bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a Validated Bioanalytical UPLC–MS/MS Method for Quantification of Neratinib: A Recent Application to Pharmacokinetic Studies in Rat Plasma
Authors: Alrobaian Majed , Panda Sagar Suman , Afzal Obaid , Kazmi Imran , Alossaimi Manal A , Al-Abbasi Fahad A , Almalki Waleed H , Soni Kriti , Alam Ozair , Alam Md Naushad , Rub Rehan A , Rahman Mahfoozur , Beg Sarwar
Published: June 2021

Neratinib, a tyrosine kinase inhibitor, was very recently approved by USFDA in 2017 as an anticancer drug to treat of HER2 positive breast cancers. The present work provides an account on the development of a validated bioanalytical UPLC–MS/MS method for quantification of neratinib and internal standard (imatinib) in rat plasma and tissue homogenates. A UPLC having a 100 mm C18 column (1.7 μm sized particles) was used with acetonitrile (0.1% formic acid): 2 mMol of ammonium acetate in water (pH 3.5) as the mobile phase. An efficient chromatographic separation was performed and detection was achieved by monitoring precursor-to-product ion transitions with m/z 557.29 → 112.06 for neratinib and m/z 494.43 → 294.17 for IS. The method demonstrated excellent linearity in the spiked plasma drug concentrating ranging between 1 and 800 ng.mL−1 (r2 = 0999), with lower limit of quantification (LLOQ) was observed at 1 ng.mL−1. Intra-assay and inter-assay precision relative standard deviations were found to be within 6.58. Mean extraction recovery for neratinib and IS were 99.44 and 99.33%, while matrix effect for neratinib and IS was ranging between −4.35 and − 3.66%, respectively. Overall, the method showed successful applicability in pharmacokinetic analysis of pure various formulations in Wistar rat plasma.
An organizing feature of bumble bee life history: worker emergence promotes queen reproduction and survival in young nests
Authors: Sarro Erica , Sun Penglin , Mauck Kerry , Rodriguez-Arellano Damaris , Yamanaka Naoki , Woodard S Hollis
Published: June 2021

Bumble bee queens initiate nests solitarily and transition to living socially once they successfully rear their first cohort of offspring. Bumble bees are disproportionately important for early season pollination, and many populations are experiencing dramatic declines. In this system, the onset of the social stage is critical for nest survival, yet the mechanisms that facilitate this transition remain understudied. Further, the majority of conservation efforts target the social stage of the bumble bee life cycle and do not address the solitary founding stage. We experimentally manipulated the timing of worker emergence in young nests of bumble bee (Bombus impatiens) queens to determine whether and how queen fecundity and survival are impacted by the emergence of workers in the nest. We found that queens with workers added to the nest exhibit increased ovary activation, accelerated egg laying, elevated juvenile hormone (JH) titres and also lower mortality relative to solitary queens. We also show that JH is more strongly impacted by the social environment than associated with queen reproductive state, suggesting that this key regulator of insect reproduction has expanded its function in bumble bees to also influence social organization. We further demonstrate that these effects are independent of queen social history, suggesting that this underlying mechanism promoting queen fecundity is reversible and short lived. Synchronization between queen reproductive status and emergence of workers in the nest may ultimately increase the likelihood of early nesting success in social systems with solitary nest founding. Given that bumble bee workers regulate queen physiology as we have demonstrated, the timing of early worker emergence in the nest likely impacts queen fitness, colony developmental trajectories and ultimately nesting success. Collectively, our findings underline the importance of conservation interventions for bumble bees that support the early nesting period and facilitate the production and maintenance of workers in young nests.
Automatization and self-maintenance of the O-GlcNAcome catalog: a smart scientific database
Authors: Malard Florian , Wulff-Fuentes Eugenia , Berendt Rex R , Didier Guillaume , Olivier-Van Stichelen Stephanie
Published: June 2021

Post-translational modifications (PTMs) are ubiquitous and essential for protein function and signaling, motivating the need for sustainable benefit and open models of web databases. Highly conserved O-GlcNAcylation is a case example of one of the most recently discovered PTMs, investigated by a growing community. Historically, details about O-GlcNAcylated proteins and sites were dispersed across literature and in non-O-GlcNAc-focused, rapidly outdated or now defunct web databases. In a first effort to fill the gap, we recently published a human O-GlcNAcome catalog with a basic web interface. Based on the enthusiasm generated by this first resource, we extended our O-GlcNAcome catalog to include data from 42 distinct organisms and released the O-GlcNAc Database v1.2. In this version, more than 14 500 O-GlcNAcylated proteins and 11 000 O-GlcNAcylation sites are referenced from the curation of 2200 publications. In this article, we also present the extensive features of the O-GlcNAc Database, including the user-friendly interface, back-end and client–server interactions. We particularly emphasized our workflow, involving a mostly automatized and self-maintained database, including machine learning approaches for text mining. We hope that this software model will be useful beyond the O-GlcNAc community, to set up new smart, scientific online databases, in a short period of time. Indeed, this database system can be administrated with little to no programming skills and is meant to be an example of a useful, sustainable and cost-efficient resource, which exclusively relies on free open-source software elements (www.oglcnac.mcw.edu).
Development of a patient-oriented Hololens application to illustrate the function of medication after myocardial infarction
Authors: Hilt Alexander D , Hierck Beerend P , Eijkenduijn Joep , Wesselius Fons J , Albayrak Armagan , Melles Marijke , Schalij Martin J , Scherptong Roderick W C
Published: June 2021

Aims

Statin treatment is one of the hallmarks of secondary prevention after myocardial infarction. Adherence to statins tends to be difficult and can be improved by patient education. Novel technologies such as mixed reality (MR) expand the possibilities to support this process. To assess if an MR medication-application supports patient education focused on function of statins after myocardial infarction.

