bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of Failure Modes and Effects Analysis methodology using Model-Based Safety Assessment approach
Authors: Savelev A S , Bersutskaya O D , Silin N D , Neretin E S
Published: July 2021

During the development of aircraft systems, the safety assessment process activities are carried out in parallel. Traditionally, safety professionals perform Functional Hazard Assessment, Preliminary System Safety Assessment, and System Safety Assessment. Despite the availability of many modern and advanced tools for performing calculations during the implementation of the System Safety Assessment, a great responsibility (and, accordingly, the risk of error) remains with the person. Model-Based Safety Assessment is a new and rapidly developing approach to evaluate the safety of airborne equipment worldwide, which improves existing methodologies for performing various analyzes, such as Failure Modes and Effects Analysis (FMEA). Implementation of FMEA using this approach requires the development of special software tools that allow both to create a model of the analyzed onboard equipment and systems, and to provide an opportunity to use this model when performing FMEA. One such tool is ANSYS Medini Analyze. Model-oriented method for performing FMEA is proposed within this article. This method fully complies with the requirements of ARP-4761 and provides possibility to minimize the likelihood of human error. Model-oriented method for performing FMEA has been probated on the example of flight control system at various levels of abstraction (system, item, functional block and hardware/software level).
Electrodynamic speed stabilizer for emergency wind power unit of an aircraft
Authors: Shirokov A A , Tishkov V V , Zdorova M V , Kaliy V A
Published: July 2021

In this paper, a new technical solution is proposed for a deeper and faster speed stabilization of an emergency aviation wind power unit (EAWPU) using an electromagnetic brake. The principle of the electromagnetic brake operation is considered and a simplified block diagram of the aircraft emergency power supply system is presented. An example of the design electromagnetic brake for installation on an EAWPU is proposed, and the results of a finite element analysis magnetic field and current density in the rotating part of the electrodynamic speed stabilizer are presented. The study of various materials and the thickness of the electromagnetic brake rotor is carried out in order to find the highest value of the braking torque. The main dependences of the braking torque on the excitation current, the rotor thickness and the EAWPU rotation speed are obtained. The simulation of the thermal processes electromagnetic brake is carried out in order to find the maximum temperature of the rotor, according to the results of which the temperature dependences on the rotor speed are constructed at different excitation currents of the electromagnetic brake.
Precise stabilization in space—Spektr-R onboard control system (RadioAstron)
Authors: Syrov A S , Sokolov V N , Shatskyi M A , Dobrynin D A
Published: July 2021

The report presents the outline of the Spektr-R onboard control system design (RadioAstron) and describes the method for attitude determination and for achievement of the pointing precision of the radio telescope during observing sessions. The required orientation accuracy is provided by a complex of information from an otroscopic instrument and astro sensors with filtering measurement noise. The achieved stabilization accuracy during the operation of the spacecraft is presented.
Role of DNA Flow Cytometry in the Diagnosis of Malignancy in Bile Duct Biopsies Using Paraffin-Embedded Tissue
Authors: Wu Bicong , Liu Yong-Jun , Rogers Jessica , Liu Yao-Zhong , Rabinovitch Peter S , Small Thomas , Swanson Paul E , Yeh Matthew M
Published: July 2021

Objectives

Histopathologic evaluation of bile biopsies for biliary strictures is frequently challenging and is affected by interobserver disagreement. Reliable ancillary tests that can help differentiate benign from malignant are not available. This study aimed to evaluate whether DNA content abnormalities detected by flow cytometry on formalin-fixed, paraffin-embedded (FFPE) tissue can help differentiate benign/reactive, dysplastic from malignant cell populations in bile duct biopsies.

Methods

We performed DNA flow cytometry on 30 FFPE bile duct biopsies in 5 well-defined diagnostic categories: (1) negative for dysplasia (NED), (2) low-grade dysplasia (LGD), (3) high-grade dysplasia (HGD), (4) carcinoma (CA), and (5) indefinite for dysplasia (IND).

Results

Abnormal DNA content was detected in 0 NED, 5 LGD (62.5%), 2 HGD (33.3%), 3 CA (60%), and 4 IND (80%) samples. As a diagnostic marker, the estimated sensitivity, specificity, positive predictive value, and negative predictive value were 63%, 100%, 100%, and 50%, respectively, for diagnosing HGD or CA.

Conclusions

DNA flow cytometry analysis is a useful ancillary test for the interpretation of bile duct biopsies. DNA content abnormalities, when correlated with histologic findings, will not only help confirm the morphologic impression but also identify patients who are at a higher risk of developing malignancy.
scAdapt: virtual adversarial domain adaptation network for single cell RNA-seq data classification across platforms and species
Authors: Zhou Xiang , Chai Hua , Zeng Yuansong , Zhao Huiying , Yang Yuedong
Published: July 2021

In single cell analyses, cell types are conventionally identified based on expressions of known marker genes, whose identifications are time-consuming and irreproducible. To solve this issue, many supervised approaches have been developed to identify cell types based on the rapid accumulation of public datasets. However, these approaches are sensitive to batch effects or biological variations since the data distributions are different in cross-platforms or species predictions. In this study, we developed scAdapt, a virtual adversarial domain adaptation network, to transfer cell labels between datasets with batch effects. scAdapt used both the labeled source and unlabeled target data to train an enhanced classifier and aligned the labeled source centroids and pseudo-labeled target centroids to generate a joint embedding. The scAdapt was demonstrated to outperform existing methods for classification in simulated, cross-platforms, cross-species, spatial transcriptomic and COVID-19 immune datasets. Further quantitative evaluations and visualizations for the aligned embeddings confirm the superiority in cell mixing and the ability to preserve discriminative cluster structure present in the original datasets.
Deep learning methods for biomedical named entity recognition: a survey and qualitative comparison
Authors: Song Bosheng , Li Fen , Liu Yuansheng , Zeng Xiangxiang
Published: July 2021

