bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of Oral Human Papillomavirus Infection: Impact of Sex, Race/Ethnicity, and Vaccination Status
Authors: Berenson Abbey B , Hirth Jacqueline M , Chang Mihyun
Published: June 2021

Background

Prior studies have demonstrated differences in oral human papillomavirus (HPV) prevalence by sex and race/ethnicity. In this study, we examined the impact of vaccination on these disparities.

Methods

We examined participants aged 18–59 years in the National Health and Nutrition Examination Survey from 2011 to 2016 who reported their HPV vaccination status and submitted an adequate oral sample (N = 9437). Oral prevalence of HPV, grouped by any, low-risk, high-risk, 4 valent (4v) HPV, 9 valent (9v) HPV, and nonvaccine types, was examined by sex, race/ethnicity, and vaccination status. Binary logistic regression was used to estimate prevalence ratios by vaccination status. Multivariable logistic regression models controlled for age, sex, and race/ethnicity.

Results

The prevalence of any, nonvaccine, low-risk, high-risk, 4vHPV, and 9vHPV types was higher among males than females, even among vaccinated participants. Examination of racial/ethnic differences demonstrated differences in all HPV groups among unvaccinated males and among low-risk types in females. In all but the 2 vaccine-type groups, the prevalence of oral HPV was notably higher among Black males compared with other groups. Significant differences were not observed by race/ethnicity among vaccinated males or females.

Conclusions

Males tested positive for oral HPV more frequently than females, even among those vaccinated. This may have resulted from a lower frequency of males being vaccinated before initiating oral sex than females. Vaccination of males at the recommended age, therefore, may decrease differences in oral HPV by sex. Racial/ethnic differences were observed only in unvaccinated individuals, suggesting these disparities will decrease as more individuals are vaccinated.
Social robots for English language teaching
Authors: Lee Hansol , Lee Jang Ho
Published: June 2021

In this series, we explore technology-related themes and topics. The series aims to discuss and demystify what may be new areas for some readers and to consider their relevance for English language teachers.
Gravity and magnetic joint inversion for basement and salt structures with the reversible-jump algorithm
Authors: Ghalenoei Emad , Dettmer Jan , Ali Mohammed Y , Kim Jeong Woo
Published: June 2021

Gravity and magnetic data resolve the Earth with variable spatial resolution, and Earth structure exhibits both discontinuous and gradual features. Therefore, model parametrization complexity should be able to address such variability by locally adapting to the resolving power of the data. The reversible-jump Markov chain Monte Carlo (rjMcMC) algorithm provides variable spatial resolution that is consistent with data information. To address the prevalent non-uniqueness in joint inversion of potential field data, we use a novel spatial partitioning with nested Voronoi cells that is explored by rjMcMC sampling. The nested Voronoi parametrization partitions the subsurface in terms of rock types, such as sedimentary, salt and basement rocks. Therefore, meaningful prior information can be specified for each type which reduces non-uniqueness. We apply nonoverlapping prior distributions for density contrast and susceptibility between rock types. In addition, the choice of noise parametrization can lead to significant trade-offs with model resolution and complexity. We adopt an empirical estimation of full data covariance matrices that include theory and observational errors to account for spatially correlated noise. The method is applied to 2-D gravity and magnetic data to study salt and basement structures. We demonstrate that meaningful partitioning of the subsurface into sediment, salt, and basement structures is achieved by these advances without requiring regularization. Multiple simulated- and field-data examples are presented. Simulation results show clear delineation of salt and basement structures while resolving variable length scales. The field data show results that are consistent with observations made in the simulations. In particular, we resolve geologically plausible structures with varying length scales and clearly differentiate salt structure and basement topography.
Improving the retrieval of high-frequency surface waves from ambient noise through multichannel-coherency-weighted stack
Authors: Liu Ya , Xia Jianghai , Xi Chaoqiang , Dai Tianyu , Ning Ling
Published: June 2021

Seismic interferometry is becoming increasingly popular in urban areas due to its ability to retrieve high-frequency surface waves from abundant anthropogenic seismic noise, hence the need for advanced processing schemes in resolving complex environments. Stacking noise cross-correlation functions is an essential step for the successful retrieval of surface waves and some nonlinear methods are developed for attenuating incoherent noise; however, these methods are susceptible to waveform distortions. In addition, a lot of attention has been focused on the improvement of the pairwise noise cross-correlation functions, while the spatial coherency of waves is less utilized. We obtain the multichannel coherency by summing the local phase coherencies in a time window and propose the multichannel-coherency-weighted stack method for accelerating the retrieval of high-frequency surface waves. A synthetic test and a real-world three-component example demonstrate the superiority of the proposed method over both the linear stack and the phase-weighted stack methods in obtaining cleaner surface waves and more accurate dispersion measurements. Our method is not limited by waveform distortions owing to its linearity. Furthermore, the proposed method has the potential to be extended to body wave retrieval from ambient noise by adjusting its parameters.
Continental-scale genomic analysis suggests shared post-admixture adaptation in the Americas
Authors: Ongaro Linda , Mondal Mayukh , Flores Rodrigo , Marnetto Davide , Molinaro Ludovica , Alarcón-Riquelme Marta E , Moreno-Estrada Andrés , Mabunda Nedio , Ventura Mario , Tambets Kristiina , Hellenthal Garrett , Capelli Cristian , Kivisild Toomas , Metspalu Mait , Pagani Luca , Montinaro Francesco
Published: June 2021

American populations are one of the most interesting examples of recently admixed groups, where ancestral components from three major continental human groups (Africans, Eurasians and Native Americans) have admixed within the last 15 generations. Recently, several genetic surveys focusing on thousands of individuals shed light on the geography, chronology and relevance of these events. However, even though gene flow could drive adaptive evolution, it is unclear whether and how natural selection acted on the resulting genetic variation in the Americas.

