bluuebunny/crossref_metadata_2025 huggingface dataset:
Resolution criteria to avoid artificial clumping in Lagrangian hydrodynamic simulations with a multiphase interstellar medium
Authors: Ploeckinger Sylvia , Nobels Folkert S J , Schaller Matthieu , Schaye Joop
Published: December 2023

Large-scale cosmological galaxy formation simulations typically prevent gas in the interstellar medium (ISM) from cooling below $\approx 10^4\, \mathrm{K}$. This has been motivated by the inability to resolve the Jeans mass in molecular gas ($\ll 10^5\, \mathrm{M}_{\odot }$) which would result in undesired artificial clumping. We show that the classical Jeans criteria derived for Newtonian gravity are not applicable in the simulated ISM if the spacing of resolution elements representing the dense ISM is below the gravitational force softening length and gravity is therefore softened and not Newtonian. We re-derive the Jeans criteria for softened gravity in Lagrangian codes and use them to analyse gravitational instabilities at and below the hydrodynamical resolution limit for simulations with adaptive and constant gravitational softening lengths. In addition, we define criteria for which a numerical runaway collapse of dense gas clumps can occur caused by oversmoothing of the hydrodynamical properties relative to the gravitational force resolution. This effect is illustrated using simulations of isolated disc galaxies with the smoothed particle hydrodynamics code swift. We also demonstrate how to avoid the formation of artificial clumps in gas and stars by adjusting the gravitational and hydrodynamical force resolutions.
The dynamical state of bars in cluster dwarf galaxies: the cases of NGC 4483 and NGC 4516
Authors: Cuomo Virginia , Morelli Lorenzo , Aguerri J Alfonso L , Corsini Enrico Maria , Debattista Victor P , Coccato Lodovico , Pizzella Alessandro , Boselli Alessandro , Buttitta Chiara , de Lorenzo-Cáceres Adriana , Ferrarese Laura , Gasparri Daniele , Lee Yun Hee , Mendez-Abreu Jairo , Roediger Joel , Zarattini Stefano
Published: December 2023

Dwarf barred galaxies are the perfect candidates for hosting slowly rotating bars. They are common in dense environments and have a relatively shallow potential well, making them prone to heating by interactions. When an interaction induces bar formation, the bar should rotate slowly. They reside in massive and centrally concentrated dark matter haloes, which slow down the bar rotation through dynamical friction. While predictions suggest that slow bars should be common, measurements of bar pattern speed, using the Tremaine–Weinberg method, show that bars are mostly fast in the local Universe. We present a photometric and kinematic characterization of bars hosted by two dwarf galaxies in the Virgo Cluster, NGC 4483, and NGC 4516. We derive the bar length and strength using the Next Generation Virgo Survey imaging and the circular velocity, bar pattern speed, and rotation rate using spectroscopy from the Multi-Unit Spectroscopic Explorer. Including the previously studied galaxy IC 3167, we compare the bar properties of the three dwarf galaxies with those of their massive counterparts from literature. Bars in the dwarf galaxies are shorter and weaker, and rotate slightly slower with respect to those in massive galaxies. This could be due to a different bar formation mechanism and/or to a large dark matter fraction in the centre of dwarf galaxies. We show that it is possible to push the application of the Tremaine–Weinberg method to the galaxy low-mass regime.
Multitechnique study of the B[e] supergiant RMC 82
Authors: Seriacopi D B , Carciofi A C , de Amorim T H , Magalhães A M , Vieira R G , de Souza A Domiciano , Rubio A , Rubinho M S , Bednarski D , Mota B C , Faes D M , Silva A C F
Published: December 2023

B[e] supergiants (sgB[e]) are rare objects whose evolutionary stage remains uncertain. Observationally, they display strong Balmer emission lines, infrared excess, and intrinsic polarization, indicating a non-spherical circumstellar envelope. We present a study of the sgB[e] RMC 82, using new spectropolarimetric data complemented by photometry from the ultraviolet (UV) to the mid-infrared. Our two-component model comprises a slow, dense equatorial wind wherein dust grains form and a fast polar wind. We applied the hdust radiative transfer code and Bayesian statistics to infer the parameters from a grid of 3240 pre-computed models. The model accurately reproduces the spectral energy distribution and polarized spectrum, but struggles to match the H α emission. Our results suggest a large mass-loss rate of $6.6 \times 10^{-6}\, \mathrm{{\rm M}_{\odot }\, yr^{-1}\, sr^{-1}}$. The dense wind is confined within an opening angle of 11°. The hottest dust grains are located at 277 R* with a temperature of 870 K. The dust grains are porous, with a density of 0.051 $\rm {g\, cm^{-3}}$. The central star was found to be significantly hotter than previous estimates (Teff = $27\, 000$ K). By comparing models with different components, we find that gas reprocesses a significant amount of UV radiation, shielding the dust. However, the dust also scatters UV photons back to the inner disc, increasing its temperature and H α emission. We conclude that self-consistent models, that account for the gas–dust interplay in the envelope, are essential for studying sgB[e] and similar objects.
X-ray polarization changes with the state transition in Cygnus X–1
Authors: Jana Arghajit , Chang Hsiang-Kuang
Published: December 2023

