bluuebunny/crossref_metadata_2025 huggingface dataset:
Discouraging Rainforest Transformation: An Ex‐ante Policy Impact Analysis
Authors: Sarwosri Arieska Wening , Wegmann Johannes , Mußhoff Oliver
Published: May 2019

Despite extensive efforts made by national and international certification agencies, Indonesian smallholder farmers’ participation in palm oil certification schemes adoption remains low. A fundamental obstacle is the smallholder practice of rainforest transformation into oil palm plantation which is forbidden by the agencies. In this context, we investigate three policies that could lead to a reduction in rainforest deforestation by smallholders: price premium on certified palm oil; the provision of environmental information; contributor recognition. In order to evaluate the influence of the policies ex‐ante, we conduct a social dilemma experiment involving rubber and oil palm smallholders in Jambi Province, Sumatra, Indonesia. The findings indicate that the price premium and provision of context‐specific environmental information could reduce rainforest transformation. However, a statistically significant effect of contributor recognition was not found.
Bacterial nanocellulose production from naphthalene
Authors: Marín Patricia , Martirani‐Von Abercron Sophie Marie , Urbina Leire , Pacheco‐Sánchez Daniel , Castañeda‐Cataña Mayra Alejandra , Retegi Aloña , Eceiza Arantxa , Marqués Silvia
Published: May 2019

Polycyclic aromatic compounds (PAHs) are toxic compounds that are released in the environment as a consequence of industrial activities. The restoration of PAH‐polluted sites considers the use of bacteria capable of degrading aromatic compounds to carbon dioxide and water. Here we characterize a new Xanthobacteraceae strain, Starkeya sp. strain N1B, previously isolated during enrichment under microaerophilic conditions, which is capable of using naphthalene crystals as the sole carbon source. The strain produced a structured biofilm when grown on naphthalene crystals, which had the shape of a half‐sphere organized over the crystal. Scanning electron microscopy (SEM) and GC‐MS analysis indicated that the biofilm was essentially made of cellulose, composed of several micron‐long nanofibrils of 60 nm diameter. A cellulosic biofilm was also formed when the cells grew with glucose as the carbon source. Fourier transformed infrared spectroscopy (FTIR) confirmed that the polymer was type I cellulose in both cases, although the crystallinity of the material greatly depended on the carbon source used for growth. Using genome mining and mutant analysis, we identified the genetic complements required for the transformation of naphthalene into cellulose, which seemed to have been successively acquired through horizontal gene transfer. The capacity to develop the biofilm around the crystal was found to be dispensable for growth when naphthalene was used as the carbon source, suggesting that the function of this structure is more intricate than initially thought. This is the first example of the use of toxic aromatic hydrocarbons as the carbon source for bacterial cellulose production. Application of this capacity would allow the remediation of a PAH into such a value‐added polymer with multiple biotechnological usages.
Does Audit Committee Accounting Expertise Help to Promote Audit Quality? Evidence from Auditor Reporting of Internal Control Weaknesses
Authors: Lisic Ling Lei , Myers Linda A. , Seidel Timothy A. , Zhou Jian
Published: May 2019

In this study, we examine whether audit committee accounting expertise helps to promote audit quality by motivating auditors to conduct diligent internal control audits and make appropriate internal control assessments because audit committee accounting expertise safeguards auditors from dismissal following adverse internal control opinions. Among clients with existing and likely internal control material weaknesses (as proxied by future restatements of audited financial statements), we find a greater likelihood of adverse internal control audit opinions when the audit committee has greater accounting expertise (measured by the proportion of accounting experts on the audit committee). Among all clients, we find a lower likelihood of subsequent auditor dismissal following an adverse internal control audit opinion when the audit committee has greater accounting expertise. In further analyses, we find that this lower likelihood of subsequent auditor dismissal occurs when at least two audit committee members possess accounting expertise. We also find some evidence that CFO influence (but not CEO influence) over the audit committee negates the increased likelihood of adverse internal control opinions when internal control material weaknesses likely exist, as well as the decreased likelihood of auditor dismissal following adverse internal control opinions. These findings have important implications for regulators and corporate nominating committees interested in promoting audit committee effectiveness.
Directors' Informational Role in Corporate Voluntary Disclosure: An Analysis of Directors from Related Industries
Authors: Ke Ruihao , Li Meng , Zhang Yuan
Published: May 2019

Boards of directors play their role in corporate governance by advising and/or monitoring managers. In the corporate disclosure literature, prior research has documented directors' monitoring role, yet empirical evidence on directors' advising role is limited. Since the advising role often entails information transfer, we examine directors who concurrently serve as directors or executives in the firms' related industries (DRIs) and hence possess valuable information about the firms' external operating environment. We hypothesize and find that more DRIs on boards are associated with more accurate management forecasts. This association is stronger when firms face greater uncertainty, and holds in settings where DRIs are unlikely to monitor managers, suggesting a distinct advising role of DRIs. Our study highlights directors' role as information suppliers and advisors who help shape corporate voluntary disclosure.
Professional Directors and Governance Quality
Authors: Wahid Aida Sijamic , Welch Kyle , Maber David A.
Published: May 2019

