bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolutionary History of Alpha Satellite DNA Repeats Dispersed within Human Genome Euchromatin
Authors: Feliciello Isidoro , Pezer Željka , Kordiš Dušan , Bruvo Mađarić Branka , Ugarković Đurđica
Published: October 2020

Major human alpha satellite DNA repeats are preferentially assembled within (peri)centromeric regions but are also dispersed within euchromatin in the form of clustered or short single repeat arrays. To study the evolutionary history of single euchromatic human alpha satellite repeats (ARs), we analyzed their orthologous loci across the primate genomes. The continuous insertion of euchromatic ARs throughout the evolutionary history of primates starting with the ancestors of Simiformes (45–60 Ma) and continuing up to the ancestors of Homo is revealed. Once inserted, the euchromatic ARs were stably transmitted to the descendant species, some exhibiting copy number variation, whereas their sequence divergence followed the species phylogeny. Many euchromatic ARs have sequence characteristics of (peri)centromeric alpha repeats suggesting heterochromatin as a source of dispersed euchromatic ARs. The majority of euchromatic ARs are inserted in the vicinity of other repetitive elements such as L1, Alu, and ERV or are embedded within them. Irrespective of the insertion context, each AR insertion seems to be unique and once inserted, ARs do not seem to be subsequently spread to new genomic locations. In spite of association with (retro)transposable elements, there is no indication that such elements play a role in ARs proliferation. The presence of short duplications at most of ARs insertion sites suggests site-directed recombination between homologous motifs in ARs and in the target genomic sequence, probably mediated by extrachromosomal circular DNA, as a mechanism of spreading within euchromatin.
Worse outcomes after conversion of thoracoscopic lobectomy for lung cancer
Authors: Gabryel Piotr , Piwkowski Cezary , Kasprzyk Mariusz , Zieliński Paweł , Roszak Magdalena , Dyszkiewicz Wojciech
Published: October 2020

OBJECTIVES

Conversion of thoracoscopic lobectomy for lung cancer to thoracotomy can adversely affect short-term outcomes, but the impact on long-term outcomes is unknown. This study aimed to identify the risk factors for conversion and to determine the influence of conversion on the outcomes of lung cancer treatment.

METHODS

This retrospective study included 1002 consecutive patients with lung cancer who underwent thoracoscopic lobectomy between 7 June 1999 and 17 July 2018. The groups of patients with and without conversion were compared in terms of possible risk factors and the short- and long-term outcomes. The survival of patients was analysed by the Kaplan–Meier method.

RESULTS

Conversion was done in 105 patients (10.5%). On multivariable logistic regression analysis, the independent risk factors for conversion were pleural adhesions (P < 0.001) and mediastinal lymph node metastases (P < 0.001). Compared with the non-conversion group, the conversion group had longer chest drainage time (4 vs 3 days, P < 0.001) and hospital stay (8 vs 6 days, P < 0.001); more frequent complications (38.1% vs 27.1%, P = 0.018), including red blood cell transfusion (10.5% vs 2%, P < 0.001) and supraventricular arrhythmia (13.3% vs 7.5%, P = 0.037); and lower 5-year survival rate in patients with stage I lung cancer (70% vs 87%, P = 0.014). Conversion did not increase in-hospital mortality.

CONCLUSIONS

Pleural adhesions and lymph node metastases increased the probability of conversion to thoracotomy. Conversion adversely affected the short-term outcomes of thoracoscopic lobectomy. Long-term outcomes of treatment of non-small-cell lung cancer could be worse in patients after conversion, but definitive conclusions cannot be made in this regard because of the absence of control of selection bias.
Patient-reported outcome measures after mitral valve repair: a comparison between minimally invasive and sternotomy
Authors: Whiteley Jennifer , Toolan Caroline , Shaw Matthew , Perin Giordano , Palmer Kenneth , Al-Rawi Omar , Modi Paul
Published: October 2020

OBJECTIVES

To compare patient-reported outcome measures of minimally invasive (MI) to sternotomy (ST) mitral valve repair.

METHODS

We included all patients undergoing isolated mitral valve surgery via either a right mini-thoracotomy (MI) or ST over a 36-month period. Patients were asked to complete a modified Composite Physical Function questionnaire. Intraoperative and postoperative outcomes, and patient-reported outcome measures were compared between 2 propensity-matched groups (n = 47/group), assessing 3 domains: ‘Recovery Time’, ‘Postoperative Pain’ (at day 2 and 1, 3, 6 and 12 weeks) and ‘Treatment Satisfaction’. Composite scores for each domain were subsequently constructed and multivariable analysis was used to determine whether surgical approach was associated with domain scores.

RESULTS

The response rate was 79%. There was no mortality in either group. In the matched groups, operative times were longer in the MI group (P < 0.001), but postoperative outcomes were similar. Composite scores for Recovery Time [ST 51.7 (31.8–62.1) vs MI 61.7 (43.1–73.9), P = 0.03] and Pain [ST 65.7 (40.1–83.1) vs MI 79.1 (65.5–89.5), P = 0.02] significantly favoured the MI group. Scores in the Treatment Satisfaction domain were high for both surgical approaches [ST 100 (82.5–100) vs MI 100 (95.0–100), P = 0.15]. The strongest independent predictor of both faster recovery parameter estimate 12.0 [95% confidence interval (CI) 5.7–18.3, P < 0.001] and less pain parameter estimate 7.6 (95% CI 0.7–14.5, P = 0.03) was MI surgery.