Methods and results

A human-centred design-approach was used to develop an MR statin tool for Microsoft HoloLens™. Twenty-two myocardial infarction patients were enrolled; 12 tested the application, 10 patients were controls. Clinical, demographic, and qualitative data were obtained. All patients performed a test on statin knowledge. To test if patients with a higher tendency to become involved in virtual environments affected test outcome in the intervention group, validated Presence- and Immersive Tendency Questionnaires (PQ and ITQ) were used. Twenty-two myocardial infarction patients (ST-elevation myocardial infarction, 18/22, 82%) completed the study. Ten out of 12 (83%) patients in the intervention group improved their statin knowledge by using the MR application (median 8 points, IQR 8). Test improvement was mainly the result of increased understanding of statin mechanisms in the body and secondary preventive effects. A high tendency to get involved and focused in virtual environments was moderately positive correlated with better test improvement (r = 0.57, P < 0.05). The median post-test score in the control group was poor (median 6 points, IQR 4).

Conclusions

An MR statin education application can be applied effectively in myocardial infarction patients to explain statin function and importance.
Influence of logging on nest density and nesting microsites of cavity-nesting birds in the subtropical forests of the Andes
Authors: Schaaf Alejandro A , García Cecilia G , Ruggera Román A , Tallei Ever , Vivanco Constanza G , Rivera Luis , Politi Natalia
Published: June 2021

Birds select nesting sites with certain characteristics associated with tree age and species that help to prevent or reduce the risk of clutch loss due to predation or unfavourable weather conditions. Logging may reduce the availability of trees and their related features that may be important for cavity nesters. Thus, the aim of this study is to evaluate the effect of logging on nest density, nesting microsite and nest success of cavity nesting birds at Piedmont forests of northwestern Argentina. We monitored these variables at different logged and unlogged sites during four consecutive reproductive seasons and analysed them using univariate analysis and generalized linear models. The main results indicate that logging reduces nest density and changes the characteristics of the nesting microsites. We found that nest success was greater in cavities located higher above the ground and found no evidence of lower nest success at logged sites. This study suggests the need for forest management actions aimed at increasing nesting sites for cavity-nesting birds. For this purpose, management should be focused on the retention of old trees with a diameter >50 cm (both living and dead). The use of reduced-impact logging techniques or forest certifications (e.g. Forest Stewardship Council) could provide alternatives in subtropical forests, as these forestry practices can ensure tree abundance and richness, providing features suitable for cavity-nesting birds (e.g. tree diameter, cavity size and height).
Developmental Nutrition Affects the Structural Integrity of a Sexually Selected Weapon
Authors: Woodman T E , Chen S , Emberts Z , Wilner D , Federle W , Miller C W
Published: June 2021

Males in many species engage in physical combat over access to mates, and sexual selection has led to the evolution of weapons to enhance contest performance. The size of these often-elaborate structures is known to be exquisitely sensitive to nutrition. However, we know very little about the degree to which nutrition affects other attributes of animal weapons that can be crucial to fighting. In this study, we investigated the impact of natural dietary variation on weapon structural integrity in a fighting insect, Narnia femorata (Hemiptera: Coreidae). Males in this species display their enlarged, spiny hind legs to other males, and these legs serve as weapons in aggressive physical contests where they are used to strike and squeeze opponents. N. femorata feeds on the fruit of prickly pear cactus and sets up territories on this plant. In North Central Florida the prickly pear Opuntia mesacantha ssp. lata blooms and begins to produce fruits in April and May. N. femorata has multiple, overlapping generations while the green fruits slowly ripen over the next several months. We examined insects reaching adulthood at two nearby time points in this range, June and July, to test the influence of the nutrition provided by ripening green cactus fruit on weapon size and its ability to resist puncture. We also raised insects on cactus with red, ripe fruit for comparison. We found a striking effect of cactus fruit phenology on weapons. Insects raised with the more mature green fruit (those in the second cohort) had 71% larger weapon area and 4.4 times greater puncture resistance than those raised on the early green fruit (those in the first cohort). In contrast, insects raised on red, ripe fruit were moderate in size, had high puncture resistance, and they changed little phenotypically from the first to second cohort. Increased structural integrity of the hind femur weapon was associated with the increased body size that came with better nutrition. This pattern highlights that cuticle thickness increased or its material properties changed when weapons were larger. Importantly, effects of nutrition on puncture resistance also transcended size. Insects of the same size had greater structural integrity if they received superior nutrition. Sexually selected weapons are often used as visual signals to conspecifics before fights, and this work hints that the size of the weapons may be a poor signal of weapon performance when nutrition is variable.
Appraising the Socio-Economic Turn in Reparations: Transitional Justice for Cholera Victims in Haiti
Authors: Lemay-Hébert Nicolas , Freedman Rosa
Published: June 2021