We examine professional directors—board members with no employment outside of serving as independent directors. We find that boards with a higher percentage of professional directors engage in more acquisitions, experience lower acquisition announcement returns, and exhibit lower performance‐turnover sensitivity and lower financial performance. We also examine the returns surrounding the appointment‐announcement dates of professional directors and find that firms experience significantly lower cumulative abnormal returns upon the appointment announcement of professional directors as compared to nonprofessional directors. The negative returns are primarily experienced by firms that face greater agency issues, suggesting that the market does not value professional directors for stricter monitoring. Overall, our findings do not lend support for calls to professionalize corporate boards.
Personality disorders of drivers killed in fatal motor vehicle accidents in Finland during 1990–2011
Authors: Räisänen T. , Hakko H. , Riipinen P. , Räty E. , Kantojärvi L.
Published: May 2019

Objective

To examine the association of personality disorders (PDs) to deaths of drivers in fatal motor vehicle accidents (FMVAs) and analyze gender differences in lifetime psychiatric disorders and medico‐legal findings at the time of accident.

Method

The study sample consisted of 4810 Finnish drivers killed in FMVAs in Finland between 1990 and 2011. Doctor‐diagnosed PD was found in 146 drivers (118 men and 28 women). The information of psychiatric morbidity was obtained from the Finnish Care Register for Health Care.

Results

The proportion of deceased drivers with PDs had increased significantly over the study period, particularly among females and those with PD not otherwise specified (NOS). Suicidality and use of medication affecting driving ability were more common among females with PD compared to males with PD. 88% of all deceased drivers with PD had comorbid psychiatric disorders.

Conclusion

Our findings indicate that PDs may predispose drivers to FMVAs, particularly females. This study emphasizes the importance of evaluating the fitness‐to‐drive of subjects with PD and especially comorbid substance use disorders, which may relate to an increased risk of fatal motor accidents.
Evaluation of a method to estimate the point prevalence of cognitive impairment and delirium in a multi‐campus Australian health service
Authors: Casey Penelope , Dārziņš Pēteris , Webb‐St Mart Melinda , Baldwin Cathryn , Riddell Kath , Johnson Claire , Cross Wendy
Published: May 2019

Objective

To design, test (pilot) and implement a study to estimate the point prevalence of cognitive impairment (CI) and delirium in a multi‐site health service.

Methods

Clinicians were trained to use the 4 A's Test (4AT) to screen for cognitive impairment and delirium, and the 3‐minute Diagnostic Interview for the Confusion Assessment Method (3D‐CAM) to detect delirium in those with abnormal 4AT results. Outcomes of interest were as follows: (a) rates of cognitive impairment and delirium and (b) feasibility of the approach measured by participation rate, “direct survey activity” time, cost and surveyor preparation.

Results

The rates of cognitive impairment and delirium were 43.8% (245/559) and 16.3% (91/559), respectively. 90.5% (563/622) of eligible adult patients from 25 acute and subacute wards were seen. “Direct survey activities” averaged 14 minutes (range 2‐45) and cost $11.48 per patient. Training evaluation indicated additional education in the 4AT and 3D‐CAM was needed.

Conclusion

Health services could use this streamlined, inexpensive method to estimate the point prevalence of cognitive impairment and delirium.
Downregulation of CCNA2 disturbs trophoblast migration, proliferation, and apoptosis during the pathogenesis of recurrent miscarriage
Authors: Li Xiao , Ma Xiao‐Ling , Tian Fu‐Ju , Wu Fan , Zhang Jing , Zeng Wei‐Hong , Lin Yi , Zhang Yan
Published: May 2019

Problem

Recurrent miscarriage (RM) is defined as two or more pregnancy losses until 24 weeks of gestation, which distresses up to 1‐5% of couples worldwide. Cyclin A2 (CCNA2) regulates the cell cycle by promoting transition through G1/S and G2/M. Little is known about CCNA2’s functions in trophoblast, although it is highly expressed in the placenta. We therefore sought to explore the role of CCNA2 in RM and early pregnancy.

Method of study

First‐trimester human placental tissues were collected from patients with RM and normal pregnant women to clarify the expression level of CCNA2. First‐trimester human villi explants culture was performed as an ex vivo model to study the functions of CCNA2. The HTR8/SVneo cells were studied for in vitro experiments. The migration, proliferation, and apoptosis levels of trophoblast were examined in the CCNA2‐knockdown and CCNA2‐overexpressing HTR8 cells.

Results

Our study revealed that CCNA2 was downregulated in trophoblast of RM first‐trimester villi. Results showed that CCNA2 promotes migration of HTR8 cells via the RhoA‐ROCK signaling and that CCNA2 increased HTR8 proliferation and inhibited their apoptosis via p53 pathway. In addition, the relationship between ROCK signaling and p53 pathway was found. Further, mechanistic research attributed the regulatory function of CCNA2 on p53 pathway to the involvement of DNA damage.

Conclusion

Our study revealed the downregulation of CCNA2 in first‐trimester chorionic villi of patients with RM and showed that this protein regulates migration, proliferation, and apoptosis in HTR8 cells, suggesting that CCNA2 may be the potential therapeutic target for RM.
Health economic implications of postoperative complications following liver resection surgery: a systematic review
Authors: Cosic Luka , Ma Ronald , Churilov Leonid , Nikfarjam Mehrdad , Christophi Christopher , Weinberg Laurence
Published: May 2019

Background

Limited data exists concerning the health economics of liver resection, with even less information on the costs emerging from complications, despite this remaining an important target from a health economic perspective. Our objective was to describe the financial burden of complications following liver resection.

