bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromosomal-Level Genome Assembly of a True Bug, Aspongopus chinensis Dallas, 1851 (Hemiptera: Dinidoridae)
Authors: Jiang Tao , Yin Zhiyong , Cai Renlian , Yu Hengmei , Lu Qin , Zhao Shuai , Tian Ying , Yan Yufang , Guo Jianjun , Chen Xiangsheng
Published: October 2021

The true bug, Aspongopus chinensis Dallas, 1851 (Hemiptera: Dinidoridae), is a fascinating insect with prolonged diapause and medicinal properties but also a notorious pest. However, because of the lack of genomic resources, an in-depth understanding of its biological characteristics is lacking. Here, we report the first genome assembly of A. chinensis anchored to 10 pseudochromosomes, which was achieved by combining PacBio long reads and Hi-C sequencing data. This chromosome-level genome assembly was 1.55 Gb in size with a scaffold N50 of 156 Mb. The benchmarking universal single-copy ortholog (BUSCO) analysis of the assembly captured 96.6% of the BUSCO genes. A total of 686,888,052 bp of repeat sequences, 18,511 protein-coding genes, and 1,749 noncoding RNAs were annotated. By comparing the A. chinensis genome with that of 8 homologous insects and 2 model organisms, 213 rapidly evolving gene families were identified, including 83 expanded and 130 contracted gene families. The functional enrichment of Gene Ontology and KEGG pathways showed that the significantly expanded gene families were primarily involved in metabolism, immunity, detoxification, and DNA/RNA replication associated with stress responses. The data reported here shed light on the ecological adaptation of A. chinensis and further expanded our understanding of true bug evolution in general.
The distribution of mutational effects on fitness in Caenorhabditis elegans inferred from standing genetic variation
Authors: Gilbert Kimberly J , Zdraljevic Stefan , Cook Daniel E , Cutter Asher D , Andersen Erik C , Baer Charles F
Published: October 2021

The distribution of fitness effects (DFE) for new mutations is one of the most theoretically important but difficult to estimate properties in population genetics. A crucial challenge to inferring the DFE from natural genetic variation is the sensitivity of the site frequency spectrum to factors like population size change, population substructure, genome structure, and nonrandom mating. Although inference methods aim to control for population size changes, the influence of nonrandom mating remains incompletely understood, despite being a common feature of many species. We report the DFE estimated from 326 genomes of Caenorhabditis elegans, a nematode roundworm with a high rate of self-fertilization. We evaluate the robustness of DFE inferences using simulated data that mimics the genomic structure and reproductive life history of C. elegans. Our observations demonstrate how the combined influence of self-fertilization, genome structure, and natural selection on linked sites can conspire to compromise estimates of the DFE from extant polymorphisms with existing methods. These factors together tend to bias inferences toward weakly deleterious mutations, making it challenging to have full confidence in the inferred DFE of new mutations as deduced from standing genetic variation in species like C. elegans. Improved methods for inferring the DFE are needed to appropriately handle strong linked selection and selfing. These results highlight the importance of understanding the combined effects of processes that can bias our interpretations of evolution in natural populations.
Inferring core processes using stochastic models of the geodynamo
Authors: Davis William , Buffett Bruce
Published: October 2021

Recent studies have represented time variations in the Earth’s axial magnetic dipole field as a stochastic process, which comprise both deterministic and random elements. To explore how these elements are affected by the style and vigour of convection in the core, as well as the core–mantle boundary conditions, we construct stochastic models from a set of numerical dynamo simulations at low Ekman numbers. The deterministic part of the stochastic model, the drift term, characterizes the slow relaxation of the dipole back to its time average. We find that these variations are predominantly accommodated by the slowest decay mode, enhanced by turbulent diffusion to enable a faster relaxation. The random part—the noise term—is set by the amplitude and timescale of variations in dipole field generation, including contributions from both velocity and internal magnetic field variations. Applying these interpretations to the palaeomagnetic field suggest that reversal rates are very sensitive to rms variations in the field generation. Less than a 50 per cent reduction in rms field generation variations is sufficient to prevent reversals for the recent magnetic field.
Lis1 mutation prevents basal radial glia-like cell production in the mouse
Authors: Penisson Maxime , Jin Mingyue , Wang Shengming , Hirotsune Shinji , Francis Fiona , Belvindrah Richard
Published: October 2021

Human cerebral cortical malformations are associated with progenitor proliferation and neuronal migration abnormalities. Progenitor cells include apical radial glia, intermediate progenitors and basal (or outer) radial glia (bRGs or oRGs). bRGs are few in number in lissencephalic species (e.g. the mouse) but abundant in gyrencephalic brains. The LIS1 gene coding for a dynein regulator, is mutated in human lissencephaly, associated also in some cases with microcephaly. LIS1 was shown to be important during cell division and neuronal migration. Here, we generated bRG-like cells in the mouse embryonic brain, investigating the role of Lis1 in their formation. This was achieved by in utero electroporation of a hominoid-specific gene TBC1D3 (coding for a RAB-GAP protein) at mouse embryonic day (E) 14.5. We first confirmed that TBC1D3 expression in wild-type (WT) brain generates numerous Pax6+ bRG-like cells that are basally localized. Second, using the same approach, we assessed the formation of these cells in heterozygote Lis1 mutant brains. Our novel results show that Lis1 depletion in the forebrain from E9.5 prevented subsequent TBC1D3-induced bRG-like cell amplification. Indeed, we observe perturbation of the ventricular zone (VZ) in the mutant. Lis1 depletion altered adhesion proteins and mitotic spindle orientations at the ventricular surface and increased the proportion of abventricular mitoses. Progenitor outcome could not be further altered by TBC1D3. We conclude that disruption of Lis1/LIS1 dosage is likely to be detrimental for appropriate progenitor number and position, contributing to lissencephaly pathogenesis.
Trade-offs among spatio-temporal management actions for a mixed-stock fishery revealed by Bayesian decision analysis
Authors: Whitlock R E , Pakarinen T , Palm S , Koljonen M L , Östergren J , Dannewitz J
Published: October 2021