The biomedical literature is growing rapidly, and the extraction of meaningful information from the large amount of literature is increasingly important. Biomedical named entity (BioNE) identification is one of the critical and fundamental tasks in biomedical text mining. Accurate identification of entities in the literature facilitates the performance of other tasks. Given that an end-to-end neural network can automatically extract features, several deep learning-based methods have been proposed for BioNE recognition (BioNER), yielding state-of-the-art performance. In this review, we comprehensively summarize deep learning-based methods for BioNER and datasets used in training and testing. The deep learning methods are classified into four categories: single neural network-based, multitask learning-based, transfer learning-based and hybrid model-based methods. They can be applied to BioNER in multiple domains, and the results are determined by the dataset size and type. Lastly, we discuss the future development and opportunities of BioNER methods.
Transcranial alternating current stimulation for treating depression: a randomized controlled trial
Authors: Wang Hongxing , Wang Kun , Xue Qing , Peng Mao , Yin Lu , Gu Xuecun , Leng Haixia , Lu Juan , Liu Hongzhi , Wang Di , Xiao Jin , Sun Zhichao , Li Ning , Dong Kai , Zhang Qian , Zhan Shuqin , Fan Chunqiu , Min Baoquan , Zhou Aihong , Xie Yunyan , Song Haiqing , Ye Jing , Liu Aihua , Gao Ran , Huang Liyuan , Jiao Lidong , Song Yang , Dong Huiqing , Tian Zichen , Si Tianmei , Zhang Xiangyang , Li Xinmin , Kamiya Atsushi , Cosci Fiammetta , Gao Keming , Wang Yuping
Published: July 2021

Treatment of depression with antidepressants is partly effective. Transcranial alternating current stimulation can provide a non-pharmacological alternative for adult patients with major depressive disorder. However, no study has used the stimulation to treat first-episode and drug-naïve patients with major depressive disorder.

We used a randomized, double-blind, sham-controlled design to examine the clinical efficacy and safety of the stimulation in treating first-episode drug-naïve patients in a Chinese Han population. From 4 June 2018 to 30 December 2019, 100 patients were recruited and randomly assigned to receive 20 daily 40-min, 77.5 Hz, 15 mA, one forehead and two mastoid sessions of active or sham stimulation (n = 50 for each group) in four consecutive weeks (Week 4), and were followed for additional 4-week efficacy/safety assessment without stimulation (Week 8). The primary outcome was a remission rate defined as the 17-item Hamilton Depression Rating Scale (HDRS-17) score ≤ 7 at Week 8. Secondary analyses were response rates (defined as a reduction of ≥ 50% in the HDRS-17), changes in depressive symptoms and severity from baseline to Week 4 and Week 8, and rates of adverse events. Data were analysed in an intention-to-treat sample.

Forty-nine in the active and 46 in the sham completed the study. Twenty-seven of 50 (54%) in the active treatment group and 9 of 50 (18%) in the sham group achieved remission at the end of Week 8. The remission rate was significantly higher in the active group compared to that in the sham group with a risk ratio of 1.78 (95% confidence interval, 1.29, 2.47). Compared with the sham, the active group had a significantly higher remission rate at Week 4, response rates at Weeks 4 and 8, and a larger reduction in depressive symptoms from baseline to Weeks 4 and 8. Adverse events were similar between the groups.

In conclusion, the stimulation on the frontal cortex and two mastoids significantly improved symptoms in first-episode drug-naïve patients with major depressive disorder and may be considered as a non-pharmacological intervention for them in an outpatient setting.
Extended Frontal Networks for Visual and Auditory Working Memory
Authors: Noyce Abigail L , Lefco Ray W , Brissenden James A , Tobyne Sean M , Shinn-Cunningham Barbara G , Somers David C
Published: July 2021

Working memory (WM) supports the persistent representation of transient sensory information. Visual and auditory stimuli place different demands on WM and recruit different brain networks. Separate auditory- and visual-biased WM networks extend into the frontal lobes, but several challenges confront attempts to parcellate human frontal cortex, including fine-grained organization and between-subject variability. Here, we use differential intrinsic functional connectivity from 2 visual-biased and 2 auditory-biased frontal structures to identify additional candidate sensory-biased regions in frontal cortex. We then examine direct contrasts of task functional magnetic resonance imaging during visual versus auditory 2-back WM to validate those candidate regions. Three visual-biased and 5 auditory-biased regions are robustly activated bilaterally in the frontal lobes of individual subjects (N = 14, 7 women). These regions exhibit a sensory preference during passive exposure to task stimuli, and that preference is stronger during WM. Hierarchical clustering analysis of intrinsic connectivity among novel and previously identified bilateral sensory-biased regions confirms that they functionally segregate into visual and auditory networks, even though the networks are anatomically interdigitated. We also observe that the frontotemporal auditory WM network is highly selective and exhibits strong functional connectivity to structures serving non-WM functions, while the frontoparietal visual WM network hierarchically merges into the multiple-demand cognitive system.
CNVIntegrate: the first multi-ethnic database for identifying copy number variations associated with cancer
Authors: Chattopadhyay Amrita , Teoh Zi Han , Wu Chi-Yun , Juang Jyh-Ming Jimmy , Lai Liang-Chuan , Tsai Mong-Hsun , Wu Chia-Hsin , Lu Tzu-Pin , Chuang Eric Y
Published: July 2021

