bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Better off with Labour’? Fiscal policy, electoral strategy and the road to John Smith’s shadow budget, 1979–92
Authors: Sloman Peter
Published: September 2021

The failure of John Smith’s ‘Shadow Budget’ to deliver a Labour victory in the 1992 general election has taken on a mythical status in narratives around the development of New Labour. This article sets the episode in a larger context by examining the development of Labour’s fiscal policies in opposition after 1979, in the face of rising inequality, public-sector austerity, and regressive tax reforms. It traces how successive election defeats drove a process of political learning, which came to revolve around the effort to reassure floating voters that a Labour government could control tax, spending and borrowing. The 1992 defeat seemed to demonstrate the difficulty of winning support for redistribution in the face of ‘tax bombshell’ attacks, and so paved the way for the more cautious and incremental fiscal politics of Gordon Brown and New Labour.
Efficacy of Ustekinumab in Crohn’s Disease With and Without Concurrent Autoimmune Skin Disease
Authors: Fradkov Elena , Sheehan Jessica , Cushing Kelly , Higgins Peter D R
Published: September 2021

Background

Approximately 33% of Crohn’s disease (CD) patients have associated autoimmune skin disease. The pathophysiology of the latter frequently involves interleukin-12/interleukin-23 signaling pathways that may also impact gut inflammation. Ustekinumab is an anti-IL-12/23 FDA-approved biologic for psoriasis and inflammatory bowel disease. However, its relative efficacy has never been studied in CD with autoimmune skin disease (CD-ASD) vs CD without autoimmune skin disease (CD-none).

Methods

This is a retrospective, single-center, case-control study comparing markers of disease activity between CD-ASD and CD-none. Biomarkers (fecal calprotectin [FCP], C-reactive protein [CRP]) prior to drug initiation and after at least 5 months of standard IBD dose ustekinumab therapy were extracted from the medical record. In addition, 2 blinded observers performed 5-point Likert scoring before and after endoscopic, pathologic, and imaging reports.

Results

In all, 395 CD patients received ustekinumab therapy (79 CD-ASD, 316 CD-none). Patients were similar in age; gender; ethnicity; CD severity, phenotype, and duration; tobacco, immunomodulator, and steroid use. Ustekinumab had greater efficacy in CD-ASD when evaluated by FCP (P = .0337) and CRP (P = .078). The CD-ASD group also showed better outcomes in Likert scores of endoscopy (P = .016), histopathology (P = .074), and imaging (P = .094). In all Likert parameters, CD-ASD had more patients with complete resolution of moderate/severe disease (P < .05). Additional subanalyses for surgeries, ulcers, abscesses, fistulas, and colitis were conducted, with colitis reaching statistical significance (P = .0011).

Conclusions

Concurrent autoimmune skin disease in CD is associated with greater ustekinumab effectiveness in controlling intestinal inflammation.
Cost-effectiveness of Venous Thromboembolism Prophylaxis After Hospitalization in Patients With Inflammatory Bowel Disease
Authors: Lee Kate E , Lim Francesca , Colombel Jean-Frederic , Hur Chin , Faye Adam S
Published: September 2021

Background

Patients with inflammatory bowel disease (IBD) have a 2- to 3-fold greater risk of venous thromboembolism (VTE) than patients without IBD, with increased risk during hospitalization that persists postdischarge. We determined the cost-effectiveness of postdischarge VTE prophylaxis among hospitalized patients with IBD.

Methods

A decision tree compared inpatient prophylaxis alone vs 4 weeks of postdischarge VTE prophylaxis with 10 mg/day of rivaroxaban. Our primary outcome was quality-adjusted life years (QALYs) over 1 year, and strategies were compared using a willingness to pay of $100,000/QALY from a societal perspective. Costs (in 2020 $USD), incremental cost-effectiveness ratios (ICERs) and number needed to treat (NNT) to prevent 1 VTE and VTE death were calculated. Deterministic 1-way and probabilistic analyses assessed model uncertainty.

Results

Prophylaxis with rivaroxaban resulted in 1.68-higher QALYs per 1000 persons compared with no postdischarge prophylaxis at an incremental cost of $185,778 per QALY. The NNT to prevent a single VTE was 78, whereas the NNT to prevent a single VTE-related death was 3190. One-way sensitivity analyses showed that higher VTE risk >4.5% and decreased cost of rivaroxaban ≤$280 can reduce the ICER to <$100,000/QALY. Probabilistic sensitivity analyses favored prophylaxis in 28.9% of iterations.

Conclusions

Four weeks of postdischarge VTE prophylaxis results in higher QALYs compared with inpatient prophylaxis alone and prevents 1 postdischarge VTE among 78 patients with IBD. Although postdischarge VTE prophylaxis for all patients with IBD is not cost-effective, it should be considered in a case-by-case scenario, considering VTE risk profile, costs, and patient preference.
A very rare case of incidental aortic valve fibrolipoma
Authors: Karsan Rickesh Bharat , Kelly Ronan , Healy Estelle , Jeganathan Reuben
Published: September 2021

Cardiac valve fibrolipomas are extremely rare. We report a case of a 38-year-old female initially presenting with palpitations and moderate aortic incompetence who was found to have a lipomatous growth of the aortic valve. She underwent aortic valve repair with good postoperative results. Histopathogy verified the lesion as a fibrolipoma. This is the first reported case of fibrolipoma in the aortic valve, whilst aiming to consider repair as a surgical option in young patients with such growths.
Evaluation of drug information from carton boxes, leaflets and pharmacy personnel: situation analysis in Myanmar
Authors: Win Zar Ni , Anantachoti Puree
Published: September 2021

Objective

This study assessed how Myanmar consumers received drug information from the drug products and dispensers of community pharmacies.