Management and conservation of populations that are harvested simultaneously present a unique set of challenges. Failure to account for differences in productivity and spatio-temporal abundance patterns can lead to over-exploitation of depleted populations and/or loss of potential yield from healthy ones. Mixed-stock fisheries (where a stock may comprise one or more populations of reared or wild origin) harvest multiple stocks, often in unknown proportions, and lack of tools for estimation of stock-specific harvest rates can hamper status evaluations and attainment of management goals. We present a method for evaluating stock-specific impacts of alternative harvest strategies, using coastal trap net fisheries for Atlantic salmon (Salmo salar) in the Baltic Sea as a case study. Our results demonstrate a large variation among stocks in coastal mixed fishery harvest rates, as well as large differences in harvest rates relative to stock-specific maximum sustainable yield (MSY) and recovery levels. Bayesian decision analysis showed that spatio-temporal management actions, such as delayed fishery opening and closed areas may be effective in improving probabilities of meeting management objectives for Baltic salmon. However, stocks did not respond uniformly to different management actions, highlighting the potential for trade-offs in reaching stock-specific targets that must be considered by managers.
Actual incidence of cerebral infarction after thoracic endovascular aortic repair: a magnetic resonance imaging study
Authors: Kotani Sohsyu , Inoue Yoshito , Oki Naohiko , Yashiro Hideki , Hachiya Takashi
Published: October 2021

OBJECTIVES

The actual incidence of cerebral infarction (CI), including asymptomatic infarction, owing to thoracic endovascular aortic repair (TEVAR) has not been reported in detail. This study was performed to investigate the incidence of post-TEVAR CI by using diffusion-weighted magnetic resonance imaging (DW-MRI) and to determine the risk factors for both symptomatic and asymptomatic CI.

METHODS

We examined 64 patients undergoing TEVAR at our institute between April 2017 and November 2020. Aortic atheroma was graded from 1 to 5 by preoperative computed tomography. Cerebral DW-MRIs were conducted 2 days after the procedure to diagnose postoperative CI.

RESULTS

A total of 44 new foci were detected by post-interventional cerebral DW-MRI in 22 patients (34.4%). Only one patient developed a symptomatic stroke (1.6%), and TEVAR was successfully completed in all cases. Debranching of the aortic arch and left subclavian artery occlusion with a vascular plug was performed in 19 (29.7%) and 12 (18.8%) patients, respectively. The number of patients with proximal landing zones 0–2 was significantly higher in the CI group than in the non-CI group (68.2% vs 11.9%; P < 0.001). The following risk factors were identified for asymptomatic CI: aortic arch debranching (P < 0.001), left subclavian artery occlusion (P = 0.001) and grade 4/5 aortic arch atheroma (P = 0.048).

CONCLUSIONS

Over one-third of the patients examined by cerebral DW-MRI after TEVAR were diagnosed with CI. High-grade atheroma and TEVAR landing in zone 0–2 were found to be positively associated with asymptomatic CI.

Clinical trial registration

02-014.
Subxiphoid thoracoscopic thymectomy for myasthenia gravis
Authors: Liu Yuanyuan , Zhang Jinghao , Wu Wenbin , Zhang Hui , Zhao Chen , Zhang Miao
Published: October 2021

We investigated the efficacy of subxiphoid thoracoscopic thymectomy in patients with myasthenia gravis. The data of 37 consecutive cases were reviewed. 2 cases of postoperative myasthenia gravis crisis and 4 cases of residual mediastinal fat tissue were recorded. Moreover, 29 patients presented the neurological outcomes, and complete stable remission was achieved in 5 (17.2%) cases. Subxiphoid thymectomy is technically feasible. High-quality evidence is warranted before this approach can be recommended.
The major histocompatibility complex: new insights from old molecules into the pathogenesis of autoimmunity
Authors: Arase Hisashi
Published: October 2021

The major histocompatibility complex (MHC) is a central molecule in the immune system. The MHC is also a highly polymorphic gene that is the most strongly involved in susceptibility to many autoimmune diseases. Therefore, the elucidation of the mechanism by which specific MHC alleles are involved in autoimmune disease susceptibility is important to our understanding of the pathogenesis of autoimmune diseases. Specific autoantibody production is observed in many autoimmune diseases, but the mechanism underlying their production remains unclear. We have found that MHC class II molecules exhibit a chaperone-like function to transport misfolded proteins in the endoplasmic reticulum to the outside of cells. Furthermore, misfolded proteins transported to the cell surface by MHC class II molecules of autoimmune disease risk alleles are major autoantibody targets. In this article, I propose a novel mechanism underlying autoimmune diseases mediated by misfolded proteins complexed with MHC class II molecules.
Activity of the combination of colistin and fosfomycin against NDM-1-producing Escherichia coli with variable levels of susceptibility to colistin and fosfomycin in a murine model of peritonitis
Authors: Le Menestrel Alice , Guerin François , Chau Françoise , Massias Laurent , Benchetrit Laura , Cattoir Vincent , Fantin Bruno , de Lastours Victoire
Published: October 2021

Background

Alternative treatments are needed against NDM-1-producing Escherichia coli. Colistin (COL) and fosfomycin (FOS) often remain active in vitro but selection of resistant mutants is frequent if used separately. We determined whether the combination of colistin and fosfomycin may be useful to treat infections with NDM-1-producing E. coli with varying levels of resistance.