In this study, we analysed the patterns of local ancestry of genomic fragments in genome-wide data for ~ 6000 admixed individuals from 10 American countries. In doing so, we identified regions characterized by a divergent ancestry profile (DAP), in which a significant over or under ancestral representation is evident.

Our results highlighted a series of genomic regions with DAPs associated with immune system response and relevant medical traits, with the longest DAP region encompassing the human leukocyte antigen locus. Furthermore, we found that DAP regions are enriched in genes linked to cancer-related traits and autoimmune diseases. Then, analysing the biological impact of these regions, we showed that natural selection could have acted preferentially towards variants located in coding and non-coding transcripts and characterized by a high deleteriousness score.

Taken together, our analyses suggest that shared patterns of post admixture adaptation occurred at a continental scale in the Americas, affecting more often functional and impactful genomic variants.
Reduced Cerebrospinal Fluid Levels of Lysophosphatidic Acid Docosahexaenoic Acid in Patients With Major Depressive Disorder and Schizophrenia
Authors: Omori Wataru , Kano Kuniyuki , Hattori Kotaro , Kajitani Naoto , Okada-Tsuchioka Mami , Boku Shuken , Kunugi Hiroshi , Aoki Junken , Takebayashi Minoru
Published: June 2021

Background

Lysophosphatidic acid (LPA) is involved in numerous biological processes, including neurodevelopment, chronic inflammation, and immunologic response in the central nervous system. Autotaxin (ATX) is a secreted enzyme that produces LPA from lysophosphatidylcholine (LPC). Previous studies have demonstrated decreased protein levels of ATX in cerebrospinal fluid (CSF) of patients with major depressive disorder (MDD). Based on those studies, the current study investigated the levels of lysophospholipids species including LPA and related metabolic enzymes, in CSF of patients with MDD and schizophrenia (SCZ).

Methods

The levels of lysophospholipids species and related metabolic enzymes were measured with either liquid chromatography-tandem mass spectrometry or enzyme-linked immunosorbent assay. Japanese patients were diagnosed with DSM-IV-TR. CSF was obtained from age- and sex-matched healthy controls (n = 27) and patients with MDD (n = 26) and SCZ (n = 27).

Results

Of all lysophospholipids species, the levels of LPA 22:6 (LPA - docosahexaenoic acid) were significantly lower in patients with MDD and SCZ than in healthy controls. These levels were negatively correlated with several clinical symptomatic scores of MDD, but not those of SCZ. In addition, the levels of LPA 22:6 were significantly correlated with the levels of LPC 22:6 among all 3 groups. On the other hand, the levels of LPA 22:6 were not correlated with ATX activity in patients with MDD and SCZ.

Conclusion

The lower levels of LPA 22:6 in patients with MDD and SCZ suggest an abnormality of LPA 22:6 metabolism. In addition, several depressive symptoms in patients with MDD were significantly associated with the lower levels of LPA 22:6, suggesting an involvement of LPA 22:6 in the pathophysiology of MDD.
The Limiting Distribution of Character Sums
Authors: Hussain Ayesha
Published: June 2021

In this paper, we consider the distribution of the continuous paths of Dirichlet character sums modulo prime $q$ on the complex plane. We also find a limiting distribution as $q \rightarrow \infty $ using Steinhaus random multiplicative functions, stating properties of this random process. This is motivated by Kowalski and Sawin’s work on Kloosterman paths.
Health management via telemedicine: Learning from the COVID-19 experience
Authors: Sun Ran , Blayney Douglas W , Hernandez-Boussard Tina
Published: June 2021

At the onset of the COVID-19 (coronavirus disease 2019) pandemic, telemedicine was rapidly implemented to protect patients and healthcare providers from infection. It is unlikely that care delivery will fully return to the pre-COVID form. Telemedicine offers many opportunities to improve care efficiency, accessibility, and patient outcomes, but many challenges exist related to technology interoperability, the digital divide, and usability. We propose that telemedicine evolve to support continuity of care throughout the patient journey, including multidisciplinary care teams and the seamless integration of data into the clinical workflow to support a learning healthcare system. Importantly, evidence is needed to support this paradigm shift in care delivery to ensure the quality and efficacy of care delivered via telemedicine. Here, we highlight gaps and opportunities that need to be addressed by the biomedical informatics community to move forward with safe and effective healthcare delivery via telemedicine.
Emerging solvatochromic push–pull dyes for monitoring the lipid order of biomembranes in live cells
Authors: Niko Yosuke , Klymchenko Andrey S
Published: June 2021

