bluuebunny/crossref_metadata_2025 huggingface dataset:
Time-Based Data in Occupational Studies: The Whys, the Hows, and Some Remaining Challenges in Compositional Data Analysis (CoDA)
Authors: Gupta Nidhi , Rasmussen Charlotte Lund , Holtermann Andreas , Mathiassen Svend Erik
Published: May 2020

Data on the use of time in different exposures, behaviors, and work tasks are common in occupational research. Such data are most often expressed in hours, minutes, or percentage of work time. Thus, they are constrained or ‘compositional’, in that they add up to a finite sum (e.g. 8 h of work or 100% work time). Due to their properties, compositional data need to be processed and analyzed using specifically adapted methods. Compositional data analysis (CoDA) has become a particularly established framework to handle such data in various scientific fields such as nutritional epidemiology, geology, and chemistry, but has only recently gained attention in public and occupational health sciences. In this paper, we introduce the reader to CoDA by explaining why CoDA should be used when dealing with compositional time-use data, showing how to perform CoDA, including a worked example, and pointing at some remaining challenges in CoDA. The paper concludes by emphasizing that CoDA in occupational research is still in its infancy, and stresses the need for further development and experience in the use of CoDA for time-based occupational exposures. We hope that the paper will encourage researchers to adopt and apply CoDA in studies of work exposures and health.
ACE2 receptor expression in testes: implications in coronavirus disease 2019 pathogenesis†
Authors: Verma Saguna , Saksena Sarini , Sadri-Ardekani Hooman
Published: May 2020

Expression of angiotensin-converting enzyme 2, receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is high in the testes, therefore SARS-CoV-2 infection and its association with male reproductive health should be investigated in male coronavirus disease 2019 patients.
The Evolution of Protest Policing in a Hybrid Regime
Authors: Wang Peng , Joosse Paul , Cho Lok Lee
Published: May 2020

Using interview data from protesters and frontline police, this article examines the evolution of protest policing, from ‘soft’ to ‘hard’ models, amid the recent unrest in Hong Kong. While ‘police-centric’ explanations in the protest policing literature tend to conceive of police as intentional decision makers who can choose among a variety of strategies, we employ a mixed embeddedness framework to find that a number of factors—external to police—have deprived the Hong Kong Police Force (HKPF) of its capacity to facilitate peaceful protest through ‘soft’ strategies of communication and negotiation. These include (1) a legitimacy crisis of governance in Hong Kong (a macro-level factor), (2) the erosion of police authority within the local political culture (a meso-level factor) and (3) stylistic changes in police–protester interactions, involving the increased use of masks and collective action frames of identification as victims of police (micro-level factors). Together, these factors have inaugurated reaction spirals which have led Hong Kong’s police–public interface to an unprecedented state of breakdown, where ‘soft’ policing is now all but impossible and where the HKPF is beset by a widely subscribed demand for its outright disbandment.
Lenvatinib suppresses cancer stem-like cells in HCC by inhibiting FGFR1–3 signaling, but not FGFR4 signaling
Authors: Shigesawa Taku , Maehara Osamu , Suda Goki , Natsuizaka Mitsuteru , Kimura Megumi , Shimazaki Tomoe , Yamamoto Koji , Yamada Ren , Kitagataya Takashi , Nakamura Akihisa , Suzuki Kazuharu , Ohara Masatsugu , Kawagishi Naoki , Umemura Machiko , Nakai Masato , Sho Takuya , Morikawa Kenichi , Ogawa Koji , Ohnishi Shunsuke , Sugiyama Masaya , Mizokami Masashi , Takeda Hiroshi , Sakamoto Naoya
Published: May 2020

In hepatocellular carcinoma (HCC), a subset of cells defined by high CD44 and CD133 expression has been reported to possess cancer stem-like cell (CSC) characteristics and to be associated with a poor prognosis. Since the approval of the multikinase inhibitor, lenvatinib, for patients with unresectable HCC, two such inhibitors (sorafenib and lenvatinib) have been employed as first-line systemic chemotherapeutics for these patients. Based on differences in the kinase-affinity profiles between these two drugs, evidence has suggested that both exert different effects on HCC, although these differences are not fully characterized. In this study, using in vitro and a preclinical in vivo xenograft mouse model, we showed that lenvatinib alone (not sorafenib or the cytotoxic agent, 5-fluorouracil) diminished CD44High/CD133High CSCs in HCC. Furthermore, western blotting and reverse transcriptase-polymerase chain reaction analysis revealed that the expression of fibroblast growth factor receptor (FGFR)-1–4 differed between CD44High/CD133High CSCs and control cells. Analysis of the effects of selective FGFR inhibitors and FGFR small interfering RNAs on CSCs in HCC revealed that lenvatinib diminished CSCs in HCC by inhibiting FGFR1–3 signaling, however, FGFR4 signaling was not impacted. Finally, we showed that FGF2 and FGF19 were involved in maintaining CD44High/CD133High CSCs in HCC, potentially, via FGFR1–3. The findings provide novel mechanistic insights into the effects of lenvatinib on CSCs in HCC and provide clues for developing effective targeted therapies against CSCs in HCC.
Irrelevant Predictions: Distractor Rhythmicity Modulates Neural Encoding in Auditory Cortex
Authors: Makov Shiri , Zion Golumbic Elana
Published: May 2020