Methods

Isogenic derivatives of E. coli CFT073 with blaNDM-1 and variable levels of resistance to colistin and fosfomycin (CFT073-NDM1, CFT073-NDM1-COL and CFT073-NDM1-FOS, respectively) were used. The combination (colistin + fosfomycin) was tested in vitro and in a fatal peritonitis murine model. Mortality and bacterial loads were determined and resistant mutants detected.

Results

Colistin MICs were 0.5, 16 and 0.5 mg/L and fosfomycin MICs were 1, 1 and 32 mg/L against CFT073-NDM1, CFT073-NDM1-COL and CFT073-NDM1-FOS, respectively. In time–kill curves, combining colistin with fosfomycin was synergistic and bactericidal against CFT073-NDM1 and CFT073-NDM1-FOS, with concentrations of 4× MIC (for both drugs), but not against CFT073-NDM1-COL (concentrations of colistin = 0.5× MIC), due to regrowth with fosfomycin-resistant mutants. Mice died less and bacterial counts were lower in spleen with the combination compared with monotherapy against all strains; the combination prevented selection of resistant mutants except for CFT073-NDM1-COL where fosfomycin-resistant mutants were found in all mice.

Conclusions

Combining colistin and fosfomycin was beneficial in vitro and in vivo against NDM-1-producing E. coli, even with strains less susceptible to colistin and fosfomycin. However, the combination failed to prevent the emergence of fosfomycin-resistant mutants against colistin-resistant strains. Combining colistin and fosfomycin constitutes an alternative for treatment of NDM-1 E. coli, except against colistin-resistant strains.
Aminoglycoside-resistance gene signatures are predictive of aminoglycoside MICs for carbapenem-resistant Klebsiella pneumoniae
Authors: Huang Yanqin , Rana Amisha P. , Wenzler Eric , Ozer Egon A. , Krapp Fiorella , Bulitta Jürgen B. , Hauser Alan R. , Bulman Zackery P.
Published: October 2021

Background

Aminoglycoside-containing regimens may be an effective treatment option for infections caused by carbapenem-resistant Klebsiella pneumoniae (CR-Kp), but aminoglycoside-resistance genes are common in these strains. The relationship between the aminoglycoside-resistance genes and aminoglycoside MICs remains poorly defined.

Objectives

To identify genotypic signatures capable of predicting aminoglycoside MICs for CR-Kp.

Methods

Clinical CR-Kp isolates (n = 158) underwent WGS to detect aminoglycoside-resistance genes. MICs of amikacin, gentamicin, plazomicin and tobramycin were determined by broth microdilution (BMD). Principal component analysis was used to initially separate isolates based on genotype. Multiple linear regression was then used to generate models that predict aminoglycoside MICs based on the aminoglycoside-resistance genes. Last, the performance of the predictive models was tested against a validation cohort of 29 CR-Kp isolates.

Results

Among the original 158 CR-Kp isolates, 91.77% (145/158) had at least one clinically relevant aminoglycoside-resistance gene. As a group, 99.37%, 84.81%, 82.28% and 10.76% of the CR-Kp isolates were susceptible to plazomicin, amikacin, gentamicin and tobramycin, respectively. The first two principal components explained 72.23% of the total variance in aminoglycoside MICs and separated isolates into four groups with aac(6′)-Ib, aac(6′)-Ib′, aac(6′)-Ib+aac(6′)-Ib′ or no clinically relevant aminoglycoside-resistance genes. Regression models predicted aminoglycoside MICs with adjusted R2 values of 56%–99%. Within the validation cohort, the categorical agreement when comparing the observed BMD MICs with the predicated MICs was 96.55%, 89.66%, 86.21% and 82.76% for plazomicin, gentamicin, amikacin and tobramycin, respectively.

Conclusions

Susceptibility to each aminoglycoside varies in CR-Kp. Detection of aminoglycoside-resistance genes may be useful to predict aminoglycoside MICs for CR-Kp.
Design and evaluation of a Women in American Medical Informatics Association (AMIA) leadership program
Authors: Grando Adela , Ancker Jessica S , Tao Donghua , Howe Rachael , Coonan Clare , Johns Merida , Chapman Wendy
Published: October 2021

