bluuebunny/crossref_metadata_2025 huggingface dataset:
Ecological assessment of the safety and biodiversity of woody introduced species in the semi-desert of the Northern Caspian lowland
Authors: Sizemskaya M L , Sapanov M K
Published: July 2023

The species diversity and safety of a 70-year-old collection of tree and shrub introduced species in the arboretum of the Dzhanybek Research Station, located in rainfed conditions of the semi-desert of the Northern Caspian region, was studied. The arboretum was created on hydromorphic meadow-chestnut soils in a mesodepression of relief in 1953. At the present stage, 75 species belonging to 23 families and 43 genera have been identified in the arboretum. It was analyzed that most of the species are represented by the family Rosaceae, the species of the families Caprifoliaceae, Elaeagnaceae, Fagaceae, Leguminosae, Oleaceae, Salicaceae, Sapindaceae, Ulmaceae are very numerous. Species with high ecological and biological potential have been identified. It is concluded that due to their own longevity, adaptive reactions, good self-renewal abilities, many species can exist for a long time and stably in semi-desert conditions. Species that can be recommended for creating sustainable socially significant plantations are proposed.
Breeding bulbous and bulbotuberiferous flower crops at the Subtropical Scientific Centre of RAS
Authors: Ryndin A V , Pashchenko O I , Slepchenko N A
Published: July 2023

Bulbous and bulbotuberiferous plants are the most popular flower crops among amateur flower growers, florists, landscape designers, introducers and breeders. These crops collected by the Federal Research Centre the Subtropical Scientific Centre of the Russian Academy of Sciences include both foreign and domestic cultivars. Breeding work within these collections has been carried out for more than 50 years, for many – for the first time in the country. The obtained cultivars are not inferior in decorative qualities to foreign ones, and they are superior in resistance. Currently, due to the limited import of foreign planting material, the demand for domestic products has significantly increased. This paper presents the results of research conducted over the last 15 years. During this period, researchers have created more than 90 cultivars of freesia, hippeastrum and tulip; an extensive hybrid fund has been collected; sources of economically valuable traits have been allocated. Currently, xiphium and crocus are included in the breeding process. In the course of the research, bulbous and bulbotuberiferous flower crops collected by FRC SSC of RAS have been replenished with 26 domestic highly decorative cultivar samples, productive and resistant to abiotic and biotic factors, including 22 freesias, 2 hippeastrums and tulips. New cultivars are different in flowering terms: 7 of them have an early flowering term, 11 – with an average, 8 – with a late one. There are six groups according to the main colour of the perianth lobes: white – 4 cultivars, yellow – 5, red – 3, medium blue – 4, pink-purple – 8, black – 2.
Simplified dynamic model of a nuclear power plant
Authors: Kanareykin Aleksandr Ivanovich
Published: July 2023

The article is devoted to the issues of nuclear energy. It considers a simplified dynamic model simulating the main processes in a nuclear power plant, including heat generation in a reactor. The basis of the proposed model is a model of heat release in the reactor, simulating the relative neutron power and temperature of the coolant in the hot thread of the circulation circuit.
Formation of the avifauna of the Zaryadye Park (Moscow) in 2018-2022
Authors: Vasilevskaya A A , Malovichko L V , Kiseleva N Y , Kuznetsova V V , Krotova E A
Published: July 2023

The article presents the results of a five-year monitoring of the bird population in the new Zaryadye Park (Moscow) and a forecast for the further development of their communities. The basis of the population of the park is, on the one hand, numerous urban species, such as the house sparrow Passer domesticus and the rock dove Columba livia, and, on the other hand, single migratory species, including those protected in Moscow. Of the 50 species noted in Zaryadye, 13 species reliably nest, and another 4 probably nest. In the future, as the forest stand matures, both new migratory and nesting species may appear in the park.
Natural flow regulation coefficient of the Kaliningrad region rivers
Authors: Akhmedova N R , Naumov V A , Kochkareva A S
Published: July 2023

The natural flow regulation coefficient is used in solving engineering and scientific problems in the field of hydrology, hydraulic engineering. The article presents the results of calculating this coefficient for the rivers of the Kaliningrad region based on the results of observations. The previously developed calculation method in the Mathcad environment was used. The range of changes in the coefficient of natural regulation of the flow of rivers in the Kaliningrad region significantly exceeds the similar range given for the rivers of the North-West of Russia. The closest stochastic relationship is in the coefficient of natural regulation of river flow in the Kaliningrad region with 30-day water discharges.
Application of the neural network approach to predict the efficiency of the use of ecological neutrality transition technologies by power plants
Authors: Guzhov S V , Torop D V , Bashlykov M S , Kudryashova A P , Sesin A A , Krylova E V
Published: July 2023