Dynamic attending theory suggests that predicting the timing of upcoming sounds can assist in focusing attention toward them. However, whether similar predictive processes are also applied to background noises and assist in guiding attention “away” from potential distractors, remains an open question. Here we address this question by manipulating the temporal predictability of distractor sounds in a dichotic listening selective attention task. We tested the influence of distractors’ temporal predictability on performance and on the neural encoding of sounds, by comparing the effects of Rhythmic versus Nonrhythmic distractors. Using magnetoencephalography we found that, indeed, the neural responses to both attended and distractor sounds were affected by distractors’ rhythmicity. Baseline activity preceding the onset of Rhythmic distractor sounds was enhanced relative to nonrhythmic distractor sounds, and sensory response to them was suppressed. Moreover, detection of nonmasked targets improved when distractors were Rhythmic, an effect accompanied by stronger lateralization of the neural responses to attended sounds to contralateral auditory cortex. These combined behavioral and neural results suggest that not only are temporal predictions formed for task-irrelevant sounds, but that these predictions bear functional significance for promoting selective attention and reducing distractibility.
Revisiting the Natural History of Pulmonary Tuberculosis: A Bayesian Estimation of Natural Recovery and Mortality Rates
Authors: Ragonnet Romain , Flegg Jennifer A , Brilleman Samuel L , Tiemersma Edine W , Melsew Yayehirad A , McBryde Emma S , Trauer James M
Published: May 2020

Background

Tuberculosis (TB) natural history remains poorly characterized, and new investigations are impossible as it would be unethical to follow up TB patients without treatment.

Methods

We considered the reports identified in a previous systematic review of studies from the prechemotherapy era, and extracted detailed data on mortality over time. We used a Bayesian framework to estimate the rates of TB-induced mortality and self-cure. A hierarchical model was employed to allow estimates to vary by cohort. Inference was performed separately for smear-positive TB (SP-TB) and smear-negative TB (SN-TB).

Results

We included 41 cohorts of SP-TB patients and 19 cohorts of pulmonary SN-TB patients in the analysis. The median estimates of the TB-specific mortality rates were 0.389 year−1 (95% credible interval [CrI], .335–.449) and 0.025 year−1 (95% CrI, .017–.035) for SP-TB and SN-TB patients, respectively. The estimates for self-recovery rates were 0.231 year−1 (95% CrI, .177–.288) and 0.130 year−1 (95% CrI, .073–.209) for SP-TB and SN-TB patients, respectively. These rates correspond to average durations of untreated TB of 1.57 years (95% CrI, 1.37–1.81) and 5.35 years (95% CrI, 3.42–8.23) for SP-TB and SN-TB, respectively, when assuming a non-TB-related mortality rate of 0.014 year−1 (ie, a 70-year life expectancy).

Conclusions

TB-specific mortality rates are around 15 times higher for SP-TB than for SN-TB patients. This difference was underestimated dramatically in previous TB modeling studies, raising concerns about the accuracy of the associated predictions. Despite being less infectious, SN-TB may be responsible for equivalent numbers of secondary infections as SP-TB due to its much longer duration.
Where Is the Implementation Science? An Opportunity to Apply Principles During the COVID-19 Pandemic
Authors: Taylor Stephanie Parks , Kowalkowski Marc A , Beidas Rinad S
Published: May 2020

The coronavirus disease 2019 pandemic represents a global crisis that has received extraordinary response from healthcare workers and scientists. One critical but potentially overlooked field in a pandemic is implementation science—the study of methods to reduce the research-to-practice gap. In this Viewpoint, we discuss the important role of implementation science during this and future pandemics and highlight considerations to maximize the utility of implementation research.
Aural philology: Herder hears Homer singing
Authors: Solanki Tanvi
Published: May 2020

In 1769, Johann Gottfried Herder describes a private reading experience of a remarkably paradoxical nature. He tells us that he can only read ‘his’ Homer properly when he hears Homer singing Greek, while silently reading and translating by means of his German thoughts and mother tongue. Herder’s performative reading is anchored in what I call aural philology, a method innovative in its emphasis on the aural dimension in reconstructively imagining historical epochs. It is one which demarcates cultural difference through practices of listening and their remediation into reading. The problem, for Herder, is how to constitute the particularity of the German people even in affective acts of reading that, however momentarily, suspend cultural differentiation through effects of presence. I distinguish Herder’s philology from Vico and others who emphasized the oral origins of the Homeric epic, along with recent theories of philology as an affective, aurally mediated process. The article is an alternative view on the role of media in enlightenment theories of literature and culture separate from Friedrich Kittler’s Discourse Networks 1800/1900. Herder’s aural philology identifies a moment in the history of aurality and cultural difference, one that does not move fixedly towards modernity.
Investigation of anisotropic spatial correlations of intra-event residuals of multiple earthquake intensity measures using latent dimensions method
Authors: Abbasnejadfard Morteza , Bastami Morteza , Fallah Afshin
Published: May 2020

