bluuebunny/crossref_metadata_2025 huggingface dataset:
Splitting the lentils: Clues to galaxy/black hole coevolution from the discovery of offset relations for non-dusty versus dusty (wet-merger-built) lenticular galaxies in theMbh–M*,spheroid andMbh–M*,galaxy diagrams
Authors: Graham Alister W
Published: February 2023

This work advances the (galaxy morphology)-dependent (black hole mass, Mbh)–(spheroid/galaxy stellar mass, M*) scaling relations by introducing ‘dust bins’ for lenticular (S0) galaxies. Doing so has led to the discovery of Mbh–M*,sph and Mbh–M*,gal relations for dusty S0 galaxies – built by major wet mergers and comprising half the S0 sample – offset from the distribution of dust-poor S0 galaxies. The situation is reminiscent of how major dry mergers of massive S0 galaxies have created an offset population of ellicular and elliptical galaxies. For a given Mbh, the dust-rich S0 galaxies have 3–4 times higher M*,sph than the dust-poor S0 galaxies, and the steep distributions of both populations in the Mbh–M*,sph diagram bracket the $M_{\rm bh} \propto M_{\rm *,sph}^{2.27+/-0.48}$ relation defined by the spiral galaxies, themselves renovated through minor mergers. The new relations offer refined means to estimate Mbh in other galaxies and should aid with: (i) constructing (galaxy morphology)-dependent black hole mass functions; (ii) estimating the masses of black holes associated with tidal disruption events; (iii) better quantifying evolution in the scaling relations via improved comparisons with high-z data by alleviating the pickle of apples versus oranges; (iv) mergers and long-wavelength gravitational wave science; (v) simulations of galaxy/black hole coevolution and semi-analytic works involving galaxy speciation; plus (vi) facilitating improved extrapolations into the intermediate-mass black hole landscape. The role of the galaxy’s environment is also discussed, and many potential projects that can further explore the morphological divisions are mentioned.
Limits on compression of cosmic rays in supernova remnants
Authors: Sushch Iurii , Brose Robert
Published: February 2023

The spectral shape of the gamma-ray emission observed for dynamically old supernova remnants that interact with molecular clouds triggered an exciting scenario of adiabatic compression and farther re-acceleration of Galactic cosmic rays (GCRs) in radiative shells of the remnants, which was extensively discussed and applied to various sources over recent years. Indeed, the observed gamma-ray spectrum from a number of remnants strongly resembles the expected spectrum of the gamma-ray emission from the compressed population of GCRs. In the following we discuss the feasibility of this scenario and show that it is very unlikely that compressed GCRs could produce sufficient amount of gamma-rays and that the observed spectral shape is putting strong limits on the allowed compression factors. Further, absence of curvature in featureless power-law spectra of evolved supernova remnants at radio wavelengths is strongly disfavouring the compression scenario for electrons and hence for hadrons. Our calculations show that the contribution of compressed electrons to the observed radio flux could reach at most $\sim 10\,$ per cent.
Coherent and incoherent structures in fuzzy dark matter haloes
Authors: Liu I-Kang , Proukakis Nick P , Rigopoulos Gerasimos
Published: February 2023

We show that fuzzy dark matter haloes exhibit spatial differentiation in the coherence of the field configuration, ranging from completely coherent in the central solitonic core to incoherent outside it, with a significant drop of the dimensionless phase-space density with increasing radius. The core is a pure condensate, overlapping perfectly with the Penrose-Onsager mode corresponding to the largest eigenvalue of the one-particle density matrix. The virialized outer halo exhibits no clear coherence as a whole upon radial and temporal averaging but can be described as a collection of local, short-lived quasi-condensate lumps, exhibiting suppressed fluctuations, which can be identified with the structures commonly referred to as granules. These localized regions are separated by vortices that form a dynamical web, inhibiting phase coherence across the entire halo. We further examine the core oscillations, finding that they are accurately described by two time-dependent parameters characterizing the size of the core, rc(t), and a crossover region, rt(t). For the haloes in our merger simulations, this feature is reflected in the (anti-)correlated oscillation of the peak value of the density power-spectrum. The halo’s turbulent vortex tangle appears to reach a quasi-equilibrium state over probed time-scales, with the incompressible component of the kinetic energy exhibiting a characteristic k−3 tail in its spectrum, indicative of a ρ ∼ r2 density profile around the quantum vortex cores. Comparison of the peak wavenumbers in the corresponding power-spectra shows the inter-vortex spacing and the granule length scale in the outer halo to be very similar and slightly above the core size.
The AGNIFS survey: spatially resolved observations of hot molecular and ionized outflows in nearby active galaxies
Authors: Riffel R A , Storchi-Bergmann T , Riffel R , Bianchin M , Zakamska N L , Ruschel-Dutra D , Bentz M C , Burtscher L , Crenshaw D M , Dahmer-Hahn L G , Dametto N Z , Davies R I , Diniz M R , Fischer T C , Harrison C M , Mainieri V , Revalski M , Rodriguez-Ardila A , Rosario D J , Schönell A J
Published: February 2023