The objective is to report on the design and evaluation of the inaugural Women in AMIA Leadership Program. A year-long leadership curriculum was developed. Survey responses were summarized with descriptive statistics and quotes selected. Twenty-four scholars participated in the program. There was a significant increase in perceived achievement of learning objectives after the program (P < .0001). The largest improvement was in leadership confidence and presence in work interactions (modal answer Neutral in presurvey from 21 responses rose to Agree in postsurvey from 24 responses). Most (92% of 13) scholars clarified leadership vision and goals and (83% of 18) would be Very Likely to recommend the program to others. The goals of the program—developing women’s leader identity, increasing networks, and accumulating experience for future programs—were achieved. The second leadership program is on its way in the United States and Australia. This study may benefit organizations seeking to develop leadership programs for women in informatics and digital health.
Can Native Plants Mitigate Climate-related Forage Dearth for Honey Bees (Hymenoptera: Apidae)?
Authors: Zhang Ge , St. Clair Ashley L , Dolezal Adam G , Toth Amy L , O’Neal Matthew E
Published: October 2021

Extreme weather events, like high temperatures and droughts, are predicted to become common with climate change, and may negatively impact plant growth. How honey bees (Apis mellifera L. [Hymenoptera: Apidae]) will respond to this challenge is unclear, especially when collecting pollen, their primary source of protein, lipids, and micro-nutrients. We explored this response with a data set from multiple research projects that measured pollen collected by honey bees during 2015–2017 in which above-average temperatures and a drought occurred in 2017. We summarized the abundance and diversity of pollen collected from July to September in replicated apiaries kept at commercial soybean and corn farms in Iowa, in the Midwestern USA. The most commonly collected pollen was from clover (Trifolium spp. [Fabales: Fabaceae]), which dramatically declined in absolute and relative abundance in July 2017 during a period of high temperatures and drought. Due to an apparent lack of clover, honey bees switched to the more drought-tolerant native species (e.g., Chamaecrista fasciculata [Michx.] Greene [Fabales: Fabaceae], Dalea purpurea Vent. [Fabales: Fabaceae], Solidago spp. [Asterales: Asteraceae]), and several species of Asteraceae. This was especially noticeable in August 2017 when C. fasciculata dominated (87%) and clover disappeared from bee-collected pollen. We discuss the potential implications of climate-induced forage dearth on honey bee nutritional health. We also compare these results to a growing body of literature on the use of native, perennial flowering plants found in Midwestern prairies for the conservation of beneficial insects. We discuss the potential for drought resistant-native plants to potentially promote resilience to climate change for the non-native, managed honey bee colonies in the United States.
Long-term outcomes in extensive disease small cell lung cancer patients treated without immune checkpoint inhibitors
Authors: Wakuda Kazushige , Yabe Michitoshi , Kodama Hiroaki , Nishioka Naoya , Miyawaki Taichi , Miyawaki Eriko , Mamesaya Nobuaki , Kobayashi Haruki , Omori Shota , Ono Akira , Kenmotsu Hirotsugu , Naito Tateaki , Murakami Haruyasu , Shimizu Tetsuo , Gon Yasuhiro , Takahashi Toshiaki
Published: October 2021

Objective

Immune checkpoint inhibitors (ICIs) combined with chemotherapy have been approved as first-line treatment for patients with untreated extensive disease-small cell lung cancer (ED-SCLC). However, there are few reports about the long-term outcomes in patients with ED-SCLC treated without ICIs. Thus, we analyzed the long-term outcomes in patients with ED-SCLC.

Methods

We retrospectively examined the medical records of patients with SCLC who were treated at our hospital between September 2002 and September 2019. The main inclusion criteria were as follows: (i) histological or cytological confirmation of SCLC, (ii) diagnosed with ED-SCLC and (iii) received chemotherapy, not including ICIs, as the first-line treatment. To assess the trends of treatment outcomes, we compared the survival outcomes between 2002–2010 (early) and 2011–2019 (late) groups.

Results

A total of 314 patients were included in this study. Patient characteristics at the time of first-line treatment were as follows: median age was 69 years; 82% of the patients were male and 70% had a performance status of 0 or 1. The median follow-up time of overall survival (OS) was 7.4 years, and 89% of the patients died. The median progression-free survival and survival time were 4.9 and 12.1 months, respectively. Five-year survival rate was 2%. There was no significant difference in survival between the early and late groups.

Conclusions

We found that the long-term outcomes in ED-SCLC patients treated without ICIs were poor. Prior to the approval of ICI treatment for ED-SCLC, there was no improvement in the OS for ~20 years.
Withdrawn as duplicate: Social Ties and the Influence of Public Policies on Individual Opinions: The Case of Same-Sex Marriage Laws
Authors: Blasco Sylvie , Moreno Galbis Eva , Tanguy Jeremy
Published: October 2021

This article has been withdrawn due to a publisher error that caused the article to be duplicated. The definitive version of this article is published under DOI https://doi.org/10.1093/jleo/ewab001.
Satisfaction among patients and caregivers receiving value-added services during the COVID-19 pandemic outbreak in a tertiary hospital in the Perak state of Malaysia
Authors: Chew Lan-Sim , Yeo Yee-Ling , Chang Chee-Tao , Chew Chii-Chii , George Doris , Rajan Philip
Published: October 2021

Objectives

Patient satisfaction was used as an indicator of service quality in the public hospitals. The pharmacy value-added services (VAS) were intensified after the COVID-19 outbreak, and evaluation of user’s satisfaction was important for service improvement.

