bluuebunny/crossref_metadata_2025 huggingface dataset:
Large-scale WGS of carbapenem-resistant Acinetobacter baumannii isolates reveals patterns of dissemination of ST clades associated with antibiotic resistance
Authors: Frenk Sammy , Temkin Elizabeth , Lurie-Weinberger Mor N. , Keren-Paz Alona , Rov Reut , Rakovitsky Nadya , Wullfhart Liat , Nutman Amir , Daikos George L. , Skiada Anna , Durante-Mangoni Emanuele , Dishon Benattar Yael , Bitterman Roni , Yahav Dafna , Daitch Vered , Bernardo Mariano , Iossa Domenico , Zusman Oren , Friberg Lena E. , Mouton Johan W. , Theuretzbacher Ursula , Leibovici Leonard , Geffen Yuval , Gershon Rina , Paul Mical , Carmeli Yehuda
Published: January 2022

Objectives

To describe the population genetics and antibiotic resistance gene distribution of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates causing infections in three Mediterranean countries.

Methods

Isolates were collected during the 2013–17 AIDA clinical trial in six hospitals in Israel, Greece and Italy. WGS, bioinformatic characterization and antibiotic resistance profiling were performed.

Results

In the 247 CRAB isolates characterized in this study, ST distribution varied by country: 29/31 (93.5%) Greek isolates, 34/41 (82.9%) Italian isolates and 70/175 (40.0%) Israeli isolates belonged to ST2. The identified ST2 isolates included eight distinct clades: 2C, 2D and 2H were significantly more common in Italy, while 2F was unique to Greece. The uncommon ST3 was not present among Greek isolates and constituted only 5/41 (12%) Italian isolates. On the other hand, it was much more common among Israeli isolates: 78/175 (44.6%) belonged to ST3. The vast majority of isolates, 240/247 (97.2%), were found to harbour acquired carbapenemases, primarily blaOXA-23. The chromosomal oxaAb (blaOXA-51-like) and ampC genes characteristic of this organism were also ubiquitous. Most (96.4%) ST3 isolates carried a broad-host-range plasmid IncP1α.

Conclusions

The geographical differences in CRAB populations support the theory that clonal spread of CRAB leads to endemicity in hospitals and regions. The close association between antibiotic resistance genes and clades, and between plasmids and STs, suggest that de novo creation of MDR A. baumannii is rare. The clustering of antibiotic resistance genes and plasmids that is unique to each clade/ST, and nearly uniform within clades/STs, suggests that horizontal transmission is rare but crucial to the clade’s/ST’s success.
Research Progress on Preparation, Mechanism, and Clinical Application of Nanofat
Authors: Ding Pengbing , Lu Enhang , Li Guan , Sun Yidan , Yang Wenhui , Zhao Zhenmin
Published: January 2022

Autologous adipose tissue is an ideal soft tissue filling material in theory, which has the advantages of easy access, comprehensive source, and high biocompatibility and is now widely used in clinical practice. Based on the above benefits of autologous fat, autologous fat grafting is an essential technique in plastic surgery. Conventional macrofat is used to improve structural changes after soft tissue damage or loss caused by various causes such as disease, trauma, or aging. Due to the large diameter of particles and to avoid serious complications such as fat embolism, blunt needles with larger diameters (2 mm) are required, making the macrofat grafting difficult to the deep dermis and subdermis. Nanofat grafting is a relatively new technology that has gained popularity in cosmetic surgery in recent years. Nanofat is produced by mechanical shuffling and filtration of microfat, which is harvested by liposuction. The harvesting and processing of nanofat are cost-effective as it does not require additional equipment or culture time. Unlike microfat, nanofat particles are too small to provide a notable volumizing effect. Studies have shown that nanofat contains abundant stromal vascular fraction cells and adipose-derived stem cells, which help reconstruct dermal support structures, such as collagen, and regenerate healthier, younger-looking skin. Moreover, the fluid consistency of nanofat allows application in tissue regeneration, such as scars, chronic wounds, and facial rejuvenation. This article reviews the current research progress on the preparation, mechanism, and clinical application of nanofat.
A topology optimization approach to structure design with self-supporting constraints in additive manufacturing
Authors: Wu Zijun , Xiao Renbin
Published: January 2022

The manufacturability model of complex structure is the premise of manufacturing, and it is necessary to consider material properties, structure design, manufacturing constraints, and so on. However, due to the inconsistent restrictions between design and manufacturing, it is not easy to obtain the manufacturable structure that matches its design performance using layer-wise manufacturing. This paper presents a topology optimization method for manufacturable form, which incorporates the self-supporting factors such as overhang angle and length based on the characteristics of the generic additive manufacturing process. The support relationship between the supporting and supported elements in self-supporting constraints is mapped to a cascade relationship between two adjacent layers. To avoid a low-density structure supporting multiple high-density ingredients, we establish a fabrication model using the smax and smin operators. Also, the sensitivity analysis and variable updating method are given under the Solid Isotropic Material with Penalization method. Furthermore, numerical examples are shown to validate the correctness and superiority of this proposed self-supporting structure design method.
Deep learning-guided attenuation correction in the image domain for myocardial perfusion SPECT imaging
Authors: Mostafapour Samaneh , Gholamiankhah Faeze , Maroufpour Sirwan , Momennezhad Mehdi , Asadinezhad Mohsen , Zakavi Seyed Rasoul , Arabi Hossein , Zaidi Habib
Published: January 2022