CONCLUSIONS

MI surgery was associated with faster recovery and less pain; treatment satisfaction and safety profiles were similar.
Maternal Epstein-Barr Virus-Specific Antibodies and Risk of Infection in Ugandan Infants
Authors: Minab Rana , Bu Wei , Nguyen Hanh , Wall Abigail , Sholukh Anton M , Huang Meei-Li , Ortego Michael , Krantz Elizabeth M , Irvine Michael , Casper Corey , Orem Jackson , McGuire Andrew T , Cohen Jeffrey I , Gantt Soren
Published: October 2020

Background

Epstein-Barr virus (EBV) infection is a major cause of malignancy worldwide. Maternal antibody is thought to prevent EBV infection because it is uncommon in early infancy. Maternal HIV infection is associated with an increased incidence of EBV infection in exposed infants, which we hypothesized results from impaired transfer of EBV-neutralizing maternal antibodies.

Methods

Among Ugandan infants followed for EBV acquisition from birth, we measured antibody binding to EBV glycoproteins (gp350, gH/gL) involved in B-cell and epithelial-cell entry, as well as viral neutralization and antibody-dependent cellular cytotoxicity (ADCC) activity in plasma samples prior to infection. These serologic data were analyzed for differences between HIV-exposed uninfected (HEU) and HIV-unexposed (HUU) infants, and for associations with incident infant EBV infection.

Results

HEU infants had significantly higher titers than HUU infants for all EBV-binding and neutralizing antibodies measured (P < .01) but not ADCC activity, which was similar between groups. No antibody measure was associated with a decreased risk of EBV acquisition in the cohort.

Conclusions

Our findings indicate that in this cohort maternal antibody did not protect infants against EBV infection through viral neutralization. The identification of protective nonneutralizing antibody functions would be invaluable for the development of an EBV vaccine.
HIV-1 Transcription but Not Intact Provirus Levels are Associated With Systemic Inflammation
Authors: Olson Alex , Coote Carolyn , Snyder-Cappione Jennifer E , Lin Nina , Sagar Manish
Published: October 2020

Individuals infected with human immunodeficiency virus (HIV) 1 have increased inflammation, which has been associated with age-associated diseases. Plasma markers, cell-associated virus levels, and ability to stimulate RNA transcription in latently infected cell lines was examined in younger and older HIV-1–infected individuals with suppressed virus. Cell-associated RNA, but not intact provirus level, had positive correlation with plasma D-dimer levels. Compared with the younger group, the older group had higher D-dimer levels and a trend toward more cell-associated RNA but similar levels of intact proviruses. Even though all measured inflammatory markers were relatively higher in the older group, this greater inflammation did not induce more HIV-1 transcription in latently infected cell lines. Inflammation and HIV-1 RNA expression increase with age despite similar levels of intact infectious HIV DNA. While plasma inflammation is correlated with HIV-1 RNA expression in peripheral blood mononuclear cells, it does not induce HIV-1 transcription in latently infected cell lines.
Associations Between Genetically Predicted Protein Levels and COVID-19 Severity
Authors: Zhu Jingjing , Wu Chong , Wu Lang
Published: October 2020

It is critical to identify potential causal targets for SARS-CoV-2, which may guide drug repurposing options. We assessed the associations between genetically predicted protein levels and COVID-19 severity. Leveraging data from the COVID-19 Host Genetics Initiative comparing 6492 hospitalized COVID-19 patients and 1 012 809 controls, we identified 18 proteins with genetically predicted levels to be associated with COVID-19 severity at a false discovery rate of <0.05, including 12 that showed an association even after Bonferroni correction. Of the 18 proteins, 6 showed positive associations and 12 showed inverse associations. In conclusion, we identified 18 candidate proteins for COVID-19 severity.
Sharing patient-generated data with healthcare providers: findings from a 2019 national survey
Authors: Turner Kea , Jo Ara , Wei Grace , Tabriz Amir Alishahi , Clary Alecia , Jim Heather S L
Published: October 2020

Objective

Our study estimates the prevalence and predictors of wearable device adoption and data sharing with healthcare providers in a nationally representative sample.

Materials and Methods

Data were obtained from the 2019 Health Information National Trend Survey. We conducted multivariable logistic regression to examine predictors of device adoption and data sharing.

Results

The sample contained 4159 individuals, 29.9% of whom had adopted a wearable device in 2019. Among adopters, 46.3% had shared data with their provider. Individuals with diabetes (odds ratio [OR], 2.39; 95% CI, 1.66–3.45; P < .0001), hypertension (OR, 2.80; 95% CI, 2.12–3.70; P < .0001), and multiple chronic conditions (OR, 1.55; 95% CI, 1.03–2.32; P < .0001) had significantly higher odds of wearable device adoption. Individuals with a usual source of care (OR, 2.44; 95% CI, 1.95–3.04; P < .0001), diabetes (OR, 1.66; 95% CI, 1.32–2.08; P < .0001), and hypertension (OR, 1.78; 95% CI, 1.44–2.20; P < .0001) had significantly higher odds of sharing data with providers.

Discussion

A third of individuals adopted a wearable medical device and nearly 50% of individuals who owned a device shared data with a provider in 2019. Patients with certain conditions, such as diabetes and hypertension, were more likely to adopt devices and share data with providers. Social determinants of health, such as income and usual source of care, negatively affected wearable device adoption and data sharing, similarly to other consumer health technologies.