We studied the polarization properties of Cygnus X–1 in both hard and soft spectral states with imaging X-ray polarimetry explorer (IXPE) observations. The polarization degree is $\sim 4~{{\ \rm per\ cent}}$, and $\sim 2.6-2.8~{{\ \rm per\ cent}}$ in the hard and soft states, respectively. The polarization angle is observed along the jet axis and remains the same in both states. Energy-dependent analysis revealed an increasing polarization with the energy. The observed polarization rules out the lamp-post corona and prefers a conical corona if the coronal geometry remains the same in the hard and soft states. The disc is not detected in the hard state but is found in the soft state in the IXPE spectra. The spectral analysis revealed that the disc emission contributes $\sim 20~{{\ \rm per\ cent}}$ of the total emission in the soft state. The scattering of the seed photons inside the corona is likely to reduce the polarization. This could explain the different polarization in different spectral states. Additionally, if the disc polarization is perpendicular to that of the corona, it could also reduce the polarization in the soft state.
Long-slit spectral study of the unusual post-interacting galaxy Arp 263
Authors: Zasov Anatoly V , Saburova Anna S , Egorov Oleg V , Lander Vsevolod Yu , Afanasiev Victor L , Uklein Roman I
Published: December 2023

Arp 263 is a single irregularly shaped galaxy with intense star formation. Its short tidal features of low brightness visible in both optics and the H i line, as well as the strong non-circular motion of atomic gas in the outskirts, give pieces of evidence of a recent merging with some intruder, non-observed directly. We carried out spectral observations of this galaxy at the 6 m telescope of the Special Astrophysical Observatory. The spectra for three positions of the spectral slit were obtained: two of them cross the central region of the galaxy and the third one runs along the nearly straight narrow chain of clumps of emission gas with a length of 4–5 kpc. We derived the profiles of velocity, fluxes, and oxygen abundances (O/H) along the slits. We confirm that within the radius of several kpc the galaxy rotates regularly. The maximal value of the rotational velocity allows us to conclude that the dark mass of the galaxy prevails over the mass of its visible components. The observed velocity profile along the peripheral star-forming chain gives pieces of evidence that it is located outside of the plane of the disc, and the gas that formed the chain is probably falling back on to the disc after being ejected from the galaxy. We discuss that the observed chain of clumps is the result of gravitational instability of the gaseous filament.
Thirty-year overview of Japanese autopsy cases of Takayasu arteritis – Results of analysis of Japanese autopsy reports
Authors: Yokouchi Yuki , Asakawa Nanae , Oharaseki Toshiaki , Takahashi Kei
Published: December 2023

Objective

The objective of the study was to analyse the trends in Takayasu arteritis (TAK) in Japan during three recent decades based on autopsy reports.

Methods

We extracted TAK cases from the Japanese Pathological Autopsy Reports published during three decades (1991–2000, 2001–10, and 2011–20) and compared the data for the number of cases, age, gender, malignant tumour complication rate, and cause of death.

Results

322 TAK cases were reported during the 30 years. They represented 0.04–0.06% of the total autopsies, with little variation among the three decades. The peak age at autopsy increased: from the 60s for 1991–2010 to the 70s for 2011–20. The malignant tumour complication rate increased to 12.2%, 18.5%, and 22.7% during the three decades. However, about half of those cases had no metastases, and malignant tumours were rarely directly involved in a TAK patient’s death. TAK-associated cardiovascular lesions accounted for most deaths.

Conclusions

Although the age at TAK onset showed little change during the 30 years, the age at autopsy has increased, suggesting that the long-term prognosis has improved. Although the malignant tumour complication rate increased with age, the most common causes of death were cardiovascular lesions.
Impact of Blood Culture Contamination on Antibiotic Use, Resource Utilization, and Clinical Outcomes: A Retrospective Cohort Study in Dutch and US Hospitals
Authors: Schinkel Michiel , Boerman Anneroos , Carroll Karen , Cosgrove Sara E , Hsu Yea-Jen , Klein Eili , Nanayakkara Prabath , Schade Rogier , Wiersinga W Joost , Fabre Valeria
Published: December 2023

Background

Blood culture contamination (BCC) has been associated with prolonged antibiotic use (AU) and increased health care utilization; however, this has not been widely reevaluated in the era of increased attention to antibiotic stewardship. We evaluated the impact of BCC on AU, resource utilization, and length of stay in Dutch and US patients.

Methods

This retrospective observational study examined adults admitted to 2 hospitals in the Netherlands and 5 hospitals in the United States undergoing ≥2 blood culture (BC) sets. Exclusion criteria included neutropenia, no hospital admission, or death within 48 hours of hospitalization. The impact of BCC on clinical outcomes—overall inpatient days of antibiotic therapy, test utilization, length of stay, and mortality—was determined via a multivariable regression model.

Results

An overall 22 927 patient admissions were evaluated: 650 (4.1%) and 339 (4.8%) with BCC and 11 437 (71.8%) and 4648 (66.3%) with negative BC results from the Netherlands and the United States, respectively. Dutch and US patients with BCC had a mean ± SE 1.74 ± 0.27 (P < .001) and 1.58 ± 0.45 (P < .001) more days of antibiotic therapy than patients with negative BC results. They also had 0.6 ± 0.1 (P < .001) more BCs drawn. Dutch but not US patients with BCC had longer hospital stays (3.36 days; P < .001). There was no difference in mortality between groups in either cohort. AU remained higher in US but not Dutch patients with BCC in a subanalysis limited to BC obtained within the first 24 hours of admission.