Solvatochromic dyes have emerged as a new class of fluorescent probes in the field of lipid membranes due to their ability to identify the lipid organization of biomembranes in live cells by changing the colour of their fluorescence. This type of solvatochromic function is useful for studying the heterogeneous features of biomembranes caused by the uneven distribution of lipids and cholesterols in live cells and related cellular processes. Therefore, a variety of advanced solvatochromic dyes have been rapidly developed over the last decade. To provide an overview of the works recently developed solvatochromic dyes have enabled, we herein present some solvatochromic dyes, with a particular focus on those based on pyrene and Nile red. As these dyes exhibit preferable photophysical properties in terms of fluorescence microscopy applications and unique distribution/localization in cellular compartments, some have already found applications in cell biological and biophysical studies. The goal of this review is to provide information to researchers who have never used solvatochromic dyes or who have not discovered applications of such dyes in biological studies.
Nocturnal Pollinators Significantly Contribute to Apple Production
Authors: Robertson Stephen M , Dowling Ashley P G , Wiedenmann Robert N , Joshi Neelendra K , Westerman Erica L
Published: June 2021

Agricultural dependency on insect-mediated pollination is increasing at the same time that pollinator populations are experiencing declines in diversity and abundance. Current pollinator research in agriculture focuses largely on diurnal pollinators, yet the evidence for pollination by moths and other nocturnal pollinators is growing. Apples are one of the most valuable and important fruits produced globally, and apple production is dependent on insect-mediated cross-pollination to generate a profitable crop. We examined contributions to apple production provided by nocturnal insects via an exclusion experiment. We compared the relative contributions to apple production provided by nocturnal and diurnal pollinators using fruit set, the likelihood of cluster pollination, and seed set. We found nocturnal pollinators capable of facilitating the production of as many apples at similar levels of pollination as diurnal pollinators. We further found evidence that nocturnal and diurnal pollinators pollinate synergistically, with pollination contributions being additive in one year of our study. Our research identifies significant contributions to apple production provided by nocturnal pollinators, which may interact with diurnal pollinators in ways that are currently unrecognized. Expansions of this research into additional pollinator-dependent crops and focused investigations on specific nocturnal insects will provide more accurate assessments of nocturnal-pollinator roles in agriculture and improve our overall understanding of pollination in agriculture.
Early Medicaid Expansion and Cancer Mortality
Authors: Barnes Justin M , Johnson Kimberly J , Adjei Boakye Eric , Schapira Lidia , Akinyemiju Tomi , Park Eliza M , Graboyes Evan M , Osazuwa-Peters Nosayaba
Published: June 2021

Background

Although Medicaid expansion is associated with decreased uninsured rates and earlier cancer diagnoses, no study has demonstrated an association between Medicaid expansion and cancer mortality. Our primary objective was to quantify the relationship between early Medicaid expansion and changes in cancer mortality rates.

Methods

We obtained county-level data from the National Center for Health Statistics for adults aged 20-64 years who died from cancer from 2007 to 2009 (preexpansion) and 2012 to 2016 (postexpansion). We compared changes in cancer mortality rates in early Medicaid expansion states (CA, CT, DC, MN, NJ, and WA) vs nonexpansion states through a difference-in-differences analysis using hierarchical Bayesian regression. An exploratory analysis of cancer mortality changes associated with the larger-scale 2014 Medicaid expansions was also performed.

Results

In adjusted difference-in-differences analyses, we observed a statistically significant decrease of 3.07 (95% credible interval = 2.19 to 3.95) cancer deaths per 100 000 in early expansion vs nonexpansion states, which translates to an estimated decrease of 5276 cancer deaths in the early expansion states during the study period. Expansion-associated decreases in cancer mortality were observed for pancreatic cancer. Exploratory analyses of the 2014 Medicaid expansions showed a decrease in pancreatic cancer mortality (−0.18 deaths per 100 000, 95% confidence interval = −0.32 to −0.05) in states that expanded Medicaid by 2014 compared with nonexpansion states.

Conclusions

Early Medicaid expansion was associated with reduced cancer mortality rates, especially for pancreatic cancer, a cancer with short median survival where changes in prognosis would be most visible with limited follow-up.
Midgut malrotation: a rare presentation of bowel obstruction in the adult
Authors: Singh Ulanda , Baker Akil
Published: June 2021

Intestinal malrotation is a rare congenital abnormality. Usually, patients with malrotation of the intestine present in the neonatal period or the first year of life while some may remain asymptomatic and present later in childhood or adulthood. The diagnosis is usually delayed due to the sequence of events being that of non-specific gastrointestinal symptoms, which culminates in either adhesive bowel obstruction or volvulus. A 59-year-old male diagnosed with a large, incarcerated, right inguinoscrotal hernia underwent emergency laparotomy, which revealed midgut malrotation and small bowel obstruction due to Ladd bands. A modified Ladd’s procedure and right inguinal herniorrhaphy was performed.
The assembly bias of emission-line galaxies
Authors: Jiménez Esteban , Padilla Nelson , Contreras Sergio , Zehavi Idit , Baugh Carlton M , Orsi Álvaro
Published: June 2021

