bluuebunny/crossref_metadata_2025 huggingface dataset:
Effector and cytolytic function of natural killer cells in anticancer immunity
Authors: Karmakar Surojit , Mishra Amrita , Pal Pradipta , Lal Girdhari
Published: October 2023

Adaptive immune cells play an important role in mounting antigen-specific antitumor immunity. The contribution of innate immune cells such as monocytes, macrophages, natural killer (NK) cells, dendritic cells, and gamma-delta T cells is well studied in cancer immunology. NK cells are innate lymphoid cells that show effector and regulatory function in a contact-dependent and contact-independent manner. The cytotoxic function of NK cells plays an important role in killing the infected and transformed host cells and controlling infection and tumor growth. However, several studies have also ascribed the role of NK cells in inducing pathophysiology in autoimmune diseases, promoting immune tolerance in the uterus, and antitumor function in the tumor microenvironment. We discuss the fundamentals of NK cell biology, its distribution in different organs, cellular and molecular interactions, and its cytotoxic and noncytotoxic functions in cancer biology. We also highlight the use of NK cell–based adoptive cellular therapy in cancer.
Gamma-irradiated Aspergillus conidia show a growth curve with a reproductive death phase
Authors: Horikiri Shigetoshi , Harada Mami , Asada Ryoko , Tsuchido Tetsuaki , Furuta Masakazu
Published: October 2023

In this study, we evaluated the effects of gamma irradiation on the germination of Aspergillus conidia and mycelial growth using microscopy and predictive microbiological modeling methods. A dose of 0.4 kGy reduced the germination rate by 20% compared to the untreated control, indicating interphase death due to the high radiation dose. The number of colonies formed (5.5%) was lower than the germination rate (69%), suggesting that most colonies died after germination. Microscopic observations revealed that mycelial elongation ceased completely in the middle of the growth phase, indicating reproductive death. The growth curves of irradiated conidia exhibited a delayed change in the growth pattern, and a decrease in slope during the early stages of germination and growth at low densities. A modified logistic model, which is a general purpose growth model that allows for the evaluation of subpopulations, was used to fit the experimental growth curves. Dose-dependent waveform changes may reflect the dynamics of the subpopulations during germination and growth. These methods revealed the occurrence of two cell death populations resulting from gamma irradiation of fungal conidia and contribute to the understanding of irradiation-induced cell death in fungi.
The underlying radial acceleration relation
Authors: Desmond Harry
Published: October 2023

The radial acceleration relation (RAR) of late-type galaxies relates their dynamical acceleration, gobs, to that sourced by baryons alone, gbar, across their rotation curves. Literature fits to the RAR have fixed the galaxy parameters on which the relation depends – distance, inclination, luminosity, and mass-to-light ratios – to their maximum a priori values with an uncorrelated Gaussian contribution to the uncertainties in gbar and gobs. In reality these are free parameters of the fit, contributing systematic rather than statistical error. Assuming a range of possible functional forms for the relation with or without intrinsic scatter (motivated by modified Newtonian dynamics with or without the external field effect), I use Hamiltonian Monte Carlo to perform the full joint inference of RAR and galaxy parameters for the Spitzer Photometry and Accurate Rotation Curves (SPARC) dataset. This reveals the intrinsic RAR underlying that observed. I find an acceleration scale $a_0=(1.19 \pm 0.04 \, \text{(stat)} \pm 0.09 \, \text{(sys)}) \: \times \: 10^{-10}$ m s−2, an intrinsic scatter $\sigma _\text{int}=(0.034 \pm 0.001 \, \text{(stat)} \pm 0.001 \, \text{(sys)})$ dex (assuming the SPARC error model is reliable), and weak evidence for the external field effect. I make summary statistics of all my analyses publicly available for future SPARC studies or applications of a calibrated RAR, for example direct distance measurement.
Behaviour of molecular hydrogen emission in three solar flares
Authors: Mulay Sargam M , Fletcher Lyndsay , Hudson Hugh , Labrosse Nicolas
Published: October 2023

We have systematically investigated ultraviolet (UV) emission from molecular hydrogen (H2) using the Interface Region Imaging Spectrograph (IRIS), during three X-ray flares of C5.1, C9.7, and X1.0 classes on 2014 October 25. Significant emission from five H2 spectral lines appeared in the flare ribbons, interpreted as photoexcitation (fluorescence) due to the absorption of UV radiation from two Si iv spectral lines. The H2 profiles were broad and consisted of two non-stationary components in red and in the blue wings of the line in addition to the stationary component. The red-wing (blue-wing) components showed small redshifts (blueshifts) of ∼5–15 km s−1 (∼5–10 km s−1). The non-thermal velocities were found to be ∼5–15 km s−1. The interrelation between intensities of H2 lines and their branching ratios confirmed that H2 emission formed under optically thin plasma conditions. There is a strong spatial and temporal correlation between Si iv and H2 emissions, but the H2 emission is more extended and diffuse, further suggesting H2 fluorescence, and – by analogy with flare ‘back-warming’ – providing a means to estimate the depth from which the H2 emission originates. We find that this is 1871 ± 157 and 1207 ± 112 km below the source of the Si iv emission, in two different ribbon locations.
A polarization study of jets interacting with turbulent magnetic fields
Authors: Meenakshi Moun , Mukherjee Dipanjan , Bodo Gianluigi , Rossi Paola
Published: October 2023