Conclusions

BCC remains associated with higher inpatient AU and health care utilization as compared with patients with negative BC results, although the impact on these outcomes differs by country.
Genomic Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2 in a County Jail
Authors: Adediran Timileyin , Zawitz Chad , Piriani Ali , Bendict Emily , Thiede Stephanie , Barbian Hannah , Aroutcheva Alla , Green Stefan J , Welbel Sharon , Weinstein Robert A , Snitkin Evan , Popovich Kyle J
Published: December 2023

Background

In the coronavirus disease 2019 (COVID-19) pandemic, correctional facilities are potential hotspots for transmission. We examined the genomic epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) early in the pandemic in one of the country's largest urban jails.

Methods

Existing SARS-CoV-2 isolates from 131 detainees at the Cook County Jail in Chicago, Illinois, from March 2020 through May 2020 were analyzed by whole-genome sequencing. Contemporaneous isolates from Rush University Medical Center (Chicago, Illinois) and the Global Initiative on Sharing All Influenza Data (GISAID) were used to identify genetic clusters containing only jail isolates. Transmission windows were identified for each pair of detainees using the date of the SARS-CoV-2–positive test and location data to determine if detainees overlapped in the jail, within a specific building, or within particular living units during transmission windows.

Results

We identified 29 jail-only clusters that contained 75 of the 132 SARS-CoV-2 isolates from detainees; of these clusters, 17 (58.6%) had individuals who overlapped in the jail during putative transmission windows. Focusing on specific buildings revealed that 2 buildings, a single- and double-cell style of housing. were associated with having detainees infected with similar SARS-CoV-2 genomes during their infectious time period (P < .001).

Conclusions

Our findings suggest that there was transmission of SARS-CoV-2 in the jail, in the setting of extensive importation of COVID-19 from the community. Numerous infection control practices at intake and during incarceration were implemented in the jail to limit viral spread. Our study shows the importance of genomic analysis in this type of settings and how it can be utilized within infection control protocols.
Phase transitions of the four-state Potts model on the square and honeycomb lattices
Authors: Peng Jhao-Hong , Jiang Fu-Jiun
Published: December 2023

It is widely believed that the phase transition for the four-state ferromagnetic Potts model on the square lattice is of pseudo-first order. Specifically, it is expected that first-order phase transition behavior is found on small lattices and that the true nature of the second-order phase transition only emerges with large system sizes. It is also intuitively expected that, for other geometries, the types of the associated phase transitions should be identical to that of the square lattice. However, after simulating more than 16 million spins for the four-state Potts model, we observe that a feature of the first-order phase transition persists on the square lattice. Additionally, a characteristic of the second-order phase transition already appears on a small honeycomb lattice. Indications of a pseudo-first-order phase transition were not found in our investigation. This suggests that a thorough analytic calculation may be required to develop a better understanding of the presented results.
Attractive gravity probe surface, positivity of quasi-local mass, and Arnowitt–Deser–Misner mass expression
Authors: Shiromizu Tetsuya , Izumi Keisuke
Published: December 2023

Under certain conditions, it is shown that the positivity of the Geroch/Hawking quasi-local mass holds for attractive gravity probe surfaces in any higher dimensions than three. We also comment on the Arnowitt–Deser–Misner mass.
Estimation and comparison of the performance of low-input and conventional agricultural production systems
Authors: Devilliers Esther , Möhring Niklas , Finger Robert
Published: December 2023

Low-input production systems aim at mitigating agriculture's environmental impact with a lower level of chemical inputs. However, comparing the performance of low-input systems to conventional ones, particularly in terms of productivity and yield, is challenging due to selection bias. First, we often lack observational data on low-input systems. Then, when available, the comparison between the two production systems is challenging due to potential endogeneity in input use and selection bias. To effectively develop policies promoting the adoption of low-input systems and assess their impact, for example, on pesticide use and yields, it is crucial to employ an econometric framework that addresses these issues. This article proposes an endogenous switching approach combined with control functions to tackle selection bias and input endogeneity simultaneously. Using unbalanced panel data on Swiss wheat production, which includes both low-input and conventional systems, our framework allows us to analyze the differentiated role of inputs as well as their price elasticity for both conventional and low-input farming systems.
The impact of spectral line wing cut-off: recommended standard method with application to MAESTRO opacity data base
Authors: Gharib-Nezhad Ehsan (Sam) , Batalha Natasha E , Chubb Katy , Freedman Richard , Gordon Iouli E , Gamache Robert R , Hargreaves Robert J , Lewis Nikole K , Tennyson Jonathan , Yurchenko Sergei N
Published: December 2023