Abstract∞

After belatedly apologizing for the cholera epidemic in Haiti, the ‘New Approach to Cholera in Haiti’ by the UN and the promise of material assistance to victims through a ‘victim-centred approach’ highlight how the victims turn and the socio-economic turn are increasingly pivotal in the field of transitional justice. In light of these growing calls, we suggest a matrix to clarify the debate made of two separate dimensions: the focus of reparations – collective versus individual – and the means of reparations – symbolic versus material. Based on fieldwork conducted in March 2017 in the communities most affected by the cholera outbreak, this article demonstrates how the tensions between reparations offered by the UN (with a preference for collective symbolic reparations) and the reparations demanded by the victims (individual material reparations) can help understand the current stalemate in Haiti, and hopefully inform the next steps in the process of remedy for the victims.
Biomarkers predictive of long-term fertility found in vaginal lipidome of gilts at weaning
Authors: Mills Kayla M , Ferreira Christina R , Stevens Jebadiah G , Stewart Kara R , Casey Theresa M
Published: June 2021

A marker indicative of the fertility potential of replacement gilts early in development would decrease culling rates in the sow herd, improve sow herd reproductive efficiency, and reduce production costs. The objective of this study was to determine if vaginal lipid profiles at 21 d postnatal (PN) could predict sow reproductive performance. Vaginal swabs of the anterior vagina were taken at 21 ± 4 d PN from gilts born on a commercial sow production facility for lipidomic analysis. Animals were followed prospectively for 2 yr and assigned to reproductive performance categories based on the observation of estrus or piglets weaned per sow per year (PSY) across two farrowings. Lipids were extracted from cellular material collected with swabs taken from high fertility (HF; n = 28; ≥26 PSY) and infertile (IF; n = 34; no estrus, no pregnancy) animals, and multiple reaction monitoring profiling was used for lipidome analysis. The relative abundance of arachidonic acid (C20:4) and docosahexaenoic acid (C22:6) was lower (P < 0.05) in IF gilts than HF gilts, whereas the abundance of the free fatty acids such as cerotic (C26:0), ximenic (C26:1), and nonadecanoic (C19:0) acids was greater (P < 0.05) in IF gilts. Additionally, eicosapentaenoic acid (C20:5), a precursor of prostaglandins, was higher (P < 0.05) in IF gilts. The perspective of having a panel of lipids captured with vaginal swabs at weaning that can predict the reproductive efficiency of gilts shows promise and warrants future research in this area.
Association between SNPs and hepatotoxicity in patients with primary central nervous system lymphoma on high-dose methotrexate therapy
Authors: Zhao Qing , Cui Yong , Zeng Chun , Ren Xiaohui , Yu Kefu , Lin Song , Zhao Zhigang , Mei Shenghui
Published: June 2021

Objectives

This study aims to evaluate the association between polymorphisms of methotrexate pathway genes and high-dose methotrexate-related hepatotoxicity in Chinese patients with primary central nervous system lymphoma.

Methods

Sixty-five patients in 411 treatment courses were enrolled and their toxicities were evaluated. The association between 30 candidate SNPs from 20 methotrexate pathway genes and high-dose methotrexate-related hepatotoxicity was analysed by PLINK and logistic regression.

Key findings

TYMS 6 bp DI + II (rs151264360; OR, 0.41; 95% CI, 0.25–0.66; P = 0.00029), MTHFD1 1958 GA + AA (rs2236225; OR, 0.55; 95% CI, 0.33–0.91; P = 0.020) and CCND1 870 GA + GG (rs9344; OR, 0.42; 95% CI, 0.24–0.73; P = 0.0024) had less risk of hepatotoxicity compared with their homozygotes (DD, GG and AA, respectively), while ABCC2 intron 29 GA + GG (rs3740065; OR, 3.14; 95% CI, 1.89–5.20; P = 0.00001) was more prevalent in patients with hepatotoxicity than TT.

Conclusions

TYMS 6 bp DI + II, MTHFD1 1958 GA + AA, CCND1 870 GA + GG genotypes were associated with a lower probability of hepatotoxicity in patients with primary central nervous system lymphoma on high-dose methotrexate therapy, and ABCC2 intron 29 GA + GG was correlated with increased risk of hepatotoxicity.
Donor Financial Capacity Drives Racial Inequality in Medical Crowdsourced Funding
Authors: Igra Mark
Published: June 2021

Americans facing large health-related expenses have increasingly turned to online crowdsourced funding for support, initiating 250,000 medical fundraisers on GoFundMe in 2018. Recent research indicates that these fundraisers yield inequitable outcomes, with White crowdfunding beneficiaries receiving higher levels of support than non-White beneficiaries. Researchers fear that racialized impressions of deservingness may be a driver of unequal returns in crowdfunding. However, rather than being a direct effect of interpersonal racism, differences in returns may be an indirect effect of the systemic racism that causes the social networks of Black and Hispanic Americans to have lower access to financial capital. This paper is the first to focus on how unequal access to monetary capital in networks of potential crowdfunding donors drives unequal returns for beneficiaries. I analyze a geographically stratified sample of 2,618 GoFundMe campaigns coded for perceived race and ethnicity of the beneficiary. I estimate donor financial capacity for each campaign based on the geography of Facebook friend networks and the most likely racial and ethnic makeup of the donor pool, based on donor surnames. I show that variations in the estimated income of potential donors can account for much of the deficit in returns. Thus, even in the absence of interpersonal discrimination, crowdfunding is unlikely to yield equitable outcomes given the current distribution of financial resources in the United States.
Exposure to relaxing words during sleep promotes slow-wave sleep and subjective sleep quality
Authors: Beck Jonas , Loretz Erna , Rasch Björn
Published: June 2021

