bluuebunny/crossref_metadata_2025 huggingface dataset:
Signaling repurposable drug combinations against COVID-19 by developing the heterogeneous deep herb-graph method
Authors: Yang Fan , Zhang Shuaijie , Pan Wei , Yao Ruiyuan , Zhang Weiguo , Zhang Yanchun , Wang Guoyin , Zhang Qianghua , Cheng Yunlong , Dong Jihua , Ruan Chunyang , Cui Lizhen , Wu Hao , Xue Fuzhong
Published: March 2022

Background

Coronavirus disease 2019 (COVID-19) has spurred a boom in uncovering repurposable existing drugs. Drug repurposing is a strategy for identifying new uses for approved or investigational drugs that are outside the scope of the original medical indication.

Motivation

Current works of drug repurposing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are mostly limited to only focusing on chemical medicines, analysis of single drug targeting single SARS-CoV-2 protein, one-size-fits-all strategy using the same treatment (same drug) for different infected stages of SARS-CoV-2. To dilute these issues, we initially set the research focusing on herbal medicines. We then proposed a heterogeneous graph embedding method to signaled candidate repurposing herbs for each SARS-CoV-2 protein, and employed the variational graph convolutional network approach to recommend the precision herb combinations as the potential candidate treatments against the specific infected stage.

Method

We initially employed the virtual screening method to construct the ‘Herb-Compound’ and ‘Compound-Protein’ docking graph based on 480 herbal medicines, 12,735 associated chemical compounds and 24 SARS-CoV-2 proteins. Sequentially, the ‘Herb-Compound-Protein’ heterogeneous network was constructed by means of the metapath-based embedding approach. We then proposed the heterogeneous-information-network-based graph embedding method to generate the candidate ranking lists of herbs that target structural, nonstructural and accessory SARS-CoV-2 proteins, individually. To obtain precision synthetic effective treatments forvarious COVID-19 infected stages, we employed the variational graph convolutional network method to generate candidate herb combinations as the recommended therapeutic therapies.

Results

There were 24 ranking lists, each containing top-10 herbs, targeting 24 SARS-CoV-2 proteins correspondingly, and 20 herb combinations were generated as the candidate-specific treatment to target the four infected stages. The code and supplementary materials are freely available at https://github.com/fanyang-AI/TCM-COVID19.
Knowledge-based BERT: a method to extract molecular features like computational chemists
Authors: Wu Zhenxing , Jiang Dejun , Wang Jike , Zhang Xujun , Du Hongyan , Pan Lurong , Hsieh Chang-Yu , Cao Dongsheng , Hou Tingjun
Published: March 2022

Molecular property prediction models based on machine learning algorithms have become important tools to triage unpromising lead molecules in the early stages of drug discovery. Compared with the mainstream descriptor- and graph-based methods for molecular property predictions, SMILES-based methods can directly extract molecular features from SMILES without human expert knowledge, but they require more powerful algorithms for feature extraction and a larger amount of data for training, which makes SMILES-based methods less popular. Here, we show the great potential of pre-training in promoting the predictions of important pharmaceutical properties. By utilizing three pre-training tasks based on atom feature prediction, molecular feature prediction and contrastive learning, a new pre-training method K-BERT, which can extract chemical information from SMILES like chemists, was developed. The calculation results on 15 pharmaceutical datasets show that K-BERT outperforms well-established descriptor-based (XGBoost) and graph-based (Attentive FP and HRGCN+) models. In addition, we found that the contrastive learning pre-training task enables K-BERT to ‘understand’ SMILES not limited to canonical SMILES. Moreover, the general fingerprints K-BERT-FP generated by K-BERT exhibit comparative predictive power to MACCS on 15 pharmaceutical datasets and can also capture molecular size and chirality information that traditional binary fingerprints cannot capture. Our results illustrate the great potential of K-BERT in the practical applications of molecular property predictions in drug discovery.
3DGT-DDI: 3D graph and text based neural network for drug–drug interaction prediction
Authors: He Haohuai , Chen Guanxing , Yu-Chian Chen Calvin
Published: March 2022

Motivation

Drug–drug interactions (DDIs) occur during the combination of drugs. Identifying potential DDI helps us to study the mechanism behind the combination medication or adverse reactions so as to avoid the side effects. Although many artificial intelligence methods predict and mine potential DDI, they ignore the 3D structure information of drug molecules and do not fully consider the contribution of molecular substructure in DDI.

Results

We proposed a new deep learning architecture, 3DGT-DDI, a model composed of a 3D graph neural network and pre-trained text attention mechanism. We used 3D molecular graph structure and position information to enhance the prediction ability of the model for DDI, which enabled us to deeply explore the effect of drug substructure on DDI relationship. The results showed that 3DGT-DDI outperforms other state-of-the-art baselines. It achieved an 84.48% macro F1 score in the DDIExtraction 2013 shared task dataset. Also, our 3D graph model proves its performance and explainability through weight visualization on the DrugBank dataset. 3DGT-DDI can help us better understand and identify potential DDI, thereby helping to avoid the side effects of drug mixing.

