bluuebunny/crossref_metadata_2025 huggingface dataset:
NIA Long Life Family Study: Objectives, Design, and Heritability of Cross-Sectional and Longitudinal Phenotypes
Authors: Wojczynski Mary K , Jiuan Lin Shiow , Sebastiani Paola , Perls Thomas T , Lee Joseph , Kulminski Alexander , Newman Anne , Zmuda Joe M , Christensen Kaare , Province Michael A
Published: November 2021

The NIA Long Life Family Study (LLFS) is a longitudinal, multicenter, multinational, population-based multigenerational family study of the genetic and nongenetic determinants of exceptional longevity and healthy aging. The Visit 1 in-person evaluation (2006–2009) recruited 4 953 individuals from 539 two-generation families, selected from the upper 1% tail of the Family Longevity Selection Score (FLoSS, which quantifies the degree of familial clustering of longevity). Demographic, anthropometric, cognitive, activities of daily living, ankle-brachial index, blood pressure, physical performance, and pulmonary function, along with serum, plasma, lymphocytes, red cells, and DNA, were collected. A Genome Wide Association Scan (GWAS) (Ilumina Omni 2.5M chip) followed by imputation was conducted. Visit 2 (2014–2017) repeated all Visit 1 protocols and added carotid ultrasonography of atherosclerotic plaque and wall thickness, additional cognitive testing, and perceived fatigability. On average, LLFS families show healthier aging profiles than reference populations, such as the Framingham Heart Study, at all age/sex groups, for many critical healthy aging phenotypes. However, participants are not uniformly protected. There is considerable heterogeneity among the pedigrees, with some showing exceptional cognition, others showing exceptional grip strength, others exceptional pulmonary function, etc. with little overlap in these families. There is strong heritability for key healthy aging phenotypes, both cross-sectionally and longitudinally, suggesting that at least some of this protection may be genetic. Little of the variance in these heritable phenotypes is explained by the common genome (GWAS + Imputation), which may indicate that rare protective variants for specific phenotypes may be running in selected families.
N-glycans from Paramecium bursaria chlorella virus MA-1D: Re-evaluation of the oligosaccharide common core structure
Authors: Speciale Immacolata , Di Lorenzo Flaviana , Notaro Anna , Noel Eric , Agarkova Irina , Molinaro Antonio , Van Etten James L , De Castro Cristina
Published: November 2021

Paramecium bursaria chlorella virus MA-1D is a chlorovirus that infects Chlorella variabilis strain NC64A, a symbiont of the protozoan Paramecium bursaria. MA-1D has a 339-kb genome encoding ca. 366 proteins and 11 tRNAs. Like other chloroviruses, its major capsid protein (MCP) is decorated with N-glycans, whose structures have been solved in this work by using nuclear magnetic spectroscopy and matrix-assisted laser desorption ionization-time of flight mass spectrometry along with MS/MS experiments. This analysis identified three N-linked oligosaccharides that differ in the nonstoichiometric presence of three monosaccharides, with the largest oligosaccharide composed of eight residues organized in a highly branched fashion. The N-glycans described here share several features with those of the other chloroviruses except that they lack a distal xylose unit that was believed to be part of a conserved core region for all the chloroviruses. Examination of the MA-1D genome detected a gene with strong homology to the putative xylosyltransferase in the reference chlorovirus PBCV-1 and in virus NY-2A, albeit mutated with a premature stop codon. This discovery means that we need to reconsider the essential features of the common core glycan region in the chloroviruses.
The dihydrofolate reductase 19-bp deletion modifies the beneficial effect of B-vitamin therapy in mild cognitive impairment: pooled study of two randomized placebo-controlled trials
Authors: Wu Yuanyuan , Smith A David , Bastani Nasser E , Refsum Helga , Kwok Timothy
Published: November 2021

Background: Higher serum homocysteine is associated with cognitive decline in older people. But homocysteine-lowering trials including folic acid (FA) show inconsistent results on cognitive decline. The reduction of FA to dihydrofolate by dihydrofolate reductase (DHFR) is slow in humans. Objective: We examined the effects of the DHFR 19-bp deletion/insertion (del/ins) polymorphism on FA-containing treatment on cognitive decline and brain atrophy in older people with mild cognitive impairment (MCI). Methods: This study used pooled data from two randomized B-vitamin trials on 545 MCI subjects who received either FA-containing B vitamins or placebo for 24 months. Subjects were typed for the DHFR genotype. Primary outcome was the Clinical Dementia Rating scale-global score (CDR-global). Secondary outcomes were CDR-sum of boxes score (CDR-SOB), memory and executive Z-scores and whole brain atrophy rate by serial MRI. Results: The proportions of subjects with del/del, del/ins and ins/ins genotype were 29.5, 44.3 and 26.1%, respectively. DHFR genotypes modified the effects of B vitamins on CDR-global, CDR-SOB and executive function Z-score (Pinteraction = 0.017, 0.014 and 0.052, respectively), with significant benefits being observed only in those with ins/ins genotype (Beta = −1.367, −0.614 and 0.315, P = 0.004, 0.014 and 0.012, respectively). The interaction was not significant for memory Z-score and whole brain atrophy rate. Notably, the supplements only slowed brain atrophy in members of the ‘ins/ins’ group who were not using aspirin. Conclusions: Our data indicate that the beneficial effects of B vitamins including FA on cognitive function are only apparent in those with ins/ins genotype, i.e. relatively better preserved DHFR activity.
Reduced nuclear NAD+ drives DNA damage and subsequent immune activation in the retina
Authors: Brown Emily E , Scandura Michael J , Mehrotra Sudeep , Wang Yekai , Du Jianhai , Pierce Eric A
Published: November 2021