We investigate the effect of the jet’s immediate surroundings on the non-thermal synchrotron emission and its polarization properties. The ambient medium is equipped with a turbulent magnetic field, which is compressed and amplified by the jets as they progress. This leads to high polarization at the forward shock surface. The randomness in the magnetic polarities of the external fields in the shocked ambient medium (SAM) results in vector cancellation of the polarized components from the jet, thereby causing depolarization of the radiation from the cocoon. We find that due to the slow decay of the fields in the SAM, such depolarization by the fields with large correlation lengths is more prominent when compared to the small-scale fields. Also, the low-power jets, which have magnetic fields comparable in strength to those in the SAM, are more severely affected by the SAM’s depolarizing effect, than the high-power ones. The turbulent backflows in the cocoon, as well as the shearing of fields near the contact discontinuity, strengthen the poloidal component in the jet. This causes internal depolarization due to the cancellation of the orthogonally polarized components along the line of sight as the field transitions from ordered toroidal to poloidal. The synchrotron maps display high-emission filaments in the cocoon with magnetic fields aligned along them. The kink instability leads to the wiggling motion of the jet’s spine, resulting in hotspot complexes in low-power sources.
A resolved study of the inner regions of nearby galaxies with an excess of young massive stars: missing link in the AGN–starburst connection?
Authors: Kauffmann Guinevere , Millán-Irigoyen Iker , Crowther Paul , Maraston Claudia
Published: October 2023

We have selected galaxies with very high levels of H α emission (EQW(H α) >700 Å.) in their central regions from the final data release of the MaNGA survey. Our study focuses on 14 very well-resolved nearby galaxies with stellar masses in the range 9.5 < log M*/(M⊙) < 11.5. We investigate a variety of procedures for selecting galaxy regions that are likely to harbour excess populations of young massive stars, finding that selection in the 2D space of extinction-corrected H α EQW and [S iii]/[S ii] line ratio produces the best results. By comparing stacked spectra covering these regions with stacked spectra covering normal starburst regions with 100 Å<EQW(H α) <200 Å, we obtain the following main results: (1) Clear signatures of excess Wolf–Rayet stars are found in half of the H α excess regions, (2) galaxy regions containing excess Wolf–Rayet stars are more often associated with the presence of high-ionization emission lines characteristic of accreting black holes. Excess [Ne iii] is detected in 4 out of 8 of the WR regions and there are tentative [Fe x] detections in 2 galaxies. (3) Regions of the galaxy with excess Wolf–Rayet stars are located where the interstellar medium has larger ionized gas turbulent velocities and higher neutral gas overdensities. We make a first attempt to constrain changes in the high-mass end of the stellar initial mass function (IMF) using the HR-pyPopStar evolutionary population synthesis models that include high-wavelength-resolution theoretical atmosphere libraries for Wolf–Rayet stars.
NLTE spectra of kilonovae
Authors: Pognan Quentin , Grumer Jon , Jerkstrand Anders , Wanajo Shinya
Published: October 2023

The electromagnetic transient following a binary neutron star merger is known as a kilonova (KN). Owing to rapid expansion velocities and small ejecta masses, KNe rapidly transition into the non-local thermodynamic equilibrium (NLTE) regime. In this study, we present synthetic NLTE spectra of KNe from 5 to 20 d after merger using the sumo spectral synthesis code. We study three homogeneous composition, 1D multizone models with characteristic electron fractions of Ye ∼ 0.35, 0.25, and 0.15. We find that emission features in the spectra tend to emerge in windows of reduced line blocking, as the ejecta are still only partially transparent even at 20 d. For the Ye ∼ 0.35 (lanthanide-free) ejecta, we find that the neutral and singly ionized species of Rb, Sr, Y, and Zr dominate the spectra, all with good potential for identification. We directly test and confirm an impact of Sr on the 10 000 Å spectral region in lanthanide-free ejecta, but also see that its signatures may be complex. We suggest the Rb i$\rm {5p^{1}}$–$\rm {5s^{1}}$ 7900 Å transition as a candidate for the λ0 ∼ 7500–7900 Å P-Cygni feature in AT2017gfo. For the Ye ∼ 0.25 and 0.15 compositions, lanthanides are dominant in the spectral formation, in particular Nd, Sm, and Dy. We identify key processes in KN spectral formation, notably that scattering and fluorescence play important roles even up to 20 d after merger, implying that the KN ejecta are not yet optically thin at this time.
Multiband extension of the wideband timing technique
Authors: Paladi Avinash Kumar , Dwivedi Churchil , Rana Prerna , Nobleson K , Susobhanan Abhimanyu , Joshi Bhal Chandra , Tarafdar Pratik , Deb Debabrata , Arumugam Swetha , Gopakumar A , Krishnakumar M A , Batra Neelam Dhanda , Debnath Jyotijwal , Kareem Fazal , Arumugam Paramasivan , Bagchi Manjari , Bathula Adarsh , Dandapat Subhajit , Desai Shantanu , Gupta Yashwant , Hisano Shinnosuke , Kharbanda Divyansh , Kikunaga Tomonosuke , Kolhe Neel , Maan Yogesh , Manoharan P K , Singha Jaikhomba , Srivastava Aman , Surnis Mayuresh , Takahashi Keitaro
Published: October 2023

