bluuebunny/crossref_metadata_2025 huggingface dataset:
Disentangling heterogeneity of psychosis expression in the general population: sex-specific moderation effects of environmental risk factors on symptom networks
Authors: Betz Linda T. , Penzel Nora , Rosen Marlene , Bhui Kamaldeep , Upthegrove Rachel , Kambeitz Joseph
Published: August 2021

Background

Psychosis expression in the general population may reflect a behavioral manifestation of the risk for psychotic disorder. It can be conceptualized as an interconnected system of psychotic and affective experiences; a so-called ‘symptom network’. Differences in demographics, as well as exposure to adversities and risk factors, may produce substantial heterogeneity in symptom networks, highlighting potential etiological divergence in psychosis risk.

Methods

To explore this idea in a data-driven way, we employed a novel recursive partitioning approach in the 2007 English National Survey of Psychiatric Morbidity (N = 7242). We sought to identify ‘network phenotypes’ by explaining heterogeneity in symptom networks through potential moderators, including age, sex, ethnicity, deprivation, childhood abuse, separation from parents, bullying, domestic violence, cannabis use, and alcohol.

Results

Sex was the primary source of heterogeneity in symptom networks. Additional heterogeneity was explained by interpersonal trauma (childhood abuse and domestic violence) in women and domestic violence, cannabis use, ethnicity in men. Among women, especially those exposed to early interpersonal trauma, an affective loading within psychosis may have distinct relevance. Men, particularly those from minority ethnic groups, demonstrated a strong network connection between hallucinatory experiences and persecutory ideation.

Conclusion

Symptom networks of psychosis expression in the general population are highly heterogeneous. The structure of symptom networks seems to reflect distinct sex-related adversities, etiologies, and mechanisms of symptom-expression. Disentangling the complex interplay of sex, minority ethnic group status, and other risk factors may help optimize early intervention and prevention strategies in psychosis.
How categorization impacts the design of requests: Asking for email addresses in call-centre interactions
Authors: Flinkfeldt Marie , Parslow Sophie , Stokoe Elizabeth
Published: August 2021

Marketing research shows that organizations tailor communication for particular customer ‘segments’, but little is known about the live design of interaction for different categories. To investigate this, we examine telephone calls to a holiday sales call-centre (for ‘seniors’) and a university admissions call-centre (for ‘young’ students). While topically different, call-takers in both datasets requested callers’ email addresses in order to progress service. Using conversation analysis, we examine how these requests were designed, where and how ‘age’ was made relevant, and how subsequent service provision was handled in a way that matched callers’ presumed age categories. Contrastive to the static notion of ‘segments’, we show how recipient design is bound up with categorial considerations while being responsive to the live unfolding of actual interaction. The article demonstrates how a comparative collection-based approach can be used to analyse the relevance of social categories in situations where this is implicit or ambiguous. (Membership categorization, customer segmentation, conversation analysis, recipient design, requests, age)*
How Do Non-Catastrophic Natural Disasters Impact Middle-Aged-to-Older Persons? Using Baseline Canadian Longitudinal Study on Aging Data to Explore Psychological Outcomes Associated with the 2013 Calgary Flood
Authors: Norberg Samantha J. , Toohey Ann M. , Hogan David B.
Published: August 2021

The objective of this study was to identify group-level health outcomes associated with the 2013 Calgary flood on Calgary participants (45–85 years of age) in the Canadian Longitudinal Study on Aging (CLSA). We compared baseline CLSA data collected on Calgary participants during the 6 months prior to and following the flood. Logistic regression models were created to explore whether select psychological outcomes were associated with the flood for participants categorized by evacuation status. Participants living in evacuated communities pre-flood had significantly lower levels of a diagnosed anxiety disorder than non-evacuated communities, which disappeared post-flood. Participants with higher household income were less likely to have post-traumatic stress disorder symptoms, worse self-rated mental health, and lower life satisfaction post-flood. Living alone reduced and female gender increased levels of perceived functional social support post-flood. Although natural disasters can shape research findings, the scope of the data being collected and the representativeness of impacted groups may challenge the ability to detect subtle impacts.
The 1783 proposal for a readymade note at the Bank of England
Authors: Batt David M.
Published: August 2021

This article analyses the 1783 proposal to issue readymade notes to the Bank of England's private banking customers. Prior to 1783, I argue that there were two broad categories under which the Bank issued its notes into circulation: (1) notes which were issued to government in relation to the Bank's role as facilitator of the fiscal revenues of state, and (2) notes which were issued to its private banking customers. The readymade note was a form of paper money which the Bank had previously been issuing only to government and, unlike the notes which the Bank originally issued to its private banking customers, was made out in advance of its being issued into circulation. I argue that the transformation suggested in the 1783 proposal was made possible by the unique relationship which the Bank had always had with the government, and I will make three observations based on identifying how this transformation took place.
L2 word recognition in French–English late bilinguals: Does modality matter?
Authors: Cornut Camille , Mahé Gwendoline , Casalis Séverine
Published: August 2021

