bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiotherapy for ductal carcinoma of the prostate: an analysis based on the Japanese radiation oncology study group survey
Authors: Kawamura Hidemasa , Nakamura Katsumasa , Yoshioka Yasuo , Itasaka Satoshi , Tomita Natsuo , Onishi Masahiro , Iwata Hiromitsu , Aizawa Takuya , Kikuchi Koyo , Nagata Kenji , Nakamura Kiyonao , Nishioka Kentaro , Ishiyama Hiromichi , Ueno Shuichi , Kokubo Masaki , Yamazaki Hideya , Watanabe Kenta , Toyoda Tatsuya , Akimoto Tetsuo ,   JROSG Working Subgroup of Urologic Oncology
Published: December 2022

Background

The clinical characteristics of prostate ductal carcinoma is still unclear, and treatment strategy has not yet been established due to its rarity. Therefore, we conducted a multicenter survey of radiation therapy for prostate ductal carcinoma in Japan.

Method

Data of patients with ductal carcinoma of the prostate treated with radiation therapy between 1996 and 2018 were extracted from the database of each facility.

Results

Fifty-two treatment records of 41 patients were collected from nine institutions. The treatment purpose and situations were varied curative intent to palliation. Twenty-eight patients received curative treatments. The median follow-up period of these patients was 68 months. Androgen deprivation therapy was combined with radiation therapy in 26 cases (93%). X-ray and particle irradiation was used. Radiation dose range was 63–78 Gy; 5-year overall survival, progression-free survival and biochemical relapse-free survival were 87.0, 79.3 and 79.3%, respectively. One patient experienced Grade 3 radiation proctitis and one experienced Grade 3 radiation cystitis. There were no Grade 4 or worse adverse events.

Conclusion

Most patient received similar treatment with adenocarcinoma of prostate, and the clinical results were compatible. For more reliable evidence, further studies are required.
The role of O-GlcNAcylation in innate immunity and inflammation
Authors: Wang Yongqiang , Fang Xiuwu , Wang Shuai , Wang Bin , Chu Feng , Tian Zhixin , Zhang Long , Zhou Fangfang
Published: December 2022

O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a highly dynamic and widespread post-translational modification (PTM) that regulates the activity, subcellular localization, and stability of target proteins. O-GlcNAcylation is a reversible PTM controlled by two cycling enzymes: O-linked N-acetylglucosamine transferase and O-GlcNAcase. Emerging evidence indicates that O-GlcNAcylation plays critical roles in innate immunity, inflammatory signaling, and cancer development. O-GlcNAcylation usually occurs on serine/threonine residues, where it interacts with other PTMs, such as phosphorylation. Thus, it likely has a broad regulatory scope. This review discusses the recent research advances regarding the regulatory roles of O-GlcNAcylation in innate immunity and inflammation. A more comprehensive understanding of O-GlcNAcylation could help to optimize therapeutic strategies regarding inflammatory diseases and cancer.
Activating transcription factor 3, glucolipid metabolism, and metabolic diseases
Authors: Hu Shuwei , Zhao Xiaojie , Li Rui , Hu Chencheng , Wu Huijuan , Li Jing , Zhang Yanqiao , Xu Yanyong
Published: December 2022

Lipids and glucose exert many essential physiological functions, such as providing raw materials or energy for cellular biosynthesis, regulating cell signal transduction, and maintaining a constant body temperature. Dysregulation of lipid and glucose metabolism can lead to glucolipid metabolic disorders linked to various metabolic diseases, such as obesity, diabetes, and cardiovascular disease. Therefore, intervention in glucolipid metabolism is a key therapeutic strategy for the treatment of metabolic diseases. Activating transcription factor 3 (ATF3) is a transcription factor that acts as a hub of the cellular adaptive-response network and plays a pivotal role in the regulation of inflammation, apoptosis, DNA repair, and oncogenesis. Emerging evidence has illustrated the vital roles of ATF3 in glucolipid metabolism. ATF3 inhibits intestinal lipid absorption, enhances hepatic triglyceride hydrolysis and fatty acid oxidation, promotes macrophage reverse cholesterol transport, and attenuates the progression of western diet-induced nonalcoholic fatty liver disease and atherosclerosis. In addition to its role in lipid metabolism, ATF3 has also been identified as an important regulator of glucose metabolism. Here, we summarize the recent advances in the understanding of ATF3, mainly focusing on its role in glucose and lipid metabolism and potential therapeutic implications.
The perceived influence of COVID-19 lockdown on the circulation of counterfeit drugs and medical supplies through the electronic market
Authors: Hamdan Iman M N
Published: December 2022

Objectives

Drugs and medical supplies counterfeiting is one of the worldwide major problems that pose a significant threat to both global public health and the economy. Nowadays, one of the major unprecedented challenges of the COVID-19 pandemic is the disastrous repercussions on the economy worldwide. The latter brought forth a noticeable rise in pharmaceutical and medical counterfeit products. Drug counterfeiting has thrived parallel to the expansion of electronic networks and the Internet during the COVID-19 pandemic. The objective of the current study is to explore the perceived influence of the COVID-19 lockdown on the circulation of counterfeit drugs and medical supplies through the electronic market in Jordan.

Methods

A cross-sectional survey study was conducted in Jordan. The questionnaire was self-administered to the public as they are the probable counterfeit medicine victims and as drug counterfeiting is a nationwide problem. To capture participants’ views, a total of 460 respondents were recruited and a simple random sampling strategy was used to collect data. The inclusion criteria were consumers aged 18 years old and above, who use the Internet when purchasing drugs and medical supplies, and are willing to participate in the study.

