bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Applications of the History of Medicine in Muslim-Majority Nations
Authors: Weber Alan S
Published: January 2023

Since the early twentieth century, a number of physicians and professional historians have argued for the integration of the history of medicine into both medical education and clinical practice. After the supplanting of the humoral model of medicine in favor of the germ theory of disease in the late nineteenth century, medical school administrators have repeatedly asked medical historians for their rationale for studying “outdated science” in medical training programs beyond antiquarianism and knowledge for knowledge’s sake. However, a number of arguments can be adduced for the use and relevance of the history of medicine, including the observations that history: 1) provides examples of inspiring or highly ethical individuals who can serve as role models in practitioner identity formation; 2) helps to develop critical analytical skills and other modes of humanistic thought and behavior directly relevant to patient care (e.g., empathy); 3) promotes culturally-competent care, since history informs culture; 4) encourages inquiry into the sociocultural factors that affect the development of modern medical ecosystems; 5) provides a philosophical tradition for critiquing ethics in the medical profession. This contribution specifically traces the potential uses of Islamic medical history in the clinic and medical schools in Muslim-majority countries, primarily in the Middle East.
Straightforward? Family Reunification for Refugees in France: Aligning Legal Standards, Institutional Practices and Procedural Guarantees
Authors: Meyer Antoine P G
Published: January 2023

This article addresses family reunification in France (réunification familiale) as an essential right of refugees and a clear legal entitlement under domestic law. It proceeds with a reality-check on access to the designated visa for families and support professionals and discusses potential grounds for future advocacy on the matter. Available data, reports and complementary feedback gained from several practitioners in the field suggest hurdles stand in both law and practice, at odds with international standards and guidance. Strengthening information, physical and financial access to the procedure and ensuring due diligence, flexibility and transparency when examining applications arguably remain on the agenda for reform. Further adjustments to both administrative and judicial options for appeal and legal aid rules could also upgrade guarantees for families, with greater chances for an effective remedy in a timeframe compatible with the stakes. Filling standing gaps in data, research and evaluation would seem equally essential for an evidence-based debate, and in calling for a proactive reunification policy that acts on its potential as a pathway towards international protection. Ultimately, while a reminder of the multiple dimensions to investigate if one is concerned with effective access to reunification beyond its legal consecration as a right, the ‘French case’ certainly illustrates the need for advocates in this field to keep widening strategies and tools, besides litigation.
The CD16 and CD32b Fc-gamma receptors regulate antibody-mediated responses in mouse natural killer cells
Authors: Aguilar Oscar A , Gonzalez-Hinojosa Maria D R , Arakawa-Hoyt Janice S , Millan Alberto J , Gotthardt Dagmar , Nabekura Tsukasa , Lanier Lewis L
Published: January 2023

Natural killer (NK) cells are innate lymphocytes capable of mediating immune responses without prior sensitization. NK cells express Fc-gamma receptors (FcγRs) that engage the Fc region of IgG. Studies investigating the role of FcγRs on mouse NK cells have been limited due to lack specific reagents. In this study, we characterize the expression and biological consequences of activating mouse NK cells through their FcγRs. We demonstrate that most NK cells express the activating CD16 receptor, and a subset of NK cells also expresses the inhibitory CD32b receptor. Critically, these FcγRs are functional on mouse NK cells and can modulate antibody-mediated responses. We also characterized mice with conditional knockout alleles of Fcgr3 (CD16) or Fcgr2b (CD32b) in the NK and innate lymphoid cell (ILC) lineage. NK cells in these mice did not reveal any developmental defects and were responsive to cross-linking activating NK receptors, cytokine stimulation, and killing of YAC-1 targets. Importantly, CD16-deficient NK cells failed to induce antibody-directed cellular cytotoxicity of antibody-coated B-cell lymphomas in in vitro assays. In addition, we demonstrate the important role of CD16 on NK cells using an in vivo model of cancer immunotherapy using anti-CD20 antibody treatment of B-cell lymphomas.
Prostate cancer disparities among American Indians and Alaskan Natives in the United States
Authors: Chu Carissa E , Leapman Michael S , Zhao Shoujun , Cowan Janet E , Washington Samuel L , Cooperberg Matthew R
Published: January 2023

Background

Americans Indians and Alaska Natives face disparities in cancer care with lower rates of screening, limited treatment access, and worse survival. Prostate cancer treatment access and patterns of care remain unknown.

Methods

We used Surveillance, Epidemiology, and End Results data to compare incidence, primary treatment, and cancer-specific mortality across American Indian and Alaska Native, Asian and Pacific Islander, Black, and White patients. Baseline characteristics included prostate-specific antigen (PSA), Gleason score (GS), tumor stage, 9-level Cancer of the Prostate Risk Assessment risk score, county characteristics, and health-care provider density. Primary outcomes were first definitive treatment and prostate cancer-specific mortality (PCSM).

Results

American Indian and Alaska Native patients were more frequently diagnosed with higher PSA, GS greater than or equal or 8, stage greater than or equal to cT3, high-risk disease overall (Cancer of the Prostate Risk Assessment risk score ≥ 6), and metastases at diagnosis than any other group. Adjusting for age, PSA, GS, and clinical stage, American Indian or Alaska Native patients with localized prostate cancer were more likely to undergo external beam radiation than radical prostatectomy and had the highest rates of no documented treatment. Five-year PCSM was higher among American Indian and Alaska Natives than any other racial group. However, after multivariable adjustment accounting for clinical and pathologic factors, county-level demographics, and provider density, American Indian and Alaska Native patient PCSM hazards were no different than those of White patients.