The wideband timing technique enables the high-precision simultaneous estimation of pulsar times of arrival (ToAs) and dispersion measures (DMs) while effectively modelling frequency-dependent profile evolution. We present two novel independent methods that extend the standard wideband technique to handle simultaneous multiband pulsar data incorporating profile evolution over a larger frequency span to estimate DMs and ToAs with enhanced precision. We implement the wideband likelihood using the libstempo python interface to perform wideband timing in the tempo2 framework. We present the application of these techniques to the data set of 14 millisecond pulsars (MSPs) observed simultaneously in Band 3 (300–500 MHz) and Band 5 (1260–1460 MHz) of the upgraded Giant Metrewave Radio Telescope (uGMRT) with a large band gap of 760 MHz as a part of the Indian Pulsar Timing Array (InPTA) campaign. We achieve increased ToA and DM precision and sub-microsecond root mean square post-fit timing residuals by combining simultaneous multiband pulsar observations done in non-contiguous bands for the first time using our novel techniques.
Effects of metallicity on the instability mass ratio of low-mass contact binary systems
Authors: Wadhwa Surjit S , Landin Natália R , Kostić Petar , Vince Oliver , Arbutina Bojan , De Horta Ain Y , Filipović Miroslav D , Tothill Nicholas F H , Petrović Jelena , Djurašević Gojko
Published: October 2023

The orbital stability of contact binary systems has been receiving considerable attention recently. Theoretical studies indicate that merger is likely to occur at very low-mass ratios, but the actual mass ratio at which merger may take place is likely to be variable and dependent on the mass of the primary. We consider the effects of metal content on the orbital stability of contact binary systems by modelling the gyration radius of a rotating and tidally distorted primary component at various values of $\rm [Fe/H]$ in the range −1.25 to +0.5. We determine the instability mass ratio range for contact binary systems with a low-mass primary 0.6 M⊙ ≤ M1 ≤ 1.4 M⊙ at various metallicity levels and show that systems with low metallicity have an instability mass ratio lower than those with higher metal content and therefore are likely to be more stable. We illustrate the effect through light-curve analysis of two otherwise very similar contact binary systems, except for different metallicity. While both would be considered unstable if metallicity was not taken into consideration, only one remains in that category after appropriate adjustments based on metallicity have been made.
Post-main sequence thermal evolution of planetesimals
Authors: Li Yuqi , Bonsor Amy , Shorttle Oliver
Published: October 2023

White dwarfs that have accreted planetary materials provide a powerful tool to probe the interiors and formation of exoplanets. In particular, the high Fe/Si ratio of some white dwarf pollutants suggests that they are fragments of bodies that were heated enough to undergo large-scale melting and iron core formation. In the Solar system, this phenomenon is associated with bodies that formed early and so had short-lived radionuclides to power their melting, and/or grew large. However, if the planetary bodies accreted by white dwarfs formed during the (pre)-main sequence lifetime of the host star, they will have potentially been exposed to a second era of heating during the star’s giant branches. This work aims to quantify the effect of stellar irradiation during the giant branches on planetary bodies by coupling stellar evolution to thermal and orbital evolution of planetesimals. We find that large-scale melting, sufficient to form an iron core, can be induced by stellar irradiation, but only in close-in small bodies: planetesimals with radii ≲ 30 km originally within ∼2 au orbiting a 1–3 M⊙ host star with solar metallicity. Most of the observed white dwarf pollutants are too massive to be explained by the accretion of these small planetesimals that are melted during the giant branches. Therefore, we conclude that those white dwarfs that have accreted large masses of materials with enhanced or reduced Fe/Si remain an indicator of planetesimal’s differentiation shortly after formation, potentially linked to radiogenic heating.
Super slowly spinning stars in close binaries
Authors: Fuller Jim , Felce Catherine
Published: October 2023

Stars in short-period binaries typically have spins that are aligned and synchronized with the orbit of their companion. In triple systems, however, the combination of spin and orbital precession can cause the star’s rotation to evolve to a highly misaligned and sub-synchronous equilibrium known as a Cassini state. We identify a population of recently discovered stars that exhibit these characteristics and which are already known to have tertiary companions. These third bodies have a suitable orbital period to allow the inner binary to evolve into the sub-synchronous Cassini state, which we confirm with orbital evolution models. We also compute the expected stellar obliquity and spin period, showing that the observed rotation rates are often slower than expected from equilibrium tidal models. However, we show that tidal dissipation via inertial waves can alter the expected spin–orbit misalignment angle and rotation rate, potentially creating the very slow rotation rates in some systems. Finally, we show how additional discoveries of such systems can be used to constrain the tidal physics and orbital evolution histories of stellar systems.
NRG/RTOG 0837: Randomized, phase II, double-blind, placebo-controlled trial of chemoradiation with or without cediranib in newly diagnosed glioblastoma
Authors: Batchelor Tracy T , Won Minhee , Chakravarti Arnab , Hadjipanayis Costas G , Shi Wenyin , Ashby Lynn S , Stieber Volker W , Robins H Ian , Gray Heidi J , Voloschin Alfredo , Fiveash John B , Robinson Clifford G , Chamarthy UshaSree , Kwok Young , Cescon Terrence P , Sharma Anand K , Chaudhary Rekha , Polley Mei-Yin , Mehta Minesh P
Published: October 2023

Background

A randomized, phase II, placebo-controlled, and blinded clinical trial (NCT01062425) was conducted to determine the efficacy of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, versus placebo in combination with radiation and temozolomide in newly diagnosed glioblastoma.