We present the hot molecular and warm ionized gas kinematics for 33 nearby (0.001 ≲ z ≲ 0.056) X-ray selected active galaxies using the H$_2\, 2.1218\, \mu$m and Br γ emission lines observed in the K band with the Gemini near-infrared integral field spectrograph. The observations cover the inner 0.04–2 kpc of each active galactic nucleus at spatial resolutions of 4–250 pc with a velocity resolution of σinst ≈ 20 ${\rm km\, s^{-1}}$. We find that 31 objects (94 per cent) present a kinematically disturbed region (KDR) seen in ionized gas, while such regions are observed in hot molecular gas for 25 galaxies (76 per cent). We interpret the KDR as being due to outflows with masses of 102–107 and 100–104 M⊙ for the ionized and hot molecular gas, respectively. The ranges of mass-outflow rates ($\dot{M}_{\rm out}$) and kinetic power ($\dot{E}_{\rm K}$) of the outflows are 10−3–101 M⊙ yr−1 and ∼1037–1043 erg s−1 for the ionized gas outflows, and 10−5–10−2 M⊙ yr−1 and 1035–1039 erg s−1 for the hot molecular gas outflows. The median coupling efficiency in our sample is $\dot{E}_{\mathrm{K}}/L_{\rm bol}\approx 1.8\times 10^{-3}$ and the estimated momentum fluxes of the outflows suggest they are produced by radiation-pressure in low-density environment, with possible contribution from shocks.
The study of thermonuclear X-ray bursts in accreting millisecond pulsar MAXI J1816−195 with NuSTAR and NICER
Authors: Mandal Manoj , Pal Sabyasachi , Chauhan Jaiverdhan , Lohfink Anne , Bharali Priya
Published: February 2023

The millisecond pulsar MAXI J1816−195 was recently discovered in an outburst by the Monitor of All-sky X-ray Image (MAXI) in 2022 May. We study different properties of the pulsar using data from the Nuclear Spectroscopic Telescope Array (NuSTAR) and the Neutron Star Interior Composition Explorer (NICER) observations. The unstable burning of accreted material on the surface of neutron stars induces thermonuclear (Type-I) bursts. Several such thermonuclear bursts have been detected by MAXI J1816−195 during its outburst. We investigate the evolution of the burst profiles with flux and energy using NuSTAR and NICER observations. During the NuSTAR observation, a total of four bursts were detected from the source. The duration of each burst is around ∼30 s and the ratio of peak to persistent count rate is ∼26 as seen from the NuSTAR data. The burst profiles are modelled using a sharp linear rise and exponential decay function to determine the burst timing parameters. The burst profiles show a relatively long tail at lower energies. The broad-band time-resolved spectra during the burst periods are successfully modelled with a combination of an absorbed blackbody along with a non-thermal component to account for the persistent emission. From our modelling results, we are able to estimate the maximum apparent emitting area of the blackbody of the neutron star to be ∼12.5 km during the peak of the outburst and the maximum distance to the object to be 8.7 kpc. Our findings for the mass accretion rate and the α factor indicate the stable burning of hydrogen via a hot CNO cycle during the bursts.
PINION: physics-informed neural network for accelerating radiative transfer simulations for cosmic reionization
Authors: Korber Damien , Bianco Michele , Tolley Emma , Kneib Jean-Paul
Published: February 2023

With the advent of the Square Kilometre Array Observatory (SKAO), scientists will be able to directly observe the Epoch of Reionization by mapping the distribution of neutral hydrogen at different redshifts. While physically motivated results can be simulated with radiative transfer codes, these simulations are computationally expensive and cannot readily produce the required scale and resolution simultaneously. Here we introduce the Physics-Informed neural Network for reIONization (PINION), which can accurately and swiftly predict the complete 4D hydrogen fraction evolution from the smoothed gas and mass density fields from pre-computed N-body simulation. We trained PINION on the C2-Ray simulation outputs and a physics constraint on the reionization chemistry equation is enforced. With only five redshift snapshots, PINION can accurately predict the entire reionization history between z = 6 and 12. We evaluate the accuracy of our predictions by analyzing the dimensionless power spectra and morphology statistics estimations against C2-Ray results. We show that while the network’s predictions are in very good agreement with simulation to redshift z > 7, the network’s accuracy suffers for z < 7. We motivate how PINION performance could be improved using additional inputs and potentially generalized to large-scale simulations.
Tests of photometry: the case of the NGC 3370 ACS field
Authors: Jang In Sung
Published: February 2023

A critical analysis and comparison of different methods for obtaining point spread function (PSF) photometry are carried out. Deep ACS observations of NGC 3370 were reduced using four distinct approaches. These reductions explore a number of methodological differences: software packages (DAOPHOT and DOLPHOT), input images (individual and stacked frames), PSF models (synthetic and empirical), and aperture correction methods (automatic and manual). A comparison of the photometry leads to the following results: (1) Photometric incompleteness between individual reductions shows only a minimal difference (<10 per cent). (2) Statistical errors are 20 per cent to 30 per cent smaller for DAOPHOT runs on stacked frames than DOLPHOT runs on individual frames. (3) Statistical errors assigned directly by the photometry codes are 25 per cent to 50 per cent smaller than the errors measured from artificial star tests. (4) Systematic errors are magnitude dependent and become larger at the faint end, at the level of σs ∼ 0.1 mag. (5) The automatic aperture correction routines in DOLPHOT result in a significant systematic error (σs ∼ 0.05 mag). (6) Individual reductions agree well at the 0.02-mag level when the systematic errors are properly corrected through artificial star tests. The reasonable agreement between the reductions leads to important implications that (i) the reduction-dependent errors can be reduced to a 1 per cent level in the luminosity distance scale, and (ii) the stacked frame photometry can be a good means to study non-variable stars in external galaxies.
Polymer simulations guide the detection and quantification of chromatin loop extrusion by imaging
Authors: Sabaté Thomas , Lelandais Benoît , Bertrand Edouard , Zimmer Christophe
Published: February 2023