When computing cross-sections from a line list, the result depends not only on the line strength, but also the line shape, pressure-broadening parameters, and line wing cut-off (i.e. the maximum distance calculated from each line centre). Pressure-broadening can be described using the Lorentz line shape, but it is known to not represent the true absorption in the far wings. Both theory and experiment have shown that far from the line centre, non-Lorentzian behaviour controls the shape of the wings and the Lorentz line shape fails to accurately characterize the absorption, leading to an underestimation or overestimation of the opacity continuum depending on the molecular species involved. The line wing cut-off is an often overlooked parameter when calculating absorption cross-sections, but can have a significant effect on the appearance of the spectrum since it dictates the extent of the line wing that contributes to the calculation either side of every line centre. Therefore, when used to analyse exoplanet and brown dwarf spectra, an inaccurate choice for the line wing cut-off can result in errors in the opacity continuum, which propagate into the modelled transit spectra, and ultimately impact/bias the interpretation of observational spectra, and the derived composition and thermal structure. Here, we examine the different methods commonly utilized to calculate the wing cut-off and propose a standard practice procedure (i.e. absolute value of 25 cm−1 for P ≤ 200 bar and 100 cm−1 for P > 200 bar) to generate molecular opacities which will be used by the open-access MAESTRO (Molecules and Atoms in Exoplanet Science: Tools and Resources for Opacities) data base. The pressing need for new measurements and theoretical studies of the far-wings is highlighted.
Alice Mustian, Playwright
Authors: McInnis David , Steggle Matthew , Teramura Misha
Published: December 2023

This article provides the first full account of Alice Mustian, a Salisbury woman who in 1614 built a theatre in her backyard and charged an audience admission to watch a group of children perform a play that she had written about some salacious neighbourhood gossip. While the fact that this remarkable incident occurred is not unknown to scholars, the primary historical evidence about the event itself has remained largely unexamined. Drawing on unexplored ecclesiastical court records in the Wiltshire and Swindon History Centre, we offer a more complete picture of the performance, its complex social context, and the motivations of the parties involved. We locate it within the field of study of lost plays; we consider how it relates to other forms of theatre and performance culture in the period; and we discuss Mustian as a female dramatist whose play offers a tantalizing glimpse of the kinds of voices whose dramatic works may not have survived into the present.
Are Analyst “Top Picks” Informative?
Authors: Birru Justin , Gokkaya Sinan , Liu Xi , Stulz René
Published: December 2023

Following the Global Settlement, analysts extensively use a top pick designation allowing for greater granularity of information among buy recommended stocks, but conflicts of interest can potentially influence this designation. Examining a novel sample of top picks, we find that a calendar-time portfolio of top picks generates an abnormal performance of 17.6% per year. Top picks have greater investment value than do buy recommendations and alternative analyst investment strategies. Both institutional and retail investors trade in response to top picks. However, only institutional investors appear to identify top picks that have greater investment value when they are announced.
Evaluation of Improvest effects on production parameters of gilts from two different genetic sire lines
Authors: Vasquez-Hidalgo Manuel A , Mellencamp Martha , Amodie Deborah , Bohrer Benjamin M , VanDeWeyer Leanne , Vonnahme Kimberly A
Published: December 2023

The objective was to evaluate the effects of Improvest on the performance and carcass characteristics of gilts from two different genetic sire lines and the performance of Improvest gilts with castrated male pigs. It was hypothesized that performance parameters observed for Improvest gilts would be similar to barrows, thus narrowing the performance gaps between traditionally managed gilts and barrows. Pigs were from Large White/Landrace dams and either Duroc–Pietrain (DP) or Duroc (D) sires. Females within each genetic sire line were randomized by weight to receive the first dose of Improvest (IMP) on day 25 of the study or to serve as a nontreated control (DP IMP gilt (n = 6 pens; 19 pigs/pen), D IMP gilt (n = 6 pens; 19 pigs/pen), DP CON gilt (n = 6 pens; 19 pigs/pen), D CON gilt (n = 6 pens; 19 pigs/pen). The second dose of Improvest was administered 6 wk later (i.e., day 67). Barrows did not receive Improvest (DP barrow [n = 10 pens; 19 to 20 pigs/pen], D barrow [n = 10 pens; 19 to 20 pigs/pen]). Average daily gain (ADG), average daily feed intake (ADFI), and gain-to-feed ratio (G:F) were measured at 21 d intervals throughout the duration of the study. The targeted weight for pigs to be marketed was 133 ± 2.5 kg. Carcass characteristics and loin quality parameters were evaluated on a subset of pigs (n = 283). Improvest-treated gilts of both genetic lines had increased (P ≤ 0.05) ADG and ADFI compared to untreated gilts during the post-second dose intervals with values exceeding that of barrows from day 84 to marketing. Overall, DP IMP gilts had increased (P ≤ 0.05) G:F post-second dose compared to DP CON gilts and DP barrows, yet all other treatments were similar. As pigs were marketed at a similar weight, there was no difference in the final weight, however, DP IMP gilts and DP barrows reached market weight sooner (P ≤ 0.05) than DP CON gilts (109.9 and 111.8 vs. 114.3 ± 0.8 d). Backfat and loin weight were greater (P < 0.01) in IMP gilts versus CON gilts, while IMP gilts and barrows had similar values within each respective genetic sire line. There were no differences between treatments (P ≥ 0.08) for pH and instrumental color of the loins. When the pass rate of loins (Japanese color score ≥ 3.0 and marbling ≥ 2.0) was evaluated, IMP gilts were at intermediate values between CON gilts and barrows for each respective genetic sire line. Overall, Improvest within a genetic line improved gilt carcass measurements so that they were more similar to barrows.
Effect of litter management systems on incidence and severity of footpad dermatitis among broilers at finisher stage
Authors: Alabi O M , Olagunju S O , Aderemi F A , Lawal T E , Oguntunji A O , Ayoola M O , Oladejo O A , Adeleye B E , Adewumi A A , Alabi B D , Tarta A
Published: December 2023