The issues of improving the environmental friendliness of power plants are relevant in Russia and in the world. The objectives of reducing greenhouse gas emissions and reducing heat losses in cooling towers are important. Reducing greenhouse gas emissions is relevant for both the urban economy and public health. Reducing thermal energy emissions from power plants within the city is also relevant, because. improves the quality of life of residents and guests of the city, reduces the load on air conditioning in summer, allows you to direct the released electrical energy to the development of the urban economy. There are many technologies that can be used to effectively utilize the thermal energy of cooling towers. The article presents those of them that have shown their technical and economic feasibility. The task of predicting the effects for a particular plant is complicated by the need to temporarily shut down part of the generating capacity, which is unacceptable for the city’s power supply system. Therefore, predictive models based on artificial neural networks are becoming the main tool. The assumptions used in solving problems of this class are shown, an example of a set of input factors is given, and the resulting errors are shown. It is shown that the combination of technologies for the transition to environmental neutrality of power plants can become the center of attraction for many urban projects that can increase economic efficiency, increase the number of jobs, develop import-substituting industries, and increase the efficiency of land use around generation facilities that were previously operated insignificantly.
Dynamics of yield formation of green and dry aboveground biomass of non-traditional fodder crops in the Saratov Right Bank
Authors: Bashinskaya O S , Kondakov K S , Zaitsev S A , Eryushev M V
Published: July 2023

The article deals with the problems of fodder production development in the Saratov region. In this regard, we paid great attention to annual fodder crops using the mogar as an example. The features of the formation of green and dry aboveground mogar biomass were described. Conducted research on the effect of seeding rate and sowing method on field germination and yield of mogar. We assessed the economic efficiency of mogar cultivation in the Saratov region. They recommended the optimal seeding rate and sowing method to obtain the maximum yield of mogar green mass.
Influence of high hydrostatic pressure treatment on licorice (Glycyrrhiza uralensis Fisch.) hard seeds germination
Authors: Yu Belyaev A , Kruglikov N A
Published: July 2023

The effects of hydrostatic pressure (from 100 to 250 MPa with different exposure options) on the germination of hard seeds of licorice (Glycyrrhiza uralensis Fisch.) were studied. Among used pressures, the best result was obtained after three times by 100 MPa exposure. In this variant, good dynamics of swelling and germination of seeds was observed, and the proportion of normal seedlings from the total number of hard seeds in the studied sample was largest. It is shown that higher levels of pressure load on licorice seeds led to a decrease in the proportion of normally developed seedlings.
Automatic recognition of defects in plasma-facing material using image processing technology
Authors: LYU 吕 Jianhua 建骅 , NIU 牛 Chunjie 春杰 , CUI 崔 Yunqiu 运秋 , CHEN 陈 Chao 超 , NI 倪 Weiyuan 维元 , FAN 范 Hongyu 红玉
Published: July 2023

Observing and analyzing surface images is critical for studying the interaction between plasma and irradiated plasma-facing materials. This paper presents a method for the automatic recognition of bubbles in transmission electron microscope (TEM) images of W nanofibers using image processing techniques and convolutional neural network (CNN). We employ a three-stage approach consisting of Otsu, local-threshold, and watershed segmentation to extract bubbles from noisy images. To address over-segmentation, we propose a combination of area factor and radial pixel intensity scanning. A CNN is used to recognize bubbles, outperforming traditional neural network models such as AlexNet and GoogleNet with an accuracy of 97.1% and recall of 98.6%. Our method is tested on both clear and blurred TEM images, and demonstrates human-like performance in recognizing bubbles. This work contributes to the development of quantitative image analysis in the field of plasma-material interactions, offering a scalable solution for analyzing material defects. Overall, this study’s findings establish the potential for automatic defect recognition and its applications in the assessment of plasma-material interactions. This method can be employed in a variety of specialties, including plasma physics and materials science.
The reproducing Kernel of the Sobolev space on an interval
Authors: Yamada Akira
Published: July 2023

Let

H
n

(
a
,
b
)

H^n(a,b)

be the one-dimensional Sobolev Hilbert space of order

n
n

on the interval

(
a
,
b
)

(a,b)

(

n
=
1
,
2
,
…

n=1,2,\dots

). The explicit form of the reproducing kernel of

H
n

(
a
,
b
)

H^n(a,b)

on finite interval was already known in the case for

n
=
1
,
2
,
3

n=1,2,3

. In this paper we obtain the explicit form of the reproducing kernel of

H
n

(
a
,
b
)

H^n(a,b)

on any interval for general

n
n

.
Tree-based subgroup discovery using electronic health record data: heterogeneity of treatment effects for DTG-containing therapies
Authors: Yang Jiabei , Mwangi Ann W , Kantor Rami , Dahabreh Issa J , Nyambura Monicah , Delong Allison , Hogan Joseph W , Steingrimsson Jon A
Published: July 2023

The rich longitudinal individual level data available from electronic health records (EHRs) can be used to examine treatment effect heterogeneity. However, estimating treatment effects using EHR data poses several challenges, including time-varying confounding, repeated and temporally non-aligned measurements of covariates, treatment assignments and outcomes, and loss-to-follow-up due to dropout. Here, we develop the subgroup discovery for longitudinal data algorithm, a tree-based algorithm for discovering subgroups with heterogeneous treatment effects using longitudinal data by combining the generalized interaction tree algorithm, a general data-driven method for subgroup discovery, with longitudinal targeted maximum likelihood estimation. We apply the algorithm to EHR data to discover subgroups of people living with human immunodeficiency virus who are at higher risk of weight gain when receiving dolutegravir (DTG)-containing antiretroviral therapies (ARTs) versus when receiving non-DTG-containing ARTs.
Augmented two-step estimating equations with nuisance functionals and complex survey data
Authors: Zhao Puying , Wu Changbao
Published: July 2023