Conclusions

Wearable device adoption and data sharing with providers may be more common than prior studies have reported; however, digital disparities were noted. Studies are needed that test implementation strategies to expand wearable device use and data sharing into care delivery.
Chemical composition and in vitro fermentation characteristics of ancient grains using canine fecal inoculum
Authors: Traughber Zachary T , He Fei , Hoke Jolene M , Davenport Gary M , de Godoy Maria R C
Published: October 2020

Human interest in ancient grains replacing traditional carbohydrate sources has reached the pet food market; however, chemical composition of these grains and their digestive properties in the canine model, specifically the fermentative characteristics, have not been established. Five ancient grain varieties were analyzed: amaranth (AM), white proso millet (WPM), oat groats (OG), quinoa (QU), and red millet (RM). Cellulose (CEL) was used as a negative control, and beet pulp (BP) was used as a positive control. Substrates were analyzed for macronutrient composition as well as free and hydrolyzed sugar profiles in addition to their in vitro fermentative characteristics. Substrates were allocated into 2 sets to allow for quantification of pH, short-chain fatty acids, and branched-chain fatty acids, as well as gas volume and composition. Samples were digested for 6 and 18 h with pepsin and pancreatin, respectively, prior to inoculation with fecal bacteria for 0, 3, 6, 9, or 12 h. Detectable levels of cereal β-glucans were observed solely in OG (3.5%), with all other substrate containing <0.35% cereal β-glucans. All test substrates had fairly similar macronutrient and starch profiles with the exception of RM that contained the highest resistant starch content (2.4%), with all other test substrates containing <0.5% resistant starch. However, the analyzed pseudocereals, AM and QU, had the highest concentrations of free glucose while the minor cereal grains, WPM, OG, and RM, contained the highest concentrations of hydrolyzed glucose. All test substrates had propionate production values similar or greater than BP after 3, 6, 9, and 12 h of fermentation, and similar or greater butyrate production values than BP after 6, 9, and 12 h. All substrates had greater (P < 0.05) changes in pH than CEL after 6, 9, and 12 h, with AM, WPM, OG, and RM having greater (P < 0.05) changes in pH than BP after 9 and 12 h. These data suggest select ancient grains have similar fermentation characteristics as BP, a moderately fermentable fiber considered the gold standard in terms of fiber sources in the pet food market today, and that OG and AM may be more fermentable during longer fermentation periods.
Confronting Colonial Amnesia
Authors: Stahn Carsten
Published: October 2020

Colonial injustice has suffered from the effects of amnesia in international law. Law has served as an instrument to justify injustice in the past and to silence its contemporary effects. The rise of the ‘Black Lives Matter’ movement, TWAIL scholarship and the current debate on racism, slavery and return of cultural colonial objects illustrate the ongoing effects of colonialism. Some seemingly neutral principles and institutions of international law contribute to colonial amnesia. This contribution argues that it is time to revisit this status quo. It draws on emerging case law, scholarship and practices to identify news ways of relational engagement with the past. It suggests a re-reading of three fundamental dimensions of post-colonial engagement with colonial injustice: intertemporality, legal subjectivity and the approach towards cultural colonial objects. It claims that international criminal law has only a modest role in relation to colonial crimes. However, some wider lessons and methods from the field of transitional justice may help to mitigate contemporary dilemmas and contribute to a more post-colonial international law.
Judges in the Lab: No Precedent Effects, No Common/Civil Law Differences
Authors: Spamann Holger , Klöhn Lars , Jamin Christophe , Khanna Vikramaditya , Liu John Zhuang , Mamidi Pavan , Morell Alexander , Reidel Ivan
Published: October 2020

In our lab, 299 real judges from seven major jurisdictions (Argentina, Brazil, China, France, Germany, India, and USA) spend up to fifty-five minutes to judge an international criminal appeals case and determine the appropriate prison sentence. The lab computer (i) logs their use of the documents (briefs, statement of facts, trial judgment, statute, precedent) and (ii) randomly assigns each judge (a) a horizontal precedent disfavoring, favoring, or strongly favoring defendant, (b) a sympathetic or an unsympathetic defendant, and (c) a short, medium, or long sentence anchor. Document use and written reasons differ between countries but not between common and civil law. Precedent effect is barely detectable and estimated to be less, and bounded to be not much greater than, that of legally irrelevant defendant attributes and sentence anchors.
3 per cent-accurate predictions for the clustering of dark matter, haloes, and subhaloes, over a wide range of cosmologies and scales
Authors: Contreras S , Angulo R E , Zennaro M , Aricò G , Pellejero-Ibañez M
Published: October 2020

Predicting the spatial distribution of objects as a function of cosmology is an essential ingredient for the exploitation of future galaxy surveys. In this paper, we show that a specially designed suite of gravity-only simulations together with cosmology-rescaling algorithms can provide the clustering of dark matter, haloes, and subhaloes with high precision. Specifically, with only three N-body simulations, we obtain the power spectrum of dark matter at z = 0 and 1 to better than 3 per cent precision for essentially all currently viable values of eight cosmological parameters, including massive neutrinos and dynamical dark energy, and over the whole range of scales explored, 0.03 < $k/{h}^{-1}\, {\rm Mpc}^{-1}$ < 5. This precision holds at the same level for mass-selected haloes and for subhaloes selected according to their peak maximum circular velocity. As an initial application of these predictions, we successfully constrain Ωm, σ8, and the scatter in subhalo-abundance-matching employing the projected correlation function of mock SDSS galaxies.
Measuring the integrated Sachs–Wolfe effect from the low-density regions of the universe
Authors: Dong Fuyu , Yu Yu , Zhang Jun , Yang Xiaohu , Zhang Pengjie
Published: October 2020