We investigate the accuracy of direct attenuation correction (AC) in the image domain for myocardial perfusion SPECT (single-photon emission computed tomography) imaging (MPI-SPECT) using residual (ResNet) and UNet deep convolutional neural networks. MPI-SPECT 99mTc-sestamibi images of 99 patients were retrospectively included. UNet and ResNet networks were trained using non-attenuation-corrected SPECT images as input, whereas CT-based attenuation-corrected (CT-AC) SPECT images served as reference. Chang’s calculated AC approach considering a uniform attenuation coefficient within the body contour was also implemented. Clinical and quantitative evaluations of the proposed methods were performed considering SPECT CT-AC images of 19 subjects (external validation set) as reference. Image-derived metrics, including the voxel-wise mean error (ME), mean absolute error, relative error, structural similarity index (SSI), and peak signal-to-noise ratio, as well as clinical relevant indices, such as total perfusion deficit (TPD), were utilized. Overall, AC SPECT images generated using the deep learning networks exhibited good agreement with SPECT CT-AC images, substantially outperforming Chang’s method. The ResNet and UNet models resulted in an ME of −6.99 ± 16.72 and −4.41 ± 11.8 and an SSI of 0.99 ± 0.04 and 0.98 ± 0.05, respectively. Chang’s approach led to ME and SSI of 25.52 ± 33.98 and 0.93 ± 0.09, respectively. Similarly, the clinical evaluation revealed a mean TPD of 12.78 ± 9.22% and 12.57 ± 8.93% for ResNet and UNet models, respectively, compared to 12.84 ± 8.63% obtained from SPECT CT-AC images. Conversely, Chang’s approach led to a mean TPD of 16.68 ± 11.24%. The deep learning AC methods have the potential to achieve reliable AC in MPI-SPECT imaging.
Heritable genome editing and cognitive biases: why broad societal consensus is the wrong standard for moving forward
Authors: Macintosh Kerry Lynn
Published: January 2022

Heritable genome editing (HGE) may one day safely correct mutations that cause serious monogenic diseases. Nevertheless, some scientists and bioethicists argue that HGE should be subject to a moratorium. In their view, no nation should proceed with clinical use absent broad societal consensus in favor of moving forward with HGE and a specific use. This article critiques this plan in light of two cognitive biases. First, human beings favor the status quo. We are primed to favor human reproduction and the human genome in their current forms and resist HGE. Second, human beings also dwell on negative information. Dr He Jiankui’s unethical and premature experiment encourages us to judge HGE and its offspring harshly. By reinforcing these biases, the proposed moratorium would make it difficult to achieve broad societal consensus in support of using HGE even to correct dangerous mutations. As an alternative, this article recommends HGE be regulated for safety and efficacy. This approach will keep scientists from using HGE prematurely, while giving society time to discuss this new technology and enact further legislation if necessary.
The Dynamics of the Debate About Gay Rights: Evidence from US Newspapers
Authors: Manning Alan , Masella Paolo
Published: January 2022

Changing attitudes are the result of a battle for hearts and minds in which agents for and against change try to persuade others. We know very little about this process. We develop a methodology for measuring the intensity and the contents of media coverage for and against an idea which we apply to attitudes to gay rights. We uncover several stylized facts: First, the diffusion process of both pro- and anti-gay rights language in the US newspapers follow an S-shaped pattern, characteristic of diffusion processes. Anti-gay rights coverage starts its diffusion process later but then catches up. Second, in the year gay marriages are introduced, we observe a dramatic increase in coverage of both pro- and anti-gay rights language; the increase in the latter is larger. The rise in coverage is still present in the 3 years after the institutional change. Third, there is substantial spatial autocorrelation in media coverage (JEL J15, Z1).
Risk Stratification for Early-Onset Colorectal Cancer Using a Combination of Genetic and Environmental Risk Scores: An International Multi-Center Study
Authors: Archambault Alexi N , Jeon Jihyoun , Lin Yi , Thomas Minta , Harrison Tabitha A , Bishop D Timothy , Brenner Hermann , Casey Graham , Chan Andrew T , Chang-Claude Jenny , Figueiredo Jane C , Gallinger Steven , Gruber Stephen B , Gunter Marc J , Guo Feng , Hoffmeister Michael , Jenkins Mark A , Keku Temitope O , Le Marchand Loïc , Li Li , Moreno Victor , Newcomb Polly A , Pai Rish , Parfrey Patrick S , Rennert Gad , Sakoda Lori C , Lee Jeffrey K , Slattery Martha L , Song Mingyang , Win Aung Ko , Woods Michael O , Murphy Neil , Campbell Peter T , Su Yu-Ru , Lansdorp-Vogelaar Iris , Peterse Elisabeth F P , Cao Yin , Zeleniuch-Jacquotte Anne , Liang Peter S , Du Mengmeng , Corley Douglas A , Hsu Li , Peters Ulrike , Hayes Richard B
Published: January 2022

Background

The incidence of colorectal cancer (CRC) among individuals aged younger than 50 years has been increasing. As screening guidelines lower the recommended age of screening initiation, concerns including the burden on screening capacity and costs have been recognized, suggesting that an individualized approach may be warranted. We developed risk prediction models for early-onset CRC that incorporate an environmental risk score (ERS), including 16 lifestyle and environmental factors, and a polygenic risk score (PRS) of 141 variants.

Methods

Relying on risk score weights for ERS and PRS derived from studies of CRC at all ages, we evaluated risks for early-onset CRC in 3486 cases and 3890 controls aged younger than 50 years. Relative and absolute risks for early-onset CRC were assessed according to values of the ERS and PRS. The discriminatory performance of these scores was estimated using the covariate-adjusted area under the receiver operating characteristic curve.

