bluuebunny/crossref_metadata_2025 huggingface dataset:
The novel dual glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide‐1 (GLP‐1) receptor agonist tirzepatide transiently delays gastric emptying similarly to selective long‐acting GLP‐1 receptor agonists
Authors: Urva Shweta , Coskun Tamer , Loghin Corina , Cui Xuewei , Beebe Emily , O'Farrell Libbey , Briere Daniel A. , Benson Charles , Nauck Michael A. , Haupt Axel
Published: June 2020

The effect of dual glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) receptor agonist (RA) tirzepatide on gastric emptying (GE) was compared to that of GLP‐1RAs in non‐clinical and clinical studies. GE was assessed following acute and chronic treatment with tirzepatide in diet‐induced obese mice versus semaglutide or long‐acting GIP analogue alone. Participants [with and without type 2 diabetes (T2DM)] from a phase 1, 4‐week multiple dose study received tirzepatide, dulaglutide or placebo. GE was assessed by acetaminophen absorption. In mice, tirzepatide delayed GE to a similar degree to that achieved with semaglutide; however, these acute inhibitory effects were abolished after 2 weeks of treatment. GIP analogue alone had no effect on GE or on GLP‐1's effect on GE. In participants with and without T2DM, once‐weekly tirzepatide (≥5 and ≥4.5 mg, respectively) delayed GE after a single dose. This effect diminished after multiple doses of tirzepatide or dulaglutide in healthy participants. In participants with T2DM treated with an escalation schedule of tirzepatide 5/5/10/10 or 5/5/10/15 mg, a residual GE delay was still observed after multiple doses. These data suggest that tirzepatide's activity on GE is comparable to that of selective GLP‐1RAs.
Premier signalement de Deudorix livia (Lepidoptera: Lycaenidae) dans le sud algérien
Authors: Haddad K. , Afoutni L. , Mebarki M. T.
Published: June 2020

First report of Deudorix livia (Lepidoptera: Lycaеnidae) in the extreme south of Algeria

As part of a study to identify new species, an expedition was organised from the 21st to the 31st of December 2019 in the extreme south of the Algerian Sahara. The authors reported the presence of Deudorix livia (Klug, 1834) (Lepidoptera: Lycaеnidae). This is the first observation of this species in Southern Algeria.
Microbial processing of plant remains is co‐limited by multiple nutrients in global grasslands
Authors: Ochoa‐Hueso Raúl , Borer Elizabeth T. , Seabloom Eric W. , Hobbie Sarah E. , Risch Anita C. , Collins Scott L. , Alberti Juan , Bahamonde Héctor A. , Brown Cynthia S. , Caldeira Maria C. , Daleo Pedro , Dickman Chris R. , Ebeling Anne , Eisenhauer Nico , Esch Ellen H. , Eskelinen Anu , Fernández Victoria , Güsewell Sabine , Gutierrez‐Larruga Blanca , Hofmockel Kirsten , Laungani Ramesh , Lind Eric , López Andrea , McCulley Rebecca L. , Moore Joslin L. , Peri Pablo L. , Power Sally A. , Price Jodi N. , Prober Suzanne M. , Roscher Christiane , Sarneel Judith M. , Schütz Martin , Siebert Julia , Standish Rachel J. , Velasco Ayuso Sergio , Virtanen Risto , Wardle Glenda M. , Wiehl Georg , Yahdjian Laura , Zamin Tara
Published: June 2020

Microbial processing of aggregate‐unprotected organic matter inputs is key for soil fertility, long‐term ecosystem carbon and nutrient sequestration and sustainable agriculture. We investigated the effects of adding multiple nutrients (nitrogen, phosphorus and potassium plus nine essential macro‐ and micro‐nutrients) on decomposition and biochemical transformation of standard plant materials buried in 21 grasslands from four continents. Addition of multiple nutrients weakly but consistently increased decomposition and biochemical transformation of plant remains during the peak‐season, concurrent with changes in microbial exoenzymatic activity. Higher mean annual precipitation and lower mean annual temperature were the main climatic drivers of higher decomposition rates, while biochemical transformation of plant remains was negatively related to temperature of the wettest quarter. Nutrients enhanced decomposition most at cool, high rainfall sites, indicating that in a warmer and drier future fertilized grassland soils will have an even more limited potential for microbial processing of plant remains.
COVID‐19 and Headache: A Primer for Trainees
Authors: Bobker Sarah M. , Robbins Matthew S.
Published: June 2020

Objective

To summarize for the trainee audience the possible mechanisms of headache in patients with COVID‐19 as well as to outline the impact of the pandemic on patients with headache disorders and headache medicine in clinical practice.

Background

COVID‐19 is a global pandemic caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2, of which a large subset of patients features neurological symptoms, commonly headache. The virus is highly contagious and is, therefore, changing clinical practice by forcing limitations on in‐person visits and procedural treatments, more quickly shifting toward the widespread adaptation of telemedicine services.

Design/Results

We review what is currently known about the pathophysiology of COVID‐19 and how it relates to possible mechanisms of headache, including indirect, potential direct, and secondary causes. Alternative options for the treatment of patients with headache disorders and the use of telemedicine are also explored.