Methods

This was a single-centre, cross-sectional, web-based study in the outpatient pharmacy in a tertiary hospital in the Perak state of Malaysia. Patients and caregivers aged 18 years and above, received at least one prescription refill using the pharmacy VAS from April to September 2020, were included. The questionnaire was adapted from a validated tool, underwent face and content validation before dissemination. The link was disseminated to the targeted population through short messages service (SMS).

Key findings

Out of 1200 invited people, 303 agreed to participate. Majority of the respondents were male (160, 52.8%), Chinese (156, 51.5%), with tertiary education (201, 66.3%) and retiree (112, 37.0%). Out of a maximum score of 5, the overall mean satisfaction score was 4.42 (SD: 0.55). The respondents were most agreeable to time-saving benefits of the pharmacy VAS (4.56 ± 0.63). Majority of the respondents felt that pharmacy VAS had made their life easier (290, 95.7%) and planned to recommend the pharmacy VAS to others (292, 96.4%) Respondents aged more than 60 (versus age 18–35, β = 2.375, P < 0.001) and those who used drive-through service (versus SPUB, β = 2.272, P = 0.001) reported higher satisfaction scores. Several suggestions were made for service improvement, including longer operating hours (18, 6.0%), upgraded communication system (9, 3.0%), smoother registration process (9, 3.0%), more polite staff (9, 3.0%), selection of preferred postage delivery time (6, 2.0%) and promotion of VAS (4, 1.3%)

Conclusions

Majority of the respondents were highly satisfied towards the pharmacy VAS. Future studies should compare the satisfaction of VAS with traditional counter service to compare the level and factors that contributed to the users’ satisfaction.
Anticancer agent α-sulfoquinovosyl-acylpropanediol enhances the radiosensitivity of human malignant mesothelioma in nude mouse models
Authors: Inamasu Eiko , Tsuchiya Tomoshi , Yamauchi Motohiro , Nishi Kodai , Matsuda Katsuya , Sugawara Fumio , Sakaguchi Kengo , Mori Ryoichi , Matsumoto Keitaro , Miyazaki Takuro , Hatachi Go , Doi Ryoichiro , Watanabe Hironosuke , Tomoshige Koichi , Matsuda Naoki , Higami Yoshikazu , Shimokawa Isao , Nakashima Masahiro , Nagayasu Takeshi
Published: October 2021

Malignant pleural mesothelioma (MPM) is a highly malignant disease that develops after asbestos exposure. Although the number of MPM cases is predicted to increase, no effective standard therapies have been established. The novel radiosensitizer α-sulfoquinovosyl-acylpropanediol (SQAP) enhances the effects of γ-radiation in human lung and prostate cancer cell lines and in animal models. In this study, we explored the radiosensitizing effect of SQAP and its mechanisms in MPM. The human MPM cell lines MSTO-211H and MESO-4 were implanted subcutaneously into the backs and thoracic cavities of immunodeficient KSN/Slc mice, then 2 mg/kg SQAP was intravenously administered with or without irradiation with a total body dose of 8 Gy. In both the orthotopic and ectopic xenograft murine models, the combination of irradiation plus SQAP delayed the implanted human MSTO-211H tumor growth. The analysis of the changes in the relative tumor volume of the MSTO-211H indicated a statistically significant difference after 8 Gy total body combined with 2 mg/kg SQAP, compared to both the untreated control (P = 0.0127) and the radiation treatment alone (P = 0.0171). After the treatment in each case, immunostaining of the harvested tumors revealed decreased cell proliferation, increased apoptosis and normalization of tumor blood vessels in the SQAP- and irradiation-treated group. Furthermore, hypoxia-inducible factor (HIF) 1 mRNA and protein expression were decreased, indicating reoxygenation in this group. In conclusion, SQAP improved hypoxic conditions in tumor tissue and may elicit a radiosensitizing effect in malignant mesothelioma models.
Quantitative analysis of the intra-beam respiratory motion with baseline drift for respiratory-gating lung stereotactic body radiation therapy
Authors: Yasue Kenji , Fuse Hiraku , Oyama Satoshi , Hanada Koichi , Shinoda Kazuya , Ikoma Hideaki , Fujisaki Tatsuya , Tamaki Yoshio
Published: October 2021

This study aimed to quantitatively clarify the baseline drift for each respiratory cycle in two respiratory-gating methods using the intra-beam respiratory motion data of lung cancer patients. The residual motion and dose distribution were calculated based on intra-beam respiratory motion data with the baseline drift. To quantify the baseline drift $\Delta$ during irradiation, it was defined as the inclination between the detected expiration point and the expiration point in the next cycle in the anterior–posterior (AP), cranial–caudal (CC) and left–right (LR) directions obtained using an in-house programme. The baseline drift value reached up to 0.74 mm/s in the CC direction as per the respiratory motion data of 10 patients. The homogeneity index (HI) of the phase-gating method tended to increase because the target was irradiated even when the amplitude position of the target differed from period to period. In contrast, the amplitude-gating method enabled irradiation considering the amplitude position of the target because the gating window was set considering the amplitude position of the respiratory motion. The respiratory-gating methods and respiratory phase in respiratory-gating lung stereotactic body radiation therapy (SBRT) must be determined based on the respiratory motion of the patients.
SARS-CoV-2 infection rates in air passengers arriving in Qatar
Authors: Butt Adeel A , Al-Halabi Anas M , Ghazouani Hafedh , Rhouma Mohamed Ben Haj , Ayoub Houssein H , Masoodi Naseer A , Borham Abdelsalam M , Hommos Ahmed A , Bertollini Roberto , Chemaitelly Hiam , Abu Raddad Laith J , Abou-Samra Abdul-Badi
Published: October 2021