Conclusions

American Indian or Alaska Native patients have more advanced prostate cancer, lower rates of definitive treatment, higher mortality, and reside in areas of less specialty care. Disparities in access appear to account for excess risks of PCSM. Focused health policy interventions are needed to address these disparities.
Competing over the continental shelf: the legal versus the geophysical entitlements
Authors: Salas Kantor Benjamin , Valdivia Torres Carolina
Published: January 2023

For the past decades, international courts and tribunals have eluded the question of whether a State’s entitlement to a continental shelf beyond 200 nautical miles (nm) may extend within 200 nm of another State. The opacity around this question steered the International Court of Justice to surprisingly divide its oral proceedings in the pending dispute between Nicaragua and Colombia, so that it could address this legal predicament first. In similar circumstances, the International Tribunal for the Law of the Sea asked Mauritius and The Maldives to deal with the same question. While this is not the first time an international court or tribunal is asked to delimit a continental shelf beyond 200 nm, it will be the first where the ‘legal’ and the ‘geophysical’ entitlements enshrined in Article 76(1) of UNCLOS face each other. This article examines the current state of international law and proposes that the overlap between both entitlements is legally permissible, but the ‘legal’ entitlement enjoys further normative strength and will guide the equitable delimitation of the continental shelf.
A review of the Guyana landmark local content law
Authors: Pereira Eduardo G , Asiago Berryl Claire , Elias-Roberts Alicia
Published: January 2023

On 31 December 2021, the historical Local Content Bill reached the final steps of the legislative process after the Guyanese President, Dr Mohamed Irfaan Ali, finally assented the Bill into law. Officially, incorporating it into the country’s legal architecture as the Local Content Act No 18 of 2021. This article reviews the said Local Content Act to determine if the said legislation meets the best industry practices or not and why.
From stress to responses: aluminium-induced signalling in the root apex
Authors: Wang Peng , Wan Ning , Horst Walter J , Yang Zhong-Bao
Published: January 2023

Aluminium (Al) toxicity is one of the major constraints for crop growth and productivity in most of the acid soils worldwide. The primary lesion of Al toxicity is the rapid inhibition of root elongation. The root apex, especially the transition zone (TZ), has been identified as the major site of Al accumulation and injury. The signalling, in particular through phytohormones in the root apex TZ in response to Al stress, has been reported to play crucial roles in the regulation of Al-induced root growth inhibition. The binding of Al in the root apoplast is the initial event leading to inhibition of root elongation. Much progress has been made during recent years in understanding the molecular functions of cell wall modification and Al resistance-related genes in Al resistance or toxicity, and several signals including phytohormones, Ca2+, etc. have been reported to be involved in these processes. Here we summarize the recent advances in the understanding of Al-induced signalling and regulatory networks in the root apex involved in the regulation of Al-induced inhibition of root growth and Al toxicity/resistance. This knowledge provides novel insights into how Al-induced signals are recognized by root apical cells, transmitted from the apoplast to symplast, and finally initiate the defence system against Al. We conclude that the apoplast plays a decisive role in sensing and transmitting the Al-induced signals into the symplast, further stimulating a series of cellular responses (e.g. exudation of organic acid anions from roots) to adapt to the stress. We expect to stimulate new research by focusing on the signalling events in the root apex in response to Al stress, particularly taking into consideration the signal transduction between the meristem zone, TZ, and elongation zone and the apoplast and symplast.
A finitary outer measure logic
Authors: Baratella Stefano
Published: January 2023

We extend classical first-order logic with a family of weak probability quantifiers, which we call submeasure quantifiers. Formulas are finitary, but infinitary deduction rules are needed. We consider first-order structures that are equipped with a countable family of submeasures (hence the name of the new quantifiers). We prove that every consistent set of sentences in the resulting logic is satisfiable in some structure as above. Then we restrict the set of formulas by requiring that no submeasure quantifier occurs within the scope of some classical quantifier. By suitably extending the deduction rules, we prove that every consistent set of sentences from the restricted class of formulas is satisfiable in some structure whose submeasures are actually outer measures. To perform the last step, we apply nonstandard techniques à la A. Robinson.
Calibration of neutron star natal kick velocities to isolated pulsar observations
Authors: Kapil Veome , Mandel Ilya , Berti Emanuele , Müller Bernhard
Published: January 2023

Current prescriptions for supernova natal kicks in rapid binary population synthesis simulations are based on fits of simple functions to single pulsar velocity data. We explore a new parametrization of natal kicks received by neutron stars in isolated and binary systems developed by Mandel & Müller, which is based on 1D models and 3D supernova simulations, and accounts for the physical correlations between progenitor properties, remnant mass, and the kick velocity. We constrain two free parameters in this model using very long baseline interferometry velocity measurements of Galactic single pulsars. We find that the inferred values of natal kick parameters do not differ significantly between single and binary evolution scenarios. The best-fitting values of these parameters are $v$ns = 520 km s−1 for the scaling prefactor for neutron star kicks, and σns = 0.3 for the fractional stochastic scatter in the kick velocities.
The physical nature of circumgalactic medium absorbers in Simba
Authors: Appleby Sarah , Davé Romeel , Sorini Daniele , Cui Weiguang , Christiansen Jacob
Published: January 2023