Availability

The source code and data are available at https://github.com/hehh77/3DGT-DDI.
Structured Sparse Regularized TSK Fuzzy System for predicting therapeutic peptides
Authors: Guo Xiaoyi , Jiang Yizhang , Zou Quan
Published: March 2022

Therapeutic peptides act on the skeletal system, digestive system and blood system, have antibacterial properties and help relieve inflammation. In order to reduce the resource consumption of wet experiments for the identification of therapeutic peptides, many computational-based methods have been developed to solve the identification of therapeutic peptides. Due to the insufficiency of traditional machine learning methods in dealing with feature noise. We propose a novel therapeutic peptide identification method called Structured Sparse Regularized Takagi–Sugeno–Kang Fuzzy System on Within-Class Scatter (SSR-TSK-FS-WCS). Our method achieves good performance on multiple therapeutic peptides and UCI datasets.
Biscuits, the World Cup and Nobel Prizes: The Puzzling Documentation of Shin Bet Interrogations
Authors: Ballas Irit , Dagan Netanel
Published: March 2022

Records kept by security authorities documenting potentially violent encounters are generally characterized by technocratic language and parsimonious content, which is intended to project an image of objective and impartial state officials. A qualitative analysis of 688 records covering interrogations of suspects in terror activities by the Israeli Security Agency (Shin Bet) presents a very different picture. They consist of representations of (1) hospitality—caring for the well-being of the person under interrogation; (2) camaraderie—amicable conversations between interrogator and interrogee; and (3) moral conviction—impassioned political or moral debates regarding the Israeli–Palestinian conflict. The analysis shows how unconventional documentation techniques in security interrogations may be used to preserve legitimacy; bolster professional prestige and makes a sophisticated use of a sense of secrecy.
Single-cell transcriptomes in the heart: when every epigenome counts
Authors: Gromova Tatiana , Gehred Natalie D , Vondriska Thomas M
Published: March 2022

The response of an organ to stimuli emerges from the actions of individual cells. Recent cardiac single-cell RNA-sequencing studies of development, injury, and reprogramming have uncovered heterogeneous populations even among previously well-defined cell types, raising questions about what level of experimental resolution corresponds to disease-relevant, tissue-level phenotypes. In this review, we explore the biological meaning behind this cellular heterogeneity by undertaking an exhaustive analysis of single-cell transcriptomics in the heart (including a comprehensive, annotated compendium of studies published to date) and evaluating new models for the cardiac function that have emerged from these studies (including discussion and schematics that depict new hypotheses in the field). We evaluate the evidence to support the biological actions of newly identified cell populations and debate questions related to the role of cell-to-cell variability in development and disease. Finally, we present emerging epigenomic approaches that, when combined with single-cell RNA-sequencing, can resolve basic mechanisms of gene regulation and variability in cell phenotype.
Gender-related presentation, surgical treatment, outcome and failure to rescue after surgery for type A aortic dissection: results from a multicentre registry
Authors: Francica Alessandra , Vendramin Igor , Salizzoni Stefano , D’Onofrio Augusto , Gatti Giuseppe , Rinaldi Mauro , Gerosa Gino , Pappalardo Aniello , Livi Ugolino , Faggian Giuseppe , Onorati Francesco
Published: March 2022

OBJECTIVES

Reports on gender-related differences in perioperative characteristics and the outcome after surgery for type A acute aortic dissection are contradictory.

METHODS

Perioperative characteristics, outcome and overall or itemized failure-to-rescue rates were collected retrospectively and dichotomized by gender in patients operated on at 5 referral institutions. A propensity score matched analysis was performed to compared males and females with similar preoperative risk profiles. Multivariable analysis assessed gender-related predictors of 30-day mortality.

RESULTS

A total of 1271 patients were collected. Females (on average, 63 years old) developed type A acute aortic dissection, with differences in clinical presentation (number of intimal tears, thoracic pain at the onset of symptoms). Female-reported characteristics included lower frozen elephant trunk and elephant trunk procedures, higher femoral perfusion, retrograde cerebral perfusion and retrograde cardiopulmonary bypass restart after deep hypothermic circulatory arrest (P < 0.05). The 30-day mortality was 19.8%, without a gender-related difference (P = 0.37). No substantial differences in hospital outcome and in items related to failure to rescue were reported. A total of 256 propensity score matched pairs of males and females were investigated. Previous differences in surgical techniques and strategies were still confirmed; however, a higher incidence of postoperative permanent coma (P = 0.02) was reported in the female population.

CONCLUSIONS

Different surgical techniques and operative strategies were used on the 2 genders, with a lower complexity in females. However, there were no differences in hospital outcome between genders, except for the higher incidence of coma in female patients.
Sex differences in mortality after first time, isolated coronary artery bypass graft surgery: a systematic review and meta-analysis of randomized controlled trials
Authors: Matthews Stacey , Buttery Amanda , O’Neil Adrienne , Sanders Julie , Marasco Silvana , Fredericks Suzanne , Martorella Geraldine , Keenan Niamh , Ghanes Anand , Wynne Rochelle
Published: March 2022

Aim

Reports of sex-specific differences in mortality after coronary artery bypass graft surgery (CABGS) are contradictory. The review aim was to determine whether CABGS is differentially efficacious than alternative procedures by sex, on short- and longer-term mortality.