Research in second language (L2) learning often considers one modality only during task completion. It is unclear if L2 performance is as accurate whatever the modality. L2 learning at school is characterized by a predominance of written materials. One might expect written L2 word recognition to be more accurate than spoken one. This modality effect could also depend on L2 proficiency and the presence of cognate items, closer orthographically than phonologically for most language pairs. Two experiments were conducted with 50 intermediate proficiency French–English bilinguals. Experiment 1 highlighted this modality effect on accuracy and a session effect reflecting a benefit from oral to written modality on latency. In Experiment 2, which included both cognate and non-cognate words, modality effect was even stronger for cognate words and cognate effect depended on modality. In both experiments, these effects depend on L2 proficiency. These findings are discussed according to bilingual word recognition models.
Developing neck circumference growth reference charts for Pakistani children and adolescents using the lambda–mu–sigma and quantile regression method
Authors: Asif Muhammad , Aslam Muhammad , Khan Saadia , Altaf Saima , Ahmad Shakeel , Qasim Muhammad , Ali Hamza , Wyszyńska Justyna
Published: August 2021

Objective:

Neck circumference (NC) is currently used as an embryonic marker of obesity and its associated risks. But its use in clinical evaluations and other epidemiological purposes requires sex and age-specific standardised cut-offs which are still scarce for the Pakistani paediatric population. We therefore developed sex and age-specific growth reference charts for NC for Pakistani children and adolescents aged 2–18 years.

Design:

Cross-sectional multi-ethnic anthropometric survey (MEAS) study.

Setting:

Multan, Lahore, Rawalpindi and Islamabad.

Participants:

The dataset of 10 668 healthy Pakistani children and adolescents aged 2–18 years collected in MEAS were used. Information related to age, sex and NC were taken as study variables. The lambda–mu–sigma (LMS) and quantile regression (QR) methods were applied to develop growth reference charts for NC.

Results:

The 5th, 10th, 25th, 50th, 75th, 90th and 95th smoothed percentile values of NC were presented. The centile values showed that neck size increased with age in both boys and girls. During 8 and 14 years of age, girls were found to have larger NC than boys. A comparison of NC median (50th) percentile values with references from Iranian and Turkish populations reveals substantially lower NC percentiles in Pakistani children and adolescents compared to their peers in the reference population.

Conclusion:

The comparative results suggest that the uses of NC references of developed countries are inadequate for Pakistani children. A small variability between empirical centiles and centiles obtained by QR procedure recommends that growth charts should be constructed by QR as an alternative method.
SPECTRALLY ACCURATE OPTION PRICING UNDER THE TIME-FRACTIONAL BLACK–SCHOLES MODEL
Authors: TOUR GERALDINE , THAKOOR NAWDHA , TANGMAN DÉSIRÉ YANNICK
Published: August 2021

We propose a Legendre–Laguerre spectral approximation to price the European and double barrier options in the time-fractional framework. By choosing an appropriate basis function, the spectral discretization is used for the approximation of the spatial derivatives of the time-fractional Black–Scholes equation. For the time discretization, we consider the popular$L1$finite difference approximation, which converges with order$\mathcal {O}((\Delta \tau )^{2-\alpha })$for functions which are twice continuously differentiable. However, when using the$L1$scheme for problems with nonsmooth initial data, only the first-order accuracy in time is achieved. This low-order accuracy is also observed when solving the time-fractional Black–Scholes European and barrier option pricing problems for which the payoffs are all nonsmooth. To increase the temporal convergence rate, we therefore consider a Richardson extrapolation method, which when combined with the spectral approximation in space, exhibits higher order convergence such that high accuracies over the whole discretization grid are obtained. Compared with the traditional finite difference scheme, numerical examples clearly indicate that the spectral approximation converges exponentially over a small number of grid points. Also, as demonstrated, such high accuracies can be achieved in much fewer time steps using the extrapolation approach.
DEMOGRAPHIC CHANGE AND PERCEPTIONS OF RACISM
Authors: Maggio Christopher
Published: August 2021

Various research has demonstrated that rapid racial demographic change may aid in triggering various forms of backlash under certain conditions. This has led scholars to speak of Whites “defending” their local environment in the face of eroding racial dominance. However, little research has addressed how perceptions of racism among minorities may be triggered under conditions of demographic change. This study attempts to fill this gap in the literature by examining the relationship between racial demographic change for Blacks, Hispanics, and Asians and perceptions of racial problems among these groups in the United States. Using standard OLS regressions, ordered logistic regressions, multinomial logistic regressions, and techniques accounting for selection into treatment, I find that Blacks and Hispanics living in counties undergoing rapid growth of Black and Hispanic populations, respectively, have higher perceptions of racial problems. Asians show no evidence of increased perceptions of racial problems in counties undergoing rapid Asian growth. For Blacks, this relationship is concentrated among those without at least a four-year degree and residents of counties with lower initial White populations (and higher initial Black populations). For Hispanics, it is similarly concentrated among those without at least a four-year degree, but also is likely stronger among residents of counties with higher initial White populations (and lower initial Hispanic populations), highlighting unique racial dynamics. This research adds to a growing body of work showing the importance of examining demographic change at the local level in order to understand some of today’s most pressing political and social issues.
The legal protection of persons living under the control of non-State armed groups
Authors: Rodenhäuser Tilman
Published: August 2021