Genome-wide chromosome conformation capture (Hi-C) has revealed the organization of chromatin into topologically associating domains (TADs) and loops, which are thought to help regulate genome functions. TADs and loops are understood as the result of DNA extrusion mediated by the cohesin complex. However, despite recent efforts, direct visualization and quantification of this process in single cells remains an open challenge. Here, we use polymer simulations and dedicated analysis methods to explore if, and under which conditions, DNA loop extrusion can be detected and quantitatively characterized by imaging pairs of fluorescently labeled loci located near loop or TAD anchors in fixed or living cells. We find that under realistic conditions, extrusion can be detected and the frequency of loop formation can be quantified from fixed cell images alone, while the lifetime of loops and the speed of extrusion can be estimated from dynamic live-cell data. Our delineation of appropriate imaging conditions and the proposed analytical methods lay the groundwork for a systematic quantitative characterization of loop extrusion in fixed or living cells.
Incoherent merger network for robust ratiometric gene expression response
Authors: Kwon Ukjin , Huang Hsin-Ho , Chávez Jorge L , Beabout Kathryn , Harbaugh Svetlana , Del Vecchio Domitilla
Published: February 2023

A ratiometric response gives an output that is proportional to the ratio between the magnitudes of two inputs. Ratio computation has been observed in nature and is also needed in the development of smart probiotics and organoids. Here, we achieve ratiometric gene expression response in bacteria Escherichia coli with the incoherent merger network. In this network, one input molecule activates expression of the output protein while the other molecule activates an intermediate protein that enhances the output’s degradation. When degradation rate is first order and faster than dilution, the output responds linearly to the ratio between the input molecules’ levels over a wide range with R2 close to 1. Response sensitivity can be quantitatively tuned by varying the output’s translation rate. Furthermore, ratiometric responses are robust to global perturbations in cellular components that influence gene expression because such perturbations affect the output through an incoherent feedforward loop. This work demonstrates a new molecular signal processing mechanism for multiplexed sense-and-respond circuits that are robust to intra-cellular context.
Actinobacillus pleuropneumoniae encodes multiple phase-variable DNA methyltransferases that control distinct phasevarions
Authors: Nahar Nusrat , Tram Greg , Jen Freda E-C , Phillips Zachary N , Weinert Lucy A , Bossé Janine T , Jabbari Jafar S , Gouil Quentin , Du Mei R M , Ritchie Matthew E , Bowden Rory , Langford Paul R , Tucker Alexander W , Jennings Michael P , Turni Conny , Blackall Patrick J , Atack John M
Published: February 2023

Actinobacillus pleuropneumoniae is the cause of porcine pleuropneumonia, a severe respiratory tract infection that is responsible for major economic losses to the swine industry. Many host-adapted bacterial pathogens encode systems known as phasevarions (phase-variable regulons). Phasevarions result from variable expression of cytoplasmic DNA methyltransferases. Variable expression results in genome-wide methylation differences within a bacterial population, leading to altered expression of multiple genes via epigenetic mechanisms. Our examination of a diverse population of A. pleuropneumoniae strains determined that Type I and Type III DNA methyltransferases with the hallmarks of phase variation were present in this species. We demonstrate that phase variation is occurring in these methyltransferases, and show associations between particular Type III methyltransferase alleles and serovar. Using Pacific BioSciences Single-Molecule, Real-Time (SMRT) sequencing and Oxford Nanopore sequencing, we demonstrate the presence of the first ever characterised phase-variable, cytosine-specific Type III DNA methyltransferase. Phase variation of distinct Type III DNA methyltransferase in A. pleuropneumoniae results in the regulation of distinct phasevarions, and in multiple phenotypic differences relevant to pathobiology. Our characterisation of these newly described phasevarions in A. pleuropneumoniae will aid in the selection of stably expressed antigens, and direct and inform development of a rationally designed subunit vaccine against this major veterinary pathogen.
The mismatch repair endonuclease MutLα tethers duplex regions of DNA together and relieves DNA torsional tension
Authors: Witte Scott J , Rosa Isabella M , Collingwood Bryce W , Piscitelli Jonathan M , Manhart Carol M
Published: February 2023