The integrated Sachs–Wolfe (ISW) effect is caused by the decay of cosmological gravitational potential and is therefore a unique probe of dark energy. However, its robust detection is still problematic. Various tensions between different data sets, different large-scale structure (LSS) tracers, and between data and the ΛCDM theory prediction exist. We propose a novel method of ISW measurement by cross-correlating cosmic microwave background (CMB) and the LSS traced by ‘low-density position’ (LDP). It isolates the ISW effect generated by low-density regions of the universe but insensitive to selection effects associated with voids. We apply it to the DR8 galaxy catalogue of the DESI Legacy imaging surveys and obtain the LDPs at z ≤ 0.6 over ∼20 000 deg2 sky coverage. We then cross-correlate with the Planck temperature map and detect the ISW effect at 3.2σ. We further compare the measurement with numerical simulations of the concordance ΛCDM cosmology and find the ISW amplitude parameter AISW = 1.14 ± 0.38 when we adopt an LDP definition radius $R_\mathrm{ s}=3^{^{\prime }}$, fully consistent with the prediction of the standard ΛCDM cosmology (AISW = 1). This agreement with ΛCDM cosmology holds for all the galaxy samples and Rs that we have investigated. Furthermore, the S/N is comparable to that of galaxy ISW measurement. These results demonstrate the LDP method as a competitive alternative to existing ISW measurement methods and provide independent checks to existing tensions.
Detection of millihertz quasi-periodic oscillations in the X-Ray binary 1RXS J180408.9−342058
Authors: Tse Kaho , Galloway Duncan K , Chou Yi , Heger Alexander , Hsieh Hung-En
Published: October 2020

Millihertz quasi-periodic oscillations (mHz QPOs) observed in neutron-star low-mass X-ray binaries (NS LMXBs) are generally explained as marginally stable thermonuclear burning on the neutron star surface. We report the discovery of mHz QPOs in an XMM–Newton observation of the transient 1RXS J180408.9−342058, during a regular bursting phase of its 2015 outburst. We found significant periodic signals in the March observation, with frequencies in the range 5–8 $\, \mathrm{mHz}$, superimposed on a strong ∼1/f power-law noise continuum. Neither the QPO signals nor the power-law noise were present during the April observation, which exhibited a 2.5 × higher luminosity and had correspondingly more frequent bursts. When present, the QPO signal power decreases during bursts and disappears afterwards, similar to the behaviour in other sources. 1RXS J180408.9−342058 is the eighth source known to date that exhibits such QPOs driven by thermonuclear burning. We examine the range of properties of the QPO signals in different sources. Whereas the observed oscillation profile is similar to that predicted by numerical models, the amplitudes are significantly higher, challenging their explanation as originating from marginally stable burning.
Constraining photoionization models with a reprojected optical diagnostic diagram
Authors: Ji Xihan , Yan Renbin
Published: October 2020

Optical diagnostic diagrams are powerful tools to separate different ionizing sources in galaxies. However, the model-constraining power of the most widely used diagrams is very limited and challenging to visualize. In addition, there have always been classification inconsistencies between diagrams based on different line ratios, and ambiguities between regions purely ionized by active galactic nuclei (AGNs) and composite regions. We present a simple reprojection of the 3D line ratio space composed of [N ii]λ6583/H α, [S ii]λλ6716, 6731/H α, and [O iii]λ5007/H β, which reveals its model-constraining power and removes the ambiguity for the true composite objects. It highlights the discrepancy between many theoretical models and the data loci. With this reprojection, we can put strong constraints on the photoionization models and the secondary nitrogen abundance prescription. We find that a single nitrogen prescription cannot fit both the star-forming locus and AGN locus simultaneously, with the latter requiring higher N/O ratios. The true composite regions stand separately from both models. We can compute the fractional AGN contributions for the composite regions, and define demarcations with specific upper limits on contamination from AGN or star formation. When the discrepancy about nitrogen prescriptions gets resolved in the future, it would also be possible to make robust metallicity measurements for composite regions and AGNs.
COG database update: focus on microbial diversity, model organisms, and widespread pathogens
Authors: Galperin Michael Y , Wolf Yuri I , Makarova Kira S , Vera Alvarez Roberto , Landsman David , Koonin Eugene V
Published: October 2020

The Clusters of Orthologous Genes (COG) database, also referred to as the Clusters of Orthologous Groups of proteins, was created in 1997 and went through several rounds of updates, most recently, in 2014. The current update, available at https://www.ncbi.nlm.nih.gov/research/COG, substantially expands the scope of the database to include complete genomes of 1187 bacteria and 122 archaea, typically, with a single genome per genus. In addition, the current version of the COGs includes the following new features: (i) the recently deprecated NCBI’s gene index (gi) numbers for the encoded proteins are replaced with stable RefSeq or GenBank\ENA\DDBJ coding sequence (CDS) accession numbers; (ii) COG annotations are updated for >200 newly characterized protein families with corresponding references and PDB links, where available; (iii) lists of COGs grouped by pathways and functional systems are added; (iv) 266 new COGs for proteins involved in CRISPR-Cas immunity, sporulation in Firmicutes and photosynthesis in cyanobacteria are included; and (v) the database is made available as a web page, in addition to FTP. The current release includes 4877 COGs. Future plans include further expansion of the COG collection by adding archaeal COGs (arCOGs), splitting the COGs containing multiple paralogs, and continued refinement of COG annotations.
Stretching DNA origami: effect of nicks and Holliday junctions on the axial stiffness
Authors: Jung Wei-Hung , Chen Enze , Veneziano Remi , Gaitanaros Stavros , Chen Yun
Published: October 2020