Methods

We conducted a systematic search and included studies reporting resource use of in‐hospital complications during the index liver resection admission. All indications for liver resection were considered. All techniques were considered. Data was collected using a data extraction table and a narrative synthesis was performed.

Results

We identified 12 eligible articles. There was considerable heterogeneity in study designs, patient populations and outcome definitions. We found weak evidence of increased costs associated with major liver resection compared to minor resections. We found robust evidence supporting the increasing economic burden arising from complications after liver resection. Acceptable evidence for increased cost due to the presence and grade of complication was found. Strong evidence concerning the association of length of stay with costs was demonstrated.

Conclusions

The presence and grade of complications increase hospital cost across diverse settings. The costing methodology should be transparent and complication grading systems should be consistent in future studies.
Morphology and severity of peri‐implantitis bone defects
Authors: Monje Alberto , Pons Ramón , Insua Angel , Nart José , Wang Hom‐Lay , Schwarz Frank
Published: May 2019

Background

Peri‐implant defect morphology has shown to potentially impact upon the reconstructive outcomes for the management of peri‐implantitis. Given the role that defect morphology plays upon the decision‐making in the treatment of peri‐implantitis, the present study aimed at assessing the morphology and severity of peri‐implantitis bone defects and to insight on the patient‐, implant‐ and site‐related variables associated to these.

Material and Methods

A cone‐beam computed tomography study was carried out to classify peri‐implantitis defects according to the type of defect, number of remaining bony walls and severity according to the extension of vertical bone loss. Three major defect categories were proposed: class I—infraosseous; class II—horizontal; class III—combined of class I and II. These were then subclassified into: (a) dehiscence; (b) 2/3‐wall; and (c) circumferential—type defect. According to the severity the defects were further subclassified into: A: advanced; M: moderate; and S: slight. In addition, 20 site‐, implant‐, and patient‐related variables were analyzed by generalized estimating equations (GEEs) of multilevel logistic regression models.

Results

Based on an a priori power calculation, 332 implants were screened in 47 peri‐implantitis patients. Of these, 158 peri‐implantitis implants were eligible. The most prevalent defect morphology type was class Ib (55%) followed by class Ia (16.5%), and class IIIb (13.9%). On the contrary, the less frequent defect was class II (1.9%). The most frequent degree of severity was M (50.6%) with S (10.1%) being the least prevalent. Buccal bone loss was significantly greater compared to the other bony walls in class I and class III defects. Age was associated with the type of defect. Age and smoking habit were associated with the morphology of the defects, while smoking habit, type of prosthesis and distance to adjacent implant were associated with the severity of the defects (vertical bone loss).

Conclusion

Peri‐implantitis defects frequently course with an infraosseous component and often with buccal bone loss. Certain patient‐, implant‐, and site‐specific variables are related with defect morphology and severity. However, morphological patterns for peri‐implantitis bone defects could not be proven (NCT NCT03777449).
Pulmonary oxygen uptake on‐kinetics can predict acute physiological responses to resistance exercise training in healthy young men
Authors: Kubo Yusuke , Fujita Daisuke , Sugiyama Shuhei , Hosokawa Masato , Nishida Yusuke
Published: May 2019

Purpose

To clarify whether pulmonary oxygen uptake kinetics () at the onset of moderate‐intensity exercise can predict acute physiological responses to resistance exercise training (RET).

Methods

We investigated the relationship between and acute metabolic and hemodynamic responses to a single RET session in 27 healthy young adult men. Cardiopulmonary exercise was on a cycle ergometer, and a single RET at 30% or 60% of one‐repetition maximum was on a bilateral leg‐extension machine. We measured the anaerobic threshold, peak and while cardiopulmonary exercising, and the rates of increase in blood lactate (Bla), heart rate (HR), systolic blood pressure (SBP) and rate pressure product (RPP) for a single RET.

Results

There were significant positive associations between and the rates of increase in Bla, HR, SBP and RPP during a single RET session (P<0·05). However, the anaerobic threshold and peak did not significantly affect these parameters.

Conclusion

The is a useful evaluation index for predicting acute physiological responses to RET.
Pancreas size and exocrine function is decreased in young children with recent‐onset Type 1 diabetes
Authors: Augustine P. , Gent R. , Louise J. , Taranto M. , Penno M. , Linke R. , Couper J. J. ,   the ENDIA Study Group
Published: May 2019

Aims

To measure pancreatic area and exocrine function in young children with recent‐onset Type 1 diabetes to determine whether the exocrine pancreas is also affected in the pathophysiology of early childhood diabetes.

Methods

Thirty‐two children (14 boys) aged 5.5 (4.5, 7.3) median (IQR) years presenting with recent‐onset Type 1 diabetes and 90 controls (44 boys) of similar age had ultrasound imaging of the pancreas. Children with Type 1 diabetes were receiving insulin and were without ketosis. Transverse and longitudinal areas of the pancreas were measured by digitalized outline. Pancreatic faecal elastase‐1 was analysed using an enzyme‐linked immunosorbent assay kit in recent‐onset Type 1 diabetes and 38 first‐degree relative control children.