In recent non-international armed conflicts in countries such as the Central African Republic, Iraq, Libya, Nigeria, South Sudan, Syria, Ukraine and Yemen, various non-State armed groups (NSAGs) have exercised control over territory and people living therein. In many cases, and for a variety of reasons, NSAGs perform some form of governance in these territories, which can include the maintenance of order or the provision of justice, health care, or social services. The significance of such measures became particularly apparent when in 2020 not only governments but also armed groups took steps to halt the spread of the COVID-19 pandemic. This article examines key legal issues that arise in these contexts. First, it analyzes the extent to which international humanitarian law protects the life and dignity of persons living under the control of NSAGs, rebutting doubts as to whether this field of international law has a role in regulating what is sometimes called “rebel governance”. Second, it provides a brief overview of aspects of the lives of people in armed group-controlled territory that are addressed by international humanitarian law and aspects that instead fall into the realm of human rights law. Third, the article discusses whether and to what extent human rights law can be said to bind NSAGs as a matter of law and flags issues that need further attention in current and future debates.
Twins Separated at Birth: Across a Country and Around the World/Twin Research: Memorial Tribute to Isaac Blickstein, MD; Infanticide and Sacrifice of Archaic-Aged Twins and Triplets; Prehistoric Twin Burials; Highlights from a Conference onThree Identical Strangers/Media Reports: An Atypical Twin Father; An Actor’s Twin Brother; Twin Link to Tulsa, Oklahoma Massacre; Superfetated Twins; Twin Comedians and Script Writers; Indian Twins’ Loss to COVID-19
Authors: Segal Nancy L.
Published: August 2021

Every reared-apart monozygotic (MZ) twin pair offers a fresh perspective on human developmental questions. This is true regardless of whether the co-twins were raised in the same country or across the globe. The members of two pairs of separated MZ female twins have recently come to attention. In one case the twins were raised by different families in Argentina; in the other case the twins were raised by different families in Sweden and Vietnam. The perceptions and perspectives of these twins are insightful. The twin research section that follows begins with a tribute to our late esteemed colleague, Dr Isaac Blickstein (1953−2020). Research concerning the infanticide and sacrifice of Archaic-aged twins and triplets and prehistoric twin burials is reviewed next. Highlights from a conference focused on the 2018 filmThree Identical Strangersare also included in this portion. The final section of this article includes media reports of an atypical twin father, an actor’s twin brother, a twin link to the 1921 Tulsa, Oklahoma massacre, the birth of superfetated twins, twin comedians and script writers and Indian twins’ tragic loss to COVID-19.
Antecedent Rainfall, Excessive Vegetation Growth and Its Relation to Wildfire Burned Areas in California
Authors: Hernández Ayala José J. , Mann Jenna , Grosvenor Elisabeth
Published: August 2021

In recent years, California has experienced wildfire seasons of increasing frequency and magnitude, especially in terms of wildfire burned areas. Here, we investigate the precipitation and vegetation growth preceding each wildfire season for the 2001–2020 period to determine if antecedent rainfall led to enhanced vegetation growth in wildfire burned areas in California. Precipitation data from the Global Precipitation Measurement (GPM) Mission and Normalized Difference Vegetation Index (NDVI) and the Enhanced Vegetation Index (EVI) data are examined to determine if antecedent rainfall and vegetation were normal, above, or below average, for the peak wet (December–February) and peak growth (March–May) periods preceding each wildfire season, as well as for the two previous wet and growth seasons. Then spatial correlations are done between precipitation and the vegetation indexes to determine the statistical significance of the relationships. Eleven of the 20 wildfire seasons were generally found to be preceded by above average levels of precipitation and vegetation growth. In three of the six seasons with more wildfire activities, linear regression model results show high positive correlations between precipitation and vegetation, suggesting that antecedent rainfall fueled vegetation growth that might have caused a significant impact on wildfire burned areas. Most of the larger wildfires in California, including the largest on record, exhibited positive correlations between antecedent rainfall and vegetation. Our results suggest that antecedent rainfall in California led to enhanced vegetation growth that later fueled more than half of the wildfire seasons analyzed in this study.
Cultivating a New Field at the Boundary Between Geoscience and Education Research
Authors: Kastens Kim A.
Published: August 2021

I was privileged to contribute to the creation of a new field, Geoscience Education Research. This liminal field, with roots in both education research and geosciences, is deepening how people think and learn about the Earth. In this article, I recount some of my twists and turns along way, and ponder whether such a zig‐zagging pathway was essential or a distraction. And if essential, what made it possible? Twenty‐first century geosciences aporous boundaries, with insights flowing in and out from health sciences, social sciences, humanities, business, and other physical sciences. Such boundary regions are fertile ground for both basic and use‐inspired research. If you feel drawn to a boundary region, perhaps my story can provide encouragement or advice.
The Landslide Hazard Chain in the Tapovan of the Himalayas on 7 February 2021
Authors: Jiang Ruochen , Zhang Limin , Peng Dalei , He Xin , He Jian
Published: August 2021

