bluuebunny/crossref_metadata_2025 huggingface dataset:
The ‘Corkscrew’ Journey of an Adaptation: Cultural Mobility in Hammett, Kurosawa, Leone, and Hill
Authors: Holtz Martin
Published: December 2021

Akira Kurosawa’s Yojimbo (1961) has long been recognized as a quasi-adaptation of Dashiell Hammett’s Red Harvest (1929), even if it relates much more closely to Hammett’s short story ‘Corkscrew’ (1925). Yojimbo was remade as the Italian Western Fistful of Dollars (1964) by Sergio Leone. The material finally ‘came home’ when Walter Hill adapted it as Last Man Standing (1996) that returns to the 1920s American desert town setting of the original story. This contribution seeks to examine the inflections of the individual incarnations that the material has undergone on its journey through various cultural contexts. The main argument is that the story of the outsider infiltrating a corrupt town and ‘cleansing’ it by playing off two gangs against each other has lent itself to commentary on transnational cultural exchange and mobility. ‘Corkscrew’ expresses anxiety over the integrity of cultural boundaries, Red Harvest expresses the inherent corruption of a ‘hermetic’ culture, Yojimbo uses the story to highlight the uneasy relation between tradition and Westernization in Japan while simultaneously drawing attention to Kurosawa’s status as ‘Western’ director and embraces a guarded cultural mobility, Fistful of Dollars empties the signs, icons, and narratives that make up the expressions of culture of any essentialist meanings and so stages cultural mobility as the shifting play of signifiers, endlessly transgressing acquired meanings and cultural boundaries, and Last Man Standing, finally, in reclaiming the Americanness of the story simultaneously forgoes any cultural specificity by reducing it to an excessive pastiche of prior elements.
Family caregivers emphasise patience and personal growth: a qualitative analysis from the Caregiving Transitions Study
Authors: Blinka Marcela D , Liu Chelsea , Sheehan Orla C , Rhodes J David , Roth David L
Published: December 2021

Background

informal caregiving for family and friends is becoming increasingly common due to the rising prevalence of chronic conditions and a shortage of affordable care options. While the impact of caregiving on caregivers’ health is well-documented, nuances in caregivers’ experiences may not be captured in quantitative studies. We aimed to better understand caregivers’ perception of their experiences through qualitative analysis.

Methods

participants were from the Caregiving Transitions Study (CTS), which is ancillary to the REasons for Geographic and Racial Differences in Stroke Study. We analysed responses from 150 caregivers to an open-ended question at the end of the CTS telephone interview concerning additional information about their caregiving experiences. We identified main themes and examined differences by sex, condition and relationship to the care recipient.

Results

four major themes were identified: cultural/family expectations; growth opportunities; and reciprocity; stressors and challenges and recommendations. Male caregivers more often indicated that their motivation for taking on this role was their sense of duty towards family, while female caregivers focused on the challenges and burden of caregiving that they experienced. Overall, caregivers highlighted the importance of patience and the positive impact of caregiving, such as opportunities for personal growth, acquiring new skills, and finding fulfillment and gratitude.

Conclusions

family caregivers shared both positive and challenging experiences as well as the impact that these experiences had on their lives. Understanding the full spectrum of the caregiving experience will help inform how the community and the health care system can best support caregivers in their roles.
Radiological identification of temporal lobe epilepsy using artificial intelligence: a feasibility study
Authors: Gleichgerrcht Ezequiel , Munsell Brent , Keller Simon S , Drane Daniel L , Jensen Jens H , Spampinato M Vittoria , Pedersen Nigel P , Weber Bernd , Kuzniecky Ruben , McDonald Carrie , Bonilha Leonardo
Published: December 2021

Temporal lobe epilepsy is associated with MRI findings reflecting underlying mesial temporal sclerosis. Identifying these MRI features is critical for the diagnosis and management of temporal lobe epilepsy. To date, this process relies on visual assessment by highly trained human experts (e.g. neuroradiologists, epileptologists). Artificial intelligence is increasingly recognized as a promising aid in the radiological evaluation of neurological diseases, yet its applications in temporal lobe epilepsy have been limited. Here, we applied a convolutional neural network to assess the classification accuracy of temporal lobe epilepsy based on structural MRI. We demonstrate that convoluted neural networks can achieve high accuracy in the identification of unilateral temporal lobe epilepsy cases even when the MRI had been originally interpreted as normal by experts. We show that accuracy can be potentiated by employing smoothed grey matter maps and a direct acyclic graphs approach. We further discuss the foundations for the development of computer-aided tools to assist with the diagnosis of epilepsy.
Drying banana seeds for ex situ conservation
Authors: Kallow Simon , Garcia Zuluaga Manuela , Fanega Sleziak Natalia , Nugraha Bayu , Mertens Arne , Janssens Steven B , Gueco Lavernee , Valle-Descalsota Michelle Lyka , Dang Vu Tuong , Toan Vu Dang , Thi Li Loan , Vandelook Filip , Dickie John B , Verboven Pieter , Swennen Rony , Panis Bart
Published: December 2021