Conclusions

Limited information exists regarding the mechanisms and timing of headache in patients with COVID‐19, though causes relate to plausible direct viral invasion of the nervous system as well as the cytokine release syndrome. Though headache care in the COVID‐19 era requires alterations, the improved preventive treatment options now available and evidence for feasibility and safety of telemedicine well positions clinicians to take care of such patients, especially in the COVID‐19 epicenter of New York City.
Winter feeding influences the cost of living in boreal passerines
Authors: Broggi Juli , Hohtola Esa , Koivula Kari
Published: June 2020

The plastic regulation of internal energy reserves is acknowledged as the main adaptive response to winter conditions of resident small birds in northern latitudes, a strategy that may be altered whenever human‐supplemented food is available. We investigated the effects of supplementary feeding on the energy management strategy of two wild passerine species, the Willow Tit Poecile montanus and Blue Tit Cyanistes caeruleus, wintering in boreal conditions by measuring body mass and the energy cost of living, i.e. basal metabolic rate. Individuals of both species were heavier, larger and exhibited a higher energy cost of living when captured at the feeders than were individuals captured away from feeders. Fed Willow Tits expended more energy in maintenance, although this difference disappeared once mass was accounted for. Conversely, Blue Tits at feeders had higher mass‐adjusted energy cost of living, but only at low ambient temperatures. The results indicate that winter feeding has species‐specific effects on overall energy management strategy and modifies the response to environmental conditions of wintering passerines.
Buildings promote higher incubation temperatures and reduce nest attentiveness in a Neotropical thrush
Authors: Batisteli Augusto F. , De Souza Leonardo B. , Santieff Isadora Z. , Gomes Guilherme , Soares Talita P. , Pini Marianela , Guillermo‐Ferreira Rhainer , Pizo Marco A. , Sarmento Hugo
Published: June 2020

Incubation is an energetically costly parental task of breeding birds. Incubating parents respond to environmental variation and nest‐site features to adjust the balance between the time spent incubating (i.e. nest attentiveness) and foraging to supply their own needs. Non‐natural nesting substrates such as human buildings impose new environmental contexts that may affect time allocation of incubating birds but this topic remains little studied. Here, we tested whether nesting substrate type (buildings vs. trees) affects the temperature inside the incubation chamber (hereafter ‘nest temperature’) in the Pale‐breasted ThrushTurdus leucomelas, either during ‘day’ (with incubation recesses) or ‘night’ periods (representing uninterrupted female presence at the nest). We also tested whether nesting substrate type affects the incubation time budget using air temperature and the day of the incubation cycle as covariates. Nest temperature, when controlled for microhabitat temperature, was higher at night and in nests in buildings but did not differ between daytime and night for nests in buildings, indicating that buildings partially compensate for incubation recesses by females with regard to nest temperature stability. Females from nests placed in buildings exhibited lower nest attentiveness (the overall percentage of time spent incubating) and had longer bouts off the nest. Higher air temperatures were significantly correlated with shorter bouts on the nest and longer bouts off the nest, but without affecting nest attentiveness. We suggest that the longer bouts off the nest taken by females of nests in buildings is a consequence of higher nest temperatures promoted by man‐made structures around these nests. Use of buildings as nesting substrate may therefore increase parental fitness due to a relaxed incubation budget, and potentially drive the evolution of incubation behaviour in certain urban bird populations.
Rotación laboral en América Latina: Intensidad y diferencias entre países
Authors: BECCARIA Luis , MAURIZIO Roxana
Published: June 2020

El estudio de la rotación laboral es muy importante en América Latina, dados sus marcados ciclos económicos y su limitada cobertura de protección social. Se estima aquí la intensidad de las transiciones desde la situación de empleo en seis países latinoamericanos en las dos primeras décadas del milenio, descomponiendo las diferencias observadas y evaluando los destinos laborales de estos trabajadores. Los países analizados muestran tasas de rotación muy diferentes, lo que se explica fundamentalmente por una incidencia disímil del empleo informal y del empleo temporal. En todos los casos, gran parte de las transiciones desde el empleo tienen como destino empleos precarios o el desempleo.
A six‐plex droplet digital RT‐PCR assay for seasonal influenza virus typing, subtyping, and lineage determination
Authors: Leong Nathaniel K. C. , Chu Daniel K. W. , Chu Julie T. S. , Tam Yat H. , Ip Dennis K. M. , Cowling Benjamin J. , Poon Leo L. M.
Published: June 2020

Background

There are two influenza A subtypes (H1 and H3) and two influenza B lineages (Victoria and Yamagata) that currently co‐circulate in humans. In this study, we report the development of a six‐plex droplet digital RT‐PCR (ddRT‐PCR) assay that can detect HA and M segments of influenza A (H1, H3, and M) and influenza B (Yamagata HA, Victoria HA, and M) viruses in a single reaction mixture. It can simultaneously detect six different nucleic acid targets in a ddRT‐PCR platform.

Methods

The six‐plex ddRT‐PCR used in this study is an amplitude‐based multiplex assay. The analytical performance of the assay was evaluated. Correlation with standard qRT‐PCR methodology was assessed using 55 clinical samples.

Results

The assay has a wide dynamic range, and it has good reproducibility within and between runs. The limit of quantification of each target in this assay ranged from 15 copies/reaction for influenza B Victoria M gene to 45 copies/reaction for influenza B Yamagata M gene. In addition, this assay can accurately quantify each of these targets in samples containing viral RNAs from two different viruses that were mixed in a highly skewed ratio. Typing, subtyping, and lineage differentiation data of 55 tested clinical respiratory specimens were found to be identical to those deduced from standard monoplex qRT‐PCR assays.