Methods

Content analysis was used to evaluate drug information attached to 3 drug categories of 30 drug samples, and simulated patient studies at 247 pharmacies of selected townships in Yangon region were performed. Descriptive statistics and independent t-test were used for data analysis.

Key findings

Among 30 proxy drug products, more than 80% provided information in English language both on the carton boxes and on leaflets. About 86.7% of leaflets were intended only for healthcare professional uses and not understandable for lay consumers. The simulated patient study found that overall drug information provided by dispensers was limited as confirmed by information providing mean score of 4.25 ± 2.06 out of a total of 18 points. Many other important information items such as drug name, concomitant drugs use, common side effects and when to stop taking medicine were rarely provided. None of the simulated patients received carton box or leaflet.

Conclusions

This study proved that Myanmar consumers did not receive enough drug information from both the products and dispensers, and thus the provision of understandable drug information for patients is required to improve patients’ safe use of medications.
MacPherson’s Conjecture via Hörmander’s Estimate
Authors: Shentu Junchao , Zhao Chen
Published: September 2021

In this note, we reprove MacPherson’s conjecture on $L^2-(n,q)$-cohomology through Demailly’s formulation of Hörmander’s estimate. This approach allows us to prove the MacPherson’s conjecture of twisted coefficient bundle endowed with a singular hermitian metric. As applications, we study the MacPherson type problem for pluri-canonical bundles.
Arakelov Theory on Arithmetic Surfaces Over a Trivially Valued Field
Authors: Chen Huayi , Moriwaki Atsushi
Published: September 2021

In this article, we consider an analogue of Arakelov theory of arithmetic surfaces over a trivially valued field. In particular, we establish an arithmetic Hilbert–Samuel theorem and study the effectivity up to $\mathbb R$-linear equivalence of pseudoeffective metrised $\mathbb R$-divisors.
Duration of Viral Nucleic Acid Shedding and Early Reinfection With Severe Respiratory Syndrome Coronavirus 2 in Healthcare Workers and First Responders
Authors: Biggerstaff Brad J , Akinbami Lara J , Hales Craig , Chan Philip A , Petersen Lyle R
Published: September 2021

We estimated the distributions of duration of SARS-CoV-2 nucleic acid shedding and time to reinfection among 137 persons with at least 2 positive nucleic acid amplification test (NAAT) results from March to September 2020. We analyzed gaps of varying length between subsequent positive and negative NAAT results and estimated a mean duration of nucleic acid shedding of 30.1 days (95% confidence interval [CI], 26.3–34.5). Mean time to reinfection was 89.1 days (95% CI, 75.3–103.5). Together, these indicate that a 90-day period between positive NAAT results can reliably define reinfection in immunocompetent persons although reinfection can occur at shorter intervals.
Interleukin-17 family members in health and disease
Authors: Chung Soo-Hyun , Ye Xiao-Qi , Iwakura Yoichiro
Published: September 2021

The interleukin-17 (IL-17) family consists of six family members (IL-17A–IL-17F) and all the corresponding receptors have been identified recently. This family is mainly involved in the host defense mechanisms against bacteria, fungi and helminth infection by inducing cytokines and chemokines, recruiting neutrophils, inducing anti-microbial proteins and modifying T-helper cell differentiation. IL-17A and some other family cytokines are also involved in the development of psoriasis, psoriatic arthritis and ankylosing spondylitis by inducing inflammatory cytokines and chemokines, and antibodies against IL-17A as well as the receptor IL-17RA are being successfully used for the treatment of these diseases. Involvement in the development of inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis and tumors has also been suggested in animal disease models. In this review, we will briefly review the mechanisms by which IL-17 cytokines are involved in the development of these diseases and discuss possible treatment of inflammatory diseases by targeting IL-17 family members.
The role of new carbapenem combinations in the treatment of multidrug-resistant Gram-negative infections
Authors: Bouza Emilio
Published: September 2021