Our thoughts alter our sleep, but the underlying mechanisms are still unknown. We propose that mental processes are active to a greater or lesser extent during sleep and that this degree of activation affects our sleep depth. We examined this notion by activating the concept of “relaxation” during sleep using relaxation-related words in 50 healthy participants. In support of our hypothesis, playing relaxing words during non-rapid eye movement sleep extended the time spent in slow-wave sleep, increased power in the slow-wave activity band after the word cue, and abolished an asymmetrical sleep depth during the word presentation period. In addition, participants reported a higher sleep quality and elevated subjective alertness. Our results support the notion that the activation of mental concepts during sleep can influence sleep depth. They provide a basis for interventions using targeted activations to promote sleep depth and sleep quality to foster well-being and health.
Newly Developed COVID-19 Bundle Greatly Reduces the Infection Fatality Rate for a Highly Vulnerable Nursing Home Population
Authors: Finger Howard J. , Rao Rani N. , Sansone Giorgio R. , Hazel Edouard J. , Silvestri-Tan Carmentina T.
Published: June 2021

This performance improvement initiative used a bundle designed to reduce the COVID-19 infection fatality rate (IFR) by ≥33% and the new infection rate (IR) to <1% among nursing home (NH) residents over a 3-month period at a large public NH in New York City. Participants were all NH residents, newly testing COVID-19 PCR positive between March 1, 2020 and June 30, 2020. Key bundle components involved close observation of all residents with vital signs taken once/shift, including O2 saturation, frequent clinical team follow-up visits for those symptomatic, and ramped-up COVID-19 PCR testing. From April to June, average IFR was 12.3%, a 49.6% reduction from the March baseline (P < 0.05), and average new IR was 5.4%, a 29.9% reduction from baseline (P < 0.05). In the 2 follow-up months, no deaths occurred with a new IR < 1%, indicating sustained improvement. Because of its simplicity, this bundle or components of it could be readily applied elsewhere after appropriate assessment.
Fostering Collaborative Research Culture Through Research Development Rounds
Authors: Babenko Oksana , Gruneir Andrea
Published: June 2021

Helping physicians to prepare for and fulfill their role as CanMEDS scholars requires collaborative research environments, which promote engagement with a research community of practice through all stages of the research process. To foster such an environment in the Department of Family Medicine, we spearheaded Research Development Rounds. Open to anyone with interest in research development, Research Development Rounds offer an opportunity for faculty, staff, residents, and other trainees to receive constructive feedback on their work that is in development from department members. Programs seeking to create a more collaborative research culture should try this approach.
Training Future International Clinical Academic Leaders Through a Structured Observership Program: Impact and Outcomes from the Initial Cohort
Authors: Kuc Karen J. , Roberts David H. , Caballero Augusto Enrique
Published: June 2021

Introduction:

Clinical observership programs have existed for many years as both formal initiatives organized at the institutional or professional society level and informal arrangements between individual physicians and prospective mentors. However, few programs longitudinally assess their impact on patient care and require implementation of a postobservership project to demonstrate learning. In 2018, the Harvard Medical School Office for External Education launched the International Clinical Leaders Observership Program (ICLOP) as an opportunity for midcareer physicians to shadow Harvard Medical School faculty in one of three specialty areas: oncology, cardiology, or diabetology. The culminating activity for each participant was presentation of a capstone project and commitment to implement it on returning home.

Methods:

We summarize here the initial cohort and results from a follow-up survey measuring the impact of the program on their subsequent patient care, academic activities, and achievements.

Results:

At 1 year of follow-up, 90% of survey respondents had implemented their project. Improvements were reported in areas of clinical, surgical, therapeutic, system, patient education, and team innovation, as well as personal benefits to the participants.

Discussion:

ICLOP is a robust and reproducible initiative that resulted in meaningful improvements in patient care and physician-related outcomes for the first cohort of participants.
CLINICAL AND MORPHOLOGIC FEATURES OF POSTERIOR STAPHYLOMA EDGES BY ULTRA-WIDEFIELD IMAGING IN PATHOLOGIC MYOPIA
Authors: Liu Lillian , Fang Yuxin , Igarashi-Yokoi Tae , Takahashi Hiroyuki , Ohno-Matsui Kyoko
Published: June 2021

Purpose:

To investigate morphologic features along posterior staphyloma edges in eyes with pathologic myopia using ultra-widefield optical coherence tomography imaging.

Methods:

Highly myopic patients (refractive error < −8 diopters or axial length ≥26.5 mm) were consecutively examined by prototype ultra-widefield optical coherence tomography with a scan width of 23 mm and depth of 5 mm. Staphyloma edges were assessed for scleral, choroidal, and retinal status, as well as measurements of angle size. Findings were correlated with pigmentary changes observed on Optos fundus photography, and multivariate logistic regression analyses were performed.