Key findings

The study indicated an increase in using electronic websites when purchasing medicines during the COVID-19 lockdown. Additionally, there was a significant correlation the between COVID-19 lockdown and the circulation of counterfeit drugs and medical supplies through the electronic market in Jordan.

Conclusions

The study indicated that the COVID-19 lockdown had influenced counterfeit drugs and medical supplies circulation through the electronic market in Jordan.
The Impact of Mixing Survey Modes on Estimates of Change: A Quasi-Experimental Study
Authors: Cernat Alexandru , Sakshaug Joseph W
Published: December 2022

Longitudinal surveys are a key data collection tool used to estimate social change. Recent developments have accelerated the move from traditional single-mode longitudinal designs to mixed-mode designs. Nevertheless, there are concerns that mixing survey modes may affect coefficients of change at the individual level. We investigate the impact of mixing survey modes on estimates of change using a quasi-experimental design implemented in a long-running UK panel study. Two types of comparisons are carried out: single-mode (face-to-face) design versus sequential mixed-mode (Web–face-to-face) design, and Web versus face to face. Across 41 variables, we find no differences in estimates of individual-level change across modes (designs). However, correlations between intercepts and slopes, an estimate of convergence of respondents, were significantly different for most variables, which led to some biases in estimates of change. Applied researchers are encouraged to do sensitivity checks to ensure their results are robust to mode effects.
Duration of seroprotection of the live attenuated SA-14-14-2 Japanese encephalitis vaccine in children in India
Authors: Preethi L , Alina M S , Chandran Lakshmi , Asvin S , Jagadeesan M , Vijayakumar T M , Chitra V , Pandey Ashok Kumar , Reddy Mahendra M , Misra Brij Ranjan , Kant Rajni , Bhukya Prudhvi Lal , Deshpande Gururaj Rao , Abraham Priya , Sapkal Gajanan , Zaman Kamran
Published: December 2022

Background

Acute encephalitis syndrome (AES) is a major public health concern in India, and the Japanese Encephalitis (JE) virus is the most common cause of viral encephalitis in Asia affecting children under the age of 15 years. In India, despite the introduction of the JE vaccine (SA-14-14-2) in the immunization programme, JE continues to account for 15–20% of AES cases to date. This study evaluates the immunogenicity of live attenuated SA-14-14-2 JE vaccine in terms of persistence of the humoral response after two doses.

Methods

A cross-sectional study was conducted among 266 children belonging to one of the JE endemic regions of Uttar Pradesh, India. Blood samples were taken from children (2–10 years) and grouped according to the duration (in years) after two doses of the vaccine (5 groups with a class interval of 2 years). Informed written consent was obtained from the parents/guardians. All the samples collected were tested for the presence of anti-JEV-specific IgG antibodies by enzyme-linked immunosorbent assay (ELISA) and further confirmed by micro neutralization test (MNT) and immunofluorescence assays.

Results

Of the 266 samples tested by ELISA for anti-JEV-specific IgG antibodies, 260 (97.74%) were negative and 6 (2.26%) were equivocal. The geometric mean immune status ratio across the five groups, 0–2 years (n = 59), 2–4 years (n = 73), 4–6 years (n = 65), 6–8 years (n = 48) and 8–10 years (n = 21) post-two doses of SA-14-14-2 JE vaccine was 1.143, 1.059, 1.138, 1.075 and 1.130, respectively, and the geometric mean titre obtained from MNT across the five groups was 10.77, 8.400, 8.453, 9.517 and 9.674, respectively.

Conclusion

The study showed a decreasing trend of anti-JEV specific IgG antibody titres across the five groups based on the duration following two doses of SA-14-14-2 vaccine. The results emphasize the significance of booster doses of vaccine for children living in endemic areas.
Immunogenicity and 1-year boostability of a three-dose intramuscular rabies pre-exposure prophylaxis schedule in adults receiving immunosuppressive monotherapy: a prospective single-centre clinical trial
Authors: Garcia Garrido Hannah M , van Put Bridget , Terryn Sanne , de Pijper Cornelis A , Stijnis Cornelis , D’Haens Geert R , Spuls Phyllis I , van de Sande Marleen G , van Gucht Steven , Grobusch Martin P , Goorhuis Abraham
Published: December 2022

Background

For immunocompromised patients (ICPs), administration of rabies immunoglobulins (RIG) after exposure is still recommended regardless of prior vaccination, due to a lack of data. We aimed to assess the 1-year boostability of a three-dose rabies pre-exposure prophylaxis (PrEP) schedule in individuals using immunosuppressive monotherapy.

Methods

In this prospective study, individuals on immunosuppressive monotherapy with a conventional immunomodulator (cIM) or a TNF-alpha inhibitor (TNFi) for a chronic inflammatory disease received a three-dose intramuscular PrEP schedule (days 0,7,21–28) with 1 mL Rabipur®, followed by a two-dose simulated post-exposure prophylaxis (PEP) schedule (days 0,3) after 12 months. Rabies neutralizing antibodies were assessed at baseline, on day 21–28 (before the third PrEP dose), day 60, month 12 and month 12 + 7 days. The primary outcome was 1-year boostability, defined as the proportion of patients with a neutralizing antibody titre of ≥ 0.5 IU/mL at month 12 + 7 days. Secondary outcomes were geometric mean titres (GMTs) and factors associated with the primary endpoint.

Results

We included 56 individuals, of whom 52 completed the study. The 1-year boostability was 90% (47/52) with a GMT of 6.16 (95% CI 3.83–9.91). All participants seroconverted at some point in the study. Early response to PrEP (at day 21–28) was significantly associated with 100% boostability (Odds Ratio 51; 95% confidence interval [5.0–6956], P < 0.01). The vaccination schedule was safe and well tolerated. No vaccine-related serious adverse events occurred.