In eukaryotic mismatch repair, MutS homologs recognize mismatches and recruit the MutLα endonuclease which introduces a nick in the newly replicated, error-containing DNA strand. The nick occurs in response to the mismatch, but at a site up to several hundred base pairs away. The MutLα nick promotes mismatch excision by an exonuclease (Exo1) or removal by the strand displacement activity of a DNA polymerase which may work in conjunction with a flap endonuclease. Models have suggested that MutL homolog endonucleases form oligomeric complexes which facilitate and are activated by strand capture mechanisms, although such models have never been explicitly tested. We present evidence that the mismatch repair MutLα endonuclease is activated by DNA–DNA associations and that it can use this property to overcome DNA torsional barriers. Using DNA ligation and pull-down experiments, we determined that the MutLα endonuclease associates two DNA duplexes. Using nuclease assays, we determined that this activity stimulates MutLα’s endonuclease function. We also observe that MutLα enhances a topoisomerase without nicking the DNA itself. Our data provide a mechanistic explanation for how MutL proteins interact with DNA during mismatch repair, and how MutL homologs participate in other processes, such as recombination and trinucleotide repeat expansions.
Clinical, histological, and molecular features of gliomas in adults with neurofibromatosis type 1
Authors: Romo Carlos G , Piotrowski Anna F , Campian Jian L , Diarte Jose , Rodriguez Fausto J , Bale Tejus A , Dahiya Sonika , Gutmann David H , Lucas Calixto-Hope G , Prichett Laura , Mellinghoff Ingo , Blakeley Jaishri O
Published: February 2023

Background

People with NF1 have an increased prevalence of central nervous system malignancy. However, little is known about the clinical course or pathologic features of NF1-associated gliomas in adults, limiting clinical care and research.

Methods

Adults (≥18 years) with NF1 and histologically confirmed non-optic pathway gliomas (non-OPGs) at Johns Hopkins Hospital, Memorial Sloan Kettering Cancer Center, and Washington University presenting between 1990 and 2020 were identified. Retrospective data were collated, and pathology was reviewed centrally.

Results

Forty-five patients, comprising 23 females (51%), met eligibility criteria, with a median of age 37 (18–68 years) and performance status of 80% (30%–100%). Tissue was available for 35 patients. Diagnoses included infiltrating (low-grade) astrocytoma (9), glioblastoma (7), high-grade astrocytoma with piloid features (4), pilocytic astrocytoma (4), high-grade astrocytoma (3), WHO diagnosis not reached (4) and one each of gliosarcoma, ganglioglioma, embryonal tumor, and diffuse midline glioma. Seventy-one percent of tumors were midline and underwent biopsy only. All 27 tumors evaluated were IDH1-wild-type, independent of histology. In the 10 cases with molecular testing, the most common genetic variants were NF1, EGFR, ATRX, CDKN2A/B, TP53, TERT, and MSH2/3 mutation. While the treatments provided varied, the median overall survival was 24 months [2–267 months] across all ages, and 38.5 [18–109] months in individuals with grade 1–2 gliomas.

Conclusions

Non-OPGs in adults with NF1, including low-grade tumors, often have an aggressive clinical course, indicating a need to better understand the pathobiology of these NF1-associated gliomas.
Green carbon science: fundamental aspects
Authors: He Mingyuan , Zhang Kun , Guan Yejun , Sun Yuhan , Han Buxing
Published: February 2023

Carbon energy has contributed to the creation of human civilization, and it can be considered that the configuration of the carbon energy system is one of the important laws that govern the operation of everything in the universe. The core of the carbon energy system is the opposition and unity of two aspects: oxidation and reduction. The operation of oxidation and reduction is based on the ternary elemental system composed of the three elements of carbon, hydrogen and oxygen. Its operation produces numerous reactions and reaction products. Ancient Chinese philosophy helps us to understand in depth the essence of green carbon science, to explore its scientific basis, and to identify the related platforms for technology development.
Workup of difficult-to-treat asthma: implications from treatable traits
Authors: Zhang Qing , Wu Wen Wen , Li Lei , McDonald Vanessa M , Chen Yu Cheng , Wang Gang , Gibson Peter G
Published: February 2023

Traditional stepwise approach usually adjusts the treatment regimen based on changes in asthma symptoms and severity to achieve good asthma control. However, due to the generalized heterogeneity and complexity of asthma, its therapeutic efficacy in difficult-to-treat asthma is limited. Recently, a precision medicine approach based on the identification and intervention of treatable traits of chronic airway disease has been proposed and appears to be of greater benefit to asthmatics. We reported a 71-year-old male with uncontrolled asthma and multiple exacerbations over the past year. He complained of persistent dyspnea despite high-dose of inhaled corticosteroids plus other controllers. Does this patient have some potential treatable traits contributing to difficult-to-treat asthma? Through a multidimensional assessment of three domains including pulmonary, extrapulmonary, and behavioral/risk factors, 15 treatable traits were identified in the patient, mainly including airflow limitation, eosinophilic airway inflammation, small airway dysfunction, exacerbation prone, dilated cardiomyopathy, diabetes mellitus, inhaler device polypharmacy, smoking, and the absence of an asthma action plan. After targeted treatment for these treatable traits, the patient experienced significant improvement in dyspnea and he could maintain good asthma control with low-dose inhaled corticosteroids and long-acting β2-agonist. This study shows that, in response to the limitation of a stepwise approach to therapy, treatable traits is a new strategy where patients are individually assessed for a specified set of treatable problems, and an individualized treatment program is developed and implemented based on this multidimensional assessment, especially for difficult-to-treat asthma.
Police Recognition of Gender Issues in Relation to Intimate Partner Domestic Violence and Abuse in Greece
Authors: Kravvariti Vasiliki , Browne Kevin
Published: February 2023