Results:

In 164 eyes diagnosed with posterior staphyloma by ultra-widefield optical coherence tomography, choroidal thinning and scleral protrusion were hallmark features of staphyloma edges, observed simultaneously in more than 95% of staphylomatous eyes. Outer neural retinal thinning was observed in 80 eyes (48.8%), whereas 15 eyes (9.1%) showed retinal pigment epithelium damage. The mean angle at the staphyloma edge was 23° ± 12.4° (range 8° to 77°). Larger angles were significant predictors of retinal thinning (adjusted odds ratio: 1.17, confidence interval: 1.09–1.25), and the staphyloma was detected by Optos pseudocolor fundus photography (adjusted odds ratio: 1.08, confidence interval: 1.02–1.15).

Conclusion:

These morphologic findings may provide a basis for exploring the natural evolution of posterior staphyloma as part of the development of pathologic myopia.
RETINAL VASCULAR ABNORMALITIES IN CHILDREN WITH NEUROFIBROMATOSIS TYPE 1
Authors: Touzé Romain , Abitbol Marc M. , Bremond-Gignac Dominique , Robert Matthieu P.
Published: June 2021

Purpose:

Retinal vascular abnormalities (RVAs) have been recently described in patients with neurofibromatosis Type 1 (NF1) as vascular tortuosity, best visible on infrared imaging. This study assessed clinical RVA's characteristics in a large series of children with NF1.

Methods:

This retrospective observational study was conducted in children (0–18 years) with an NF1 diagnosis. Using near-infrared imaging, RVAs were classified according to the nature of vessels involvement and their degree of tortuosity.

Results:

Retinal imaging from 140 children, with a median age of 8.8 years (1.5–18), was included; 52 patients (37.1%) (81 eyes) exhibited RVAs. These RVAs comprised 96% (50/52) of simple vascular tortuosity and 17% (9/52) of a corkscrew pattern. A corkscrew pattern involved only small veins, whereas simple vascular tortuosity could affect both arteries and veins. No statistically significant age correlation was observed, but evolution of RVAs from simple vascular tortuosity to corkscrew pattern was observed in 5 cases.

Conclusion:

Retinal vascular abnormalities occurred in 37.1% of children with NF1. These abnormalities may result from NF1 promoting localized tortuosity in both small arteries and veins, whereas only small second-order or tertiary-order venules evolve to a highly tortuous pattern.
Pain, cannabis use, and physical and mental health indicators among veterans and nonveterans: results from the National Epidemiologic Survey on Alcohol and Related Conditions-III
Authors: Enkema Matthew C. , Hasin Deborah S. , Browne Kendall C. , Stohl Malki , Shmulewitz Dvora , Fink David S. , Olfson Mark , Martins Silvia S. , Bohnert Kipling M. , Sherman Scott E. , Cerda Magdalena , Wall Melanie , Aharonovich Efrat , Keyhani Salomeh , Saxon Andrew J.
Published: June 2021

Chronic pain is associated with mental and physical health difficulties and is prevalent among veterans. Cannabis has been put forth as a treatment for chronic pain, and changes in laws, attitudes, and use patterns have occurred over the past 2 decades. Differences in prevalence of nonmedical cannabis use and cannabis use disorder (CUD) were examined across 2 groups: veterans or nonveterans and those reporting or not reporting recent pain. Data from the National Epidemiologic Survey on Alcohol and Related Conditions-III (2012-2013; n = 36,309) were analyzed using logistic regression. Prevalence differences (PDs) for 3 cannabis outcomes (1) past-year nonmedical cannabis use, (2) frequent (≥3 times a week) nonmedical use, and (3) DSM-5 CUD were estimated for those reporting recent moderate to severe pain (veterans or nonveterans) and veterans reporting or not reporting recent pain. Difference in differences was calculated to investigate PDs on outcomes associated with residence in a state with medical cannabis laws (MCLs). Associations between physical and mental health and cannabis variables were tested. The results indicated that the prevalence of recent pain was greater among veterans (PD = 7.25%, 95% confidence interval (CI) [4.90-9.60]). Among veterans, the prevalence of frequent cannabis use was greater among those with pain (PD = 1.92%, 98% CI [0.21-3.63]), and among veterans residing in a state with MCLs, the prevalence of CUD was greater among those reporting recent pain (PD = 3.88%, 98% CI [0.36-7.39]). Findings failed to support the hypothesis that cannabis use improves mental or physical health for veterans with pain. Providers treating veterans with pain in MCL states should monitor such patients closely for CUD.
Direct to consumer genetic and genomic testing with associated implications for advanced nursing practice
Authors: Aleman Kristy M. , Chipman Melanie , Peck Jessica L. , Hughes Ashley K. , Murphey Christina
Published: June 2021