Results

Pancreatic area and exocrine function were reduced in Type 1 diabetes. Mean transverse area (SD) in Type 1 diabetes was 6.82 cm2 (1.61) vs. 8.31 cm2 (1.74) in controls, adjusted estimate (95% CI) 1.45 (‐2.12, ‐0.79), P < 0.001; longitudinal area was 1.28 cm2 (0.44) vs. 1.55 cm2 (0.43), adjusted estimate (95% CI) ‐0.27 (‐0.45, ‐0.09), P = 0.003. Faecal elastase‐1 levels in Type 1 diabetes were 455 (323, 833) ug/g, median (IQR) vs. 1408 μg/g (1031, 1989) in controls, P < 0.001.

Conclusion

Pancreatic area and accompanying subclinical exocrine function were reduced in very young children with recent‐onset Type 1 diabetes. This supports changes in the exocrine pancreas in the pathophysiology of Type 1 diabetes presenting in early life.
Quantification of pulmonary/systemic shunt ratio by single‐acquisition phase‐contrast cardiovascular magnetic resonance
Authors: Dunn Terence Sean , Patel Pratik , Abazid Bassem , Nagaraj Hosakote M. , Desai Ravi V. , Gupta Himanshu , Lloyd Steven G.
Published: May 2019

Purpose

Phase‐contrast cardiovascular magnetic resonance (PC‐CMR) quantification of intracardiac shunt (measuring the pulmonary to systemic flow ratio, Qp/Qs) is typically determined by measuring flow through planes perpendicular the pulmonary trunk (PA) and ascending aorta (Ao). This method is subject to error from presence of background velocity offsets and requires two scan acquisitions. We evaluated an alternate PC‐CMR technique for quantifying Qp/Qs using a single modified plane that encompasses both the PA and Ao.

Material and Methods

In 53 patients evaluated for intracardiac shunting, PC‐CMR measurement in the individual Ao and PA planes and also in a single‐acquisition plane was obtained and Qp/Qs calculated by each method. Bland–Altman analysis was performed to evaluate the agreement between the two methods.

Results

The 95% confidence limits of agreement ranged from −0.52 to +0.34 indicating good agreement between the two methods. There was excellent agreement on the clinically relevant threshold value of Qp/Qs ratio of 1.5 (representing criteria for surgical correction of shunt).

Conclusions

Qp/Qs determined from the single‐acquisition approach agrees well with that of the individual PA and Ao method and offers potential improved accuracy (due to background velocity offset).
Behaviour before beauty: Signal weighting during mate selection in the butterfly Papilio polytes
Authors: Westerman Erica L. , Antonson Nicholas , Kreutzmann Sydney , Peterson Alexandra , Pineda Skyy , Kronforst Marcus R. , Olson‐Manning Carrie F.
Published: May 2019

Mating displays often contain multiple signals. Different combinations of these signals may be equally successful at attracting a mate, as environment and signal combination may influence relative signal weighting by choosy individuals. This variation in signal weighting among choosy individuals may facilitate the maintenance of polymorphic displays and signalling behaviour. One group of animals known for their polymorphic patterning are Batesian mimetic butterflies, where the interaction of sexual selection and predation pressures is hypothesized to influence the maintenance of polymorphic wing patterning and behaviour. Males in the female‐limited polymorphic Batesian mimetic butterfly Papilio polytes use female wing pattern and female activity levels when determining whom to court. They court stationary females with mimetic wing patterns more often than stationary females with non‐mimetic, male‐like wing patterns and active females more often than inactive females. It is unclear whether females modify their behaviour to increase (or decrease) their likelihood of receiving male courtship, or whether non‐mimetic females spend more time in cryptic environments than mimetic females, to compensate for their lack of mimicry‐driven predation protection (at the cost of decreased visibility to males). In addition, relative signal weighting of female wing pattern and activity to male mate selection is unknown. To address these questions, we conducted a series of observational studies of a polymorphic P. polytes population in a large butterfly enclosure. We found that males exclusively courted active females, irrespective of female wing pattern. However, males did court active non‐mimetic females significantly more often than expected given their relative abundance in the population. Females exhibited similar activity levels, and selected similar resting environments, irrespective of wing pattern. Our results suggest that male preference for non‐mimetic females may play an active role in the maintenance of the non‐mimetic female form in natural populations, where males are likely to be in the presence of active, as well as inactive, mimetic and non‐mimetic females.
Can we use psychoactive drugs to treat pruritus?
Authors: Reszke Radomir , Szepietowski Jacek C.
Published: May 2019

Pruritus is a frequent complaint both in dermatology and general medicine. This burdensome symptom has a complex and multifactorial pathogenesis, with the key involvement of central nervous system in its development. Psychoactive drugs (psychopharmaceuticals) encompass several therapeutic groups utilized mainly in psychiatry. However, these drugs are occasionally used in dermatological practice and may contribute to alleviation of pruritus in a variety of cutaneous and extracutaneous disorders. This review article summarizes the role of H1‐antihistamines, antidepressants, antipsychotics and antiepileptics in managing pruritus.
The Effect of Shareholder Approval of Equity Issuances Around the World
Authors: Holderness Clifford G.
Published: May 2019

Mandatory shareholder approval of equity issuances varies considerably across and within countries. In the United States and a few other countries, management typically needs the approval of only its board of directors to issue common stock. In most countries, however, by law or stock exchange rule, shareholders must vote to approve equity issuances when using certain methods or contemplating offers that exceed a specified fraction of outstanding shares. In some countries, shareholders must approve all equity issuances. Even in the United States, shareholder approval is mandatory under certain circumstances.