Mutations in NMNAT1, a key enzyme involved in the synthesis of NAD+ in the nucleus, lead to an early onset severe inherited retinal degeneration (IRD). We aimed to understand the role of nuclear NAD+ in the retina and to identify the molecular mechanisms underlying NMNAT1-associated disease, using a mouse model that harbors the p.V9M mutation in Nmnat1 (Nmnat1V9M/V9M). We identified temporal transcriptional reprogramming in the retinas of Nmnat1V9M/V9M mice prior to retinal degeneration, which begins at 4 weeks of age, with no significant alterations in gene expression at 2 weeks of age and over 2600 differentially expressed genes by 3 weeks of age. Expression of the primary consumer of NAD+ in the nucleus, PARP1, an enzyme involved in DNA damage repair and transcriptional regulation, as well as 7 other PARP family enzymes, was elevated in the retinas of Nmnat1V9M/V9M. This was associated with elevated levels of DNA damage, PARP-mediated NAD+ consumption and migration of Iba1+/CD45+ microglia/macrophages to the subretinal space in the retinas of Nmnat1V9M/V9M mice. These findings suggest that photoreceptor cells are especially sensitive to perturbation of genome homeostasis, and that PARP-mediated cell death may play a role in other genetic forms of IRDs, and potentially other forms of neurodegeneration.
Efficacy, Safety, and Tolerability of Ansofaxine (LY03005) Extended-Release Tablet for Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding, Phase 2 Clinical Trial
Authors: Mi Weifeng , Yang Fude , Li Huafang , Xu Xiufeng , Li Lehua , Tan Qingrong , Wang Guoqiang , Zhang Kerang , Tian Feng , Luo Jiong , Xia Jielai , Yuan Kai , Lu Lin , Deng Jiahui , Tian Jingwei , Zhang Hongyan
Published: November 2021

Background

Ansofaxine (LY03005) extended-release tablet is a potential triple reuptake inhibitor of serotonin, norepinephrine, and dopamine. This study assessed the efficacy, safety, and appropriate dosage of ansofaxine for the treatment of major depressive disorder (MDD).

Methods

A multicenter, randomized, double-blind, placebo-controlled, dose-finding, Phase 2 clinical trial was conducted in China. Eligible patients with MDD (18–65 years) were randomly assigned to receive fixed-dose ansofaxine extended-release tablets (40, 80, 120, or 160 mg/d) or placebo for 6 weeks. The primary outcome measure was a change in the total score on the 17-item Hamilton Depression Rating Scale from baseline to week 6.

Results

A total of 260 patients were recruited from October 2015 to September 2017, and 255 patients received the study drug as follows: 40 mg (n = 52), 80 mg (n = 52), 120 mg (n = 51), and 160 mg (n = 51) ansofaxine and placebo (n = 49). Significant differences were found in mean changes in 17-item Hamilton Depression Rating Scale total scores at week 6 in the 4 ansofaxine groups vs placebo (−12.46; χ2 = −9.71, P = .0447). All doses of ansofaxine were generally well-tolerated. Treatment-related adverse events occurred in 141 patients (303 cases), yielding incidence rates of 51.92%, 65.38%, 56.86%, and 62.75% in the 40-, 80-, 120-, and 160-mg ansofaxine groups and 38.78% in the placebo group.

Conclusion

Active doses (40, 80, 120, and 160 mg/d) of ansofaxine in a controlled setting were safe, tolerated, and effective in improving depression symptoms in MDD patients.
Tropical Quantum Field Theory, Mirror Polyvector Fields, and Multiplicities of Tropical Curves
Authors: Mandel Travis , Ruddat Helge
Published: November 2021

We introduce algebraic structures on the polyvector fields of an algebraic torus that serve to compute multiplicities in tropical and log Gromov–Witten theory while also connecting to the mirror symmetry dual deformation theory of complex structures. Most notably these structures include a tropical quantum field theory and an $L_{\infty }$-structure. The latter is an instance of Getzler’s gravity algebra, and the $l_2$-bracket is a restriction of the Schouten–Nijenhuis bracket. We explain the relationship to string topology in the Appendix (thanks to Janko Latschev).
Development and Implementation of One-Step, Broad-Spectrum, High-Sensitivity Drug Screening by Tandem Mass Spectrometry in a Pediatric Population
Authors: Tesfazghi Merih T , Bardelmeier Rick , Saunders Al N , Riley Sarah M , Roper Stephen M , Dietzen Dennis J
Published: November 2021

Background

Drug screening by immunoassay is common in pediatric populations. However, false-positive and -negative results due to antibody cross-reactivity and dilute urine are frequent and underappreciated. Accurate ascertainment of drug exposure in children has significant clinical and medico-legal consequences.

Design and Methods

We developed and characterized an LC–MS/MS drug screening assay to supplant immunoassay and detect 38 compounds at the lowest concentrations distinguishable from analytic noise. Once implemented, we conducted a retrospective analysis of 3985 pediatric urine drug screens performed a year before (n = 1663) and after (n = 2322) implementation to examine the frequency and breadth of drug detection in our pediatric population.