Statistical inference in the presence of nuisance functionals with complex survey data is an important topic in social and economic studies. The Gini index, Lorenz curves, and quantile shares are among the commonly encountered examples. The nuisance functionals are usually handled by a plug-in nonparametric estimator and the main inferential procedure can be carried out through a two-step generalized empirical likelihood method. Unfortunately, the resulting inference is not efficient and the nonparametric version of the Wilks’ theorem breaks down even under simple random sampling. We propose an augmented estimating equations method with nuisance functionals and complex surveys. The second step augmented estimating functions obey the Neyman orthogonality condition and automatically handle the impact of the first step plug-in estimator, and the resulting estimator of the main parameters of interest is invariant to the first step method. More importantly, the generalized empirical likelihood-based Wilks’ theorem holds for the main parameters of interest under the design-based framework for commonly used survey designs, and the maximum generalized empirical likelihood estimators achieve the semiparametric efficiency bound. Performances of the proposed methods are demonstrated through simulation studies and an application using the dataset from the New York City Social Indicators Survey.
Feasibility of three-dimensional artificial intelligence algorithm integration with intracardiac echocardiography for left atrial imaging during atrial fibrillation catheter ablation
Authors: Di Biase Luigi , Zou Fengwei , Lin Aung N , Grupposo Vito , Marazzato Jacopo , Tarantino Nicola , Della Rocca Domenico , Mohanty Sanghamitra , Natale Andrea , Alhuarrat Majd Al Deen , Haiman Guy , Haimovich David , Matthew Richard A , Alcazar Jaclyn , Costa Graça , Urman Roy , Zhang Xiaodong
Published: July 2023

Aims

Intracardiac echocardiography (ICE) is a useful but operator-dependent tool for left atrial (LA) anatomical rendering during atrial fibrillation (AF) ablation. The CARTOSOUND FAM Module, a new deep learning (DL) imaging algorithm, has the potential to overcome this limitation. This study aims to evaluate feasibility of the algorithm compared to cardiac computed tomography (CT) in patients undergoing AF ablation.

Methods and results

In 28 patients undergoing AF ablation, baseline patient information was recorded, and three-dimensional (3D) shells of LA body and anatomical structures [LA appendage/left superior pulmonary vein/left inferior pulmonary vein/right superior pulmonary vein/right inferior pulmonary vein (RIPV)] were reconstructed using the DL algorithm. The selected ultrasound frames were gated to end-expiration and max LA volume. Ostial diameters of these structures and carina-to-carina distance between left and right pulmonary veins were measured and compared with CT measurements. Anatomical accuracy of the DL algorithm was evaluated by three independent electrophysiologists using a three-anchor scale for LA anatomical structures and a five-anchor scale for LA body. Ablation-related characteristics were summarized. The algorithm generated 3D reconstruction of LA anatomies, and two-dimensional contours overlaid on ultrasound input frames. Average calculation time for LA reconstruction was 65 s. Mean ostial diameters and carina-to-carina distance were all comparable to CT without statistical significance. Ostial diameters and carina-to-carina distance also showed moderate to high correlation (r = 0.52–0.75) except for RIPV (r = 0.20). Qualitative ratings showed good agreement without between-rater differences. Average procedure time was 143.7 ± 43.7 min, with average radiofrequency time 31.6 ± 10.2 min. All patients achieved ablation success, and no immediate complications were observed.

Conclusion

DL algorithm integration with ICE demonstrated considerable accuracy compared to CT and qualitative physician assessment. The feasibility of ICE with this algorithm can potentially further streamline AF ablation workflow.
Atrial extrasystoles enhance low-voltage fractionation electrograms in patients with atrial fibrillation
Authors: van Schie Mathijs S , Liao Rongheng , Ramdat Misier Nawin L , Knops Paul , Heida Annejet , Taverne Yannick J H J , de Groot Natasja M S
Published: July 2023

Background and aims

Atrial extrasystoles (AES) provoke conduction disorders and may trigger episodes of atrial fibrillation (AF). However, the direction- and rate-dependency of electrophysiological tissue properties on epicardial unipolar electrogram (EGM) morphology is unknown. Therefore, this study examined the impact of spontaneous AES on potential amplitude, -fractionation, -duration, and low-voltage areas (LVAs), and correlated these differences with various degrees of prematurity and aberrancy.

Methods and results

Intra-operative high-resolution epicardial mapping of the right and left atrium, Bachmann’s Bundle, and pulmonary vein area was performed during sinus rhythm (SR) in 287 patients (60 with AF). AES were categorized according to their prematurity index (>25% shortening) and degree of aberrancy (none, mild/opposite, moderate and severe). In total, 837 unique AES (457 premature; 58 mild/opposite, 355 moderate, and 154 severe aberrant) were included. The average prematurity index was 28% [12–45]. Comparing SR and AES, average voltage decreased (−1.1 [−1.2, −0.9] mV, P < 0.001) at all atrial regions, whereas the amount of LVAs and fractionation increased (respectively, +3.4 [2.7, 4.1] % and +3.2 [2.6, 3.7] %, P < 0.001). Only weak or moderate correlations were found between EGM morphology parameters and prematurity indices (R2 < 0.299, P < 0.001). All parameters were, however, most severely affected by either mild/opposite or severely aberrant AES, in which the effect was more pronounced in AF patients. Also, there were considerable regional differences in effects provoked by AES.