The differences in the stock market reaction to shareholder‐approved equity issuances and to issues undertaken unilaterally by management are strikingly and consistently large. When shareholders approve stock issuances, whether public or rights offerings, or private placements, the average announcement returns are significantly positive, on the order of 2%. But when managers issue stock without shareholder approval, as in the case of U.S. public offerings, returns are significantly negative and 4% lower, on average, than for shareholder‐approved issues. What's more, the closer in time the shareholder vote is to the issue date, and the greater the required plurality (say, two‐thirds instead of half the vote required for approval), the more positive is the market reaction to the issue—and these findings hold for each of the three main kinds of offerings that take place in all 23 countries in the author's sample.

Also telling, in countries where shareholder approval is required, such as Sweden and Malaysia, rights offers predominate over public issues. But in countries like the U.S. and Japan, where managers may generally issue stock without shareholder approval, public offers predominate over rights issues. These findings suggest that agency problems—the tendency of corporate managements to put their own interests before their shareholders'—play a major role in equity issuances. Such findings are also largely inconsistent with the adverse selection, market timing, and signaling explanations that currently dominate academic thinking about equity issuances by public corporations.
The Early Returns to International Hedge Fund Activism: 2000–2010
Authors: Becht Marco , Franks Julian , Grant Jeremy , Wagner Hannes
Published: May 2019

In this summary of their recent article in the Review of Financial Studies, the authors provide an overview of the methods and findings of the first comprehensive study of worldwide hedge fund activism—one that examined the effectiveness of some 1,740 separate “engagements” of public companies by 330 different hedge funds operating in 23 countries in Asia, Europe, and North America during the period 2000‐2010.

The study reports, first of all, that the incidence of shareholder activism is greatest in companies and countries with high institutional ownership, particularly U.S. institutions. In virtually all countries, with the possible exception of Japan, large holdings by institutional investors increased the probability that companies would be targeted by activists. Nevertheless, in all countries (except for the United States), foreign institutions—especially U.S. funds investing in non‐U.S. companies—have played a more important role than domestic institutional investors in supporting activism.

The authors also report that those engagements that succeeded in producing “outcomes” were accompanied by positive and significant abnormal stock returns, not only upon the announcement of the activist's block purchase, but throughout the entire holding period. “Outcomes” were identified as taking one of four forms: (1) increases in dividends or stock buybacks; (2) replacement of board members; (3) corporate restructurings such as sales or spinoffs of businesses; and (4) takeover (or sale) of the entire company. But if such outcomes were associated with high shareholder returns, in the many cases where there were no such outcomes, the eventual, holding‐period returns to shareholders, even after taking account of the initially positive market reaction to news of the engagement, were indistinguishable from zero.

The authors found that activists succeeded in achieving at least one of their proposed outcomes in roughly one out of two (53%) of the 1,740 engagements. But this success rate varied considerably across countries, ranging from a high of 61% for North American companies, to 50% for European companies, but only 18% engagements of Asian companies—with Japan, again, a country of high disclosure returns but unfulfilled expectations and disappointing outcomes. Outcomes also tended to be strongly associated with the roughly 25% of the total engagements that involved two or more activists (referred to as “wolfpacks”) and produced very high returns.
The role of patients in the delivery of safe care in hospital: Study protocol
Authors: Chegini Zahra , Janati Ali , Bababie Javad , Pouraghaei Mahboub
Published: May 2019

Aim

This paper outlines the protocol for a study aimed at exploring perspectives about the role of patients’ in the delivery of safe care in hospital.

Design

Qualitative exploratory study.

Methods

Research Ethics Committee approval for this study was obtained in October 2018. The study will be conducted between February–April 2019 with data collected through focus group discussions and semi‐structured interviews and will involve patients and healthcare professionals from hospitals in Tabriz. A descriptive qualitative approach will be adopted, and the data will be managed and analysed using MAXQDA 10 software.

Discussion

The role of patients in furthering their own safety whilst in hospital cannot be underestimated and the results from this study can be used to support the development of practical strategies that address the delivery of safe hospital care and which involve patients and their caregivers.
Targeting EZH2 as a novel therapeutic strategy for sorafenib‐resistant thyroid carcinoma
Authors: Wang Zhengshi , Dai Jiaqi , Yan Jie , Zhang Yun , Yin Zhiqiang
Published: May 2019