Conclusion

In patients using immunosuppressive monotherapy, a three-dose rabies PrEP schedule followed by a two-dose PEP schedule is immunogenic, with all patients seroconverting at some point in the study. Although boostability 7 days after PEP was not 100%, nobody would wrongly be denied RIG when only administered to those who responded early to PrEP while reducing the administration of RIG by 73%.
Structure–function analyses of coiled-coil immune receptors define a hydrophobic module for improving plant virus resistance
Authors: Wu Xiujuan , Zhang Xuan , Wang Hongwei , Fang Rong-xiang , Ye Jian
Published: December 2022

Plant immunity relies on nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) that detect microbial patterns released by pathogens, and activate localized cell death to prevent the spread of pathogens. Tsw is the only identified resistance (R) gene encoding an NLR, conferring resistance to tomato spotted wilt orthotospovirus (TSWV) in pepper species (Capsicum, Solanaceae). However, molecular and cellular mechanisms of Tsw-mediated resistance are still elusive. Here, we analysed the structural and cellular functional features of Tsw protein, and defined a hydrophobic module to improve NLR-mediated virus resistance. The plasma membrane associated N-terminal 137 amino acid in the coiled-coil (CC) domain of Tsw is the minimum fragment sufficient to trigger cell death in Nicotiana benthamiana plants. Transient and transgenic expression assays in plants indicated that the amino acids of the hydrophobic groove (134th–137th amino acid) in the CC domain is critical for its full function and can be modified for enhanced disease resistance. Based on the structural features of Tsw, a super-hydrophobic funnel-like mutant, TswY137W, was identified to confer higher resistance to TSWV in a SGT1 (Suppressor of G-two allele of Skp1)-dependent manner. The same point mutation in a tomato Tsw-like NLR protein also improved resistance to pathogens, suggesting a feasible way of structure-assisted improvement of NLRs.
Can bronchial secretion cultures identify the etiologic agent of COVID-19-associated pulmonary aspergillosis in ICU patients? Comparison with a species-specific Aspergillus PCR in serum
Authors: Siopi Maria , Antonopoulou Stavroula , Mantzana Paraskevi , Georgiou Panagiota-Christina , Vourli Sophia , Protonotariou Efthymia , Vagiakou Eleni , Skoura Lemonia , Pournaras Spyros , Meletiadis Joseph
Published: December 2022

Aspergillus spp. isolated from non-BAL cultures of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) patients may reflect colonization rather than infection. Sera (n = 181) from 49 adult ICU CAPA patients (24 probable and 25 possible CAPA) with bronchial secretions (BS) culture positive for Aspergillus spp. were collected and tested for Aspergillus DNA detection by species-specific real-time PCR. Overall, 30/49 (61%) patients were PCR positive. BS culture/serum PCR agreement was moderate (21/30; 70%). Based on serum PCR positive patients, all CAPAs were due to A. fumigatus (80%), A. flavus (10%), and A. terreus (10%). No A. niger/A. nidulans or mixed infections were found despite positive BS cultures.
Planet engulfment signatures in twin stars
Authors: Behmard Aida , Sevilla Jason , Fuller Jim
Published: December 2022

Planet engulfment can be inferred from enhancement of refractory elements in the photosphere of the engulfing star following accretion of rocky planetary material. Such refractory enrichments are subject to stellar interior mixing processes, namely thermohaline mixing induced by an inverse mean-molecular-weight gradient between the convective envelope and radiative core. Using mesa stellar models, we quantified the strength and duration of engulfment signatures following planet engulfment. We found that thermohaline mixing dominates during the first ∼5–45 Myr post-engulfment, weakening signatures by a factor of ∼2 before giving way to depletion via gravitational settling on longer time-scales. Solar metallicity stars in the 0.5–1.2 M⊙ mass range have observable signature time-scales of ∼1 Myr–8 Gyr, depending on the engulfing star mass and amount of material engulfed. Early type stars exhibit larger initial refractory enhancements but more rapid depletion. Solar-like stars (M = 0.9–1.1 M⊙) maintain observable signatures (>0.05 dex) over time-scales of ∼20 Myr–1.7 Gyr for nominal 10 M⊕ engulfment events, with longer-lived signatures occurring for low-metallicity and/or hotter stars (1 M⊙, ∼2–3 Gyr). Engulfment events occurring well after the zero-age main sequence produce larger signals due to suppression of thermohaline mixing by gravitational settling of helium (1 M⊙, ∼1.5 Gyr). These results indicate that it may be difficult to observe engulfment signatures in solar-like stars that are several Gyr old.
A low-mass companion desert among intermediate-mass visual binaries: The scaled-up counterpart to the brown dwarf desert
Authors: Duchêne Gaspard , Oon Jner Tzern , De Rosa Robert J , Kantorski Patrick , Coy Brandon , Wang Jason J , Thomas Sandrine , Patience Jenny , Pueyo Laurent , Nielsen Eric L , Konopacky Quinn
Published: December 2022