Results

Increasing values of ERS and PRS were associated with increasing relative risks for early-onset CRC (odds ratio per SD of ERS = 1.14, 95% confidence interval [CI] = 1.08 to 1.20; odds ratio per SD of PRS = 1.59, 95% CI = 1.51 to 1.68), both contributing to case-control discrimination (area under the curve = 0.631, 95% CI = 0.615 to 0.647). Based on absolute risks, we can expect 26 excess cases per 10 000 men and 21 per 10 000 women among those scoring at the 90th percentile for both risk scores.

Conclusions

Personal risk scores have the potential to identify individuals at differential relative and absolute risk for early-onset CRC. Improved discrimination may aid in targeted CRC screening of younger, high-risk individuals, potentially improving outcomes.
Patient Decision-Making Factors in Aggressive Treatment of Low-Risk Prostate Cancer
Authors: Basak Ramsankar , Usinger Deborah S , Chen Ronald C , Shen Xinglei
Published: January 2022

Background

Active surveillance (AS) is underutilized for low-risk prostate cancer. This study examines decision-making factors associated with AS vs aggressive treatment in a population-based cohort of low-risk patients.

Methods

Newly diagnosed patients (n = 599) were enrolled through the North Carolina Central Cancer Registry from 2011 to 2013 and surveyed regarding 5 factors that may impact treatment decision making: perceived cancer aggressiveness, aggressiveness of treatment intent, most important goal (eg, cure, quality of life), primary information source, and primary decision maker. We examined the association between treatment decision-making factors with patient choice for AS vs aggressive treatment using multivariable logistic regression analysis.

Results

This is a sociodemographically diverse cohort reflective of the population-based design, with 37.6% overall (47.6% among very low-risk patients) choosing AS. Aggressive treatment intent (odds ratio [OR] = 7.09, 95% confidence interval [CI] = 4.57 to 11.01), perceived cancer aggressiveness (OR = 4.93, 95% CI = 2.71 to 8.97), most important goal (cure vs other, OR = 1.72, 95% CI = 1.12 to 2.63), and primary information source (personal and family vs physician, OR = 1.76, 95% CI = 1.10 to 2.82) were associated with aggressive treatment. Overall, 88.4% of patients (92.2% among very low-risk) who indicated an intent to treat the cancer “not very aggressively” chose AS.

Conclusions

These data from the patient’s perspective shed new light on potentially modifiable factors that can help further increase AS uptake among low-risk patients. Helping more low-risk patients feel comfortable with a “not very aggressive” treatment approach may be especially important, which can be facilitated through patient education interventions to improve the understanding of the cancer diagnosis and AS having a curative intent.
Biotic effects dominate the inter-annual variability in ecosystem carbon exchange in a Tibetan alpine meadow
Authors: Xu Mingjie , Sun Yi , Zhang Tao , Zhang Yangjian , Zhu Juntao , He Yongtao , Wang Liwei , Yu Guirui
Published: January 2022

The alpine meadow ecosystem in Tibet is fragile and sensitive, and its carbon sink function with respect to climate change has become a matter of widespread concern. Therefore, this study aims to clarify the inter-annual variations (IAVs) in the carbon fluxes in an alpine meadow and to further quantify the contributions of the driving factors to the IAVs. Based on 7 years of flux data (2012–2018) and the corresponding climatic and biotic data, a set of look-up tables was used to separate and quantify the IAV sources. Furthermore, linear perturbation analyses were employed to quantify the contributions of each key factor. During 2012–2018, the net ecosystem productivity (NEP), gross primary productivity (GPP) and ecosystem respiration (Re) of this alpine meadow were 3.31 ± 26.90, 210.18 ± 48.35 and 206.88 ± 28.45 g C m−2 y−1, respectively, which indicated relatively large IAVs. When the contributions of climatic and biotic effects were distinguished and quantified, the dominant effects of biotic factors emerged. Additionally, negative interactions between climatic and biotic effects were detected. Among the climatic factors, only soil water content contributed relatively more to the IAVs and played a role in regulating the interactions between climatic and biotic effects. These results suggest that biotic effects must be carefully considered to reduce the uncertainties associated with future carbon flux estimates.
Complicated jejunal diverticulosis with intestinal perforation and obstruction: delay in hospital visit during confinement due to COVID-19
Authors: Ponce Beti María S , Palacios Huatuco René M , Picco Santiago , Capra Alejandro E , Perussia Daniel G , Suizer Alejando M
Published: January 2022

Diverticulosis of the small bowel is a rare entity. It can cause acute, complications such as diverticulitis, perforation, intestinal bleeding and obstruction. During the pandemic, patients were reluctant to visit hospitals for fear of contracting coronavirus disease 2019. This caused the patients to wait until the extreme deterioration of many acute surgical conditions. An 83-year-old man with multiple comorbidities showed up at the emergency department with generalized abdominal pain of 7 days of evolution. The computed tomography scan revealed a large distention of the small intestine and a small inflammatory abscess. He was transferred to the operating room where a segment of the jejunum affected by multiple diverticula located on the mesenteric side of the intestine and a mesenteric abscess related to a perforated jejunal diverticulum were identified. Complicated jejunal diverticulosis is a difficult entity to diagnose, which can cause significant morbidity and mortality. To avoid this, its timely diagnosis is essential.
“Nothing Made Them Change Their Minds about the Medical Industry”: Medical Abuse, Incarceration, and Healing in Toni Morrison’sHome
Authors: Allen Patrick S
Published: January 2022