Multi-drug resistant (MDR) Gram-negative bacteria represent a growing threat, with an increasing prevalence of carbapenem-resistant Enterobacterales (CRE) infections, for which treatment options are limited. New treatment combinations composed of a β-lactam antibiotic plus a potent β-lactamase inhibitor (BLI) with anti-carbapenemase activity have been developed, including two carbapenem/BLI combinations that are commercially available—meropenem/vaborbactam (Vabomere® in the US, Vaborem® in Europe; Melinta Therapeutics) and imipenem/cilastatin/relebactam (Recarbrio®; Merck Sharp & Dohme), plus one other (meropenem/nacubactam) in early clinical development. This review provides a summary of the preclinical evidence supporting the use of carbapenem/BLI combinations and presents the clinical evidence across a range of MDR Gram-negative infections, with a focus on the use of meropenem/vaborbactam. All three BLIs have shown in vivo activity against Klebsiella pneumoniae carbapenemase and other class A carbapenemases. In 2019, meropenem/vaborbactam was listed in the WHO’s list of essential medicines, because of its activity against priority 1 antibiotic-resistant pathogens. Meropenem/vaborbactam has considerable in vitro and in vivo activity against CRE, and in vitro evidence showing a low potential for resistance at clinically relevant doses. In randomized trials, meropenem/vaborbactam was non-inferior to piperacillin/tazobactam in patients with complicated urinary tract infection and more effective than the best-available treatment in patients with serious CRE infections. Meropenem/vaborbactam is well tolerated and, based on clinical experience, demonstrated lower toxicity compared with the combination regimens that have previously been the standard of care. In conclusion, carbapenem/BLI combinations represent an important therapeutic strategy in patients with MDR Gram-negative infections.
Large diversity of linezolid-resistant isolates discovered in food-producing animals through linezolid selective monitoring in Belgium in 2019
Authors: Timmermans Michaël , Bogaerts Bert , Vanneste Kevin , De Keersmaecker Sigrid C J , Roosens Nancy H C , Kowalewicz Carole , Simon Guillaume , Argudín Maria A , Deplano Ariane , Hallin Marie , Wattiau Pierre , Fretin David , Denis Olivier , Boland Cécile
Published: September 2021

Background

Linezolid is a critically important antibiotic used to treat human infections caused by MRSA and VRE. While linezolid is not licensed for food-producing animals, linezolid-resistant (LR) isolates have been reported in European countries, including Belgium.

Objectives

To: (i) assess LR occurrence in staphylococci and enterococci isolated from different Belgian food-producing animals in 2019 through selective monitoring; and (ii) investigate the genomes and relatedness of these isolates.

Methods

Faecal samples (n = 1325) and nasal swab samples (n = 148) were analysed with a protocol designed to select LR bacteria, including a 44–48 h incubation period. The presence of LR chromosomal mutations, transferable LR genes and their genetic organizations and other resistance genes, as well as LR isolate relatedness (from this study and the NCBI database) were assessed through WGS.

Results

The LR rate differed widely between animal host species, with the highest rates occurring in nasal samples from pigs and sows (25.7% and 20.5%, respectively) and faecal samples from veal calves (16.4%). WGS results showed that LR determinants are present in a large diversity of isolates circulating in the agricultural sector, with some isolates closely related to human isolates, posing a human health risk.

Conclusions

LR dedicated monitoring with WGS analysis could help to better understand the spread of LR. Cross-selection of LR transferable genes through other antibiotic use should be considered in future action plans aimed at combatting antimicrobial resistance and in future objectives for the rational use of antibiotics in a One Health perspective.
Ethnicity, Banking and Local Economic Development: Evidence from Ethiopia
Authors: Regasa Dereje , Fielding David , Roberts Helen
Published: September 2021

A unique dataset is used to uncover one mechanism generating regional and ethnic inequality in Ethiopia. Individual banks’ location decisions depend on the degree of similarity between the ethnic composition of each locality and the ethnic composition of the bank’s board of directors. Using ethnic similarity as an instrument for bank location and climate as an instrument for economic development, we model both local banking provision and local economic development. Our model predicts that if the ethnic composition of all boards reflected the national population, then banks would have an incentive to operate in a wider range of locations.
Evaluation of the International Classification of Health Interventions (ICHI) in the coding of common surgical procedures
Authors: Fung Kin Wah , Xu Julia , Ameye Filip , Burelle Lisa , MacNeil Janice
Published: September 2021

Objective

To evaluate the International Classification of Health Interventions (ICHI) in the clinical and statistical use cases.

Materials and Methods

We identified 300 most-performed surgical procedures as represented by their display names in an electronic health record. For comparison with existing coding systems, we coded the procedures in ICHI, SNOMED CT, International Classification of Diseases (ICD)-10-PCS, and CCI (Canadian Classification of Health Interventions), using postcoordination (modification of existing codes by adding other codes), when applicable. Failure analysis was done for cases where full representation was not achieved. The ICHI encoding was further evaluated for adequacy to support statistical reporting by the Organisation for Economic Co-operation and Development (OECD) and European Union (EU) categories of surgical procedures.

Results

After deduplication, 229 distinct procedures remained. Without postcoordination, ICHI achieved full representation in 52.8%. A further 19.2% could be fully represented with postcoordination. SNOMED CT was the best performing overall, with 94.3% full representation without postcoordination, and 99.6% with postcoordination. Failure analysis showed that “method” and “target” constituted most of the missing information for ICHI encoding. For all OECD/EU surgical categories, ICHI coding was adequate to support statistical reporting. One OECD/EU category (“Hip replacement, secondary”) required postcoordination for correct assignment.