We present a high-contrast imaging survey of intermediate-mass (1.75–4.5 M⊙) stars to search the most extreme stellar binaries, i.e. for the lowest mass stellar companions. Using adaptive optics at the Lick and Gemini observatories, we observed 169 stars and detected 24 candidates companions, 16 of which are newly discovered, and all but three are likely or confirmed physical companions. Despite obtaining sensitivity down to the substellar limit for 75 per cent of our sample, we do not detect any companion below 0.3 M⊙, strongly suggesting that the distribution of stellar companions is truncated at a mass ratio of qmin ≳ 0.075. Combining our results with known brown dwarf companions, we identify a low-mass companion desert to intermediate-mass stars in the range 0.02 ≲ q ≲ 0.05, which quantitatively matches the known brown dwarf desert among solar-type stars. We conclude that the formation mechanism for multiple systems operates in a largely scale-invariant manner and precludes the formation of extremely uneven systems, likely because the components of a protobinary accrete most of their mass after the initial cloud fragmentation. Similarly, the mechanism to form ‘planetary’ (q ≲ 0.02) companions likely scales linearly with stellar mass, probably as a result of the correlation between the masses of stars and their protoplanetary discs. Finally, we predict the existence of a sizable population of brown dwarf companions to low-mass stars and of a rising population of planetary-mass objects towards ${\approx}1\,M_\mathrm{Jup}$ around solar-type stars. Improvements on current instrumentation will test these predictions.
A measurement of the distance to the Galactic centre using the kinematics of bar stars
Authors: Leung Henry W , Bovy Jo , Mackereth J Ted , Hunt Jason A S , Lane Richard R , Wilson John C
Published: December 2022

The distance to the Galactic centre R0 is a fundamental parameter for understanding the Milky Way, because all observations of our Galaxy are made from our heliocentric reference point. The uncertainty in R0 limits our knowledge of many aspects of the Milky Way, including its total mass and the relative mass of its major components, and any orbital parameters of stars employed in chemo-dynamical analyses. While measurements of R0 have been improving over a century, measurements in the past few years from a variety of methods still find a wide range of R0 being somewhere within 8.0 to $8.5\, \mathrm{kpc}$. The most precise measurements to date have to assume that Sgr A* is at rest at the Galactic centre, which may not be the case. In this paper, we use maps of the kinematics of stars in the Galactic bar derived from APOGEE DR17 and Gaia EDR3 data augmented with spectrophotometric distances from the astroNN neural-network method. These maps clearly display the minimum in the rotational velocity vT and the quadrupolar signature in radial velocity vR expected for stars orbiting in a bar. From the minimum in vT, we measure $R_0 = 8.23\pm 0.12\, \mathrm{kpc}$. We validate our measurement using realistic N-body simulations of the Milky Way. We further measure the pattern speed of the bar to be $\Omega _\mathrm{bar} = 40.08\pm 1.78\, \mathrm{km\, s}^{-1}\,\mathrm{kpc}^{-1}$. Because the bar forms out of the disc, its centre is manifestly the barycentre of the bar+disc system and our measurement is therefore one of the most robust and accurate measurements of R0 to date.
A comparative analysis of the chemical compositions of Gaia-Enceladus/Sausage and Milky Way satellites using APOGEE
Authors: Fernandes Laura , Mason Andrew C , Horta Danny , Schiavon Ricardo P , Hayes Christian , Hasselquist Sten , Feuillet Diane , Beaton Rachael L , Jönsson Henrik , Kisku Shobhit , Lacerna Ivan , Lian Jianhui , Minniti Dante , Villanova Sandro
Published: December 2022

We use data from the 17th data release of the Apache Point Observatory Galactic Evolution Experiment (APOGEE 2) to contrast the chemical composition of the recently discovered Gaia Enceladus/Sausage system (GE/S) to those of 10 Milky Way (MW) dwarf satellite galaxies: LMC, SMC, Boötes I, Carina, Draco, Fornax, Sagittarius, Sculptor, Sextans, and Ursa Minor. Our main focus is on the distributions of the stellar populations of those systems in the [Mg/Fe]–[Fe/H] and [Mg/Mn]–[Al/Fe] planes, which are commonly employed in the literature for chemical diagnosis and where dwarf galaxies can be distinguished from in situ populations. We show that, unlike MW satellites, a GE/S sample defined purely on the basis of orbital parameters falls almost entirely within the locus of ‘accreted’ stellar populations in chemical space, which is likely caused by an early quenching of star formation in GE/S. Due to a more protracted history of star formation, stars in the metal-rich end of the MW satellite populations are characterized by lower [Mg/Mn] than those of their GE/S counterparts. The chemical compositions of GE/S stars are consistent with a higher early star formation rate (SFR) than MW satellites of comparable and even higher mass, suggesting that star formation in the early universe was strongly influenced by other parameters in addition to mass. We find that the direction of the metallicity gradient in the [Mg/Mn]–[Al/Fe] plane of dwarf galaxies is an indicator of the early SFR of the system.
Rapid decline in the lightcurves of luminous supernovae by jet-driven bipolar explosions
Authors: Akashi Muhammad , Michaelis Amir , Soker Noam
Published: December 2022

We calculate the lightcurves of jet-driven bipolar core collapse supernova (CCSN) explosions into a bipolar circumstellar matter (CSM) and show that an equatorial observer finds the lightcurves to possess a rapid, and even an abrupt drop. The scenario that might lead to such an explosive morphology is a common envelope evolution (CEE), where shortly before the CCSN explosion the red-supergiant progenitor interacts with a more compact companion that spirals-in and spins-up the core. The companion can be a main sequence star, a neutron star, or a black hole. The binary interaction ejects a shell through an intensive wind and the CEE ejects a denser gas in the equatorial plane. We assume that the companion accretes mass and launches jets. We conduct three-dimensional (3D) hydrodynamical simulations where we launch weak jets, the shaping jets, into the dense shell and show that the interaction forms a bipolar CSM. As a result of the rapid pre-collapse core rotation jets drive the CCSN explosion. We simulate the interaction of the jets with the bipolar CSM and use a simple scheme to calculate the lightcurves. We show that the abrupt drop in the lightcurve of an observer not too close to the polar directions can account for the lightcurve of the hydrogen poor luminous supernova (LSN) SN 2018don.
Polarized radio emission unveils the structure of the pre-supernova circumstellar magnetic field and the radio emission in SN1987A
Authors: Petruk O , Beshley V , Orlando S , Bocchino F , Miceli M , Nagataki S , Ono M , Loru S , Pellizzoni A , Egron E
Published: December 2022