Pododermatitis, or footpad dermatitis (FPD), is a welfare concern affecting broiler chickens globally. In the humid tropics, where high temperatures and humidity prevail, the impact of pododermatitis on broiler performance characteristics and behavior becomes even more significant hence this investigation. One hundred and eighty male broilers were used for this experiment out of 200 birds initially procured at day old. They were brooded and reared on deep litter and at 21 days of age, they were randomly allotted to the experimental unit. There were three treatments each with three replicates in a completely randomized design. The three litter management systems constituted the treatment groups. In the first treatment (t-A), litter materials were changed on a weekly basis and replaced with fresh ones while in the second treatment (t-B), the litter materials were turned or raked once a week, and in the third treatment (t-C), the litter materials were left untouched. The litter material used across all treatments was wood shavings and t-C served as control. The experimental birds were fed ad libitum during the trial. Data on daily feed intake, incidence and severity of paw lesions, and weekly body weights were taken while the experiment lasted 35 days. Test of mobility and aggression were carried out on the birds from each group on the last day of the experiment. The moisture content and pH of litter materials of each replicate were taken weekly from day 21 till the end of the experiment. Data were later subjected to analysis of variance statistically. The results revealed that broilers on t-A performed better (P < 0.05) than those on t-B and t-C for feed intake, live weight, weight gain, and feed utilization. However, FPD was pronounced among broilers on t-C and much more severe. A positive correlation was observed between the values of litter moisture content, litter pH, and incidence and severity of FPD. Birds on t-C were dull in appearance and inactive. In conclusion, FPD has a detrimental impact on the performance characteristics and behavior of broiler chickens in the humid tropics. However, the severity depends on the management system adopted. By adopting appropriate management practices such as weekly replacement of litter with fresh ones, it is possible to alleviate the negative consequences of FPD, improve broiler welfare, and enhance the sustainability of the poultry industry in these regions.
Prevalence of Cryptosporidium and microsporidial infection in HIV-infected individuals
Authors: Didarlu Hasan , Mahami-Oskouei Mahmoud , Varshochi Mojtaba , Hatam-Nahavandi Kareem , Shahrivar Firooz , Bahadory Saeed , Barac Aleksandra , Ahmadpour Ehsan
Published: December 2023

Background

Microsporidia and Cryptosporidium are obligate intracellular protozoa. These medically important species are recognized as opportunistic organisms in intestinal complications in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome patients.

Methods

The current cross-sectional study was designed and conducted from August 2016 to August 2017 to determine intestinal Cryptosporidium and microsporidia spp. in HIV-infected individuals from the Behavioral Diseases Counseling Center, Tabriz, Iran, by modified acid-fast and modified trichrome staining and nested polymerase chain reaction (PCR) and real-time PCR.

Results

Of 100 HIV-infected persons, 21.0% (95% confidence interval [CI] 13.0 to 30.0) and 18.0% (95% CI 11.0 to 26.0) were identified as Cryptosporidium and microsporidia, respectively, by the microscopic method. Of these 100 HIV-infected persons, 18.0% (95% CI 11.0 to 26.0) and 14.0% (95% CI 7.0 to 22.0) were positive for Cryptosporidium and microsporidia, respectively, by the molecular method. The predominant species of microsporidia in patients was Enterocytozoon bieneusi (85.7% [95% CI 57.0 to 98.0]) and Encephalitozoon cuniculi (14.3% [95% CI 1.7 to 42.0]), which were found by quantitative real-time PCR and its high-resolution melting tool.

Conclusions

As far as we know, this study is the first to estimate the prevalence of infection with Cryptosporidium and microsporidia among HIV-infected persons in northwest of Iran. The prevalence of intestinal microsporidiosis and cryptosporidiosis in this area in HIV-infected people was higher than the global prevalence of infection among immunocompromised patients. In addition to the need for further studies to prove protozoan pathogenicity in the aforementioned group, preventive measures should be considered.
Combined PDE4+MEK inhibition shows antiproliferative effects in NRAS Q61 mutated melanoma preclinical models
Authors: Louveau Baptiste , Reger De Moura Coralie , Jouenne Fanélie , Sadoux Aurélie , Allayous Clara , Da Meda Laetitia , Bernard-Cacciarella Mélanie , Baroudjian Barouyr , Lebbé Céleste , Mourah Samia , Dumaz Nicolas
Published: December 2023

Upregulation of phosphodiesterase type 4 (PDE4) has been associated with worse prognosis in several cancers. In melanomas harboring NRAS mutations, PDE4 upregulation has been shown to trigger a switch in signaling from BRAF to RAF1 which leads to mitogen-activated protein kinase pathway activation. Previous in vitro evidence showed that PDE4 inhibition induced death in NRAS
Q61mut melanoma cells and such a strategy may thus be a relevant therapeutic option in those cases with no molecular targeted therapies approved to date. In this study, we generated patient-derived xenografts (PDX) from two NRAS
Q61mut melanoma lesions. We performed ex vivo histoculture drug response assays and in vivo experiments. A significant ex vivo inhibition of proliferation with the combination of roflumilast+cobimetinib was observed compared to dimethyl sulfoxyde control in both models (51 and 67%). This antiproliferative effect was confirmed in vivo for PDX-1 with a 56% inhibition of tumor growth. To decipher molecular mechanisms underlying this effect, we performed transcriptomic analyses and revealed a decrease in MKI67, RAF1 and CCND1 expression under bitherapy. Our findings strengthen the therapeutic interest of PDE4 inhibitors and support further experiments to evaluate this approach in metastatic melanoma.
Unusual Presentation of Solitary Penile Metastasis of Prostate Cancer on 68Ga-PSMA PET/CT
Authors: Bin Essa Noora Essa , Alderaibi Alaa Khalid , Fraioli Francesco
Published: December 2023