Methods

Patients with newly diagnosed glioblastoma were randomly assigned 2:1 to receive (1) cediranib (20 mg) in combination with radiation and temozolomide; (2) placebo in combination with radiation and temozolomide. The primary endpoint was 6-month progression-free survival (PFS) based on blinded, independent radiographic assessment of postcontrast T1-weighted and noncontrast T2-weighted MRI brain scans and was tested using a 1-sided Z test for 2 proportions. Adverse events (AEs) were evaluated per CTCAE version 4.

Results

One hundred and fifty-eight patients were randomized, out of which 9 were ineligible and 12 were not evaluable for the primary endpoint, leaving 137 eligible and evaluable. 6-month PFS was 46.6% in the cediranib arm versus 24.5% in the placebo arm (P = .005). There was no significant difference in overall survival between the 2 arms. There was more grade ≥ 3 AEs in the cediranib arm than in the placebo arm (P = .02).

Conclusions

This study met its primary endpoint of prolongation of 6-month PFS with cediranib in combination with radiation and temozolomide versus placebo in combination with radiation and temozolomide. There was no difference in overall survival between the 2 arms.
The R2R3-MYB transcription factor EVER controls the emission of petunia floral volatiles by regulating epicuticular wax biosynthesis in the petal epidermis
Authors: Skaliter Oded , Bednarczyk Dominika , Shor Ekaterina , Shklarman Elena , Manasherova Ekaterina , Aravena-Calvo Javiera , Kerzner Shane , Cna’ani Alon , Jasinska Weronika , Masci Tania , Dvir Gony , Edelbaum Orit , Rimon Ben , Brotman Yariv , Cohen Hagai , Vainstein Alexander
Published: October 2023

The epidermal cells of petunia (Petunia × hybrida) flowers are the main site of volatile emission. However, the mechanisms underlying the release of volatiles into the environment are still being explored. Here, using cell-layer-specific transcriptomic analysis, reverse genetics by virus-induced gene silencing and clustered regularly interspaced short palindromic repeat (CRISPR), and metabolomics, we identified EPIDERMIS VOLATILE EMISSION REGULATOR (EVER)—a petal adaxial epidermis-specific MYB activator that affects the emission of volatiles. To generate ever knockout lines, we developed a viral-based CRISPR/Cas9 system for efficient gene editing in plants. These knockout lines, together with transient-suppression assays, revealed EVER's involvement in the repression of low-vapor-pressure volatiles. Internal pools and annotated scent-related genes involved in volatile production and emission were not affected by EVER. RNA-Seq analyses of petals of ever knockout lines and EVER-overexpressing flowers revealed enrichment in wax-related biosynthesis genes. Liquid chromatography/gas chromatography–MS analyses of petal epicuticular waxes revealed substantial reductions in wax loads in ever petals, particularly of monomers of fatty acids and wax esters. These results implicate EVER in the emission of volatiles by fine-tuning the composition of petal epicuticular waxes. We reveal a petunia MYB regulator that interlinks epicuticular wax composition and volatile emission, thus unraveling a regulatory layer in the scent-emission machinery in petunia flowers.
Work Hours, Free Time, and Economic Output
Authors: Parr Tom
Published: October 2023

My aim in this article is to contribute to defences of working time policies by attempting to meet an objection that comes from those who condemn these measures on the alleged grounds that they reduce economic output. What is more, as I emphasize throughout, it is possible to rebut such a concern in a fashion that is consistent with the demands of liberal anti-perfectionism. In itself, this is a philosophically striking and politically significant result. However, beyond this, much of the value of my discussion lies in the details of how to meet the relevant objection, and perhaps especially in my novel liberal defence of the ideal of the stationary state.
Prevalence and factors associated with fatigue in patients with axial spondyloarthritis: a systematic review and meta-analysis
Authors: Tang Haoming , Singh Benjamin Sachdev Manjit , Fong Warren
Published: October 2023

Objectives

Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease associated with significant morbidity. Fatigue, a widely recognized disease manifestation, has considerable impacts on patients’ work productivity, physical function and mental well-being. However, the reported prevalence of fatigue varies across studies, and pooled data are currently lacking. We aimed to characterize the prevalence of fatigue in patients with axSpA and to identify factors associated with fatigue.

Methods

A systematic review and a meta-analysis were conducted to determine the global prevalence of fatigue in patients with axSpA. Databases including CINAHL, Embase, Medline, Cochrane Library, PubMed and Google Scholar were searched from inception until April 2023. Data were extracted, and the quality of studies was assessed. A pooled prevalence of fatigue was determined by using a random-effects model. Meta-analyses were used to determine the observed heterogeneity via subgroup analysis and associations between relevant predictors and the presence of fatigue.

Results

Thirty eligible articles were included in the study, including 7893 patients with axSpA. The pooled prevalence of fatigue in patients with axSpA was 0.56 (95% CI: 0.49, 0.63; I2 = 94.6%), with significant levels of heterogeneity. Among the factors of heterogeneity explored, the geographical region of the study (P = 0.0013) was significant for being a possible source. Poorer quality of life was associated with more fatigue (P < 0.05).