The aim of the research was to understand the perceptions and beliefs of police officers who work and support victims of intimate partner domestic violence and abuse (DVA) and evaluate the way it is recorded. A sample was collected from eight police departments in Greece. The head of each police department was approached by the researcher and asked to distribute a structured questionnaire to front-line police officers who work with DVA victims. In total 358 police officers completed the questionnaire. Overall, nearly twice as many police officers referred to female victims (n = 170) compared to male victims (n = 83) of DVA. The police officers indicated that female victims usually suffered from severe physical violence/GBH (43%) and psychological abuse (27%), whereas male victims were most likely to disclose minor physical injuries and verbal abuse (49%) and less psychological violence (10%). An arrest was the most common response for both female and male victims (51% and 60%, respectively). Police participants indicated that offenders against males were more likely to be charged (28%) but less likely to be convicted (4%), whereas the opposite was reported for offenders of female victims (14% and 13%, respectively). If the offender was known to the police, the opinion was they were less likely to be prosecuted. Police respondents reported no significant differences for female and male victims as to causal factors and reasons for NOT reporting DVA. These were discrimination (31%), few DVA services (23%), intimidation (15%), shame and stigma of media reports (14%), lack of community support (6%), and personal reasons (9%).
Malnutrition and sarcopenia worsen short- and long-term outcomes in internal medicine inpatients
Authors: Carretero Gómez Juana , Galeano Fernández Tomás F , Vidal Ríos Antonio S , Pérez Palacios María R , García García Gema M , García Carrasco Carolina , Romero Requena Jorge M , Fernández Recio José M , Nevado López-Alegría Leticia , Pijierro Amador Agustín , Arévalo Lorido José C
Published: February 2023

Purpose

This work aims to describe patients hospitalized in internal medicine wards in terms of nutrition and sarcopenia. It also seeks to evaluate short- and long-term mortality related to malnutrition and sarcopenia.

Methods

This cross-sectional study collected data on consecutive patients admitted to a single center’s internal medicine ward. Patients were recruited in May and October 2021. Malnutrition was determined by the Mini-Nutritional Assessment-Short Form (MNA-SF) and sarcopenia by the Strength, Assistance in walking, Rise from a chair, Climb stairs, and Falls questionnaire (SARC-F scale) and handgrip strength test. Patients who were hospitalized for >48 hours were excluded.

Results

The sample included 619 patients with a mean ± SD age of 76.0 ± 14.8 years of which 50.6% were women. Patients were classified into three groups based on malnutrition: group 1 (MNA-SF 12–14 points) (no risk) included 158 patients, group 2 (MNA-SF 8–12 points) (high risk) included 233 patients, and group 3 (MNA-SF 0–7 points) (malnourished) included 228 patients. Malnourished patients had more dysphagia, significantly lower protein and albumin levels, and significantly higher inflammatory marker levels and pressure ulcers. In-hospital mortality was significantly higher in groups 2 and 3 (p < .00001). The worst outcome (mortality and readmissions or mortality) was more common among malnourished patients (p = .0001). Inflammation, comorbidity, and sarcopenia were most closely associated with negative outcomes.

Conclusion

Malnutrition upon admission is associated with worse short- and long-term outcomes in internal medicine inpatients. Sarcopenia, multimorbidity, and inflammation—measured by albumin, C-reactive protein, or their ratios—are key risk factors. Early identification of malnutrition and sarcopenia through active screening is important in caring for internal medicine patients.
Predictors of self-reported research self-efficacy and perception of research amongst medical students in the United Kingdom: a national cross-sectional survey
Authors: Osunronbi Temidayo , Adeboye William , Faluyi David , Sofela Jasmine , Shoker Serena , O'Riordan Marguerite , Mitoko Christine A , Mberu Valentine K , Mandangu Chenai , Madume Rachael , Kolawole Adebola I , Jones Robert I , Inyang Deborah , Ibrahim Ummulkhulsum , Ibeanusi Ikenna M , Fofanah Isata J , Corriero Anna C , Chimba Chimba , Akhionbare Izieduwa , Ahmad Zain , Adamu-Biu Fatima , Abraha Semhar , Abankwa Efua , Sofela Agbolahan ,   REMED-UK collaborators, Abdelhafiz Dima , Adebayo Ayanfe , Afolabi Oluwafemi , Awow Fatima , Crankson Akua , Exley Henry , Frame Lauren , Johnson Ola , Kufuor Risata A , Madu William , McCutcheon Calum , Mohamed Suaad , Munyebvu Samantha R , Nelson-Rowe Ellen , Shah Max , Stewart Oonagh , Watts Alice
Published: February 2023

Purpose

There has been a decline in the number of academic clinicians in the UK, and there are ethnic/gender disparities in the academic workforce. Higher research self-efficacy (RSE) and a positive perception of research (PoR) amongst students are associated with a higher motivation to engage in academic medicine. Hence, this study aimed to determine the factors that influence RSE and PoR amongst UK medical students.

Methods

This is a multicentre cross-sectional survey of medical students in 36 UK medical schools in the 2020/21 academic year. Multiple linear regression was used to investigate the association between students’ demographics and RSE/PoR. P-values less than a Bonferroni-corrected significance level of .05/28 = .0018 were considered statistically significant.