Results

Using immunoassay, 23% (293/1269) of samples from the general pediatric and 37% (147/394) of nursery populations had presumptively positive results. Of the presumptive positive compounds, 85% (288/338) from the general pediatric population and 40% (65/162) from the nursery cohort were confirmed by mass spectrometry. After LC–MS/MS implementation, 31% (628/2052) of general pediatric, and 18% (48/270) of the nursery samples were positive for 1 or more compounds. In the nursery population, immunoassays over-detected the presence of THC but under-detected exposure to cocaine.

Conclusion

A broadly targeted, analytically sensitive LC–MS/MS drug screening assay detects a larger number and variety of compounds in a single step compared to a screen-then-confirm approach initiated by immunoassay in our pediatric population. Rapid delivery of accurate results enables timely, appropriate disposition of patients in a variety of settings including the emergency department and labor/delivery.
Evaluation of Preanalytical Point-of-Care Testing Errors and Their Impact on Productivity in the Emergency Department in the United States
Authors: Kazmierczak Steven C , Morosyuk Svetlana , Rajkumar Rahul
Published: November 2021

Background

Preanalytical errors due to poor sample quality or improper sample handling may occur with point-of-care testing (POCT).

Methods

A retrospective analysis was conducted using deidentified records for 15 479 i-STAT® cartridges run at the Oregon Health & Science University Emergency Department (ED) between December 2015 and August 2016. Data were collected from electronic health records and device middleware for CG4+, CHEM8+, and Troponin cartridges. The frequency of POCT errors was evaluated by cartridge type. The effect of user experience on error frequency, impact of error on hospital length of stay (LOS), and test turnaround time (TAT) were all evaluated. Direct costs incurred due to Chem8+ and Troponin cartridge waste and indirect costs as avoidable nursing staff labor were estimated over 2 years.

Results

A total of 935 erroneous results were identified (6.0% of all cartridges). Three hundred seventy-two (2.4%) were unusable results, and 563 (3.6%) were cartridge errors, of which 163 were classified by device error codes as poor sample quality/improper sample handling. Error rates were inversely correlated with user experience based on number of tests performed during the 9-month period. Compared to nonerroneous results, test TATs and LOS were significantly longer with erroneous results (P < 0.01). Over 2 years, direct costs incurred due to cartridge waste was $45 000, and indirect cost was estimated between 486 and 729 h in avoidable nursing labor.

Conclusions

Preanalytical POCT errors were inversely correlated with user experience and significantly impacted clinical productivity in the ED based on LOS and test TAT.
Characterizing styles of clinical note production and relationship to clinical work hours among first-year residents
Authors: Gong Jen J , Soleimani Hossein , Murray Sara G , Adler-Milstein Julia
Published: November 2021

Objective

To characterize variation in clinical documentation production patterns, how this variation relates to individual resident behavior preferences, and how these choices relate to work hours.

Materials and Methods

We used unsupervised machine learning with clinical note metadata for 1265 progress notes written for 279 patient encounters by 50 first-year residents on the Hospital Medicine service in 2018 to uncover distinct note-level and user-level production patterns. We examined average and 95% confidence intervals of median user daily work hours measured from audit log data for each user-level production pattern.

Results

Our analysis revealed 10 distinct note-level and 5 distinct user-level production patterns (user styles). Note production patterns varied in when writing occurred and in how dispersed writing was through the day. User styles varied in which note production pattern(s) dominated. We observed suggestive trends in work hours for different user styles: residents who preferred producing notes in dispersed sessions had higher median daily hours worked while residents who preferred producing notes in the morning or in a single uninterrupted session had lower median daily hours worked.

Discussion

These relationships suggest that note writing behaviors should be further investigated to understand what practices could be targeted to reduce documentation burden and derivative outcomes such as resident work hour violations.

Conclusion

Clinical note documentation is a time-consuming activity for physicians; we identify substantial variation in how first-year residents choose to do this work and suggestive trends between user preferences and work hours.
Compatibility of a Beta-cyfluthrin-Based ‘Attract-and-Kill’ Device with Tamarixia radiata (Hymenoptera: Eulophidae) for Suppression of Diaphorina citri (Hemiptera: Liviidae) on Residential Citrus
Authors: Chow Andrew , Sétamou Mamoudou
Published: November 2021

The Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Liviidae), is a serious threat to the U.S. citrus industry because it spreads huanglongbing (HLB), a bacterial and incurable citrus disease. The nymphal parasitoid, Tamarixia radiata Waterston (Hymenoptera: Eulophidae), has been extensively released for biological control of D. citri in South Texas since 2010 but provides insufficient control. An ‘attract-and-kill’ (AK) device was evaluated for its compatibility with T. radiata for suppression of D. citri on dooryard citrus. The AK device is visually attractive to D. citri adults because it is the same color as young citrus flush and kills individuals on contact with the toxicant beta-cyfluthrin. This study evaluated 1) lethality of AK devices to T. radiata adults under lab conditions; 2) efficacy of AK devices for year-round psyllid suppression on individual dooryard lemon trees; 3) discovery and parasitism of D. citri colonies by T. radiata on lemon trees with or without AK devices. Contact with AK devices for 5 s or more was lethal to adult parasitoids. Deployment of 20 AK devices per tree provided significant year-round suppression of D. citri on infested lemon trees and reduced mean attack intensity (cumulative psyllid-days) of adults by 66% and nymphs by 82%. Discovery and parasitism rates of D. citri colonies by T. radiata were similar on control trees and trees protected by AK devices. An AK device that targets adult psyllids could be used to effectively complement biological control of D. citri by T. radiata in residential landscapes.
Identification of Sex Pheromone Components of KoreanDioryctria abietella(Lepidoptera: Pyralidae) Population and Synergism of Pheromone and Pine Cone Volatile Blends
Authors: Lee Sung-Chan , Lee Jae-Woo , Lee Dong Ha , Huh Min-Jung , Nam Il , Park Ji-Hong , Jung Myunghee , Park Il-Kwon
Published: November 2021