Conclusion

More than half of patients with axSpA experience fatigue, with poorer quality of life being associated with more fatigue.
Development of a dose estimation system for external exposure assessment at the late phase for individuals living in areas affected by the Fukushima nuclear accident
Authors: Yajima Kazuaki , Hasegawa Shin , Takahashi Tomoyuki , Aono Tatsuo
Published: October 2023

Although the elevated ambient dose equivalent (ADE) rates in areas radiologically affected by the 2011 Fukushima nuclear plant accident decreased as time passed, the assessment of Fukushima residents’ external dose is still important. A dose estimation system for external exposure assessment at the late phase for individuals living in Fukushima Prefecture was developed for this purpose. The developed system enables the estimations of external doses over the future based on an individual behavioral pattern and ADE-rate distributions from aerial monitoring data and its predicted ADE rate. To validate the system, the estimated results were compared with the measured readings of personal dosemeters. The results indicate that the developed system properly reproduced the individual external doses of subjects living in areas where the outdoor ADE rates exceeded 0.2 μSv h−1.
Recent developments at the Calibration Laboratory for radiation protection instruments and dosemeters of the Paul Scherrer Institute
Authors: Kasprzak Malgorzata , Geser Federico A , Sliz Malgorzata , Yukihara Eduardo , Mayer Sabine
Published: October 2023

The Calibration Laboratory of the Paul Scherrer Institute is responsible for the calibration and verification of radiation protection instruments and dosemeters for internal as well as external customers, such as nuclear power plants and hospitals. The Laboratory is authorised by the Federal Institute of Metrology METAS to perform legal verifications and is accredited as an inspection body, according to ISO 17020, and as a calibration laboratory, according to ISO 17025 by the Swiss Accreditation Service. In addition to routine activities (e.g. calibration of dosemeters, irradiation of passive and active dosemeters on phantoms), the Laboratory is involved in various research and development projects with the goal of supporting the increasingly complex calibration needs and to comply with new regulations, particularly those related to clearance limits in free release measurements. Here we present an overview of the currently on-going projects, which include the investigation of Monte Carlo methods for the calibration of clearance monitors and the development of new calibration procedures for wipe test counters. We also discuss the challenges encountered in these projects, since different stakeholders, ranging from legal authorities to equipment manufacturers and users, are involved in the calibration process.
Initial approach to application of gamma spectroscopy to alpha particles dosimetry in BNCT
Authors: Knake Natalia , Prokopowicz Rafał , Cybowska Justyna , Kwiatkowski Roch , Zawadka Antoni , Gryziński Michał A
Published: October 2023

The aim of the study is to show a method of real-time determination of the dose deposited in a tissue-like medium by α-particles emitted from the 10B(n,α)7Li reaction. The applied research method is to determine the correlation between the measured density of α-particle traces and measured in real time the 478 keV prompt-gamma rays derived from the 10B(n,α)7Li reaction. To achieve this aim, an appropriate construction of an experimental set-up is needed. The experimental set-up built for the purpose of the measurements carried out in the MARIA Reactor at the National Centre for Nuclear Research in Świerk, Poland, is presented. The main challenges related to obtaining optimal conditions for the measurement of the 478 keV gamma photons; the preliminary results of spectrometric measurements and further studies are also discussed.
CIEMAT participation in the seven EURADOS intercomparisons for whole-body dosemeters in photon and beta fields (2008–20)
Authors: Rodriguez Rafael , Romero Ana M , Lopez José L
Published: October 2023

Regular participation in intercomparisons (ICs) is an excellent way to test the reliability of results in laboratories. This work presents the analysis and conclusions of the results obtained by the CIEMAT dosimetry system in the last seven EURADOS ICs of whole-body dosemeters in fields of photons and beta radiation. Compliance with the criteria established in the ISO14146 standard, as well as the behavior of the CIEMAT personal dosemeters in all these ICs, has provided the necessary confidence for its use in the individual monitoring of workers during these years.
A practical method for routine eye lens dosimetry of staff in interventional radiology
Authors: Bergans Niki , Vandermaesen Alexander , Vanheule Jeroen , Bogaerts Ria
Published: October 2023

Hospital staff doing fluoroscopy-guided interventions receive the highest doses and are at risk of exceeding the new occupational eye lens dose limit of 20 mSv. Since the introduction of the new limit in the International Commission on Radiological Protection recommendations different eye lens dose monitoring techniques have been tested on phantoms. This study uses real-life dose data to assess the need for routine eye lens dose monitoring. The correlation of eye lens dose and Hp (10) measured with a whole-body dosemeter above the lead apron was investigated as an alternative to dedicated eye lens dosimetry. A survey taken among the medical personnel allowed to determine the preferred method for measuring eye lens doses in daily practice.
Plasmodium falciparumOPA3‐like protein (PfOPA3) is essential for maintenance of mitochondrial homeostasis and parasite proliferation
Authors: Narwal Monika , Jain Shilpi , Rathore Sumit , Mohmmed Asif
Published: October 2023