Human copy number variations (CNVs) and copy number alterations (CNAs) are DNA segments (>1000 base pairs) of duplications or deletions with respect to the reference genome, potentially causing genomic imbalance leading to diseases such as cancer. CNVs further cause genetic diversity in healthy populations and are predominant drivers of gene/genome evolution. Initiatives have been taken by the research community to establish large-scale databases to comprehensively characterize CNVs in humans. Exome Aggregation Consortium (ExAC) is one such endeavor that catalogs CNVs, of nearly 60 000 healthy individuals across five demographic clusters. Furthermore, large projects such as the Catalogue of Somatic Mutations in Cancer (COSMIC) and the Cancer Cell Line Encyclopedia (CCLE) combine CNA data from cancer-affected individuals and large panels of human cancer cell lines, respectively. However, we lack a structured and comprehensive CNV/CNA resource including both healthy individuals and cancer patients across large populations. CNVIntegrate is the first web-based system that hosts CNV and CNA data from both healthy populations and cancer patients, respectively, and concomitantly provides statistical comparisons between copy number frequencies of multiple ethnic populations. It further includes, for the first time, well-cataloged CNV and CNA data from Taiwanese healthy individuals and Taiwan Breast Cancer data, respectively, along with imported resources from ExAC, COSMIC and CCLE. CNVIntegrate offers a CNV/CNA-data hub for structured information retrieval for clinicians and scientists towards important drug discoveries and precision treatments.

Database URL: http://cnvintegrate.cgm.ntu.edu.tw/
Aberrant lung lipids cause respiratory impairment in a Mecp2-deficient mouse model of Rett syndrome
Authors: Vashi Neeti , Ackerley Cameron , Post Martin , Justice Monica J
Published: July 2021

Severe respiratory impairment is a prominent feature of Rett syndrome, an X-linked disorder caused by mutations in methyl CpG-binding protein 2 (MECP2). Despite MECP2’s ubiquitous expression, respiratory anomalies are attributed to neuronal dysfunction. Here, we show that neutral lipids accumulate in mouse Mecp2-mutant lungs, whereas surfactant phospholipids decrease. Conditional deletion of Mecp2 from lipid-producing alveolar epithelial 2 (AE2) cells causes aberrant lung lipids and respiratory symptoms, whereas deletion of Mecp2 from hindbrain neurons results in distinct respiratory abnormalities. Single-cell RNA sequencing of AE2 cells suggests lipid production and storage increase at the expense of phospholipid synthesis. Lipid production enzymes are confirmed as direct targets of MECP2-directed nuclear receptor co-repressor 1/2 transcriptional repression. Remarkably, lipid-lowering fluvastatin improves respiratory anomalies in Mecp2-mutant mice. These data implicate autonomous pulmonary loss of MECP2 in respiratory symptoms for the first time and have immediate impacts on patient care.
Identifying oligodendrocyte enhancers governing Plp1 expression
Authors: Kim Dongkyeong , An Hongjoo , Fan Chuandong , Park Yungki
Published: July 2021

Oligodendrocytes (OLs) produce myelin in the central nervous system (CNS), which accelerates the propagation of action potentials and supports axonal integrity. As a major component of CNS myelin, proteolipid protein 1 (Plp1) is indispensable for the axon-supportive function of myelin. Notably, this function requires the continuous high-level expression of Plp1 in OLs. Equally important is the controlled expression of Plp1, as illustrated by Pelizaeus–Merzbacher disease for which the most common cause is PLP1 overexpression. Despite a decade-long search, promoter–distal OL enhancers that govern Plp1 remain elusive. We have recently developed an innovative method that maps promoter–distal enhancers to genes in a principled manner. Here, we applied it to Plp1, uncovering two OL enhancers for it (termed Plp1-E1 and Plp1-E2). Remarkably, clustered regularly interspaced short palindromic repeats (CRISPR) interference epigenome editing showed that Plp1-E1 and Plp1-E2 do not regulate two genes in their vicinity, highlighting their exquisite specificity to Plp1. Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) data show that Plp1-E1 and Plp1-E2 are OL-specific enhancers that are conserved among human, mouse and rat. Hi-C data reveal that the physical interactions between Plp1-E1/2 and PLP1 are among the strongest in OLs and specific to OLs. We also show that Myrf, a master regulator of OL development, acts on Plp1-E1 and Plp1-E2 to promote Plp1 expression.
Tracheal window resection and reconstruction via sternocleidomastoid flap for invasive thyroid carcinoma
Authors: Xia Xin , Cai Yonghua , Zhu Xiaoli , Zhu Yingying , Shen Le , Zhou Yalin , Diao Wenwen , Chen Xingming
Published: July 2021

OBJECTIVES

The aim of this study was to present surgical techniques and evaluate outcomes of a sternocleidomastoid muscle (SCM) myoperiosteal flap used for the reconstruction of tracheal or laryngotracheal defects after the radical resection of invasive thyroid carcinoma.