The next generation of spectroscopic surveys will target emission-line galaxies (ELGs) to produce constraints on cosmological parameters. We study the large-scale structure traced by ELGs using a combination of a semi-analytical model of galaxy formation, a code that computes the nebular emission from H ii regions using the properties of the interstellar medium, and a large-volume, high-resolution N-body simulation. We consider fixed number density samples where galaxies are selected by their H α, [O iii] λ5007, or [O ii] λλ3727–3729 emission-line luminosities. We investigate the assembly bias signatures of these samples, and compare them to those of stellar mass- and star formation rate-selected samples. Interestingly, we find that the [O iii]- and [O ii]-selected samples display scale-dependent bias on large scales and that their assembly bias signatures are also scale dependent. Both these effects are more pronounced for lower number density samples. The [O iii] and [O ii] emitters that contribute most to the scale dependence tend to have a low gas-phase metallicity and are preferentially found in low-density regions. We also measure the baryon acoustic oscillation (BAO) feature and the β parameter related to the growth rate of overdensities. We find that the scale of the BAO peak is roughly the same for all selections and that β is scale dependent at large scales. Our results suggest that ELG samples include environmental effects that should be modelled in order to remove potential systematic errors that could affect the estimation of cosmological parameters.
Core-envelope haloes in scalar field dark matter with repulsive self-interaction: fluid dynamics beyond the de Broglie wavelength
Authors: Dawoodbhoy Taha , Shapiro Paul R , Rindler-Daller Tanja
Published: June 2021

Scalar field dark matter (SFDM) comprised of ultralight bosons has attracted great interest as an alternative to standard, collisionless cold dark matter (CDM) because of its novel structure-formation dynamics, described by the coupled Schrödinger–Poisson equations. In the free-field (‘fuzzy’) limit of SFDM (FDM), structure is inhibited below the de Broglie wavelength, but resembles CDM on larger scales. Virialized haloes have ‘solitonic’ cores of radius ∼λdeB, surrounded by CDM-like envelopes. When a strong enough repulsive self-interaction (SI) is also present, structure can be inhibited below a second length-scale, λSI, with λSI > λdeB – called the Thomas–Fermi (TF) regime. FDM dynamics differ from CDM because of quantum pressure, and SFDM-TF differs further by adding SI pressure. In the small-λdeB limit, however, we can model all three by fluid conservation equations for a compressible, γ = 5/3 ideal gas, with ideal gas pressure sourced by internal velocity dispersion and, for the TF regime, an added SI pressure, PSI ∝ ρ2. We use these fluid equations to simulate halo formation from gravitational collapse in 1D, spherical symmetry, demonstrating for the first time that SFDM-TF haloes form with cores the size of RTF, the radius of an SI-pressure-supported (n = 1)-polytrope, surrounded by CDM-like envelopes. In comparison with rotation curves of dwarf galaxies in the local Universe, SFDM-TF haloes pass the [‘too-big-to-fail’ + ‘cusp–core’]-test if RTF ≳ 1 kpc.
Intervening or associated? Machine learning classification of redshifted H i 21-cm absorption
Authors: Curran S J
Published: June 2021

In a previous paper, we presented the results of applying machine learning to classify whether an H i 21-cm absorption spectrum arises in a source intervening the sightline to a more distant radio source or within the host of the radio source itself. This is usually determined from an optical spectrum giving the source redshift. However, not only will this be impractical for the large number of sources expected to be detected with the Square Kilometre Array, but bright optical sources are the most ultraviolet luminous at high redshift and so bias against the detection of cool, neutral gas. Adding another 44, mostly newly detected absorbers, to the previous sample of 92, we test four different machine learning algorithms, again using the line properties (width, depth, and number of Gaussian fits) as features. Of these algorithms, three gave some improvement over the previous sample, with a logistic regression model giving the best results. This suggests that the inclusion of further training data, as new absorbers are detected, will further increase the prediction accuracy above the current ≈80 per cent. We use the logistic regression model to classify the zabs = 0.42 absorption towards PKS 1657−298 and find this to be associated, which is consistent with a previous study that determined zem ≈ 0.42 from the K-band magnitude–redshift relation.
Powerful multiphase outflows in the central region of Cygnus A
Authors: Riffel R A
Published: June 2021

We use Gemini Near-Infrared Integral Field Spectrograph (NIFS) observations of the inner 3.5 × 3.5 kpc2 of the radio galaxy Cygnus A to map the gas excitation and kinematics at a spatial resolution of 200 pc. The emission of the ionized gas shows a biconical morphology, with half-opening angle of 45○ and oriented along the position angle of the radio jet. Coronal line emission is seen within the cone, up to 1.75 kpc from the nucleus, with higher ionization gas observed in the easterly side. The H2 and [Fe ii] emission lines are consistent with excitation by the central AGN, with some contribution of shocks to the south-west of the nucleus. The gas visual extinction and electron density are larger than those from optical-based measurements, consistent with the fact that near-IR observations penetrate deeply into the gas emission structure, probing denser and more obscured regions. The gas kinematics shows two components: (i) a rotating disc with kinematic position angle of Ψ0 = 21○ ± 2○, seen both in ionized and molecular gas, and (ii) outflows with velocities of up to 600 km s−1 observed within the ionization cone in ionized gas and restricted to inner 0.5 arcsec in molecular gas. The mass outflow rate in ionized gas is in the range $\sim \! 100\!-\!280\, {\rm M_\odot \, yr^{-1}}$ and the kinetic power of the outflow corresponds to 0.3–3.3 per cent of the AGN bolometric luminosity, indicating that the outflows in Cygnus A may be effective in suppressing star formation.
Investigating cosmological GAN emulators using latent space interpolation
Authors: Tamosiunas Andrius , Winther Hans A , Koyama Kazuya , Bacon David J , Nichol Robert C , Mawdsley Ben
Published: June 2021