Conclusions

The six‐plex ddRT‐PCR test was demonstrated to be highly suitable for detecting dual influenza infection cases. This assay is expected to be a useful diagnostic tool for clinical and research use.
An Honorable Harvest: Universal Owners Must Take Responsibility for Their Portfolios
Authors: Alexander Frederick
Published: June 2020

Despite a maturing industry of ESG professionals and coordinated efforts by shareholders calling for more responsible corporate behavior, we continue to see unabated climate and water crises, growing political instability, and continuing abuses of human rights in supply chains. The founder of a movement called The Shareholder Commons argues that to help business to address these systemic challenges, corporate responsibility must move beyond the company‐by‐company decision‐making model. An economy based on market competition cannot rely on individual businesses to adopt basic sustainability rules that take priority over profit. Critical sustainability boundaries must be implemented collectively to be effective.

The crux of the problem is that although shareholder returns derive mainly from efficiency and productivity gains, they can also result from careless exploitation of common resources or powerless workers. And the competition for margin and capital makes it difficult for companies to recognize, let alone forgo, profitable exploitation. A sustainable economy demands that we help companies to distinguish between honorable and dishonorable profits, and to find ways to eliminate or offset the latter. The author holds out a model of capitalism that limits the availability of choices that exploit negative externalities and inequality while preserving the principles and practices that create value and a reasonable sharing of gains among all stakeholders.

Universal owners—long‐term diversified investors—appear to be in the best position to formulate and enforce such a model, given the current design and practices of our capital markets. Such global investors have the incentive and power to engage in the collective decision‐making necessary for a sustainable economy. The power exerted by institutional investors through their allocation and stewardship of equity capital can be used to insist on more sustainable business practices. Because they are diversified across thousands of companies, universal owners can bypass the competitive bottleneck for margin and capital that holds sustainability back at the company level. These large investors can work together to establish authentic sustainability boundaries for the companies they invest in; and by so doing, they can allow us to leverage all the good work done to date on disclosure and ESG integration, and so realize a world in which companies continue to compete for profits, but also for a truly honorable harvest.
Global Public‐Private Investment Partnerships: A Financing Innovation with Positive Social Impact
Authors: Bolton Patrick , Musca Xavier , Samama Frédéric
Published: June 2020

Global bond markets, along with banks and governments, are the main source of funding for investment in environmentally friendly infrastructure and the transition to clean energy. Although such bonds are a relatively recent innovation, the green bond market has grown rapidly from its start in 2008 to around $800 billion in outstanding issues. The problem, however, is that green bonds, which represent less than 1% of global bond markets, have been issued disproportionately by government‐sponsored entities, corporations, and municipalities in developed markets. In the emerging market countries where the infrastructure investments are most needed, they barely exist.

The authors describe a new investment vehicle, called the AP EGO fund, whose mission and MO are to channel the vast global pools of institutional savings that are now invested in low or (even negative) yield fixed‐income assets—as much as $17 trillion in 2019—to higher‐return emerging markets green investments, in particular sustainable infrastructure, by creating a new asset class: emerging‐market green bonds issued by banks.

The AP EGO fund is premised on and involves a reworking of the public‐private partnership (PPP) into a form they call the global public‐private investment partnership (or GPPIP). Unlike the PPP, which combines a public agency with a private operator, the GPPIP has four instead of just two partners. In addition to the standard public agency and the private concession operator, there is a development bank—in this case the International Finance Corporation (IFC), which is the financial markets affiliate of the World Bank—and private investors that include emerging‐market banks as well as global institutional investors.

Along with the mediating role played by a public agency like the IFC, the AP EGO Fund is fundamentally different from other PPPs in that it takes the form of a special purpose securitization vehicle whose shares are backed by a pool of green bonds issued by emerging market banks in multiple emerging market countries. And besides its application to a new asset class, the fund also breaks new ground by applying a securitization technique with a fund structure designed with an embedded “first‐loss” protection to a global pool of green bonds originated in emerging market economies. By means of this structuring, the green‐bond‐backed fund shares issued by the AP EGO are now providing developed market institutional investors with somewhat higher‐yielding fixed income securities that nevertheless carry an investment‐grade rating.
“Non‐Financial” Is a Misnomer, but Doesn't Have to Be a Missed Opportunity
Authors: Glazerman Gail , Cohen Jeff
Published: June 2020

With enterprise values now representing increasing multiples of companies' net book assets, investors are clearly looking beyond financial reporting for enhanced insights and understanding of when and how companies are adding value. This shift includes growing attention to environmental, social, and governance (ESG) information. Although ESG data presents its own unique challenges, dismissing it as “non‐financial” can be misleading.

When explicitly linked to a company's long‐term value creation strategy, ESG information can serve as a valuable input to more farsighted financial analysis. Market‐driven initiatives, notably that of the Sustainability Accounting Standards Board (SASB), aim to standardize a subset of business‐critical, industry‐specific sustainability data for investors. Research indicates such approaches can generate positive outcomes not only for providers of financial capital, but for their portfolio companies and markets in general.

In illustrating these concepts, the authors explore ESG impacts in three sectors and industries, while examining how access to consistent, comparable, reliable sustainability information in those sectors can augment an analysis of traditional business fundamentals.

One example focuses on water management in the Oil & Gas Exploration & Production industry, a major environmental issue where geographic considerations can shed light on company‐specific exposures to cost increases, production disruptions, increased CapEx and R&D spending, as well as the potential for asset write‐downs.

In the Food & Beverage sector, health and nutrition concerns are shown to be changing consumer preferences, triggering regulatory action, and reshaping companies' product portfolios—with significant implications for the companies' brand values and ability to compete for market share.