Conclusion

In the clinical use case of capturing information in the electronic health record, ICHI was outperformed by the clinically oriented procedure coding systems (SNOMED CT and CCI), but was comparable to ICD-10-PCS. Postcoordination could be an effective and efficient means of improving coverage. ICHI is generally adequate for the collection of international statistics.
Filling the knowledge gap in the reproductive biology of land hermit crabs (Decapoda: Anomura: Coenobitidae): captive breeding to explore incubation times and frequency
Authors: Liu Shi-Sheng , Fang Wei-Ta , Hsu Chia-Hsuan
Published: September 2021

Land hermit crabs are widely distributed in tropical and subtropical regions, and play important roles in the coastal-forest ecosystem, such as contributing to seed dispersal and scavenging; however, they face serious threats such as habitat loss and smuggling for the exotic pet trade. Information on their reproductive biology is thus crucial for formulating and promoting conservation policies to their benefit. We conducted captive breeding for over 10 years, compiling records for four of the 10 years, and report the incubation times and frequency and the successful rate of release of larvae during captive breeding of five species of Coenobitidae: Coenobita brevimanusDana, 1852, C. cavipesStimpson, 1858, C. rugosus H. Milne Edwards, 1837, C. perlatus H. Milne Edwards, 1837, and C. purpureusStimpson, 1858. Results indicate that C. cavipes had the longest incubation period of more than 30 days and C. purpureus the shortest, approximately 20 days. Four of the species bred an average of 3.5 times per year, whereas C. cavipes bred once or twice per year. The success rate of larval release for all five species was 60%–70% over four years. Unsuccessful larval release may have been caused by human and environmental interference. Although further research is required because only small samples of each species were studied, the reported data may help to fill gaps in our knowledge on the reproductive biology of land hermit crabs.
Beyond Anonymity: Network Affordances, Under Deindividuation, Improve Social Media Discussion Quality
Authors: Jaidka Kokil , Zhou Alvin , Lelkes Yphtach , Egelhofer Jana , Lecheler Sophie
Published: September 2021

The online sphere allows people to be personally anonymous while simultaneously being socially identifiable. Twitter users can use a pseudonym but signal allegiance to a political party in their profile (e.g., #MAGA). We explore the interplay of these two dimensions of anonymity on a custom-built social media platform that allowed us to examine the causal effects of personal and social anonymity on discussion quality. We find no support for the hypothesis that personal anonymity breeds incivility or lowers discussion quality in discussions on gun rights. On the other hand, when personal anonymity is combined with social identifiability (operationalized as political party visibility), it improves several features linked to discussion quality, that is, higher rationality and lower incivility. We discuss the mechanisms that might explain the results and offer recommendations for future experiments about the design of social media platforms.
Influencer-Generated Reference Groups
Authors: Lee Jeffrey K , Junqué de Fortuny Enric
Published: September 2021

This article explores the idea that consumer influencers can shape reference group meanings in social media. Through a survey in which over 5,000 participants provided open-ended reference group associations for 25 major brands, the authors find that social media influencers can either strengthen or change brand reference group associations. Specifically, the typicality of the influencer (relative to a brand’s stereotypical consumer) can shape ideas about the perceived homogeneity of the brand’s consumers, which ultimately influences the strength and tightness of brand associations. This research combines seminal theories regarding cultural and sociological influences on branding, concepts relating to stereotype change, and a multi-method approach to assess new digital flows of cultural meaning from consumer influencers to brands.
Reproductive Patterns Drive the Gene Flow and Spatial Dispersal of Euschistus heros (Hemiptera: Pentatomidae)
Authors: Hickmann Frederico , Cordeiro Erick Goes , Soares Patrícia Lima , Aurélio Mateus Souza L , Schwertner Cristiano Feldens , Corrêa Alberto Soares
Published: September 2021

Euschistus heros (Hemiptera: Pentatomidae) has two allopatric strains with a hybrid zone in central Brazil. Asymmetric dispersal and gene flow between these strains of E. heros have been observed, where the South strain (SS) moves more quickly to the northern regions of the country than the North strain (NS) to the southern areas. In addition, SS generally has a bigger body size and presents dark brown coloration, and NS is usually smaller in size and presents light brown coloration. Here, we studied the reproductive behavior and tested for the presence of assortative mating and reproductive barriers between the two allopatric strains of E. heros. Nonrandom mating was observed in the SS strain based on mating choice trials and the reproductive isolation indexes. SS females and males prefer to mate with their co-specific (same strain) partner, while NS insects showed no mating preference. The insect’s pronotum width was positively associated with the mating choice suggesting size-assortative mating in E. heros. Reciprocal crosses between strains yielded similar reproductive outputs when compared with pure strain crosses, suggesting similar fitness of hybrid pure strains. The asymmetric gene flow in the hybridization zone that favors SS seems to be associated with the reproductive behavior of the species, which favors the typical phenotype found in the SS populations.
Correlated Population Genetic Structure in a Three-Tiered Host-Parasite System: The Potential for Coevolution and Adaptive Divergence
Authors: Colosimo Giuliano , Jackson Anna C , Benton Amanda , Varela-Stokes Andrea , Iverson John , Knapp Charles R , Welch Mark
Published: September 2021