Considering spatial correlation of multiple earthquake intensity measures (IMs) is of particular importance in loss assessment of spatially distributed assets. This subject has been investigated in previous studies under the assumption of isotropy. Considering the fact that the assumption of isotropy is not valid in general, the present study employs a non-separable covariance model based on latent dimensions method to investigate anisotropic properties of spatial correlations and cross-correlations of intra-event residuals of multiple earthquake IMs. This method leads to the generation of valid covariance matrix in order to model anisotropic spatially distributed multivariate random fields. Two sets of IMs are considered in this study; the first set consists of peak ground intensity values (acceleration, velocity, and displacement), and the second set consists of spectral accelerations at three different periods. Data of 10 earthquake events in California and Japan are utilized in this study to estimate parameters of marginal and cross-covariance models. Moreover, parameters of covariance model of regional site condition, which is considered as average shear wave velocity of top 30 m of soil profile (Vs30), are obtained in order to investigate the effect of local sited conditions on spatial correlations of IMs. It is shown that maximum range and anisotropy ratio of covariance models of intra-event residuals of IMs are correlated with those of Vs30 values. Also, it is observed that the anisotropy direction of residuals of IMs is consistent with anisotropy direction of Vs30 values. Finally, predictive models are proposed to obtain marginal and cross-covariance functions for different earthquake IMs considering anisotropy.
Policy Process And Non-State Actors’ Influence On The 2014 Mexican Soda Tax
Authors: Carriedo Angela , Lock Karen , Hawkins Benjamin
Published: May 2020

In January 2014, Mexico introduced a soda tax of 1 Mexican Peso (MXP) per litre. The aim of this paper is to examine the political context out of which this policy emerged, the main drivers for the policy change, and the role of stakeholders in setting the policy agenda and shaping the policy design and outcomes. Thirty-one semi-structured interviews were conducted with key stakeholders, and 145 documents, including peer-reviewed papers, policy briefs, press releases, industry, government, and CSO reports, were analysed. An iterative thematic analysis was conducted based on relevant theories of the policy process using a complementary approach, including Stages Heuristic Model, Policy Triangle Framework, and Multiple Streams Model. Results showed that a major motivation was the new administration seeking funds as they entered government. The soda tax was supported by a key group of legislators, civil society actors and by academics promoting evidence on health effects. However, the policy measure was challenged by the food and beverage industries (F&BI). Non-state actors were both formally and informally involved in setting the agenda, regardless of some of them having opposing interests on the soda tax policy. Approaches used by non-state actors to influence the agenda included: calls for action, marketing strategies, coalition building, challenging evidence, and engaging in public–private partnerships (PPPs). The effectiveness of the soda tax was highly debated and resulted in public polarization, although the framing of the outcomes was instrumental in influencing fiscal policies elsewhere. This study contributes to the debate around implementing fiscal policies for health and how power is exercised and framed in the agenda-setting phase of policy development. The article examines how the F&BI sought to influence the national strategy for obesity prevention. It argues that the experience of the soda tax campaign empowered policy advocates, strengthening national and international civil society networks.
Uterine lavage: ethics of research and clinical applications
Authors: Pennings Guido
Published: May 2020

Uterine lavage is presented as a way to perform aneuploidy screening without IVF. The feasibility of this method was tested in a research study. This study combined a number of highly contentious ethical issues: the creation of embryos for research (very early), abortion and (moderate) payments to research participants. It is concluded that the study largely fulfils the criteria of ethical research but that the researchers should have avoided a number of steps. These steps were the inclusion of infertility patients, the performance of the research in a middle-income country and the double destination of the embryos. The next question then becomes whether it would be acceptable to apply the method in a clinical setting. Two elements complicate the introduction in the clinic: low success rate of embryo collection and risk of unintended pregnancy. The application of the method in the clinic may lead to very complicated ethical and legal situations for which both patients and doctors should be prepared.
Characteristics and Long-Term Outcomes of Pregnancy-Onset Inflammatory Bowel Disease: A Case-Control Study
Authors: Yu Amy , Friedman Sonia , Ananthakrishnan Ashwin N
Published: May 2020

Background

Inflammatory bowel disease (IBD) frequently affects women during their reproductive years. Although the impact of pregnancy in patients with established IBD has been widely studied, the characteristics and outcomes of patients who develop a new diagnosis of IBD during pregnancy or the postpartum year (“pregnancy-onset”) is not well characterized.

Methods

We identified all patients with pregnancy-onset IBD between 2006 and 2018 at 2 major academic referral centers. Patient and disease characteristics were abstracted and compared to those of control patients with IBD not diagnosed during pregnancy or postpartum. Diagnostic and therapeutic interventions were noted, as were long-term outcomes including disease treatment course, hospitalizations, and surgery.

Results

We identified 50 patients with pregnancy-onset IBD and 100 control patients matched for year of diagnosis. The mean age of diagnosis and duration of follow-up was similar among both patients and control patients (aged 30.4 vs 28.5 years). Among patients with pregnancy-onset disease, 30% noted symptom onset in the first trimester, 22% in the second, 24% in the third, and 24% in the postpartum year. Patients with pregnancy-onset IBD were more likely to be diagnosed with ulcerative colitis compared with control patients (76% vs 56%; P = 0.02). On multivariable analysis, pregnancy onset-disease had a 4-fold increase in the risk of hospitalization (28% vs 13%; adjusted odds ratio 4.18; 95% confidence interval, 1.26-13.91). This increased risk persisted even after excluding any index hospitalizations during pregnancy.