On February 7, 2021, a catastrophic landslide occurred in Chamoli, India on the southern hills of the Himalayas (N, E). About 28 × 106 m3 of landslide mass detached from the mountain face, entrained deposits in the valley and riverbed, and generated a huge debris flood along the Dhauliganga River. In this study, the geomorphological and volumetric characteristics of the disaster chain were interpreted from satellite images. The full process of the disaster chain and the erosion, deposition and flow discharge processes were reproduced using a cell‐based analysis program, Erosion–Deposition Debris Flow Analysis (EDDA). The results indicate a peak flow discharge of the debris flood at Tapovan Hydropower Station of about 25,000–28,000 m3/s. The main erosion and deposition zones are distributed along the valley floor and the Dhauliganga River, respectively. This study serves as basis for understanding the disaster chain dynamics in high mountain areas.
Electrical Conductivity of Aqueous NaCl at High Pressure and Low Temperature: Application to Deep Subsurface Oceans of Icy Moons
Authors: Pan Yilong , Yong Wenjun , Secco Richard A.
Published: August 2021

Sodium chloride (NaCl) may be an antifreeze in subsurface oceans of icy moons, so its electrical conductivity provides information on properties and processes complementing models of internal structure. We conducted experimental measurements of electrical conductivity of aqueous NaCl (NaCl(aq)) at 212–1,713 MPa and 233–295 K in a multianvil press, simulating high‐pressure and low‐temperature (HPLT) conditions of the subsurface oceans of icy moons such as Titan and Ganymede. A numerical model is proposed with , where σ is the conductivity (S/m), T the temperature (K), c* the NaCl(aq) molality (mol/kg), ρ the water density (g/cm3), ρ0 the NaCl(aq) density at standard condition (g/cm3), Λ0 is the limiting equivalent conductance (S cm2 equiv−1). We used this to generate conductivity distributions over a wide range of HPLT and at different concentrations. Significantly high electrical conductivity and large temperature sensitivity allow our data to provide useful experimental reference for future flyby observations.
Downscaling CESM2 in CLM5 to Hindcast Preindustrial Equilibrium Line Altitudes for Tropical Mountain Glaciers
Authors: Heavens Nicholas G.
Published: August 2021

Tropical mountain glaciers are an important water resource and highly impacted by recent climate change. Tropical mountain glaciation also occurred in the recent and deep past, which presents opportunities for better validating paleoclimate simulations in continental interiors and mountainous regions but requires bridging global model scales (hundreds of kilometers) with the 1–10 km scale of glaciers when paleotopography is poorly known. Here, we hindcast tropical mountain glaciation in preindustrial time by using global climate model meteorology to force standalone simulations in its land component that use high‐resolution topography to resolve selected tropical mountain glaciers. These simulations underestimate observed equilibrium line altitudes (ELAs) by 249 330 m, but the simulated ELA and snow lines capture observed intermountain ELA variability. Errors in large‐scale model precipitation and ELA reconstruction uncertainty are the main contributors to this bias.
A Metamorphic Origin for Europa's Ocean
Authors: Melwani Daswani Mohit , Vance Steven D. , Mayne Matthew J. , Glein Christopher R.
Published: August 2021

Europa likely contains an iron‐rich metal core. For it to have formed, temperatures within Europa reached1250 K. Going up to that temperature, accreted chondritic minerals — for example, carbonates and phyllosilicates — would partially devolatilize. Here, we compute the amounts and compositions of exsolved volatiles. We find that volatiles released from the interior would have carried solutes, redox‐sensitive species, and could have generated a carbonic ocean in excess of Europa's present‐day hydrosphere, and potentially an earlyatmosphere. No late delivery of cometary water was necessary. Contrasting with prior work,could be the most abundant solute in the ocean, followed by,, and. However, gypsum precipitation going from the seafloor to the ice shell decreases the dissolved S/Cl ratio, such that ClS at the shallowest depths, consistent with recently inferred endogenous chlorides at Europa's surface. Gypsum would form a 3–10 km thick sedimentary layer at the seafloor.
Reply to Comment on “An Active Plume Eruption on Europa During Galileo Flyby E26 as Indicated by Energetic Proton Depletions”
Authors: Huybrighs H. L. F. , Roussos E. , Blöcker A. , Krupp N. , Futaana Y. , Barabash S. , Hadid L. Z. , Holmberg M. K. G. , Witasse O.
Published: August 2021

In Huybrighs et al. (2020, https://doi.org/10.1029/2020gl087806) we investigated energetic proton depletions along Galileo's Europa flyby E26. Based on a particle tracing analysis, we proposed that depletions are caused by perturbed electromagnetic fields combined with atmospheric charge exchange and possible plumes. One depletion feature identified as a plume signature was shown to be an artifact (Jia et al., 2021, https://doi.org/10.1029/2020gl091550). Despite that, here we emphasize that Huybrighs et al. (2020, https://doi.org/10.1029/2020gl087806) demonstrates that plumes can cause proton depletions and that these features should be sought after. Furthermore, the conclusions on the importance of perturbed electromagnetic fields and atmospheric charge exchange on the depletions are unaffected. We suggest that the artifact's cause is a mistagging of protons as heavier ions by EPD. The artifact prevents us from confirming or excluding that there is a plume‐associated depletion. We also address comments on the MHD simulations and demonstrate that 540–1,040 keV losses are not necessarily inconsistent with 115–244 keV losses by plume‐associated charge exchange.
Night‐Time Ionospheric Localized Enhancements (NILE) Observed in North America Following Geomagnetic Disturbances
Authors: Chartier A. T. , Datta‐Barua S. , McDonald S. E. , Bust G. S. , Tate J. , Goncharenko L. P. , Romeo G. , Schaefer R. K.
Published: August 2021