Methods and results

EMBASE, CINAHL, Medline, and the Cochrane Library were searched. Inclusion criteria: English language, randomized controlled trials from 2010, comparing isolated CABGS to alternative revascularization. Analyses were included Mantel–Haenszel fixed-effects modelling, risk of bias (Cochrane RoB2), and quality assessment (CONSORT). PROSPERO Registration ID: CRD42020181673. The search yielded 4459 citations, and full-text review of 29 articles revealed nine studies for inclusion with variable time to follow-up. Risk of mortality for women was similar in pooled analyses [risk ratio (RR) 0.94, 95% confidence interval (CI) 0.84–1.05, P = 0.26] but higher in sensitivity analyses excluding ‘high risk’ patients (RR 1.22, 95% CI 1.01–1.48, P = 0.04). At 30 days and 10 years, in contrast to men, women had an 18% (RR 0.82, 95% CI 0.66–1.02, P = 0.08) and 19% (RR 0.81, 95% CI 0.69–0.95, P = 0.01) mortality risk reduction. At 1–2 years women had a 7% (RR 1.07, 95% CI 0.69–1.64, P = 0.77), and at 2–5 years a 25% increase in risk of mortality compared with men (RR 1.25, 95% CI 1.03–1.53, P = 0.03). Women were increasingly under-represented over time comprising 41% (30 days) to 16.7% (10 years) of the pooled population.

Conclusion

Meta-analysis revealed inconsistent sex-specific differences in mortality after CABGS. Trials with sex-specific stratification are required to ensure appropriate sex-differentiated treatments for revascularization.
Biotechnological use of dairy by-products for the production and microencapsulation of the food preservative enterocin CRL35
Authors: Farizano Juan V , Díaz Vergara Ladislao I , Masias Emilse , Baillo Ayelén A , Torino María I , Fadda Silvina , Vanden Braber Noelia L , Montenegro Mariana A , Saavedra Lucila , Minahk Carlos
Published: March 2022

Bacteriocins from Gram-positive bacteria have been proposed as natural food preservative and there is a need for large-scale production for commercial purposes. The aim of the present work is to evaluate whey, a cheese industrial by-product, for the production and microencapsulation of enterocin CRL35. Whey proved to be a promising basal medium for bacterial growth although the bacteriocin production was quite low. However, it could be much favored with the addition of yeast extract at concentrations as low as 0.5%. Besides improving bacteriocin production, this peptide was successfully microencapsulated by spray drying using whey protein concentrate and a chitosan derivative as wall materials. Microcapsules averaging 10 ± 5 μm diameter were obtained, with good structural integrity and high antimicrobial activity with a stability of at least 12 weeks at 4°C. In summary, sustainable bacteriocin production and microencapsulation was achieved recycling whey or its derivatives. In addition, the formulation owns high antimicrobial activity with a long shelf life. The development of a food preservative may represent a green solution for handling whey.
Effects of temperature and water saturation on the elastic moduli of sandstone and mudstone from the Lufeng geothermal field: experimental results and theoretical model
Authors: Zou Guangui , Zeng Hu , Gong Fei , Yin Caiyun , Li Shengqi , Peng Suping , Xu Zhengwei
Published: March 2022

The key issue in the 3-D seismic exploration of geothermal reservoirs is to determine how the petrophysical properties of geothermal reservoirs change with temperature. In this paper, physical experiments on six rock samples from the Yunnan Lufeng geothermal field were used to analyse the effect of temperature on the elastic moduli of dry rock. The laboratory measurements show that under formation pressure conditions, the bulk modulus and shear modulus of the studied rock decrease linearly with increasing temperature, and the rock moduli exhibit approximately linear relationships with temperature. Gassmann's equation can be used to predict the influence of pore fluid on the P- and S-wave velocities of the rocks. To include the temperature effect in Gassmann's equation, we separately considered the rock matrix and pore fluid; we combined thermoelastic theory to introduce the influence of temperature on the rock into Gassmann's equation and directly considered the influence of temperature on the pore fluid. The effects of fluid on the physical properties of rocks were evaluated based on Gassmann's equation while considering the effect of temperature. The results show that the rock shear modulus is affected by temperature more than the bulk modulus is, which implies that the S-wave information is more sensitive to temperature. When the uniform water saturation is less than 95 per cent, temperature is the main factor influencing the rock bulk modulus. When the uniform water saturation is greater than 95 per cent, the fluid is the main factor influencing the rock bulk modulus, and the rock shear modulus is affected by only temperature. Fluid replacement with Gassmann's equation achieves results that are more consistent with laboratory measurements when the influence of temperature is considered. Gassmann's equation considering the effect of temperature reveals crucial dependences of the seismic wave velocities and elastic moduli on temperature and fluid content.
An algorithm to assess the heating strategy of buildings in cold climates: a case study of Germany
Authors: Mazhar Abdur Rehman , Zou Yuliang , Zeng Cheng , Shen Yongliang , Liu Shuli
Published: March 2022