Conclusions

Patients with pregnancy-onset IBD more commonly develop ulcerative colitis and have a higher risk of disease-related hospitalizations.
Indirect effect of oral azithromycin on the gut resistome of untreated children: a randomized controlled trial
Authors: Oldenburg Catherine E , Hinterwirth Armin , Worden Lee , Sié Ali , Dah Clarisse , Ouermi Lucienne , Coulibaly Boubacar , Zhong Lina , Chen Cindi , Ruder Kevin , Lietman Thomas M , Keenan Jeremy D , Doan Thuy
Published: May 2020

Background

Antibiotic use by one individual may affect selection for antimicrobial resistance in close contacts. Here we evaluated whether oral antibiotic treatment of one child within a household affected the gut resistome of an untreated cohabiting child.

Methods

Households with at least two children <5 y of age were randomized in a 1:1 fashion to a 5d course of azithromycin or placebo. To evaluate indirect effects of azithromycin treatment on the gut resistome, we randomly assigned one child in the house to azithromycin and one to placebo. In placebo households, each child received placebo. We performed DNA sequencing of rectal swabs collected 5 d after the last antibiotic dose. We estimated risk ratios for the presence of genetic resistance determinants at the class level using modified Poisson models for children in azithromycin households compared with placebo households and assessed the composition of the resistome using permutational analysis of variance (PERMANOVA).

Results

Of 58 children (n = 30 azithromycin households, n = 28 placebo households) with post-treatment rectal swabs, genetic resistance determinants were common but there was no significant difference at the class (p = 0.54 for macrolides) or gene (p = 0.94 for structure by PERMANOVA, p = 0.94 for diversity) level between untreated children in azithromycin households compared with placebo households.

Conclusions

The results are encouraging that one child's antibiotic use may not influence the resistome of another child.

Trial registration: ClinicalTrials.gov NCT03187834.
Moth flame optimizer-based solution approach for unit commitment and generation scheduling problem of electric power system
Authors: Bhadoria Ashutosh , Marwaha Sanjay
Published: May 2020

This paper proposes a new approach based on the moth flame optimizer algorithm. Moth flame optimizer simulates the natural fervent navigation technique adopted by moths looking for a source of light. The proposed method is further improved by priority list-based ordering; the unit commitment problem (UCP) is a non-linear, non-convex, and combinatorial complex optimization problem. It contains both continuous and discrete variables. This further increases its complexity. Moth flame optimizer is very good at obtaining a commitment pattern: allocation of power on the committed units obtained by mixed-integer quadratic programming method. Heuristic search strategies are used to adopt for the repair of minimum up and downtime, and spinning reserve constraints. MFO effectiveness is tested on the standard UCP reference IEEE model buses 14 and 30, and 10 and 20 units. The efficiency of the projected algorithms is compared to classical PSO, PSOLR, HPSO, PSOSQP, hybrid MPSO, IBPSO, LCA-PSO, NPSO, PSO-GWO, and various other evolutionary algorithms. The comparison result shows that MFO can lead to all methods reported earlier in literature.
Understanding help-seeking behaviour in relation to psychosocial support services among Japanese cancer patients
Authors: Matsui Tomoko , Hirai Kei , Gondo Yasuyuki , Sato Shinichi
Published: May 2020

Background

There are various psychosocial support services for cancer patients in Japan; however, their utilization rate is lower than in Western countries. The aim of this study was to investigate the actual status of the utilization of such services and the related factors of their use, using the transtheoretical model.

Methods

We conducted an Internet survey of cancer outpatients. They were asked for information on their demographics, physical status and the usage of and intention to use psychosocial support services, and to answer the Hospital Anxiety and Depression Scale.

Results

Data of 712 participants were analyzed; 111 had made use of psychosocial support services (15.6%). Participants who were younger, female, had breast cancer, experience with hormone therapy and did not have a good performance status (Karnofsky Performance Scale) more often used such services when comparing users/experiencers with non-users/inexperienced. Of the inexperienced, 538 were in the Precontemplation stage (89.5%), 62 were in the Contemplation stage (10.3%) and one was in the Preparation stage (0.2%). Approximately 35% of those in the Precontemplation stage would correspond to adjustment disorders or major depression.

Conclusions

We showed the degree of cancer patients who have used the psychosocial support services and its contents and revealed the factors related to the utilization of such services in Japan. Our study supports previous reports that cancer patients with high levels of distress do not necessarily seek support, and thus future studies should also examine other modifiable factors considering the medical settings.
Genetic assays for guano-based identification of species and sex in bats of the United States and Canada
Authors: Guan Xin , Britzke Eric R , Piaggio Antoinette J , Bergman David L , Van Pelt Lolita , Lance Richard F
Published: May 2020

Bat guano is a noninvasive, data-rich genetic resource. However, the constituent bat DNA is relatively scant, degraded, and complexed with polymerase chain reaction inhibitors. It also is comingled with a rich pool of nontarget DNA from microbes, parasites, and dietary items. We designed and tested new DNA assays for bat species identification (COX1-Bat) and sex identification (XGXYC) for use with guano and other challenging samples. We reviewed previously published assays that can be used with guano samples to obtain the same species and sex data, and attempted to validate these assays for species in which they had not previously been tested. Our results demonstrate that guano-derived DNA can be used successfully to 1) identify nearly all US and Canadian bats at the species level, or to one of three Myotis species clusters, and 2) identify the sex of at least 23 US and Canadian bat species. Our newly developed assays, and validation of previously published assays, for guano-based identification of species and sex in bats, significantly enhance the power of noninvasive sampling and genetic analysis for bat studies, management, and conservation.
Predicting the Pathologic Complete Response After Neoadjuvant Pembrolizumab in Muscle-Invasive Bladder Cancer
Authors: Bandini Marco , Ross Jeffrey S , Raggi Daniele , Gallina Andrea , Colecchia Maurizio , Lucianò Roberta , Giannatempo Patrizia , Farè Elena , Pederzoli Filippo , Bianchi Marco , Colombo Renzo , Gandaglia Giorgio , Fossati Nicola , Marandino Laura , Capitanio Umberto , Deho’ Federico , Ali Siraj M , Madison Russell , Chung Jon H , Salonia Andrea , Briganti Alberto , Montorsi Francesco , Necchi Andrea
Published: May 2020