The axial stiffness of DNA origami is determined as a function of key nanostructural characteristics. Different constructs of two-helix nanobeams with specified densities of nicks and Holliday junctions are synthesized and stretched by fluid flow. Implementing single particle tracking to extract force–displacement curves enables the measurement of DNA origami stiffness values at the enthalpic elasticity regime, i.e. for forces larger than 15 pN. Comparisons between ligated and nicked helices show that the latter exhibit nearly a two-fold decrease in axial stiffness. Numerical models that treat the DNA helices as elastic rods are used to evaluate the local loss of stiffness at the locations of nicks and Holliday junctions. It is shown that the models reproduce the experimental data accurately, indicating that both of these design characteristics yield a local stiffness two orders of magnitude smaller than the corresponding value of the intact double-helix. This local degradation in turn leads to a macroscopic loss of stiffness that is evaluated numerically for multi-helix DNA bundles.
Europe PMC in 2020
Authors: Ferguson Christine , Araújo Dayane , Faulk Lynne , Gou Yuci , Hamelers Audrey , Huang Zhan , Ide-Smith Michele , Levchenko Maria , Marinos Nikos , Nambiar Rakesh , Nassar Maaly , Parkin Michael , Pi Xingjun , Rahman Faisal , Rogers Frances , Roochun Yogmatee , Saha Shyamasree , Selim Mohamed , Shafique Zunaira , Sharma Shrey , Stephenson David , Talo' Francesco , Thouvenin Arthur , Tirunagari Santosh , Vartak Vid , Venkatesan Aravind , Yang Xiao , McEntyre Johanna
Published: October 2020

Europe PMC (https://europepmc.org) is a database of research articles, including peer reviewed full text articles and abstracts, and preprints - all freely available for use via website, APIs and bulk download. This article outlines new developments since 2017 where work has focussed on three key areas: (i) Europe PMC has added to its core content to include life science preprint abstracts and a special collection of full text of COVID-19-related preprints. Europe PMC is unique as an aggregator of biomedical preprints alongside peer-reviewed articles, with over 180 000 preprints available to search. (ii) Europe PMC has significantly expanded its links to content related to the publications, such as links to Unpaywall, providing wider access to full text, preprint peer-review platforms, all major curated data resources in the life sciences, and experimental protocols. The redesigned Europe PMC website features the PubMed abstract and corresponding PMC full text merged into one article page; there is more evident and user-friendly navigation within articles and to related content, plus a figure browse feature. (iii) The expanded annotations platform offers ∼1.3 billion text mined biological terms and concepts sourced from 10 providers and over 40 global data resources.
Exposure to intimate partner violence and children’s dynamic skill accumulation: evidence from a UK longitudinal study
Authors: Anderberg Dan , Moroni Gloria
Published: October 2020

Children are increasingly recognized as secondary victims of intimate partner violence. This paper uses a unique UK longitudinal child development survey to study the relationship between verbal and physical abuse experienced by mothers and children’s development up to the age of seven. Estimating production functions for cognitive, social, and socio-emotional skills, we find that exposure during pre-school years has a quantitatively important negative effect on socio-emotional skills among toddlers and negatively affects cognitive and social skills after the age of three. The estimated impact on cognitive development is consistent with measures of cognitive skills based on school-based tests.
In Planta Monitoring of Cold-Responsive Promoter Activity Reveals a Distinctive Photoperiodic Response in Cold Acclimation
Authors: Tominaga Yoko , Suzuki Kensaku , Uemura Matsuo , Kawamura Yukio
Published: October 2020

Plant cold acclimation involves complicated pathways that integrate signals from temperature changes and light conditions. To understand plant responses to environmental signals in detail, molecular events that are regulated by temperature and light must be investigated at the whole-plant level in a nondestructive way. Using the promoter of COR15A connected to the luciferase reporter gene as a cold-responsive indicator, we developed an in planta monitoring system for gene expression under controlled temperature and photoperiod conditions. COR15A promoter activity was intensified by day–night cycles at 2�C, while its induction was abruptly suppressed in the dark at 8�C or higher, indicating a difference in responsiveness to photocycle between these two acclimation conditions. Freeze–thawing tests of whole plants proved that lower acclimation temperature resulted in higher tolerance to freezing, consistent with the temperature-dependent induction of COR15A. Inhibition of photosynthetic electron transport by 3-(3,4-dichlorophenyl)-1,1-dimethylurea eliminated the responsiveness to the day–night cycles at 2�C, indicating a possibility that the photosynthetic redox and/or the accumulation of photosynthates modulate COR15A responsiveness to photoperiod during cold acclimation, in addition to the well-known regulation by CBF (C-repeat binding factor) genes. These findings indicate that the cold-responsive promoter is regulated by distinctive mechanisms dependent on temperature and simultaneously affected by photocycle and photosynthesis.
Early Physical Therapist Interventions for Patients With COVID-19 in the Acute Care Hospital: A Case Report Series
Authors: Eggmann Sabrina , Kindler Angela , Perren Andrea , Ott Natalie , Johannes Frauke , Vollenweider Rahel , Balma Théophile , Bennett Claire , Silva Ivo Neto , Jakob Stephan M
Published: October 2020

Objective

The aim of this case series was to describe the experience of Swiss physical therapists in the treatment of patients with COVID-19 during their acute care hospital stay and to discuss challenges and potential strategies in the clinical management of these patients.