METHODS

A retrospective study was performed for patients at Peking Union Medical College Hospital from January 2008 to December 2018 of papillary thyroid carcinoma with tracheal or laryngotracheal invasion. Patients were enrolled only when they received window resection and reconstruction via an SCM myoperiosteal flap. The primary outcome was a stable airway, and the secondary outcome was survival.

RESULTS

A total of 15 invasive thyroid carcinoma patients were enrolled in this study. Laryngotracheal and tracheal reconstruction were performed in 11 and 4 patients respectively, with a median vertical defect of 3.5 cm (3.0, 4.5). A stable airway was achieved in 14 patients postoperatively. One patient experienced tracheal stenosis and received a second operation of tracheal sleeve resection and end-to-end anastomosis 105 days after the first operation. Tracheostomy was conducted in 5 out of 15 patients in whom the vertical defects were larger than 4 cm, and the tubes were extubated after a median time of 56 days (32, 84). The median observation time was 55 months (48, 86), and all 15 patients achieved a stable airway and showed no evidence of local recurrence at the end of follow-up.

CONCLUSIONS

For thyroid carcinoma with tracheal or laryngotracheal invasions, window resection with the SCM myoperiosteal flap reconstruction presented positive results in terms of a stable airway as well as oncological outcomes. The SCM myoperiosteal flap can be an appropriate reconstruction strategy, especially when the defects reach the thyroid cartilage.
Supravalvular aortic stenosis repair: surgical training of 2 repair techniques using 3D-printed models
Authors: Hussein Nabil , Honjo Osami , Barron David J , Yoo Shi-Joon
Published: July 2021

There are a number of techniques used in the surgical treatment of supravalvular aortic stenosis with excellent results; however, junior surgeons’ experience may be limited due to its rare nature. Simulation with 3D-printed models provides a safe platform for surgeons to rehearse surgical techniques prior to patient application but must replicate all features of surgical anatomy. Here, we describe how software manipulation can be used to accurately reproduce the surgical anatomy in supravalvular aortic stenosis and be used to train surgeons in 2 different techniques.
Limited Neutralization of Authentic Severe Acute Respiratory Syndrome Coronavirus 2 Variants Carrying E484K In Vitro
Authors: Widera Marek , Wilhelm Alexander , Hoehl Sebastian , Pallas Christiane , Kohmer Niko , Wolf Timo , Rabenau Holger F , Corman Victor M , Drosten Christian , Vehreschild Maria J G T , Goetsch Udo , Gottschalk Rene , Ciesek Sandra
Published: July 2021

Whether monoclonal antibodies are able to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern has been investigated using pseudoviruses. In this study we show that bamlanivimab, casirivimab, and imdevimab efficiently neutralize authentic SARS-CoV-2, including variant B.1.1.7 (alpha), but variants B.1.351 (beta) and P.2 (zeta) were resistant against bamlanivimab and partially resistant to casirivimab.

Whether antibodies are able to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variantshas been investigated using pseudoviruses. We show that authentic SARS-CoV-2 carrying E484K were resistant against bamlanivimab and less susceptible to casirivimab, convalescent and vaccine-elicited sera.
Evaluating Health Related Quality of Life and Emotions in Muslim and Jewish Kidney Transplant Patients
Authors: Tarabeih Mahdi , Bokek-Cohen Ya’arit , Azuri Pazit
Published: July 2021

Background

The scholarship on the impact of the source of the donated kidney (living donor = LD or deceased donor = DD) and the ethnoreligious background on the quality of life post-transplantation has received little scientific attention. The purpose of the present research is to evaluate health related quality of life and psychological feelings among kidney transplant (KT) recipients.

Methods

262 renal recipients completed the Health Related Quality Of Life (WHOQOL-BREF) questionnaire and answered the Transplant Effects Questionnaire (TxEQ) questionnaire assessing their post-transplantation emotional and psychological responses.

Results

KT Recipients reported medium levels of physical, psychological, social, and environmental dimensions of HRQOL. Muslim recipients reported significantly higher levels of physical, psychological, and social dimensions of HRQOL than Jews. Recipients of kidneys from LD reported higher levels of HRQOL. Recipients of kidney from a LD reported significantly higher levels of guilt and responsibility to be healthy.

Conclusions

Our findings indicate that receiving a graft from a LD contributes to the HRQOL in the physical, psychological, and environmental dimensions. Hence, donations from LD should be encouraged, by investing efforts in promoting public awareness of the importance of donating kidneys by LDs. Muslim kidney recipients enjoy better physical, social, and psychological HRQOL; this difference can be explained by the supportive and embracing familial and social networks characterizing traditional Arab communities. Post-transplantation support programs should be designed in order to provide further support and improve emotional and psychological responses to postoperative reality.
Is There Still a German IR Discourse? Investigations in the Semi-Periphery of an Academic Discipline
Authors: Steffek Jens , Lasshof Yannick
Published: July 2021