The detected polarized radio emission from the remnant of SN1987A opens the possibility to unveil the structure of the pre-supernova (pre-SN) magnetic field (MF) in the circumstellar medium. Properties derived from direct measurements would be of importance for understanding the progenitor stars and their MFs. As the first step to this goal, we adopted the hydrodynamic (HD) data from an elaborated three-dimensional (3D) numerical model of SN1987A. We have developed an approximate method for ‘reconstruction’ of 3D MF structure inside SN remnant on the 'HD background’. This method uses the distribution of the MF around the progenitor as the initial condition. With such a 3D magnetohydrodynamic model, we have synthesized the polarization maps for a number of SN1987A models and compared them to the observations. In this way, we have tested different initial configurations of the MF as well as a structure of the synchrotron emission in SN987A. We have recovered the observed polarization pattern and we have found that the radial component of the ambient pre-SN MF should be dominant on the length-scale of the present-day radius of SN1987A. The physical reasons for such a field are discussed.
Two substellar survivor candidates: one found and one missing
Authors: Walters N , Farihi J , Marsh T R , Breedt E , Cauley P W , von Hippel T , Hermes J J
Published: December 2022

This study presents observations of two possible substellar survivors of post-main sequence engulfment, currently orbiting white dwarf stars. Infrared and optical spectroscopy of GD 1400 reveals a 9.98 h orbital period, where the benchmark brown dwarf has M2 = 68 ± 8 MJup, Teff ≈ 2100 K, and a cooling age under 1 Gyr. A substellar mass in the lower range of allowed values is favoured by the gravitational redshift of the primary. Synthetic brown dwarf spectra are able to reproduce the observed CO bands, but lines below the bandhead are notably overpredicted. The known infrared excess towards PG 0010+281 is consistent with a substellar companion, yet no radial velocity or photometric variability is found despite extensive searches. Three independent stellar mass determinations all suggest enhanced mass-loss associated with binary evolution, where the youngest total age for an isolated star is 7.5 ± 2.5 Gyr. A possible solution to this conundrum is the cannibalization of one or more giant planets, which enhanced mass-loss post-main sequence, but were ultimately destroyed. PG 0010 + 281 is likely orbited by a debris disc that is comfortably exterior to the Roche limit, adding to the growing number of non-canonical discs orbiting white dwarfs. At present, only L-type (brown) dwarfs are known to survive direct engulfment during the post-main sequence, whereas T- and Y-type substellar companions persist at wide separations. These demographics indicate that roughly 50 MJup is required to robustly avoid post-main sequence annihilation, suggesting all closely orbiting giant planets are consumed, which may contribute to mass-loss and magnetic-field generation in white dwarfs and their immediate progenitors.
The two z ∼ 13 galaxy candidates HD1 and HD2 are likely not lensed
Authors: Lee Rui Zhe , Pacucci Fabio , Natarajan Priyamvada , Loeb Abraham
Published: December 2022

The discovery of two ultraviolet (UV)-bright galaxy candidates at z ∼ 13, HD1 and HD2, laid the foundation for a new race to study the early Universe. Previous investigations suggested that they are powered either by a supermassive black hole or by an extreme, transient burst of star formation. Given their uncertain nature, we investigate whether these sources could be lensed by a hitherto undetected, faint foreground galaxy. We find that at the current limiting magnitude with which HD1 and HD2 were imaged, there is only a $7.39{{\ \rm per\ cent}}$ probability they are strongly lensed by spherical deflectors and that the hypothetical lensing galaxy was too faint to be detected. Meanwhile, with the limiting magnitudes of the Hubble Space Telescope (HST) and JWST, the theoretical probability would drop precipitously to 0.058 and $0.0012{{\ \rm per\ cent}}$, respectively. We further find it unlikely that the luminosities of both sources can be accounted for by lensing that produces a single, resolved image with sufficiently high magnification. Alternatively, in the unlikely event that their brightness results from lensing by an elliptical isothermal galaxy, there is a $30.9 {{\ \rm per\ cent}}$ probability that the lensing galaxy is too faint to be observable at the current limiting magnitude. Future HST (JWST) imaging will drop this probability to $0.245 {{\ \rm per\ cent}}$ ($0.0025 {{\ \rm per\ cent}}$). In summary, while deep imaging with HST and JWST is required to discard the lensing hypothesis entirely, it is unlikely that the exceptional luminosity of the two z ∼ 13 sources can be accounted for by gravitational lensing.
Low-redshift quasars in the SDSS Stripe 82 – III. MOS observations
Authors: Bettoni D , Falomo R , Paiano S , Kotilainen J K , Stone M B
Published: December 2022