Toni Morrison’s Home (2012) takes up issues of (anti-)Blackness, eugenics, and the healing powers of communities of Black women. In the novel, Cee, the protagonist’s sister, is hired as a “helper” (explicitly not a “nurse”) for a white eugenicist. Cee is essentially incarcerated at the doctor’s home office, where she is reduced to a sort of living cadaver upon whom the doctor experiments, leaving her unable to bear children. Upon being rescued from the doctor, Cee is nurtured back to health by a community of lay Black women in the South. Morrison’s novel critiques a history of anti-Black racism in the medical field that has situated Black persons (especially Black women) as particularly susceptible to abuse, malpractice, and incomplete or nonexistent care. I situate my discussion of Home alongside an exploration of forced sterilizations of incarcerated Black and Latinx women in US corrections facilities to illustrate Morrison’s illumination of historical and ongoing racial injustices in the entangled US medical, legal, and military systems. This essay explores the modes by which communities of Black women practice an ethics of care for one another and collectively resist anti-Black biopolitical systems. In taking on the role of healers, the Black women in this novel deny white attempts at control over Black persons’ bodies, lives, and reproduction. Morrison’s novel instead presents a move toward Black liberation, care, and safety that sets the stage for thinking about contemporary health and legal issues—namel,y anti-Black racism and the disproportionality of negative outcomes for Black persons in US medical systems.
Air Pollution Exposure and the Development of Chronic Rhinosinusitis in the Active Duty Population
Authors: Elam Trevor , Raiculescu Sorana , Biswal Shyam , Zhang Zhenyu , Orestes Michael , Ramanathan Murugappan
Published: January 2022

Introduction

It has been shown that combat environment exposure, including burn pits that produce particulate matter 2.5 (PM2.5), is associated with lower respiratory tract disease in the military population with increased hypothetical risk of upper respiratory disease, but no study has been done that examines the effects of non-combat environmental exposures on the development of chronic rhinosinusitis (CRS) in the active duty population. The primary goal of this study is to evaluate how air pollution exposure correlates to the development of CRS in active duty service members in the United States.

Methods

The military electronic medical record was queried for active duty service members diagnosed with CRS by an otolaryngologist between January 2016 and January 2018, who have never deployed, stationed in the United States from 2015 to 2018 (n = 399). For each subject, the 1-year mean exposure of PM2.5, particulate matter 10 (PM10), nitrogen dioxide (NO2), and ozone was calculated. The control group was comprised of the same criteria except these patients were diagnosed with cerumen impaction and matched to the case group by age and gender (n = 399). Pollution exposure was calculated based on the Environmental Protection Agency’s data tables for each subject. Values were calculated using chi-square test for categorical variables and the Mann–Whitney U-test for continuous variables.

Results

Matched cases and controls (n = 399) with 33.1% male showed a statistically significant odds ratio (OR) of 5.99 (95% CI, 2.55-14.03) for exposure of every 5 µg/m3 of PM2.5 increase and the development of CRS when controlling for age, gender, and diagnosis year. When further adjusting for smoking status, the OR was still statistically significant at 3.15 (95% CI, 1.03-9.68). Particulate matter 10, ozone, and NO2 did not show any statistical significance. Odds ratios remained statistically significant when further adjusting for PM10 and ozone, but not NO2. Dose-dependent curves largely did not show a statistical significance; however, they did trend towards increased exposure of PM2.5 leading to an elevated OR.

Conclusion

This study showed that PM2.5 exposure is a major independent contributor to the development of CRS. Exposure to elevated levels produced statistically significant odds even among smokers and remained significant when controlling for other measured pollutants. There is still much to be understood about the genesis of CRS. From a pollution exposure perspective, a prospective cohort study would better elucidate the risk of the development of CRS among those exposed to other pollutants.
The Gravitational-wave Optical Transient Observer (GOTO): prototype performance and prospects for transient science
Authors: Steeghs D , Galloway D K , Ackley K , Dyer M J , Lyman J , Ulaczyk K , Cutter R , Mong Y-L , Dhillon V , O’Brien P , Ramsay G , Poshyachinda S , Kotak R , Nuttall L K , Pallé E , Breton R P , Pollacco D , Thrane E , Aukkaravittayapun S , Awiphan S , Burhanudin U , Chote P , Chrimes A , Daw E , Duffy C , Eyles-Ferris R , Gompertz B , Heikkilä T , Irawati P , Kennedy M R , Killestein T , Kuncarayakti H , Levan A J , Littlefair S , Makrygianni L , Marsh T , Mata-Sanchez D , Mattila S , Maund J , McCormac J , Mkrtichian D , Mullaney J , Noysena K , Patel M , Rol E , Sawangwit U , Stanway E R , Starling R , Strøm P , Tooke S , West R , White D J , Wiersema K
Published: January 2022

The Gravitational-wave Optical Transient Observer (GOTO) is an array of wide-field optical telescopes, designed to exploit new discoveries from the next generation of gravitational wave detectors (LIGO, Virgo, and KAGRA), study rapidly evolving transients, and exploit multimessenger opportunities arising from neutrino and very high energy gamma-ray triggers. In addition to a rapid response mode, the array will also perform a sensitive, all-sky transient survey with few day cadence. The facility features a novel, modular design with multiple 40-cm wide-field reflectors on a single mount. In 2017 June, the GOTO collaboration deployed the initial project prototype, with 4 telescope units, at the Roque de los Muchachos Observatory (ORM), La Palma, Canary Islands. Here, we describe the deployment, commissioning, and performance of the prototype hardware, and discuss the impact of these findings on the final GOTO design. We also offer an initial assessment of the science prospects for the full GOTO facility that employs 32 telescope units across two sites.
Stellar winds and photoionization in a spiral arm
Authors: Ali Ahmad A , Bending Thomas J R , Dobbs Clare L
Published: January 2022