Conclusion

Unipolar EGM characteristics during spontaneous AES are mainly directional-dependent and not rate-dependent. AF patients have more direction-dependent conduction disorders, indicating enhanced non-uniform anisotropy that is uncovered by spontaneous AES.
Biosorption and bioreduction of aqueous chromium (VI) by different Spirulina strains
Authors: Meng Guoqing , Liu Jinghua , Ma Jingwen , Liu Xueqin , Zhang Fengyun , Guo Yanfeng , Wang Chuanbao , Song Lei
Published: July 2023

Spirulina has emerged as a promising microorganism for the treatment of industrial heavy metal ions in wastewater due to their simplicity of cultivation and harvesting, rich functional binding groups, and high bioreductive activity during the uptake process. While the capacities of biosorption and bioreduction for heavy metal ions differ significantly among various algal strains. Therefore, the physiological characteristics were investigated to identify the different Spirulina strains, and the chromium (VI) adsorption capacities of the algal strains were also evaluated. In this study, it was found that algal strains YCX2643 and CLQ1848 performed higher removal efficiency (86.5% and 83.7%) than the other four Spirulina strains (59.4%, 56.3%, 65.6%, and 66.5%, respectively). Moreover, the mechanisms of chromium (VI) ions binding and biotransformation in the Spirulina cell were scrutinized by FTIR (Fourier transform infrared) spectroscopy and scanning electron microscopy (SEM), and it indicated that the varieties of cellular components involved in high binding affinity may cause the higher biosorption and bioreduction of aqueous chromium (VI) in algal strains YCX2643 and CLQ1848, which could be used as promising biosorbents in the removing heavy metal pollutants from wastewaters.
Efficient disruption of CmHk1 using CRISPR/Cas9 ribonucleoprotein delivery in Cordyceps militaris
Authors: Choi Hyeongju , Park Sung-Won , Oh Junsang , Kim Cheol Soo , Sung Gi-Ho , Sang Hyunkyu
Published: July 2023

Cordyceps militaris, an entomopathogenic ascomycete, produces edible medicinal mushrooms known to have medicinal and therapeutic functions. To develop the genetic transformation system in C. militaris, green fluorescent protein (GFP) mutants of C. militaris were generated by PEG-mediated protoplast transformation. The CRISPR/Cas9 ribonucleoprotein (RNP) targeting the class III histidine kinase of C. militaris (CmHk1) was then delivered into protoplasts of C. militaris through the transformation system. Mutations induced by the RNP in selected mutants were detected: 1 nt deletion (6 mutants), 3 nt deletion with substitution of 1 nt (1 mutant), insertion of 85 nts (1 mutant), 41 nts (2 mutants), and 35 nts (5 mutants). An in vitro sensitivity assay of the mutants indicated that knockout of CmHk1 reduced sensitivity to two fungicides, iprodione and fludioxonil, but increased sensitivity to osmotic stresses compared to the wild type. Summing up, the CRISPR/Cas9 RNP delivery system was successfully developed, and our results revealed that CmHk1 was involved in the fungicide resistance and osmotic stress in C. militaris.
Assessing Progression of Biologic Therapies Based on Smoking Status in Patients With Crohn’s Disease
Authors: Alizadeh Madeline , Ali Osman , Cross Raymond K
Published: July 2023

Background

Active smoking is a well-established risk factor for developing Crohn’s disease (CD) and negatively impacts overall disease progression. Patients who start or continue smoking after CD diagnosis are at risk for poor outcomes, higher therapeutic requirements, and have higher rates of relapse. However, it remains unclear if the exposure to smoking leads to increased sequencing through treatment therapies, especially biologics.

Methods

The Study of Prospective Adult Research Cohort with IBD (SPARC IBD) registry has been collecting patient-reported outcomes data in real-time, as well as laboratory, endoscopic, and pathologic samples from 17 tertiary referral centers since 2016. In this study, we conducted a retrospective review of the SPARC clinical registry collected between December 2016 and January 2021 from 1 participating site, the University of Maryland School of Medicine’s Inflammatory Bowel Disease Program. A total of 619 patients were enrolled in the SPARC IBD database. Four hundred twenty-five patients with CD were included for initial review of completeness of data; of these, 144 patients were excluded due to missing data on smoking status and/or biologic treatment, resulting in a final cohort of 281 patients. We collected and analyzed baseline demographic and clinical characteristics. The final cohort was categorized into 3 exposure groups: current, former, and never smokers. Our outcome of interest was number biologics used, categorized into 3 groups: 0, 1, or ≥2 biologics.

Results

One hundred seventy-two never smokers, 70 former smokers, and 39 current smokers were identified. Current, former, and never smokers had no statistically significant differences in number of biologics used (ie, biologic sequencing). However, statistically significant independent risk factors for increased sequencing of biologics were identified. These risk factors included female sex, ileocolonic disease location, younger age at diagnosis, and prolonged disease duration; none of these factors remained significant in adjusted analyses.