Finally, in Aerospace & Defense, lapses in business ethics such as bribery of government officials present a governance challenge that comes with the risk of value‐destroying fines and penalties and, even more significant, associated reductions in revenues.
A Preliminary Analysis of SASB Reporting: Disclosure Topics, Financial Relevance, and the Financial Intensity of ESG Materiality
Authors: Busco Cristiano , Consolandi Costanza , Eccles Robert G. , Sofra Elena
Published: June 2020

At the end of 2018, the Sustainability Accounting Standards Board (SASB) released its corporate reporting standards for material environment, social, and governance (ESG) issues. These SASB standards are analogous to FASB's but deal with ESG activities that help the companies create value over the long term and have been endorsed by large asset management firms such as BlackRock.

The authors analyze the quality of ESG reporting by the 91 companies that adopted SASB's framework. While the number of such companies is still small, their results are encouraging, an indication of better things to come. Using three measures of effectiveness, Disclosure Topic Compliance Index (DTCI), Financial Relevance Compliance Index (FRCI), and Financial Intensity Compliance Index (FICI), the authors found that most companies are doing a good to very good job of reporting and companies tend to focus on measures with the highest financial relevance. Scores on these three measures were similar across industry sectors except for a few cases where the DTCI score is low.

They presented cases of three SASB standard companies: 1) Sunrun, a residential solar panel company that uses some hazardous materials, 2) Suncor, an integrated oil and gas company, and 3) Target, a retail company in a highly competitive industry needing to keep costs low while also managing an extensive supply chain responsibly.

These 91 companies have demonstrated that reporting according to SASB standards can be done well. This success should encourage other companies to follow and the authors offer a seven‐step process to adopt SASB standards.
Low levels of AMPK promote epithelial‐mesenchymal transition in lung cancer primarily through HDAC4‐ and HDAC5‐mediated metabolic reprogramming
Authors: Feng Shoujie , Zhang Li , Liu Xiucheng , Li Guangbin , Zhang Biao , Wang Ziwen , Zhang Hao , Ma Haitao
Published: June 2020

AMP‐activated protein kinase (AMPK) serves as a “supermetabolic regulator” that helps maintain cellular energy homeostasis. However, the role of AMPK in glucose metabolism reprogramming in lung cancer remains unclear. Here, our study shows that low AMPK expression correlates with metastasis and clinicopathologic parameters of non–small‐cell lung cancer. Low AMPK significantly enhances the Warburg effect in HBE and A549 cells, which in turn induces the expression of mesenchymal markers and enhances their invasion and migration. At the mechanistic level, low AMPK up‐regulates HK2 expression and glycolysis levels through HDAC4 and HDAC5. Collectively, our findings demonstrate that low AMPK‐induced metabolism can promote epithelial‐mesenchymal transition progression in normal bronchial epithelial cells and lung cancer cells, and increase the risk for tumour metastasis.
Defibrotide inhibits donor leucocyte‐endothelial interactions and protects against acute graft‐versus‐host disease
Authors: García‐Bernal David , Palomo Marta , Martínez Carlos M. , Millán‐Rivero José E. , García‐Guillén Ana I. , Blanquer Miguel , Díaz‐Ricart Maribel , Sackstein Robert , Carreras Enric , Moraleda Jose M.
Published: June 2020

Allogeneic hematopoietic stem cell transplantation (allo‐HCT) is an effective therapy for the treatment of high‐risk haematological malignant disorders and other life‐threatening haematological and genetic diseases. Acute graft‐versus‐host disease (aGvHD) remains the most frequent cause of non‐relapse mortality following allo‐HCT and limits its extensive clinical application. Current pharmacologic agents used for prophylaxis and treatment of aGvHD are not uniformly successful and have serious secondary side effects. Therefore, more effective and safe prophylaxis and therapy for aGvHD are an unmet clinical need. Defibrotide is a multi‐target drug successfully employed for prophylaxis and treatment of veno‐occlusive disease/sinusoidal obstruction syndrome. Recent preliminary clinical data have suggested some efficacy of defibrotide in the prevention of aGvHD after allo‐HCT. Using a fully MHC‐mismatched murine model of allo‐HCT, we report here that defibrotide, either in prophylaxis or treatment, is effective in preventing T cell and neutrophil infiltration and aGvHD‐associated tissue injury, thus reducing aGvHD incidence and severity, with significantly improved survival after allo‐HCT. Moreover, we performed in vitro mechanistic studies using human cells revealing that defibrotide inhibits leucocyte‐endothelial interactions by down‐regulating expression of key endothelial adhesion molecules involved in leucocyte trafficking. Together, these findings provide evidence that defibrotide may represent an effective and safe clinical alternative for both prophylaxis and treatment of aGvHD after allo‐HCT, paving the way for new therapeutic approaches.
New mechanism of nerve injury in Alzheimer’s disease: β‐amyloid‐induced neuronal pyroptosis
Authors: Han Chenyang , Yang Yi , Guan Qiaobing , Zhang Xiaoling , Shen Heping , Sheng Yongjia , Wang Jin , Zhou Xiaohong , Li Wenyan , Guo Li , Jiao Qingcai
Published: June 2020