We present multi-object optical spectroscopy of the galaxies in the environment of 12 low-redshift (z < 0.5) quasars and of 11 inactive massive galaxies chosen to match the properties of the quasar host galaxies to probe physical association and possible events of recent star formation (SF). The quasars are selected from a sample of QSOs in the Sloan Digital Sky Survey (SDSS) Stripe 82 region for which both the host galaxy and the large-scale environments were previously investigated. The new observations complement those reported in our previous works on close companion galaxies of nearby quasars. For the whole data set, we find that for about half (19 out of 44) of the observed QSOs, there is at least one associated companion galaxy. In addition to the new spectroscopic observations, we add data from the SDSS data base for the full sample of objects. We find that the incidence of companion galaxies in the fields of QSO (17 per cent) is not significantly different from that of inactive galaxies (19 per cent) similar to quasar hosts in redshift and mass. Nevertheless, the companions of quasars exhibit more frequently emission lines than those of inactive galaxies, suggesting a moderate link between the nuclear activity and recent SF in their environments.
Super-critical accretion of medium-weight seed black holes in gaseous proto-galactic nuclei
Authors: Sassano Federica , Capelo Pedro R , Mayer Lucio , Schneider Raffaella , Valiante Rosa
Published: December 2022

Accretion at sustained or episodic super-Eddington (SE) rates has been proposed as a pathway to grow efficiently light seeds produced by Pop-III stars. We investigate if SE accretion can be sustained onto a black hole (BH) with MBH ∼ 103 M⊙ in the centre of a gas-rich proto-galaxy at z = 15. We perform high-resolution smoothed-particle hydrodynamical simulations, including two different sub-grid models for SE accretion, one based on the slim disc paradigm, and one inspired by recent radiation-magnetohydrodynamical simulations by Jiang and collaborators. Radiative feedback has the form of a thermal dump to surrounding gas particles, with the radiative efficiency being set according to the different SE accretion models. We find that, in all simulations, star formation, BH feedback, and interactions between clumps and the BH rapidly quench accretion after ∼1 Myr, irrespective of the sub-grid model used for accretion. Quenching is stronger in the model based on the simulations of Jiang and collaborators relative to the slim disc model because of its higher radiative efficiency. The SE growth phase is always very brief, lasting a few 0.1 Myr. In the most optimistic case, the BH reaches a mass of ∼104 M⊙. We extrapolate the final BH masses from z = 15 to z ∼ 6, assuming subsequent galaxy mergers will replenish the gas reservoir and trigger new cycles of SE accretion. We find that at most BH seeds would grow to ∼106 M⊙, comparable to the mass of massive BHs in spiral galaxies such as the Milky Way, but falling short of the mass of the high-redshift quasars.
Observational constraints on maximum mass limit and physical properties of anisotropic strange star models by gravitational decoupling in Einstein–Gauss–Bonnet gravity
Authors: Maurya S K , Singh Ksh Newton , Govender M , Ray Saibal
Published: December 2022

In this work, we are guided by the gravitational wave events GW 170817 and GW 190814 together with observations of neutron stars PSR J1614-2230, PSR J1903+6620, and LMC X-4 to model compact objects within the framework of Einstein–Gauss–Bonnet (EGB) gravity. In addition, we employ the extended gravitational decoupling (EGD) method to explore the impact of anisotropy by varying the decoupling parameter. We model strange quark stars in which the interior stellar fluid obeys the MIT Bag equation of state which represents a degenerated Fermi gas comprising of up, down, and strange quarks. In order to close the system of field equations describing the seed solution, we employ the Buchdahl ansatz for one of the metric functions. The θ sector is solved under the bifurcation: $\epsilon =\theta ^0_0$ and $P_r=\theta ^1_1$ leading to two new families of solutions. In order to test the physical viability of the models, we vary the EGB parameter (α) or the decoupling constant (β) to achieve the observed masses and radii of compact objects. Our models are able to account for low-mass stars for a range of β values while α is fixed. The present models mimic the secondary component of the GW 190814 with a mass range of 2.5–2.67 M⊙ and radii typically of the order of 11.76$^{+0.14}_{-0.19}$ km for large values of the EGB parameter and the decoupling constant. The energy exchange between fluids inside the stellar object is sensitive to model parameters which lead to stable configurations.
Displacement and dissociation of oligonucleotides during DNA hairpin closure under strain
Authors: Ding Fangyuan , Cocco Simona , Raj Saurabh , Manosas Maria , Nguyen Thao Thi Thu , Spiering Michelle M , Bensimon David , Allemand Jean-François , Croquette Vincent
Published: December 2022

The hybridization kinetic of an oligonucleotide to its template is a fundamental step in many biological processes such as replication arrest, CRISPR recognition, DNA sequencing, DNA origami, etc. Although single kinetic descriptions exist for special cases of this problem, there are no simple general prediction schemes. In this work, we have measured experimentally, with no fluorescent labelling, the displacement of an oligonucleotide from its substrate in two situations: one corresponding to oligonucleotide binding/unbinding on ssDNA and one in which the oligonucleotide is displaced by the refolding of a dsDNA fork. In this second situation, the fork is expelling the oligonucleotide thus significantly reducing its residence time. To account for our data in these two situations, we have constructed a mathematical model, based on the known nearest neighbour dinucleotide free energies, and provided a good estimate of the residence times of different oligonucleotides (DNA, RNA, LNA) of various lengths in different experimental conditions (force, temperature, buffer conditions, presence of mismatches, etc.). This study provides a foundation for the dynamics of oligonucleotide displacement, a process of importance in numerous biological and bioengineering contexts.
Smoking Cessation Among Gender Minority Populations, Cis-women, and Cis-men: Findings From the International Tobacco Control Netherlands Survey
Authors: Nagelhout Gera E , Poole Nikita L , Geboers Cloé , Magnée Tessa , Kaag Anne Marije , van den Brand Floor A , van den Putte Bas , de Vries Hein , Fong Geoffrey T , Willemsen Marc C
Published: December 2022

Introduction

Little is known about smoking cessation among gender minority populations compared to cisgender individuals (whose gender matches their sex assigned at birth). We examined differences between smokers from gender minority populations, cis-women, and cis-men in the heaviness of smoking, quit intentions, use of cessation assistance, quit attempts (ever tried and number), and triggers for thinking about quitting.