Three subspecies of Northern Bahamian Rock Iguanas, Cyclura cychlura, are currently recognized: C. c. cychlura, restricted to Andros Island, and C. c. figginsi and C. c. inornata, native to the Exuma Island chain. Populations on Andros are genetically distinct from Exuma Island populations, yet genetic divergence among populations in the Exumas is inconsistent with the 2 currently recognized subspecies from those islands. The potential consequences of this discrepancy might include the recognition of a single subspecies throughout the Exumas rather than 2. That inference also ignores evidence that populations of C. cychlura are potentially adaptively divergent. We compared patterns of population relatedness in a three-tiered host-parasite system: C. cychlura iguanas, their ticks (genus Amblyomma, preferentially parasitizing these reptiles), and Rickettsia spp. endosymbionts (within tick ectoparasites). Our results indicate that while C. c. cychlura on Andros is consistently supported as a separate clade, patterns of relatedness among populations of C. c. figginsi and C. c. inornata within the Exuma Island chain are more complex. The distribution of the hosts, different tick species, and Rickettsia spp., supports the evolutionary independence of C. c. inornata. Further, these patterns are also consistent with two independent evolutionarily significant units within C. c. figginsi. Our findings suggest coevolutionary relationships between the reptile hosts, their ectoparasites, and rickettsial organisms, suggesting local adaptation. This work also speaks to the limitations of using neutral molecular markers from a single focal taxon as the sole currency for recognizing evolutionary novelty in populations of endangered species.
Monoterpenoid biosynthesis by engineered microbes
Authors: Liu Yurou , Ma Xiaoqiang , Liang Hong , Stephanopoulos Gregory , Zhou Kang
Published: September 2021

Monoterpenoids are C10 isoprenoids and constitute a large family of natural products. They have been used as ingredients in food, cosmetics, and therapeutic products. Many monoterpenoids such as linalool, geraniol, limonene, and pinene are volatile and can be found in plant essential oils. Conventionally, these bioactive compounds are obtained from plant extracts by using organic solvents or by distillation method, which are costly and laborious if high-purity product is desired. In recent years, microbial biosynthesis has emerged as alternative source of monoterpenoids with great promise for meeting the increasing global demand for these compounds. However, current methods of production are not yet at levels required for commercialization. Production efficiency of monoterpenoids in microbial hosts is often restricted by high volatility of the monoterpenoids, a lack of enzymatic activity and selectivity, and/or product cytotoxicity to the microbial hosts. In this review, we summarize advances in microbial production of monoterpenoids over the past 3 years with particular focus on the key metabolic engineering strategies for different monoterpenoid products. We also provide our perspective on the promise of future endeavors to improve monoterpenoid productivity.
Comparative Lipid Profile Analysis of Hermetia illucens Larvae Fed Food Waste at Different Days of Age Using an LC-MS-Based Lipidomics Approach
Authors: Li Mengmeng , Wang Guiying , Shang Rongsheng , Xu Qinglong , Zhang Jincheng , Sun Ran , Li Lusheng
Published: September 2021

A lipidomics approach based on liquid chromatography–tandem mass spectrometry (LC-MS) was applied to analyze the molecular-level mechanism of lipid deposition in Hermetia illucens (H. illucens) larvae fed food waste (FW) at different days of age. The H. illucens larvae reared on FW substrates generally became larger, heavier, and fatter at 5–15 d of age. A large amount of glycerolipids (GL) were deposited, while glycerophospholipids (GP), sphingolipids, and derivatized lipids became relatively less abundant during the growth stage of the larvae. Forty-three subclasses of 3,205 lipid molecules were identified in larvae, and 139 lipids (79 upregulated and 60 downregulated during larval growth and development) were identified as potential biomarkers (variable importance in projection > 1; P < 0.05). The differential lipids were mainly enriched in 19 metabolic pathways, of which 9 metabolic pathways related to lipids, including GL and GP metabolisms. The results demonstrate that the lipid composition and mechanisms changed during the growth and development stage of H. illucens larvae. To the best of our knowledge, this is the first work exploring the molecular-level mechanism of lipid deposition during the growth and development stage of H. illucens larvae. The findings provide novel information for determining and utilizing the nutritional value of H. illucens larvae.
Organization of the State: Home Assignment and Bureaucrat Performance
Authors: Xu Guo , Bertrand Marianne , Burgess Robin
Published: September 2021

How to allocate personnel is a central question in the organization of the state. We link survey data on the performance of 1471 elite civil servants in India to their personnel records between 1975 and 2005 to study how home allocations affect their performance and careers. Using exogenous variation in home assignment generated by an allocation rule, we find that bureaucrats assigned to their home states are perceived to be less effective and more likely to be suspended. These negative effects are driven by states with higher levels of corruption and cohorts with greater numbers of home state officers. (JEL: J45, O43, D73, M5)
Adaptive plasticity in response to light and nutrient availability in the clonal plantDuchesnea indica
Authors: Wang Mo-Zhu , Li Hong-Li , Liu Chun-Xiang , Dong Bi-Cheng , Yu Fei-Hai
Published: September 2021