We study the nature of the low-redshift circumgalactic medium (CGM) in the Simba  cosmological simulations as traced by ultraviolet absorption lines around galaxies in bins of stellar mass ($\mbox{$M_\star $}\, > 10^{10}{\rm M}_\odot$) for star-forming, green valley and quenched galaxies at impact parameters r⊥ ≤ 1.25r200. We generate synthetic spectra for H i , Mg ii , C ii , Si iii , C iv , and O vi , fit Voigt profiles to obtain line properties, and estimate the density, temperature, and metallicity of the absorbing gas. We find that CGM absorbers are most abundant around star-forming galaxies with $\mbox{$M_\star $}\, < 10^{11}\,\,{\rm M}_{\odot }$, while the abundance of green valley galaxies show similar behaviour to those of quenched galaxies, suggesting that the CGM ‘quenches’ before star formation ceases. H i  absorbing gas exists across a broad range of cosmic phases [condensed gas, diffuse gas, hot halo gas, and Warm-Hot Intergalactic Medium (WHIM)], while essentially all low ionization metal absorption arises from condensed gas. O vi absorbers are split between hot halo gas and the WHIM. The fraction of collisionally ionized CGM absorbers is $\sim 25{\text{--}}55{{\ \rm per\ cent}}$ for C iv  and $\sim 80{\text{--}}95{{\ \rm per\ cent}}$ for O vi , depending on stellar mass and impact parameter. In general, the highest column density absorption features for each ion arise from dense gas. Satellite gas, defined as that within 10r1/2,⋆, contributes $\sim 3{{\ \rm per\ cent}}$ of overall H i  absorption but $\sim 30{{\ \rm per\ cent}}$ of Mg ii  absorption, with the fraction from satellites decreasing with increasing ion excitation energy.
MeerKAT discovery of 13 new pulsars in Omega Centauri
Authors: Chen W , Freire P C C , Ridolfi A , Barr E D , Stappers B , Kramer M , Possenti A , Ransom S M , Levin L , Breton R P , Burgay M , Camilo F , Buchner S , Champion D J , Abbate F , Venkatraman Krishnan V , Padmanabh P V , Gautam T , Vleeschower L , Geyer M , Grießmeier J-M , Men Y P , Balakrishnan V , Bezuidenhout M C
Published: January 2023

The most massive globular cluster in our Galaxy, Omega Centauri, is an interesting target for pulsar searches, because of its multiple stellar populations and the intriguing possibility that it was once the nucleus of a galaxy that was absorbed into the Milky Way. The recent discoveries of pulsars in this globular cluster and their association with known X-ray sources was a hint that, given the large number of known X-ray sources, there is a much larger undiscovered pulsar population. We used the superior sensitivity of the MeerKAT radio telescope to search for pulsars in Omega Centauri. In this paper, we present some of the first results of this survey, including the discovery of 13 new pulsars; the total number of known pulsars in this cluster currently stands at 18. At least half of them are in binary systems and preliminary orbital constraints suggest that most of the binaries have light companions. We also discuss the ratio between isolated and binaries pulsars, and how they were formed in this cluster.
The sculpting of rectangular and jet-like morphologies in supernova remnants by anisotropic equatorially confined progenitor stellar winds
Authors: Velázquez P F , Meyer D M-A , Chiotellis A , Cruz-Álvarez A E , Schneiter E M , Toledo-Roy J C , Reynoso E M , Esquivel A
Published: January 2023

Thermonuclear and core-collapse supernova remnants (SNRs) are the nebular leftovers of defunct stars. Their morphology and emission properties provide insights into the evolutionary history of the progenitor star. But while some SNRs are spherical, as expected from a point-like explosion expanding into a roughly uniform medium, many others exhibit complex non-spherical morphologies that are often not easily explained. In this work, we use 3D magnetohydrodynamic simulations to show that rectangular and jet-like morphologies can be explained by supernovae (SNe), either type Ia or type II, expanding within anisotropic, bipolar stellar wind bubbles driven by the progenitor star. The stellar wind has an anisotropic density distribution, which channels the SN ejecta differently depending on the anisotropy characteristics. We compute synthetic thermal (X-ray) and non-thermal (synchrotron) emission maps from our numerical simulations to compare with observations. We find rectangular morphologies are generated when the stellar wind has a high-mass loss rate and forms a dense, narrow disc at the equatorial region. Instead, a jet-like or ear-like morphology is obtained when the stellar wind develops a wide, dense disc. Stellar winds with low mass-loss rates do not strongly influence the SNR morphology. Finally, our synthetic synchrotron and X-ray maps for the high mass-loss rate case qualitatively agree with the observations of the SNRs G332.5-5.6 and G290.1-0.8.
Cocoon breakout and escape from the ejecta of neutron star mergers
Authors: Hamidani Hamid , Ioka Kunihito
Published: January 2023