Aims and Methods

We used cross-sectional data from the 2020 International Tobacco Control Netherlands Survey. Among smoking respondents, we distinguished (1) cis-women (female sex, identified as women, and having feminine gender roles; n = 670), (2) cis-men (male sex, identified as men, and having masculine gender roles; n = 897), and (3) gender minorities (individuals who were intersex, who identified as nonbinary, genderqueer, had a sex/gender identity not listed, whose gender roles were not feminine or masculine, or whose gender identity and/or roles were not congruent with sex assigned at birth; n = 220).

Results

Although gender minorities did not differ from cis-women and cis-men in the heaviness of smoking, plans to quit smoking, and quit attempts, they were significantly more likely to use cessation assistance (20% in the past 6 months) than cis-women (12%) and cis-men (9%). Gender minorities were also significantly more likely to report several triggers for thinking about quitting smoking, for example, quit advice from a doctor, an anti-smoking message/campaign, and the availability of a telephone helpline.

Conclusion

Despite equal levels of quit attempts and heaviness of smoking, gender minority smokers make more use of smoking assistance, and respond stronger to triggers for thinking about quitting smoking.

Implications

Smoking cessation counselors should be sensitive to the stressors that individuals from any minority population face, such as stigmatization, discrimination, and loneliness, and should educate their smoking clients on effective coping mechanisms to prevent relapse into smoking after they experience these stressors. Developing tailored smoking cessation programs or campaigns specifically for gender minority populations can also be useful. Based on the results of our subgroup analyses, programs or campaigns for younger gender minority smokers could focus on the availability of telephone helplines and on how friends and family think about their smoking behavior.
Efficacy and Safety of Avapritinib in Treating Unresectable or Metastatic Gastrointestinal Stromal Tumors: A Phase I/II, Open-Label, Multicenter Study
Authors: Li Jian , Zhang Xinhua , Deng Yanhong , Wu Xin , Zheng Zhichao , Zhou Yongjian , Cai Shirong , Zhang Yanqiao , Zhang Jun , Tao Kaixiong , Cui Yuehong , Cao Hui , Shen Kuntang , Yu Jiren , Zhou Ye , Ren Wenxiao , Qu Chenglin , Zhao Wanqi , Hu Jin , Wang Wei , Yang Jason , Shen Lin
Published: December 2022

Background

Avapritinib is a type 1 kinase inhibitor designed to potently and selectively inhibit oncogenic KIT/PDGFRA mutants by targeting the kinase active conformation. This multicenter, single-arm, open-label, phase I/II bridging study of NAVIGATOR in Chinese patients evaluated the safety and the antineoplastic activity of avapritinib in Chinese patients with unresectable/metastatic gastrointestinal stromal tumors (GIST).

Methods

Phase I comprised dose escalation for safety and phase II dose determination. Phase II comprised dose expansion for safety/efficacy evaluations in patients with PDGFRA D842V mutations or patients having received at least 3 lines of therapy without PDGFRA D842V mutations. The primary endpoints were recommended phase II dose, safety, and Independent Radiology Review Committee (IRRC)-assessed objective response rate (ORR).

Results

No dose-limiting toxicities occurred (n = 10); the recommended phase II dose was avapritinib 300 mg once daily orally. Fifty-nine patients initially received avapritinib 300 mg. Common grade ≥3 treatment-related adverse events were anemia, decreased white blood cell count, increased blood bilirubin levels, and decreased neutrophil count. In patients with PDGFRA D842V mutations, IRRC- and investigator-assessed ORRs were 75% and 79%, respectively; clinical benefit rates were both 86%. Median duration of response/progression-free survival were not reached. IRCC- and investigator-assessed ORRs in patients in the fourth- or later-line setting were 22% and 35%, respectively. Median progression-free survivals were 5.6 months for both. Overall survival data were immature and not calculated.

Conclusion

Avapritinib was generally well tolerated and showed marked anti-tumor activity in Chinese patients with GIST bearing PDGFRA D842V mutations and notable efficacy as fourth- or later-line monotherapy (ClinicalTrials.gov Identifier: NCT04254939).
A close-in planet orbiting giant star HD 167768
Authors: Teng Huan-Yu , Sato Bun’ei , Kunitomo Masanobu , Takarada Takuya , Omiya Masashi , Harakawa Hiroki , Xiao Guang-Yao , Liu Yu-Juan , Izumiura Hideyuki , Kambe Eiji , Yoshida Michitoshi , Itoh Yoichi , Ando Hiroyasu , Kokubo Eiichiro , Ida Shigeru
Published: December 2022

We report the detection of a giant planet orbiting the G-type giant star HD 167768 from radial velocity measurements using the High Dispersion Echelle Spectrograph (HIDES) at Okayama Astrophysical Observatory (OAO). HD 167768 has a mass of $1.08_{-0.12}^{+0.14}\, M_{\odot }$, a radius of $9.70_{-0.25}^{+0.25}\, R_{\odot }$, a metallicity of $[\mbox{Fe}/\mbox{H}]=-0.67_{-0.08}^{+0.09}$, and a surface gravity of $\log g = 2.50_{-0.06}^{+0.06}$. The planet orbiting the star is a warm Jupiter, having a period of $20.6532_{-0.0032}^{+0.0032}\:\mbox{d}$, a minimum mass of $0.85_{-0.11}^{+0.12}\, M_{\rm {J}}$, and an orbital semimajor axis of $0.1512_{-0.0063}^{+0.0058}\:\mbox{au}$. The planet has one of the shortest orbital periods among those ever found around deeply evolved stars (log g < 3.5) using radial velocity methods. The equilibrium temperature of the planet is 1874 K, as high as a hot Jupiter. The radial velocities show two additional regular variations at 41 d and 95 d, suggesting the possibility of outer companions in the system. Follow-up monitoring will enable validation of the periodicity. We also calculated the orbital evolution of HD 167768 b and found that the planet will be engulfed within 0.15 Gyr.
Non-inflammatory pain in inflammatory arthritis
Authors: Das Dhivya , Choy Ernest
Published: December 2022