Methods

We report 11 cases of patients with COVID-19 from 5 Swiss hospitals that illustrate the various indications for physical therapy, clinical challenges, potential treatment methods, and short-term response to treatment.

Results

Physical therapists actively treated patients with COVID-19 on wards and in the intensive care unit. Interventions ranged from patient education, to prone positioning, to early mobilization and respiratory therapy. Patients were often unstable with quick exacerbation of symptoms and a slow and fluctuant recovery. Additionally, many patients who were critically ill developed severe weakness, postextubation dysphagia, weaning failure, or presented with anxiety or delirium. In this setting, physical therapy was challenging and required specialized and individualized therapeutic strategies. Most patients adopted the proposed treatment strategies, and lung function and physical strength improved over time.

Conclusion

Physical therapists clearly have a role in the COVID-19 pandemic. Based on our experience in Switzerland, we recommend that physical therapists routinely screen and assess patients for respiratory symptoms and exercise tolerance on acute wards. Treatment of patients who are critically ill should start as soon as possible to limit further sequelae. More research is needed for awake prone positioning and early breathing exercises as well as post-COVID rehabilitation.

Impact

To date, there are few data on the physical therapist management of patients with COVID-19. This article is among the first to describe the role of physical therapists in the complex pandemic environment and to describe the potential treatment strategies for countering the various challenges in the treatment of these patients.
A neutrophil signature is strongly associated with increased cardiovascular risk in gout
Authors: Vedder Daisy , Gerritsen Martijn , Nurmohamed Michael T , van Vollenhoven Ronald F , Lood Christian
Published: October 2020

Objective

To investigate the association between neutrophil activation and cardiovascular risk in gout patients. We hypothesize that neutrophil activation mediates inflammation and therefore takes part in atherogenesis in gout patients.

Method

Patient data were collected from 75 consecutive gout patients participating in the Reade gout cohort Amsterdam. Levels of neutrophil extracellular traps (NETs) and neutrophil activation (calprotectin and peroxidase activity) were analysed by ELISA and fluorimetry in plasma and compared with healthy controls. Markers of neutrophil activation were related to clinical markers of cardiovascular risk, including BMI, smoking, blood pressure, lipid profile and 10 year risk of cardiovascular mortality (EU-SCORE).

Results

Increased levels of NETs were found in gout patients, although increased levels were not associated with cardiovascular risk. However, markers of neutrophil activation, including peroxidase activity correlated with waist:hip ratio (β = 0.33, P < 0.001), cholesterol ratio (β = 0.46, P < 0.005) and triglycerides (β = 0.60, P < 0.001) as well as the 10 year risk of cardiovascular mortality (β = 0.44, P = 0.001). Calprotectin levels were elevated in hypertension (P = 0.005) and diabetes (P = 0.02). Finally, gout patients with high levels of both peroxidase and calprotectin (‘neutrophil activation signature’) had a markedly elevated cardiovascular risk score (P = 0.001), with 68% of the patients having high cardiovascular risk (odds ratio 2.9, P = 0.03).

Conclusion

We demonstrated elevated levels of neutrophil activation markers, MPO and calprotectin in gout patients as compared with healthy controls. Of note, neutrophil activation markers were associated with several risk factors for cardiovascular disease, including hyperlipidaemia, hypertension and diabetes. Finally, the presence of a neutrophil activation signature was strongly associated with an increased 10 year risk of cardiovascular mortality. Further studies are needed to determine whether gout-specific factors and/or cardiovascular risk factors contribute to the elevated neutrophil activation observed in these patients.
EXPOSURE TO EXTREMELY LOW-FREQUENCY MAGNETIC FIELDS IN LOW- AND MIDDLE-INCOME COUNTRIES: AN OVERVIEW
Authors: Baaken Dan , Wollschläger Daniel , Samaras Theodoros , Schüz Joachim , Deltour Isabelle
Published: October 2020

To compare extremely low-frequency magnetic field (ELF-MF) exposure in the general population in low- and middle-income countries (LMICs) with high-income countries (HIC), we carried out a systematic literature search resulting in 1483 potentially eligible articles; however, only 25 studies could be included in the qualitative synthesis. Studies showed large heterogeneity in design, exposure environment and exposure assessment. Exposure assessed by outdoor spot measurements ranged from 0.03 to 4μT. Average exposure by indoor spot measurements in homes ranged from 0.02 to 0.4μT. Proportions of homes exposed to a threshold of ≥0.3μT were many times higher in LMICs compared to HIC. Based on the limited data available, exposure to ELF-MF in LMICs appeared higher than in HIC, but a direct comparison is hampered by a lack of representative and systematic monitoring studies. Representative measurement studies on residential exposure to ELF-MF are needed in LMICs together with better standardisation in the reporting.
Pancreatic Ductal Adenocarcinoma Tumor Suppressors Rgs8–16
Authors: Choudhuri Shreoshi Pal , Wilkie Thomas Martin
Published: October 2020

Introduction

G protein‐coupled receptors (GPCRs) are the largest family of targets for approved drugs, but rarely exploited in cancer treatment. Kras oncogenic mutations (e.g. KrasG12D) are found in over 90% of human pancreatic ductal adenocarcinoma (PDA) and can be activated by protein kinases and GPCR signaling. Regulator of G protein signaling (Rgs) proteins modulate GPCR signaling by accelerating the GTPase activity of Gq‐ and Gi‐class alpha subunits. Rgs genes are often upregulated in primary cancers. We showed that Rgs8::GFP and Rgs16::GFP reporter genes are highly expressed in an oncogenic Kras (KrasG12D)‐dependent PDA model at initiation and throughout progression. Furthermore, activating alleles of Gq that are resistant to Rgs inhibition are found in benign precursors of PDA in humans. By contrast, Rgs16 down‐regulation is associated with increased lymph node metastasis in PDA. Here we test our hypothesis that Rgs8–16 deletion will accelerate PDA initiation, progression, and metastasis.