The ability of seeds to withstand drying is fundamental to ex situ seed conservation but drying responses are not well known for most wild species including crop wild relatives. We look at drying responses of seeds of Musa acuminata and Musa balbisiana, the two primary wild relatives of bananas and plantains, using the following four experimental approaches: (i) We equilibrated seeds to a range of relative humidity (RH) levels using non-saturated lithium chloride solutions and subsequently measured moisture content (MC) and viability. At each humidity level we tested viability using embryo rescue (ER), tetrazolium chloride staining and germination in an incubator. We found that seed viability was not reduced when seeds were dried to 4% equilibrium relative humidity (eRH; equating to 2.5% MC). (ii) We assessed viability of mature and less mature seeds using ER and germination in the soil and tested responses to drying. Findings showed that seeds must be fully mature to germinate and immature seeds had negligible viability. (iii) We dried seeds extracted from ripe/unripe fruit to 35–40% eRH at different rates and tested viability with germination tests in the soil. Seeds from unripe fruit lost viability when dried and especially when dried faster; seeds from ripe fruit only lost viability when fast dried. (iv) Finally, we dried and re-imbibed mature and less mature seeds and measured embryo shrinkage and volume change using X-ray computer tomography. Embryos of less mature seeds shrank significantly when dried to 15% eRH from 0.468 to 0.262 mm3, but embryos of mature seeds did not. Based on our results, mature seeds from ripe fruit are desiccation tolerant to moisture levels required for seed genebanking but embryos from immature seeds are mechanistically less able to withstand desiccation, especially when water potential gradients are high.
Carthaginians Beyond the Ocean: Comparison, Justification, and Inversion in the Hypothesis of the Carthaginian Discovery of America
Authors: Fernández Camacho Pamina
Published: December 2021

After the American continent was discovered, Spanish intellectuals exerted their ingenuity in an attempt to explain the existence of those hitherto unknown territories, and engaged in controversies about the moral and legal right to exploit them. The use of classical sources as authorities was common in those debates. In this article, we focus on the mention by Ps.-Aristotle and Diodorus of an island in the Atlantic Ocean, discovered and exploited by Carthaginians until the colonization process came to a dramatic end. We study the use of this story in connection with America, exploring its role in the controversy about rights of discovery and its implications for the debate about the ethnicity of indigenous peoples and the justification of their conquest. This led to the establishment of a comparison between the ancient colonization of Spain by the Carthaginians and the colonization of America by the Spaniards, where the latter was presented as an improvement or positive reverse of the former. Finally, we present the hypothesis that this Carthaginian colonization, as it was imagined in the early sixteenth century, was inspired by contemporary events taking place in America, and that this had an impact on the understanding of ancient Spanish history for centuries.
Fast vs. ultraslow thrombolytic infusion regimens in patients with obstructive mechanical prosthetic valve thrombosis: a pilot randomized clinical trial
Authors: Sadeghipour Parham , Saedi Sedigheh , Saneei Leila , Rafiee Farnaz , Yoosefi Siamak , Parsaee Mozhgan , Siami Rashide , Saberi Milad , Pouraliakbar Hamidreza , Ghadrdoost Behshid , Bakhshandeh Hooman , Peighambari Mohammad Mehdi , Farrashi Melody , Mohebbi Bahram , Naderi Nasim , Amin Ahmad , Maleki Majid , Khajali Zahra , De Caterina Raffaele
Published: December 2021

Aims

Thrombolysis is an alternative to surgery for mechanical prosthetic valve thrombosis (MPVT). Randomized clinical trials have yet to test the safety and efficacy of a proposed ultraslow thrombolytic infusion regimen.

Methods and results

This single-centre, open-label, pilot randomized clinical trial randomized adult patients with acute obstructive MPVT to an ultraslow thrombolytic regimen [25 mg of recombinant tissue-type plasminogen activator (rtPA) infused in 25 h] and a fast thrombolytic regimen (50 mg of rtPA infused in 6 h). If thrombolysis failed, a repeated dose of 25 mg of rtPA for 6 h was administered in both groups up to a cumulative dose of 150 mg or the occurrence of a complication. The primary outcome was a complete MPVT resolution (>75% fall in the obstructive gradient by transthoracic echocardiography, <10° limitation in opening and closing valve motion angles by fluoroscopy, and symptom improvement). The key safety outcome was a Bleeding Academic Research Consortium type III or V major bleeding. Overall, 120 patients, including 63 (52.5%) women, at a mean age of 36.3 ± 15.3 years, were randomized. Complete thrombolysis success was achieved in 51 patients (85.0%) in the ultraslow-regimen group and 47 patients (78.3%) in the fast-regimen group [odds ratio 1.58; 95% confidence interval (CI) 0.25–1.63; P = 0.34]. One case of transient ischaemic attack and three cases of intracranial haemorrhage (absolute risk difference −6.6%; 95%CI −12% −0.3%; P = 0.07) were observed only in the fast-regimen group.

Conclusion

The ultraslow thrombolytic regimen conferred a high thrombosis resolution rate without major complications. Such findings should be replicated in more adequately powered trials.
Outpatient prescription patterns of COVID-19 drugs in the metropolitan area of Mexico City
Authors: Fuentes-Gonzalez Maria F , Ordinola Navarro Alberto , Carmona-Aguilera Zully , Hernández-Jimenez Carlos A , Benitez-Altamirano Gustavo M , Beltran-Ontiveros Luis D , Lopez-Vejar Cesar , Ramirez-Hinojosa Juan P , Vera-Lastra Olga , Lopez Luis Bruno A
Published: December 2021

Background

We aimed to describe the use of drugs with apparent efficacy in ambulatory patients with confirmed COVID-19 and the relationship of Google Trends searches with prescriptions and the total number of COVID-19 cases in Mexico City.