Thyroid carcinoma is the most common endocrine malignancy. Surgery, post‐operative selective iodine‐131 and thyroid hormone suppression were the most common methods for the therapy of thyroid carcinoma. Although most patients with differentiated thyroid carcinoma (DTC) showed positive response for these therapeutic methods, some patients still have to face the radioactive iodine (RAI)‐refractory problems. Sorafenib is an oral multikinase inhibitor for patients with advanced RAI refractory DTC. However, the side effects and drug resistance of sorafenib suggest us to develop novel drugs and strategies for the therapy of thyroid carcinoma. In this study, we firstly found that patients with sorafenib resistance showed no significant change in rapidly accelerated fibrosarcoma and VEGFR expression levels compared with sorafenib sensitive patients. Moreover, a further miRNAs screen by qRT‐PCR indicated that miR‐124‐3p and miR‐506‐3p (miR‐124/506) were remarkably reduced in sorafenib insensitive patients. With a bioinformatics prediction and functional assay validation, we revealed that enhancer of zeste homolog 2 (EZH2) was the direct target for miR‐124/506. Interestingly, we finally proved that the sorafenib resistant cells regained sensitivity for sorafenib by EZH2 intervention with miR‐124/506 overexpression or EZH2 inhibitor treatment in vitro and in vivo, which will lead to the decreased tri‐methylation at lysine 27 of histone H3 (H3K27me3) and increased acetylated lysine 27 of histone H3 (H3K27ac) levels. Therefore, we conclude that the suppression of EZH2 represents a potential target for thyroid carcinoma therapy.
Folic acid deficiency enhanced microglial immune response via the Notch1/nuclear factor kappa B p65 pathway in hippocampus following rat brain I/R injury and BV2 cells
Authors: Cheng Man , Yang Liu , Dong Zhiping , Wang Mengying , Sun Yan , Liu Huan , Wang Xuan , Sai Na , Huang Guowei , Zhang Xumei
Published: May 2019

Recent studies revealed that folic acid deficiency (FD) increased the likelihood of stroke and aggravated brain injury after focal cerebral ischaemia. The microglia‐mediated inflammatory response plays a crucial role in the complicated pathologies that lead to ischaemic brain injury. However, whether FD is involved in the activation of microglia and the neuroinflammation after experimental stroke and the underlying mechanism is still unclear. The aim of the present study was to assess whether FD modulates the Notch1/nuclear factor kappa B (NF‐κB) pathway and enhances microglial immune response in a rat middle cerebral artery occlusion‐reperfusion (MCAO) model and oxygen‐glucose deprivation (OGD)‐treated BV‐2 cells. Our results exhibited that FD worsened neuronal cell death and exaggerated microglia activation in the hippocampal CA1, CA3 and Dentate gyrus (DG) subregions after cerebral ischaemia/reperfusion. The hippocampal CA1 region was more sensitive to ischaemic injury and FD treatment. The protein expressions of proinflammatory cytokines such as tumour necrosis factor‐α, interleukin‐1β and interleukin‐6 were also augmented by FD treatment in microglial cells of the post‐ischaemic hippocampus and in vitro OGD‐stressed microglia model. Moreover, FD not only dramatically enhanced the protein expression levels of Notch1 and NF‐κB p65 but also promoted the phosphorylation of pIkBα and the nuclear translocation of NF‐κB p65. Blocking of Notch1 with N‐[N‐(3, 5‐difluorophenacetyl)‐l‐alanyl]‐S‐phenylglycine t‐butyl ester partly attenuated the nuclear translocation of NF‐κB p65 and the protein expression of neuroinflammatory cytokines in FD‐treated hypoxic BV‐2 microglia. These results suggested that Notch1/NF‐κB p65 pathway‐mediated microglial immune response may be a molecular mechanism underlying cerebral ischaemia‐reperfusion injury worsened by FD treatment.
Association between age at first childbirth and type 2 diabetes in Chinese women
Authors: Qu Xueqi , Wang Hanyu , Zhou Shiyuan , Fang Zhe , Li Jingyuan , Tang Kun
Published: May 2019

Aims/Introduction

The present study aims to explore the relationship between age at first childbirth and developing type 2 diabetes, and analyze potential modifiers of its relationship.

Materials and Methods

The data were obtained from the baseline survey of a large‐scale cohort study in 10 diverse areas of China. Multivariate logistic regressions were used to analyze the association between developing type 2 diabetes and the age at first childbirth. Adjustments were made in each model on sociodemographic, socioeconomic and reproductive covariates. Subgroup analyses were further carried out to investigate the effects of reproductive factors, body mass index at 25 years of age and hypertension on the above‐mentioned association.

Results

Women who have their first child at age <20 years (odds ratio [OR] 1.33, 95% confidence interval [CI] 1.22–1.44) and between the ages of 20 and 24 years (OR 1.16, 95% CI 1.10–1.23) were more likely to be diagnosed with type 2 diabetes compared with those who have their first child between the ages of 25 and 29 years; equal to or more than three parities (OR 1.44, 95% CI 1.30–1.60), premenopausal status (OR 1.58, 95% CI 0.99–2.54), overweight at age 25 years (OR 1.62, 95% CI 1.37–1.93) and hypertension (OR 1.37, 95% CI 1.22–1.53) are all conditions found to increase the odds of developing type 2 diabetes in those who have their their first child at an early age (<20 years).