Generative adversarial networks (GANs) have been recently applied as a novel emulation technique for large-scale structure simulations. Recent results show that GANs can be used as a fast and efficient emulator for producing novel weak lensing convergence maps as well as cosmic web data in 2D and 3D. However, like any algorithm, the GAN approach comes with a set of limitations, such as an unstable training procedure, inherent randomness of the produced outputs, and difficulties when training the algorithm on multiple data sets. In this work, we employ a number of techniques commonly used in the machine learning literature to address the mentioned limitations. Specifically, we train a GAN to produce weak lensing convergence maps and dark matter overdensity field data for multiple redshifts, cosmological parameters, and modified gravity models. In addition, we train a GAN using the newest Illustris data to emulate dark matter, gas, and internal energy distribution data simultaneously. Finally, we apply the technique of latent space interpolation as a tool for understanding the feature space of the GAN algorithm. We show that the latent space interpolation procedure allows the generation of outputs with intermediate cosmological parameters that were not included in the training data. Our results indicate a 1–20 per cent difference between the power spectra of the GAN-produced and the test data samples depending on the data set used and whether Gaussian smoothing was applied. Similarly, the Minkowski functional analysis indicates a good agreement between the emulated and the real images for most of the studied data sets.
A microlensing search of 700 million VVV light curves
Authors: Husseiniova Andrea , McGill Peter , Smith Leigh C , Evans N Wyn
Published: June 2021

The VISTA Variables in the Via Lactea (VVV) survey and its extension have been monitoring about 560 deg2 of sky centred on the Galactic bulge and inner disc for nearly a decade. The photometric catalogue contains of order 10$^9$ sources monitored in the $K_s$ band down to 18 mag over hundreds of epochs from 2010 to 2019. Using these data we develop a decision tree classifier to identify microlensing events. As inputs to the tree, we extract a few physically motivated features as well as simple statistics ensuring a good fit to a microlensing model both on and off the event amplification. This produces a fast and efficient classifier trained on a set of simulated microlensing events and catacylsmic variables, together with flat baseline light curves randomly chosen from the VVV data. The classifier achieves 97 per cent accuracy in identifying simulated microlensing events in a validation set. We run the classifier over the VVV data set and then visually inspect the results, which produces a catalogue of 1959 microlensing events. For these events, we provide the Einstein radius crossing time via a Bayesian analysis. The spatial dependence on recovery efficiency of our classifier is well characterized, and this allows us to compute spatially resolved completeness maps as a function of Einstein crossing time over the VVV footprint. We compare our approach to previous microlensing searches of the VVV. We highlight the importance of Bayesian fitting to determine the microlensing parameters for events with surveys like VVV with sparse data.
Shock–multicloud interactions in galactic outflows – II. Radiative fractal clouds and cold gas thermodynamics
Authors: Banda-Barragán W E , Brüggen M , Heesen V , Scannapieco E , Cottle J , Federrath C , Wagner A Y
Published: June 2021

Galactic winds are crucial to the cosmic cycle of matter, transporting material out of the dense regions of galaxies. Observations show the coexistence of different temperature phases in such winds, which is not easy to explain. We present a set of 3D shock–multicloud simulations that account for radiative heating and cooling at temperatures between $10^2$ and $10^7\, \rm K$. The interplay between shock heating, dynamical instabilities, turbulence, and radiative heating and cooling creates a complex multiphase flow with a rain-like morphology. Cloud gas fragments and is continuously eroded, becoming efficiently mixed and mass loaded. The resulting warm mixed gas then cools down and precipitates into new dense cloudlets, which repeat the process. Thus, radiative cooling is able to sustain fast-moving dense gas by aiding condensation of gas from warm clouds and the hot wind. In the ensuing outflow, hot gas with temperatures ${\gtrsim}10^6\, \rm K$ outruns the warm and cold phases, which reach thermal equilibrium near ${\approx}10^4$ and ${\approx}10^2\, \rm K$, respectively. Although the volume filling factor of hot gas is higher in the outflow, most of the mass is concentrated in dense gas cloudlets and filaments with these temperatures. More porous multicloud layers result in more vertically extended outflows, and dense gas is more efficiently produced in more compact layers. The cold phase is not accelerated by ram pressure, but, instead, precipitates from warm and mixed gas out of thermal equilibrium. This cycle can explain the presence of high-velocity H i gas with $N_{\rm H\, \small {I}}=10^{19\!-\!21}\, \rm cm^{-2}$ and $\Delta v_{{\rm FWHM}}\lesssim 37\, \rm km\, s^{-1}$ in the Galactic Centre outflow.
Get Smart: Outcomes, Influence, and Responsibility
Authors: Milam Per-Erik
Published: June 2021