The role of different stellar feedback mechanisms in giant molecular clouds is not well understood. This is especially true for regions with many interacting clouds as would be found in a galactic spiral arm. In this paper, building on previous work by Bending et al., we extract a $500{\, \mathrm{pc}}\times 500{\, \mathrm{pc}}\times {100}{\, \mathrm{pc}}$ section of a spiral arm from a galaxy simulation. We use smoothed particle hydrodynamics to re-simulate the region at higher resolution (1 M⊙ per particle). We present a method for momentum-driven stellar winds from main-sequence massive stars, and include this with photoionization, self-gravity, a galactic potential, and interstellar medium heating/cooling. We also include cluster-sink particles with accretion radii of 0.78 pc to track star/cluster formation. The feedback methods are as robust as previous models on individual cloud scales (e.g. Dale et al.). We find that photoionization dominates the disruption of the spiral arm section, with stellar winds only producing small cavities (at most ∼30 pc). Stellar winds do not affect the resulting cloud statistics or the integrated star formation rate/efficiency, unlike ionization, which produces more stars, and more clouds of higher density and higher velocity dispersion compared to the control run without feedback. Winds do affect the sink properties, distributing star formation over more low-mass sinks (∼102 M⊙) and producing fewer high-mass sinks (∼103 M⊙). Overall, stellar winds play at best a secondary role compared to photoionization, and on many measures, they have a negligible impact.
A full spectral-timing model to map the accretion flow in black hole binaries: the low/hard state of MAXI J1820+070
Authors: Kawamura Tenyo , Axelsson Magnus , Done Chris , Takahashi Tadayuki
Published: January 2022

The nature and geometry of the accretion flow in the low/hard state of black hole binaries is currently controversial. While most properties are generally explained in the truncated disc/hot inner flow model, the detection of a broad residual around the iron line argues for strong relativistic effects from an untruncated disc. Since spectral fitting alone is somewhat degenerate, we combine it with the additional information in the fast X-ray variability and perform a full spectral-timing analysis for NICER and NuSTAR data on a bright low/hard state of MAXI J1820+070. We model the variability with propagating mass accretion rate fluctuations by combining two separate current insights: that the hot flow is spectrally inhomogeneous, and that there is a discontinuous jump in viscous time-scale between the hot flow and variable disc. Our model naturally gives the double-humped shape of the power spectra, and the increasing high-frequency variability with energy in the second hump. Including reflection and reprocessing from a disc truncated at a few tens of gravitational radii quantitatively reproduces the switch in the lag-frequency spectra, from hard lagging soft at low frequencies (propagation through the variable flow) to the soft lagging hard at the high frequencies (reverberation from the hard X-ray continuum illuminating the disc). The viscous time-scale of the hot flow is derived from the model, and we show how this can be used to observationally test ideas about the origin of the jet.
Constraining ultra light dark matter with the Galactic nuclear star cluster
Authors: Toguz Firat , Kawata Daisuke , Seabroke George , Read Justin I
Published: January 2022

We use the Milky Way’s nuclear star cluster (NSC) to test the existence of a dark matter ‘soliton core’, as predicted in ultra-light dark matter (ULDM) models. Since the soliton core size is proportional to $m_{\rm DM}^{-1}$, while the core density grows as $m_{\rm DM}^{2}$, the NSC (dominant stellar component within ∼3 pc) is sensitive to a specific window in the dark matter particle mass, mDM. We apply a spherical isotropic Jeans model to fit the NSC line-of-sight velocity dispersion data, assuming priors on the precisely measured Milky Way’s supermassive black hole (SMBH) mass and the well-measured NSC density profile. We find that the current observational data reject the existence of a soliton core for a single ULDM particle with mass in the range 10−20.4 eV ≲ mDM ≲ 10−18.5 eV, assuming that the soliton core structure is not affected by the Milky Way’s SMBH. We test our methodology on mock data, confirming that we are sensitive to the same range in ULDM mass as for the real data. Dynamical modelling of a larger region of the Galactic centre, including the nuclear stellar disc, promises tighter constraints over a broader range of mDM. We will consider this in future work.
Dust distributions in the magellanic clouds
Authors: Chen B-Q , Guo H-L , Gao J , Yang M , Liu Y-L , Jiang B-W
Published: January 2022

We present high-resolution maps of the dust reddening in the Magellanic Clouds (MCs). The maps cover the Large and Small Magellanic Cloud (LMC and SMC) area and have a spatial angular resolution between ∼26 arcsec and 55 arcmin. Based on the data from the optical and near-infrared (IR) photometric surveys, including the Gaia Survey, the SkyMapper Southern Survey (SMSS), the Survey of the Magellanic Stellar History (SMASH), the Two Micron All Sky Survey (2MASS), and the near-IR YJKS VISTA survey of the Magellanic Clouds system (VMC), we have obtained multiband photometric stellar samples containing over 6 million stars in the LMC and SMC area. Based on the measurements of the proper motions and parallaxes of the individual stars from Gaia Early Data Release 3 (Gaia EDR3), we have built clean samples that contain stars from the LMC, SMC, and Milky Way (MW), respectively. We apply the spectral energy distribution (SED) fitting to the individual sample stars to estimate their reddening values. As a result, we have derived the best-fitting reddening values of ∼1.9 million stars in the LMC, 1.5 million stars in the SMC, and 0.6 million stars in the MW, which are used to construct dust reddening maps in the MCs. Our maps are consistent with those from the literature. The resultant high-resolution dust maps in the MCs are not only important tools for reddening correction of sources in the MCs, but also fundamental for the studies of the distribution and properties of dust in the two galaxies.
Faint intermediate luminosity optical transients (ILOTs) from engulfing exoplanets on the Hertzsprung gap
Authors: Gurevich Omer , Bear Ealeal , Soker Noam
Published: January 2022