A 75-year-old patient was referred with biochemical recurrence for prostate cancer. The patient underwent 68Ga-PSMA (prostate-specific membrane antigen) PET/CT scan, which revealed a focal PSMA activity in the proximal left lateral penile margin. Although a subsequent ultrasound did not identify the abnormality, MRI pelvis revealed a 10-mm lesion in the left proximal corpus cavernosum. This lesion was consistent with metastatic acinar adenocarcinoma of the prostate on postresection histopathology. This unusual presentation of asymptomatic, histopathology-proven, penile solitary metastases was documented 3 years after robotic-assisted laparoscopic prostatectomy and pelvic external beam radiotherapy.
Naringenin alleviates cognitive dysfunction in rats with cerebral ischemia/reperfusion injury through up-regulating hippocampal BDNF-TrkB signaling: involving suppression in neuroinflammation and oxidative stress
Authors: Zhu Xiao-Qin , Gao Dong
Published: December 2023

Cognitive dysfunction is one of the common complications of cerebral ischemia-reperfusion (CI/R) injury after ischemic stroke. Neuroinflammation and oxidative stress are the core pathological mechanism of CI/R injury. The activation of brain derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling antagonize cognitive dysfunction in a series of neuropathy. Naringenin (NAR) improves cognitive function in many diseases, but the role of NAR in CI/R injury-induced cognitive dysfunction remains unexplored. The study aimed to explore the potential protective effects of NAR in CI/R injury-induced cognitive dysfunction and underlying mechanism. The rats were exposed to transient middle cerebral artery occlusion (MCAO) and then treated with distilled water or NAR (50 or 100 mg/kg/day, p.o.) for 30 days. The Y-maze test, Novel object recognition test and Morris water maze test were performed to assess cognitive function. The levels of oxidative stress and inflammatory cytokines were measured by ELISA. The expressions of BDNF/TrkB signaling were detected by Western blot. NAR prevented cognitive impairment in MCAO-induced CI/R injury rats. Moreover, NAR inhibited oxidative stress (reduced levels of malondialdehyde and 4-hydroxynonenal, increased activities of superoxide dismutase and Glutathione peroxidase) and inflammatory cytokines (reduced levels of tumor necrosis factor-α, Interleukin-1β and Interleukin-6), up-regulated the expressions of BDNF and p-TrkB in hippocampus of MCAO-induced CI/R rats. NAR ameliorated cognitive dysfunction of CI/R rats via inhibiting oxidative stress, reducing inflammatory response, and up-regulating BDNF/TrkB signaling pathways in the hippocampus.
Contingency learning on the proportional congruency effect of the Stroop task is manifest in deviant processing
Authors: Suzuki Kota
Published: December 2023

Objective

The proportion congruency effect has been reported in interference tasks. The mostly congruent block is the frequent condition, and the mostly incongruent block is the rare condition for congruent stimuli, whereas the mostly congruent block is the rare condition, and the mostly incongruent block is the frequent condition for incongruent stimuli. This study examined the cognitive mechanism underlying the proportion congruency effect in the two-choice Stroop task using event-related potential components related to deviant processing.

Method

Stimuli were Kanji characters meaning ‘red’ and ‘blue’ painted by congruent and incongruent colors. Participants were required to provide a two-choice button-press response corresponding to the colors. The congruent and incongruent stimuli were presented on rare (20%) and frequent (80%) conditions.

Results

N1 was enhanced in the rare condition relative to the frequent condition for both congruent and incongruent stimuli. The results suggested that colors and characters were not processed independently in the N1 time range, which made selective attention to the relevant feature difficult. Posterior negativity from 200 to 250 ms was also different between rare and frequent conditions, indicating the presence of visual mismatch negativity for congruent and incongruent stimuli. It was considered that the distinction between congruent and incongruent stimuli was evident in mostly incongruent blocks, indicating that the selective attention mechanism was not actively engaged.

Conclusion

The proportion congruency effect was explained by contingency learning rather than selective attention in the present task. The cognitive mechanisms underlying the proportion congruency effect are reflected by deviant event-related potential components.
Neoantigen Cancer Vaccines and Different Immune Checkpoint Therapies Each Utilize Both Converging and Distinct Mechanisms that in Combination Enable Synergistic Therapeutic Efficacy
Authors: Keshari Sunita , Shavkunov Alexander S. , Miao Qi , Saha Akata , Williams Charmelle D. , Highsmith Anna M. , Pineda Josué E. , Alspach Elise , Hu Kenneth H. , Pauken Kristen E. , Chen Ken , Gubin Matthew M.
Published: December 2023