Methods

Between March 2020 and February 2021, we surveyed 350 patients confirmed to have COVID-19 across 3 hospitals in Mexico City for their ambulatory prescriptions. We analysed the correlation between prescription patterns of 4 drugs with apparent efficacy against COVID-19, Google Trends searches for these drugs, and the overall number of confirmed COVID-19 cases in Mexico City.

Results

We included 350 patients, of whom 59% were women with a median age of 38 years (interquartile range, 29–51), and 72% had a bachelor’s degree or higher. There were ambulatory medical prescriptions in 172 (49%) patients, and self-prescriptions were reported in 99 (28%) patients. The prescription rate was high for hydroxychloroquine/azithromycin (19%) and dexamethasone (25%). There was a decrease in the prescription of hydroxychloroquine (P < 0.001) and a strong positive correlation between hydroxychloroquine (r = 0.66; 95% confidence interval, 0.11–0.90; P = 0.02) prescription and online searches for hydroxychloroquine. There was a strong positive correlation between online searches for azithromycin, dexamethasone, ivermectin, and vitamin D and the number of confirmed COVID-19 cases.

Conclusions

During the COVID-19 pandemic, there was a high proportion of prescriptions for hydroxychloroquine/azithromycin and dexamethasone despite their unproven efficacy. Analysis of Google Trends showed a strong correlation between the overall number of confirmed COVID-19 cases and searches for such drugs, suggesting a higher rate of prescriptions. Analysis of online searches could thus help to actively survey public health behaviours in the future.
A remote sensing-guided forest inventory concept using multispectral 3D and height information from ZiYuan-3 satellite data
Authors: Wallner Adelheid , Friedrich Stefan , Geier Emanuel , Meder-Hokamp Christoph , Wei Zillin , Kindu Mengistie , Tian Jiaojiao , Döllerer Martin , Schneider Thomas , Knoke Thomas
Published: December 2021

Increased frequencies of storms and droughts due to climate change are changing central European forests more rapidly than in previous decades. To monitor these changes, multispectral 3D remote sensing (RS) data can provide relevant information for forest management and inventory. In this case study, data of the multispectral 3D-capable satellite system ZiYuan-3 (ZY-3) were used in a RS-guided forest inventory concept to reduce the field sample size compared to the standard grid inventory. We first pre-stratified the forest area via the ZY-3 dataset into coniferous, broadleaved and mixed forest types using object-based image analysis. Each forest type was then split into three height strata using the ZY-3 stereo module-derived digital canopy height model (CHM). Due to limited sample sizes, we reduced the nine to six strata. Then, for each of the six strata, we randomly selected representative segments for inventory plot placement. We then conducted field inventories in these plots. The collected field data were used to calculate forest attributes, such as tree species composition, timber volume and canopy height at plot level (terrestrially measured tree height and height information from ZY-3 CHM). Subsequently, we compared the resulting forest attributes from the RS-guided inventory with the reference data from a grid inventory based only on field plots. The difference in mean timber volumes to the reference was +30.21 m3ha−1 (8.99 per cent) for the RS-guided inventory with terrestrial height and −11.32 m3ha−1 (−3.37 per cent) with height information from ZY-3 data. The relative efficiency (RE) indicator was used to compare the different sampling schemes. The RE as compared to a random reduction of the sample size was 1.22 for the RS-guided inventory with terrestrial height measurements and 1.85 with height information from ZY-3 data. The results show that the presented workflow based on 3D ZY-3 data is suitable to support forest inventories by reducing the sample size and hence potentially increase the inventory frequency.
Survey Deficiencies as Quality Indicators in Oregon Assisted Living Communities
Authors: Tunalilar Ozcan , Lin Sunny , Carder Paula
Published: December 2021

Background and Objectives

License inspection data have commonly been used as a quality measure for nursing homes but have not yet been used to assess the quality of assisted living/residential care (AL/RC) communities. Drawing on resource dependency theory, we test the hypothesis that structural and environmental characteristics influence AL/RC quality as measured by deficiency citations (“deficiencies”) issued during license inspections.

Research Design and Methods

Using data from 526 licensed AL/RC communities in Oregon that received a license inspection visit between 2008 and 2016, we examined the prevalence of deficiencies by type and year. We estimated regression models to identify structural and environmental characteristics associated with the number of deficiencies.

Results

Most (79%) inspections resulted in at least one deficiency. The most common deficiencies concerned medications and treatments (57%), change of condition and monitoring (48%), and resident health services (45%). Structural characteristics associated with higher odds of receiving one or more deficiencies included larger size, memory care designation, shorter administrative tenure, and for-profit status. Environmental characteristics associated with higher odds of receiving one or more deficiencies included rural location, lower unemployment, and market concentration. The number and likelihood of a given community receiving a deficiency decreased over time.