Once relegated to the margins of the responsibility debate, moral influence theories have recently been rehabilitated. This paper offers a moral influence theory with two parts: a theory of responsibility as influenceability and an act-consequentialist justification of blame. I defend this account against six concerns commonly raised both by opponents and by advocates of similar views. Some concerns target act consequentialism, claiming that it 1) permits blaming innocents; 2) permits coercion, manipulation, and other objectionable forms of influence; and 3) fails to capture intuitions about desert. Other concerns target responsibility as influenceability, claiming that influenceability accounts are 4) unsophisticated, 5) make ascriptions of responsibility dependent on assessments of permissible blame, and 6) have various counterintuitive implications.
Characterizing the Value of Morally Responsible Agency
Authors: Robichaud Philip
Published: June 2021

Moral influence theories of responsibility justify practices of praising and blaming by pointing to their effects on the development of our reasons-responsive capacities. Exercising these capacities has instrumental value—for example, they enable agents to act rightly and to flourish—but some argue that it is also intrinsically valuable. In this paper, I develop a value theory of morally responsible agency. I show how the value realized by exercising agency depends on the moral valence of the action performed and the skill with which agency is exercised. I then argue that moral influence theorists who accept this axiology have reason to adopt a more ambitious approach such that our responsibility practices should aim to cultivate maximally skilled and maximally good agents.
Mutational landscape of plasma cell-free DNA identifies molecular features associated with therapeutic response in patients with colon cancer. A pilot study
Authors: Cervena Klara , Pardini Barbara , Urbanova Marketa , Vodenkova Sona , Eva Pazourkova , Veskrnova Veronika , Levy Miroslav , Buchler Tomas , Mokrejs Martin , Naccarati Alessio , Vodicka Pavel , Vymetalkova Veronika
Published: June 2021

Cell-free DNA (cfDNA) has recently been used as a non-invasive diagnostic tool for detecting tumour-specific mutations. cfDNA may also be used for monitoring disease progression and treatment response, but so far researchers focused on one or few genes only. A genomic profile may provide better information on patient prognosis compared to single specific mutations.

In this hypothesis-generating study, we profiled by whole exome sequencing serial plasma samples from 10 colon cancer (CC) patients collected before and after 5-fluorouracil-based therapy, and one year after diagnosis to determine alterations associated with treatment response. In parallel, genome profiling was also performed in patients’ corresponding tumour tissue to ascertain the molecular landscape of resistant tumours.

The mutation concordance between cfDNA and tumour tissue DNA was higher in more advanced tumour stages than in the early stages of the disease. In non-responders, a specific mutation profile was observed in tumour tissues (TPSD1 p.Ala92Thr, CPAMD8 p.Arg341Gln, OBP2A p.ArgTyr123CysHis). A pathogenic APC mutation (p.Ser1315Ter) was detected only in cfDNA of one poor responder one year after the diagnosis and after therapy termination. Another poor responder presented a likely pathogenic TP53 mutation (p.Arg110Pro) in cfDNA of all plasma samplings and in tumour tissue.

In conclusion, cfDNA could be used for genetic characterisation of CC patients and might be clinically useful for non-invasive therapy response monitoring.
Chirality matters: stereo-defined phosphorothioate linkages at the termini of small interfering RNAs improve pharmacology in vivo
Authors: Jahns Hartmut , Taneja Nate , Willoughby Jennifer L S , Akabane-Nakata Masaaki , Brown Christopher R , Nguyen Tuyen , Bisbe Anna , Matsuda Shigeo , Hettinger Matt , Manoharan Rajar M , Rajeev Kallanthottathil G , Maier Martin A , Zlatev Ivan , Charisse Klaus , Egli Martin , Manoharan Muthiah
Published: June 2021

A critical challenge for the successful development of RNA interference-based therapeutics therapeutics has been the enhancement of their in vivo metabolic stability. In therapeutically relevant, fully chemically modified small interfering RNAs (siRNAs), modification of the two terminal phosphodiester linkages in each strand of the siRNA duplex with phosphorothioate (PS) is generally sufficient to protect against exonuclease degradation in vivo. Since PS linkages are chiral, we systematically studied the properties of siRNAs containing single chiral PS linkages at each strand terminus. We report an efficient and simple method to introduce chiral PS linkages and demonstrate that Rp diastereomers at the 5′ end and Sp diastereomers at the 3′ end of the antisense siRNA strand improved pharmacokinetic and pharmacodynamic properties in a mouse model. In silico modeling studies provide mechanistic insights into how the Rp isomer at the 5′ end and Sp isomer at the 3′ end of the antisense siRNA enhance Argonaute 2 (Ago2) loading and metabolic stability of siRNAs in a concerted manner.
Structural and biochemical insight into the mechanism of dual CpG site binding and methylation by the DNMT3A DNA methyltransferase
Authors: Emperle Max , Bangalore Disha M , Adam Sabrina , Kunert Stefan , Heil Hannah S , Heinze Katrin G , Bashtrykov Pavel , Tessmer Ingrid , Jeltsch Albert
Published: June 2021