We follow the evolution of four observed exoplanets to the time when the respective parent star of each planet evolves off the main sequence and engulfs its planet to start a common envelope evolution (CEE), concluding that in each case this process powers an intermediate luminosity optical transient (ILOT; luminous red nova). We characterize the final thousands of days of the orbital decay towards a CEE and determine the properties of the star at the onset of the CEE. We scale the properties of the ILOT V1309 Scorpii to the properties of a planet that enters a CEE inside a star on and near the Hertzsprung gap to estimate the duration and luminosity of the expected ILOT. Based on these, we estimate that for a planet of Jupiter mass the ILOT will last for several days and reach a luminosity of several thousand solar luminosity. This type of ILOTs are less luminous than classical novae. Because of the small amount of expected dust and the small amount of energy that an accretion process on to the planet can release, such ILOTs can teach us on the merger at the onset of CEE of stellar companions. Our study adds to the variety of ILOTs that planets can power as they interact with a more massive companion.
Role of the companion lensing galaxy in the CLASS gravitational lens B1152+199
Authors: Zhang M , Yuan Q , Liu J-Y , Zhang L
Published: January 2022

We reinvestigate the Cosmic Lens All-Sky Survey (CLASS) gravitational lens B1152+199 using archived Hubble Space Telescope (HST) data and Very Long Baseline Interferometry (VLBI) data. A consistent luminosity ratio within effective radius between the host galaxy and the X-galaxy is measured from HST tri-band images, which leads to a mass ratio between the two galaxies as rb ∼ 2. To determine the role of the X-galaxy in the lens system, we modelled the dual-lens system with constraints from the VLBI-resolved jet components and the HST images. The 8.4-GHz global-VLBI data currently provide the most stringent constraints to the mass model, especially to the radial power-law slope. The optimized models for this two-image three-component radio lens favour a steeper-than-isothermal inner slope. The jet bending in image B was also investigated and it turned out to be rather a misalignment than a curvature. The goodness-of-fit indicates that the role of the X-galaxy is crucial in the lens system if three pairs of resolved jet components are to be fitted. When we imported the optimal model from radio constraints to optical modelling with the HST tri-band data, the optimization kept the consistency of the optimal model and successfully reproduced the features observed in the HST images. This implies that the diffuse emission discovered in the HST images is actually a detection of the secondary lensing effects from the companion lens.
The Multiple-Computations Theorem and the Physics of Singling Out a Computation
Authors: Hemmo Meir , Shenker Orly
Published: January 2022

The problem of multiple-computations discovered by Hilary Putnam presents a deep difficulty for functionalism (of all sorts, computational and causal). We describe in outline why Putnam’s result, and likewise the more restricted result we call the Multiple-Computations Theorem, are in fact theorems of statistical mechanics. We show why the mere interaction of a computing system with its environment cannot single out a computation as the preferred one amongst the many computations implemented by the system. We explain why nonreductive approaches to solving the multiple-computations problem, and in particular why computational externalism, are dualistic in the sense that they imply that nonphysical facts in the environment of a computing system single out the computation. We discuss certain attempts to dissolve Putnam’s unrestricted result by appealing to systems with certain kinds of input and output states as a special case of computational externalism, and show why this approach is not workable without collapsing to behaviorism. We conclude with some remarks about the nonphysical nature of mainstream approaches to both statistical mechanics and the quantum theory of measurement with respect to the singling out of partitions and observables.
TRIM21 suppresses CHK1 activation by preferentially targeting CLASPIN for K63-linked ubiquitination
Authors: Zhu Xuefei , Xue Jingwei , Jiang Xing , Gong Yamin , Gao Congwen , Cao Ting , Li Qian , Bai Lulu , Li Yuwei , Xu Gaixia , Peng Bin , Xu Xingzhi
Published: January 2022

Expression of the E3 ligase TRIM21 is increased in a broad spectrum of cancers; however, the functionally relevant molecular pathway targeted by TRIM21 overexpression remains largely unknown. Here, we show that TRIM21 directly interacts with and ubiquitinates CLASPIN, a mediator for ATR-dependent CHK1 activation. TRIM21-mediated K63-linked ubiquitination of CLASPIN counteracts the K6-linked ubiquitination of CLASPIN which is essential for its interaction with TIPIN and subsequent chromatin loading. We further show that overexpression of TRIM21, but not a TRIM21 catalytically inactive mutant, compromises CHK1 activation, leading to replication fork instability and tumorigenesis. Our findings demonstrate that TRIM21 suppresses CHK1 activation by preferentially targeting CLASPIN for K63-linked ubiquitination, providing a potential target for cancer therapy.
Evaluation of Liver and Renal Toxicity in Peptide Receptor Radionuclide Therapy for Somatostatin Receptor Expressing Tumors: A 2-Year Follow-Up
Authors: Duan Heying , Ferri Valentina , Fisher George Albert , Shaheen Shagufta , Davidzon Guido Alejandro , Iagaru Andrei , Mari Aparici Carina
Published: January 2022

Background

Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin receptor (SSR) analogs is now an established systemic treatment for neuroendocrine tumors (NET). However, more short- and long-term data about renal and hepatotoxicity is needed. Here we present our experience in this clinical scenario.