Metabolic pathways and proteins responsible for maintaining mitochondrial dynamics and homeostasis in the Plasmodium parasite, the causative agent of malaria, remain to be elucidated. Here, we identified and functionally characterized a novel OPA3‐like domain‐containing protein in P. falciparum (PfOPA3). We show that PfOPA3 is expressed in the intraerythrocytic stages of the parasite and localizes to the mitochondria. Inducible knock‐down of PfOPA3 using GlmS ribozyme hindered the normal intraerythrocytic cycle of the parasites; specifically, PfOPA3‐iKD disrupted parasite development as well as parasite division and segregation at schizont stages, which resulted in a drastic reduction in the number of merozoites progenies. Parasites lacking PfOPA3 show severe defects in the development of functional mitochondria; the mitochondria showed reduced activity of mtETC but not ATP synthesis, as evidenced by reduced activity of complex III of the mtETC, and increased sensitivity for drugs targeting DHODH as well as complex III, but not to the drugs targeting complex V. Further, PfOPA3 downregulation leads to reduction in the level of mitochondrial proton transport uncoupling protein (PfUCP) to compensate reduced activity of complex III and maintain proton efflux across the inner membrane. The reduced activity of DHODH, which is responsible for pyrimidine biosynthesis required for nuclear DNA synthesis, resulted in a significant reduction in parasite nuclear division and generation of progeny. In conclusion, we show that PfOPA3 is essential for the functioning of mtETC and homeostasis required for the development of functional mitochondria as well as for parasite segregation, and thus PfOPA3 is crucial for parasite survival during blood stages.
Schwannomatosis: a Realm Reborn: year one
Authors: Planet Martin , Kalamarides Michel , Peyre Matthieu
Published: October 2023

Purpose of review

In 2022, an international consensus recommendation revised the nomenclature for neurofibromatosis type 2 (NF2) and Schwannomatosis (SWN), now grouped under the umbrella term Schwannomatosis, and defined new diagnostic criteria.

Recent findings

This review describes the molecular criteria for diagnosis of schwannomatosis and the subsequent diagnosis strategy, while setting out the most recent advances in our understanding of the natural history, pathology, molecular biology and treatment of schwannomatosis-associated tumors, including schwannomas, meningiomas and ependymomas.

Somatic mutation screening should become a new standard for the diagnosis of NF2-, LTZTR1-, SMARCB1- and 22q-schwannomatosis to discriminate those conditions. Constitutional events in NF2-Schwannomatosis have a major influence on disease severity and justifiably motivate ongoing efforts on gene replacement therapy research. On the other hand, underlying mechanisms of disease severity and associated pain remain largely unknown in non-NF2-SWN and independent of germline mutation. Research efforts therefore focus on pain relief in ongoing trials and the discovery of new molecular mechanisms underlying schwannoma tumorigenesis/pain/neuropathies.
Promises of oncolytic viral therapy for adult and children with brain glioma
Authors: Patiño-García Ana , Alonso Marta M. , Gállego Pérez-Larraya Jaime
Published: October 2023

Purpose of review

The purpose of this review is to give an overview of early clinical studies addressing the safety and efficacy of oncolytic immunovirotherapy in adults and children with brain gliomas, and to highlight the extensive potential for the development of this therapeutic alternative.

Recent findings

The lack of curative treatments and poor prognosis of high-grade glioma patients warrants research on innovative therapeutic alternatives such as oncolytic immunovirotherapy. Engineered modified oncolytic viruses exert both a direct lytic effect on tumor cells and a specific antitumor immune response. Early clinical trials of different DNA and RNA oncolytic viruses, mainly Herpes Simplex Virus Type-1 and adenovirus based platforms, have consistently demonstrated an acceptable safety profile, hints of efficacy and the potential of this therapy to reshape the tumor microenvironment in both adult and pediatric patients with glioma, thus constituting the basis for the development of more advanced clinical trials.

The future landscape of oncolytic immunovirotherapy is still plenty of challenges and opportunities to enable its full therapeutic potential in both adult and children with brain gliomas.
Building Sustainable Reconstructive Microsurgery in Countries with Limited Resources: The Rwandan Experience
Authors: Shyaka Ian , Nezerwa Yves , Mukagaju Francoise , Dang Rushil R. , Furaha Charles , Ntirenganya Faustin
Published: October 2023

Background:

Reconstructive microsurgery practice has been well adopted in developed countries, but this has not been the same in low- and middle-income countries (LMICs). Injuries related to road traffic accidents are highest in these countries, with 93% of the world's fatalities on the roads occurring in LMICs. The objective of this study was to highlight the need for sustainable microsurgery in LMICs and share strategies undertaken in Rwanda.

Methods:

We review the contemporary literature about the needs and challenges facing reconstructive microsurgery in LMICs. We describe the strategies undertaken in Rwanda towards developing microsurgery. We also report the outcomes of the first ever microsurgery visiting professorship organized in the country and the steps taken towards achieving sustainable microsurgery practice in Rwanda.

Results:

There is a huge unmet need for reconstructive microsurgery in LMICs. Most of the microsurgical operations in these countries are done in short term surgical mission setups. No data focusing on sustaining reconstructive microsurgery in LMICs has been described in the contemporary literature. There is a 2.5-fold increase in the number of trained plastic surgeons in Rwanda over the past 5 years, with increasing skills in microsurgery and opportunities for formal overseas fellowships.