‘Non-inflammatory’ pain, pain that is not associated with measures of inflammation, is common in patients with inflammatory arthritis including RA. One important cause of non-inflammatory pain is concomitant fibromyalgia. Systematic review has shown that fibromyalgia is common in inflammatory arthritis including RA affecting 1 in 5 patients and is associated with higher disease activity scores due to inflated tender joint count and patient global assessment. Consequently, many patients with RA and concomitant fibromyalgia may fail to reach treatment target and switch to alternate disease modifying drugs frequently. European Alliance of Association for Rheumatology has highlighted that concomitant fibromyalgia is an important consideration in assessing difficult-to-treat RA. The incidence and prevalence of fibromyalgia are higher in RA than the general population, raising the possibility that fibromyalgia may be ‘secondary’ to RA rather than a concomitant disease. The precise mechanisms whereby patients with RA develop fibromyalgia are unknown. In this review, we discussed fibromyalgia in RA, its clinical impact and epidemiology as well as data suggesting fibromyalgia might be ‘secondary’. Lastly, we reviewed potential pathogenic mechanisms which included inflammatory cytokines sensitizing nociceptive neurones, temporal summation, also known as windup, from chronic pain and impaired coping from poor quality sleep and mental well-being. Deciphering the exact mechanisms may lead to treatment strategies that prevent development of secondary fibromyalgia and will address a common factor associated with difficult-to-treat RA.
Associations between evening shift work, irregular sleep timing, and gestational diabetes in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b)
Authors: Wallace Danielle A , Reid Kathryn , Grobman William A , Facco Francesca L , Silver Robert M , Pien Grace W , Louis Judette , Zee Phyllis C , Redline Susan , Sofer Tamar
Published: December 2022

Study Objectives

Shift work is a risk factor for cardiometabolic disease, possibly through effects on sleep–wake rhythms. We hypothesized that evening (afternoon and night combined) and irregular (irregular/on-call or rotating combined) shift work during pregnancy is associated with increased odds of preeclampsia, preterm birth, and gestational diabetes mellitus (GDM), mediated by irregular sleep timing.

Methods

The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b) is a prospective cohort study (n = 10 038) designed to investigate risk factors for adverse pregnancy outcomes. Medical outcomes were determined with medical record abstraction and/or questionnaires; sleep midpoint was measured in a subset of participants with ≥5-day wrist actigraphy (ActiWatch). We estimated the association of evening and irregular shift work during pregnancy with preeclampsia, preterm birth, and GDM using logistic regression, adjusted for adversity (cumulative variable for poverty, education, health insurance, and partner status), smoking, self-reported race/ethnicity, and age. Finally, we explored whether the association between shiftwork and GDM was mediated by variability in sleep timing.

Results

Evening shift work is associated with approximately 75% increased odds of developing GDM (adjusted OR = 1.75, 95% CI: 1.12–2.66); we did not observe associations with irregular shifts, preterm birth, or preeclampsia after adjustment. Pregnant evening shift workers were found to have approximately 45 minutes greater variability in sleep timing compared to day workers (p < .005); sleep-timing variability explained 25% of the association between evening shift work and GDM in a mediation analysis.

Conclusions

Evening shift work was associated with GDM, and this relationship may be mediated by variability in sleep timing.
Transient Methionine Deprivation Triggers Histone Modification and Potentiates Differentiation of Induced Pluripotent Stem Cells
Authors: Ozawa Hiroki , Kambe Azusa , Hibi Kodai , Murakami Satoshi , Oikawa Akira , Handa Tetsuya , Fujiki Katsunori , Nakato Ryuichiro , Shirahige Katsuhiko , Kimura Hiroshi , Shiraki Nobuaki , Kume Shoen
Published: December 2022

Human induced pluripotent stem cells (iPSCs) require high levels of methionine (Met). Met deprivation results in a rapid decrease in intracellular S-adenosyl-methionine (SAM), poising human iPSCs for differentiation and leading to the apoptosis of undifferentiated cells. Met deprivation triggers rapid metabolic changes, including SAM, followed by reversible epigenetic modifications. Here, we show that short-term Met deprivation impairs the pluripotency network through epigenetic modification in a 3D suspension culture. The trimethylation of lysine 4 on histone H3 (H3K4me3) was drastically affected compared with other histone modifications. Short-term Met deprivation specifically affects the transcription start site (TSS) region of genes, such as those involved in the transforming growth factor β pathway and cholesterol biosynthetic process, besides key pluripotent genes such as NANOG and POU5F1. The expression levels of these genes decreased, correlating with the loss of H3K4me3 marks. Upon differentiation, Met deprivation triggers the upregulation of various lineage-specific genes, including key definitive endoderm genes, such as GATA6. Upon differentiation, loss of H3K27me3 occurs in many endodermal genes, switching from a bivalent to a monovalent (H3K4me3) state. In conclusion, Met metabolism maintains the pluripotent network with histone marks, and their loss potentiates differentiation.