The goal of therapeutic cancer vaccines and immune checkpoint therapy (ICT) is to eliminate cancer by expanding and/or sustaining T cells with anti-tumor capabilities. However, whether cancer vaccines and ICT enhance anti-tumor immunity by distinct or overlapping mechanisms remains unclear. Here, we compared effective therapeutic tumor-specific mutant neoantigen (NeoAg) cancer vaccines with anti-CTLA-4 and/or anti-PD-1 ICT in preclinical models. Both NeoAg vaccines and ICT induce expansion of intratumoral NeoAg-specific CD8 T cells, though the degree of expansion and acquisition of effector activity was much more substantial following NeoAg vaccination. Further, we found that NeoAg vaccines are particularly adept at inducing proliferating and stem-like NeoAg-specific CD8 T cells. Single cell T cell receptor (TCR) sequencing revealed that TCR clonotype expansion and diversity of NeoAg-specific CD8 T cells relates to their phenotype and functional state associated with specific immunotherapies employed. Effective NeoAg vaccines and ICT required both CD8 and CD4 T cells. While NeoAg vaccines and anti-PD-1 affected the CD4 T cell compartment, it was to less of an extent than observed with anti-CTLA-4, which notably induced ICOS+Bhlhe40+Th1-like CD4 T cells and, when combined with anti-PD-1, a small subset of Th2-like CD4 T cells. Although effective NeoAg vaccines or ICT expanded intratumoral M1-like iNOS+macrophages, NeoAg vaccines expanded rather than suppressed (as observed with ICT) M2-like CX3CR1+CD206+macrophages, associated with the vaccine adjuvant. Further, combining NeoAg vaccination with ICT induced superior efficacy compared to either therapy in isolation, highlighting the utility of combining these modalities to eliminate cancer.

Highlights

NeoAg cancer vaccines utilize distinct mechanisms from αCTLA-4 or αPD-1 ICT

NeoAg vaccines induce TCF1+stem-like and proliferating NeoAg-specific CD8 T cells

CD8 TCR clonotype expansion relates to phenotype and functional state associated with immunotherapy

NeoAg vaccines induce partially distinct macrophage remodeling from ICT

NeoAg vaccines synergize with ICT, exceeding combination αCTLA-4/αPD-1 ICT efficacy
The BioGenome Portal: a web-based platform for biodiversity genomics data management
Authors: Righi Emilio , Guigó Roderic
Published: December 2023

Biodiversity genomics projects are underway with the aim of sequencing the genomes of all eukaryotic species on Earth. Here we describe the BioGenome Portal, a web-based application to facilitate organization and access to the data produced by biodiversity genomics projects. The portal integrates user-generated data with data deposited in public repositories. The portal generates sequence status reports that can be eventually ingested by designated meta-data tracking systems, facilitating the coordination task of these systems. The portal is open-source and fully customizable. It can be deployed at any site with minimum effort, contributing to the democratization of biodiversity genomics projects. Here, we illustrate the features of the BioGenome Portal through two specific instances. One instance corresponds to the Earth Biogenome Project, the worldwide umbrella for most biodiversity genomics projects. The other instance corresponds to the Catalan Initiative for the Earth Biogenome Project, a regional project aiming to sequencing the genomes of the species of the Catalan Linguistic Area.
An AAV capsid reprogrammed to bind human Transferrin Receptor mediates brain-wide gene delivery
Authors: Huang Qin , Chan Ken Y. , Lou Shan , Keyes Casey , Wu Jason , Botticello-Romero Nuria R , Zheng Qingxia , Johnston Jencilin , Mills Allan , Brauer Pamela P. , Clouse Gabrielle , Pacouret Simon , Harvey John W. , Beddow Thomas , Hurley Jenna K. , Tobey Isabelle G. , Powell Megan , Chen Albert T. , Barry Andrew J. , Eid Fatma-Elzahraa , Chan Yujia A. , Deverman Benjamin E.
Published: December 2023

Developing vehicles that efficiently deliver genes throughout the human central nervous system (CNS) will broaden the range of treatable genetic diseases. We engineered an AAV capsid, BI-hTFR1, that binds human Transferrin Receptor (TfR1), a protein expressed on the blood-brain barrier (BBB). BI-hTFR1 was actively transported across a human brain endothelial cell layer and, relative to AAV9, provided 40–50 times greater reporter expression in the CNS of humanTFRCknock-in mice. The enhanced tropism was CNS-specific and absent in wild type mice. When used to deliverGBA1, mutations of which cause Gaucher disease and are linked to Parkinson’s disease, BI-hTFR1 substantially increased brain and cerebrospinal fluid glucocerebrosidase activity compared to AAV9. These findings establish BI-hTFR1 as a promising vector for human CNS gene therapy.
Spatially Dependent Tissue Distribution of Thyroid Hormones by Plasma Thyroid Hormone Binding Proteins
Authors: Bagga Anish D. , Johnson Brian P. , Zhang Qiang
Published: December 2023

Plasma thyroid hormone (TH) binding proteins (THBPs), including thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin (ALB), carry THs to extrathyroidal sites, where THs are unloaded locally and then taken up via membrane transporters into the tissue proper. The respective roles of THBPs in supplying THs for tissue uptake are not completely understood. To investigate this, we developed a spatial human physiologically based kinetic (PBK) model of THs, which produces several novel findings.(1)Contrary to postulations that TTR and/or ALB are the major local T4 contributors, the three THBPs may unload comparable amounts of T4 inLiver, a rapidly perfused organ; however, their contributions in slowly perfused tissues follow the order of abundances of T4TBG, T4TTR, and T4ALB. The T3 amounts unloaded from or loaded onto THBPs in a tissue acting as a T3 sink or source respectively follow the order of abundance of T3TBG, T3ALB, and T3TTR regardless of perfusion rate.(2)Any THBP alone is sufficient to maintain spatially uniform TH tissue distributions.(3)The TH amounts unloaded by each THBP species are spatially dependent and nonlinear in a tissue, with ALB being the dominant contributor near the arterial end but conceding to TBG near the venous end.(4)Spatial gradients of TH transporters and metabolic enzymes may modulate these contributions, producing spatially invariant or heterogeneous TH tissue concentrations depending on whether the blood-tissue TH exchange operates in near-equilibrium mode. In summary, our modeling provides novel insights into the differential roles of THBPs in local TH tissue distribution.