Background

In the PURE-01 study (NCT02736266), we aimed to evaluate the ability to predict the pathologic complete response (pT0N0) after pembrolizumab by using clinical and tumor biomarkers.

Methods

In an open-label, single-arm, phase 2 study, 3 courses of 200 mg pembrolizumab preceding radical cystectomy were administered in patients with T2-4aN0M0 muscle-invasive bladder cancer. The analyses included a comprehensive genomic profiling and programmed cell-death-ligand-1 (PD-L1)–combined positive score assessment (CPS; Dako 22C3 antibody) of pre- and posttherapy samples. Multivariable logistic regression analyses evaluated baseline clinical T stage and tumor biomarkers in association with pT0N0 response. Corresponding coefficients were used to develop a calculator of pT0N0 response based on the tumor mutational burden (TMB), CPS, and the clinical T stage. Decision-curve analysis was also performed. All statistical tests were 2-sided.

Results

From February 2017 to June 2019, 112 patients with biomarker data were enrolled (105 with complete TMB and CPS data). Increasing TMB and CPS values featured a linear association with logistic pT0N0 probabilities (P = .02 and P = .004, respectively). For low TMB values (≤11 mut/Mb, median value, n = 53), pT0N0 probability was not associated with increasing CPS. Conversely, for high TMB values (>11 mut/Mb, n = 52), pT0N0 was statistically significantly associated with higher CPS (P = .004). The C index of the pT0N0 probability calculator was 0.77. On decision-curve analysis, the net benefit of the model was higher than the “treat-all” option within the clinically meaningful threshold probabilities of 40%-50%.

Conclusions

The study presents a composite biomarker-based pT0N0 probability calculator that reveals the complex interplay between TMB and CPS, added to the clinical T stage.
Loss of total phenols from leaf litter of two shrub species: dual responses to alpine forest gap disturbance during winter and the growing season
Authors: He Wei , Yang Wanqin
Published: May 2020

Aims

Alpine forest gaps can control understory ecosystem processes by manipulating hydrothermal dynamics. Here, we aimed to test the role of alpine forest gap disturbance on total phenol loss (TPL) from the decomposing litter of two typical shrub species (willow, Salix paraplesia Schneid., and bamboo, Fargesia nitida (Mitford) Keng f.).

Methods

We conducted a field litterbag experiment within a representative fir (Abies faxoniana Rehd.) forest based on ‘gap openness treatments’ (plot positions in the gap included the gap center south, gap center north, canopy edge, expanded edge and closed canopy). The TPL rate and litter surface microbial abundance (fungi and bacteria) of the two shrub species were measured during the following periods over 2 years: snow formation (SF), snow cover (SC), snow melting (ST), the early growing season (EG) and the late growing season (LG).

Important Findings

At the end of the study, we found that snow cover depth, freeze–thaw cycle frequency and the fungal copies g−1 to bacterial copies g−1 ratio had significant effects on litter TPL. The abundances of fungi and bacteria decreased from the gap center to the closed canopy during the SF, SC, ST and LG periods and showed the opposite trend during the EG periods. The rate of TPL among plot positions closely followed the same trend as microbial abundance during the first year of incubation. In addition, both species had higher rates of TPL in the gap center than at other positions during the first winter, first year and entire 2-year period. These findings suggest that alpine forest gap formation accelerates litter TPL, although litter TPL exhibits dual responses to gap disturbance during specific critical periods. In conclusion, reduced snow cover depth and duration during winter warming under projected climate change scenarios or as gaps vanish may slow litter TPL in alpine biomes.
Malignant triton tumor below the peritoneal reflection: a case report
Authors: Seddighzadeh Rachael Price , Brower Steven , Tzeng Jausheng , Serur Anna
Published: May 2020

Malignant triton tumor (MTT) is a rare subtype of malignant peripheral nerve sheath tumors (MPNSTs) histologically defined by rhabdomyoblastic differentiation. MTTs are primarily found in the head, neck, extremities and trunk, but rare cases of MTT within the buttock, the mediastinum and the retroperitoneum have also been documented. We present the case of a 47-year-old male patient who initially presented with right flank pain and hematuria in July 2019, who was found to have a large pelvic mass below peritoneal reflection. Complete resection of the mass was performed, and pathology identified the mass as a MTT.
Retrograde orbits excess among observable interstellar objects
Authors: Marčeta Dušan , Novaković Bojan
Published: May 2020