The cocoon is an inevitable product of a jet propagating through ambient matter, and takes a fair fraction of the jet energy. In short gamma-ray bursts (sGRBs), the ambient matter is the ejecta from the merger of neutron stars, expanding with a high velocity ∼0.2c, in contrast to the static stellar envelope in collapsars. Using 2D relativistic hydrodynamic simulations with the ejecta density profile as ρ ∝ r−2, we find that the expansion makes a big difference; only 0.5–5 per cent of the cocoon mass escapes from (faster than) the ejecta, with an opening angle 20°–30°, while it is $\sim 100{{\ \rm per\ cent}}$ and spherical in collapsars. We also analytically obtain the shares of mass and energies for the escaped and trapped cocoons. Because the mass of the escaped cocoon is small and the trapped cocoon is concealed by the ejecta and the escaped cocoon, we suggest that it is unlikely that cooling emission from the sGRB-jet heated cocoon was observed as a counterpart to the gravitational wave event GW170817.
Broad-line region in NGC 4151 monitored by two decades of reverberation mapping campaigns – I. Evolution of structure and kinematics
Authors: Chen Yong-Jie , Bao Dong-Wei , Zhai Shuo , Fang Feng-Na , Hu Chen , Du Pu , Yang Sen , Yao Zhu-Heng , Li Yan-Rong , Brotherton Michael S , McLane Jacob N , Zastrocky T E , Olson Kianna A , Bon Edi , Bai Hua-Rui , Fu Yi-Xin , Liu Jun-Rong , Wang Yi-Lin , Maithil Jaya , Kobulnicky H A , Dale D A , Adelman C , Caradonna M J , Carter Z , Favro J , Ferguson A J , Gonzalez I M , Hadding L M , Hagler H D , Murphree G , Oeur M , Rogers C J , Roth T , Schonsberg S , Stack T R , Wang Jian-Min
Published: January 2023

We report the results of long-term reverberation mapping campaigns of the nearby active galactic nuclei (AGNs) NGC 4151, spanning from 1994 to 2022, based on archived observations of the FAST Spectrograph Publicly Archived Programs and our new observations with the 2.3 m telescope at the Wyoming Infrared Observatory. We reduce and calibrate all the spectra in a consistent way, and derive light curves of the broad H β line and 5100 Å continuum. Continuum light curves are also constructed using public archival photometric data to increase sampling cadences. We subtract the host galaxy contamination using Hubble Space Telescope imaging to correct fluxes of the calibrated light curves. Utilizing the long-term archival photometric data, we complete the absolute flux-calibration of the AGN continuum. We find that the H β time delays are correlated with the 5100 Å luminosities as $\tau _{\rm H\beta }\propto L_{5100}^{0.46\pm 0.16}$. This is remarkably consistent with Bentz et al. (2013)’s global size–luminosity relationship of AGNs. Moreover, the data sets for five of the seasons allow us to obtain the velocity-resolved delays of the H β line, showing diverse structures (outflows, inflows, and discs). Combining our results with previous independent measurements, we find the measured dynamics of the H β broad-line region (BLR) are possibly related to the long-term trend of the luminosity. There is also a possible additional ∼1.86 yr time lag between the variation in BLR radius and luminosity. These results suggest that dynamical changes in the BLR may be driven by the effects of radiation pressure.
DUSTiER (DUST in the Epoch of Reionization): dusty galaxies in cosmological radiation-hydrodynamical simulations of the Epoch of Reionization with RAMSES-CUDATON
Authors: Lewis Joseph S W , Ocvirk Pierre , Dubois Yohan , Aubert Dominique , Chardin Jonathan , Gillet Nicolas , Thélie Émilie
Published: January 2023

In recent years, interstellar dust has become a crucial topic in the study of the high redshift Universe. Evidence points to the existence of large dust masses in massive star forming galaxies already during the Epoch of Reionization, potentially affecting the escape of ionizing photons into the intergalactic medium. Moreover, correctly estimating dust extinction at UV wavelengths is essential for precise ultra-violet luminosity function (UVLF) prediction and interpretation. In this paper, we investigate the impact of dust on the observed properties of high redshift galaxies, and cosmic reionization. To this end, we couple a physical model for dust production to the fully coupled radiation-hydrodynamics cosmological simulation code RAMSES-CUDATON, and perform a 16 cMpc3 h−3, 20483, simulation, that we call DUSTiER for DUST in the Epoch of Reionization. It yields galaxies with dust masses and UV slopes roughly compatible with constraints at z ≥5. We find that extinction has a dramatic impact on the bright end of the UVLF, even as early as $\rm z=8$, and our dusty UVLFs are in better agreement with observations than dust-less UVLFs. The fraction of obscured star formation rises up to 45 per cent at $\rm z=5$, consistent with some of the latest results from ALMA. Finally, we find that dust reduces the escape of ionizing photons from galaxies more massive than 1010 M⊙ (brighter than ≈ −18 $\rm M_{AB1600}$) by >10 per cent, and possibly up to 80–90 per cent for our most massive galaxies. Nevertheless, we find that the ionizing escape fraction is first and foremost set by neutral Hydrogen in galaxies, as the latter produces transmissions up to 100 times smaller than through dust alone.
Where are the missing symbiotic stars? Uncovering hidden symbiotic stars in public catalogues
Authors: Akras Stavros
Published: January 2023

Theoretical predictions of the population of Galactic symbiotic stars (SySts) are highly inconsistent with the current known population. Despite intense effort over the past decades, observations are still far below the predictions. The majority of known SySts so far are identified based on selection criteria established in the optical regime. The recent discovery of SU Lyn with very faint optical emission lines uncloaked a subgroup of SySts with accreting-only white dwarfs. In this particular case, the luminous red giant may overshadow the dimmed white dwarf companion. A new approach to search for this subgroup of SySts is presented, employing GALEX UV and 2MASS/AllWISE IR photometry. The FUV-NUV colour index is an indicator, direct or indirect, for the presence of hot compact companions. The cross-match of the Catalogue of Variable Stars III obtained from the All-Sky Automated Survey for SuperNovae (ASAS-SN) with the GALEX, 2MASS, and AllWISE catalogues result in a sample of 814 potential SySt candidates. From them, 105 sources have photometric measurements from both FUV and NUV bands and 35 exhibit FUV-NUV<1, similar to what it is expected from known SySts. Five known SySts are recovered, while two new genuine SySts are discovered in spectroscopic follow-up observations after the detection of the typical emission lines.
Magnetic fields do not suppress global star formation in low metallicity dwarf galaxies
Authors: Whitworth David J , Smith Rowan J , Klessen Ralf S , Mac Low Mordecai-Mark , Glover Simon C O , Tress Robin , Pakmor Rüdiger , Soler Juan D
Published: January 2023