Phenotypic plasticity enables plants to buffer against environmental stresses and match their phenotypes to local conditions. However, consistent conclusive evidence for adaptive plasticity has only been obtained for a few traits. More studies on a wider variety of plant functional traits and environmental factors are still needed to further understand the adaptive significance of plasticity. We grew 21 genotypes of the stoloniferous clonal plant Duchesnea indica under different light and nutrient conditions, and used selection gradient analyses to test the adaptive value (benefits) of morphological and physiological plasticity responding to variation in light and nutrient availability. Plants grown in shade exhibited lower values for fitness measures (fruit number, ramet number and biomass), shortened thinner internode length and decreased adult leaf chlorophyll content, but higher petiole length, specific leaf area and old leaf chlorophyll content, than plants grown without shade. Plants grown in the low nutrient condition had shorter petiole length, thicker and smaller leaf area, lower chlorophyll content, but higher fruit number and root:shoot ratio than plants grown under the high nutrient condition. Selection gradient analyses revealed that plasticity of petiole length and old leaf chlorophyll content in response to light variation was adaptive, and plasticity of old and adult leaf chlorophyll content in response to nutrient variation was adaptive. Therefore, the adaptive value of plasticity in different traits depends on the specific ecological context. Our findings contribute to understanding the adaptive significance of phenotypic plasticity of clonal plants in response to environmental variation.
Three-dimensional printed personalized drug devices with anatomical fit: a review
Authors: Pinho Ludmila A G , Gratieri Tais , Gelfuso Guilherme M , Marreto Ricardo Neves , Cunha-Filho Marcilio
Published: September 2021

Objectives

Three-dimensional printing (3DP) has opened the era of drug personalization, promising to revolutionize the pharmaceutical field with improvements in efficacy, safety and compliance of the treatments. As a result of these investigations, a vast therapeutic field has opened for 3DP-loaded drug devices with an anatomical fit. Along these lines, innovative dosage forms, unimaginable until recently, can be obtained. This review explores 3DP-engineered drug devices described in recent research articles, as well as in patented inventions, and even devices already produced by 3DP with drug-loading potential.

Key findings

3D drug-loaded stents, implants and prostheses are reviewed, along with devices produced to fit hard-to-attach body parts such as nasal masks, vaginal rings or mouthguards. The most promising 3DP techniques for such devices and the complementary technologies surrounding these inventions are also discussed, particularly the scanners useful for mapping body parts. Health regulatory concerns regarding the new use of such technology are also analysed.

The scenario discussed in this review shows that for wearable 3DP drug devices to become a tangible reality to users, it will be necessary to overcome the existing regulatory barriers, create new interfaces with electronic systems and improve the mapping mechanisms of body surfaces.
Chrysophanol exerts neuroprotective effects via interfering with endoplasmic reticulum stress apoptotic pathways in cell and animal models of Alzheimer’s disease
Authors: Li Xinquan , Cheng Yaxun , Qin Yunpeng , Gao Huawu , Wang Guangyun , Song Hang , Wang Yan , Cai Biao
Published: September 2021

Objectives

Chrysophanol (CHR), also well-known as Rhei radix et rhizome, is a crucial component in traditional Chinese medicine. It has been widely studied as a potential treatment for many diseases due to its anti-inflammatory effects. However, there are very few studies to establish the potential therapeutic effect of CHR in cell and animal models of Alzheimer’s disease (AD). Therefore, we aim to investigate whether CHR could be used as a potential therapeutic approach to patients with AD and further disclose the underlying mechanism. Increasing studies have shown that endoplasmic reticulum (ER) calcium (Ca2+) homeostasis emerges as a central player in AD pathogenesis. Moreover, augmentation of ER stress (ERS) promotes neuronal apoptosis, and excessive oxidative stress is an inducer of ERS. Therefore, we believe that ERS-mediated apoptosis may be one of the causes of AD.

Methods

This study examined the neuroprotective effects of CHR on AD rats and AD cell models and explored its potential mechanism.

Key findings

CHR could reduce the damage of neurons. In AD cell models, CHR significantly inhibited Aβ 25-35-induced neuronal damage, reduced the number of apoptotic cells and improved cell survival rate. Western blot showed that the expression of caspases 3, 9 and 12 was decreased after CHR treatment, and CHR also affected the ERS signalling pathway. In addition, the higher expression of pro-apoptotic proteins in the AD cell model was reduced after CHR treatment by inhibiting GRP78 signalling. Further studies have shown that overexpressed protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) inhibited the regulatory effect of CHR on PERK and weakened the neuroprotective effect of CHR on the AD cell model.

Conclusions

This study revealed a novel mechanism through which CHR plays a neuroprotective role by regulating ERS when it comes to the therapy of AD.
Typhoid fever in travellers: estimating the risk of acquisition by country
Authors: Forster Daniel P , Leder Karin
Published: September 2021

Background

Typhoid fever is a notifiable disease within Australia. Although studies in endemic regions give an indication of acquisition risk, many countries lack reliable data, and little is known of the absolute or relative risk in Australian travellers. By combining notified case data with travel statistics provided by the Australian Bureau of Statistics, the aim of this study was to give an indication of risk for typhoid acquisition among Australian travellers.

Methods

Australian typhoid notifications between 1st January 2010 and 30th June 2017 were grouped by country of acquisition and age category (<15 or ≥15 years). Australian travel data were used to inform time at risk and incidence rate of Australian typhoid notifications pertaining to country and region of acquisition. Salmonella Paratyphi infections, though notifiable, were excluded as the focus was vaccine preventable illness. Data from New South Wales and Victoria were used to examine the incidence in those acquiring infection in their country of birth (COB) against travellers who did not.