In this work, we investigate the orbital distribution of interstellar objects (ISOs), observable by the future wide-field National Science Foundation Vera C. Rubin Observatory (VRO). We generate synthetic population of ISOs and simulate their ephemerides over a period of 10 yr, in order to select those that may be observed by the VRO, based on the nominal characteristics of this survey. We find that the population of the observable ISOs should be significantly biased in favour of retrograde objects. The intensity of this bias is correlated with the slope of the size-frequency distribution (SFD) of the population, as well as with the perihelion distances. Steeper SFD slopes lead to an increased fraction of the retrograde orbits, and also of the median orbital inclination. On the other hand, larger perihelion distances result in more symmetric distribution of orbital inclinations. We believe that this is a result of Holetschek’s effects, which is already suggested to cause observational bias in orbital distribution of long-period comets. The most important implication of our findings is that an excess of retrograde orbits depends on the sizes and the perihelion distances. Therefore, the prograde/retrograde orbits ratio and the median inclination of the discovered population could, in turn, be used to estimate the SFD of the underlying true population of ISOs.
Probing compact dark matter with gravitational wave fringes detected by the Einstein Telescope
Authors: Liao Kai , Tian Shuxun , Ding Xuheng
Published: May 2020

Unlike the electromagnetic radiation from astrophysical objects, gravitational waves (GWs) from binary star mergers have much longer wavelengths and are coherent. For ground-based GW detectors, when the lens object between the source and the Earth has mass ∼1−105 M⊙, the diffraction effect should be considered since the chirping wavelengths are comparable to the scale of the barrier (its Schwarzschild radius). The waveform will thus be distorted as the fringes. In this work, we show that signals from the third-generation GW detectors like the Einstein Telescope (ET) would be a smoking gun for probing the nature of compact dark matter (CDM) or primordial black holes. Detection of the lensing effects becomes harder when the lens mass is smaller. ET is more sensitive than LIGO, the constraint is available for CDM mass >5 M⊙ while LIGO can only detect the mass >100 M⊙. For a null search of the fringes, one-year observation of ET can constrain the CDM density fraction to ∼10−2 to 10−5 in the mass range MCDM = 10−100 M⊙.
Stellar activity with LAMOST. III. Temporal variability pattern in Pleiades, Praesepe, and Hyades
Authors: Fang Xiang-Song , Bidin Christian Moni , Zhao Gang , Zhang Li-Yun , Bharat Kumar Yerra
Published: May 2020

We present the results from a systematic study of temporal variation of stellar activity in young late-type stars. We used multi-epoch LAMOST (Large sky Area Multi-Object fiber Spectroscopic Telescope) low-resolution spectra of over 300 member candidates in three young open clusters: Pleiades, Praesepe, and Hyades. The spectral measurements of TiO band strength near 7050 Å (TiO2) and equivalent width of H α line (EWH α) are used as the tracers of cool spot coverage and chromospheric emission strength, respectively. The analysis of time-variation patterns of these two tracers suggested that there exist detectable variabilities in TiO2 and EWH α, and their time-scales are in the wide range from days to years. Results showed that more active stars, younger and fast rotators, tend to have larger activity variations. There is a tendency of anticorrelation between temporal variations in TiO2 and EWH α. Also, appreciable anticorrelation in the rotational phase between H α emission and K2 brightness is detected in some M dwarfs, indicating spatial co-location of the plages with cool star-spots; however, cool stars do not always show such co-location features. Furthermore, spot coverage and H α emission were evident at all rotational phases of several M dwarfs, indicating a basal level of activity, perhaps due to many small and randomly located active regions in the atmosphere.
New constraints on the magnetization of the cosmic web using LOFAR Faraday rotation observations
Authors: O’Sullivan S P , Brüggen M , Vazza F , Carretti E , Locatelli N T , Stuardi C , Vacca V , Vernstrom T , Heald G , Horellou C , Shimwell T W , Hardcastle M J , Tasse C , Röttgering H
Published: May 2020

Measuring the properties of extragalactic magnetic fields through the effect of Faraday rotation provides a means to understand the origin and evolution of cosmic magnetism. Here, we use data from the LOFAR Two-Metre Sky Survey (LoTSS) to calculate the Faraday rotation measure (RM) of close pairs of extragalactic radio sources. By considering the RM difference (ΔRM) between physical pairs (e.g. double-lobed radio galaxies) and non-physical pairs (i.e. close projected sources on the sky), we statistically isolate the contribution of extragalactic magnetic fields to ΔRM along the line of sight between non-physical pairs. From our analysis, we find no significant difference between the ΔRM distributions of the physical and non-physical pairs, limiting the excess Faraday rotation contribution to <1.9 rad m−2 (${\sim}95{{\ \rm per\ cent}}$ confidence). We use this limit with a simple model of an inhomogeneous universe to place an upper limit of 4 nG on the cosmological co-moving magnetic field strength on Mpc scales. We also compare the RM data with a more realistic suite of cosmological magnetohydrodynamical simulations that explore different magnetogenesis scenarios. Both magnetization of the large-scale structure by astrophysical processes such as galactic and AGN outflows, and simple primordial scenarios with seed magnetic field strengths <0.5 nG cannot be rejected by the current data; while stronger primordial fields or models with dynamo amplification in filaments are disfavoured.
Modelling fibroid pathology: development and manipulation of a myometrial smooth muscle cell macromolecular crowding model to alter extracellular matrix deposition
Authors: Winter Ann , Salamonsen Lois A , Evans Jemma
Published: May 2020