Discussion and Implications

Resource dependency theory constitutes a useful framework to consider the role of structural and environmental factors that affect AL/RC quality, including resident needs, institutional knowledge, resource availability, and market pressure. License inspection data are a viable option for assessing the quality of AL/RC communities.
Analysis of fungal high-mannose structures using CAZymes
Authors: Kołaczkowski Bartłomiej M , Jørgensen Christian I , Spodsberg Nikolaj , Stringer Mary A , Supekar Nitin T , Azadi Parastoo , Westh Peter , Krogh Kristian B R M , Jensen Kenneth
Published: December 2021

Glycoengineering ultimately allows control over glycosylation patterns to generate new glycoprotein variants with desired properties. A common challenge is glycan heterogeneity, which may affect protein function and limit the use of key techniques such as mass spectrometry. Moreover, heterologous protein expression can introduce nonnative glycan chains that may not fulfill the requirement for therapeutic proteins. One strategy to address these challenges is partial trimming or complete removal of glycan chains, which can be obtained through selective application of exoglycosidases. Here, we demonstrate an enzymatic O-deglycosylation toolbox of a GH92 α-1,2-mannosidase from Neobacillus novalis, a GH2 β-galactofuranosidase from Amesia atrobrunnea and the jack bean α-mannosidase. The extent of enzymatic O-deglycosylation was mapped against a full glycosyl linkage analysis of the O-glycosylated linker of cellobiohydrolase I from Trichoderma reesei (TrCel7A). Furthermore, the influence of deglycosylation on TrCel7A functionality was evaluated by kinetic characterization of native and O-deglycosylated forms of TrCel7A. This study expands structural knowledge on fungal O-glycosylation and presents a ready-to-use enzymatic approach for controlled O-glycan engineering in glycoproteins expressed in filamentous fungi.
Interaction of huntingtin with PRMTs and its subsequent arginine methylation affects HTT solubility, phase transition behavior and neuronal toxicity
Authors: Ratovitski Tamara , Jiang Mali , O'Meally Robert N , Rauniyar Priyanka , Chighladze Ekaterine , Faragó Anikó , Kamath Siddhi V , Jin Jing , Shevelkin Alexey V , Cole Robert N , Ross Christopher A
Published: December 2021

Huntington’s disease (HD) is an incurable neurodegenerative disorder caused by a CAG expansion in the huntingtin gene (HTT). Post-translational modifications of huntingtin protein (HTT), such as phosphorylation, acetylation and ubiquitination, have been implicated in HD pathogenesis. Arginine methylation/dimethylation is an important modification with an emerging role in neurodegeneration; however, arginine methylation of HTT remains largely unexplored. Here we report nearly two dozen novel arginine methylation/dimethylation sites on the endogenous HTT from human and mouse brain and human cells suggested by mass spectrometry with data-dependent acquisition. Targeted quantitative mass spectrometry identified differential arginine methylation at specific sites in HD patient-derived striatal precursor cell lines compared to normal controls. We found that HTT can interact with several type I protein arginine methyltransferases (PRMTs) via its N-terminal domain. Using a combination of in vitro methylation and cell-based experiments, we identified PRMT4 (CARM1) and PRMT6 as major enzymes methylating HTT at specific arginines. Alterations of these methylation sites had a profound effect on biochemical properties of HTT rendering it less soluble in cells and affected its liquid–liquid phase separation and phase transition patterns in vitro. We found that expanded HTT 1-586 fragment can form liquid-like assemblies, which converted into solid-like assemblies when the R200/205 methylation sites were altered. Methyl-null alterations increased HTT toxicity to neuronal cells, while overexpression of PRMT 4 and 6 was beneficial for neuronal survival. Thus, arginine methylation pathways that involve specific HTT-modifying PRMT enzymes and modulate HTT biochemical and toxic properties could provide targets for HD-modifying therapies.
Identification of the active site and characterization of a novel sporulation-specific cysteine protease YabG fromBacillus subtilis
Authors: Yamazawa Ryuji , Kuwana Ritsuko , Takeuchi Kenji , Takamatsu Hiromu , Nakajima Yoshitaka , Ito Kiyoshi
Published: December 2021

In order to characterize the probable protease gene yabG found in the genomes of spore-forming bacteria, Bacillus subtilis yabG was expressed as a 35 kDa His-tagged protein (BsYabG) inEscherichia coli cells. During purification using Ni-affinity chromatography, the 35 kDa protein was degraded via several intermediates to form a 24 kDa protein. Furthermore, it was degraded after an extended incubation period. The effect of protease inhibitors, including certain chemical modification reagents, on the conversion of the 35 kDa protein to the 24 kDa protein was investigated. Reagents reacting with sulphhydryl groups exerted significant effects strongly suggesting that the yabG gene product is a cysteine protease with autolytic activity. Site-directed mutagenesis of the conserved Cys and His residues indicated that Cys218 and His172 are active site residues. No degradation was observed in the C218A/S and H172A mutants. In addition to the chemical modification reagents, benzamidine inhibitedGraphical Abstract the degradation of the 24 kDa protein. Determination of the N-terminal amino acid sequences of the intermediates revealed trypsin-like specificity for YabG protease. Based on the relative positions of His172 and Cys218 and their surrounding sequences, we propose the classification of YabG as a new family of clan CD in the MEROPS peptidase database.
Adult height in relation to the risk of colorectal cancer among the Japanese population: an evaluation based on systematic review and meta-analysis
Authors: Shrestha Rachana Manandhar , Mizoue Tetsuya , Sawada Norie , Matsuo Keitaro , Wada Keiko , Tanaka Keitaro , Lin Yingsong , Sugawara Yumi , Takimoto Hidemi , Kimura Takashi , Ito Hidemi , Kitamura Tetsuhisa , Sakata Ritsu , Tanaka Shiori , Inoue Manami ,   for the Research Group for the Development and Evaluation of Cancer Prevention Strategies in Japan
Published: December 2021

Objective

The association between adult-attained height and risk of colorectal cancer remains elusive among the Japanese population. We performed a systematic review and meta-analysis of epidemiological studies in Japan.