The present study was designed to investigate the role of β‐amyloid (Aβ1‐42) in inducing neuronal pyroptosis and its mechanism. Mice cortical neurons (MCNs) were used in this study, LPS + Nigericin was used to induce pyroptosis in MCNs (positive control group), and Aβ1‐42 was used to interfere with MCNs. In addition, propidium iodide (PI) staining was used to examine cell permeability, lactate dehydrogenase (LDH) release assay was employed to detect cytotoxicity, immunofluorescence (IF) staining was used to investigate the expression level of the key protein GSDMD, Western blot was performed to detect the expression levels of key proteins, and enzyme‐linked immunosorbent assay (ELISA) was utilized to determine the expression levels of inflammatory factors in culture medium, including IL‐1β, IL‐18 and TNF‐α. Small interfering RNA (siRNA) was used to silence the mRNA expression of caspase‐1 and GSDMD, and Aβ1‐42 was used to induce pyroptosis, followed by investigation of the role of caspase‐1‐mediated GSDMD cleavage in pyroptosis. In addition, necrosulfonamide (NSA), an inhibitor of GSDMD oligomerization, was used for pre‐treatment, and Aβ1‐42 was subsequently used to observe the pyroptosis in MCNs. Finally, AAV9‐siRNA‐caspase‐1 was injected into the tail vein of APP/PS1 double transgenic mice (Alzheimer's disease mice) for caspase‐1 mRNA inhibition, followed by observation of behavioural changes in mice and measurement of the expression of inflammatory factors and pyroptosis‐related protein. As results, Aβ1‐42 could induce pyroptosis in MCNs, increase cell permeability and enhance LDH release, which were similar to the LPS + Nigericin‐induced pyroptosis. Meanwhile, the expression levels of cellular GSDMD and p30‐GSDMD were up‐regulated, the levels of NLRP3 inflammasome and GSDMD‐cleaved protein caspase‐1 were up‐regulated, and the levels of inflammatory factors in the medium were also up‐regulated. siRNA intervention in caspase‐1 or GSDMD inhibited Aβ1‐42‐induced pyroptosis, and NSA pre‐treatment also caused the similar inhibitory effects. The behavioural ability of Alzheimer's disease (AD) mice was relieved after the injection of AAV9‐siRNA‐caspase‐1, and the expression of pyroptosis‐related protein in the cortex and hippocampus was down‐regulated. In conclusion, Aβ1‐42 could induce pyroptosis by GSDMD protein, and NLRP3‐caspase‐1 signalling was an important signal to mediate GSDMD cleavage, which plays an important role in Aβ1‐42‐induced pyroptosis in neurons. Therefore, GSDMD is expected to be a novel therapeutic target for AD.
Polysaccharides derived from Balanophora polyandra significantly suppressed the proliferation of ovarian cancer cells through P53‐mediated pathway
Authors: Qu Jiayuan , He Yumin , Shi Yue , Gai Liyue , Xiao Li , Peng Fan , Li Zicheng , Wang Xiaomin , Yuan Chengfu
Published: June 2020

Ovarian cancer (OC) is ranked the first among the cancers threatening women's health. It attracts tremendous attention of cancer researchers because of its extremely high mortality rate. Recent studies have indicated that traditional herbal medicines (THMs) can play a pivotal role in cancer prevention and treatment. THMs are gaining popularity as a source of anti‐cancer agents. The plant of Balanophora polyandra, which has been used as a traditional herbal medicine, has been known for exhibiting potential haemostatic, analgesic, anti‐inflammatory and anti‐cancer properties. However, few studies on inhibitory effect of B. polyandra on OC have been performed. In the present study, we found that B. polyandra polysaccharides (BPP) induced cell cycle arrest at S phase, triggered apoptosis and inhibited migration and invasion of OC cells. Furthermore, we also found that there was a potential and close relationship between BPP and P53‐mediated pathway. Overall, these findings suggest that BPP can be a potential therapeutic agent for the treatment of OC.
Hinokiflavone induces apoptosis via activating mitochondrial ROS/JNK/caspase pathway and inhibiting NF‐κB activity in hepatocellular carcinoma
Authors: Mu Wan , Cheng Xuefang , Zhang Xue , Liu Ying , Lv Qianzhou , Liu Gaolin , Zhang Jigang , Li Xiaoyu
Published: June 2020

Hepatocellular carcinoma (HCC) is the sixth most common malignancy with limited treatment options. Hinokiflavone (HF), a natural biflavonoid, has shown to inhibit the proliferation of melanoma, whereas its antitumour effect against HCC and the underlying mechanisms remain elusive. Here, we aimed at evaluating its antitumour effect against HCC in both in vitro and in vivo. Cell counting kit 8, colony formation assay, PI/RNase staining and Western blotting revealed that HF inhibited the proliferation of HCC cells via G0/G1 cell cycle arrest with p21/p53 up‐regulation. DAPI staining, Annexin V‐FITC/PI staining and Western blotting confirmed that HF triggered caspase‐dependent apoptosis. Moreover, HF increased the levels of mitochondrial reactive oxygen species (mtROS) and activated c‐Jun N‐terminal kinase (JNK) pathway, as measured by MitoSOX Red staining and Western blotting. After respectively inhibiting mtROS (Mito‐TEMPO) and JNK (SP600125), HF‐induced apoptosis was reversed. Additionally, Western blotting documented that HF suppressed nuclear factor kappa B (NF‐κB) activity and the anti‐apoptotic genes downstream, contributing to cell apoptosis. Finally, in vivo studies demonstrated that HF significantly impaired tumour growth in HCC xenograft. Collectively, these findings suggested that HF induced apoptosis through activating mtROS/JNK/caspase pathway and inhibiting NF‐κB signalling, which may represent a novel therapeutic agent for treating HCC.
Incidence and risk factors for dupilumab associated ocular adverse events: a real‐life prospective study
Authors: Touhouche A.T. , Cassagne M. , Bérard E. , Giordano‐Labadie F. , Didier A. , Fournié P. , Paul C. , Tauber M.
Published: June 2020

Background

Dupilumab is approved for use in moderate‐to‐severe atopic dermatitis (AD) and as an add‐on maintenance treatment in patients suffering from severe asthma with type 2 inflammation. Ocular adverse events (OAEs) have been reported with dupilumab almost exclusively in patients treated for AD.