Current treatment options for uterine fibroids are limited to hormonal manipulation or surgical intervention. We aimed to develop an in vitro model to mirror collagen deposition and extracellular matrix (ECM) formation, the principal features of uterine fibroids, to enable testing of novel therapeutics. Macromolecular crowding with Ficoll 400 and Ficoll 70 in cultures of human uterine myometrial smooth muscle cells containing ascorbic acid, provided the basis for this model. These culture conditions mimic the ‘crowded’ nature of the in vivo extracellular environment by incorporating neutral, space-filling macromolecules into conventional cell cultures. This method of culture facilitates appropriate ECM deposition, thus closely representing the in vivo fibrotic phenotype of uterine fibroids. Macromolecular crowding in Ficoll cultures containing ascorbic acid reduced myometrial smooth muscle cell proliferation and promoted collagen production. Under these conditions, collagen was processed for extracellular deposition as demonstrated by C-propeptide cleavage from secreted procollagen. The fibrosis marker activin was increased relative to its natural inhibitor, follistatin, in crowded culture conditions while addition of exogenous follistatin reduced collagen (Col1A1) gene expression. This in vitro model represents a promising development for the testing of therapeutic interventions for uterine fibroids. However, it does not recapitulate the full in vivo pathology which can include specific genetic and epigenetic alterations that have not been identified in the myometrial smooth muscle (hTERT-HM) cell line. Following screening of potential therapeutics using the model, the most promising compounds will require further assessment in the context of individual subjects including those with genetic changes implicated in fibroid pathogenesis.
Restriction endonucleases that cleave RNA/DNA heteroduplexes bind dsDNA in A-like conformation
Authors: Kisiala Marlena , Kowalska Monika , Pastor Michal , Korza Henryk J , Czapinska Honorata , Bochtler Matthias
Published: May 2020

Restriction endonucleases naturally target DNA duplexes. Systematic screening has identified a small minority of these enzymes that can also cleave RNA/DNA heteroduplexes and that may therefore be useful as tools for RNA biochemistry. We have chosen AvaII (G↓GWCC, where W stands for A or T) as a representative of this group of restriction endonucleases for detailed characterization. Here, we report crystal structures of AvaII alone, in specific complex with partially cleaved dsDNA, and in scanning complex with an RNA/DNA hybrid. The specific complex reveals a novel form of semi-specific dsDNA readout by a hexa-coordinated metal cation, most likely Ca2+ or Mg2+. Substitutions of residues anchoring this non-catalytic metal ion severely impair DNA binding and cleavage. The dsDNA in the AvaII complex is in the A-like form. This creates space for 2′-OH groups to be accommodated without intra-nucleic acid steric conflicts. PD-(D/E)XK restriction endonucleases of known structure that bind their dsDNA targets in the A-like form cluster into structurally similar groups. Most such enzymes, including some not previously studied in this respect, cleave RNA/DNA heteroduplexes. We conclude that A-form dsDNA binding is a good predictor for RNA/DNA cleavage activity.
FATCAT 2.0: towards a better understanding of the structural diversity of proteins
Authors: Li Zhanwen , Jaroszewski Lukasz , Iyer Mallika , Sedova Mayya , Godzik Adam
Published: May 2020

FATCAT 2.0 server (http://fatcat.godziklab.org/), provides access to a flexible protein structure alignment algorithm developed in our group. In such an alignment, rotations and translations between elements in the structure are allowed to minimize the overall root mean square deviation (RMSD) between the compared structures. This allows to effectively compare protein structures even if they underwent structural rearrangements in different functional forms, different crystallization conditions or as a result of mutations. The major update for the server introduces a new graphical interface, much faster database searches and several new options for visualization of the structural differences between proteins
One fly–one genome: chromosome-scale genome assembly of a single outbred Drosophila melanogaster
Authors: Adams Matthew , McBroome Jakob , Maurer Nicholas , Pepper-Tunick Evan , Saremi Nedda F , Green Richard E , Vollmers Christopher , Corbett-Detig Russell B
Published: May 2020

A high quality genome assembly is a vital first step for the study of an organism. Recent advances in technology have made the creation of high quality chromosome scale assemblies feasible and low cost. However, the amount of input DNA needed for an assembly project can be a limiting factor for small organisms or precious samples. Here we demonstrate the feasibility of creating a chromosome scale assembly using a hybrid method for a low input sample, a single outbred Drosophila melanogaster. Our approach combines an Illumina shotgun library, Oxford nanopore long reads, and chromosome conformation capture for long range scaffolding. This single fly genome assembly has a N50 of 26 Mb, a length that encompasses entire chromosome arms, contains 95% of expected single copy orthologs, and a nearly complete assembly of this individual's Wolbachia endosymbiont. The methods described here enable the accurate and complete assembly of genomes from small, field collected organisms as well as precious clinical samples.
Misactivation of multiple starvation responses in yeast by loss of tRNA modifications
Authors: Bruch Alexander , Laguna Teresa , Butter Falk , Schaffrath Raffael , Klassen Roland
Published: May 2020