Methods

We systematically searched the MEDLINE (PubMed) and Ichushi databases and complemented it with manual search to identify eligible studies. We extracted relative risks or odds ratios from the selected studies and conducted meta-analysis to estimate the summary relative risk with 95% confidence interval. We made the final judgment based on a consensus of the research group members considering both epidemiological evidence and biological plausibility.

Results

This systematic review identified four cohort and one case–control studies among the Japanese. The meta-analysis of these five studies showed the summary relative risk of 1.21 (95% confidence interval: 1.07–1.35) of overall colorectal cancer for the highest vs. lowest categories of height. In the analysis by the cancer subsite, the association was significant for colon cancer with a summary relative risk of 1.26 (95% confidence interval: 1.10–1.45) but not for rectal cancer 1.05 (95% confidence interval: 0.71–1.54). In the analysis by sex, tall stature was associated with a significantly increased risk of overall colorectal cancer in both sexes; the summary relative risk was 1.21 (95% confidence interval: 1.04–1.41) in men and 1.20 (95% confidence interval: 1.00–1.44) in women, respectively.

Conclusions

The evidence to support that adult-attained height is associated with increased risk of colorectal cancer (colon cancer) among the Japanese population is ‘probable’.
Bilateral synchronous intravaginal testicular torsion presenting with unilateral testicular pain
Authors: Taheem Muhesh Kumar , Ziada M , Arumugam V , Lamond Z , Almpanis S
Published: December 2021

An adolescent presented with a 5 hour of history of unilateral testicular pain and examination findings in keeping with a unilateral testicular torsion. On scrotal exploration, there was evidence of bilateral testicular torsion and bilateral orchidopexy was subsequently performed. Intravaginal bilateral testicular torsion is scarcely reported in adolescents and adults. Both unilateral and bilateral testicular torsions in adolescents are commonly associated with anatomical anomalies, which were not evident in this case. Despite warming the symptomatic testis for 40 minutes, viability was indeterminate. Guidelines remain equivocal about adequate reperfusion period before considering orchiectomy. Interval sonographic follow-up is recommended to assess testicular atrophy; however, considerable variation exists in practice. This is an atypical case of bilateral synchronous testicular torsion demonstrable by an absence of classical risk-factors, alongside unilateral clinical signs and symptoms. Inconsistency in guidelines for attempted reperfusion could result in orchiectomy where testicular salvage is possible.
Evaluation of Candida auris acquisition in US international travellers using a culture-based screening protocol
Authors: Turbett Instructor Sarah E , Becker Doctoral Student Margaret , Belford Medical Technologist Barbara , Kelly Research Technologist Meagan , Desrosiers Medical Technologist Lisa , Oliver Research Nurse Elizabeth , Branda Associate Professor John A , Walters Epidemiologist Maroya , Walker Epidemiologist Allison Taylor , LaRocque Associate Professor Regina , Ryan Professor Edward T
Published: December 2021

We establish the feasibility of evaluating US international travellers for Candida auris acquisition using a culture-based screening protocol. Candida auris was not identified in any of the travellers in this small cohort; further study is needed to determine the overall risk and risk factors for travel-associated acquisition.
Multiwavelength observations of the Blazar 4C  + 28.07
Authors: Zargaryan Davit , Mackey Jonathan , Barnouin Thibault , Aharonian Felix
Published: December 2021

The active galactic nucleus 4C  + 28.07 is a flat-spectrum radio quasar, one of the brightest at γ-ray energies. We study its multiwavelength emission by analysing ∼12.3 yr of Fermi-LAT data in the γ-ray band and Swift-X-Ray Telescope (XRT)/Ultraviolet/Optical Telescope (UVOT) available data in X-ray and optical-to-ultraviolet bands. In the γ-ray band, five flaring periods have been detected, and quasi-simultaneously with these flaring times, the X-ray and UVOT data detected by Swift-XRT/UVOT have also been analysed. In one of the brightest flare periods (Flare 5; observed on 2018 October 12), the γ-ray flux reached (6.7 ± 0.81) × 10−6 photon cm−2 s−1 (∼31 × higher than the mean flux over 12.3 yr) with detection significance of σ = 6.1. The estimated variability time (∼2 h) constrains the γ-ray emitting region size to ≤9 × 1014 cm, which is close to the black hole radius. The spectral energy distributions (SEDs) in the γ-ray band for the ∼12.3 yr of data show an early cut-off at ∼14 GeV; beyond ∼60 GeV, however, the spectrum hardens and is detected up to ∼316 GeV. Similar spectral behaviour is also noticeable for the SEDs of flares, which can be linked to the photon absorption by the emitting region’s internal and external narrow-band radiation fields. In the quiescent period, the γ-ray emission was described by the synchrotron self-Compton scenario, while the external photons contributions from the disc and the broad-line region were required to explain the short-term flaring γ-ray emission. Considering the significance of the obtained results from 4C  + 28.07, we compared the parameters with 3C 279 and M87, to motivate further studies.
Genomic Signatures of Sexual Selection on Pollen-Expressed Genes in Arabis alpina
Authors: Gutiérrez-Valencia Juanita , Fracassetti Marco , Horvath Robert , Laenen Benjamin , Désamore Aurélie , Drouzas Andreas D , Friberg Magne , Kolář Filip , Slotte Tanja
Published: December 2021