Direct-to-consumer genetic and genomic testing (DTCGT) has paved the way for consumers to gain information about their genetic makeup. Consumers may seek DTCGT to estimate ethnic background, identify genetic relations, or obtain raw DNA information that can be used for other purposes, such as testing for paternity and identifying genetically linked illnesses. Despite robust progress in genetic and genomic testing, most people have a low exposure threshold to DTCGT. Patient consumers may unnecessarily experience anxiety if they do not have a health care provider (HCP) to consult and review their results. Presently, there is a knowledge gap in how accurately HCPs can interpret and communicate genetic test results to patients compared with genetic specialists who may be inaccessible to underserved populations. Genetic and genomic information is rapidly progressing in health care and can identify patients at increased risk for certain diseases and improve patient care and outcomes. Appropriate use of genetic and genomic testing and knowing the limitations and difficulties of current testing available are integral to the success of HCPs in using these results in health promotion and improving quality of life. Health care providers should be aware of DTCGT recommendations and implications for patients, be prepared to counsel patients who present with testing results in hand, seeking advisement, and be competent in determining the need for further diagnostic testing or referral to a specialist genetic counselor.
Anomalous functional connectivity within the default-mode network in treatment-naive patients possessing first-episode major depressive disorder
Authors: Yu Renqiang , Tan Huan , Peng Gang , Du Lian , Wang Peijia , Zhang Zhiwei , Lyu Fajin
Published: June 2021

Background and Objective:

Previous studies have shown that the default-mode network (DMN) has a substantial role in patients with major depressive disorder (MDD). However, there is a shortage of information regarding variations in the functional connectivity (FC) of the DMN of treatment-naive patients with first-episode MDD. The present study aims to explore the FC of the DMN in such patients.

Methods:

The study population consisted of 33 patients and 35 controls, paired regarding age, gender, education level, and health condition. Depression severity was assessed through the Hamilton Depression Scale (HAM-D), and subjects underwent evaluation during the resting-state through functional magnetic resonance imaging (rs-fMRI). To assess the result, we used FC and ICA. We used Spearman's correlation test to detect potential correlations between anomalous FC and severity of HAM-D scores.

Results:

We have found a decreased FC in the left medial orbitofrontal gyrus (MOFG) and right marginal gyrus (SMG) in depressive patients compared to controls. There was a negative correlation between abnormal FC in the right SMG and HAM-D scores. We have not found any increase in FC of the DMN in treatment-naive, first-episode of MDD patients.

Conclusions:

Our study provided evidence of a negative correlation between abnormal FC in the DMN and severity of depression symptoms measured by HAM-D in treatment-naive MDD patients. This finding could shed some light on the relevance of DMN for understanding the pathophysiology of cognitive impairment in MDD.
Increased immune activation and signs of neuronal injury in HIV-negative people on preexposure prophylaxis
Authors: Robertson Josefina , Edén Arvid , Nyström Kristina , Hagberg Lars , Yilmaz Aylin , Gostner Johanna M. , Fuchs Dietmar , Nilsson Staffan , Blennow Kaj , Zetterberg Henrik , Gisslén Magnus
Published: June 2021

Objective:

Persistent immune activation in the central nervous system and systemically are common in people living with HIV (PLHIV) despite antiretroviral therapy. It is not known whether this is generated by HIV replication or by other components such as coinfections and lifestyle-related factors.

Design:

The aim of this study was to determine the importance of different factors; it is crucial to find well matched HIV-negative controls. In this context, HIV-negative persons on preexposure prophylaxis (PrEP) may constitute a suitable control group to PLHIV with similar lifestyle-related factors.

Methods:

Cerebrospinal fluid (CSF) and blood were collected from 40 HIV-negative persons on PrEP and 20 controls without PrEP. Biomarkers of immune activation, blood--brain barrier (BBB) integrity and neuronal injury were analysed.

Results:

CSF and serum β2-microglobulin, serum neopterin and CSF neurofilament light protein were higher in persons on PrEP compared with controls. Furthermore, persons on PrEP had higher CSF/plasma albumin ratio, and matrix metalloproteinase-3 concentrations, indicating BBB dysfunction. Of persons on PrEP, 90% were cytomegalovirus (CMV)-positive compared to 65% of the controls. CMV-positive individuals as a group had higher levels of serum β2-microglobulin than CMV-negative individuals (P < 0.05). Drug users had higher serum β2-microglobulin compared to nonusers (P < 0.01).

Conclusion:

HIV-negative persons on PrEP had higher levels of biomarkers for immune activation, BBB impairment and neuronal injury, compared with volunteers without PrEP. Moreover, serum β2-microglobulin was higher in CMV-positive than in CMV-negative individuals and in drug users compared with nonusers. These findings are important to consider when analysing immune activation and CNS injury in PLHIV, and emphasize the importance of appropriate controls.
Xpert HPV as a Screening Tool for Anal Histologic High-Grade Squamous Intraepithelial Lesions in Women Living With HIV
Authors: Ellsworth Grant B. , Stier Elizabeth A. , Chiao Elizabeth Y. , Lensing Shelly Y. , Darragh Teresa , Jay Naomi , Berry-Lawhorn J. Michael , Einstein Mark , Barroso Luis F. , Cranston Ross D. , Levine Rebecca , Guiot Humberto M. , French Audrey L. , Goldstone Stephen E. , Preiser Wolfgang , Claassen Mathilda , Palefsky Joel M. , Wilkin Timothy J. ,   AIDS Malignancy Consortium
Published: June 2021

Background:

Women living with HIV (WLWH) experience high rates of anal cancer. Screening using anal cytology, high-resolution anoscopy (HRA) with biopsies, can histologically diagnose anal cancer precursors called high-grade squamous intraepithelial lesions (HSIL). The low specificity of screening using anal cytology results in HRA referral for many WLWH without HSIL. Screening using high-risk human papillomavirus (HR-HPV) may improve specificity.