Among 352 174 airline travellers entering Qatar, 8236 (2.34%) tested positive on or within the first 7 days of arrival, with 3789 (1.08%) testing positive at the time of arrival and the remaining 4447 (1.26%) testing negative at arrival but positive 1 week later.
Pit and tracheid anatomy explain hydraulic safety but not hydraulic efficiency of 28 conifer species
Authors: Song Yanjun , Poorter Lourens , Horsting Angelina , Delzon Sylvain , Sterck Frank
Published: October 2021

Conifers face increased drought mortality risks because of drought-induced embolism in their vascular system. Variation in embolism resistance may result from species differences in pit structure and function, as pits control the air seeding between water-transporting conduits. This study quantifies variation in embolism resistance and hydraulic conductivity for 28 conifer species grown in a 50-year-old common garden experiment and assesses the underlying mechanisms. Conifer species with a small pit aperture, high pit aperture resistance, and large valve effect were more resistant to embolism, as they all may reduce air seeding. Surprisingly, hydraulic conductivity was only negatively correlated with tracheid cell wall thickness. Embolism resistance and its underlying pit traits related to pit size and sealing were more strongly phylogenetically controlled than hydraulic conductivity and anatomical tracheid traits. Conifers differed in hydraulic safety and hydraulic efficiency, but there was no trade-off between safety and efficiency because they are driven by different xylem anatomical traits that are under different phylogenetic control.
Luminosity functions of globular clusters in five nearby spiral galaxies using HST/ACS images
Authors: Lomelí-Núñez Luis , Mayya Y D , Rodríguez-Merino L H , Ovando P A , Rosa-González D
Published: October 2021

We here present the luminosity function (LF) of globular clusters (GCs) in five nearby spiral galaxies using the samples of GC candidates selected in Hubble Space Telescope mosaic images in F435W, F555W, and F814W filters. Our search, which surpasses the fractional area covered by all previous searches in these galaxies, has resulted in the detection of 158 GC candidates in M81, 1123 in M101, 226 in NGC 4258, 293 in M51, and 173 in NGC 628. The LFs constructed from this data set, after correcting for relatively small contamination from reddened young clusters, are lognormal in nature, which was hitherto established only for the Milky Way (MW) and Andromeda among spiral galaxies. The magnitude at the turn-over (TO) corresponds to MV0(TO) = −7.41 ± 0.14 in four of the galaxies with Hubble types Sc or earlier, in excellent agreement with MV(TO) = −7.40 ± 0.10 for the MW. The TO magnitude is equivalent to a mass of ∼3 × 105 M⊙ for an old, metal-poor population. MV0(TO) is fainter by ∼1.16 magnitude for the fifth galaxy, M 101, which is of Hubble type Scd. The TO dependence on Hubble type implies that the GCs in early-type spirals are classical GCs, which have a universal TO, whereas the GC population in late-type galaxies is dominated by old disc clusters, which are in general less massive. The radial density distribution of GCs in our sample galaxies follows the Sérsic function with exponential power-law indices, and effective radii of 4.0–9.5 kpc. GCs in the sample galaxies have a mean specific frequency of 1.10 ± 0.24, after correcting for magnitude and radial incompleteness factors.
Action-based distribution function modelling for constraining the shape of the Galactic dark matter halo
Authors: Hattori Kohei , Valluri Monica , Vasiliev Eugene
Published: October 2021

We estimate the 3D density profile of the Galactic dark matter (DM) halo within r ≲ 30 kpc from the Galactic centre by using the astrometric data for halo RR Lyrae stars from Gaia DR2. We model both the stellar halo distribution function and the Galactic potential, fully taking into account the survey selection function, the observational errors, and the missing line-of-sight velocity data for RR Lyrae stars. With a Bayesian method, we infer the model parameters, including the density flattening of the DM halo q, which is assumed to be constant as a function of radius. We find that 99 per cent of the posterior distribution of q is located at q > 0.963, which strongly disfavours a flattened DM halo. We cannot draw any conclusions as to whether the Galactic DM halo at $r \lesssim 30 \, \mathrm{kpc}$ is prolate, because we restrict ourselves to axisymmetric oblate halo models with q ≤ 1. Our DM density profile might be biased especially in the inner few kpc, due to the uncertainty in the baryonic distribution. Our result is in tension with predictions from cosmological hydrodynamical simulations that advocate more oblate (〈q〉 ∼ 0.8 ± 0.15) DM haloes within ${\sim}15{{\ \rm per\ cent}}$ of the virial radius for Milky-Way-sized galaxies. An alternative possibility, based on our validation tests with a cosmological simulation, is that the true value q of the Galactic halo could be consistent with cosmological simulations but that disequilibrium in the Milky Way potential is inflating our measurement of q by 0.1–0.2. As a by-product, our model constrains the DM density in the Solar neighbourhood to be $\rho _{\mathrm{DM},\odot } = (9.01^{+0.18}_{-0.20})\times 10^{-3}{\,\rm M_\odot} \mathrm{pc}^{-3} = 0.342^{+0.007}_{-0.007}$ GeVcm−3, consistent with other recent measurements.
The impact of void environment on AGN
Authors: Ceccarelli Laura , Duplancic Fernanda , Garcia Lambas Diego
Published: October 2021