Results

Nine hundred twenty-three cases of typhoid were notified over the period of review, 96% of which were acquired overseas. The greatest determinant of risk was travel destination, with countries in south Asia associated with highest crude incidence rate (252 per 100 000 person-years), particularly Bangladesh. Younger age and immigrants returning to their COB were generally associated with higher risk of acquisition.

Conclusions

The risk of typhoid fever in Australian travellers to endemic regions is considerable. Immigrants returning to their COB appear to be at higher risk and it is likely that this risk extends to their traveling dependents. These findings help clinicians and public health officials to plan and advise pre-travel vaccination strategies with at-risk individuals and groups. Additional sociodemographic data collection with Australian typhoid notifications would enhance the surveillance of differing international travel risk groups leaving Australia.
Clinical characteristics and risk factors for COVID-19-associated Candidemia
Authors: Omrani Ali S , Koleri Junais , Ben Abid Fatma , Daghfel Joanne , Odaippurath Thasneem , Peediyakkal Mohamed Zuhail , Baiou Anas , Sarsak Enas , Elayana Mahmoud , Kaleeckal Anvar , Almaslamani Muna A
Published: September 2021

Patients with COVID-19-associated candidemia (CAC) in an intensive care unit (ICU) were matched 1:2 with those without candidemia, based on ICU admission date and length of stay in ICU being at least equal to that before candidemia in the corresponding case. The incidence rate of CAC was 2.34 per 1000 ICU days. Eighty cases could be matched to appropriate controls. In the multivariate conditional logistic regression analysis, age (P 0.001), and sequential organ failure assessment score (P 0.046) were the only risk factors independently associated with CAC. Tocilizumab and corticosteroids therapy were not independently associated with candidemia.

Lay summary

In COVID-19 patients who need medical care in an intensive care unit, the risk of developing bloodstream Candida infection is higher in older patients and in those who have a more severe critical illness. Treatment with steroids or tocilizumab does not seem to affect the risk of candida bloodstream infection in these patients.
A consistent reduced-speed-of-light formulation of cosmic ray transport valid in weak- and strong-scattering regimes
Authors: Hopkins Philip F , Squire Jonathan , Butsky Iryna S
Published: September 2021

We derive a consistent set of moment equations for cosmic ray (CR)-magnetohydrodynamics, assuming a gyrotropic distribution function (DF). Unlike previous efforts, we derive a closure, akin to the M1 closure in radiation hydrodynamics (RHD), that is valid in both the nearly isotropic DF and/or strong-scattering regimes, and the arbitrarily anisotropic DF or free-streaming regimes, as well as allowing for anisotropic scattering and transport/magnetic field structure. We present the appropriate two-moment closure and equations for various choices of evolved variables, including the CR phase space DF f, number density n, total energy e, kinetic energy ϵ, and their fluxes or higher moments, and the appropriate coupling terms to the gas. We show that this naturally includes and generalizes a variety of terms including convection/fluid motion, anisotropic CR pressure, streaming, diffusion, gyro-resonant/streaming losses, and re-acceleration. We discuss how this extends previous treatments of CR transport including diffusion and moment methods and popular forms of the Fokker–Planck equation, as well as how this differs from the analogous M1-RHD equations. We also present two different methods for incorporating a reduced speed of light (RSOL) to reduce time-step limitations: In both, we carefully address where the RSOL (versus true c) must appear for the correct behaviour to be recovered in all interesting limits, and show how current implementations of CRs with an RSOL neglect some additional terms.
Formation of the first galaxies in the aftermath of the first supernovae
Authors: Abe Makito , Yajima Hidenobu , Khochfar Sadegh , Dalla Vecchia Claudio , Omukai Kazuyuki
Published: September 2021

We perform high-resolution cosmological hydrodynamic simulations to study the formation of the first galaxies that reach the masses of 108 − 9 h−1 M⊙ at z = 9. The resolution of the simulations is high enough to resolve minihaloes and allow us to successfully pursue the formation of multiple Population (Pop) III stars, their supernova (SN) explosions, resultant metal-enrichment of the inter-galactic medium (IGM) in the course of the build-up of the system. Metals are ejected into the IGM by multiple Pop III SNe, but some of the metal-enriched gas falls back on to the halo after $\gtrsim 100~\rm Myr$. The star formation history of the first galaxy depends sensitively on the initial mass function (IMF) of Pop III stars. The dominant stellar population transits from Pop III to Pop II at z ∼ 12−15 in the case of power-law Pop III IMF, dn/dM ∝ M−2.35 with the mass range 10−500 M⊙. At z ≲ 12, stars are stably formed in the first galaxies with a star formation rate of ∼10−3−10−1 M⊙ yr −1. In contrast, for the case with a flat IMF, gas-deprived first galaxies form due to frequent Pop III pair-instability SNe, resulting in the suppression of subsequent Pop II star formation. In addition, we calculate UV continuum, Lyα- and Hα-line fluxes from the first galaxies. We show that the James Webb Space Telescope will be able to detect both UV continuum, Lyα and Hα line emission from first galaxies with halo mass ≳ 109 M⊙ at z ≳ 10.
The two phases of core formation – orbital evolution in the centres of ellipticals with supermassive black hole binaries
Authors: Frigo M , Naab T , Rantala A , Johansson P H , Neureiter B , Thomas J , Rizzuto F
Published: September 2021