Fertilization in angiosperms involves the germination of pollen on the stigma, followed by the extrusion of a pollen tube that elongates through the style and delivers two sperm cells to the embryo sac. Sexual selection could occur throughout this process when male gametophytes compete for fertilization. The strength of sexual selection during pollen competition should be affected by the number of genotypes deposited on the stigma. As increased self-fertilization reduces the number of mating partners, and the genetic diversity and heterozygosity of populations, it should thereby reduce the intensity of sexual selection during pollen competition. Despite the prevalence of mating system shifts, few studies have directly compared the molecular signatures of sexual selection during pollen competition in populations with different mating systems. Here we analyzed whole-genome sequences from natural populations of Arabis alpina, a species showing mating system variation across its distribution, to test whether shifts from cross- to self-fertilization result in molecular signatures consistent with sexual selection on genes involved in pollen competition. We found evidence for efficient purifying selection on genes expressed in vegetative pollen, and overall weaker selection on sperm-expressed genes. This pattern was robust when controlling for gene expression level and specificity. In agreement with the expectation that sexual selection intensifies under cross-fertilization, we found that the efficacy of purifying selection on male gametophyte-expressed genes was significantly stronger in genetically more diverse and outbred populations. Our results show that intra-sexual competition shapes the evolution of pollen-expressed genes, and that its strength fades with increasing self-fertilization rates.
PsrA is a novel regulator contributes to antibiotic synthesis, bacterial virulence, cell motility and extracellular polysaccharides production in Serratia marcescens
Authors: Pan Xuewei , Tang Mi , You Jiajia , Osire Tolbert , Sun Changhao , Fu Weilai , Yi Ganfeng , Yang Taowei , Yang Shang-Tian , Rao Zhiming
Published: December 2021

Serratia marcescens is a Gram-negative bacterium of the Enterobacteriaceae family that can produce numbers of biologically active secondary metabolites. However, our understanding of the regulatory mechanisms behind secondary metabolites biosynthesis in S. marcescens remains limited. In this study, we identified an uncharacterized LysR family transcriptional regulator, encoding gene BVG90_12635, here we named psrA, that positively controlled prodigiosin synthesis in S. marcescens. This phenotype corresponded to PsrA positive control of transcriptional of the prodigiosin-associated pig operon by directly binding to a regulatory binding site (RBS) and an activating binding site (ABS) in the promoter region of the pig operon. We demonstrated that L-proline is an effector for the PsrA, which enhances the binding affinity of PsrA to its target promoters. Using transcriptomics and further experiments, we show that PsrA indirectly regulates pleiotropic phenotypes, including serrawettin W1 biosynthesis, extracellular polysaccharide production, biofilm formation, swarming motility and T6SS-mediated antibacterial activity in S. marcescens. Collectively, this study proposes that PsrA is a novel regulator that contributes to antibiotic synthesis, bacterial virulence, cell motility and extracellular polysaccharides production in S. marcescens and provides important clues for future studies exploring the function of the PsrA and PsrA-like proteins which are widely present in many other bacteria.
Membrane-dependent relief of translation elongation arrest on pseudouridine- and N1-methyl-pseudouridine-modified mRNAs
Authors: Svitkin Yuri V , Gingras Anne-Claude , Sonenberg Nahum
Published: December 2021

Expression of therapeutically important proteins has benefited dramatically from the advent of chemically modified mRNAs that feature decreased lability and immunogenicity. This had a momentous effect on the rapid development of COVID-19 mRNA vaccines. Incorporation of the naturally occurring pseudouridine (Ψ) or N1-methyl-pseudouridine (N1mΨ) into in vitro transcribed mRNAs prevents the activation of unwanted immune responses by blocking eIF2α phosphorylation, which inhibits translation. Here, we report that Ψs in luciferase (Luc) mRNA exacerbate translation pausing in nuclease-untreated rabbit reticulocyte lysate (uRRL) and promote the formation of high-order-ribosome structures. The major deceleration of elongation occurs at the Ψ-rich nucleotides 1294–1326 of Ψ-Luc mRNA and results in premature termination of translation. The impairment of translation is mainly due to the shortage of membranous components. Supplementing uRRL with canine microsomal membranes (CMMs) relaxes the impediments to ribosome movement, resolves collided ribosomes, and greatly enhances full-size luciferase production. CMMs also strongly stimulated an extremely inefficient translation of N1mΨ-Luc mRNA in uRRL. Evidence is presented that translational pausing can promote membrane recruitment of polysomes with nascent polypeptides that lack a signal sequence. Our results highlight an underappreciated role of membrane binding to polysomes in the prevention of ribosome collision and premature release of nascent polypeptides.
Manipulating spatial alignment of donor and acceptor in host–guest MOF for TADF
Authors: Liu Xiao-Ting , Hua Weijie , Nie Hong-Xiang , Chen Mingxing , Chang Ze , Bu Xian-He
Published: December 2021