Methods

Eighty-six patients with progressive SSR-expressing malignancies underwent PRRT with Lu-177 Dotatate and were followed up for up to 2 years. Laboratory tests were done 1 week before each cycle and every 2 months at follow-up. Hepatic and renal toxicity was determined based on NCI CTCAE V5.0.

Results

55/86 (64%) patients completed all 4 cycles of PRRT; 18/86 (20.9%) are currently being treated; 13/86 (15.1%) had to discontinue PRRT: 4/13 (31%) due to hematologic toxicity, 9/13 (69%) due to non-PRRT-related comorbidities. Out of the patients who finished treatment, only transient grade 2 toxicities were observed during PRRT: hypoalbuminemia in 5.5% (3/55), and renal toxicity (serum creatinine and estimated glomerular filtration rate) in 1.8% (1/55). No grade 3 or 4 liver and renal toxicity occurred. Patients presenting with impaired liver or renal function prior to PRRT, either improved or had stable findings. No deterioration was observed.

Conclusion

Peptide receptor radionuclide therapy does not have a negative impact on liver and renal function, even in patients with pre-existing impaired parameters. No grade 3 or 4 hepatic or renal toxicity was identified. Only transient grade 2 hypoalbuminemia in 5.5% and nephrotoxicity in 1.8% of patients were seen during PRRT.
Modeling the Cost-Effectiveness of Adjuvant Osimertinib for Patients with Resected EGFR-mutant Non-Small Cell Lung Cancer
Authors: Lemmon Christopher A , Zabor Emily C , Pennell Nathan A
Published: January 2022

Introduction

The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor osimertinib was recently approved for resected EGFR-mutant stages IB-IIIA non-small cell lung cancer due to improved disease-free survival (DFS) in this population compared with placebo. This study aimed to evaluate the cost-effectiveness (CE) of this strategy.

Materials and Methods

We constructed a Markov model using post-resection health state transitions with digitized DFS data from the ADAURA trial to compare cost and quality-adjusted life years (QALYs) of 3 years of adjuvant osimertinib versus placebo over a 10-year time horizon. An overall survival (OS) benefit of 5% was assumed. Costs and utility values were derived from Medicare reimbursement data and literature. A CE threshold of 3 times the gross domestic product per capita was used. Sensitivity analyses were performed.

Results

The incremental cost-effectiveness ratio for adjuvant osimertinib was $317 119 per QALY-gained versus placebo. Initial costs of osimertinib are higher in years 1-3. Costs due to progressive disease (PD) are higher in the placebo group through the first 6.5 years. Average pre-PD, post-PD, and total costs were $2388, $379 047, and $502 937, respectively, in the placebo group, and $505 775, $255 638, and $800 697, respectively, in the osimertinib group. Sensitivity analysis of OS gains reaches CE with an hazard ratio (HR) of 0.70-0.75 benefit of osimertinib over placebo. A 50% discount to osimertinib drug cost yielded an ICER of $115 419.

Conclusions

Three-years of adjuvant osimertinib is CE if one is willing to pay $317 119 more per QALY-gained. Considerable OS benefit over placebo or other economic interventions will be needed to reach CE.
Isotemporal Substitution of Sedentary Behavior With Moderate to Vigorous Physical Activity Is Associated With Lower Risk of Disability: A Prospective Longitudinal Cohort Study
Authors: Chiba Ippei , Lee Sangyoon , Bae Seongryu , Makino Keitaro , Shinkai Yohei , Katayama Osamu , Harada Kenji , Yamashiro Yukari , Takayanagi Naoto , Shimada Hiroyuki
Published: January 2022

Objective

The purpose of the study was to estimate, using an isotemporal substitution model, the effect of replacing sedentary behavior (SB) with physical activity on the incidence of disability in community-dwelling older adults.

Methods

This 2-year longitudinal cohort study enrolled 3691 community-dwelling older adults (57.2% women; mean age = 74.0 [SD = 5.0] years). Individuals with dementia, stroke, Parkinson disease, depression, low Mini-Mental State Examination scores, dependence on basic activities of daily living, and missing data were excluded. Physical activity and potential confounding factors were investigated as a baseline survey of disability incidence, defined by Japanese long-term care insurance certification, for 2 years in 2 regions. Physical activity data (SB, light-intensity physical activity, and moderate- to vigorous-intensity physical activity [MVPA]) were measured using triaxial accelerometers for 14 days, and daily mean time spent in each physical activity parameter was computed in increments of 10 minutes. The relationship between baseline physical activity and disability incidence adjusted for potential confounders was analyzed using multilevel Cox proportional hazards regression analyses with an isotemporal substitution model.

Results

The disability incidence rate was 3.8%, excluding individuals who could not be followed-up. Replacing 10 minutes of SB per day with MVPA was associated with a decreased disability incidence (hazard ratio = 0.870; 95% CI = 0.766–0.988), whereas no evidence was found for replacing SB with light-intensity physical activity (hazard ratio = 0.980; 95% CI = 0.873–1.10).

Conclusions

Replacing SB with MVPA was associated with a lower risk of disability. These findings are helpful for establishing disability prevention strategies.