Conclusions

The study concluded that having the first child at an early age is associated with an increased likelihood of developing type 2 diabetes later in life; reproductive factors, overweight at age 25 years and status of hypotension could modify such an association.
The profile of cytokines (IL‐2, IFN‐γ, IL‐4, IL‐10, IL‐17A, and IL‐23) in active alopecia areata
Authors: Gautam Ram Kishan , Singh Yogita , Gupta Aastha , Arora Pooja , Khurana Ananta , Chitkara Anubhuti
Published: May 2019

Background

Alopecia areata (AA) is an autoimmune disease due to aberrant T‐cell response against hair follicle self‐antigens. Previous studies support the role of Th1 cytokines in pathogenesis of AA, but the role of Th2, Th17, and Treg cytokines remains to be fully elucidated.

Objectives

To assess the serum levels of cytokines secreted by Th1 (IL‐2, IFN‐γ), Th2 (IL‐4), Th17 (IL‐23, IL‐17A), and Treg (IL‐10) pathways in patients of active AA and to correlate their levels with the severity of the disease.

Material and methods

Forty patients with untreated active AA of the scalp and forty age‐ and sex‐matched healthy controls were included. Serum levels of cytokines IL‐2, IFN‐γ, IL‐17A, IL‐23, IL‐4, and IL‐10 were measured using enzyme‐linked immunosorbent assay.

Results

Serum levels of cytokines IL‐2, IFN‐γ, IL‐17A, and IL‐10 were significantly raised while serum levels of IL‐23 were nonsignificantly raised in AA patients as compared to controls. The levels of IL‐4 were significantly lower in AA patients as compared to controls. (P < 0.05). Also, significant positive correlation was found between increase in SALT Score and serum levels of IL‐2, IL‐17A, and IL‐23. (P < 0.05).

Conclusion

Th1 and Th17 pathways play a central role in the initiation and progression of AA, while Th2 pathway is suppressed in active AA. Treg pathway may be opposing Th1 and Th17 pathway and causes disease localization. The instant study lays the groundwork for understanding the pathogenesis of AA and suggests the role of implicated cytokines as potential therapeutic targets and as biomarkers of disease activity.
Roadmap to functional cure of chronic hepatitis B: An expert consensus
Authors: Ning Qin , Wu Di , Wang Gui-Qiang , Ren Hong , Gao Zhi-Liang , Hu Peng , Han Mei-Fang , Wang Yan , Zhang Wen-Hong , Lu Feng-Min , Wang Fu‐Sheng
Published: May 2019

Hepatitis B virus (HBV) infection continues to be a major public health issue worldwide. HBsAg loss is associated with functional remission and improved long‐term outcome, and is considered to be a ‘functional cure’ (also referred to as clinical or immunologic cure) for chronic hepatitis B. This ideal goal of therapy can be achieved using optimized combination regimens with direct‐acting antivirals [eg nucleos(t)ide analogues (NAs)] and immunomodulators [eg pegylated interferon alpha2a (Peg‐IFN)] in selected patients with chronic hepatitis B. Among different combination therapies currently available, those with NA lead‐in followed by Peg‐IFN in virally suppressed patients has been demonstrated to be effective. This review provides an updated overview of the evidence supporting the use of combination therapies and summarizes expert consensus on the roadmap to attain functional cure for chronic hepatitis B patients.
Soil seed banks in the floodplain of a large river: A test of hypotheses on seed bank composition in relation to flooding and established vegetation
Authors: Greulich Sabine , Chevalier Richard , Villar Marc
Published: May 2019

Questions

This study investigates soil seed banks in relation to established vegetation in the floodplain of a large river with high‐energy floods. It addresses the composition of seed banks and extant vegetation over a wide flooding and succession gradient. Tested hypotheses were: (a) species richness and seed bank density are highest in mid‐succession habitats; (b) seed bank variability increases with succession; (c) the proportion of species in the established vegetation with permanent seed banks declines with succession; and (d) similarity between vegetation and seed bank declines with succession.

Location

Mareau‐aux‐Prés, the Loire River, close to Orléans, France.

Methods

Seed banks and vegetation were sampled in five habitats from a succession series: (a) Pioneer vegetation of shores and sandbanks; (b) softwood shrubs; (c) softwood forest; (d) mature forest; and (e)Elytrigia‐dominated grasslands. Sample units were 5 m × 5 m plots. Soil samples were taken from the upper 6 cm. Seed banks were studied via the seedling emergence method, followed by screening of sediment for remaining seeds. Composition of seed banks was compared to that of vegetation using the Sørenson similarity index.

Results

Seed bank density varied between 260 and 11,260 seeds/m2. Clear differences between habitats existed in the composition of species in seed banks and established vegetation. Seeds of most dominant species were distributed across the whole range of floodplain habitats but species were more restricted in the vegetation. Species richness and seed bank densities did not vary with succession as expected, but the proportion of species that produce persistent seed banks did decline with succession.