The flat stellar density cores of massive elliptical galaxies form rapidly due to sinking supermassive black holes (SMBHs) in gas-poor galaxy mergers. After the SMBHs form a bound binary, gravitational slingshot interactions with nearby stars drive the core regions towards a tangentially biased stellar velocity distribution. We use collisionless galaxy merger simulations with accurate collisional orbit integration around the central SMBHs to demonstrate that the removal of stars from the centre by slingshot kicks accounts for the entire change in velocity anisotropy. The rate of strong (unbinding) kicks is constant over several hundred Myr at $\sim 3 \ \mathrm{ M}_\odot\, \rm yr^{-1}$ for our most massive SMBH binary (MBH = 1.7 × 1010 M⊙). Using a frequency-based orbit classification scheme (box, x-tube, z-tube, rosette), we demonstrate that slingshot kicks mostly affect box orbits with small pericentre distances, leading to a velocity anisotropy of β ≲ −0.6 within several hundred Myr as observed in massive ellipticals with large cores. We show how different SMBH masses affect the orbital structure of the merger remnants and present a kinematic tomography connecting orbit families to integral field kinematic features. Our direct orbit classification agrees remarkably well with a modern triaxial Schwarzschild analysis applied to simulated mock kinematic maps.
Periodic variability of the z = 2.0 quasar QSO B1312+7837
Authors: Minev M , Ivanov V D , Trifonov T , Ovcharov E , Fabrika S , Sholukhova O , Vinokurov A , Valcheva A , Nedialkov P
Published: September 2021

We report here the first results from a 15-yr long variability monitoring of the z = 2.0 quasar QSO B1312+7837. It shows luminosity changes with a period P ∼ 6.13 yr (P ∼ 2.04 yr at rest frame) and amplitude of ∼0.2 mag, superimposed on a gradual dimming at a rate of ∼0.55 mag per 100 yr. Two false periods associated with power peaks in the data windowing function were discarded. The measured period is confirmed with a bootstrapping Monte Carlo simulation. A damped random walk model yields a better fit to the data than a sine-function model, but at the cost of employing some high-frequency variations which are typically not seen in quasars. We consider the possible mechanisms driving this variability, and conclude that orbital motion of two supermassive black holes – result from a recent galaxy merger – is a possible explanation.
Gravitational self-lensing in populations of massive black hole binaries
Authors: Kelley Luke Zoltan , D’Orazio Daniel J , Di Stefano Rosanne
Published: September 2021

The community may be on the verge of detecting low-frequency gravitational waves from massive black hole binaries (MBHBs), but no examples of binary active galactic nuclei (AGN) have been confirmed. Because MBHBs are intrinsically rare, the most promising detection methods utilize photometric data from all-sky surveys. Gravitational self-lensing has recently been proposed as a method of detecting AGN in close separation binaries. In this study, we calculate the detectability of lensing signatures in realistic populations of simulated MBHBs. Within our model assumptions, we find that VRO’s LSST should be able to detect tens to hundreds of self-lensing binaries, with the rate uncertainty depending primarily on the orientation of AGN discs relative to their binary orbits. Roughly a quarter of lensing detectable systems should also show detectable Doppler boosting signatures. If AGN discs tend to be aligned with the orbit, lensing signatures are very nearly achromatic, while in misaligned configurations, the bluer optical bands are lensed more than redder ones. Whether substantial obscuring material (e.g. a dusty torus) will be present in close binaries remains uncertain, but our estimates suggest that a substantial fraction of systems would still be observable in this case.
Varying fundamental constants principal component analysis: additional hints about the Hubble tension
Authors: Hart Luke , Chluba Jens
Published: September 2021

Varying fundamental constants (VFC; e.g. the fine-structure constant, αEM) can arise in numerous extended cosmologies. Through their effect on the decoupling of baryons and photons during last scattering and reionization, these models can be directly constrained using measurements of the cosmic microwave background (CMB) temperature and polarization anisotropies. Previous investigations focused mainly on time-independent changes to the values of fundamental constants. Here we generalize to time-dependent variations. Instead of directly studying various VFC parametrizations, we perform a model-independent principal component analysis (PCA), directly using an eigenmode decomposition of the varying constant during recombination. After developing the formalism, we use Planck 2018 data to obtain new VFC limits, showing that three independent VFC modes can be constrained at present. No indications for significant departures from the standard model are found with Planck data. Cosmic variance limited modes are also compared and simple forecasts for the Simons Observatory are carried out, showing that in the future improvements of the current constraints by a factor of ≃3 can be anticipated. Our modes focus solely on VFC at redshifts z ≥ 300. This implies that they do not capture some of the degrees of freedom relating to the reionization era. This aspect provides important new insights into the possible origin of the Hubble tension, hinting that indeed a combined modification of recombination and reionization physics could be at work. An extended PCA, covering both recombination and reionization simultaneously, could shed more light on this question, as we emphasize here.