Thermally activated delayed fluorescence (TADF) was achieved when electron-rich triphenylene (Tpl) donors were confined to a cage-based porous metal-organic framework (MOF) host (NKU-111) composed of electron-deficient 2,4,6-tri(pyridin-4-yl)-1,3,5-triazine (Tpt) acceptor as the ligand. The spatially separated donor and acceptor molecules in a face-to-face stacking pattern generated strong through-space charge transfer (CT) interactions with a small energy splitting between the singlet and triplet excited states (∼0.1 eV), which enabled TADF. The resulting Tpl@NKU-111 exhibited an uncommon enhanced emission intensity as the temperature increased. Extensive steady-state and time-resolved spectroscopic measurements and first-principles simulations revealed the chemical and electronic structure of this compound in both the ground and low-lying excited states. A double-channel (T1, T2) intersystem crossing mechanism with S1 was found and explained as single-directional CT from the degenerate HOMO−1/HOMO of the guest donor to the LUMO+1 of one of the nearest acceptors. The rigid skeleton of the compound and effective through-space CT enhanced the photoluminescence quantum yield (PLQY). A maximum PLQY of 57.36% was achieved by optimizing the Tpl loading ratio in the host framework. These results indicate the potential of the MOFs for the targeted construction and optimization of TADF materials.
Fossil Felidae (Carnivora: Mammalia) from the Yuanmou hominid site, southern China (Late Miocene) and its significance in the living environment of the fossil ape
Authors: Jiangzuo Qigao , Li Shijie , Fu Jiao , Wang Shiqi , Ji Xueping , Duan Mei , Che Decai
Published: December 2021

The Yuanmou hominid site is a rare Late Miocene fossil locality in southern China, where thousands of fossil specimens of the ape Lufengpithecus hudiensis have been found. These have been well studied, but the taxonomy of other mammalian groups is not fully understood. This is especially the case for large predator Felidae, which play a key role in the palaeo-environment in which these fossil apes lived. Here we study the systematics of fossil Felidae from Yuanmou, which is composed of four species of machairodonts: Amphimachairodus cf. horribilis, Longchuansmilus xingyongi gen. & sp. nov., aff. Yoshi sp., Machairodontinae gen. & sp. indet. and one species of feline, Felinae gen. & sp. indet. Longchuansmilus xingyongi is a member of Machairodontini, related to Lokotunjailurus and possibly two derived species of Paramachaerodus, i.e. P. orientalis and P. maximiliani. The high diversity of machairodonts suggests a unique palaeo-environment of the Yuanmou Basin during the Late Miocene, different from northern Eurasia or modern south-eastern Asia. An analysis of body size and intraguild competition suggests that aff. Yoshi sp. and Machairodontinae gen. & sp. indet. are probably regular predators of the fossil great ape, which may have pushed the high evolutionary rate of the fossil ape.
Preoperative evaluation in thoracic surgery: limits of the patient's functional operability and consequence for perioperative anaesthesiologic management
Authors: Starke Henning , von Dossow Vera , Karsten Jan
Published: December 2021

Purpose of review

Preoperative evaluation of older and more morbid patients in thoracic surgery is getting more advanced. In this context, early risk stratification has a crucial role for adequate informed decision-making, and thus for generating favourable effects of clinical outcome.

Recent findings

Recent findings confirm that many risk factors impair mortality and morbidity beyond classical medical findings like results of lung function tests and values of the revised cardiac risk index. Especially results from holistic views on patients’ functional status like frailty assessments are linked with long-term survival after lung resection.

A comprehensive risk stratification by anaesthesiologists generates valuable guidance for the best strategy of clinical treatment. This includes preoperative, peri-operative and postoperative interventions, provided by interdisciplinary healthcare providers, resulting in an Early Risk Stratification and Strategy (’ERSAS’) pathway.
Increased psoas tendon running angle in patients with Legg-Calvé-Perthes disease: a new theory for the aetiology of children with avascular femoral head necrosis
Authors: Nakagawa Keisuke , Kitano Toshio
Published: December 2021

The cause of Legg-Calvé-Perthes disease (LCPD) remains unknown. We propose a new hypothesis that the iliopsoas muscle and/or tendon affects the progression of ischemic necrosis of the femoral head as an anatomical factor. The purpose of this study was to test this hypothesis by measuring the psoas major tendon angle (PMTA) and cross-sectional area (CSA) of the iliopsoas muscle on MRI. We selected three predetermined axial MRI scans at the level of the psoas major tendon origin, the femoral head, and the lesser trochanter. We calculated the proximal, distal, and combined PMTA and compared these angles between the LCPD group and the transient synovitis (TS) group as a control. Our results revealed that the proximal PMTAs of the LCPD-affected sides were significantly greater than in the TS controls (P < 0.05), while there were no significant differences in the proximal PMTA, combined PMTA, and CSA. This result indicates that the psoas major tendon of the patient with LCPD curves sharply on the anterior capsule of the hip joint more than in the control group patients. This sudden curve of the psoas major tendon may be involved in the development of LCPD. We measured PMTAs in patients with LCPD. Our findings suggested that the running curve of the psoas major tendon is an anatomical factor that influences the development of mechanically-induced ischemia in LCPD.
Clinico-radiological factors predicting the failure risk of conservative management in moderate to severe pediatric idiopathic flexible flatfoot
Authors: Kang Michael Seungcheol , Bae Kunhyung , Kim Ho Yeon , Park Soo-Sung
Published: December 2021