Results

In total, 1573 individuals participated from 36 medical schools. There were no ethnic differences in PoR or RSE scores. Although there were no gender differences in PoR, female students had lower RSE scores than male students (adjusted β = −1.75; 95% CI: −2.62, −0.89). Research experience before medical school (adjusted β = 3.02; 95% CI: 2.11, 3.93), being in the clinical training phase (adjusted β = 1.99; 95% CI: 1.09, 2.90), and completing a degree before medical school (adjusted β = 3.66; 95% CI: 2.23, 5.09) were associated with higher RSE.

Conclusion

There were no associations between the predictor variables and PoR. Female students had lower self-reported RSE scores. Future studies should investigate the role of targeted research mentorship in improving RSE amongst female medical students.
Role of denosumab in bone erosions in rheumatoid arthritis
Authors: Stefania Silvia , Rotondo Cinzia , Mele Angiola , Trotta Antonello , Cantatore Francesco Paolo , Corrado Addolorata
Published: February 2023

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic inflammation and synovitis which evolve into joint destruction and deformity. Bone abnormalities are represented by marginal bone erosions and iuxta-articular and generalized osteoporosis. Overactivation of osteoclasts along with dysregulation of osteoblasts are the key events. Bone resorption is mediated by the receptor activator of nuclear factor (NF)-κB (RANK) ligand (RANK-L), responsible for the differentiation, proliferation, and activation of osteoclasts. RANK-L binds its receptor RANK, localized on the surface of preosteoclasts and mature osteoclasts promoting osteoclastogenesis. High levels of RANK-L were demonstrated in active RA patients. Denosumab, a fully human monoclonal antibody, binds RANK-L and suppresses the RANK–RANK-L signaling pathway leading to the inhibition of osteoclastogenesis. A retrospective analysis of published studies such as clinical trials evidenced the efficacy of denosumab in preventing bone erosion progression in RA patients.

Key messages Key questions to answer in future include the following: Could denosumab be associated with other biologic therapies in RA patients? Could denosumab block the progression of bone damage in RA? Could denosumab be used for the prevention of bone erosion in RA?
Visual Hallucinations in Psychosis: The Curious Absence of the Primary Visual Cortex
Authors: van Ommen Marouska M , van Laar Teus , Renken Remco , Cornelissen Frans W , Bruggeman Richard
Published: February 2023

Background and Hypothesis

Approximately one-third of patients with a psychotic disorder experience visual hallucinations (VH). While new, more targeted treatment options are warranted, the pathophysiology of VH remains largely unknown. Previous studies hypothesized that VH result from impaired functioning of the vision-related networks and impaired interaction between those networks, including a possible functional disconnection between the primary visual cortex (V1) and higher-order visual processing regions. Testing these hypotheses requires sufficient data on brain activation during actual VH, but such data are extremely scarce.

Study Design

We therefore recruited seven participants with a psychotic disorder who were scanned in a 3 T fMRI scanner while indicating the occurrence of VH by pressing a button. Following the scan session, we interviewed participants about the VH experienced during scanning. We then used the fMRI scans to identify regions with increased or decreased activity during VH periods versus baseline (no VH).

Study Results

In six participants, V1 was not activated during VH, and in one participant V1 showed decreased activation. All participants reported complex VH such as human-like beings, objects and/or animals, during which higher-order visual areas and regions belonging to the vision-related networks on attention and memory were activated.

Discussion

These results indicate that VH are associated with diffuse involvement of the vision-related networks, with the exception of V1. We therefore propose a model for the pathophysiology of psychotic VH in which a dissociation of higher-order visual processing areas from V1 biases conscious perception away from reality and towards internally generated percepts.
Converting donation to transaction: how platform capitalism exploits relational labor in non-profit fundraising
Authors: Zheng Wenjuan
Published: February 2023

Viewing platforms as a new kind of factory and playground, scholars have investigated how the platform economy transforms work and entertainment. As dominant platforms continue to encroach on new markets and sectors, including the non-profit sector, few have examined the ramifications when they serve as a plaza for civic action. Despite the civic orientation of these platform activities, platforms can reconfigure the charity event and mediate civic interaction through the permissive power they possess to extract surplus value from users’ online interactions invisibly. Drawing from the ethnographic fieldwork of the two non-governmental organizations (NGOs) participating in a crowdfunding event in China, I show how the platform company creates a competition-based civic event to mobilize thousands of NGOs to crowdfund on their social media platform. In particular, the platform induced NGO workers working for those organizations to mobilize their networks for fundraising. Performing relational labor to persuade friends, families and acquaintances to give donations as a job responsibility deviated from the norms of reciprocity, which incurred workers’ emotional, social and even financial costs. Invisibly, the platform extracts social capital from workers’ relational labor.
The Feasibility and Acceptability of a Needs-Oriented Psychoeducational Intervention Among Caregivers of Adolescent and Young Adult Cancer Patients
Authors: Cheng Qinqin , Ng Marques S. N. , Chen Yongyi , Li Xuying , Liu Gaoming , Zhang Mengyue , So Winnie K. W.
Published: February 2023

Background

Little is known about the psychoeducational interventions for caregivers of adolescent and young adult (AYA) cancer patients.

Objective

To evaluate the feasibility and acceptability of a needs-oriented psychoeducational intervention among caregivers of AYA cancer patients.