Objectives

The objectives of this study were to describe the incidence and nature of dupilumab‐induced OAEs and to assess the potential predisposing factors.

Patients and methods

We conducted a prospective, single‐centre, real‐life study in adult AD patients treated with dupilumab, who were systematically examined by an ophthalmologist before and during treatment.

Results

Forty‐six patients were included prospectively with a median age of 41.1 years and a median initial SCOring Atopic Dermatitis of 46.0 (IQR: 34.5–55.5). OAEs concerned 34.8% of patients and were mostly of mild to moderate severity. Two patients had to discontinue treatment due to OAE. The majority of patients developed or aggravated dry eye disease, with superficial punctate keratitis (SPK). Six patients developed conjunctivitis. Dupilumab‐induced OAEs were associated with the following pre‐existing parameters: dry eye disease with SPK (Odds ratio (OR); 6.3 [95% confidence interval (CI): 1.3–31.6]), eyelid eczema (OR: 8.7 [95%CI: 1.8–40.6]), history of food allergy (OR 3.8 (95% CI: 1.002–14,070) and IgE serum level> 1000 kU/L (OR:10.6 [CI 95%: 1.2–91.3]).

Conclusion

Atopic dermatitis patients with eyelid eczema or dry eye disease symptoms may be referred to an ophthalmologist before starting dupilumab to consider initiating preventive eye hydration measures. Further multicentric and translational studies are warranted to better explain OAEs pathophysiology.
Exploring the role of social support and social media for lifestyle interventions to prevent weight gain with young adults: Focus group findings
Authors: Allman‐Farinelli M. , Nour M.
Published: June 2020

Background

Young adults gain more weight annually than other adults and may be destined for future obesity. Effective interventions are needed, and social support may be a key element for success. The present study explores how best to leverage social media to support young adults with their health goals in a healthy lifestyle programme.

Method

Young adults aged 18–25 years were recruited from the community to a series of four focus groups led by an experienced facilitator who used a discussion guide developed a priori. The discussion explored their opinions regarding which social media platforms were appropriate for providing social support, the types of support that were relevant (family and friends versus strangers) and factors that would encourage peer‐to‐peer communication in a healthy lifestyle intervention. Sessions were audio‐taped, transcribed and analysed using the qualitative software, nvivo, version 11 (QSR International Pty Ltd., Melbourne, VIC, Australia). Themes were generated using an inductive approach informed by the Theory of Social Identity and Social Influence Model of Consumer Participation.

Results

Thirty‐three people (12 male) participated. Facebook was the most popular platform for facilitating social support as a result of its private group capabilities and already being embedded into their daily routines. The preference was to be grouped with strangers who shared similar goals in smaller groups of participants. The discussions highlighted the integral role of a credible and relatable health coach to serve as a mentor, mediator and role model.

Conclusions

The learnings from this research will be applied to optimise engagement within social media support groups in lifestyle interventions.
Nursing’s metaparadigm, climate change and planetary health
Authors: Kalogirou Maya Reshef , Olson Joanne , Davidson Sandra
Published: June 2020

This paper offers a theoretical discussion on why the nursing profession has had a delayed response to the issue of climate change. We suggest this delay may have been influenced by the early days of nursing's professionalization. Specifically, we examine nursing's professional mandate, the generally accepted metaparadigm, and the grand theorists’ conceptualizations of both the environment and the nurse–environment relationship. We conclude that these works may have encouraged nurses to conceptualize the environment, as well as their relationship with it, mainly in terms of the individual patient, and as such, nurses have not been encouraged to understand these concepts from a broader perspective. By not having the philosophical and theoretical foundations to understand the environment in relation to society, it is not surprising that nurses have had a delayed response to climate change and may not have viewed it as a professional concern. A planetary health perspective is suggested as a theoretical basis for nursing education, research and practice. Taking on a planetary health perspective could help nurses progress the profession and move healthcare systems towards supporting a climate‐resilient future.
Heterosis of leaf and rhizosphere microbiomes in field‐grown maize
Authors: Wagner Maggie R. , Roberts Joseph H. , Balint‐Kurti Peter , Holland James B.
Published: June 2020

Macroorganisms’ genotypes shape their phenotypes, which in turn shape the habitat available to potential microbial symbionts. This influence of host genotype on microbiome composition has been demonstrated in many systems; however, most previous studies have either compared unrelated genotypes or delved into molecular mechanisms. As a result, it is currently unclear whether the heritability of host‐associated microbiomes follows similar patterns to the heritability of other complex traits.

We take a new approach to this question by comparing the microbiomes of diverse maize inbred lines and their F1 hybrid offspring, which we quantified in both rhizosphere and leaves of field‐grown plants using 16S‐v4 and ITS1 amplicon sequencing.

We show that inbred lines and hybrids differ consistently in the composition of bacterial and fungal rhizosphere communities, as well as leaf‐associated fungal communities. A wide range of microbiome features display heterosis within individual crosses, consistent with patterns for nonmicrobial maize phenotypes. For leaf microbiomes, these results were supported by the observation that broad‐sense heritability in hybrids was substantially higher than narrow‐sense heritability.