Two-thirds of the final energy consumption of the EU residential sector goes towards space heating of buildings, yet a huge portion of the population still suffers from energy poverty. Identifying optimum heating strategies of current buildings would be a solution to this crisis, which is the main aim of the developed algorithm in this research. The algorithm incorporates a modified version of the simple hourly method from the ISO 13790 standard to determine the hourly heating load and indoor temperatures of buildings based on any heating strategy. Flexibility in the input of building and weather data make this tool versatile with practicality towards building users and policymakers. With this algorithm, a case study to evaluate three commonly used domestic heating strategies has been established for nine different residential buildings in typical cold winter conditions in Germany. Most EU households heat their buildings either continuously throughout the day at fixed temperatures, sporadically at fixed times or at peak loads during the evening. The continuous heating strategy is rated the best consuming minimal energy with consistent temperatures and optimal thermal comfort ranges. The sporadic and peak load heating strategies provide fluctuating indoor temperatures with high standard deviations of up to 8.70°C while consuming a similar cumulative energy to the continuous heating strategy. Additionally, both these aforementioned strategies augment energy poverty and promote indoor mould formation on the building envelope caused by water vapor condensation. Consequently, this algorithm can be applicable to any building type of any region.
A randomized controlled trial of a pharmacist-led intervention to enhance knowledge of Vietnamese patients with type 2 diabetes mellitus
Authors: Nguyen Thao H , Tran Tam T T , Nguyen Nguyet K , Diep Han G , Vo Son D , Taxis Katja , Pham Suol T , Nguyen Thang
Published: March 2022

Objectives

We aimed to assess whether a pharmacist-led intervention enhances knowledge, medication adherence and glycemic control in patients with type 2 diabetes mellitus (T2DM).

Methods

We conducted a single-blinded randomized controlled trial in Vietnam. Individuals with T2DM were recruited from a general hospital and randomly allocated to intervention and routine care. The intervention group received routine care plus counselling intervention by a pharmacist, including providing drug information and answering individual patients’ queries relating to T2DM and medications, which had not been done in routine care. We assessed the outcomes: knowledge score as measured by the Diabetes Knowledge Questionnaire, self-reported adherence and fasting blood glucose (FBG) at the 1-month follow-up.

Key findings

A total of 165 patients (83 intervention, 82 control) completed the study; their mean age was 63.33 years, and 49.1% were males. The baseline characteristics of the patients were similar between the groups. At 1-month follow-up, the pharmacist’s intervention resulted in an improvement in all three outcomes: knowledge score [B = 5.527; 95% confidence intervals (CI): 3.982 to 7.072; P < 0.001], adherence [odds ratio (OR) = 9.813; 95% CI: 2.456 to 39.205; P = 0.001] and attainment of target FBG (OR = 1.979; 95% CI: 1.029 to 3.806; P = 0.041).

Conclusions

The pharmacist-led intervention enhanced disease knowledge, medication adherence and glycemic control in patients with T2DM. This study provides evidence of the benefits of pharmacist counselling in addition to routine care for T2DM outpatients in a Vietnam population.
Emotional and Gendered Sense-Making through Apologies for Conflict-Related Sexual Violence
Authors: Dolan Emma
Published: March 2022

This article examines the specific, gendered discourses, which can be uncovered within political apologies for conflict-related sexual violence (CRSV) and sexualized torture. While apologies are often perceived as either cynical, normatively “empty” gestures that seek to carry out strategic interests or as attempts by political actors to (albeit, often inadequately) emphasize their commitment to addressing past violence and associated cultures of impunity, a feminist analysis of two cases of apology for CRSV (the Japanese imperial “comfort women” and the United States’ infamous Abu Ghraib torture “scandal”) demonstrates that political apologies are rich affective–discursive, deliberately emotional sites at which CRSV is explained and/or accounted for by the state. Specifically, I trace how political apologies operate to discursively and affectively claim and renounce institutional responsibility for CRSV through the common-sense but “slippery” gendered logics of rational/emotional and public/private.
Child Emotion Regulation Capacity Moderates the Association Between Parent Behaviors and Child Distress During Pediatric Venipuncture
Authors: Constantin Kaytlin L , Lupo-Flewelling Kathryn , Moline Rachel L , McMurtry C Meghan
Published: March 2022

Objectives

Medical needle procedures are a common source of pain, distress, and fear for children, which can worsen over time and lead to needle noncompliance and avoidance, if unaddressed. Children’s pain experience is multiply determined by external (e.g., parent behaviors) and internal (e.g., cognitive and affective) factors. Some parent behaviors (e.g., reassurance, giving control to child, empathy, apologies, criticism) have related to poor child pain experiences. No research has examined how children’s internal emotion regulation, commonly measured via heart rate variability (HRV), may buffer, or strengthen this association. This study is the first to examine child HRV in relation to pain experiences, and as a moderator between a constellation of parent behaviors (reassurance, giving control, empathy) and child pain, fear, and distress.

Methods

Sixty-one children aged 7–12 years undergoing venipuncture and a parent participated. Child HRV was measured before the procedure. After venipuncture, children rated their pain and fear. Parent and child behaviors during venipuncture were coded using the “distress promoting” and “distress” composites of the Child-Adult Medical Procedure Interaction Scale-Revised.

Results

Children with lower HRV displayed greater distress. Child HRV moderated the positive association between parent behaviors (reassurance, giving control, empathy) and child distress such that the association was strongest among children with low HRV.