Methods

In this 2-arm (parallel-group), pilot randomized controlled trial, participants were randomized to the intervention or control group. Participants in the control group received usual care, whereas those in the intervention group received a needs-oriented psychoeducational intervention via WeChat as well as the usual care. Feasibility was evaluated on recruitment, attrition, and adherence rates and the data collection process. Acceptability was assessed based on participants’ satisfaction with and perceived usefulness of the intervention, collected using a questionnaire. In addition, a semistructured interview was conducted to explore their experiences.

Results

Twenty-four caregivers of AYA cancer patients were recruited, with a consent rate of 61.5%. The attrition and response rates 5 weeks after baseline were 8.3% and 91.7%. Among the 12 participants in the intervention group, 10 (83.3%) completed all of the 5 weekly sessions. Most of the participants were satisfied with the program and perceived its usefulness. The semistructured interviews revealed 3 major categories: facilitators of participation, perception of the intervention, and perceived benefits.

Conclusions

The needs-oriented psychoeducational intervention delivered through WeChat is feasible for and acceptable to caregivers of AYA cancer patients. A full-scale study is warranted to examine the effects of this intervention on caregivers’ health outcomes.

Implications for Practice

The WeChat-based, needs-oriented psychoeducational intervention may be beneficial to improve caregivers’ health outcomes.
Vitamin C and Transferrin Reduce RNA Methylation in Mouse Embryonic Stem Cells
Authors: Brandt Gabrielle , Sedivy Laura J. , Mitchell Matthew , Phiel Christopher J.
Published: February 2023

Methylation of mRNA on adenosine bases (referred to as m6A) is the most common internal modification of mRNA in eukaryotic cells. Recent work has revealed a detailed view of the biological significance of m6A-modified mRNA, with a role in mRNA splicing, control of mRNA stability, and mRNA translation efficiency. Importantly, m6A is a reversible modification, and the primary enzymes responsible for methylating (Mettl3/Mettl14) and demethylating RNA (FTO/Alkbh5) have been identified. Given this reversibility, we are interested in understanding how m6A addition/removal is regulated. Recently, we identified glycogen synthase kinase-3 (Gsk-3) activity as a mediator of m6A regulation via controlling the levels of the FTO demethylase in mouse embryonic stem cells (ESCs), with Gsk-3 inhibitors and Gsk-3 knockout both leading to increased FTO protein and decreased m6A mRNA levels. To our knowledge, this remains one of the only mechanisms identified for the regulation of m6A modifications in ESCs. Several small molecules that have been shown to promote the retention of pluripotency of ESCs, and interestingly, many have connections to the regulation of FTO and m6A. Here we show that the combination of Vitamin C and transferrin potently reduces levels of m6A and promotes retention of pluripotency in mouse ESCs. Combining Vitamin C and transferrin should prove to be valuable in growing and maintaining pluripotent mouse ESCs.
Antibody landscape of C57BL/6 mice cured of B78 melanoma via immunotherapy
Authors: Hoefges A , McIlwain SJ , Erbe AK , Mathers N , Xu A , Melby D , Tetreault K , Le T , Kim K , Pinapati RS , Garcia B , Patel J , Heck M , Feils AS , Tsarovsky N , Hank JA , Morris ZS , Ong IM , Sondel PM
Published: February 2023

1

Antibodies can play an important role in innate and adaptive immune responses against cancer, and in preventing infectious disease. Flow cytometry analysis of sera of immune mice that were previously cured of their melanoma through a combined immunotherapy regimen with long-term memory showed strong antibody-binding against melanoma tumor cell lines. Using a high-density whole-proteome peptide array, we assessed potential protein-targets for antibodies found in immune sera. Sera from 6 of these cured mice were analyzed with this high-density, whole-proteome peptide array to determine specific antibody-binding sites and their linear peptide sequence. We identified thousands of peptides that were targeted by 2 or more of these 6 mice and exhibited strong antibody binding only by immune, not naive sera. Confirmatory studies were done to validate these results using 2 separate ELISA-based systems. To the best of our knowledge, this is the first study of the “immunome” of protein-based epitopes that are recognized by immune sera from mice cured of cancer via immunotherapy.

summary

Hoefges et al. utilized a whole-proteome peptide array approach to show that C57BL/6 mice develop a large repertoire of antibodies against linear peptide sequences of their melanoma after receiving a curative immunotherapy regimen consisting of radiation and an immunocytokine.
SP2G: an imaging and analysis pipeline revealing the inter and intra-patient migratory diversity of glioblastoma
Authors: Crestani Michele , Kakogiannos Nikolaos , Iannelli Fabio , Dini Tania , Maderna Claudio , Giannotta Monica , Pelicci Giuliana , Maiuri Paolo , Monzo Pascale , Gauthier Nils C.
Published: February 2023

Glioblastomas are heterogeneous, primary brain tumors hiding several sub-populations. Patient-derived xenografts are considered gold-standards to study glioblastoma invasion. However, they present many disadvantages, including time consumption, complex standardization, high cost. To counteract these issues and rapidly identify the most invasive sub-populations, we developed anin vivomimicry platform named SP2G (SPheroid SPreading on Grids). Live imaging of tumor-derived spheroids spreading on gridded micro patterns mimicking the brain vasculature recapitulated 3D motility features observed in brain or 3D matrices. Using patient-derived samples coupled with a semi-automated macro suite, SP2G easily characterized and sorted differences in cell migration and motility modes. Moreover, SP2G exposed the hidden intra-patient heterogeneity in cell motility that correlated molecularly to specific integrins. Thus, SP2G constitute a versatile and potentially pan-cancer workflow to identify the diverse invasive tumor sub-populations in patient-derived specimens. SP2G includes an integrative tool, available as open-source Fiji macro suite, for therapeutic evaluations at single patient level.