Impact

These results suggest that feasible changes in daily behavior, such as replacing 10 minutes of SB with MVPA daily, might have a protective effect on disability incidence. Clarifying these associations is useful for developing disability prevention strategies and may help reduce the incidence of disability in community-dwelling older adults.
Rapid antigen testing in COVID-19 management for school-aged children: an observational study in Cheshire and Merseyside, UK
Authors: Hughes David M , Bird Sheila M , Cheyne Christopher P , Ashton Matthew , Campbell Melisa C , García-Fiñana Marta , Buchan Iain
Published: January 2022

Background

Twice weekly lateral flow tests (LFTs) for secondary school children was UK Government policy from 8 March 2021. We evaluate use of LFTs (both supervised at test centres, and home test kits) in school-aged children in Cheshire and Merseyside.

Methods

We report (i) number of LFT positives (ii) proportion of LFT positive with confirmatory reverse transcription polymerase chain reaction (PCR) test within 2 days, and (iii) agreement between LFT-positive and confirmatory PCR, and dependence of (i–iii) on COVID-19 prevalence.

Findings

1 248 468 LFTs were taken by 211 255 12–18 years old, and 163 914 by 52 116 5–11 years old between 6 November 2020 and 31 July 2021. Five thousand three hundred and fourteen (2.5%) 12–18 years old and 1996 (3.8%) 5–11 years old returned LFT positives, with 3829 (72.1%) and 1535 (76.9%) confirmatory PCRs, and 3357 (87.7%) and 1383 (90.1%) confirmatory PCR-positives, respectively.

Monthly proportions of LFT positive with PCR negative varied between 4.7% and 35.3% in 12–18 years old (corresponding proportion of all tests positive: 9.7% and 0.3%).

Deprivation and non-White ethnicity were associated with reduced uptake of confirmatory PCR.

Interpretation

Substantial inequalities in confirmatory testing need more attention to avoid further disadvantage through education loss. When prevalence is low additional measures, including confirmatory testing, are needed. Local Directors of Public Health taking more control over schools testing may be needed.

Funding

DHSC, MRC, NIHR, EPSRC.
A Runx1-enhancer Element eR1 Identified Lineage Restricted Mammary Luminal Stem Cells
Authors: Matsuo Junichi , Mon Naing Naing , Douchi Daisuke , Yamamura Akihiro , Kulkarni Madhura , Heng Dede Liana , Chen Sabirah , Nuttonmanit Napat , Li Ying , Yang Henry , Lee May Yin , Tam Wai Leong , Osato Motomi , Chuang Linda Shyue Huey , Ito Yoshiaki
Published: January 2022

Mammary gland homeostasis is maintained by adult tissue stem-progenitor cells residing within the luminal and basal epithelia. Dysregulation of mammary stem cells is a key mechanism for cancer development. However, stem cell characterization is challenging because reporter models using cell-specific promoters do not fully recapitulate the mammary stem cell populations. We previously found that a 270-basepair Runx1 enhancer element, named eR1, marked stem cells in the blood and stomach. Here, we identified eR1 activity in a rare subpopulation of the ERα-negative luminal epithelium in mouse mammary glands. Lineage-tracing using an eR1-CreERT2 mouse model revealed that eR1+ luminal cells generated the entire luminal lineage and milk-secreting alveoli—eR1 therefore specifically marks lineage-restricted luminal stem cells. eR1-targeted-conditional knockout of Runx1 led to the expansion of luminal epithelial cells, accompanied by elevated ERα expression. Our findings demonstrate a definitive role for Runx1 in the regulation of the eR1-positive luminal stem cell proliferation during mammary homeostasis. Our findings identify a mechanistic link for Runx1 in stem cell proliferation and its dysregulation in breast cancer. Runx1 inactivation is therefore likely to be an early hit in the cell-of-origin of ERα+ luminal type breast cancer.
Effects of a dry acidulant addition to prevent Salmonella contamination in poultry feed
Authors: Jeffrey Andrea M , Aldrich Greg C , Huss Anne R , Knueven Carl , Jones Cassandra K , Zumbaugh Charles A
Published: January 2022

Salmonella subs. serovar Enteritidis is a potential biological pathogen of concern in the poultry industry. Contamination of the bacterium on eggshells has led to human illnesses. With the implementation of new regulations, animal feed manufacturing continues to be under more stringent requirements. Specifically, there is zero tolerance for Salmonella Pullorum, Gallinarum, or Enteritidis in poultry feed. For this reason, it is important to determine an effective method of reducing or preventing Salmonella contamination in feed for poultry. Therefore, the objective of this study was to evaluate the impact of sodium bisulfate (SBS; Jones-Hamilton, Co., Walbridge, OH) added to poultry mash to reduce or prevent Salmonella growth over time. A single, commercially produced all-flock poultry mash was mixed with four different levels of SBS: 0.0%, 0.25%, 0.50%, and 0.70%. After SBS addition, the treated mash was inoculated with Salmonella enterica subsp, enterica serovar Enteritidis (ATCC 13076) and enumerated for Salmonella on days 0, 1, 2, 7, and 14 post-inoculation by plating on xylose lysine deoxycholate agar. There was no significant effect of SBS inclusion level on the reduction of Salmonella (P = 0.23); however, there was a significant effect of time across treatments (P < 0.0001). Additionally, there was no inclusion level × time interaction (P = 0.68). These results suggest that while SBS inclusion has no effect on Salmonella concentrations, storage time is effective at reducing or eliminating Salmonella contamination in poultry feed.