Methods:

Two hundred seven WLWH (63% non-Hispanic black) were screened for anal histologic HSIL (hHSIL) using cytology, HRA-guided biopsies, and Xpert HPV. Xpert performance for predicting anal hHSIL was compared with that of cytology. Usng Xpert 5 HPV genotypic results and accompanying cycle thresholds, receiver operator characteristic curve and recursive partitioning analyses were used to create predictive models for hHSIL.

Results:

The performance of Xpert to predict hHSIL was not different from that of cytology with a sensitivity (Sn) of 89% and specificity (Sp) of 49%. Interpretation of Xpert was modified using genotypic results and receiver operator characteristic curve analysis, which produced a screen with an Sn and Sp of 75% and 84% for hHSIL, respectively. Another reinterpretation of Xpert was created using recursive partitioning and cycle thresholds, which predicted hHSIL with an Sn and Sp of 75% and 86%, respectively. The detection of HPV-16 was highly predictive of hHSIL in all analyses. These modified screening tests would reduce HRA referral in this population by almost half compared with anal cytology.

Conclusions:

Xpert HPV is an alternative to anal cytology to screen for anal HSIL and can be optimized to reduce the number of unnecessary HRAs performed in WLWH.
Differences in Cardiac Magnetic Resonance Imaging Markers Between Patients With COVID-19-associated Myocardial Injury and Patients With Clinically Suspected Myocarditis
Authors: Maurus Stephan , Weckbach Ludwig T. , Marschner Constantin , Kunz Wolfgang G. , Ricke Jens , Kazmierczak Philip M. , Bieber Stephanie , Brado Johannes , Kraechan Angelina , Hellmuth Johannes C. , Hausleiter Joerg , Massberg Steffen , Grabmaier Ulrich , Curta Adrian
Published: June 2021

Purpose:

Coronavirus 2019 disease (COVID-19) has been shown to affect the myocardium, resulting in a worse clinical outcome. In this registry study, we aimed to identify differences in cardiac magnetic resonance imaging (CMRI) between COVID-19 and all-cause myocarditis.

Materials and Methods:

We examined CMRI of patients with COVID-19 and elevated high-sensitivity serum troponin levels performed between March 31st and May 5th and compared them to CMRI of patients without SARS-CoV-2 infection with suspected myocarditis in the same time period. For this purpose, we evaluated Lake-Louise Criteria for myocarditis by determining nonischemic myocardial injury via T1-mapping, extracellular volume, late gadolinium enhancement, and myocardial edema (ME) by T2-mapping and fat-saturated T2w imaging (T2Q).

Results:

A total of 15 of 18 (89%) patients with COVID-19 had abnormal findings. The control group consisted of 18 individuals. There were significantly fewer individuals with COVID-19 who had increased T2 (5 vs. 10; P=0.038) and all-cause ME (7 vs. 15; P=0.015); thus, significantly fewer patients with COVID-19 fulfilled Lake-Louise Criteria (6 vs. 17; P<0.001). In contrast, nonischemic myocardial injury was not significantly different. In the COVID-19 group, indexed end-diastolic volume of the left ventricle showed a significant correlation to the extent of abnormal T1 (R
2=0.571; P=0.017) and extracellular volume (R
2=0.605; P=0.013) and absolute T1, T2, and T2Q (R
2=0.644; P=0.005, R
2=0.513; P=0.035 and R
2=0.629; P=0.038, respectively); in the control group, only extracellular volume showed a weak correlation (R
2=0.490; P=0.046).

Conclusions:

Cardiac involvement in COVID-19 seems to show less ME than all-cause myocarditis. Abnormal CMRI markers correlated to left ventricle dilation only in the COVID-19 group. Larger comparative studies are needed to verify our findings.
Rapid Metabolic Recovery of Donor Circulatory Death Liver Graft Using Whole Blood Perfusion: A Pig Study
Authors: Yoshimoto Syuhei , Ohara Masayuki , Torai Shinji , Kasamatsu Hiroo , Ishikawa Jun , Kimura Takahiro , Nadahara Soichi , Kobayashi Eiji
Published: June 2021

Background.

Ex vivo perfusion technology has been actively developed to solve the problem of severe donor shortage. In this study, the ex vivo metabolic characteristics of porcine donation after circulatory death (DCD) liver in short-term perfusion using whole or diluted blood were compared with those of the in vivo transplanted state to evaluate their initial response to resuscitation.

Methods.

The porcine DCD model was constructed by clamping the thoracic aorta. After 60 min of blood flow cessation, retrieved livers were flushed with 500 mL of heparin saline (20 000 IU/L) followed by perfusion with 500 mL of cold histidine-tryptophan-ketoglutarate solution. The liver grafts were immersed in cold histidine-tryptophan-ketoglutarate solution for 60 min. Subsequently, normothermic ex vivo perfusion was performed with 20 000 IU/L of heparin added to the collected blood (whole blood group) or medium mixed with 10% whole blood (dilution group) for 3 h. Blood from the portal vein, the hepatic artery, and infra hepatica inferior vena cava was collected hourly and metabolomic analyses were performed. The other liver graft was heterotopically transplanted as a control (in vivo group). Each experiment was conducted once.

Results.

The guanosine levels demonstrated similar fluctuating trends in the whole blood and in vivo groups. In contrast, the levels increased during the perfusion in the diluted blood group. Fluctuations in choline metabolism demonstrated similar trends in the whole blood and in vivo groups.