We study the population of active galaxies in void environment in the Sloan Digital Sky Survey. We use optical spectroscopic information to analyse characteristics of the emission lines of galaxies, accomplished by WHAN and BPT diagrams. Also, we study Wide-field Infrared Survey Explorer(WISE) mid-IR colours to assess active galactic nucleus (AGN) activity. We investigate these different AGN classification schemes, both optical and mid-IR, and their dependence on the spatial location with respect to the void centres. To this end, we define three regions: void, the spherical region defined by voidcentric distance relative to void radius (distance/rvoid) smaller than 0.8, comprising overdensities lesser than −0.9, an intermediate/transition shell region (namely, void-wall) 0.8 < distance/rvoid < 1.2, and a region sufficiently distant from voids, the field: distance/rvoid > 2. We find statistical evidence for a larger fraction of AGN and star-forming galaxies in the void region, regardless of the classification scheme addressed (either BPT, WHAN, or WISE). Moreover, we obtain a significantly stronger nuclear activity in voids compared to the field. We find an unusually large fraction of the most massive black holes undergoing strong accretion when their host galaxies reside in voids. Our results suggest a strong influence of the void environment on AGN mechanisms associated with galaxy evolution.
Bar-driven leading spiral arms in a counter-rotating dark matter halo
Authors: Lieb Emma , Collier Angela , Madigan Ann-Marie
Published: October 2021

An overwhelming majority of galactic spiral arms trail with respect to the rotation of the galaxy, though a small sample of leading spiral arms has been observed. The formation of these leading spirals is not well understood. Here we show, using collisionless N-body simulations, that a barred disc galaxy in a retrograde dark matter halo can produce long-lived (∼3 Gyr) leading spiral arms. Due to the strong resonant coupling of the disc to the halo, the bar slows rapidly and spiral perturbations are forced ahead of the bar. We predict that such a system, if observed, will also host a dark matter wake oriented perpendicular to the stellar bar. More generally, we propose that any mechanism that rapidly decelerates the stellar bar will allow leading spiral arms to flourish.
Radii of young star clusters in nearby galaxies
Authors: Brown Gillen , Gnedin Oleg Y
Published: October 2021

We measure the projected half-light radii of young star clusters in 31 galaxies from the Legacy Extragalactic UV Survey (LEGUS). We implement a custom pipeline specifically designed to be robust against contamination, which allows us to measure radii for 6097 clusters. This is the largest sample of young star cluster radii currently available. We find that most (but not all) galaxies share a common cluster radius distribution, with the peak at around 3 pc. We find a clear mass–radius relation of the form Reff ∝ M0.24. This relation is present at all cluster ages younger than 1 Gyr, but with a shallower slope for clusters younger than 10 Myr. We present simple toy models to interpret these age trends, finding that high-mass clusters are more likely to be not tidally limited and expand. We also find that most clusters in LEGUS are gravitationally bound, especially at older ages or higher masses. Lastly, we present the cluster density and surface density distributions, finding a large scatter that appears to decrease with cluster age. The youngest clusters have a typical surface density of 100$\, \mathrm{ M}_\odot \, \mathrm{pc}^{-2}$.
Detecting Selection in Multiple Populations by Modeling Ancestral Admixture Components
Authors: Cheng Jade Yu , Stern Aaron J , Racimo Fernando , Nielsen Rasmus
Published: October 2021

One of the most powerful and commonly used approaches for detecting local adaptation in the genome is the identification of extreme allele frequency differences between populations. In this article, we present a new maximum likelihood method for finding regions under positive selection. It is based on a Gaussian approximation to allele frequency changes and it incorporates admixture between populations. The method can analyze multiple populations simultaneously and retains power to detect selection signatures specific to ancestry components that are not representative of any extant populations. Using simulated data, we compare our method to related approaches, and show that it is orders of magnitude faster than the state-of-the-art, while retaining similar or higher power for most simulation scenarios. We also apply it to human genomic data and identify loci with extreme genetic differentiation between major geographic groups. Many of the genes identified are previously known selected loci relating to hair pigmentation and morphology, skin, and eye pigmentation. We also identify new candidate regions, including various selected loci in the Native American component of admixed Mexican-Americans. These involve diverse biological functions, such as immunity, fat distribution, food intake, vision, and hair development.
ViroidDB: a database of viroids and viroid-like circular RNAs
Authors: Lee Benjamin D , Neri Uri , Oh Caleb J , Simmonds Peter , Koonin Eugene V
Published: October 2021

We introduce ViroidDB, a value-added database that attempts to collect all known viroid and viroid-like circular RNA sequences into a single resource. Spanning about 10 000 unique sequences, ViroidDB includes viroids, retroviroid-like elements, small circular satellite RNAs, ribozyviruses, and retrozymes. Each sequence's secondary structure, ribozyme content, and cluster membership are predicted via a custom pipeline optimized for handling circular RNAs. The data can be explored via a purpose-built user interface that features visualizations, multiple sequence alignments, and a portal for downloading bulk data. Users can browse the data by sequence type, taxon, or typo-tolerant search of metadata fields. The database is freely accessible at https://viroids.org.
CompoDynamics: a comprehensive database for characterizing sequence composition dynamics
Authors: Jiang Shuai , Du Qiang , Feng Changrui , Ma Lina , Zhang Zhang
Published: October 2021