Conclusion:

With dedicated local champions, a comprehensive approach, and reliable partners, establishing sustainable microsurgery services is possible in countries with limited resources. In our experience, the fly-in-fly-out microsurgical missions aimed at mainly providing surgical care to patients seem to have a limited long-term impact and sustainability. We recommend integrating these missions into planned microsurgical initiatives of pre-existing local plastic surgery training programs.
A Novel Method to Determine Patient Skin Type: The Skin Analyzer
Authors: Mohamed Youssef , Koussayer Bilal , Randolph Ellie M. , West William , Morris Julia A. , Le Nicole K. , Whalen Kristen , Gemayel Kristina , Al Bayati Mahmood J. , Troy Jared , Laun Jake
Published: October 2023

Measuring skin color for medical research in an objective and nonbiased manner usually requires expensive equipment such as spectrophotometry and requires the subject to be present in person. We present a novel method to measure skin color from photographs using the Skin Analyzer application as a more effective, accessible, and efficient alternative. A desktop application, the Skin Analyzer, was developed to convert skin samples collected from digital images to the L*a*b color space and uses those values to calculate an individual typology angle that correlates to a Fitzpatrick skin type. To assess accuracy in variable lighting, six known colors representing the six Fitzpatrick skin types were printed and photographed in 15 separate locations within the hospital. To account for user variability in sample selection, interrater reliability was calculated with data generated by 13 untrained users testing the app on six subjects. The accuracy of measuring known values, which is the classification accuracy, was calculated to be 80%. Krippendorff alpha test was used to evaluate interrater reliability. The obtained alpha of 0.84 indicates a high interrater reliability. The high accuracy and reliability make the Skin Analyzer a suitable method of objectively determining Fitzpatrick skin type from images. The app may be used to investigate the effects of skin tone in various areas of interest, especially in retrospective studies where skin colorimeters cannot be used.
Clinical Practice Patterns, Health Resource Use and Risk Factors for Severe Conditions Among Children Hospitalized With COVID-19 in Japan
Authors: Okubo Yusuke , Uda Kazuhiro , Miyairi Isao
Published: October 2023

Background:

The trends in clinical practice patterns and health resource use, as well as risk factors for severe conditions among children hospitalized with coronavirus disease-2019 (COVID-19), remain unclear.

Materials and Methods:

We conducted a retrospective observational study consisting of 9876 children hospitalized with COVID-19 during 2020–2022 using the Medical Data Vision database in Japan. We investigated trends in patient characteristics, health resource use, treatment patterns and laboratory data. Additionally, log-binomial regression models were used to investigate the risk factors associated with severe COVID-19 among pediatric inpatients with COVID-19.

Results:

We observed decreasing trends in the lengths of hospital stays, healthcare costs, computed tomography use, and antibiotic use, and increasing trends in treatment with intravenous hydration and use of antipyretics, antiepileptics, antiemetics and antivirals from the first wave to the seventh wave of COVID-19 pandemic. During the 3-year period, the risk of severe COVID-19 was almost stable at 3%. Risk factors associated with severe COVID-19 were children less than 1 year old [risk ratio (RR): 1.69; 95% confidence interval (CI): 1.02–2.78], the number of complex chronic diseases (RR for 1 disease: 4.49; 95% CI: 2.76–7.32; RR for 2 or more diseases: 10.2; 95% CI: 5.19–20.3) and asthma (RR: 1.84; 95% CI: 1.06–3.20).

Conclusions:

Our study observed the changes in practice patterns and health resource use for children hospitalized with COVID-19 and identified risk factors associated with severe COVID-19. These findings indicate the importance of vigilant monitoring and tailored treatment strategies in children with these risk factors.
The Minimal Utility of Analyzing Ureteropelvic Junction Tissue at the Time of Pyeloplasty
Authors: Bash Jasper C. , Bassale Solange , Isharwal Sudhir
Published: October 2023

Introduction:

Ureteropelvic junction obstruction is a common cause of upper tract obstruction that often necessitates surgical intervention because of its severe implications. A high proportion of these surgeries include pathologic analysis of this tissue with unclear clinical value. We examined our institution's practices concerning sending the ureteropelvic junction (UPJ) specimens for pathology analysis, its clinical value, and the associated costs for both pediatric and adult cases.

Methods:

We performed retrospective chart review using Current Procedural Terminology codes for pyeloplasty over 8 years. Clinical variables were extracted from operative reports, path reports, and postoperative clinic notes. Pathology results were classified dichotomously as “benign” or “malignant” and subsequently assigned to 1 of 4 categories—inflammation, fibrosis, muscular hyperplasia, or no atypical findings.

Results:

Two hundred sixty-nine pyeloplasty surgeries were included, 68% of which were in children. Pathologic analysis was requested in most of the cases (91%), and this was slightly more common in adults (94%) than in pediatric patients (90%). All available pathology reports found benign findings in the UPJ specimen, mostly commonly categorized as “normal.” No cases of malignancy were noted. At the list price for pathologic analysis, $103,027 was spent over 8 years without the discovery of clinically significant pathology findings.

Conclusions:

There was a lack of clinically meaningful results from pathologic analysis of UPJ specimens excised during pyeloplasty. A UPJ specimen should not be routinely sent for pathologic analysis rather selectively if there is clinical concern for nonbenign etiology of UPJ obstruction.
Treating obesity in type 1 diabetes mellitus – review of efficacy and safety
Authors: Freeby Matthew , Lane Kyrstin
Published: October 2023

Purpose of review

Obesity is an epidemic in the United States with serious concomitant co-morbid conditions; people living with type 1 diabetes mellitus (T1D) are not immune to the risk either. Weight gain in T1D is likely multifactorial, due to genetic, environmental and treatment-related factors. FDA-approved and other adjunctive weight loss therapies may benefit people living with T1D but there are risks to consider when providing recommendations or prescribing medications.