Teaser

Cracking the inter and intra-patient diversity in Glioblastoma migration profiles
Evaluation of Known Human PDE Inhibitors Against Nematode PDE4s
Authors: Anindya Clianta S , Hoffman Charles S
Published: February 2023

Parasitic nematodes are responsible for more than one and a half billion infections world-wide. The drugs developed against these infections only target a few different proteins. As drug resistance is becoming more common, there is a need to develop new drugs against new targets. Cyclic Nucleotide Phosphodiesterases (PDEs), are enzymes that hydrolyze the cyclic molecules of cyclic AMP and cyclic GMP. Physical properties of mammalian PDEs have led them to become well-established as drug targets. Mammals possess 11 families of PDEs, many of which are the target of selective and potent drugs. Nematodes have 6 PDE genes representing 6 families, which have not been well-studied;C. elegans, is a model organism nematode that would allow people to assess the therapeutic benefit of targeting PDEs. The Hoffman Lab has developed a platform for discovering PDE inhibitors and has carried out high-throughput screens (HTS) to help identify inhibitors of mammalian PDE4, PDE7, PDE8, and PDE11 families. The PDE4 family inC. elegansis of particular interest as work inC. eleganssuggests that it may be involved in neuronal function. However, research has shown that two compounds developed against mammalian PDE4s generally do not work onC. elegansPDE4. Therefore, the goal of this project is to screen a collection of compounds discovered by the Hoffman Lab to identify the compounds that will affectC. elegansor parasitic nematode PDE4s to find compounds that could then be tested for their effect onC. elegansand parasitic nematodes. This research could then identify an effective new target for drug development to treat infections by parasitic nematodes.

Parasitic nematodes are the soil worms responsible for more than one and a half billion infections around the world. While drugs are being developed against them, these drugs are designed against relatively few proteins, which is a problem as drug resistance becomes more common. Therefore, there is a need for new drugs. PDEs are enzymes that hydrolyze the signaling molecules cAMP and cGMP. Mammalian PDEs have been well-established as drug targets. In nematodes, there are 6 PDE genes representing 6 families of the 11 families found in mammals. Additionally, a free-living model organism nematode,Caenorhabditis elegans(C. elegans) can be used to assess the impact of PDE inhibition on nematode biology. In the Hoffman Lab, they have developed a platform for discovering PDE inhibitors and have used these in high throughput screens to identify inhibitors of mammalian PDE4, PDE7, PDE8, and PDE11 families. The PDE4 family inC. elegansis of particular interest as work inC. eleganssuggests that it may be involved in neuronal function. However, research has shown that compounds developed against mammalian PDE4s generally do not work onC. elegansPDE4. Therefore, by the end of this project we hope to identify the compounds that do work on nematode PDE4s that could be used to test whether they have the potential to treat these infections.
What confidence and the eyes can tell about interacting with a partner
Authors: Sanchez Rémi , Tomei Anne-Catherine , Mamassian Pascal , Vidal Manuel , Desantis Andrea
Published: February 2023

Perceptual confidence reflects the ability to evaluate the evidence that supports perceptual decisions. It is thought to play a critical role in guiding decision-making, but only a few empirical studies have actually investigated the function of confidence. To address this issue, we designed a perceptual task in which participants provided a confidence judgment on the accuracy of their perceptual decision. Then, they viewed the response of a machine or human partner, and they were instructed to decide whether to keep or change their initial response. We observed that confidence predicted participants’ decision to keep or change their initial responses more than task difficulty and perceptual accuracy. This suggests that confidence, as a subjective evaluation of uncertainty, enables us to weigh our decisions, driving the interaction with a partner. Furthermore, confidence judgments could be predicted by pre-response pupil dynamics, suggesting that arousal changes are linked to confidence computations. This study contributes to our understanding of the function of confidence in decision-making and highlights the possibility of using pupil dynamics as a proxy of confidence.
PhageDPO: Phage Depolymerase Finder
Authors: Vieira Maria , Duarte José , Domingues Rita , Oliveira Hugo , Dias Oscar
Published: February 2023

Bacteriophages are the most predominant and genetically diverse biological entities on Earth. They are bacterial viruses which encode numerous proteins with potential antibacterial activity. However, most bacteriophage-encoded proteins have no assigned function, hindering the discovery of novel antibacterial agents. In particular, there has been a growing interest in exploring recombinant bacteriophage depolymerases from the fundamental standpoint, but mostly for biotechnological applications to control bacterial pathogens. Due to the lack of efficient identification tools, we developedPhageDPO, the first developed tool that predicts depolymerases in bacteriophage genomes using machine learning methods.

Availability and implementation

PhageDPOwas integrated into a Galaxy framework available online at: bit.ly/phagedpo.