(9Z,11E)-tetradecadienyl acetate (9Z,11E-14:OAc) and (3Z,6Z,9Z,12Z,15Z)-pentacosapentaene (C25 pentaene), known as the sex pheromone of the European Dioryctria abietella population, were identified in the Korean D. abietella population. The ratio of 9Z,11E-14:OAc to C25 pentaene extracted from female pheromone glands was 1:23. The electroantennogram (EAG) response of male antennae to 9Z,11E-14:OAc was stronger than to C25 pentaene, whereas an opposite EAG response was observed in female antennae. Major volatile compounds in mature Korean pine cone (Pinus koraiensis), such as limonene, myrcene, and (-)-α-pinene, elicited dose-dependent EAG responses of male and female antennae. In field attraction testing, traps baited with 100:1,000, 100:2,000, and 100:3,000 ug of 9Z,11E-14:OAc to C25 pentaene were the most attractive to male D. abietella. More males were attracted to traps baited with 9Z,11E-14:OAc+C25 pentaene+limonene than traps baited with 9Z,11E-14:OAc+C25 pentaene. This showed that limonene acted as a synergist to sex pheromone. Delta traps, wing traps, and diamond traps were superior to bucket traps for capturing D. abietella males. This study showed that pheromone traps baited with 100:1,000 ~ 100:3,000 ug of 9Z,11E-14:OAc to C25 pentaene and limonene will be useful for the exact monitoring of D. abietella flight phenology in Pinus koraiensis Sieb. & Zucc. (Pinales: Pinaceae) forests.
Nontarget Impacts of Herbicides on Spiders in Orchards
Authors: Schmidt-Jeffris Rebecca A , Moretti Erica A , Bergeron Paul E , Zilnik Gabriel
Published: November 2021

Spiders are key predators in many agroecosystems, including orchards. Despite the importance of spiders in biological control, pesticide nontarget effects on this group are poorly described. This is especially true for herbicides, which spiders frequently encounter as they move between the ground cover and tree canopy. We sought to determine the nontarget effects of seven herbicides used in orchards on three species of spiders that are commonly found in Washington state (USA) orchards: Pelegrina aeneola (Curtis) (Araneae: Salticidae), Philodromus cespitum (Walckenaer) (Araneae: Philodromidae), and Phanias watonus (Chamberlin & Ivie) (Araneae: Salticidae). Immature spiders were collected from orchards and used in laboratory assays. Single spiders were placed in vials with dried herbicide residues and mortality was evaluated after 1, 2, and 5 d. We also evaluated herbicide impacts on prey consumption rates and on spider movement using motion-tracking software. Only oxyfluorfen caused significant spider mortality. P. cespitum seemed to be less acutely sensitive to oxyfluorfen than the two salticid species. Several herbicide treatments significantly increased locomotion in P. cespitum, whereas rimsulfuron numerically decreased movement of P. aeneola. Sulfonylurea herbicides (rimsulfuron, halosulfuron) decreased prey consumption of P. aeneola. Our work indicates that although spiders may be less acutely sensitive to some pesticides than beneficial insects, they can be affected by sublethal effects of herbicides. Future work should determine if herbicide applications impact spider abundance in the field and reduce biological control services. In general, more work is needed on the impacts of herbicides on natural enemies.
Evaluating the Practice of Universal Jurisdiction Through the Concept of Legitimacy
Authors: Rosen Natalie
Published: November 2021

This article examines the practice of universal criminal jurisdiction with respect to the core international crimes, namely war crimes, genocide, crimes against humanity and torture, while using the concept of legitimacy to analyse the grounds for compliance (viz. the implementation and application) with that principle, or lack thereof, particularly with the unconditional form of universal jurisdiction. The concept of legitimacy has been in the centre of the discourse on the effectiveness of public international law since the end of 1980s, and rests on the assumption that a rule that is perceived as legitimate exerts stronger pull for compliance and is subsequently likely to be exercised more effectively than a rule which is regarded as illegitimate. The added value of the article to the debate on universal jurisdiction lies with its methodical breaking down of legitimacy into three heads: legitimacy of source, legitimacy of process and legitimacy of outcome, which provides new insights and perspectives regarding the much-contested universal jurisdiction practice. The article starts with discussing different approaches to legitimacy and then moves to apply them to the principle of universal jurisdiction as generally practised over the last two decades, using the three-head-taxonomy of legitimacy of source, legitimacy of process and legitimacy of outcome, as well as the typology offered by Thomas Franck of the factors influencing a norm or an institution’s perception as legitimate.
First Reports of Macrosaccus morrisella (Lepidoptera: Gracillariidae) Feeding on Soybean, Glycine max (Fabales: Fabaceae)
Authors: Koch Robert L , Moisan-De Serres Joseph , Ribeiro Arthur V
Published: November 2021