DNMT3A/3L heterotetramers contain two active centers binding CpG sites at 12 bp distance, however their interaction with DNA not containing this feature is unclear. Using randomized substrates, we observed preferential co-methylation of CpG sites with 6, 9 and 12 bp spacing by DNMT3A and DNMT3A/3L. Co-methylation was favored by AT bases between the 12 bp spaced CpG sites consistent with their increased bending flexibility. SFM analyses of DNMT3A/3L complexes bound to CpG sites with 12 bp spacing revealed either single heterotetramers inducing 40° DNA bending as observed in the X-ray structure, or two heterotetramers bound side-by-side to the DNA yielding 80° bending. SFM data of DNMT3A/3L bound to CpG sites spaced by 6 and 9 bp revealed binding of two heterotetramers and 100° DNA bending. Modeling showed that for 6 bp distance between CpG sites, two DNMT3A/3L heterotetramers could bind side-by-side on the DNA similarly as for 12 bp distance, but with each CpG bound by a different heterotetramer. For 9 bp spacing our model invokes a tetramer swap of the bound DNA. These additional DNA interaction modes explain how DNMT3A and DNMT3A/3L overcome their structural preference for CpG sites with 12 bp spacing during the methylation of natural DNA.
Affirming the Abuse Liability and Addiction Potential of Menthol: Differences in Subjective Appeal to Smoking Menthol Versus Non-Menthol Cigarettes Across African American and White Young Adult Smokers
Authors: Cohn Amy M , Alexander Adam C , Ehlke Sarah J
Published: June 2021

Introduction

Menthol cigarettes are popular among young adults and are disproportionately used by African American smokers. Menthol’s minty and cooling sensations have been hypothesized to enhance the appeal and reinforcement of smoking; however, differences in menthol’s subjective appeal across races have been inconsistent. This secondary data analysis examined differences in subjective appeal for smoking menthol versus non-menthol cigarettes between African American and White young adult smokers.

Methods

Young adults (ages 18–24) recruited from Amazon Mechanical Turk (December 2018–January 2019) completed an online survey of tobacco use behavior. Past year smokers (n = 1726) answered questions about subjective responses to smoking (reward, satisfaction, throat hit, craving reduction, and aversion).

Results

Significantly more African American (73.2%) compared to White (52.4%) smokers preferred menthol cigarettes (p < .001). Menthol smokers reported greater positive and negative subjective responses to smoking than non-menthol smokers. Positive and negative subjective response were both associated with greater smoking intensity and lower cigarette harm perceptions. Interactions of menthol preference and race on indices of subjective appeal also emerged. African American non-menthol smokers reported lower levels of satisfaction, reward, and craving reduction compared to White non-menthol smokers.

Conclusions

The relationship between menthol preference and subjective response to smoking differs by race. Menthol is rated as more appealing than non-menthol smoking, and appeal indices were linked to smoking intensity and lower harm perceptions, indicating greater abuse liability of menthol cigarettes. Policies that ban menthol cigarettes may have a particularly positive impact on the cigarette smoking of African American young adult smokers.

Implications

The FDA issued an Advanced Notice of Proposed Rule Making to examine the role menthol in tobacco products to inform regulations to restrict or ban flavors. This study showed that menthol smokers reported greater appeal to smoking than non-menthol smokers; and an interaction of race x menthol preference showed African American non-menthol smokers reported the lowest levels of appeal to smoking. Multiple indices of cigarette appeal were positively correlated with smoking intensity and lower cigarette harm perceptions, highlighting the addiction potential of menthol cigarettes. Findings suggest a menthol cigarette ban could help reduce tobacco use among young adults.
The State of the Science on Cancer Diagnosis as a “Teachable Moment” for Smoking Cessation: A Scoping Review
Authors: Puleo Gabriella E , Borger Tia , Bowling William R , Burris Jessica L
Published: June 2021

Introduction

Theoretically, a cancer diagnosis has the potential to spur health behavior changes in physical activity, diet, substance use, medication adherence, and the like. The Teachable Moment heuristic is a parsimonious, transtheoretical framework for understanding the conditions under which behavior change might occur, with constructs that include affective, cognitive, and social factors. Application of the Teachable Moment to smoking cessation after cancer diagnosis might aid selection of predictors in observational studies and inform how to optimally design interventions to promote quit attempts and sustain abstinence, as many smoking cessation interventions for cancer survivors do not yield positive outcomes.

Aims and Methods

This scoping review of 47 studies that span nearly 20 years of literature examines the measurement of the Teachable Moment constructs and what empirical support they have in explaining cancer survivors’ smoking behavior.

Results

From this review, it appears the construct of affective response is more widely explored than risk perceptions, social role, and self-concept. Strong, negative affective responses (e.g., anxiety, general distress) may be a powerful contributor to continued smoking after a cancer diagnosis. Risk perceptions may also play a role in smoking behavior, such that never and former smokers espouse stronger perceptions of smoking-related risks than current smokers. Finally, due to a paucity of studies, the role of cancer survivors’ self-concept (e.g., identity as a “cancer survivor”) and changes in their social role (e.g., employee, athlete) are unclear contributors to their smoking behavior. In summary, the Teachable Moment holds promise in its application to smoking cessation after a cancer diagnosis, though more direct research is needed.

Conclusions

This scoping review of the scientific literature is the first formal test of the extent to which cancer diagnosis has been explored as a “teachable moment” for smoking cessation, with results that provide insight into issues of measurement precision and breadth as well as empirical support of the “teachable moment” heuristic.
Development and validation of an occupational health triage tool
Authors: Steel J S , Luyten J , Godderis L
Published: June 2021

Background

As work and health are closely interlinked, it is important to carefully monitor employees. However, limited resources restrict in-depth follow-up.