Conclusion

To date, this is the first study assessing the association of smoking and sequencing of biologics. Although current or former smokers were not found to sequence through more biologics when compared with never smokers, smoking is a well-established risk factor for poor health outcomes, and efforts should be made to counsel patients to quit. Further, additional research must be done to stratify risk to patients based on amount of tobacco exposure.
SARS-CoV-2 mRNA vaccine-induced immune responses in rheumatoid arthritis
Authors: Limoges Marc-André , Lortie Audrey , Demontier Élodie , Quenum Akouavi Julite Irmine , Lessard Félix , Drouin Zacharie , Carrier Nathalie , Nguimbus Leopold Mbous , Beaulieu Marie-Claude , Boire Gilles , Piché Alain , Allard-Chamard Hugues , Ramanathan Sheela , Roux Sophie
Published: July 2023

Our objective was to characterize T and B cell responses to vaccination with SARS-CoV-2 antigens in immunocompromised rheumatoid arthritis (RA) patients. In 22 RA patients, clinical and biological variables were analyzed before and 4 weeks after each of 3 messenger RNA (mRNA) vaccine doses and compared with unmatched healthy individuals. Sequentially sampled peripheral blood mononuclear cells and sera were collected to determine immune profiles and to analyze the T cell response to a spike peptide pool and B cell specificity to the receptor-binding domain (RBD). Anti-spike antibodies were detectable in 6 of 22 RA patients after 1 dose of vaccine with increasing titers after each booster dose, although the overall response was lower compared with that in healthy control individuals. Responding patients after the first dose were more likely to have RA antibodies and a higher baseline proportion of circulating follicular B cells. In RA patients, the mRNA vaccine elicited a robust CD4+ T response to a spike peptide pool following the first and second doses. Consistent with the serologies, RBD-specific B cells exhibited a modest increase after the first dose and the second dose resulted in marked increases only in a fraction of the RA patients to both ancestral and omicron RBD. Our results highlight the importance of multidose COVID-19 vaccination in RA patients to develop a protective humoral response. However, these patients rapidly develop specific T CD4+ responses, despite delayed B cell responses.
Caveolin-1 is essential for the increased release of glutamate in the anterior cingulate cortex in neuropathic pain mice
Authors: Yang Jun-Xia , Zhao Wei-Nan , Jiang Yan-Yu , Ma Yu , Chen Dan-Dan , Lin Zhi-Hua , Yin Meng-Bing , Ren Kun-Peng
Published: July 2023

Neuropathic pain has a complex pathogenesis. Here, we examined the role of caveolin-1 (Cav-1) in the anterior cingulate cortex (ACC) in a chronic constriction injury (CCI) mouse model for the enhancement of presynaptic glutamate release in chronic neuropathic pain. Cav-1 was localized in glutamatergic neurons and showed higher expression in the ACC of CCI versus sham mice. Moreover, the release of glutamate from the ACC of the CCI mice was greater than that of the sham mice. Inhibition of Cav-1 by siRNAs greatly reduced the release of glutamate of ACC, while its overexpression (induced by injecting Lenti-Cav-1) reversed this process. The chemogenetics method was then used to activate or inhibit glutamatergic neurons in the ACC area. After 21 days of injection of AAV-hM3Dq in the sham mice, the release of glutamate was increased, the paw withdrawal latency was shortened, and expression of Cav-1 in the ACC was upregulated after intraperitoneal injection of 2 mg/kg clozapine N-oxide. Injection of AAV-hM4Di in the ACC of CCI mice led to the opposite effects. Furthermore, decreasing Cav-1 in the ACC in sham mice injected with rAAV-hM3DGq did not increase glutamate release. These findings suggest that Cav-1 in the ACC is essential for enhancing glutamate release in neuropathic pain.
Low-ionization iron-rich broad absorption-line quasar SDSS J 1652+2650: physical conditions in the ejected gas from excited Fe ii and metastable He i
Authors: Balashev S A , Ledoux C , Noterdaeme P , Boissé P , Krogager J-K , López S , Telikova K N
Published: July 2023

We present high-resolution VLT/UVES spectroscopy and a detailed analysis of the unique broad absorption-line system towards the quasar SDSS J 165252.67+265001.96. This system exhibits low-ionization metal absorption lines from the ground states and excited energy levels of Fe ii and Mn ii, and the meta-stable $2\, ^3S$ excited state of He i. The extended kinematics of the absorber encompasses three main clumps with velocity offsets of −5680, −4550, and −1770 km s−1 from the quasar emission redshift, z = 0.3509 ± 0.0003, derived from [O ii] emission. Each clump shows moderate partial covering of the background continuum source, Cf ≈ [0.53; 0.24; 0.81]. We discuss the excitation mechanisms at play in the gas, which we use to constrain the distance of the clouds from the active galactic nucleus (AGN) as well as the density, temperature, and typical sizes of the clouds. The number density is found to be nH ∼ 104 cm−3 and the temperature Te ∼ 104 K, with longitudinal cloudlet sizes of ≳0.01 pc. cloudy photoionization modelling of He i⋆, which is also produced at the interface between the neutral and ionized phases, assuming the number densities derived from Fe ii, constrains the ionization parameter to be log U ∼ −3. This corresponds to distances of a few 100 pc from the AGN. We discuss these results in the more general context of associated absorption-line systems and propose a connection between FeLoBALs and the recently identified molecular-rich intrinsic absorbers. Studies of significant samples of FeLoBALs, even though rare per se, will soon be possible due to large dedicated surveys paired with high-resolution spectroscopic follow-ups.
Towards ultra metal-poor DLAs: linking the chemistry of the most metal-poor DLA to the first stars
Authors: Welsh Louise , Cooke Ryan , Fumagalli Michele , Pettini Max
Published: July 2023