Key Points

Thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin (ALB) are plasma thyroid hormone (TH) binding proteins (THBPs) that carry THs from the thyroid gland to extrathyroidal tissues.

The respective roles of the 3 THBP species in unloading THs once arriving at a tissue are not completely understood.

Here we developed a spatial human kinetic model of THs and showed that the three THBPs may unload comparable amounts of thyroxine (T4) in the liver but TBG is dominant in contributing T4 in tissues slowly perfused by blood as well as in contributing triiodothyronine (T3) regardless of the tissue’s perfusion rate.

The TH amounts unloaded by each THBP species are spatially dependent and nonlinear, with ALB being the dominant contributor near the arterial end but conceding to TBG near the venous end in a tissue.

Our model provides novel insights into the differential roles of THBPs in local TH tissue distribution.
Variation in echolocation call emission of Neotropical insect-eating bats in response to shifting ambient temperatures
Authors: Iturralde Pólit Paula , Araya-Salas Marcelo , Goerlitz Holger R. , Chaverri Gloriana
Published: December 2023

The sensory systems of animals are essential for them to respond to environmental cues and signals. However, their functionality might be altered by climate change. Most bats, for example, rely on acoustic signal emission for acquiring food, but their high-frequency echolocation calls are strongly attenuated in the air. Attenuation in air changes with changing weather conditions, which can lead to shifts in echo-based prey detection distance. However, bats adjust call parameters to the task and environment, and this behavioural plasticity may also help them to counteract potential increases in sound attenuation to keep echo detectability constant. We explored this ability in a community of insectivorous bats in a montane forest of Costa Rica. We recorded bat echolocation calls in response to experimentally increased temperatures, simulating intermediate and arguably realistic projected climate change scenarios. We calculated atmospheric attenuation and detection distance for each temperature and echolocation call. We found some changes in source level and call duration, yet not in peak frequency, and responses were not consistent across species with increasing atmospheric attenuation. This might be explained by several non-mutually exclusive reasons, including that the experimental increase in temperature and change of atmospheric attenuation were not sufficient to affect close-range prey detection. Ultimately, this study contributes to our understanding of sensory system adaptation under the pressure imposed by climate change.

SUMMARY STATEMENT

Studying adjustments in bats’ call parameters can reveal responses to the pressure imposed by climate change.
Order of arrival and nutrient supply alter outcomes of coinfection with two fungal pathogens
Authors: Green Elizabeth T. , Grunberg Rita L. , Mitchell Charles E.
Published: December 2023

A pathogen arriving on a host typically encounters a diverse community of microbes that can shape priority effects, other within-host interactions, and infection outcomes. In plants, environmental nutrients can drive tradeoffs between host growth and defense and can mediate interactions between coinfecting pathogens. Nutrients may thus alter the outcome of pathogen priority effects for the host, but this possibility has received little experimental investigation. To disentangle the relationship between nutrient availability and coinfection dynamics, we factorially manipulated nutrient availability and order of arrival of two foliar fungal pathogens (Rhizoctonia solaniandColletotrichum cereale) on the host grass tall fescue (Festuca arundinacea) and tracked disease outcomes. Overall,C. cerealeinfection facilitated infection byR. solani, increasing its infection rate regardless of their order of inoculation. Additionally, simultaneous andC. cereale-first inoculations decreased plant growth and – in plants that did not receive nutrient addition – increased leaf nitrogen concentrations compared to uninoculated plants. Nutrient addition did not influence infection rates, severity of infection, or plant biomass. These findings highlight the importance of understanding the intricate associations between the order of pathogen arrival, host nutrient availability, and host defense to better predict infection outcomes.
How to control unpredictable others in court-net sports
Authors: Yamamoto Yuji , Yokoyama Keiko , Kijima Akifumi , Okumura Motoki , Shima Hiroyuki , Gohara Kazutoshi
Published: December 2023

Competition in sports does not involve a single solution because individuals aim to behave unpredictably, thereby preventing others from predicting their actions. This study determined how individuals in court net sports tried to control others’ unpredictable behavior, thereby addressing the gap of the lack of clarity about strategies employed by individuals in competitive situations. We employed a switching hybrid dynamics model, considering external inputs when analyzing individual behaviors. The study shows that skilled individuals, unlike intermediate players, exhibit greater regularity in their behavior, lead others to anticipate this regularity, and employ strategies to disrupt these expectations. This strategy exploits the principles of active human inference, implying that competition involves cooperation. We revealed this by analyzing both human decision-making and behavior in actual matches as discrete and continuous dynamical systems. This strategy helps policymakers adopt a new policy targeting cooperation with competitors, which would increase competitiveness in our daily lives.