Macrosaccus morrisella (Fitch) is a tiny leaf-mining moth native to North America. In this publication, we provide first reports of this insect feeding on soybean, Glycine max (L.) Merr., in Canada and the United States, describe its injury to soybean, and briefly review leaf miners associated with soybean. Further efforts related to M. morrisella should focus on its geographic extent of infestation of soybean, impacts to soybean, and ecology in the agricultural landscape.
Laboratory Evaluation of Flight Capacities ofAedes japonicus(Diptera: Culicidae) Using a Flight Mill Device
Authors: Krupa Eva , Gréhal Alexa-Lou , Esnault Jérémy , Bender Christelle , Mathieu Bruno
Published: November 2021

Dispersion expands the distribution of invasive species and as such, it is a key factor of the colonization process. Aedes japonicus japonicus (Theobald, 1901) is an invasive species of mosquito and a vector of various viruses. It was detected in the northeast of France in 2014. The population of this species can expand its distribution by several kilometers per year. However, though flight capacities play an active part in the dispersion of Ae. japonicus, they remain unknown for this species. In this study, we investigated the flight capacities of Ae. japonicus in a laboratory setting using the flight mill technique. We evaluated the influence of age on flight. We recorded videos of individual flights with a camera mounted on Raspberry Pi. We extracted data on distance, duration, and speed of flight using the Toxtrac and Boris software. Our analysis showed a median flight distance of 438 m with a maximum of 11,466 m. Strong flyers, which represented 10% of the females tested, flew more than 6,115 m during 4 h and 28 min at a speed of 1.7 km per h. As suspected, Ae. japonicus is a stronger flyer than the other invasive species Aedes albopictus (Skuse, 1894) (Diptera: Culicidae). To our knowledge, this is the first flight mill study conducted on Ae. japonicus and therefore the first evaluation of its flight capacity. In the future, the flight propensity of Ae. japonicus determined in this study can be included as a parameter to model the colonization process of this invasive vector species.
Challenges needed to be overcome in multi-institutional surgical trials: accumulated experience in the JCOG Colorectal Cancer Study Group (CCSG)
Authors: Kataoka Kozo , Fujita Shin , Inomata Masafumi , Takii Yasumasa , Ohue Masayuki , Shiozawa Manabu , Akagi Tomonori , Ikeda Masataka , Tsukamoto Shunsuke , Tsukada Yuichiro , Ito Masaaki , Ikeda Satoshi , Ueno Hideki , Shida Dai , Kanemitsu Yukihide
Published: November 2021

JCOG-CCSG has been conducting several surgical trials and experienced several challenges. The first point is the appropriate timing of conducting the trial. Once a certain number of surgeons acquire the new technique and its utility is accepted, it suddenly becomes difficult to maintain ‘equipoise’ between the standard and new treatment, which may lead to poor patient accrual. Smooth preparation and commencement of the trial at an appropriate timing is necessary for its success. Second is the appropriate quality assurance of surgery. High-level quality assurance will strengthen the comparability of randomized control trials and minimize the heterogeneity among hospitals. On the other hand, it may impair the generalizability of the trial. Large observational studies help to bridge the gap of heterogeneity among hospitals. Third is the selection of an appropriate endpoint. Overall survival (OS) is the gold-standard primary endpoint; however, the number of events is much less due to more effective treatment. JCOG0212 and JCOG0404 were unable to demonstrate the non-inferiority of omission of lateral lymph node dissection and laparoscopic surgery partly due to a lack of power. Disease-free survival (DFS) is also a promising candidate for primary endpoint, but as in JCOG0603, special attention must be paid when DFS does not correlate with OS. Although careful discussion is required because the precision of the hazard ratio depends on the number of events, an alternative population-level summary of variables, including restricted mean survival time, can be considered as the primary endpoint. Future surgical trials should be planned considering these points.
The effects and the mechanisms of naringenin from Artemisia ordosica Krasch on allergic rhinitis based on mast cell degranulation model and network pharmacology
Authors: Niu Yixuan , She Zhanfei , Su Changhai , Zhao Qingchun , Wang Shumin , Xiao Bin
Published: November 2021

Objectives

The ethyl acetate extraction of Artemisia ordosica Krasch (AOK) root showed anti-allergic rhinitis (AR) effect, while the active compounds and pharmacological targets were unknown.

Methods

The P815 degranulation was established by cell counting kit 8 assay, β-hexosaminidase releasing assay and toluidine blue staining. The flavonoids were screened in vitro. Then toluidine blue staining and ELISA were carried out to investigate the anti-inflammatory effects of the active compound. Network pharmacology was implemented to explain the mechanisms of the active compound. iGEMDOCK was used to investigate the binding between active compound and hub targets.

Key findings

C48/80 was the optimum reagent in triggering P815 degranulation. Naringenin could significantly decrease P815 degranulation. Meanwhile, naringenin could remarkably increase the IL-4 and decrease the tumour necrosis factor-α. The effect of naringenin on AR was achieved by regulating multiple targets (e.g. AKT1, MAPK3, VEGFA) and pathways (e.g. pathways in cancer, VEGF signalling pathway). Nine hub proteins were obtained by topological analysis. Multiple hydrogen bonds and van der Waals forces were formed between the naringenin and the residues of hub proteins.