Conclusions

Findings suggest children with lower HRV, indicative of lower emotion regulation capacity, may be at risk of experiencing higher levels of distress and may be more vulnerable to distress when facing parent reassurance, giving control, and empathy verbalizations during venipuncture.
Cut-down assisted percutaneous gastrostomy tube placement in morbidly obese patient
Authors: Vishwakarma Unnati , Hlayhel Ahmad , Yanagawa Franz S
Published: March 2022

Enteral and parenteral nutrition is primarily indicated in patients that lack adequate oral intake to support their metabolic needs. Percutaneous endoscopic gastrostomy (PEG) has become the preferred procedure of choice. With the increasing prevalence of obesity in the USA, there is a need for special interventions for PEG tube placements in overweight and obese patients. Some challenges that frequently arise with obese patients include sub-optimal transillumination, insufficient abdominal landmarks and inability to estimate the abdominal and gastric walls. We present a case of a patient with persistent dysphagia requiring enteral nutrition with an unconventional placement of a PEG tube given patient’s large body habitus.
Evaluation of RT-LAMP Assay for Rapid Detection of SARS-CoV-2
Authors: Li Ya-Ping , Cao Xun-Jie , Luo Xin , Xie Tian-Ao , Liu Wan-Jun , Xie Shi-Ming , Lin Min , Guo Xu-Guang
Published: March 2022

Objective

To evaluate the accuracy of the reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in community or primary-care settings.

Method

We systematically searched the Web of Science, Embase, PubMed, and Cochrane Library databases. We conducted quality evaluation using ReviewManager software (version 5.0). We then used MetaDisc software (version 1.4) and Stata software (version 12.0) to build forest plots, along with a Deeks funnel plot and a bivariate boxplot for analysis.

Result

Overall, the sensitivity, specificity, and diagnostic odds ratio were 0.79, 0.97, and 328.18, respectively. The sensitivity for the subgroup with RNA extraction appeared to be higher, at 0.88 (0.86–0.90), compared to the subgroup without RNA extraction, at 0.50 (0.45–0.55), with no significant difference in specificity.

Conclusion

RT-LAMP assay exhibited high specificity regarding current SARS-CoV-2 infection. However, its overall sensitivity was relatively moderate. Extracting RNA was found to be beneficial in improving sensitivity.
Pulsational pair-instability supernovae: gravitational collapse, black hole formation, and beyond
Authors: Rahman N , Janka H-T , Stockinger G , Woosley S E
Published: March 2022

We investigate the final collapse of rotating and non-rotating pulsational pair-instability supernova progenitors with zero-age-main-sequence masses of 60, 80, and 115 M⊙ and iron cores between 2.37 and 2.72 M⊙ by 2D hydrodynamics simulations. Using the general relativistic NADA-FLD code with energy-dependent three-flavour neutrino transport by flux-limited diffusion allows us to follow the evolution beyond the moment when the transiently forming neutron star (NS) collapses to a black hole (BH), which happens within 350–580 ms after bounce in all cases. Because of high neutrino luminosities and mean energies, neutrino heating leads to shock revival within ≲ 250 ms post bounce in all cases except the rapidly rotating 60 M⊙ model. In the latter case, centrifugal effects support a 10 per cent higher NS mass but reduce the radiated neutrino luminosities and mean energies by ∼20 per cent and ∼10 per cent, respectively, and the neutrino-heating rate by roughly a factor of two compared to the non-rotating counterpart. After BH formation, the neutrino luminosities drop steeply but continue on a 1–2 orders of magnitude lower level for several 100 ms because of aspherical accretion of neutrino and shock-heated matter, before the ultimately spherical collapse of the outer progenitor shells suppresses the neutrino emission to negligible values. In all shock-reviving models BH accretion swallows the entire neutrino-heated matter and the explosion energies decrease from maxima around 1.5 × 1051 erg to zero within a few seconds latest. Nevertheless, the shock or a sonic pulse moves outward and may trigger mass-loss, which we estimate by long-time simulations with the prometheus code. We also provide gravitational-wave signals.
Unicorns and giraffes in the binary zoo: stripped giants with subgiant companions
Authors: El-Badry Kareem , Seeburger Rhys , Jayasinghe Tharindu , Rix Hans-Walter , Almada Silvia , Conroy Charlie , Price-Whelan Adrian M , Burdge Kevin
Published: March 2022