The Ionospheric Data Assimilation Four‐Dimensional (IDA4D) technique has been coupled to Sami3, which is another model of the ionosphere (SAMI3). In this application, ground‐based and space‐based GPS total electron content (TEC) data have been assimilated into SAMI3, while in‐situ electron densities, autoscaled ionosonde NmF2, and reference GPS stations have been used for validation. IDA4D/SAMI3 shows that night‐time ionospheric localized enhancements (NILE) are formed following geomagnetic storms in November 2003 and August 2018. The NILE phenomenon appears as a moderate, longitudinally extended enhancement of NmF2 at 30°–40°N MLAT, occurring in the late evening (20–24 LT) following much larger enhancements of the equatorial anomaly crests in the main phase of the storms. The NILE appears to be caused by upward and northward plasma transport around the dusk terminator, which is consistent with eastward polarization electric fields. Independent validation confirms the presence of the NILE, and indicates that IDA4D is effective in correcting random errors and systematic biases in SAMI3. In all cases, biases and root‐mean‐square errors are reduced by the data assimilation, typically by a factor of 2 or more. During the most severe part of the November 2003 storm, the uncorrected ionospheric error on a GPS 3D position at 1LSU (Louisiana) is estimated to exceed 34 m. The IDA4D/SAMI3 specification is effective in correcting this down to 10 m.
The Critical Effect of Subgrid‐Scale Scheme on Simulating the Climate Impacts of Deforestation
Authors: Wang Dashan , Wu Jie , Huang Maoyi , Li Laurent Z. X. , Wang Dagang , Lin Ting , Dong Li , Li Qi , Yang Long , Zeng Zhenzhong
Published: August 2021

Land surface schemes (LSSs) in Earth System Models simulate how vegetation regulates land‐atmosphere fluxes of heat, water, carbon, and momentum. Despite advances in the spatial resolution of regional climate modeling, significant land cover changes occured at sub‐grid scale still not properly treated. Here, we investigate the response of evapotranspiration, representing the fluxes of heat and water, to deforestation in Southeast Asian Massif by employing three LSSs (Noah mosaic, Noah‐MP and Community Land Model (CLM)) with different approaches in representing sub‐grid variability, implemented in the Weather Research and Forecasting model. Two experiments, with and without satellite‐observed deforestation, were performed for each scheme. Results show that the simulations are highly sensitive to the subgrid‐scale approaches embedded in the LSSs. Compared with the observed historical climate, CLM outperforms other schemes and Noah mosaic shows the largest bias. However, if we target the simulation of the climate impacts of land cover change, the Noah mosaic scheme taking the sub‐grid approach can better capture the response of evapotranspiration to deforestation. The NoahMP and CLM schemes underestimate the evapotranspiration response in the grid cells where the dominant land cover type has not changed, but overestimate the response in those grid cells with dominant type changed, which is a characteristic of dominant‐grid approach. To improve our understanding of climate impacts induced by fine‐scale land cover change, future efforts to better represent subgrid‐scale variability and land‐atmosphere flux exchange in climate models are desirable.
PreMevE Update: Forecasting Ultra‐Relativistic Electrons Inside Earth's Outer Radiation Belt
Authors: Sinha Saurabh , Chen Yue , Lin Youzuo , Pires de Lima Rafael
Published: August 2021

Energetic electrons inside Earth's Van Allen belts pose a major radiation threat to space‐borne electronics that often play vital roles in modern society. Ultra‐relativistic electrons with energies greater than or equal to two megaelectron‐volt (MeV) are of particular interest, and thus forecasting these ≥2 MeV electrons has a significant meaning to all space sectors. Here, we update the latest development of the predictive model for MeV electrons in the outer radiation belt. The new version, called PREdictive MEV Electron (PreMevE)‐2E, forecasts ultra‐relativistic electron flux distributions across the outer belt, with no need for in situ measurements of the trapped MeV electron population except at the geosynchronous orbit (GEO). Model inputs include precipitating electrons observed in low‐Earth‐orbits by NOAA satellites, upstream solar wind speeds and densities from solar wind monitors, as well as ultra‐relativistic electrons measured by one Los Alamos GEO satellite. We evaluated 32 supervised machine learning models that fall into four different classes of linear and neural network architectures, and successfully tested ensemble forecasting by using groups of top‐performing models. All models are individually trained, validated, and tested by in situ electron data from NASA's Van Allen Probes mission. It is shown that the final ensemble model outperforms individual models at most L‐shells, and this PreMevE‐2E model can provide 25‐h (∼1‐day) and 50‐h (∼2‐day) forecasts with high mean performance efficiency and correlation values. Our results also suggest that this new model is dominated by nonlinear components at L‐shells <∼4 for ultra‐relativistic electrons, different from the dominance of linear components for 1 MeV electrons as previously discovered.
A high-resolution temporal atlas of the SARS-CoV-2 translatome and transcriptome
Authors: Kim Doyeon , Kim Sukjun , Park Joori , Chang Hee Ryung , Chang Jeeyoon , Ahn Junhak , Park Heedo , Park Junehee , Son Narae , Kang Gihyeon , Kim Jeonghun , Kim Kisoon , Park Man-Seong , Kim Yoon Ki , Baek Daehyun
Published: August 2021

COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which infected >200 million people resulting in >4 million deaths. However, temporal landscape of the SARS-CoV-2 translatome and its impact on the human genome remain unexplored. Here, we report a high-resolution atlas of the translatome and transcriptome of SARS-CoV-2 for various time points after infecting human cells. Intriguingly, substantial amount of SARS-CoV-2 translation initiates at a novel translation initiation site (TIS) located in the leader sequence, termed TIS-L. Since TIS-L is included in all the genomic and subgenomic RNAs, the SARS-CoV-2 translatome may be regulated by a sophisticated interplay between TIS-L and downstream TISs. TIS-L functions as a strong translation enhancer for ORF S, and as translation suppressors for most of the other ORFs. Our global temporal atlas provides compelling insight into unique regulation of the SARS-CoV-2 translatome and helps comprehensively evaluate its impact on the human genome.
Co-targeting CDK4/6 and AKT with endocrine therapy prevents progression in CDK4/6 inhibitor and endocrine therapy-resistant breast cancer
Authors: Alves Carla L. , Ehmsen Sidse , Terp Mikkel G. , Portman Neil , Tuttolomondo Martina , Gammelgaard Odd L. , Hundebøl Monique F. , Kaminska Kamila , Johansen Lene E. , Bak Martin , Honeth Gabriella , Bosch Ana , Lim Elgene , Ditzel Henrik J.
Published: August 2021

CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy have shown impressive efficacy in estrogen receptor-positive advanced breast cancer. However, most patients will eventually experience disease progression on this combination, underscoring the need for effective subsequent treatments or better initial therapies. Here, we show that triple inhibition with fulvestrant, CDK4/6i and AKT inhibitor (AKTi) durably impairs growth of breast cancer cells, prevents progression and reduces metastasis of tumor xenografts resistant to CDK4/6i-fulvestrant combination or fulvestrant alone. Importantly, switching from combined fulvestrant and CDK4/6i upon resistance to dual combination with AKTi and fulvestrant does not prevent tumor progression. Furthermore, triple combination with AKTi significantly inhibits growth of patient-derived xenografts resistant to combined CDK4/6i and fulvestrant. Finally, high phospho-AKT levels in metastasis of breast cancer patients treated with a combination of CDK4/6i and endocrine therapy correlates with shorter progression-free survival. Our findings support the clinical development of ER, CDK4/6 and AKT co-targeting strategies following progression on CDK4/6i and endocrine therapy combination, and in tumors exhibiting high phospho-AKT levels, which are associated with worse clinical outcome.
Current gene panels account for nearly all homologous recombination repair-associated multiple-case breast cancer families
Authors: Matis Thibaut S. , Zayed Nadia , Labraki Bouchra , de Ladurantaye Manon , Matis Théophane A. , Camacho Valenzuela José , Hamel Nancy , Atayan Adrienne , Rivera Barbara , Tabach Yuval , Tonin Patricia N. , Orthwein Alexandre , Mes-Masson Anne-Marie , El Haffaf Zaki , Foulkes William D. , Polak Paz
Published: August 2021

It was hypothesized that variants in underexplored homologous recombination repair (HR) genes could explain unsolved multiple-case breast cancer (BC) families. We investigated HR deficiency (HRD)-associated mutational signatures and second hits in tumor DNA from familial BC cases. No candidates genes were associated with HRD in 38 probands previously tested negative with gene panels. We conclude it is unlikely that unknown HRD-associated genes explain a large fraction of unsolved familial BC.
3D geometry of femoral reaming for bone graft harvesting
Authors: Gehweiler Dominic , Schmitz Nina , Gueorguiev Boyko , Zderic Ivan , Grünwald Leonard , Richards Geoff , Wähnert Dirk , Raschke Michael J.
Published: August 2021

The reamer-irrigator-aspirator (RIA) technique allows to collect large bone graft amounts without the drawbacks of iliac crest harvesting. Nevertheless, clinical cases with occurrence of femur fractures have been reported. Therefore, this study aimed to systematically investigate the three-dimensional geometry of the reamed bone as a function of the reaming diameter and its influence on the associated potential fracture pattern. Forty-five intact fresh-frozen human cadaveric femora underwent computed tomography (CT). They were randomized to three groups (n = 15) for reaming at a diameter of either 1.5 mm (Group 1), 2.5 mm (Group 2) or 4.0 mm (Group 3) larger than their isthmus using RIA. Reaming was followed by a second CT scan, biomechanical testing until failure and a third CT scan. All CT scans of each femur were aligned via rigid registration, and fracture lines were visualized. Subsequently, a decrease in wall thickness, cross-sectional area, and harvested bone volume have been evaluated. The total volume of the bone graft was significantly higher for Group 3 (7.8 ± 2.9 ml) compared to Group 1 (2.9 ± 1.1 ml) and Group 2 (3.0 ± 1.1 ml). The maximal relative decrease of the wall thickness was located medially (72.7%) in the third (61.4%), fourth (18.2%) and second (9.1%) eighth for all groups. As the diameter of the reaming increased, an overlap of the fracture line with the maximal relative decrease in wall thickness and a maximal average relative decrease of the cross-sectional area became more frequent. This suggests that a reaming-associated fracture is most likely to occur in this region.
Comparison of seven single cell whole genome amplification commercial kits using targeted sequencing
Authors: Biezuner Tamir , Raz Ofir , Amir Shiran , Milo Lilach , Adar Rivka , Fried Yael , Ainbinder Elena , Shapiro Ehud
Published: August 2021