Sequence compositions of nucleic acids and proteins have significant impact on gene expression, RNA stability, translation efficiency, RNA/protein structure and molecular function, and are associated with genome evolution and adaptation across all kingdoms of life. Therefore, a devoted resource of sequence compositions and associated features is fundamentally crucial for a wide range of biological research. Here, we present CompoDynamics (https://ngdc.cncb.ac.cn/compodynamics/), a comprehensive database of sequence compositions of coding sequences (CDSs) and genomes for all kinds of species. Taking advantage of the exponential growth of RefSeq data, CompoDynamics presents a wealth of sequence compositions (nucleotide content, codon usage, amino acid usage) and derived features (coding potential, physicochemical property and phase separation) for 118 689 747 high-quality CDSs and 34 562 genomes across 24 995 species. Additionally, interactive analytical tools are provided to enable comparative analyses of sequence compositions and molecular features across different species and gene groups. Collectively, CompoDynamics bears the great potential to better understand the underlying roles of sequence composition dynamics across genes and genomes, providing a fundamental resource in support of a broad spectrum of biological studies.
Association of the chronic kidney disease urinary proteomic predictor CKD273 with clinical risk factors of graft failure in kidney allograft recipients
Authors: Rambabova-Bushljetik Irena , Metzger Jochen , Siwy Justyna , Dohcev Saso , Bushljetikj Oliver , Filipce Venko , Trajceska Lada , Mischak Harald , Spasovski Goce
Published: October 2021

Background

Kidney transplantation is the best treatment option for end-stage kidney disease but is still associated with long-term graft failure. In this study, we evaluated the application of urinary proteomics to identify grafts with high failure risk before initial decline of estimated glomerular filtration rate (eGFR) with irreversible graft changes.

Methods

Fifty-two living donor kidney transplant recipients (KTR) with 8-year follow-up were enrolled. All patients underwent clinical examination and had a routine laboratory screening at 3, 6, 12, 24, 36, 48 and 96 months post-transplantation, including creatinine, urea, albumin and 24-h proteinuria. Graft function was estimated according to Nankivell. Urine samples at Month 24 were analysed by capillary electrophoresis coupled mass spectrometry followed by classification with the chronic kidney disease classifier CKD273.

Results

CKD273 showed significant correlation with serum creatinine at every time point and moderate inverse correlation for the slope in glomerular filtration rates by Nankivell (r = −0.29, P = 0.05). Receiver operating characteristics analysis for graft loss and death within the next 6 years after proteomic analysis resulted in an area under curve value of 0.89 for CKD273 being superior to 0.67 for Nankivell eGFR. Stratification into CKD273-positive and -negative patient groups revealed a hazard ratio of 16.5 for prevalence of graft loss in case of CKD273 positivity.

Conclusions

Using a representative KTR cohort with 8-year follow-up, we could demonstrate significant value of CKD273 for risk stratification of graft loss. This study provides the conceptual basis for further evaluation of CKD273 as a prognostic tool for long-term graft function risk stratification by large prospective clinical trials.
NIH Tobacco Research and the Emergence of Tobacco Regulatory Science
Authors: Meissner Helen I , Sharma Kriti , Mandal Rachel J , Garcia-Cazarin Mary , Wanke Kay L , Moyer Jonathan , Liggins Charlene
Published: October 2021

Introduction

This study explores how the emergence of FDA-funded Tobacco Regulatory Science (TRS) research complements and perhaps influenced the direction of tobacco research supported by NIH.

Aims and Methods

New NIH- and FDA-funded tobacco projects awarded in fiscal years (FY) 2011–2020 were identified using internal NIH databases of awarded grants. Project abstracts and research aims were coded by the authors to characterize research domains and tobacco products studied.

Results

Between FY 2011 and 2020, NIH funded 1032 and FDA funded 322 new tobacco projects. For the years and grant activity codes studied, the number of new NIH tobacco projects declined while FDA’s increased; combined the number of new projects held steady. Much of NIH research included smoking combustibles (43.7%). The most common products in FDA research were cigarettes (74.8%) and e-cigarettes/ENDS (48.1%). Most NIH (58.6%) and FDA (67.7%) projects included research on the determinants of tobacco use. Another area of apparent overlap was health effects (29.5% NIH and 30.1% FDA). Projects unique to NIH included treatment interventions (33.3%), disease pathology/progression (17.8%) and neurobiology (18.9%). A minority of both NIH and FDA projects included populations particularly vulnerable to tobacco product use.

Conclusions

In total, support for new tobacco research supported by NIH and FDA combined remained steady for the time period covered, though there was a concomitant decline in NIH tobacco projects with the increase in FDA-funded TRS projects for the activity codes studied. Despite the apparent overlap in some areas, both NIH and FDA support research that is unique to their respective missions.

Implications

NIH continues to support tobacco research that falls within and outside of FDA’s regulatory authorities. This research still is needed not only to bolster the evidence base for regulatory decisions at the national and state levels, but also to advance a comprehensive scientific agenda that can inform multiple levels of influence on tobacco control, use and addiction. It will be important to continue monitoring FDA-funded TRS and NIH-funded tobacco research portfolios to ensure that the level of support for and focus of the research is sufficient to address the burden of tobacco-related morbidity and mortality.