We present new Keck/HIRES data of the most metal-poor damped Ly α (DLA) system currently known. By targeting the strongest accessible Fe ii features, we have improved the upper limit of the [Fe/H] abundance determination by ∼1 dex, finding [Fe/H] < −3.66 (2σ). We also provide the first upper limit on the relative abundance of an odd-atomic number element for this system [Al/H] < −3.82 (2σ). Our analysis thus confirms that this zabs ≃ 3.08 DLA is not only the most metal-poor DLA but also the most iron-poor DLA currently known. We use the chemistry of this DLA, combined with a stochastic chemical enrichment model, to probe its enrichment history. We find that this DLA is best modelled by the yields of an individual Population III progenitor rather than multiple Population III stars. We then draw comparisons with other relic environments and, particularly, the stars within nearby ultra-faint dwarf galaxies. We identify a star within Boötes I, with a similar chemistry to that of the DLA presented here, suggesting that it may have been born in a gas cloud that had similar properties. The extremely metal-poor DLA at redshift zabs ≃ 3.08 (i.e. ∼2 Gyr after the Big Bang) may reside in one of the least polluted environments in the early Universe.
EYA2 tyrosine phosphatase inhibition reduces MYC and prevents medulloblastoma progression
Authors: Wolin Arthur R , Vincent Melanie Y , Hotz Taylor , Purdy Stephen C , Rosenbaum Sheera R , Hughes Connor J , Hsu Jessica Y , Oliphant Michael U J , Armstrong Brock , Wessells Veronica , Varella-Garcia Marileila , Galbraith Matthew D , Pierce Angela , Wang Dong , Venkataraman Sujatha , Danis Etienne , Veo Bethany , Serkova Natalie , Espinosa Joaquin M , Gustafson Daniel L , Vibhakar Rajeev , Ford Heide L
Published: July 2023

Background

Medulloblastoma is the most common pediatric brain malignancy. Patients with the Group 3 subtype of medulloblastoma (MB) often exhibit MYC amplification and/or overexpression and have the poorest prognosis. While Group 3 MB is known to be highly dependent on MYC, direct targeting of MYC remains elusive.

Methods

Patient gene expression data were used to identify highly expressed EYA2 in Group 3 MB samples, assess the correlation between EYA2 and MYC, and examine patient survival. Genetic and pharmacological studies were performed on EYA2 in Group 3 derived MB cell models to assess MYC regulation and viability in vitro and in vivo.

Results

EYA2 is more highly expressed in Group 3 MB than other MB subgroups and is essential for Group 3 MB growth in vitro and in vivo. EYA2 regulates MYC expression and protein stability in Group 3 MB, resulting in global alterations of MYC transcription. Inhibition of EYA2 tyrosine phosphatase activity, using a novel small molecule inhibitor (NCGC00249987, or 9987), significantly decreases Group 3 MB MYC expression in both flank and intracranial growth in vivo. Human MB RNA-seq data show that EYA2 and MYC are significantly positively correlated, high EYA2 expression is significantly associated with a MYC transcriptional signature, and patients with high EYA2 and MYC expression have worse prognoses than those that do not express both genes at high levels.

Conclusions

Our data demonstrate that EYA2 is a critical regulator of MYC in Group 3 MB and suggest a novel therapeutic avenue to target this highly lethal disease.
An arginine-to-histidine mutation in flavanone-3-hydroxylase results in pink strawberry fruits
Authors: Xu Pengbo , Li Xinyu , Fan Junmiao , Tian Shuhua , Cao Minghao , Lin Anqi , Gao Qinhua , Xiao Kun , Wang Chong , Kuang Huiyun , Lian Hongli
Published: July 2023

Fruit color is a very important external commodity factor for consumers. Compared to the most typical red octoploid strawberry (Fragaria × ananassa), the pink strawberry often sells for a more expensive price and has a higher economic benefit due to its outstanding color. However, few studies have examined the molecular basis of pink-colored strawberry fruit. Through an EMS mutagenesis of woodland strawberry (Fragaria vesca), we identified a mutant with pink fruits and green petioles. Bulked-segregant analysis sequencing analysis and gene function verification confirmed that the responsible mutation resides in a gene encoding flavanone-3-hydroxylase (F3H) in the anthocyanin synthesis pathway. This nonsynonymous mutation results in an arginine-to-histidine change at position 130 of F3H. Molecular docking experiments showed that the arginine-to-histidine mutation results in a reduction of intermolecular force-hydrogen bonding between the F3H protein and its substrates. Enzymatic experiments showed a greatly reduced ability of the mutated F3H protein to catalyze the conversion of the substrates and hence a blockage of the anthocyanin synthesis pathway. The discovery of a key residue in the F3H gene controlling anthocyanin synthesis provides a clear target of modification for the molecular breeding of strawberry varieties with pink-colored fruits, which may be of great commercial value.
An Anatomy Lesson for Democrats
Authors: Huq Aziz Z
Published: July 2023