In non-English-speaking countries, international relations (IR) scholars often face considerable pressure to publish in international journals and address international debates. At the same time, they are expected to cater to national publics, politicians, and funding agencies. In this article, we investigate how German IR scholars navigate this terrain and whether a national IR discourse still exists in Germany. To answer this question, we analyze citation patterns and the formulation of the puzzle in twenty-five volumes of the Zeitschrift für Internationale Beziehungen, the German flagship journal of IR. We find that two-thirds of scholarly works cited in those articles are written in English. References to German-language literature cluster in articles written by authors without disciplinary affiliation in IR. The majority of research puzzles are also situated firmly in international discourses, while only a minority really target German debates. We conclude that not much of a distinctively German conversation over matters of IR is left, at least in academia. What is still there revolves around German foreign policy, theory issues, and, to some extent, European studies. On most other issues, authors link up directly to international debates even when addressing their German colleagues in German.
Megafauna Rewilding: Addressing Amnesia and Myopia in Biodiversity Law and Policy
Authors: Trouwborst Arie
Published: July 2021

Large mammals (megafauna) are disproportionately important for ecosystem functioning and biodiversity, but have been lost to disproportionate degrees, mostly in prehistoric times. Against the background of scientific knowledge regarding the state of ecosystems before a man-made wave of extinctions significantly reduced the numbers and diversity of megafauna on most continents, this article examines how (inter)national law and policy relate to efforts to restore large herbivores, omnivores and carnivores to terrestrial ecosystems around the world. Such megafauna rewilding, involving the (re)introduction of vanished species or proxies thereof, poses significant challenges to current laws and policies at national and domestic levels. These tend to have institutionalised a collective amnesia and myopia regarding what is ‘natural’ and ‘indigenous’. The success of future megafauna restoration efforts will partly depend on an understanding of what it takes to navigate, adjust or redesign applicable legal frameworks, and the article tables a research agenda to that end.
Artificial Diets With Different Protein Levels for RearingSpodoptera frugiperda(Lepidoptera: Noctuidae)
Authors: Truzi Caio Cesar , Vieira Natalia Fernanda , de Souza Joice Mendonça , De Bortoli Sergio Antonio
Published: July 2021

Spodoptera frugiperda (J.E. Smith, 1797) (Lepidoptera: Noctuidae) is a pest of great economic importance which can feed on more than 300 plant species. As it is polyphagous, its host plants may have variable physical and chemical constitutions. This may influence larval development, as protein and carbohydrate levels are important factors for adequate biological development. The aim of this study was to evaluate insect developmental parameters as well as to compare the food consumption of S. frugiperda larvae reared using diets with different protein levels under laboratory conditions. Three artificial diet formulations were used: one typically used for routine laboratory rearing, based on bean, wheat germ and brewer’s yeast (D1); one containing half the original amount of protein (D2), and the other with twice the original amount of protein (D3). The relative consumption rate (RCR), relative growth rate (RGR), and efficiency of conversion of ingested food (ECI) for S. frugiperda fourth instar larvae varied among diets. The protein present in the diet influenced the duration of larval and pupal periods and pupal weight, but did not affect larval survival, fecundity and longevity of adults. The different protein levels in the diets did not negatively influence population growth, so these three diet variations can be used for mass rearing in the laboratory. However, the influence of these diets on successive generations of the insect remains untested.
Prognostic model with alkaline phosphatase, lactate dehydrogenase and presence of Gleason pattern 5 for worse overall survival in low-risk metastatic hormone-sensitive prostate cancer
Authors: Tsuzuki Shunsuke , Kawano Shota , Fukuokaya Wataru , Mori Keiichiro , Nishikawa Hideomi , Tashiro Kojiro , Watanabe Daisuke , Uchimoto Taizo , Nishimura Kazuki , Yano Yusuke , Murakami Masaya , Koike Yusuke , Hata Kenichi , Koide Haruhisa , Miki Jun , Abe Hirokazu , Yamada Hiroki , Naruoka Takehito , Sugaya Shingo , Kimura Takahiro , Tomita Masayuki , Nakajo Hiroshi , Egawa Shin
Published: July 2021

Background

Randomized trials showed the survival benefits of the combined use of androgen receptor axis-targeted agents with androgen deprivation therapy in metastatic hormone-sensitive prostate cancer (mHSPC), regardless of the risk. However, treating patients with low-risk mHSPC with such intensive treatment is still debatable.

Methods

This retrospective study included 155 low-risk patients among 467 mHSPC patients treated in our affiliated institutions. The association between predictive factors and treatment outcomes was estimated using the Kaplan–Meier method and log-rank test. Predictive factors for castration resistant prostate cancer (CRPC)-free survival were investigated using Cox regression analyses.

Results

During the median follow-up of 39 months, 38.7% of patients developed CRPC and 14.2% died. In the multivariate analyses, a presence of Gleason pattern 5 (hazard ratio [HR] 2.04), high alkaline phosphatase (HR 1.007) and high lactate dehydrogenase (HR 1.009) were significant predictive factors for shorter CRPC-free survival. Finally, 155 patients were stratified into favorable- and unfavorable-risk groups based on the numbers of the predictive factors. The overall survival (OS) in the unfavorable-risk group (total scores: 2–3) was significantly worse than that of the favorable-risk group (total score: 0–1) (P = 0.02). This prognostic model was assessed with 50 low-risk mHSPC patients from the external validation dataset and found both the time to CRPC, and the OS in the unfavorable-risk group was significantly worse than that of the favorable-risk group (P < 0.01).

Conclusions

The combination of Gleason pattern 5, high alkaline phosphatase and lactate dehydrogenase can predict those with worse OS in low-risk mHSPC patients.
Ethnic Differences in Survival Among Lung Cancer Patients: A Systematic Review
Authors: Price Sarah N , Flores Melissa , Hamann Heidi A , Ruiz John M
Published: July 2021

Background

Despite a substantially worse risk factor profile, Hispanics in the United States experience lower incidence of many diseases and longer survival than non-Hispanic Whites (NHWs), an epidemiological phenomenon known as the Hispanic Health Paradox (HHP). This systematic review evaluated the published longitudinal literature to address whether this pattern extends to lung cancer survival.