Many studies concluded that magnetic fields suppress star formation in molecular clouds and Milky Way like galaxies. However, most of these studies are based on fully developed fields that have reached the saturation level, with little work on investigating how an initial weak primordial field affects star formation in low metallicity environments. In this paper, we investigate the impact of a weak initial field on low metallicity dwarf galaxies. We perform high-resolution arepo simulations of five isolated dwarf galaxies. Two models are hydrodynamical, two start with a primordial magnetic field of 10$^{-6} \, \mu$G and different sub-solar metallicities, and one starts with a saturated field of 10$^{-2} \, \mu$G. All models include a non-equilibrium, time-dependent chemical network that includes the effects of gas shielding from the ambient ultraviolet field. Sink particles form directly from the gravitational collapse of gas and are treated as star-forming clumps that can accrete gas. We vary the ambient uniform far ultraviolet field, and cosmic ray ionization rate between 1 per cent and 10 per cent of solar values. We find that the magnetic field has little impact on the global star formation rate (SFR), which is in tension with some previously published results. We further find that the initial field strength has little impact on the global SFR. We show that an increase in the mass fractions of both molecular hydrogen and cold gas, along with changes in the perpendicular gas velocity dispersion and the magnetic field acting in the weak-field model, overcome the expected suppression in star formation.
ExoMol line lists – XLVIII. High-temperature line list of thioformaldehyde (H2CS)
Authors: Mellor Thomas , Owens Alec , Tennyson Jonathan , Yurchenko Sergei N
Published: January 2023

A comprehensive rotation–vibration (ro–vibrational) line list of thioformaldehyde (1H212C32S) that is applicable for elevated temperatures (${2000}{\, \mathrm{K}}$) is presented. The new MOTY line list covers the 0–8000 cm−1 range (wavelengths $\lambda \gt {1.3}{\, \mu \mathrm{m}})$ and contains around 43.5 billion transitions between 52.3 million states with rotational excitation up to J = 120. Line list calculations utilize a newly determined empirically refined potential energy surface (PES) – the most accurate H2CS PES to date – a previously published high-level ab initio dipole moment surface, and the use of an exact kinetic energy operator for solving the ro–vibrational Schrödinger equation. Post-processing of the MOTY line list is performed by replacing calculated energy levels with empirically derived values, vastly improving the accuracy of predicted line positions in certain spectral windows and making the line list suitable for high-resolution applications. The MOTY line list is available from the ExoMol data base at www.exomol.com and the CDS astronomical data base.
EANO guideline on rational molecular testing of gliomas, glioneuronal, and neuronal tumors in adults for targeted therapy selection
Authors: Capper David , Reifenberger Guido , French Pim J , Schweizer Leonille , Weller Michael , Touat Mehdi , Niclou Simone P , Euskirchen Philipp , Haberler Christine , Hegi Monika E , Brandner Sebastian , Le Rhun Emilie , Rudà Roberta , Sanson Marc , Tabatabai Ghazaleh , Sahm Felix , Wen Patrick Y , Wesseling Pieter , Preusser Matthias , van den Bent Martin J
Published: January 2023

The mainstay of treatment for adult patients with gliomas, glioneuronal and neuronal tumors consists of combinations of surgery, radiotherapy, and chemotherapy. For many systemic cancers, targeted treatments are a part of the standard of care, however, the predictive significance of most of these targets in central nervous system (CNS) tumors remains less well-studied. Despite that, there is increasing use of advanced molecular diagnostics that identify potential targets, and tumor-agnostic regulatory approvals on targets also present in CNS tumors have been granted. This raises the question of when and for which targets it is meaningful to test in adult patients with CNS tumors. This evidence-based guideline reviews the evidence available for targeted treatment for alterations in the RAS/MAPK pathway (BRAF, NF1), in growth factor receptors (EGFR, ALK, fibroblast growth factor receptor (FGFR), neurotrophic tyrosine receptor kinase (NTRK), platelet-derived growth factor receptor alpha, and ROS1), in cell cycle signaling (CDK4/6, MDM2/4, and TSC1/2) and altered genomic stability (mismatch repair, POLE, high tumor mutational burden (TMB), homologous recombination deficiency) in adult patients with gliomas, glioneuronal and neuronal tumors. At present, targeted treatment for BRAF p.V600E alterations is to be considered part of the standard of care for patients with recurrent gliomas, pending regulatory approval. For approved tumor agnostic treatments for NTRK fusions and high TMB, the evidence for efficacy in adult patients with CNS tumors is very limited, and treatment should preferably be given within prospective clinical registries and trials. For targeted treatment of CNS tumors with FGFR fusions or mutations, clinical trials are ongoing to confirm modest activity so far observed in basket trials. For all other reviewed targets, evidence of benefit in CNS tumors is currently lacking, and testing/treatment should be in the context of available clinical trials.
Appendicularians and marine snowin situvertical distribution in Argentinean Patagonia
Authors: Giménez Eloísa M , Nocera Ariadna C , Temperoni Brenda , Winkler Gesche
Published: January 2023