The extensive political science, sociology, and legal literatures on democratic backsliding all tend to approach the issue in the same way: Start with a recent example of democratic decay. Then reason back from that example to generate a more extensive account of backsliding mechanisms or consequences. In contrast, Norwegian political scientist and sociologist Stein Ringen, in a book called How Democracies Live: Power, Statecraft, and Freedom in Modern Societies, offers a diagnosis of democratic backsliding that flips this standard sequence of analysis. Rather than beginning with case studies, Ringen offers an investigation of five “core” concepts of political theory. Those who seek to ameliorate democracy's current woes, he contends, should start with this sort of very general anatomy lesson. Only with the resulting conceptual map of political theory can they develop specific lessons for the task of managing democratic revival today. By negative implication, Ringen suggests, reformers will be led astray by starting with a specific case. The latter approach, he implies, causes them to overlook or misconstrue basic elements of the political order that must be fixed before the democratic ship can be righted. This review considers whether Ringen's anatomy-inspired method yields insights and, further, whether, more generally, an anatomical approach to political concepts can deepen our understanding of democracy and its present travails. It offers reasons for skepticism on both counts. It may well be possible to construct a taxonomy of political concepts to clarify the terms of democratic survival. But the specific taxonomy of core concepts offered in How Democracies Live does not plainly succeed.
Whole exome sequencing of a German sarcoidosis family with four affected and one spontaneous remission case
Authors: Kvacskay Peter , El Jammal Thomas , Lorenz Hanns-Martin , Pacheco Yves , Calender Alain
Published: July 2023

Objectives

To analyse genetic mechanisms triggering familial sarcoidosis, whole exome screening of a family of six persons with four cases of sarcoidosis and two healthy controls was performed integrating progressive and spontaneous remission cases and evaluating involved genetic alterations that could potentially determine the individual course of the disease.

Methods

Clinical diagnostic criteria in patients of the selected sarcoidosis family were according to American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and other Granulomatous Disorders guidelines. Exome screening of four patients and the two intrafamilial healthy relatives was performed by paired-end (2 × 100 bp) sequencing. We then selected the gene variants considered pathogenic on the basis of a series of prediction software applications and presence only in members of the family affected by sarcoidosis, after subtracting the common variations observed in healthy subjects.

Results

Four persons out of six family members were affected by sarcoidosis. Fifty genes with uncommon in silico pathogenic variants could be identified that differentiated affected and healthy family members. One patient with sarcoidosis showed spontaneous remission whereas the remaining three patients required immunosuppressive treatment. Subtraction analysis revealed 18 genes that distinguished the three progressive cases from the patient with spontaneous remission.

Conclusion

The genetic analysis of these cases with familial sarcoidosis identified several involved genes and functional pathways that could help in understanding the basic mechanisms that determine the development of the disease and that discriminate spontaneously regressive and progressive forms.
Prognostic significance of pericardial effusion in systemic sclerosis-associated pulmonary hypertension: analysis from the PHAROS Registry
Authors: Luo Yiming , Gordon Jessica K , Xu Jiehui , Kolstad Kathleen D , Chung Lorinda , Steen Virginia D , Bernstein Elana J ,   PHAROS Investigators, Csuka Mary E , Derk Chris T , Domsic Robyn T , Fischer Aryeh , Frech Tracy , Goldberg Avram Z , Hant Faye , Hinchcliff Monique , Horn Evelyn , Hummers Laura , Hsu Vivien , Kafaja Susanna , Khanna Dinesh , Molitor Jerry , Saketkoo Lesley , Shapiro Lee , Silver Rick , Simms Robert
Published: July 2023

Objectives

Pulmonary hypertension (PH) is a leading cause of death in patients with SSc. The purpose of this study was to determine the prognostic significance of pericardial effusion in patients with SSc-PH.

Methods

Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS) is a prospective multicentre registry which enrolled patients with newly diagnosed SSc-PH from 2005 to 2016. The prognostic impact of pericardial effusion status, including those who ever or never had pericardial effusion, and those who had persistent or intermittent pericardial effusion, was analysed. Kaplan–Meier survival analyses, log-rank test, and multivariable Cox proportional hazards regression were performed.

Results

Of the 335 patients with SSc-PH diagnosed by right heart catheterization and documentation of pericardial effusion presence or absence on echocardiogram, 166 (50%) ever had pericardial effusion. Ever having pericardial effusion was not predictive of survival (log-rank test P = 0.49). Of the 245 SSc-PH patients who had at least two echocardiograms, 44% had a change in pericardial effusion status over an average of 4.3 years of follow up. Having a persistent pericardial effusion was an independent predictor of survival [adjusted hazard ratio (aHR)=2.34, 95% CI 1.20, 4.64, P = 0.002], while intermittent pericardial effusion was not a predictor of survival (aHR = 0.89, 95% CI 0.52, 1.56, P = 0.68), in a multivariable-adjusted analysis.

Conclusion

Persistent pericardial effusion, but not ever having had pericardial effusion or intermittent pericardial effusion, was independently associated with poorer survival. Incorporating information from serial echocardiograms may help clinicians better prognosticate survival in their SSc-PH patients.
Construct validity and reliability of the Assessment of Systemic Sclerosis-Associated Raynaud’s Phenomenon (ASRAP) questionnaire
Authors: Pauling John D , Yu Lan , Frech Tracy M , Herrick Ariane L , Hummers Laura K , Shah Ami A , Denton Christopher P , Saketkoo Lesley Ann , Withey Jane , Khanna Dinesh , Domsic Robyn T
Published: July 2023

Objectives

Assessment of construct validity and reliability of a novel patient-reported outcome (PRO) instrument for assessing the severity and impact of RP in SSc.