Methods

We made the Rgs8–16 double knockout (dKO) and crossed it into pancreas‐specific KrasG12D (KC) mutant mice (termed KCR8–16). Caerulein (analog of the Gq‐coupled GPCR agonist CCK) induced acute and chronic pancreatitis, PDA initiation and progression. Response to caerulein was compared in KC and KCR8–16 mice using physiologic, histologic and immunologic assays.

Results

Caerulein induced Rgs16 expression in acute pancreatitis within 2 days in Rgs16::GFP transgenic mice, and they recovered normally within 7days. Although deletion of Rgs8–16 did not cause PDA initiation, Rgs8–16 dKO mice took longer to recover from caerulein‐induced pancreatitis than normal mice. PDA initiation and progression was greatly accelerated in KCR8–16 compared to KC mice. Caerulein treatment caused the entire pancreas to transform to aggressive PDA within 7 days in KCR8–16 mice, whereas KC pancreata showed milder acinar‐to‐ducal metaplasia and differentiated, early stage PDA. Cell proliferation and epithelial‐to‐mesenchymal transmission (EMT) was amplified in KCR8–16 mice, with increased Ki67 and EMT marker expression, suggesting a greater potential for metastasis.

Discussion

We find Rgs8 and Rgs16 are tumor suppressors in PDA initiation and progression. Little is known about GPCR expression and function in PDA. Few GPCR‐targeted therapeutics exist for PDA. The KCR8–16 and Rgs16::GFP mice we developed provide excellent models for screening ligands to identify GPCRs involved in PDA initiation and progression. KCR8–16 hypersensitivity to Gq‐coupled ligands provides a model for rapid in vivo validation of PDA therapeutics.

Support or Funding Information

This work supported by NCI CA161624 and UT Southwestern Cancer Center Pilot Project Award to RAB and TMW

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Contraception, Abortion and More: Understanding Health Disparities for LBGTQ Patients in their Own Words [10G]
Authors: Hoffmann Jennifer , Bergin Ashlee
Published: October 2020

INTRODUCTION:

Lesbian, Gay, Bisexual, Transgender and Queer (LGBTQ) women experience numerous obstacles to accessing equitable reproductive healthcare. These barriers lead to known disparities in health outcomes between LGBTQ women and their straight counterparts. Despite these disparities, few published research studies specifically explore the health experiences of LGBTQ women in regards to contraception, abortion and obstetric care. This qualitative, grounded theory study seeks to address that gap.

METHODS:

Purposive sampling was used to recruit English speaking, LGBTQ individuals aged 18- to 45-year-old living in Kentucky. Participants (n = 10) were recruited and in-depth audio recorded interviews were performed. The transcriptions were then uploaded to Atlas.ti and analyzed using the Constant Comparative Method to identify relevant themes.

RESULTS:

Six themes were identified, including: identifying LGBTQ friendly practices, establishing trust and rapport, covert and overt provider bias, provider ignorance of LGBTQ health-specific issues, patient education and counseling, and additional barriers for transgender patients. These themes were sorted into a conceptual paradigm that represents three phases of the health care experience relating to care within the scope of Ob/Gyn: Pre-visit inquiry, direct provider interaction, and post-provider effects.

CONCLUSION:

Participants identified numerous barriers for LGBTQ patients seeking care within an Ob/Gyn practice. These barriers included a uniform difficulty with identifying receptive and adequately trained providers, perceived covert and overt bias, as well as difficulty establishing trust and rapport. Finally, while all LGBTQ women experienced some aspect of bias, the difficulties faced by transgender patients in accessing reproductive health care were notably more challenging.
Vaginal CO2 Laser Versus Topical Estriol Treatment for Vaginal Atrophy in Postmenopausal Women: 1-Year Follow-up [20P]
Authors: Cruz Vera , Wajsfeld Tali , Steiner Marcelo , Pompei Luciano , Fernandes Cesar
Published: October 2020

INTRODUCTION:

Vulvovaginal atrophy (VVA) affects up to 50% of postmenopausal women with great impact on quality of life and sexual function. Vaginal CO2 laser is a promising therapeutic, but its long-term efficacy is unknown.

METHODS:

45 postmenopausal women were randomized in 3 groups on a double-blind, placebo-controlled study: L group (vaginal fractional CO2 laser), E group (topical Estriol), or LE group (combination of both). Assessments at 12 weeks (week 20) and 1-year after treatment completion were conducted using Vaginal Health Index (VHI), Visual Analog Scale for VVA symptoms (dyspareunia, dryness, and burning), Female Sexual Function Index (FSFI), and maturation value of Meisels.