Advances in whole genome amplification (WGA) techniques enable understanding of the genomic sequence at a single cell level. Demand for single cell dedicated WGA kits (scWGA) has led to the development of several commercial kit. To this point, no robust comparison of all available kits was performed. Here, we benchmark an economical assay, comparing all commercially available scWGA kits. Our comparison is based on targeted sequencing of thousands of genomic loci, including highly mutable regions, from a large cohort of human single cells. Using this approach we have demonstrated the superiority of Ampli1 in genome coverage and of RepliG in reduced error rate. In summary, we show that no single kit is optimal across all categories, highlighting the need for a dedicated kit selection in accordance with experimental requirements.
Migrations of cancer cells through the lens of phylogenetic biogeography
Authors: Chroni Antonia , Miura Sayaka , Oladeinde Olumide , Aly Vivian , Kumar Sudhir
Published: August 2021

Malignant cells leave their initial tumor of growth and disperse to other tissues to form metastases. Dispersals also occur in nature when individuals in a population migrate from their area of origin to colonize other habitats. In cancer, phylogenetic biogeography is concerned with the source and trajectory of cell movements. We examine the suitability of primary features of organismal biogeography, including genetic diversification, dispersal, extinction, vicariance, and founder effects, to describe and reconstruct clone migration events among tumors. We used computer-simulated data to compare fits of seven biogeographic models and evaluate models’ performance in clone migration reconstruction. Models considering founder effects and dispersals were often better fit for the clone phylogenetic patterns, especially for polyclonal seeding and reseeding of metastases. However, simpler biogeographic models produced more accurate estimates of cell migration histories. Analyses of empirical datasets of basal-like breast cancer had model fits consistent with the patterns seen in the analysis of computer-simulated datasets. Our analyses reveal the powers and pitfalls of biogeographic models for modeling and inferring clone migration histories using tumor genome variation data. We conclude that the principles of molecular evolution and organismal biogeography are useful in these endeavors but that the available models and methods need to be applied judiciously.
Biomolecular imaging of colorectal tumor lesions using a FITC-labeled scFv-Cκ fragment antibody
Authors: Kim Hyung Il , Kim Jinhyeon , Kim Hyori , Lee Hyeri , Yoon Yong Sik , Hwang Sung Wook , Park Sang Hyoung , Yang Dong-Hoon , Ye Byong Duk , Byeon Jeong-Sik , Yang Suk-Kyun , Kim Sun Young , Myung Seung-Jae
Published: August 2021

For the sensitive diagnosis of colorectal cancer lesions, advanced molecular imaging techniques using cancer-specific targets have emerged. However, issues regarding the clearance of unbound probes and immunogenicity remain unresolved. To overcome these limitations, we developed a small-sized scFv antibody fragment conjugated with FITC for the real-time detection of colorectal cancer by in vivo molecular endoscopy imaging. A small-sized scFv fragment can target colon cancer secreted protein-2 (CCSP-2), highly expressed in colorectal adenocarcinoma tissues; moreover, its full-length IgG probe has been used for molecular imaging previously. To assess the efficacy of anti-CCSP-2 scFv-FITC, surgical specimens were obtained from 21 patients with colorectal cancer for ex vivo molecular fluorescence analysis, histology, and immunohistochemistry. Orthotopic mice were administered with anti-CCSP-2 scFv-FITC topically and intravenously, and distinct tumor lesions were observed by real-time fluorescence colonoscopy. The fluorescence imaging of human colon cancer specimens allowed the differentiation of malignant tissues from non-malignant tissues (p < 0.05), and the CCSP-2 expression level was found to be correlated with the fluorescence intensity. Here, we demonstrated the feasibility and safety of anti-CCSP-2 scFv-FITC for molecular imaging as well as its potential in real-time fluorescence colonoscopy for the differential diagnosis of tumor lesions.
Enhanced CD4+ and CD8+ T cell infiltrate within convex hull defined pancreatic islet borders as autoimmune diabetes progresses
Authors: Dwyer Alexander J. , Ritz Jacob M. , Mitchell Jason S. , Martinov Tijana , Alkhatib Mohannad , Silva Nubia , Tucker Christopher G. , Fife Brian T.
Published: August 2021