Detailed in situ vertical and temporal distribution of appendicularians, marine snow, fecal pellets, nano- and microplankton were recorded simultaneously with environmental data in the San Jorge Gulf, Argentinean Patagonia (45°–47°S). Data were taken at a fixed station over 36 h in February 2014 with an autonomous Video Plankton Recorder and a FlowCAM®. The water column was thermally stratified with a pycnocline at ~ 40 m. Appendicularians dominated in the upper 65 m with a condensed pattern above the pycnocline at high chlorophyll a concentrations, matching the subsurface chlorophyll maximum layer at ~ 20 m. Our results suggest the absence of vertical migration of appendicularians. Marine snow, strongly correlated with appendicularians, showed high concentrations above the pycnocline, whereas fecal pellets from krill were distributed throughout the water column. Discarded houses of appendicularians or their mucus fragments were the main components of marine snow aggregates, with phytoplankton, detritus and krill pellets also contributing. Nanoplankton dominated over microplankton, with vertical distribution patterns that might depend on local grazing pressure and advective processes. Our study, the first one in the region using underwater imagery, emphasizes the leading contribution of appendicularians to marine snow aggregates in the San Jorge Gulf and their potential implications in the bentho-pelagic coupling.
Exploring training needs of newly graduated medical doctors to inform the undergraduate simulation-based curriculum: a national Delphi consensus study
Authors: Breindahl Niklas , Khan Farsana , Skipper Mads , Nielsen Anders Bo , Friis Mikkel Lønborg , Paltved Charlotte , Jensen Rune Dall , Kurtzhals Jørgen A L , Konge Lars , Nayahangan Leizl Joy
Published: January 2023

Purpose

Mastering technical procedures is a key component in succeeding as a newly graduated medical doctor and is of critical importance to ensure patient safety. The efficacy of simulation-based education has been demonstrated but medical schools have different requirements for undergraduate curricula. We aimed to identify and prioritize the technical procedures needed by newly graduated medical doctors.

Methods

We conducted a national needs assessment survey using the Delphi technique to gather consensus from key opinion leaders in the field. In the first round, a brainstorm was conducted to identify all potential technical procedures. In the second round, respondents rated the need for simulation-based training of each procedure using the Copenhagen Academy for Medical Education and Simulation Needs Assessment Formula (CAMES-NAF). The third round was a final elimination and prioritization of the procedures.

Results

In total, 107 experts from 21 specialties answered the first round: 123 unique technical procedures were suggested. Response rates were 58% and 64% in the second and the third round, respectively. In the third round, 104 procedures were eliminated based on the consensus criterion, and the remaining 19 procedures were included and prioritized. The top five procedures were: (i) insert peripheral intravenous catheter, (ii) put on personal protection equipment, (iii) perform basic airway maneuvers, (iv) perform basic life support, and (v) perform radial artery puncture.

Conclusion

Based on the Delphi process a final list of 19 technical procedures reached expert consensus to be included in the undergraduate curriculum for simulation-based education.
Sustained clinical knowledge improvements from simulation experiences with Simulation via Instant Messaging—Birmingham Advance
Authors: Zhou Dengyi , Davitadze Meri , Ooi Emma , Ng Cai Ying , Allison Isabel , Thomas Lucretia , Hanania Thia , Blaggan Parisha , Evans Nia , Chen Wentin , Melson Eka , Boelaert Kristien , Karavitaki Niki , Kempegowda Punith ,   on behalf of SIMBA and CoMICs team
Published: January 2023

Background

Simulation via Instant Messaging—Birmingham Advance (SIMBA) delivers simulation-based learning through WhatsApp and Zoom, helping to sustain continuing medical education (CME) for postgraduate healthcare professionals otherwise disrupted by the coronavirus (COVID-19) pandemic. This study aimed to assess whether SIMBA helped to improve clinical knowledge and if this improvement in knowledge was sustained over time.

Methods

Two SIMBA sessions—thyroid and pituitary—were conducted in July–August 2020. Each session included simulation of various real-life cases and interactive discussion. Participants’ self-reported confidence, acceptance, and knowledge were measured using surveys and multiple-choice questions pre- and post-simulation and in a 6- to 12-week follow-up period. The evaluation surveys were designed using Moore’s 7 Levels of CME Outcomes Framework.

Results

A total of 116 participants were included in the analysis. Significant improvement was observed in participants’ self-reported confidence in approach to simulated cases (thyroid, n = 37, P < .0001; pituitary, n = 79, P < .0001). Significant improvement in clinical knowledge was observed following simulation (thyroid, n = 37, P < .0001; pituitary, n = 79, P < .0001). For both sessions, retention of confidence and knowledge was seen at 6–12 weeks’ follow-up.