Conclusions

Floodplains of large rivers provide an excellent context to test hypotheses about the processes that influence the links between seed banks and standing vegetation. In the case of high‐energy floods and high sediment dynamics, the methods commonly used to study seed banks can, however, be questioned.
The effects of impacts on the cooling rates of iron meteorites
Authors: Lyons Richard J. , Bowling Timothy J. , Ciesla Fred J. , Davison Thomas M. , Collins Gareth S.
Published: May 2019

Iron meteorites provide a record of the thermal evolution of their parent bodies, with cooling rates inferred from the structures observed in the Widmanstätten pattern. Traditional planetesimal thermal models suggest that meteorite samples derived from the same iron core would have identical cooling rates, possibly providing constraints on the sizes and structures of their parent bodies. However, some meteorite groups exhibit a range of cooling rates or point to uncomfortably small parent bodies whose survival is difficult to reconcile with dynamical models. Together, these suggest that some meteorites are indicating a more complicated origin. To date, thermal models have largely ignored the effects that impacts would have on the thermal evolution of the iron meteorite parent bodies. Here we report numerical simulations investigating the effects that impacts at different times have on cooling rates of cores of differentiated planetesimals. We find that impacts that occur when the core is near or above its solidus, but the mantle has largely crystallized can expose iron near the surface of the body, leading to rapid and nonuniform cooling. The time period when a planetesimal can be affected in this way can range between 20 and 70 Myr after formation for a typical 100 km radius planetesimal. Collisions during this time would have been common, and thus played an important role in shaping the properties of iron meteorites.
Genome‐scale sampling suggests cryptic epigenetic structuring and insular divergence in Canada lynx
Authors: Meröndun Justin , Murray Dennis L. , Shafer Aaron B. A.
Published: May 2019

Determining the molecular signatures of adaptive differentiation is a fundamental component of evolutionary biology. A key challenge is to identify such signatures in wild organisms, particularly between populations of highly mobile species that undergo substantial gene flow. The Canada lynx (Lynx canadensis) is one species where mainland populations appear largely undifferentiated at traditional genetic markers, despite inhabiting diverse environments and displaying phenotypic variation. Here, we used high‐throughput sequencing to investigate both neutral genetic structure and epigenetic differentiation across the distributional range of Canada lynx. Newfoundland lynx were identified as the most differentiated population at neutral genetic markers, with demographic modelling suggesting that divergence from the mainland occurred at the end of the last glaciation (20–33 KYA). In contrast, epigenetic structure revealed hidden levels of differentiation across the range coincident with environmental determinants including winter conditions, particularly in the peripheral Newfoundland and Alaskan populations. Several biological pathways related to morphology were differentially methylated between populations, suggesting that epigenetic modifications might explain morphological differences seen between geographically peripheral populations. Our results indicate that epigenetic modifications, specifically DNA methylation, are powerful markers to investigate population differentiation in wild and non‐model systems.
Virus perception at the cell surface: revisiting the roles of receptor‐like kinases as viral pattern recognition receptors
Authors: Teixeira Ruan M. , Ferreira Marco Aurélio , Raimundo Gabriel A. S. , Loriato Virgílio A. P. , Reis Pedro A. B. , Fontes Elizabeth P. B.
Published: May 2019

Activation of antiviral innate immune responses depends on the recognition of viral components or viral effectors by host receptors. This virus recognition system can activate two layers of host defence, pathogen‐associated molecular pattern (PAMP)‐triggered immunity (PTI) and effector‐triggered immunity (ETI). While ETI has long been recognized as an efficient plant defence against viruses, the concept of antiviral PTI has only recently been integrated into virus–host interaction models, such as the RNA silencing‐based defences that are triggered by viral dsRNA PAMPs produced during infection. Emerging evidence in the literature has included the classical PTI in the antiviral innate immune arsenal of plant cells. Therefore, our understanding of PAMPs has expanded to include not only classical PAMPS, such as bacterial flagellin or fungal chitin, but also virus‐derived nucleic acids that may also activate PAMP recognition receptors like the well‐documented phenomenon observed for mammalian viruses. In this review, we discuss the notion that plant viruses can activate classical PTI, leading to both unique antiviral responses and conserved antipathogen responses. We also present evidence that virus‐derived nucleic acid PAMPs may elicit the NUCLEAR SHUTTLE PROTEIN‐INTERACTING KINASE 1 (NIK1)‐mediated antiviral signalling pathway that transduces an antiviral signal to suppress global host translation.
Land value capture: The impossible tax
Authors: Loo Edwin
Published: May 2019

Lessons from Singapore
The role of leaf width and conductances to CO2 in determining water use efficiency in C4 grasses
Authors: Cano Francisco Javier , Sharwood Robert E. , Cousins Asaph B. , Ghannoum Oula
Published: May 2019

C4 plants achieve higher photosynthesis (An) and intrinsic water use efficiency (iWUE) than C3 plants, but processes underpinning the variability in An and iWUE across the three C4 subtypes remain unclear, partly because we lack an integrated framework for quantifying the contribution of diffusional and biochemical limitations to C4 photosynthesis.

We exploited the natural diversity among C4 grasses to develop an original mathematical approach for estimating eight key processes of C4 photosynthesis and their relative limitations to An. We also developed a new formulation to estimate mesophyll conductance (gm) based on actual hydration rates of CO2 by carbonic anhydrases.

We found a positive relationship between gm and iWUE and an inverse correlation with gsw among C4 grasses. We also revealed subtype‐specific regulatory processes of iWUE that may be related to known anatomical traits characterising each C4 subtype. Leaf width was an important determinant of iWUE and showed significant correlations with key limitations of An, especially among NADP‐ME species.

In conclusion, incorporating leaf width in breeding trials may unlock new opportunities for C4 crops because the revealed negative relationship between leaf width and iWUE may translate into higher crop and canopy WUE.