Previously, combined loss of different anticodon loop modifications was shown to impair the function of distinct tRNAs in Saccharomyces cerevisiae. Surprisingly, each scenario resulted in shared cellular phenotypes, the basis of which is unclear. Since loss of tRNA modification may evoke transcriptional responses, we characterized global transcription patterns of modification mutants with defects in either tRNAGlnUUG or tRNALysUUU function. We observe that the mutants share inappropriate induction of multiple starvation responses in exponential growth phase, including derepression of glucose and nitrogen catabolite-repressed genes. In addition, autophagy is prematurely and inadequately activated in the mutants. We further demonstrate that improper induction of individual starvation genes as well as the propensity of the tRNA modification mutants to form protein aggregates are diminished upon overexpression of tRNAGlnUUG or tRNALysUUU, the tRNA species that lack the modifications of interest. Hence, our data suggest that global alterations in mRNA translation and proteostasis account for the transcriptional stress signatures that are commonly triggered by loss of anticodon modifications in different tRNAs.
Studying RNA–DNA interactome by Red-C identifies noncoding RNAs associated with various chromatin types and reveals transcription dynamics
Authors: Gavrilov Alexey A , Zharikova Anastasiya A , Galitsyna Aleksandra A , Luzhin Artem V , Rubanova Natalia M , Golov Arkadiy K , Petrova Nadezhda V , Logacheva Maria D , Kantidze Omar L , Ulianov Sergey V , Magnitov Mikhail D , Mironov Andrey A , Razin Sergey V
Published: May 2020

Non-coding RNAs (ncRNAs) participate in various biological processes, including regulating transcription and sustaining genome 3D organization. Here, we present a method termed Red-C that exploits proximity ligation to identify contacts with the genome for all RNA molecules present in the nucleus. Using Red-C, we uncovered the RNA–DNA interactome of human K562 cells and identified hundreds of ncRNAs enriched in active or repressed chromatin, including previously undescribed RNAs. Analysis of the RNA–DNA interactome also allowed us to trace the kinetics of messenger RNA production. Our data support the model of co-transcriptional intron splicing, but not the hypothesis of the circularization of actively transcribed genes.
Host cell factors stimulate HIV-1 transcription by antagonizing substrate-binding function of Siah1 ubiquitin ligase to stabilize transcription elongation factor ELL2
Authors: Wu Jun , Xue Yuhua , Gao Xiang , Zhou Qiang
Published: May 2020

The Siah1 and Siah2 ubiquitin ligases are implicated in diverse biological processes ranging from cellular stress responses, signaling to transcriptional regulation. A key substrate of Siah1 is ELL2, which undergoes proteolysis upon polyubiquitination. ELL2 stimulates transcriptional elongation and is a subunit of the Super Elongation Complex (SEC) essential for HIV-1 transactivation. Previously, multiple transcriptional and post-translational mechanisms are reported to control Siah's expression and activity. Here we show that the activity of Siah1/2 can also be suppressed by host cell factor 1 (HCF1), and the hitherto poorly characterized HCF2, which themselves are not degraded but can bind and block the substrate-binding domain (SBD) of Siah1/2 to prevent their autoubiquitination and trans-ubiquitination of downstream targets including ELL2. This effect stabilizes ELL2 and enhances the ELL2-SEC formation for robust HIV-1 transactivation. Thus, our study not only identifies HCF1/2 as novel activators of HIV-1 transcription through inhibiting Siah1 to stabilize ELL2, but also reveals the SBD of Siah1/2 as a previously unrecognized new target for HCF1/2 to exert this inhibition.
Topological constraints of RNA pseudoknotted and loop-kissing motifs: applications to three-dimensional structure prediction
Authors: Xu Xiaojun , Chen Shi-Jie
Published: May 2020

An RNA global fold can be described at the level of helix orientations and relatively flexible loop conformations that connect the helices. The linkage between the helices plays an essential role in determining the structural topology, which restricts RNA local and global folds, especially for RNA tertiary structures involving cross-linked base pairs. We quantitatively analyze the topological constraints on RNA 3D conformational space, in particular, on the distribution of helix orientations, for pseudoknots and loop-loop kissing structures. The result shows that a viable conformational space is predominantly determined by the motif type, helix size, and loop size, indicating a strong topological coupling between helices and loops in RNA tertiary motifs. Moreover, the analysis indicates that (cross-linked) tertiary contacts can cause much stronger topological constraints on RNA global fold than non-cross-linked base pairs. Furthermore, based on the topological constraints encoded in the 2D structure and the 3D templates, we develop a 3D structure prediction approach. This approach can be further combined with structure probing methods to expand the capability of computational prediction for large RNA folds.
Importance of the lactation period in developmental programming in rodents
Authors: Rodríguez-González Guadalupe L , Bautista Claudia J , Rojas-Torres Karen I , Nathanielsz Peter W , Zambrano Elena
Published: May 2020

Lactation is a critical period during which maternal nutritional and environmental challenges affect milk composition and, therefore, organ differentiation, structure, and function in offspring during the early postnatal period. Evidence to date shows that lactation is a vulnerable time during which transient insults can have lasting effects, resulting in altered health outcomes in offspring in adult life. Despite the importance of the developmental programming that occurs during this plastic period of neonatal life, there are few comprehensive reviews of the multiple challenges—especially to the dam—during lactation. This review presents milk data from rodent studies involving maternal nutritional challenges and offspring outcome data from studies involving maternal manipulations during lactation. Among the topics addressed are maternal nutritional challenges and the effects of litter size and artificial rearing on offspring metabolism and neural and endocrine outcomes. The lactation period is an opportunity to correct certain functional deficits resulting from prenatal challenges to the fetus, but, if not personalized, can also lead to undesirable outcomes related to catch up-growth and overnutrition.