Our results support our hypothesis that at least some heterotic host traits affect microbiome composition in maize.
The Medicago truncatula Vacuolar iron Transporter‐Like proteins VTL4 and VTL8 deliver iron to symbiotic bacteria at different stages of the infection process
Authors: Walton Jennifer H. , Kontra‐Kováts Gyöngyi , Green Robert T. , Domonkos Ágota , Horváth Beatrix , Brear Ella M. , Franceschetti Marina , Kaló Péter , Balk Janneke
Published: June 2020

The symbiotic relationship between legumes and rhizobium bacteria in root nodules has a high demand for iron, and questions remain regarding which transporters are involved. Here, we characterize two nodule‐specific Vacuolar iron Transporter‐Like (VTL) proteins in Medicago truncatula.

Localization of fluorescent fusion proteins and mutant studies were carried out to correlate with existing RNA‐seq data showing differential expression of VTL4 and VTL8 during early and late infection, respectively.

The vtl4 insertion lines showed decreased nitrogen fixation capacity associated with more immature nodules and less elongated bacteroids. A mutant line lacking the tandemly‐arranged VTL4–VTL8 genes, named 13U, was unable to develop functional nodules and failed to fix nitrogen, which was almost fully restored by expression of VTL8 alone. Using a newly developed lux reporter to monitor iron status of the bacteroids, a moderate decrease in luminescence signal was observed in vtl4 mutant nodules and a strong decrease in 13U nodules. Iron transport capability of VTL4 and VTL8 was shown by yeast complementation.

These data indicate that VTL8, the closest homologue of SEN1 in Lotus japonicus, is the main route for delivering iron to symbiotic rhizobia. We propose that a failure in iron protein maturation leads to early senescence of the bacteroids.
The diversified defocus profile of the near‐work environment and myopia development
Authors: Choi Kai Yip , Mok Angela Yuen‐ting , Do Chi‐wai , Lee Paul Hong , Chan Henry Ho‐lung
Published: June 2020

Purpose

To quantify the defocus characteristics in the near‐work environment at home and investigate the relationship with subsequent myopia progression.

Methods

Fifty subjects (aged 7–12 years) were recruited and followed for 1 year. The home near‐work environment (writing desk) was measured at a baseline home‐visit using the Kinect‐for‐Windows to capture a 3‐dimensional image. The depth values of the image were then converted into scene defocus with respect to the subject’s viewpoint. The defocus characteristics were quantified as the dioptric volume (the total amount of net defocus, or DV) and standard deviation of the defocus values (SDD). Information on home size, time spent outdoors, and in front of a desk were also obtained. Univariate correlation, and multivariate regression were used to assess the association between myopia progression, defocus characteristics, and other co‐variates.

Results

The baseline spherical equivalent refraction (M) and refraction change over 1 year (∆M) were − 1.51 ± 2.02 D and − 0.56 ± 0.45 D respectively. DV was not significantly correlated with ∆M (Spearman’s ρ = −0.25, p = 0.08), while SDD was negatively correlated to ∆M (Spearman’s ρ = −0.42, p = 0.003). Although SDD was not a significant predictor in multivariate analysis, the regional DV at 15°–20° eccentricity was significant (p = 0.001). Home size (F2,50 = 7.01, p = 0.002) and time spent outdoors (Independent t = −2.13, p = 0.04) were also associated with ∆M, but not time spent in front of desk (Independent t = 0.78, p = 0.44).

Conclusion

The defocus profile in the home environment within the para‐central field of view is associated with childhood refractive error development.
Managing policy‐making in the local climate governance landscape: The role of network administrative organizations and member cities
Authors: Nguyen Long Le Anh , Krause Rachel M.
Published: June 2020

Trans‐municipal networks (TMNs) have reshaped the landscape around local government action on global climate policy. Past research has focused on why cities join TMNs and the impact that membership has on local action. This study considers a potential reverse effect: namely, that cities' membership choices position them to influence TMNs' overall priorities. In considering this, we emphasize the role of network administrative organizations (NAOs) and posit that the multiple climate‐related networks, which share members and operate in overlapping geographic and issue spaces, are bound together as part of a meta‐network. We utilize social network analysis and data on membership in four climate‐related TMNs to examine the factors that shape how cities can influence meta‐network priorities. We find that cities with local vulnerabilities tend to be located in network positions that enable them to influence the meta‐network's overall priorities.
Transient childhood wheeze is associated with less atopy in adolescence
Authors: Lodge Caroline Jane , Lowe Adrian John , Abramson Michael John , Svanes Cecilie , Zaloumis Sophie G. , Thomas Paul S. , Dharmage Shyamali Chandrika
Published: June 2020

Background

The relationships between childhood wheeze phenotypes and subsequent allergic conditions other than asthma, including hay fever, eczema and sensitization, have not been widely reported. We aimed to investigate this relationship up to late adolescence.

Methods

Using five childhood wheeze phenotypes defined from 620 children in a high‐atopy risk birth cohort (Melbourne Atopy Cohort Study), we investigated their relationships with sensitization, eczema, hay fever and fractional exhaled nitric oxide (FeNO) at ages 12 and/or 18 years using logistic and linear regression models.