Conclusions

Naringenin might be one of the effective ingredients of AOK against AR. And its effects could achieve through regulating multiple targets and pathways.
Neuroprotective effects of synthetic borneol and natural borneol based on the neurovascular unit against cerebral ischaemic injury
Authors: Xie Qian , Li Jinxiu , Dong Taiwei , Yuan Jianmei , Lu Danni , Ma Rong , Li Hongyan , Li Yong , Ren Mihong , Chen Hai , Wang Jian
Published: November 2021

Objectives

Natural borneol and synthetic borneol were commonly used to treat ischaemic stroke in clinical practice. This study evaluated their different neuroprotective effects on the remodelling and repair of the neurovascular unit (NVU) after cerebral ischaemia.

Methods

We evaluated the different effects of borneol through neurological test and staining methods in cerebral ischaemia injury. Western blot, immunohistochemistry and transmission electron microscopy were used to evaluate the reparative effects of borneol on NVU.

Key findings

The prevention and treatment of borneol could prolong recovery time, reduce body temperature and cerebral infarction rate and improve pathological conditions. Further investigations revealed that borneol could inhibit the expression of DII4, Hes1, Hes5 and p65 and increase the Nissl body number and microvessel density. They also inhibited the activation of the microglia. It was also observed through an ultramicroelectron microscope that the structural stability of the NVU has also been repaired. Moreover, natural borneol shows better results in most indicators when compared with synthetic borneol.

Conclusions

Natural borneol showed a stronger effectiveness and had better regulation and neuroprotection on the NVU when compared with synthetic borneol, indicating that it may be better to use natural borneol in the prescription of Chinese patent medicine in clinical practice.
Fully automated rigid image registration versus human registration in postoperative spine stereotactic body radiation therapy: a multicenter non-inferiority study
Authors: Koide Yutaro , Shimizu Hidetoshi , Miyauchi Risei , Haimoto Shouichi , Tanaka Hiroshi , Watanabe Yui , Adachi Sou , Kato Daiki , Aoyama Takahiro , Kitagawa Tomoki , Tachibana Hiroyuki , Kodaira Takeshi
Published: November 2021

To confirm the fully automated rigid image registration (A-RIR) accuracy in postoperative spine stereotactic body radiation therapy (SBRT), we conducted a multicenter non-inferiority study compared to the human rigid image registration (H-RIR). Twenty-eight metastatic cancer patients who underwent postoperative spine SBRT are enrolled—image registration (IR) of planning computed tomography (CT) and CT-myelogram for delineating the spinal cord. The adopted A-RIR workflow is a contour-focused algorithm performing a rigid registration by maximizing normalized mutual information (NMI) restricted to the data contained within the automatically extracted contour. Three radiation oncologists (ROs) from multicenters were prompted to review two blinded registrations and choose one for clinical use. Indistinguishable cases were allowed to vote equivalent, counted A-RIR side. A-RIR is considered non-inferior to H-RIR if the lower limit of the 95% confidence interval (CI) of A-RIR preferable/equivalent is greater than 0.45. We also evaluated the NMI improvement from the baseline and the translational/rotational errors between A-RIR and H-RIR. The A-RIR preferable/equivalent was selected in 21 patients (0.75, 95% CI: 0.55–0.89), demonstrating non-inferiority to H-RIR. The A-RIR’s NMI improvement was greater than H-RIR in 24 patients: the mean value ± SD was 0.225 ± 0.115 in A-RIR and 0.196 ± 0.114 in H-RIR (P < 0.001). The absolute translational error was 0.38 ± 0.31 mm. The rotational error was −0.03 ± 0.20, 0.05 ± 0.19, −0.04 ± 0.20 degrees in axial, coronal, and sagittal planes (range: −0.66–0.52). In conclusion, A-RIR shows non-inferior to H-RIR in CT and CT-myelogram registration for postoperative spine SBRT planning.
MADS-box transcription factors determine the duration of temporary winter dormancy in closely related evergreen and deciduousIrisspp.
Authors: Li Danqing , Shao Lingmei , Zhang Jiao , Wang Xiaobin , Zhang Dong , Horvath David P , Zhang Liangsheng , Zhang Jiaping , Xia Yiping
Published: November 2021

Winter dormancy (WD) is a crucial strategy for plants coping with potentially deadly environments. In recent decades, this process has been extensively studied in economically important perennial eudicots due to changing climate. However, in evergreen monocots with no chilling requirements, dormancy processes are so far a mystery. In this study, we compared the WD process in closely related evergreen (Iris japonica) and deciduous (I. tectorum) iris species across crucial developmental time points. Both iris species exhibit a ‘temporary’ WD process with distinct durations, and could easily resume growth under warm conditions. To decipher transcriptional changes, full-length sequencing for evergreen iris and short read RNA sequencing for deciduous iris were applied to generate respective reference transcriptomes. Combining results from a multipronged approach, SHORT VEGETATIVE PHASE and FRUITFULL (FUL) from MADS-box was associated with a dormancy- and a growth-related module, respectively. They were co-expressed with genes involved in phytohormone signaling, carbohydrate metabolism, and environmental adaptation. Also, gene expression patterns and physiological changes in the above pathways highlighted potential abscisic acid and jasmonic acid antagonism in coordinating growth and stress responses, whereas differences in carbohydrate metabolism and reactive oxygen species scavenging might lead to species-specific WD durations. Moreover, a detailed analysis of MIKCCMADS-box in irises revealed common features described in eudicots as well as possible new roles for monocots during temporary WD, such as FLOWERING LOCUS C and FUL. In essence, our results not only provide a portrait of temporary WD in perennial monocots but also offer new insights into the regulatory mechanism underlying WD in plants.
Volatile-mediated plant–plant interactions: volatile organic compounds as modulators of receiver plant defence, growth, and reproduction
Authors: Brosset Agnès , Blande James D
Published: November 2021