We analyse two binary systems containing giant stars, V723 Mon (‘the Unicorn’) and 2M04123153+6738486 (‘the Giraffe’). Both giants orbit more massive but less luminous companions, previously proposed to be mass-gap black holes. Spectral disentangling reveals luminous companions with star-like spectra in both systems. Joint modelling of the spectra, light curves, and spectral energy distributions robustly constrains the masses, temperatures, and radii of both components: the primaries are luminous, cool giants ($T_{\rm eff,\, giant} = 3800$ and $4000\, \rm K$, $R_{\rm giant}= 22.5$ and $25\, {\rm R}_{\odot }$) with exceptionally low masses ($M_{\rm giant} \approx 0.4\, {\rm M}_{\odot }$) that likely fill their Roche lobes. The secondaries are only slightly warmer subgiants ($T_{\rm eff,\, 2} = 5800$ and $5150\, \rm K$, $R_2= 8.3$ and $9\, {\rm R}_{\odot }$) and thus are consistent with observed UV limits that would rule out main-sequence stars with similar masses ($M_2 \approx 2.8$ and ${\approx}1.8\, {\rm M}_{\odot }$). In the Unicorn, rapid rotation blurs the spectral lines of the subgiant, making it challenging to detect even at wavelengths where it dominates the total light. Both giants have surface abundances indicative of CNO processing and subsequent envelope stripping. The properties of both systems can be reproduced by binary evolution models in which a $1{-}2\, {\rm M}_{\odot }$ primary is stripped by a companion as it ascends the giant branch. The fact that the companions are also evolved implies either that the initial mass ratio was very near unity, or that the companions are temporarily inflated due to rapid accretion. The Unicorn and Giraffe offer a window into into a rarely observed phase of binary evolution preceding the formation of wide-orbit helium white dwarfs, and eventually, compact binaries containing two helium white dwarfs.
Hαemission in local galaxies: star formation, time variability, and the diffuse ionized gas
Authors: Tacchella Sandro , Smith Aaron , Kannan Rahul , Marinacci Federico , Hernquist Lars , Vogelsberger Mark , Torrey Paul , Sales Laura , Li Hui
Published: March 2022

The nebular recombination line H α is widely used as a star formation rate (SFR) indicator in the local and high-redshift Universe. We present a detailed H α radiative transfer study of high-resolution isolated Milky-Way and Large Magellanic Cloud simulations that include radiative transfer, non-equilibrium thermochemistry, and dust evolution. We focus on the spatial morphology and temporal variability of the H α emission, and its connection to the underlying gas and star formation properties. The H α and H β radial and vertical surface brightness profiles are in excellent agreement with observations of nearby galaxies. We find that the fraction of H α emission from collisional excitation amounts to fcol ∼ 5–$10{{\ \rm per\ cent}}$, only weakly dependent on radius and vertical height, and that scattering boosts the H α luminosity by $\sim 40{{\ \rm per\ cent}}$. The dust correction via the Balmer decrement works well (intrinsic H α emission recoverable within 25 per cent), though the dust attenuation law depends on the amount of attenuation itself both on spatially resolved and integrated scales. Important for the understanding of the H α–SFR connection is the dust and helium absorption of ionizing radiation (Lyman continuum [LyC] photons), which are about $f_{\rm abs}\approx 28{{\ \rm per\ cent}}$ and $f_{\rm He}\approx 9{{\ \rm per\ cent}}$, respectively. Together with an escape fraction of $f_{\rm esc}\approx 6{{\ \rm per\ cent}}$, this reduces the available budget for hydrogen line emission by nearly half ($f_{\rm H}\approx 57{{\ \rm per\ cent}}$). We discuss the impact of the diffuse ionized gas, showing – among other things – that the extraplanar H α emission is powered by LyC photons escaping the disc. Future applications of this framework to cosmological (zoom-in) simulations will assist in the interpretation of spectroscopy of high-redshift galaxies with the upcoming James Webb Space Telescope.
Evolution of the dust trail of comet 17P/Holmes
Authors: Gritsevich Maria , Nissinen Markku , Oksanen Arto , Suomela Jari , Silber Elizabeth A
Published: March 2022

The massive outburst of the comet 17P/Holmes in 2007 October is the largest known outburst by a comet thus far. We present a new comprehensive model describing the evolution of the dust trail produced in this phenomenon. The model comprises of multiparticle Monte Carlo simulation including the solar radiation pressure effects, gravitational disturbance caused by Venus, Earth and Moon, Mars, Jupiter and Saturn, and gravitational interaction of the dust particles with the parent comet itself. Good accuracy of computations is achieved by its implementation in Orekit, which executes Dormad-Prince numerical integration methods with higher precision. We demonstrate performance of the model by simulating particle populations with sizes from 0.001 to 1 mm with corresponding spherically symmetric ejection speed distribution, and towards the Sun outburst modelling. The model is supplemented with and validated against the observations of the dust trail in common nodes for 0.5 and 1 revolutions. In all cases, the predicted trail position showed a good match to the observations. Additionally, the hourglass pattern of the trail was observed for the first time within this work. By using variations of the outburst model in our simulations, we determine that the assumption of the spherical symmetry of the ejected particles leads to the scenario compatible with the observed hourglass pattern. Using these data, we make predictions for the two-revolution dust trail behaviour near the outburst point that should be detectable by using ground-based telescopes in 2022.
Multiple Mechanisms of Photoreceptor Spectral Tuning inHeliconiusButterflies
Authors: McCulloch Kyle J. , Macias-Muñoz Aide , Mortazavi Ali , Briscoe Adriana D.
Published: March 2022