This study aimed to investigate the clinico-radiological factors of related future surgical treatment in patients with pediatric flexible flatfoot (FFF) who first visited the orthopedic clinic before the age of 10 years. Sixty-five patients diagnosed with moderate/severe idiopathic FFF deformity between the ages of 2–10 years were included. We developed prognostic models for the risk of the surgery during the follow-up period. Twenty (30.8%) patients required surgical treatment, and all of them underwent calcaneal lengthening osteotomy. Among them, 7 (10.8%) patients required concomitant Achilles-lengthening surgery. Unilateral involvement, older age, smaller calcaneal pitch angle, and higher talo-first metatarsal malalignment were considered high-risk factors for pediatric FFF surgery. Prognostic models identified three prognostic risk groups based on those factors, and survival curves revealed significant differences among the groups. Our prognostic models help predict the failure risk of conservative management of pediatric idiopathic FFF. Level of Evidence: Level III, prognostic study.
Macrophage inhibitory cytokine-1 produced by melanoma cells contributes to melanoma tumor growth and metastasis in vivo by enhancing tumor vascularization
Authors: Lee Jaeseob , Jin Young-June , Lee Moon-Sung , Lee Hansoo
Published: December 2021

Macrophage inhibitory cytokine-1 (MIC-1) has been reported to be elevated in various human cancers including melanoma; however, the function of MIC-1 in cancer remains unclear. In this study, we attempt to clarify the role of MIC-1 in tumor pathogenesis by employing the orthotopic B16F1 melanoma mouse model in which serum MIC-1 levels are positively correlated with tumor size. By stably transfecting a MIC-1 expression construct into B16F1 melanoma cells, we increased the expression and secretion levels of MIC-1. This increase in MIC-1 expression significantly enhanced the growth of tumors derived from B16F1 cells in vivo, despite not affecting in vitro cell growth. The elevated MIC-1 expression in B16F1 cells also resulted in lymph node metastasis in B16F1 tumor-bearing mice, significantly increasing mortality. Interestingly, among small melanoma tumors of similar size, tumors derived from the MIC-1-transfected B16F1 cells exhibited enhanced blood vessel formation compared with those of mock transfectant cells. Also, more MIC-1 was found in well-vascularized tumor regions than in poorly vascularized tumor regions. Moreover, conditioned medium (CM) of the MIC-1-transfected melanoma cells enhanced the angiogenic properties of endothelial cells more than CM of mock transfectant cells. Notably, hypoxic culture conditions forced parental B16F1 cells to secrete more endothelial cell-stimulating factors, among which the function of MIC-1 was confirmed by blocking the effects with an anti-MIC-1 antibody. Taken together, these results suggest that the MIC-1 produced by melanoma cells in response to oxygen deprivation promotes tumor vascularization during melanoma development in vivo, leading to enhanced tumor growth and metastasis.
The Nurse Practitioner as Both Servant Leader and Clinical Leader
Authors: Maglione Joyce L.
Published: December 2021

Servant leadership prioritizes the needs of others. This leadership approach developed by Robert Greenleaf emphasizes a service-oriented holistic model of leadership. The characteristics of servant leadership within the context of a primary healthcare setting with the nurse practitioner as both servant-leader and clinical leader are examined in this article.
Outcome of bystander cardiopulmonary resuscitation after out-of-hospital cardiac arrest in Beijing
Authors: Shi Xian , Wu Yang , Li Haibin , Ma Shengkui , Li Dou , Gao Ding , Cui Hao , Yu Changxiao , Yang Song , Tang Ziren , Shao Fei
Published: December 2021

Aim:

We aimed to investigate the association between bystander cardiopulmonary resuscitation (CPR) and survival of patients with out-of-hospital cardiac arrests (OHCA) in Beijing.

Methods:

This observational study analyzed adult patients with OHCA treated by the Beijing emergency medical service (EMS) from January 2013 to December 2017. Data were collected in a Utstein style with a 1-year follow-up and a primary outcome of survival to hospital discharge. Secondary outcomes were return of spontaneous circulation (ROSC), survival to admission, favorable neurological outcome at hospital discharge, and survival and favorable neurological outcomes of up to 1 year.

Results:

A total of 5016 patients with OHCA from Beijing's urban area were recorded by EMS, wherein 765 patients (15.25%) underwent bystander CPR. The data were propensity score-matched forage, sex, location, witness, aetiology, initial rhythm, and call to EMS arrival to compare the difference between the occurrence and nonoccurrence of bystander CPR. The survival upon the discharge of patients who experienced bystander CPR was superior to that of patients who did not receive bystander CPR (3.7% vs 1.2%, respectively; P 
< 0.001). Moreover, patients with OHCA resuscitated with bystander CPR achieved better outcomes of ROSC, survival to admission, favorable neurological outcome at hospital discharge, survival and favorable neurological outcome after 1 year compared with those who were not resuscitated with bystander CPR.

Conclusion:

Survival and neurological outcome of patients who underwent bystander CPR was better than those who underwent nonbystander CPR in Beijing. However, the rate of bystander CPR was low.