients were screened in our laboratory for COVID-19 diagnostic by RT-qPCR using nasopharyngeal swab. Overall, 4,691 of the 43,399 were found to be positive, and 200 were retrieved for RAD testing allowing comparison of diagnostic accuracy between RAD and RT-qPCR. Cycle threshold (Ct) and time from symptoms onset (TSO) were included as covariates.

Results

The overall sensitivity, specificity, PPV, NPV, LR-, and LR+ of RAD compared with RT- qPCR were 72% (95%CI 62%–81%), 99% (95% CI95%–100%), 99% (95%CI 93%–100%), and 78% (95%CI 70%–85%), 0.28 (95%CI 0.21-0.39), and 72 (95%CI 10-208) respectively. Sensitivity was higher for patients with Ct ≤ 25 regardless of TSO: TSO ≤ 4 days 92% (95%CI 75%–99%), TSO > 4 days 100% (95%CI 54%–100%), and asymptomatic 100% (95%CI 78-100%). Overall, combining RAD and RT-qPCR would allow reducing from only 4% the number of RT-qPCR needed.

Conclusion

This study highlights the risk of misdiagnosing COVID-19 in 28% of patients if RAD is used alone. Thus, negative results from RAD needs to be confirmed by RT-qPCR prior to making treatment decisions. A stepwise analysis that combines RAD and RT-qPCR would be an efficient screening procedure for COVID-19 detection and may facilitate the control of the outbreak.
Elevated Angiopoietin-2 inhibits thrombomodulin-mediated anticoagulation in critically ill COVID-19 patients
Authors: Hultström Michael , Fromell Karin , Larsson Anders , Quaggin Susan E , Betsholtz Christer , Frithiof Robert , Lipcsey Miklos , Jeansson Marie
Published: January 2021

Several studies suggest that hypercoagulation and endothelial dysfunction play central roles in severe forms of COVID-19 infections. We hypothesized that the high levels of the inflammatory cytokine Angiopoietin-2 (ANGPT2) reported in hospitalized COVID-19 patients might promote hypercoagulation through ANGPT2 binding to thrombomodulin with resulting inhibition of thrombin/thrombomodulin-mediated physiological anticoagulation. Plasma was collected from critically ill COVID-19 patients treated in the intensive care unit (ICU) at Uppsala University Hospital and ANGPT2 was measured at admission (61 patients) and after ten days (40 patients). ANGPT2 levels were compared with biochemical parameters, clinical outcome, and survival. We found that ANGPT2 levels were increased in COVID-19 patients in correlation with disease severity, hypercoagulation, and mortality. To test causality, we administered ANGPT2 to wildtype mice and found that it shortened bleeding time in a tail injury model. In further support of a role for ANGPT2 in physiological coagulation, bleeding time was increased in endothelial-specificAngpt2knockout mice. Usingin vitroassays, we found that ANGPT2 inhibited thrombomodulin-mediated anticoagulation and protein C activation in human donor plasma. Our data reveal a novel mechanism for ANGPT2 in hypercoagulation and suggest that Angiopoietin-2 inhibition may be tested in the treatment of hypercoagulation in severe COVID-19 infection.
The impact of the first wave of COVID-19 on those with lifelong conditions: a case study of congenital heart disease
Authors: Wray Jo , Pagel Christina , Chester Adrian H. , Kennedy Fiona , Crowe Sonya
Published: January 2021

Objectives

Globally, health care systems have been stretched to the limit by the COVID-19 pandemic. Significant changes have had to be made to the way in which non-COVID-19 related care has been delivered. Our objective was to understand, from the perspective of patients with a chronic, life-long condition (congenital heart disease, CHD) and their parents/carers, the impact of COVID-19 on the delivery of care, how changes were communicated and whether health care providers should do anything differently in a subsequent wave of COVID-19 infections.

Design and setting

A series of asynchronous discussion forums set up and moderated by three patient charities via their Facebook pages.

Participants

Patients with CHD and parents/carers of patients with CHD.

Main outcome measures

Qualitative responses to questions posted on the discussion forums.

Results

The forums ran over a 6-week period and involved 111 participants. Following thematic analysis of the transcripts, we identified three themes and ten subthemes related to individual condition-related factors, patient-related factors and health professional/centre factors that may have influenced how patients and parents/carers experienced changes to service delivery as a result of COVID-19.

Conclusions

Our findings, whilst collected in relation to patients with CHD, are not necessarily specific to this population and we believe reflect the experiences of many thousands of people with life-long conditions in the UK. Drawing on what participants told us in the discussion forums, we have developed recommendations related to communication, service delivery and support during the pandemic that would, we think, improve patients’ experience of care and, potentially, their outcomes. Although the data were collected specifically in relation to COVID-19, a number of these recommendations are relevant to the wider delivery of care to patients with chronic underlying health conditions and reflect principles of good communication and service delivery.