Recent findings

We performed a PubMed search of studies assessing clinical outcomes of both approved and off-label medications used in the treatment of type 1 diabetes. Search terms included ‘type 1 diabetes, obesity’ and the following: (1) metformin, (2) pramlintide, (3) glucagon-like peptide-1 (GLP-1) receptor agonists, (4) dual GLP-1 and gastric inhibitory polypeptide (GIP) agonists, (5) sodium-glucose cotransporter-2 (SGLT-2) inhibitors, (6) surgical treatment of obesity, (7) insulin pump, (8) insulin, (9) medical nutrition therapy, (10) diabetes self-management education, (11) exercise, (12) naltrexone-buproprion, (13) orlistat, and (14) phentermine-topiramate.

Weight loss treatments provide a wide-range of benefits in reducing both morbidity and mortality in those who are obese. Treatments also have varying adverse effect profiles which may impact T1D treatment. In this review, we aim to summarize study outcomes in people with T1D, including risks and benefits, of on- and off-label weight loss treatments.
Emergency Medical Treatment and Labor Act: Impact on Health Care, Nursing, Quality, and Safety
Authors: Schultz Theresa Ryan , Forbes Jacqueline , Hafen Packard Ashley
Published: October 2023

Nurse knowledge and expertise in Emergency Medical Treatment and Labor Act (EMTALA) laws are a prerequisite to meet emergency department practice laws and regulatory standards. The EMTALA is a federal law that requires anyone coming to an emergency department for care to be stabilized and treated, regardless of their insurance status or ability to pay. Regulatory standard infractions resulting from an EMTALA violation complaint may include (1) penalties and/or fines, (2) future unannounced Centers for Medicare & Medicaid Services surveys, (3) documented Centers for Medicare & Medicaid Services deficiencies that require timely response, action plan, and audit for expected outcomes, (4) Medicare/Medicaid nonpayment for services, and (5) termination of a hospital's Medicare agreement. The consequences of EMTALA violations target physicians and hospitals; however, nurses are most often the first provider the patient encounters upon arrival to the emergency department. It is therefore essential that nurses maintain a proficient understanding of EMTALA laws, which requires special training, monitoring, periodic competency assessment strategies, and continuing education throughout their career. Furthermore, additional clinician education is needed on how to manage the complex expectations that are imposed on health care providers by regulatory policy. Doing this promotes safe, effective, patient-centered, timely, and efficient health care regulations from the beginning of one's introduction to the health care industry and throughout his or her career. This article seeks to (a) emphasize nursing staff's responsibility for EMTALA adherence, (b) identify the gaps among health care quality, safety, and nursing workforce competency standards that are imposed to meet the demands of EMTALA laws, and (c) provide recommendations for continuing education, monitoring, and periodic competency assessment strategies that may strengthen EMTALA compliance.
Duped by dumping syndrome: Non-Endemic Vibrio cholerae bacteremia in an immunocompetent host with gastric bypass surgery, a case report
Authors: Reyes Fabiola , Pecora Nicole , Weiss Zoe F
Published: October 2023

Extra-intestinal infection with non-O1/non-O139 strains of Vibrio cholerae (NOVC) is rare, though bacteremia and hepatobiliary manifestations have been reported. Reduced stomach acid, or hypochlorhydria, can increase risk of V. cholerae infection. We describe a 42-year-old woman with hypochlorhydria due to untreated Helicobacter pylori infection, gastric-bypass surgery, and chronic proton pump inhibitors (PPI) exposure, who developed acute diarrhea following raw oyster consumption. Her symptoms were attributed to rapid gastric emptying (dumping syndrome) after a negative limited stool work-up. She had persistent diarrhea, weight loss, and after five months was admitted with acute cholecystitis and NOVC bacteremia, requiring cholecystectomy. This is the first reported case of NOVC bacteremia and cholecystitis in a patient with gastric bypass. This case highlights the potential for NOVC biliary carriage, the role of hypochlorhydria as a risk factor for Vibrio infection, and the importance of excluding infectious diarrhea in patients with new onset of symptoms compatible with dumping syndrome and a relevant travel history.
Separate orexigenic hippocampal ensembles shape dietary choice by enhancing contextual memory and motivation
Authors: Yang Mingxin , Singh Arashdeep , McDougle Molly , Décarie-Spain Léa , Kanoski Scott , de Lartigue Guillaume
Published: October 2023

The hippocampus (HPC), traditionally known for its role in learning and memory, has emerged as a controller of food intake. While prior studies primarily associated the HPC with food intake inhibition, recent research suggests a critical role in appetitive processes. We hypothesized that orexigenic HPC neurons differentially respond to fats and/or sugars, potent natural reinforcers that contribute to obesity development. Results uncover previously-unrecognized, spatially-distinct neuronal ensembles within the dorsal HPC (dHPC) that are responsive to separate nutrient signals originating from the gut. Using activity-dependent genetic capture of nutrient-responsive HPC neurons, we demonstrate a causal role of both populations in promoting nutrient-specific preference through different mechanisms. Sugar-responsive neurons encode an appetitive spatial memory engram for meal location, whereas fat-responsive neurons selectively enhance the preference and motivation for fat intake. Collectively, these findings uncover a neural basis for the exquisite specificity in processing macronutrient signals from a meal that shape dietary choices.