Methods

Searches of Medline, PubMed, Embase, Web of Science, and the Cochrane Library were conducted for publications dated from January 1, 2000, to July 18, 2018. Records were restricted to articles written in English, employing a longitudinal design, and reporting a direct survival comparison (overall survival [OS], cancer-specific survival [CSS]) between NHW and Hispanic lung cancer patients.

Results

A final sample of 29 full-text articles were included, with 28 fully adjusted models of OS and 21 of CSS included. Overall, 26 (92.9%) OS models and 20 (95.2%) CSS models documented either no difference (OS = 16, CSS = 11) or a Hispanic survival advantage (OS = 10, CSS = 9). Both larger studies and those including foreign-born Hispanics were more likely to show a Hispanic survival advantage, and 2 studies of exclusively no-smokers showed a survival disadvantage. A number of reporting gaps were identified including Hispanic background and sociodemographic characteristics.

Conclusions

Hispanics exhibit similar or better survival in the context of lung cancer relative to NHWs despite a considerably worse risk factor profile. These findings support the HHP in the context of lung cancer. Further research is needed to understand the potential mechanisms of the HHP as it relates to lung cancer.
Simulating gas giant exoplanet atmospheres with Exo-FMS: comparing semigrey, picket fence, and correlated-k radiative-transfer schemes
Authors: Lee Elspeth K H , Parmentier Vivien , Hammond Mark , Grimm Simon L , Kitzmann Daniel , Tan Xianyu , Tsai Shang-Min , Pierrehumbert Raymond T
Published: July 2021

Radiative-transfer (RT) is a fundamental part of modelling exoplanet atmospheres with general circulation models (GCMs). An accurate RT scheme is required for estimates of the atmospheric energy transport and for gaining physical insight from model spectra. We implement three RT schemes for Exo-FMS: semigrey, non-grey ‘picket fence’, and real gas with correlated-k. We benchmark the Exo-FMS GCM, using these RT schemes to hot Jupiter simulation results from the literature. We perform a HD 209458b-like simulation with the three schemes and compare their results. These simulations are then post-processed to compare their observable differences. The semigrey scheme results show qualitative agreement with previous studies in line with variations seen between GCM models. The real gas model reproduces well the temperature and dynamical structures from other studies. After post-processing our non-grey picket fence scheme compares very favourably with the real gas model, producing similar transmission spectra, emission spectra, and phase curve behaviours. Exo-FMS is able to reliably reproduce the essential features of contemporary GCM models in the hot gas giant regime. Our results suggest the picket fence approach offers a simple way to improve upon RT realism beyond semigrey schemes.
Bridges and gaps at low-eccentricity first-order resonances
Authors: Antoniadou Kyriaki I , Libert Anne-Sophie
Published: July 2021

Previous works on the divergence of first-order mean-motion resonances (MMRs) have studied in detail the extent of the pericentric and apocentric libration zones of adjacent first-order MMRs, highlighting possible bridges between them in the low eccentricity circular restricted three-body problem. Here, we describe the previous results in the context of periodic orbits and show that the so-called circular family of periodic orbits is the path that can drive the passage between neighbouring resonances under dissipative effects. We illustrate that the circular family can bridge first-order and higher order resonances, while its gaps at first-order MMRs can serve as boundaries that stop transitions between resonances. In particular, for the Sun–asteroid–Jupiter problem, we show that, during the migration of Jupiter in the protoplanetary disc, a system initially evolving below the apocentric branch of a first-order MMR follows the circular family and can either be captured into the pericentric branch of an adjacent first-order MMR if the orbital migration is rapid or in a higher order MMR in case of slow migration. Radial transport via the circular family can be extended to many small body and planetary system configurations undergoing dissipative effects (e.g. tidal dissipation, solar mass-loss, and gas drag).
From dust to planets – I. Planetesimal and embryo formation
Authors: Coleman Gavin A L
Published: July 2021

Planet formation models begin with proto-embryos and planetesimals already fully formed, missing out a crucial step, the formation of planetesimals/proto-embryos. In this work, we include prescriptions for planetesimal and proto-embryo formation arising from pebbles becoming trapped in short-lived pressure bumps, in thermally evolving viscous discs to examine the sizes and distributions of proto-embryos and planetesimals throughout the disc. We find that planetesimal sizes increase with orbital distance, from ∼10 km close to the star to hundreds of kilometres further away. Proto-embryo masses are also found to increase with orbital radius, ranging from $10^{-6}{\, {\rm M}_{\oplus }}$ around the iceline, to $10^{-3}{\, {\rm M}_{\oplus }}$ near the orbit of Pluto. We include prescriptions for pebble and planetesimal accretion to examine the masses that proto-embryos can attain. Close to the star, planetesimal accretion is efficient due to small planetesimals, whilst pebble accretion is efficient where pebble sizes are fragmentation limited, but inefficient when drift dominated due to low accretion rates before the pebble supply diminishes. Exterior to the iceline, planetesimal accretion becomes inefficient due to increasing planetesimal eccentricities, whilst pebble accretion becomes more efficient as the initial proto-embryo masses increase, allowing them to significantly grow before the pebble supply is depleted. Combining both scenarios allows for more massive proto-embryos at larger distances, since the accretion of planetesimals allows pebble accretion to become more efficient, allowing giant planet cores to form at distances upto $10{\, {\rm au}}$. By including more realistic initial proto-embryo and planetesimal sizes, as well as combined accretion scenarios, should allow for a more complete understanding in the beginning to end process of how planets and planetary systems form.
The first ALMA survey of protoplanetary discs at 3 mm: demographics of grain growth in the Lupus region
Authors: Tazzari M , Testi L , Natta A , Williams J P , Ansdell M , Carpenter J M , Facchini S , Guidi G , Hogherheijde M , Manara C F , Miotello A , van der Marel N
Published: July 2021