Conclusions

SIMBA increased participants’ clinical knowledge on simulated cases and this improvement was retained up to 6–12 weeks after the session. Further studies are required to explore long-term retention and whether it translates to improved real-world clinical practice.
Learning from Shared News: When Abundant Information Leads to Belief Polarization
Authors: Bowen T Renee , Dmitriev Danil , Galperti Simone
Published: January 2023

We study learning via shared news. Each period agents receive the same quantity and quality of firsthand information and can share it with friends. Some friends (possibly few) share selectively, generating heterogeneous news diets across agents. Agents are aware of selective sharing and update beliefs by Bayes’s rule. Contrary to standard learning results, we show that beliefs can diverge in this environment, leading to polarization. This requires that (i) agents hold misperceptions (even minor) about friends’ sharing and (ii) information quality is sufficiently low. Polarization can worsen when agents’ friend networks expand. When the quantity of firsthand information becomes large, agents can hold opposite extreme beliefs, resulting in severe polarization. We find that news aggregators can curb polarization caused by news sharing. Our results hold without media bias or fake news, so eliminating these is not sufficient to reduce polarization. When fake news is included, it can lead to polarization but only through misperceived selective sharing. We apply our theory to shed light on the polarization of public opinion about climate change in the United States.
Identification of novel Mendelian disorders of the epigenetic machinery (MDEMs)-associated functional mutations and neurodevelopmental disorders
Authors: Li S , Li H , Liu D , Xing Q , Chen X , Zhang H , Wen J , Zhu H , Liang D , Li Z , Wu L
Published: January 2023

Background

Mendelian disorders of the epigenetic machinery (MDEMs) are a newly identified group of neurodevelopmental disorders (NDDs) and multiple congenital anomalies caused by mutations in genes encoding components of the epigenetic machinery. Many studies have shown that MDEM-associated mutations may disrupt the balance of chromatin states and trigger dysplasia.

Aim

To help eight Chinese families with NDDs acquire a definitive diagnosis.

Methods

In this study, we used whole-exome sequencing to diagnose eight unrelated Chinese families with NDDs. We also verified the potential pathogenic variants by Sanger sequencing and analyzed the changes in gene expression along with histone methylation modifications.

Results

Eight variants of six epigenetic machinery genes were identified, six of which were novel. Six variants were pathogenic (P) or likely pathogenic (LP), while two novel missense variants (c.5113T>C in CHD1 and c.10444C>T in KMT2D) were classified to be variants of uncertain significance (VUS). Further functional studies verified that c.5113T>C in CHD1 results in decreased protein levels and increased chromatin modifications (H3K27me3). In addition, c.10444C>T in KMT2D led to a significant decrease in mRNA transcription and chromatin modifications (H3K4me1). Based on experimental evidence, these two VUS variants could be classified as LP.

Conclusion

This study provided a definitive diagnosis of eight families with NDDs and expanded the mutation spectrum of MDEMs, enriching the pathogenesis study of variants in epigenetic machinery genes.
Epigenetic changes in inflammatory arthritis monocytes contribute to disease and can be targeted by JAK inhibition
Authors: Peeters Janneke G C , Boltjes Arjan , Scholman Rianne C , Vervoort Stephin J , Coffer Paul J , Mokry Michal , Vastert Sebastiaan J , van Wijk Femke , van Loosdregt Jorg
Published: January 2023

Objectives

How the local inflammatory environment regulates epigenetic changes in the context of inflammatory arthritis remains unclear. Here we assessed the transcriptional and active enhancer profile of monocytes derived from the inflamed joints of JIA patients, a model well-suited for studying inflammatory arthritis.

Methods

RNA sequencing and H3K27me3 chromatin immunoprecipitation sequencing (ChIP-seq) were used to analyse the transcriptional and epigenetic profile, respectively, of JIA synovial fluid-derived monocytes.

Results

Synovial-derived monocytes display an activated phenotype, which is regulated on the epigenetic level. IFN signalling-associated genes are increased and epigenetically altered in synovial monocytes, indicating a driving role for IFN in establishing the local inflammatory phenotype. Treatment of synovial monocytes with the Janus-associated kinase (JAK) inhibitor ruxolitinib, which inhibits IFN signalling, transformed the activated enhancer landscape and reduced disease-associated gene expression, thereby inhibiting the inflammatory phenotype.

Conclusion

This study provides novel insights into epigenetic regulation of inflammatory arthritis patient-derived monocytes and highlights the therapeutic potential of epigenetic modulation for the treatment of inflammatory rheumatic diseases.
COMPARISON OF THE 64- AND 80-DETECTOR ROW COMPUTED TOMOGRAPHY AMONG THE CT NUMBER AND RADIATION DOSE DURING LOWER EXTREMITY COMPUTED TOMOGRAPHY ANGIOGRAPHY
Authors: Moriwake Ryo , Masuda Takanori , Yamamoto Akira , Ikenaga Hiroyuki , Yoshida Koji , Takei Yasutaka , Yao Daiki , Ono Atsushi , Hiratsuka Junichi , Tamada Tsutomu
Published: January 2023

To compare the computed tomography (CT) number and the radiation dose between the 64 (group A) and 80-detector row (group B) during lower extremity computed tomography angiography (LE-CTA). We enrolled 144 patients underwent LE-CTA and compared the CT number for the popliteal arteries, radiation dose and the rate of the optimal CT number during the LE-CTA exceeding 200 HU between the two groups. The CT number for the popliteal arteries and mean dose-length product was significantly higher in Group A than in Group B (P < 0.01). The rate of the optimal CT number for the popliteal arteries was 23.6% with Group B scanner and 56.9% with Group A (P < 0.05). The 64-detector row CT was significantly higher in the CT number for the popliteal arteries, radiation dose and rate of the optimal CT number during the LE-CTA than the 80-detector row. Depiction ability did not improve by using a high CT scanner with a wider detector during LE-CTA.
Wnt/BMP Mediated Metabolic Reprogramming Preserves Multipotency of Neural Crest-Like Stem Cells
Authors: Mehrotra Pihu , Ikhapoh Izuagie , Lei Pedro , Tseropoulos Georgios , Zhang Yali , Wang Jianmin , Liu Song , Bronner Marianne E , Andreadis Stelios T
Published: January 2023