Aims

This study was aimed to develop a low-cost screening instrument for employees’ overall health status, that can be used across industries and that allows triaging workers to in-depth health surveillance in case of indications of health or functioning problems.

Methods

We developed a new questionnaire-based algorithm built on multiple predictors to assess the need for further follow-up. We used a systematic review, Delphi panel (n = 9) and focus group (n = 5) to determine the predictors, tested for language pitfalls in a pilot study and evaluated the questionnaire’s validity in two separate studies. Study 1 (n = 60) analysed the discriminatory power of the instrument by comparing it to the assessment of an occupational physician in a sample of employees from diverse occupational settings. Study 2 (n = 869) appraised the factor structure and internal consistency of the screening tool in a sample of employees from the hospital sector.

Results

Risk factors, current physical and mental health, functioning, absenteeism, job satisfaction and lifestyle were identified as the most relevant predictors. Study 1 showed the survey had good criterion validity (area under the curve = 0.72). Study 2 (N = 869, 28% response) demonstrated the internal consistency (Cronbach’s α = 0.94), and a factor analysis confirmed a second-order factor structure with adequate model fit (comparative fit index = 0.96, root mean square error of approximation = 0.04 and standardized root mean square residual = 0.07).

Conclusions

This questionnaire can be used to triage workers for occupational health follow-up and can, additionally, be useful to describe the epidemiology of work-related illness.
Transcondylar Approach for Resection of Medullary Cavernous Malformation: 2-Dimensional Operative Video
Authors: Erkmen Kadir , Al-Mefty Ossama
Published: June 2021

Cavernous malformations located within the brainstem present with a high rate of neurological symptoms and carry a more aggressive course in both pediatric and adult populations.
1,2
Cavernomas within the medulla are the rarest form, representing only 5% of all brainstem lesions.
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Repeated hemorrhage of brainstem cavernomas is associated with significant and cumulative neurological deficits and thus requires treatment.
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Microsurgical resection has become the optimal mode of treatment with the aim of resecting the live malformation and not merely the multiaged, organized hematoma.
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This is best achieved by approaching the cavernoma at the location where it projects to the surface and entering the lesion through a safe brainstem anatomic zone. For ventrally located lesions in the medulla, a transcondylar skull base approach provides a direct trajectory to the entry zone through a short surgical distance without the need to manipulate or retract neurovascular structures.
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Neuronavigation and intraoperative neurophysiological monitoring of somatosensory evoked potential, motor, and lower cranial nerves are adjuncts to increase patient safety. Radiosurgery for the treatment of brainstem cavernous malformations has been proposed; however, it demonstrates high risk and variable and often poor response rates.
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We present a surgical video demonstrating the transcondylar approach and resection of a medullary cavernoma in a 54-yr-old woman who has had multiple known prior hemorrhages and presented with a new onset of facial numbness and weakness, ataxia, and left body sensory loss. The patient consented to surgery and to photograph publication.

 Images at 1:28, 1:43 (left), 2:02 from Al-Mefty O, Operative Atlas of Meningiomas, © LWW, 1997,
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with permission.

 Images at 1:43 (right) from Arnautovic et al,
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with permission from JNSPG.
Australian Parties, Not Voters, Drive Under-Representation of Women
Authors: Martinez i Coma Ferran , McDonnell Duncan
Published: June 2021

The Australian House of Representatives contains far fewer women than men. But is this because parties of left and right discriminate against women or because voters do? Using a new dataset comprising 7271 House candidates from 2001 to 2019, firstly, we find that the percentage of women candidates is increasing, but is consistently higher for parties of the left than the right. Secondly, women tend to be selected more by parties of both left and right in unsafe seats. Thirdly, all else being equal, voters reward women running for Labor with over 1400 votes more, are neutral towards those of the Liberals and Greens, but tend to penalise women standing for the Nationals. We conclude that, overall, it is parties, not voters, driving under-representation of women in Australia’s lower house.
Seed Mucilage: Biological Functions and Potential Applications in Biotechnology
Authors: Tsai Allen Yi-Lun , McGee Robert , Dean Gillian H , Haughn George W , Sawa Shinichiro
Published: June 2021

In plants, the diaspore (seed dispersal unit) may include a seed coat and/or pericarp to protect the embryo and assist in dispersion. In many species, the seed coat and/or pericarp secrete a gelatinous mixture of cell wall polysaccharides known as mucilage. In several species, mucilage synthesis, secretion and modification have been studied extensively as model systems for the investigation of plant cell wall structure and function. Despite this, efforts toward understanding the role of mucilage have received less attention. Mucilage has been hypothesized to impact seed dispersal through interaction with soil, protecting the seed in the gut following ingestion by animals or affecting the ability of seeds to sink or float in water. Mucilage has been found to influence seed germination and seedling establishment, most often during abiotic stress, probably by maintaining seed hydration when water is scarce. Finally, mucilage has been documented to mediate interactions with various organisms. Advances in transgenic technology should enable the genetic modification of mucilage structure and function in crop plants. Cells synthesizing mucilage may also be a suitable platform for creating custom polysaccharides or proteins with industrial applications. Thus, in the near future, it is likely that research on seed mucilage will expand well beyond the current focus. Here we summarize our understanding of the biological functions of mucilage and provide an outlook on the future of mucilage research.