We present the first ALMA survey of protoplanetary discs at 3 mm, targeting 36 young stellar objects in the Lupus star-forming region with deep observations (sensitivity 20–50 $\mu$Jy beam−1) at ∼0.35 arcsec resolution (∼50 au). Building on previous ALMA surveys at 0.89 and 1.3 mm that observed the complete sample of Class II discs in Lupus at a comparable resolution, we aim to assess the level of grain growth in the relatively young Lupus region. We measure 3 mm integrated fluxes, from which we derive disc-averaged 1–3 mm spectral indices. We find that the mean spectral index of the observed Lupus discs is $\alpha _\mathrm{1-3\, mm}=2.23\pm 0.06$, in all cases $\alpha _\mathrm{1-3\, mm}\lt 3.0$, with a tendency for larger spectral indices in the brightest discs and in transition discs. Furthermore, we find that the distribution of spectral indices in Lupus discs is statistically indistinguishable from that of the Taurus and Ophiuchus star-forming regions. Assuming the emission is optically thin, the low values $\alpha _\mathrm{1-3\, mm}\le 2.5$ measured for most discs can be interpreted with the presence of grains larger than 1 mm. The observations of the faint discs in the sample can be explained without invoking the presence of large grains, namely through a mixture of optically thin and optically thick emission from small grains. However, the bright (and typically large) discs do inescapably require the presence of millimetre-sized grains in order to have realistic masses. Based on a disc mass argument, our results challenge previous claims that the presence of optically thick substructures may be a universal explanation for the empirical millimetre size-luminosity correlation observed at 0.89 mm.
Increased miR-6875-5p inhibits plasmacytoid dendritic cell differentiation via the STAT3/E2-2 pathway in recurrent spontaneous abortion
Authors: Zhu Xiao-Xiao , Yin Xun-Qiang , Hei Guo-Zhen , Wei Ran , Guo Qiang , Zhao Lin , Zhang Zhen , Chu Chu , Fu Xiao-Xiao , Xu Ke , Li Xia
Published: July 2021

Recurrent spontaneous abortion (RSA) is a common complication of early pregnancy. Dendritic cells (DCs) are thought to confer fetal–maternal immunotolerance and play a crucial role in ensuring a successful pregnancy. A decrease of plasmacytoid dendritic cells (pDCs) was found to be involved in RSA, but the underlying mechanisms of decreased pDC in RSA remain unclear. MicroRNAs (miRNAs) play critical roles in RSA as well as the development, differentiation and functional regulation of pDCs; however, the regulatory effect of miRNAs on pDC in RSA has not been fully investigated. Here we demonstrated that both the proportion of pDC and signal transducer and activator of transcription (STAT3)/transcription factor 4 (Tcf4/E2-2) expression decreased in the peripheral blood mononuclear cells and decidua of patients with RSA compared to those with normal pregnancy (NP), and there was a significantly positive correlation between pDC and STAT3 mRNA. MiRNA microarray assay and quantitative reverse transcription PCR results showed that miR-6875-5p expression was markedly increased in women with RSA and negatively correlated with mRNA expression level of STAT3. Up-regulated miR-6875-5p could sensitively discriminate patients with RSA from NP subjects. Overexpression of miR-6875-5p significantly down-regulated the mRNA expression of STAT3 and E2-2 as well as the protein and phosphorylation level of STAT3, while miR-6875-5p knockdown showed opposite results. Dual luciferase reporter verified that miR-6875-5p regulated STAT3 expression by directly binding to its 3'untranslated region. Overall, our results suggested that increased miR-6875-5p is involved in RSA by decreasing the differentiation of pDCs via inhibition of the STAT3/E2-2 signaling pathway. miR-6875-5p may be explored as a promising diagnostic marker and therapeutic target for RSA.
Limited occurrence of the profunda morph of the quagga mussels (Dreissena rostriformis bugensis) in the Volga River reservoirs of Russia and limited genetic differences between morphs in Russia and North America
Authors: Pavlova Vera V , Stolbunova Veronika V , Elgin Ashley K
Published: July 2021