The evolution of color vision is often studied through the lens of receptor gain relative to an ancestor with fewer spectral classes of photoreceptor. For instance, in Heliconius butterflies, a genus-specific UVRh opsin duplication led to the evolution of UV color discrimination in Heliconius erato females, a rare trait among butterflies. However, color vision evolution is not well understood in the context of loss. In Heliconius melpomene and Heliconius ismenius lineages, the UV2 receptor subtype has been lost, which limits female color vision in shorter wavelengths. Here, we compare the visual systems of butterflies that have either retained or lost the UV2 photoreceptor using intracellular recordings, ATAC-seq, and antibody staining. We identify several ways these butterflies modulate their color vision. In H. melpomene, chromatin reorganization has downregulated an otherwise intact UVRh2 gene, whereas in H. ismenius, pseudogenization has led to the truncation of UVRh2. In species that lack the UV2 receptor, the peak sensitivity of the remaining UV1 photoreceptor cell is shifted to longer wavelengths. Across Heliconius, we identify the widespread use of filtering pigments and co-expression of two opsins in the same photoreceptor cells. Multiple mechanisms of spectral tuning, including the molecular evolution of blue opsins, have led to the divergence of receptor sensitivities between species. The diversity of photoreceptor and ommatidial subtypes between species suggests that Heliconius visual systems are under varying selection pressures for color discrimination. Modulating the wavelengths of peak sensitivities of both the blue- and remaining UV-sensitive photoreceptor cells suggests that Heliconius species may have compensated for UV receptor loss.
MarcoPolo: a method to discover differentially expressed genes in single-cell RNA-seq data without depending on prior clustering
Authors: Kim Chanwoo , Lee Hanbin , Jeong Juhee , Jung Keehoon , Han Buhm
Published: March 2022

The standard analysis pipeline for single-cell RNA-seq data consists of sequential steps initiated by clustering the cells. An innate limitation of this pipeline is that an imperfect clustering result can irreversibly affect the succeeding steps. For example, there can be cell types not well distinguished by clustering because they largely share the global structure, such as the anterior primitive streak and mid primitive streak cells. If one searches differentially expressed genes (DEGs) solely based on clustering, marker genes for distinguishing these types will be missed. Moreover, clustering depends on many parameters and can often be subjective to manual decisions. To overcome these limitations, we propose MarcoPolo, a method that identifies informative DEGs independently of prior clustering. MarcoPolo sorts out genes by evaluating if the distributions are bimodal, if similar expression patterns are observed in other genes, and if the expressing cells are proximal in a low-dimensional space. Using real datasets with FACS-purified cell labels, we demonstrate that MarcoPolo recovers marker genes better than competing methods. Notably, MarcoPolo finds key genes that can distinguish cell types that are not distinguishable by the standard clustering. MarcoPolo is built in a convenient software package that provides analysis results in an HTML file.
Eukaryotic tRNA sequences present conserved and amino acid-specific structural signatures
Authors: Westhof Eric , Thornlow Bryan , Chan Patricia P , Lowe Todd M
Published: March 2022

Metazoan organisms have many tRNA genes responsible for decoding amino acids. The set of all tRNA genes can be grouped in sets of common amino acids and isoacceptor tRNAs that are aminoacylated by corresponding aminoacyl-tRNA synthetases. Analysis of tRNA alignments shows that, despite the high number of tRNA genes, specific tRNA sequence motifs are highly conserved across multicellular eukaryotes. The conservation often extends throughout the isoacceptors and isodecoders with, in some cases, two sets of conserved isodecoders. This study is focused on non-Watson–Crick base pairs in the helical stems, especially GoU pairs. Each of the four helical stems may contain one or more conserved GoU pairs. Some are amino acid specific and could represent identity elements for the cognate aminoacyl tRNA synthetases. Other GoU pairs are found in more than a single amino acid and could be critical for native folding of the tRNAs. Interestingly, some GoU pairs are anticodon-specific, and others are found in phylogenetically-specific clades. Although the distribution of conservation likely reflects a balance between accommodating isotype-specific functions as well as those shared by all tRNAs essential for ribosomal translation, such conservations may indicate the existence of specialized tRNAs for specific translation targets, cellular conditions, or alternative functions.
Grand rights and opera reuse today
Authors: Cuntz Alexander
Published: March 2022

This article studies the economic role of grand rights in the incentives to stage and reuse works from the opera canon. It complements previous research on the incentives to create new opera in the way it looks at copyright taxing availability and follow-on creativity around works. Based on a unique dataset of global opera performances, we find that changes in copyright status increase the number of total performances individual works receive on stage once copyright expires. Moreover, we provide preliminary evidence on chilling, long-term effects of status around premiering operas, and revivals at the beginning of the copyright term. Based on these findings, we discuss limitations of the study and novel options for copyright policy frameworks.
Credit, banking fragility, and economic performance
Authors: Creel Jérôme , Hubert Paul , Labondance Fabien
Published: March 2022

This article explores the role of banking fragility for the relationship between private credit and economic growth and bridges two literatures, one on the link between credit and economic growth and the other on the effects of banking fragility on credit dynamics. We consider two types of banking fragility on both the asset and liability sides: nonperforming loans and the ratio of bank capital to assets. Using a standard growth model framework and a dynamic generalized method of moment panel estimator on data for European Union countries, we find that banking fragility has a negative effect on economic growth. A consequence of considering banking fragility is that credit appears to have a positive effect on economic growth only when banking fragility is relatively low.
A Case of Burkholderia pseudomallei Mycotic Aneurysm Linked to Exposure in the Caribbean via Whole-Genome Sequencing
Authors: Speiser Lisa J , Kasule Sabirah , Hall Carina M , Sahl Jason W , Wagner David M , Saling Chris , Kole Amy , Meltzer Andrew J , Davila Victor , Orenstein Robert , Grys Thomas , Graf Erin
Published: March 2022