It is firmly established that plants respond to biotic and abiotic stimuli by emitting volatile organic compounds (VOCs). These VOCs provide information on the physiological status of the emitter plant and are available for detection by the whole community. In the context of plant–plant interactions, research has focused mostly on the defence-related responses of receiver plants. However, responses may span hormone signalling and both primary and secondary metabolism, and ultimately affect plant fitness. Here we present a synthesis of plant–plant interactions, focusing on the effects of VOC exposure on receiver plants. An overview of the important chemical cues, the uptake and conversion of VOCs, and the adsorption of VOCs to plant surfaces is presented. This is followed by a review of the substantial VOC-induced changes to receiver plants affecting both primary and secondary metabolism and influencing plant growth and reproduction. Further research should consider whole-plant responses for the effective evaluation of the mechanisms and fitness consequences of exposure of the receiver plant to VOCs.
The epigenetic mechanisms regulating floral hub genes and their potential for manipulation
Authors: Yamaguchi Nobutoshi
Published: November 2021

Gene regulatory networks formed by transcription factors play essential roles in the regulation of gene expression during plant reproductive development. These networks integrate endogenous, phytohormonal, and environmental cues. Molecular genetic, biochemical, and chemical analyses performed mainly in Arabidopsis have identified network hub genes and revealed the contributions of individual components to these networks. Here, I outline current understanding of key epigenetic regulatory circuits identified by research on plant reproduction, and highlight significant recent examples of genetic engineering and chemical applications to modulate the epigenetic regulation of gene expression. Furthermore, I discuss future prospects for applying basic plant science to engineer useful floral traits in a predictable manner as well as the potential side effects.
Conflicted presence: The many arrivals of Palestinians in Lebanon
Authors: Feldman Ilana
Published: November 2021

No refugee arrival is ever a single event. Arrival repeats, but it is not the same each time. Each arrival is shaped by previous experience as well as future expectation. Considering the multiple layers that constitute refugee arrival is thus necessary to understand such experiences. Palestinians, who have experienced many arrivals, offer an instructive case. This article focuses on Lebanon, where Palestinian presence has always been challenged, and challenging. And this presence has also undergone many changes over the years. Approaching presence through the lens of the built environment, it explores how the construction, inhabitation, and destruction of buildings change over time and are historically layered. The article takes up three distinct moments in Palestinian history in Lebanon: (1) the early years/first arrival; (2) the time of revolution [thawra]; and (3) rebuilding after destruction by Israeli invasion and the Lebanese civil war. Together, these snapshots of different layers in cumulative arrival offer a textured image of Palestinian presence. An exploration of these layers shows that the formal recognition that derives from hereness is often the smaller part of its impact. Presence has a power that regularly defies the discursive, legal, and even affective limits that people and governments seek to put on it.
Massive stars dying alone: the remote environment of supernova 2010jp and its associated late-time source
Authors: Corgan Austin , Smith Nathan , Andrews Jennifer , Filippenko Alexei V , Van Dyk Schuyler D
Published: November 2021

We present late-time images of the site of the peculiar jet-driven Type IIn supernova (SN) 2010jp, including Hubble Space Telescope images taken 2–5 yr post-explosion and deep ground-based images over a similar time. These are used to characterize its unusually remote environment and to constrain the progenitor’s initial mass and age. The position of SN 2010jp is found to reside along a chain of diffuse starlight that is probably an outer spiral arm or tidal tail of the interacting galaxy pair NGC 2207/IC 2163. There is one bright H ii region projected within 1 kpc, and there is faint extended H α emission immediately surrounding the continuum source at the position of SN 2010jp, which has MF555W = −7.7 ± 0.2 mag. In principle, the lingering light could arise from late-time circumstellar material (CSM) interaction, an evolved supergiant, a host star cluster, or some combination of these. Steady flux over 3 yr and a lack of strong, spatially unresolved H α emission make ongoing CSM interaction unlikely. If an evolved supergiant dominates, its observed luminosity implies an initial mass $\lesssim\!{22}$ M⊙ and an age $\gtrsim\!{8}$ Myr. If the source is a star cluster, then its colour and absolute magnitude imply an age of 8–13 Myr and a modest cluster initial mass of log(M/M⊙) = 3.6–3.8. Extended H α emission out to a radius of ∼30 pc reveals a faint evolved H ii region, pointing to recent star formation with at least one late O-type star. Based on these various clues, we conclude that the progenitor of SN 2010jp had a likely initial mass of 18–22 M⊙.
The ‘breaking the chains’ migration model for super-Earth formation: the effect of collisional fragmentation
Authors: Esteves Leandro , Izidoro André , Bitsch Bertram , Jacobson Seth A , Raymond Sean N , Deienno Rogerio , Winter Othon C
Published: November 2021