The notion that T cell insulitis increases as type 1 diabetes (T1D) develops is unsurprising, however, the quantitative analysis of CD4+ and CD8+ T cells within the islet mass is complex and limited with standard approaches. Optical microscopy is an important and widely used method to evaluate immune cell infiltration into pancreatic islets of Langerhans for the study of disease progression or therapeutic efficacy in murine T1D. However, the accuracy of this approach is often limited by subjective and potentially biased qualitative assessment of immune cell subsets. In addition, attempts at quantitative measurements require significant time for manual analysis and often involve sophisticated and expensive imaging software. In this study, we developed and illustrate here a streamlined analytical strategy for the rapid, automated and unbiased investigation of islet area and immune cell infiltration within (insulitis) and around (peri-insulitis) pancreatic islets. To this end, we demonstrate swift and accurate detection of islet borders by modeling cross-sectional islet areas with convex polygons (convex hulls) surrounding islet-associated insulin-producing β cell and glucagon-producing α cell fluorescent signals. To accomplish this, we used a macro produced with the freeware software ImageJ equipped with the Fiji Is Just ImageJ (FIJI) image processing package. Our image analysis procedure allows for direct quantification and statistical determination of islet area and infiltration in a reproducible manner, with location-specific data that more accurately reflect islet areas as insulitis proceeds throughout T1D. Using this approach, we quantified the islet area infiltrated with CD4+ and CD8+ T cells allowing statistical comparison between different age groups of non-obese diabetic (NOD) mice progressing towards T1D. We found significantly more CD4+ and CD8+ T cells infiltrating the convex hull-defined islet mass of 13-week-old non-diabetic and 17-week-old diabetic NOD mice compared to 4-week-old NOD mice. We also determined a significant and measurable loss of islet mass in mice that developed T1D. This approach will be helpful for the location-dependent quantitative calculation of islet mass and cellular infiltration during T1D pathogenesis and can be combined with other markers of inflammation or activation in future studies.
Effects of chronic cholinergic stimulation associated with aerobic physical training on cardiac morphofunctional and autonomic parameters in spontaneously hypertensive rats
Authors: Gardim Camila B. , Veiga Ana Catarine , Aguilar Bruno A. , Philbois Stella V. , Souza Hugo C. D.
Published: August 2021

We investigated hemodynamic, cardiac morphofunctional, and cardiovascular autonomic adaptations in spontaneously hypertensive rats (SHRs) after aerobic physical training associated with chronic cholinergic stimulation. Fifty-four SHRs were divided into two groups: trained and untrained. Each group was further subdivided into three smaller groups: vehicle, treated with pyridostigmine bromide at 5 mg/kg/day, and treated with pyridostigmine bromide at 15 mg/kg/day. The following protocols were assessed: echocardiography, autonomic double pharmacological blockade, heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS). Physical training and pyridostigmine bromide reduced BP and HR and increased vagal participation in cardiac autonomic tonic balance. The associated responses were then potentialized. Treatment with pyridostigmine bromide increased HRV oscillation of both low frequency (LF: 0.2–0.75 Hz) and high frequency (HF: 0.75–3 Hz). However, the association with physical training attenuated HF oscillations. Additionally, treatment with pyridostigmine bromide also increased LF oscillations of BPV. Both treatment groups promoted morphofunctional adaptations, and associated increased ejection volume, ejection fraction, cardiac output, and cardiac index. In conclusion, the association of pyridostigmine bromide and physical training promoted greater benefits in hemodynamic parameters and increased vagal influence on cardiac autonomic tonic balance. Nonetheless, treatment with pyridostigmine bromide alone seems to negatively affect BPV and the association of treatment negatively influences HRV.
Machine learning assisted prediction of the Young’s modulus of compositionally complex alloys
Authors: Khakurel Hrishabh , Taufique M. F. N. , Roy Ankit , Balasubramanian Ganesh , Ouyang Gaoyuan , Cui Jun , Johnson Duane D. , Devanathan Ram
Published: August 2021

We identify compositionally complex alloys (CCAs) that offer exceptional mechanical properties for elevated temperature applications by employing machine learning (ML) in conjunction with rapid synthesis and testing of alloys for validation to accelerate alloy design. The advantages of this approach are scalability, rapidity, and reasonably accurate predictions. ML tools were implemented to predict Young’s modulus of refractory-based CCAs by employing different ML models. Our results, in conjunction with experimental validation, suggest that average valence electron concentration, the difference in atomic radius, a geometrical parameter λ and melting temperature of the alloys are the key features that determine the Young’s modulus of CCAs and refractory-based CCAs. The Gradient Boosting model provided the best predictive capabilities (mean absolute error of 6.15 GPa) among the models studied. Our approach integrates high-quality validation data from experiments, literature data for training machine-learning models, and feature selection based on physical insights. It opens a new avenue to optimize the desired materials property for different engineering applications.
Theory of mind affects the interpretation of another person's focus of attention
Authors: Dawson Jessica , Kingstone Alan , Foulsham Tom
Published: August 2021

People are drawn to social, animate things more than inanimate objects. Previous research has also shown gaze following in humans, a process that has been linked to theory of mind (ToM). In three experiments, we investigated whether animacy and ToM are involved when making judgements about the location of a cursor in a scene. In Experiment 1, participants were told that this cursor represented the gaze of an observer and were asked to decide whether the observer was looking at a target object. This task is similar to that carried out by researchers manually coding eye-tracking data. The results showed that participants were biased to perceive the gaze cursor as directed towards animate objects (faces) compared to inanimate objects. In Experiments 2 and 3 we tested the role of ToM, by presenting the same scenes to new participants but now with the statement that the cursor was generated by a ‘random’ computer system or by a computer system designed to seek targets. The bias to report that the cursor was directed toward faces was abolished in Experiment 2, and minimised in Experiment 3. Together, the results indicate that people attach minds to the mere representation of an individual's gaze, and this attribution of mind influences what people believe an individual is looking at.