The quagga mussel Dreissena rostriformis bugensis is a highly invasive species. It plays an important role in benthic communities, influencing their structure and functioning. Two morphs of this mussel have been described: a shallow-water (i.e. the typical) morph and a deep-water morph, profunda. Currently, profunda has been found in several water bodies only within the nonnative range of D. r. bugensis. In North America, the profunda morph is widespread and abundant in the Laurentian Great Lakes. In Europe, profunda was found for the first time in 2009 in the Cheboksary Reservoir, which is located on the central part of the Volga River. A 2016 search for profunda in the four deepest Volga reservoirs (Cheboksary, Kuybyshev, Saratov and Volgograd) failed to find this morph even at the site where it was found in 2009. Traditional and outline-based morphometric analyses showed that only the shallow-water morph individuals inhabited studied sites at depths of 25–33 m. The present study revealed that morphological differences between the typical and profunda morphs from both the European and North American ranges were accompanied by limited genetic differences. Microsatellite analysis showed only minor differences in allele frequencies between morphs sampled in 2019 from the Cheboksary Reservoir; these differences were not significant after correction for null alleles. High phenotypic and ecological plasticity of D. r. bugensis may facilitate its invasion success.
Ribosome heterogeneity inDrosophila melanogastergonads through paralog-switching
Authors: Hopes Tayah , Norris Karl , Agapiou Michaela , McCarthy Charley G P , Lewis Philip A , O’Connell Mary J , Fontana Juan , Aspden Julie L
Published: July 2021

Ribosomes have long been thought of as homogeneous macromolecular machines, but recent evidence suggests they are heterogeneous and could be specialised to regulate translation. Here, we have characterised ribosomal protein heterogeneity across 4 tissues of Drosophila melanogaster. We find that testes and ovaries contain the most heterogeneous ribosome populations, which occurs through a combination of paralog-enrichment and paralog-switching. We have solved structures of ribosomes purified from in vivo tissues by cryo-EM, revealing differences in precise ribosomal arrangement for testis and ovary 80S ribosomes. Differences in the amino acid composition of paralog pairs and their localisation on the ribosome exterior indicate paralog-switching could alter the ribosome surface, enabling different proteins to regulate translation. One testis-specific paralog-switching pair is also found in humans, suggesting this is a conserved site of ribosome heterogeneity. Overall, this work allows us to propose that mRNA translation might be regulated in the gonads through ribosome heterogeneity, providing a potential means of ribosome specialisation.
Analysis of gene expression and mutation data points on contribution of transcription to the mutagenesis by APOBEC enzymes
Authors: Chervova Almira , Fatykhov Bulat , Koblov Alexander , Shvarov Evgeny , Preobrazhenskaya Julia , Vinogradov Dmitry , Ponomarev Gennady V , Gelfand Mikhail S , Kazanov Marat D
Published: July 2021

Since the discovery of the role of the APOBEC enzymes in human cancers, the mechanisms of this type of mutagenesis remain little understood. Theoretically, targeting of single-stranded DNA by the APOBEC enzymes could occur during cellular processes leading to the unwinding of DNA double-stranded structure. Some evidence points to the importance of replication in the APOBEC mutagenesis, while the role of transcription is still underexplored. Here, we analyzed gene expression and whole genome sequencing data from five types of human cancers with substantial APOBEC activity to estimate the involvement of transcription in the APOBEC mutagenesis and compare its impact with that of replication. Using the TCN motif as the mutation signature of the APOBEC enzymes, we observed a correlation of active APOBEC mutagenesis with gene expression, confirmed the increase of APOBEC-induced mutations in early-replicating regions and estimated the relative impact of transcription and replication on the APOBEC mutagenesis. We also found that the known effect of higher density of APOBEC-induced mutations on the lagging strand was highest in middle-replicating regions and observed higher APOBEC mutation density on the sense strand, the latter bias positively correlated with the gene expression level.
Differential ATAC-seq and ChIP-seq peak detection using ROTS
Authors: Faux Thomas , Rytkönen Kalle T , Mahmoudian Mehrad , Paulin Niklas , Junttila Sini , Laiho Asta , Elo Laura L
Published: July 2021

Changes in cellular chromatin states fine-tune transcriptional output and ultimately lead to phenotypic changes. Here we propose a novel application of our reproducibility-optimized test statistics (ROTS) to detect differential chromatin states (ATAC-seq) or differential chromatin modification states (ChIP-seq) between conditions. We compare the performance of ROTS to existing and widely used methods for ATAC-seq and ChIP-seq data using both synthetic and real datasets. Our results show that ROTS outperformed other commonly used methods when analyzing ATAC-seq data. ROTS also displayed the most accurate detection of small differences when modeling with synthetic data. We observed that two-step methods that require the use of a separate peak caller often more accurately called enrichment borders, whereas one-step methods without a separate peak calling step were more versatile in calling sub-peaks. The top ranked differential regions detected by the methods had marked correlation with transcriptional differences of the closest genes. Overall, our study provides evidence that ROTS is a useful addition to the available differential peak detection methods to study chromatin and performs especially well when applied to study differential chromatin states in ATAC-seq data.
How Women Shape Negativity in Parliamentary Speeches—A Sentiment Analysis of Debates in the Austrian Parliament
Authors: Haselmayer Martin , Dingler Sarah C , Jenny Marcelo
Published: July 2021

Though negativity in political debates influences citizens’ attitudes towards legislative institutions, research on how Members of Parliaments (MPs) use negative language remains scant. This study shows how the gender of speakers and the context of debates influence the level of negativity in parliamentary speeches. We argue that female MPs use less negative language than male colleagues due to gender differences in socialisation and stereotypical expectations. Applying sentiment analysis with word embeddings to 20 years of plenary speeches in the Austrian parliament, we find that speeches by women MPs are less negative on average compared to those of their male colleagues. A more balanced gender distribution within a party group decreases differences in tone by lowering the negativity of male speakers. A growing share of women in parliament can thus change the tone of debates, which might enhance the legitimacy of political institutions and the quality of democracy.