Planets between 1 and 4 R⊕ (Earth radius) with orbital periods <100 d are strikingly common. The migration model proposes that super-Earths migrate inwards and pile up at the disc inner edge in chains of mean motion resonances. After gas disc dispersal, simulations show that super-Earth’s gravitational interactions can naturally break their resonant configuration leading to a late phase of giant impacts. The instability phase is key to matching the orbital spacing of observed systems. Yet, most previous simulations have modelled collisions as perfect accretion events, ignoring fragmentation. In this work, we investigate the impact of imperfect accretion on the ‘breaking the chains’ scenario. We performed N-body simulations starting from distributions of planetary embryos and modelling the effects of pebble accretion and migration in the gas disc. Our simulations also follow the long-term dynamical evolution of super-Earths after the gas disc dissipation. We compared the results of simulations where collisions are treated as perfect merging events with those where imperfect accretion and fragmentation are allowed. We concluded that the perfect accretion is a suitable approximation in this regime, from a dynamical point of view. Although fragmentation events are common, only ∼10 per cent of the system mass is fragmented during a typical ‘late instability phase’, with fragments being mostly reacreted by surviving planets. This limited total mass in fragments proved to be insufficient to alter qualitatively the final system dynamical configuration – e.g. promote strong dynamical friction or residual migration – compared to simulations where fragmentation is neglected.
Kinetic simulations of imbalanced turbulence in a relativistic plasma: Net flow and particle acceleration
Authors: Hankla Amelia M , Zhdankin Vladimir , Werner Gregory R , Uzdensky Dmitri A , Begelman Mitchell C
Published: November 2021

Turbulent high-energy astrophysical systems often feature asymmetric energy injection: for instance, Alfvén waves propagating from an accretion disc into its corona. Such systems are ‘imbalanced’: the energy fluxes parallel and antiparallel to the large-scale magnetic field are unequal. In the past, numerical studies of imbalanced turbulence have focused on the magnetohydrodynamic regime. In this study, we investigate externally driven imbalanced turbulence in a collision-less, ultrarelativistically hot, magnetized pair plasma using 3D particle-in-cell (PIC) simulations. We find that the injected electromagnetic momentum efficiently converts into plasma momentum, resulting in net motion along the background magnetic field with speeds up to a significant fraction of lightspeed. This discovery has important implications for the launching of accretion disc winds. We also find that although particle acceleration in imbalanced turbulence operates on a slower time-scale than in balanced turbulence, it ultimately produces a power-law energy distribution similar to balanced turbulence. Our results have ramifications for black hole accretion disc coronae, winds, and jets.
The variability of brightest cluster galaxies at high radio frequencies
Authors: Rose Tom , Edge Alastair , Kiehlmann Sebastian , Baek Junhyun , Chung Aeree , Jung Tae-Hyun , Kim Jae-Woo , Readhead Anthony C S , Sedgewick Aidan
Published: November 2021

Variability of a galaxy’s core radio source can be a significant consequence of active galactic nucleus accretion. However, this variability has not been well studied, particularly at high radio frequencies. As such, we report on a campaign monitoring the high radio frequency variability of 20 nearby, cool-core brightest cluster galaxies. From our representative sample, we show that most vary significantly on time-scales of approximately 1 yr and longer. Our highest cadence observations are at 15 GHz and are from the Owens Valley Radio Observatory. They have a median time interval of 7 d and mostly span between 8 and 13 yr. We apply a range of variability detection techniques to the sources’ light curves to analyse changes on week to decade long time-scales. Most notably, at least half of the sources show 20 per cent peak to trough variability on 3 yr time-scales, while at least a third vary by 60 per cent on 6 yr time-scales. Significant variability, which is important to studies of the Sunyaev–Zel’dovich Effect in the radio/sub-mm, is therefore a common feature of these sources. We also show how the variability relates to spectral properties at frequencies of up to 353 GHz using data from the Korean VLBI network, the NIKA2 instrument of the IRAM 30-m telescope, and the SCUBA-2 instrument of the James Clerk Maxwell Telescope.
Quenched, bulge-dominated, but dynamically cold galaxies in IllustrisTNG and their real-world counterparts
Authors: Lu Shengdong , Xu Dandan , Wang Sen , Wang Yunchong , Mao Shude , Xia Xiaoyang , Vogelsberger Mark , Hernquist Lars
Published: November 2021

Galaxy morphologies, kinematics, and stellar populations are thought to be linked to each other. However, both simulations and observations have pointed out mismatches therein. In this work, we study the nature and origin of the present-day quenched, bulge-dominated, but dynamically cold galaxies within a stellar mass range of $10.3\, \leqslant \, \log \, M_{\ast }/\mathrm{M_{\odot }}\, \leqslant \, 11.2$ in the IllustrisTNG-100 Simulation. We compare these galaxies with a population of normal star-forming dynamically cold disc galaxies and a population of normal quenched dynamically hot elliptical galaxies within the same mass range. The populations of the present-day quenched and bulge-dominated galaxies (both being dynamically cold and hot) used to have significantly higher star formation rates and flatter morphologies at redshift of z ∼ 2. They have experienced more frequent larger mass-ratio mergers below z ∼ 0.7 in comparison to their star-forming disc counterparts, which is responsible for the formation of their bulge-dominated morphologies. The dynamically cold populations (both being star forming and quenched) have experienced more frequent prograde and tangential mergers especially below z ∼ 1, in contrast to the dynamically hot ellipticals, which have had more retrograde and radial mergers. Such different merging histories can well explain the differences on the cold and hot dynamical status among these galaxies. We point out that the real-world counterparts of these dynamically cold and hot bulge-dominated quenched populations are the fast- and slow-rotating early-type galaxies, respectively, as seen in observations and hence reveal the different evolution paths of these two distinct populations of early-type galaxies.