Results

‘Early Persistent wheeze’ was associated with the increased risk of eczema (odds ratio: 3.69; 95% CI: 1.23, 11.12) and sensitization (4.52; 1.50, 13.64) at 12 years. ‘Intermediate Onset wheeze’ was associated with the increased risk of eczema at 12 years (2.57; 1.11, 5.97), hay fever at 12 (2.87; 1.44, 5.74) and 18 years (2.19; 1.20, 4.02), sensitization at 12 (2.25; 1.17, 4.34) and 18 years (2.46; 1.18, 5.12), and raised FeNO at 18 years. ‘Late Onset wheeze’ was associated with the increased risk of hay fever at 12 (5.18; 1.11, 24.20) and 18 years (4.20; 1.03, 17.11) and sensitization at 12 years (3.27; 0.81, 13.27). In contrast, ‘Early Transient wheeze’ was associated with the reduced risk of eczema (0.44; 0.20, 0.96), hay fever (0.57; 0.33, 0.99) and sensitization (0.59; 0.35, 0.99) at 18 years and a lower FeNO compared with ‘Never/Infrequent wheezers’.

Conclusions

Persistent wheeze phenotypes were associated with allergic outcomes up to 18 years with ‘Intermediate Onset wheeze’ being the most atopic group. In contrast, ‘Early Transient wheezers’ had less risk of allergic outcomes at 18 years. This protective effect may reassure parents of wheezy infants and young children.
Novel insights regarding anaphylaxis in children ‐ With a focus on prevalence, diagnosis, and treatment
Authors: Nagakura Ken‐Ichi , Sato Sakura , Asaumi Tomoyuki , Yanagida Noriyuki , Ebisawa Motohiro
Published: June 2020

Anaphylaxis is a serious allergic reaction that occurs rapidly and causes a life‐threatening response involving the whole body. This reaction often leads to difficulty in breathing and can result in death. The estimated prevalence of anaphylaxis is 0.05%–2%, which is reported to be increasing in children. Although drugs and venom are the most common causes of anaphylaxis in adults, food is the most common cause of anaphylaxis in children. An interesting association between food‐dependent exercise‐induced anaphylaxis (FDEIA) and oral immunotherapy (OIT) has recently been reported. A provocation test to determine the diagnostic and augmenting factors of FDEIA has been reported in recent years. Remarkably, several articles showed allergic symptoms without exercise in children with FDEIA and in those with FDEIA development after OIT. Regarding OIT, full‐dose OIT poses a risk of adverse reactions, including anaphylaxis. Recent trials have shown the efficacy and safety of low‐dose OIT in patients with food‐induced anaphylaxis. In this review, we summarized the novel insights regarding anaphylaxis in the pediatric population.
Variation in RNA‐editing sites of chloroplast protein‐coding genes in early‐maturity mutant induced by carbon‐ion beam in Sweet Sorghum
Authors: Liu Ruiyuan , Li Wenjian , Lu Dong , Li Jiangang , Qu Ying , Jin Wenjie , Dong Xicun
Published: June 2020

Using prediction and experimental determination, we compared the RNA‐editing sites in chloroplast protein‐coding genes in an early‐maturity mutant (KFJT‐1) induced by carbon‐ion beam irradiation in sweet sorghum and its wild type (KFJT‐CK). Twenty‐two and 20 editing sites were identified in the KFJT‐CK and KFJT‐1 chloroplast, respectively, and the differential editing sites between KFJT‐CK and KFJT‐1 were mainly in mat, ndh and rpo genes. Furthermore, mutations in RNA‐editing sites in KFJT‐1 affected the structure of the encoded protein, which implying that RNA‐editing events might influence the function of essential genes. Finally, a comparative analysis of the RNA‐editing events between KFJT‐1 and other 10 Poaceae species revealed that the RNA‐editing sites in matK‐1002, rpoC1‐1163 and rpoC2‐242 were unique to KFJT‐1. This suggested that RNA‐editing events due to carbon‐ion beam irradiation affected the structure of the encode proteins, thereby influenced their biological functions. This study is the first to report on the variation in chloroplast RNA‐editing patterns induced by carbon‐ion beams irradiation, and its effect on the chloroplast in KFJT‐1 at the post‐transcriptional level.
Identification of novel seed longevity genes related to oxidative stress and seed coat by genome‐wide association studies and reverse genetics
Authors: Renard Joan , Niñoles Regina , Martínez‐Almonacid Irene , Gayubas Beatriz , Mateos‐Fernández Rubén , Bissoli Gaetano , Bueso Eduardo , Serrano Ramón , Gadea José
Published: June 2020

Seed longevity is a polygenic trait of relevance for agriculture and for understanding the effect of environment on the ageing of biological systems. In order to identify novel longevity genes, we have phenotyped the natural variation of 270 ecotypes of the model plant, Arabidopsis thaliana, for natural ageing and for three accelerated ageing methods. Genome‐wide analysis, using publicly available single‐nucleotide polymorphisms (SNPs) data sets, identified multiple genomic regions associated with variation in seed longevity. Reverse genetics of 20 candidate genes in Columbia ecotype resulted in seven genes positive for seed longevity (PSAD1, SSLEA, SSTPR, DHAR1, CYP86A8, MYB47 and SPCH) and five negative ones (RBOHD, RBOHE, RBOHF, KNAT7 and SEP3). In this uniform genetic background, natural and accelerated ageing methods provided similar results for seed‐longevity in knock‐out mutants. The NADPH oxidases (RBOHs), the dehydroascorbate reductase (DHAR1) and the photosystem I subunit (PSAD1) highlight the important role of oxidative stress on seed ageing. The cytochrome P‐450 hydroxylase, CYP86A8, and the transcription factors, MYB47, KNAT7 and SEP3, support the protecting role of the seed coat during seed ageing.