RESULTS:

Of the 45 women, 6 were lost to follow-up at 1-year. No adverse effects were reported throughout the study. The average VHI score was significantly higher at week 20 in all study arms. VHI scores and symptoms of dyspareunia, dryness and burning were similar at week 20 and 1-year (p=0.59) in the L group. Both estrogen treated groups with and without combined laser had significant lower VHI scores (p=0.02 and p=0.0001, respectively) and worsening symptoms of hydration and burning when compared to week 20. Patient perception of symptoms on FSFI was similar in all study arms at week 20 and 1-year (p=0.5).

CONCLUSION:

Improvement of VVA symptoms persisted 1-year after fractional CO2 treatment. Outcomes of Estriol therapy alone or associated with laser were not maintained 1-year after treatment, although estriol remains a safe treatment option for VVA symptoms.
The Impact of Intrapartum Uterine Rupture on Perinatal Outcomes [21T]
Authors: Yule Casey S. , Happe Sarah K. , McIntire Donald D. , Wells C. Edward
Published: October 2020

INTRODUCTION:

To describe maternal and neonatal outcomes of pregnancies complicated by uterine rupture at a single institution.

METHODS:

Retrospective review of pregnancies complicated by uterine rupture from 2009-2016. Uterine rupture was defined as a uterine defect involving the entire thickness of the uterine wall. Maternal and neonatal outcomes were analyzed. If cesarean delivery was performed, time was calculated from decision to perform surgery to skin incision. Standard statistical analysis was performed.

RESULTS:

There were 40 cases of uterine rupture with an overall rate of 4.9 ruptures per 10,000 births. The rupture rate did not change over time (P=0.23). Of primary uterine ruptures, 93% received uterine stimulants for labor induction or augmentation. Compared with primary ruptures, secondary ruptures occurred at an earlier gestational age (P<0.001) and were associated with less blood loss (P=0.024). Uterine rupture resulted in the need for transfusion in 55%, hysterectomy in 27%, and maternal admission to the intensive care unit in 17%. Emergent delivery for maternal or fetal indications occurred with a decision to incision time averaging 10 minutes. Catastrophic neonatal outcomes were observed despite decision to incision times averaging 19 minutes for infants with acidemia, 17 minutes for infants with hypoxic ischemic encephalopathy, and 13 minutes for cases resulting in neonatal death.

CONCLUSION:

Uterine rupture is a serious complication for women and their infants undergoing induction or augmentation of labor and for those pursuing a trial of labor after a cesarean delivery. Despite expedient decision to incision times, intrapartum uterine rupture may result in catastrophic perinatal outcomes.
Pregnancies Lost and Found: Improving Follow Up for Patients With Pregnancies of Unknown Location [4R]
Authors: Latteman Lindsey , Hosein Safiyah , Garber Laurel M. , Leung Andrea , Paoletti Andrew , Gurney Elizabeth Price
Published: October 2020

INTRODUCTION:

Patients with pregnancy of unknown location (PUL) are followed with serial beta human chorionic gonadotropin (bhCG) levels until definitive diagnosis. Historically, our institution's OB/GYN residents maintained an ad hoc database of PUL patients, separate from the electronic medical record (EMR) and patients had poor follow up compliance. We hypothesized that by integrating PUL management into the EMR, standardizing follow-up procedures, and providing consistent faculty oversight, we could increase patient compliance with follow-up.

METHODS:

Changes to PUL management were undertaken through a Quality Improvement (QI) project, including: templated EMR notes, standardized patient contact and follow-up algorithms, and twice-weekly faculty supervision. We compared patient compliance with follow-up and EMR documentation pre- and post-QI intervention. 91 subjects were required per group to detect the predicted difference in compliance of 20% to 40%.

RESULTS:

177 records were reviewed (92 pre-QI; 86 post-QI). Demographics and admitting diagnoses were similar between groups. Post-QI more patients with PUL completed follow up (67.4% vs. 53.2%, p=0.047); more patients had EMR documentation of any follow up (100% vs.70.7%, p<0.001) and of a final diagnosis (90.7% vs. 31.5%, p<0.001); more patients were contacted at standard intervals (PUL, 86.7% vs. 53.7%, p<0.001; ectopic, 100% vs. 72.7%, p=0.006). However, despite regular faculty supervision, EMR documentation of attending oversight was unchanged (47.7% vs. 39.1%, p=0.32).

CONCLUSION:

We observed statistically significant improvements in patient compliance with standard follow up, in EMR documentation of care, and in provider adherence to follow up algorithm, as a result of this QI project at our institution.
Application of Opposing Triangle Flaps in Three Different Kinds of Conjoined Twins
Authors: Liu Xiangqi , Li Jun , He Weijing , Zhang Shuai , Dong Chenbin
Published: October 2020

BACKGROUND

Conjoined twins are a rare congenital anomaly. If separation of the conjoined organs is feasible, reconstruction of the skin and tissue defects is a challenge for the plastic surgeon. This article describes the use of opposing triangle flaps in the separation of three different kinds of conjoined twins.

METHODS

Plastic surgeons measured each conjoined area and designated the vertical length as a and the width as b. The length of the base of the opposing triangle flap was calculated to match a, and the height of the triangle to match b.

RESULTS

After detailed calculations and careful surgery, the area of the opposing triangle flaps nearly covered the areas exposed after separation, and the three conjoined twins achieved primary closure of their wounds. The pygopagus and ischiopagus twins recovered uneventfully. The omphalopagus twins developed a wound infection, but after daily wound care, the twins recovered within a week.

CONCLUSIONS

With precise calculations, the opposing triangle flap is a feasible and effective method for defect closure after separation of conjoined twins in certain cases. Clinicians may prefer this technique because it avoids the complications and second surgery necessitated by tissue expanders.