Conclusions.

Ex vivo machine perfusion with whole blood over a short time resulted in a metabolic trend similar to that in the in vivo model. Further studies in this regard are warranted to progress in the utilization of DCD organs.
GSER (a Genome Size Estimator using R): a pipeline for quality assessment of sequenced genome libraries through genome size estimation
Authors: Valdebenito-Maturana Braulio , Riadi Gonzalo
Published: June 2021

The first step in any genome research after obtaining the read data is to perform a due quality control of the sequenced reads. In ade novogenome assembly project, the second step is to estimate two important features, the genome size and ‘bestk-mer’, to start the assembly tests with differentde novoassembly software and its parameters. However, the quality control of the sequenced genome libraries as a whole, instead of focusing on the reads only, is frequently overlooked and realized to be important only when the assembly tests did not render the expected results. We have developed GSER, a Genome Size Estimator using R, a pipeline to evaluate the relationship betweenk-mers and genome size, as a means for quality assessment of the sequenced genome libraries. GSER generates a set of charts that allow the analyst to evaluate the library datasets before starting the assembly. The script which runs the pipeline can be downloaded fromhttp://www.mobilomics.org/GSER/downloadsorhttp://github.com/mobilomics/GSER.
Functional analysis of colonization factor antigen I positive enterotoxigenic Escherichia coli identifies genes implicated in survival in water and host colonization
Authors: Abd El Ghany Moataz , Barquist Lars , Clare Simon , Brandt Cordelia , Mayho Matthew , Joffre´ Enrique , Sjöling Åsa , Turner A. Keith , Klena John D. , Kingsley Robert A. , Hill-Cawthorne Grant A. , Dougan Gordon , Pickard Derek
Published: June 2021

Enterotoxigenic

Escherichia coli

(ETEC) expressing the colonization pili CFA/I are common causes of diarrhoeal infections in humans. Here, we use a combination of transposon mutagenesis and transcriptomic analysis to identify genes and pathways that contribute to ETEC persistence in water environments and colonization of a mammalian host. ETEC persisting in water exhibit a distinct RNA expression profile from those growing in richer media. Multiple pathways were identified that contribute to water survival, including lipopolysaccharide biosynthesis and stress response regulons. The analysis also indicated that ETEC growing in vivo in mice encounter a bottleneck driving down the diversity of colonizing ETEC populations.
Modelling the effect of an improved trace and isolate system in the wake of a highly transmissible Covid-19 variant with potential vaccine escape
Authors: Bowie Cam
Published: June 2021

Objective

How helpful would a properly functioning find, test, trace, isolate and support (FTTIS) system be now in the UK with new Covid-19 infections at a low level and half the adult population immunised but with a highly transmissible variant becoming predominant?

Design

a dynamic causal model of Covid-19 supplied with the latest available empirical data is used to assess the impact of a new highly transmissible variant.

Setting

the United Kingdom.

Participants

a population based study.

Interventions

scenarios are used to explore a Covid-19 transmission rate 50% more and twice the current rate with or without a more effective FTTIS system.

Main outcome measures

incidence, death rate and reproductive ratio

Results

a small short third wave of infections occurs which does not occur if FTTIS effectiveness is improved from 25% to 30%.

Conclusion

a modest improvement in FTTIS would prevent a third wave caused by a highly transmissible virus.
TaxoNERD: deep neural models for the recognition of taxonomic entities in the ecological and evolutionary literature
Authors: Le Guillarme Nicolas , Thuiller Wilfried
Published: June 2021

Given the biodiversity crisis, we more than ever need to access information on multiple taxa (e.g. distribution, traits, diet) in the scientific literature to understand, map and predict all-inclusive biodiversity. Tools are needed to automatically extract useful information from the ever-growing corpus of ecological texts and feed this information to open data repositories. A prerequisite is the ability to recognise mentions of taxa in text, a special case of named entity recognition (NER). In recent years, deep learning-based NER systems have become ubiquitous, yielding state-of-the-art results in the general and biomedical domains. However, no such tool is available to ecologists wishing to extract information from the biodiversity literature.

We propose a new tool called TaxoNERD that provides two deep neural network (DNN) models to recognise taxon mentions in ecological documents. To achieve high performance, DNN-based NER models usually need to be trained on a large corpus of manually annotated text. Creating such a gold standard corpus (GSC) is a laborious and costly process, with the result that GSCs in the ecological domain tend to be too small to learn an accurate DNN model from scratch. To address this issue, we leverage existing DNN models pretrained on large biomedical corpora using transfer learning. The performance of our models is evaluated on four GSCs and compared to the most popular taxonomic NER tools.

Our experiments suggest that existing taxonomic NER tools are not suited to the extraction of ecological information from text as they performed poorly on ecologically-oriented corpora, either because they do not take account of the variability of taxon naming practices, or because they do not generalise well to the ecological domain. Conversely, a domain-specific DNN-based tool like TaxoNERD outperformed the other approaches on an ecological information extraction task.

Efforts are needed in order to raise ecological information extraction to the same level of performance as its biomedical counterpart. One promising direction is to leverage the huge corpus of unlabelled ecological texts to learn a language representation model that could benefit downstream tasks. These efforts could be highly beneficial to ecologists on the long term.