Melioidosis, an infection caused by Burkholderia pseudomallei, has a very high risk of mortality when treated, with an even higher risk of fatality if undiagnosed or not treated appropriately. It is endemic to Asia, Australia, South America, and the Caribbean; however, the number of melioidosis cases reported in the United States has been increasing. Therefore, physicians should be aware of this clinical entity and its possible presentations. Mycotic aneurysms due to B. pseudomallei are extremely rare, accounting for ~1%–2% of cases. Here we describe a rare case of melioidosis presenting as a mycotic aneurysm in the United States, highlight the potential for diagnostic challenges and epidemiologic concerns, and provide a review of mycotic aneurysm cases due to B. pseudomallei published to date.
Update to “Homologous Recombination Repair Defect May Predict Treatment Response to Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumors”
Authors: Zhu Mojun , Bekaii-Saab Tanios
Published: March 2022

This letter to the editor reports subsequent rechallenge with peptide receptor radionuclide therapy (PRRT) in a patient with pancreatic neuroendocrine tumor bearing BRCA1 mutation previously treated with PRRT.
Stigma and Health Disparities
Authors: Bart-Plange Diane-Jo , Trawalter Sophie
Published: March 2022

Members of many socially stigmatized and historically exploited groups are more likely to be ill, to be injured, and to die prematurely relative to members of socially privileged and historically advantaged groups. This is true in the United States and elsewhere. These disparities are often large, pervasive, and persistent, and constitute a public health crisis. Although pervasive, such large and pervasive disparities along lines of stigma are not obligatory. In the present chapter, we examine how stigma operates at the individual, interpersonal, and structural level to produce broad patterns of mental and physical health disparities. We then suggest some initial steps at the individual, interpersonal, and structural levels to reduce health disparities along the lines of stigma.
Peak Performance
Authors: Hatfield Johannes Lunde , Roberts Glyn C. , Lemyre Pierre-Nicolas
Published: March 2022

Peak performance has been investigated in the realm of sports for almost a century. Considerably fewer resources have been provided for studying peak performance in music. While musicians are usually left to their own devices, aspiring athletes are provided substantial support, knowledge, and resources on their journey toward excellence. In this chapter, our aim is to close this gap by providing musicians with access to basic psychological skills that have been adopted from peak performance techniques in sports. Two thematic questions will be addressed: Why can musicians benefit from psychological skills when pursuing peak performance? How can musicians apply psychological skills to their daily activities? In answering these questions, psychological skills such as goal setting, arousal regulation, concentration, and imagery are presented as foundational psychological skills in peak performance in music. Finally, hands-on examples of each psychological skill are discussed from a musical and an athletic perspective.
Learning Models of PTSD
Authors: Lissek Shmuel , Berg Hannah
Published: March 2022

Compared to anxiety disorders, posttraumatic stress disorder (PTSD) may be more clearly attributable to discrete, aversive learning events capable of evoking both conditioned fear responding to stimuli associated with the event and more general overreactivity—or failure to adapt—to intense, novel, or fear-related stimuli. The relatively straightforward link between PTSD and these basic, evolutionarily old learning processes of conditioning, sensitization, and habituation affords models of PTSD comprising fundamental, experimentally tractable mechanisms of learning that have been well characterized across a variety of mammalian species including humans. Though such learning mechanisms have featured prominently in explanatory models of psychological maladjustment to trauma for at least 100 years, much of the empirical testing of these models has occurred only in the past three decades. This chapter delineates the variety of theories forming this long-standing tradition of learning-based models of PTSD; details empirical evidence for such models; attempts an integrative account of results from this literature; and delineates limitations of, and future directions for, studies testing learning correlates of PTSD.
War Crimes, Atrocities, and Resistance in Colombia
Authors: Kaplan Oliver
Published: March 2022

Colombia has historically ranked as one of the most violent countries in the world. Yet it has not experienced genocide and is therefore not usually considered in texts on mass atrocities. This chapter reviews the diverse forms of atrocities in Colombia that a variety of armed actors have committed in recent history. It identifies several extermination campaigns that some have referred to as genocides as well as other patterns of massacres, forced displacements, and targeted political killings. Beyond these grave harms, the chapter also documents the widespread responses by the government and civil society to these atrocities. It concludes with a characterization of the continuing threats of violence in Colombia as well as a research agenda that offers hope for making the phrase nunca más (“never again”) a reality.
Surgical Research
Authors: Wall Anji , Testa Giuliano
Published: March 2022

Surgical research is a wide-ranging field that includes innovative procedures, novel devices, novel procedures, questioning established operative procedures, sham surgical placebo-controlled trials, perioperative care pathways, national registry studies, risk assessment modeling, and qualitative research. This chapter discusses these various types of surgical research, provides examples of surgical research trials that fit into these categories, and highlights the central ethical considerations in assessing each type of surgical research trial. Ultimately, the chapter shows that research ethics guidelines and benchmarks can be broadly applied to ethical questions regarding surgical research but must be tailored to the context of the surgical research study.