Neural crest-like stem cells resembling embryonic neural crest cells (NCs) can be derived from adult human tissues such as the epidermis. However, these cells lose their multipotency rapidly in culture limiting their expansion for clinical use. Here, we show that the multipotency of keratinocyte-derived NCs (KC-NCs) can be preserved by activating the Wnt and BMP signaling axis, promoting expression of key NC-specifier genes and ultimately enhancing their differentiation potential. We also show that transcriptional changes leading to multipotency are linked to metabolic reprogramming of KC-NCs to a highly glycolytic state. Specifically, KC-NCs treated with CHIR and BMP2 rely almost exclusively on glycolysis for their energy needs, as seen by increased lactate production, glucose uptake, and glycolytic enzyme activities. This was accompanied by mitochondrial depolarization and decreased mitochondrial ATP production. Interestingly, the glycolytic end-product lactate stabilized β-catenin and further augmented NC-gene expression. Taken together, our study shows that activation of the Wnt/BMP signaling coordinates the metabolic demands of neural crest-like stem cells governing decisions regarding multipotency and differentiation, with possible implications for regenerative medicine.
Early newborn bathing and associated factors among mothers in Afar Region, Northeast Ethiopia
Authors: Getachew Gebru , Ibrahim Ibrahim Mohammed , Mulugeta Yisahak , Ahmed Kedir Y
Published: January 2023

Background

Delaying newborn bathing for 24 h after childbirth protects the baby from hypothermia, infection and hypoglycaemia and provides an opportunity for mother–baby emotional bonding. However, no previously published study has investigated the early newborn bathing practices of pastoral mothers in Ethiopia. This study aims to investigate early newborn bathing and associated factors among mothers in Afar Region, Northeast Ethiopia.

Methods

Institution-based cross-sectional study was conducted from May to June 2021. A systematic random sampling technique was used to recruit 386 mothers, and the data collection was performed using an interviewer-administered questionnaire. Multivariable logistic regression modelling was used to examine the association between explanatory variables (including sociodemographic, obstetric, health service and health literacy factors) and early newborn bathing.

Results

The overall prevalence of early newborn bathing among postpartum mothers was 73.1% with a 95% confidence interval (CI) from 68.4 to 77.5%. Mothers who attained college or higher education [adjusted odds ratio (AOR) = 0.21; 95% CI 0.06–0.66], those who were from urban areas (AOR = 0.19; 95% CI 0.09–0.42) and those who gave birth using operational delivery (e.g. caesarean section and instrumental delivery) (AOR = 0.01; 95% CI 0.01–0.04) were less likely to practice early newborn bathing.

Conclusion

The practice of early newborn bathing was unacceptably high in pastoral communities of the Afar Region. There is a need for interventions specifically targeting at uneducated and rural mothers as part of the implementation to improve the essential newborn care practices of mothers in pastoral communities in Ethiopia.
Geographically targeted chronic infection screening: lessons from a hepatitis B pilot study in the UK
Authors: O'Ferrall Angus M , MacElhinney-West Alison , Bell Mark S , Haslam Michael P , Walker Gemma , Norton Donna , Burns Sean A , Ferrier Graham , Easom Nicholas J W
Published: January 2023

Chronic hepatitis B (CHB) most commonly occurs following infection in early childhood. Prevalence varies markedly around the globe. Country of birth is therefore a strong predictor of CHB risk in adults. We used country of birth census data to predict CHB risk and carry out geographically targeted screening in East Yorkshire, UK. Despite engaging individuals born in high-prevalence countries with testing, we observed lower than expected prevalence in targeted highest-risk areas, which may indicate barriers to testing for people with undiagnosed CHB. Improved strategies for engagement with high-risk groups will be key for viral hepatitis elimination.
Late-Season Decline: A New Bacterial Disease of Corn Identified in the Texas Panhandle
Authors: Obasa Ken , Kolomiets Michael , Reed Blayne , Coker Dennis , Bell Jourdan , Heflin Kevin
Published: January 2023

The genus Pantoea has historically been associated with two diseases of corn, Stewart's wilt caused by P. stewartii and necrotic or white leaf spots or streaks and stalk rot caused by P. ananatis. In 2020 and 2021, a sudden and unusual decline of corn stands was observed in corn fields in two counties in the Texas High Plains region. Symptoms observed included initial light green, elongated, slightly translucent, and nonchlorotic streaked lesions with nonwavy margins that developed on leaf blades during corn vegetative growth stages, with lesions becoming necrotic at the onset of crop reproduction. Additionally, stunting of affected plants, poor ear development, and stalk rot were associated with affected stands. Diagnosis of symptomatic tissues consistently recovered bacteria. BLAST searches of the partial 16S rRNA sequences of the bacterial isolates identified them as belonging to the genus Pantoea. Investigations of the pathogenicity of two bacterial isolates, B566 and B623, under greenhouse conditions relying on Koch's postulates resulted in the development of symptoms identical to those observed on symptomatic field corn plants. The two bacteria were also successfully recovered from symptomatic leaf and stem tissues, thus satisfying Koch's postulates. Sequence analysis showed that these isolates are closely related to P. ananatis but also phylogenetically distinct. The findings from this study provide evidence for a new disease of corn caused by two Pantoea species that can result in stand decline of infected corn plants.