Methods

An international multicentre study validation study of the 27-item Assessment of Systemic Sclerosis-Associated Raynaud’s Phenomenon (ASRAP) and 10-item short-form (ASRAP-SF) questionnaires. The relationship between ASRAP questionnaires and demographics, clinical phenotype and legacy instruments for assessing SSc-RP severity, disability and pain was assessed. Repeatability was evaluated at 1 week. Anchor-based statements of health status facilitated assessment of ASRAP thresholds of meaning.

Results

A total of 420 SSc subjects were enrolled. There was good correlation between ASRAP (and ASRAP-SF) with RP visual analogue scale (VAS) and Scleroderma Health Assessment Questionnaire RP VAS (rho range 0.648–0.727, P < 0.001). Correlation with diary-based assessment of SSc-RP attack frequency and duration was lower (rho range 0.258–0.504, P < 0.001). ASRAP questionnaires had good correlation with instruments for assessing disability, hand function, pain and global health assessment (rho range 0.427–0.575, P < 0.001). Significantly higher ASRAP scores were identified in smokers, patients with active digital ulceration (DU), previous history of DU and calcinosis (P < 0.05 for all comparisons). There was excellent repeatability at 1 week among patients with stable SSc-RP symptoms (intra-class coefficients of 0.891 and 0.848, P < 0.001). Patient-acceptable symptom state thresholds for ASRAP and ASRAP-SF were 45.34 and 45.77, respectively. A preliminary Minimally Important Clinical Difference threshold of 4.17 (95% CI 0.53, 7.81, P = 0.029) was estimated.

Conclusion

ASRAP and ASRAP-SF questionnaires are valid and reliable novel PRO instruments for assessing the severity and impact of SSc-RP.
Developing an Inclusive Scholarship Curriculum for Medical Students
Authors: Deptola Amber , Hudson Darrell , Mattar Caline , Chung Koong-Nah , Kallogjeri Dorina , Chamberlain Aaron , Aagaard Eva
Published: July 2023

Problem

As part of a curriculum renewal, in 2020, Washington University School of Medicine in St. Louis sought to create an integrated curriculum that allows students to explore 4 academic career pathways (advocacy/global health, education, innovation, and research) and engage in scholarship activities—the Inquiry Curriculum. The curriculum needed to focus on foundational scholarship skills that would be applicable to all pathways. This article describes the process used to develop the curriculum learning objectives and lessons learned from initial implementation.

Approach

The authors used a modified Delphi process to survey faculty experts from the 4 pathways to determine the objectives (March–May 2020). Twenty-four faculty were surveyed about 48 initial objectives created using Glassick’s scholarship criteria. After 2 rounds, 28 objectives met consensus. Further oversight committee review and revisions by session leads resulted in 77 unique objectives for 23 sessions in the curriculum that launched in spring 2021.

Outcomes

Four themes were identified from student feedback: (1) the Inquiry Curriculum framework creates opportunities for students to gain exposure to various approaches to understanding and addressing health care problems, (2) the curriculum targeted higher-level objectives for traditional research content and lower-level objectives for nontraditional content, (3) Glassick’s criteria provided a useful structure for students to understand the rationale for and ordering of content, and (4) the curriculum had natural overlap with content often taught elsewhere in the curriculum, including evidence-based medicine, health equity, public and population health, and quality improvement and patient safety.

Next Steps

The authors plan to consolidate sessions where there is redundancy, expand other sessions that require more time, and more purposefully discuss prior content when redundancy is intentional. Exploring other potential measures of curricular success, such as student learning outcomes, scholarly productivity, and impact on future scholarship engagement and career paths, is part of ongoing work.
Radiomic Signatures Based on Mammography and Magnetic Resonance Imaging as New Markers for Estimation of Ki-67 and HER-2 Status in Breast Cancer
Authors: Fan Ying , Zhao Dan , Su Juan , Yuan Wendi , Niu Shuxian , Guo Wei , Jiang Wenyan
Published: July 2023

Objective

The aim of the study is to investigate the values of intratumoral and peritumoral regions based on mammography and magnetic resonance imaging for the prediction of Ki-67 and human epidermal growth factor (HER-2) status in breast cancer (BC).

Methods

Two hundred BC patients were consecutively enrolled between January 2017 and March 2021 and divided into training (n = 133) and validation (n = 67) groups. All the patients underwent breast mammography and magnetic resonance imaging screening. Features were derived from intratumoral and peritumoral regions of the tumor and selected using the least absolute shrinkage and selection operator regression to build radiomic signatures (RSs). Receiver operating characteristic curve analysis and the DeLong test were performed to assess and compare each RS.

Results

For each modality, the combined RSs integrating features from intratumoral and peritumoral regions always showed better prediction performance for predicting Ki-67 and HER-2 status compared with the RSs derived from intratumoral or peritumoral regions separately. The multimodality and multiregional combined RSs achieved the best prediction performance for predicting the Ki-67 and HER-2 status with an area under the receiver operating characteristic curve of 0.888 and 0.868 in the training cohort and 0.800 and 0.848 in the validation cohort, respectively.

Conclusions

Peritumoral areas provide complementary information to intratumoral regions of BC. The developed multimodality and multiregional combined RSs have good potential for noninvasive evaluation of Ki-67 and HER-2 status in BC.