bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel transcription factor negatively regulates antioxidant response, cell wall integrity and virulence in the fungal insect pathogen, Beauveria bassiana
Authors: Zhao Xin , Luo Tingying , Huang Shuaishuai , Peng Ning , Yin Ying , Luo Zhibing , Zhang Yongjun
Published: January 2021

Genomic data have identified a class of fungal specific transcription factors (FsTFs) that are thought to regulate unique aspects of fungal gene expression, although the functions of many of these proteins remain unknown. Here, a novel FsTF (BbStf1), which features a leucine zipper dimerization domain and a fungal transcription factor regulatory middle homology region, was characterized in Beauveria bassiana, a filamentous insect fungal pathogen. Transcriptional activation and nuclear localization were experimentally confirmed for BbStf1. Disruption of Bbstf1 resulted in increased tolerance to oxidative stress and cell wall perturbation, accompanied by increased peroxidase (POD) and superoxide dismutase (SOD) activities and ratio of reduced/oxidized glutathione (GSH/GSSG), and by thickened cell wall and altered composition. Gene expression profile analysis revealed that transcription patterns of antioxidant enzyme and cell wall integrity‐involved genes were altered in the ∆Bbstf1, including some BbStf1‐targeted genes clarified with evidence. The ∆Bbstf1 strain displayed greater virulence to Galleria mellonella in the bioassays through both topical infection and intrahaemocoel injection due to more rapid proliferation in the haemocoel as compared to the wild‐type strain. Altogether, BbStf1 acts as a negative regulator of antioxidant response, cell wall integrity and virulence in B. bassiana.
A novel antisense long non‐coding RNA participates in asexual and sexual reproduction by regulating the expression of GzmetE in Fusarium graminearum
Authors: Wang Jie , Zeng Wenping , Xie Jiatao , Fu Yanping , Jiang Daohong , Lin Yang , Chen Weidong , Cheng Jiasen
Published: January 2021

Fusarium graminearum is an important worldwide pathogen that causes Fusarium head blight in wheat, barley, maize and other grains. LncRNAs play important roles in many biological processes, but little is known about their functions and mechanisms in filamentous fungi. Here, we report that a natural antisense RNA, GzmetE‐AS, is transcribed from the opposite strand of GzmetE. GzmetE encodes a homoserine O‐acetyltransferase, which is important for sexual development and plant infection. The expression of GzmetE‐AS was increased significantly during the conidiation stage, while GzmetE was upregulated in the late stage of sexual reproduction. Overexpression of GzmetE‐AS inhibited the transcription of GzmetE. In contrast, the expression of GzmetE was significantly increased in GzmetE‐AS transcription termination strain GzmetE‐AS‐T. Furthermore, GzmetE‐AS‐T produced more perithecia and facilitated the ascospore discharge, resembling the phenotype of GzmetE overexpressing strains. However, overexpression of GzmetE‐AS in ∆dcl1/2 strain cannot inhibit the expression of GzmetE, and the GzmetE nat‐siRNA is also significantly reduced in ∆dcl1/2 mutant. Taken together, we have identified a novel antisense lncRNA GzmetE‐AS, which is involved in asexual and sexual reproduction by regulating its antisense gene GzmetE through RNAi pathway. Our findings reveal that the lncRNA plays critical roles in the development of F. graminearum.
Assessment of Overseas Subsidiary Survival in Chinese Provinces: A Longitudinal Study of Indian Multinationals
Authors: Das Khanindra Ch. , Mahalik Mantu Kumar
Published: January 2021

This study provides a longitudinal survival assessment of Indian subsidiaries in Chinese provinces. We construct a panel dataset of Indian subsidiaries operating in Chinese provinces during 2004–2017 and examine survival using a panel probit model and Cox regression. The results support the real options perspective, the economic geography approach and the institution‐based view. Subsidiary exits were associated with smaller size, albeit higher in the manufacturing sector. There is a positive impact of sub‐national economic geography factors on subsidiary survival. The finding contributes to the South–South investment literature as it highlights the role of sub‐national factors in shaping subsidiary survival.
International Best Practice and the Constitution, Democracy and Rights Commission
Authors: Schleiter Petra , Fleming Thomas G.
Published: January 2021

The UK government has pledged to establish a Constitution, Democracy and Rights Commission. This body will have a wide remit to recommend potentially sweeping constitutional change. This article draws on international experience and best practice to outline how the commission might best organise the process to produce proposals which are widely supported, fit for purpose, and durable. We argue that to achieve these goals the commission’s organisation should reflect three key principles: impartiality, expertise, and public participation. This would reflect international best practice and build on recent domestic developments. We argue that these principles can best be achieved if the commission works through a citizens’ assembly that combines members of the public with party politicians. This would be a new departure for the UK, but a necessary one given the scale of the government’s constitutional reform agenda, and its stated goal of restoring public trust in politics.
Triplication of small bowel with perforated peptic ulcer: Report of a rarity with literature review
Authors: Joda Ali Egab , Hussein Nawzat
Published: January 2021

Triplication of small bowel is an extremely rare variant of enteric duplication with only one previously reported case in a neonate. Most enteric duplications are presented in neonates as intestinal obstruction. Herein we present a case of 3‐year‐old girl with acute abdomen due to perforation of triplicated ileum aiming to highlight the characteristic presenting features, the diagnostic difficulties and challenges of surgical intervention for this condition.
Effects of stem removal on physicochemical properties and sensory quality of tencha beverages (Camellia sinensis; Chuanxiaoye)
Authors: Xiao Zhipeng , Tao Meng , Liu Zhengquan
Published: January 2021

Fresh tea leaves (Camellia sinensis; Chuanxiaoye) used to make tencha tea are a combination of the stem and leaf. Tencha made from the leaf alone is considered a high‐quality tencha beverage with a seaweed‐like aroma, mellow taste, and a green appearance. However, no study has investigated the differences between these two variants. In this study, the effects of stem removal on physicochemical properties and sensory quality of tencha beverage were investigated. The appearance feature, taste, and aroma were evaluated, and the results indicated that stem removal improved the quality of tencha beverages. The water extract, total free amino acids, total catechin, epigallocatechin gallate, caffeine, and chlorophyll were higher in leaf‐only tencha (LOT) than in leaf and stem tencha (LST), whereas the crude fiber and phenol ammonia ratios were lower in LOT than in LST. Principal component analysis and hierarchical clustering analysis further discriminated between the tencha beverages with different stem contents. This study provided a theoretical basis for quality control by adopting a stem–leaf separation process in tencha manufacturing.

Practical Application

This research provides theoretical guidance for improving tencha quality during manufacturing.
Protective effect of Ganoderma lucidum spore extract in trimethylamine‐N‐oxide‐induced cardiac dysfunction in rats
Authors: Liu Yadi , Lai Guoxiao , Guo Yinrui , Tang Xiaocui , Shuai Ou , Xie Yizhen , Wu Qingping , Chen Diling , Yuan Xujiang
Published: January 2021

Previous research has shown that the extracts from the Ganoderma lucidum spore (GS) have potentially cardioprotective effects, but there is still abundant room for development in determining its mechanism. In this study, the rat model of cardiac dysfunction was established by intraperitoneal injection of trimethylamine‐N‐oxide (TMAO), and the extracts of GS (oil, lipophilic components, and polysaccharides) were given intragastrically at a dose of 50 mg/kg/day to screen the pharmacological active components of GS. After 50 days of treatments, we found that the extraction from GS reduced the levels of total cholesterol, triglyceride, and low‐density lipoprotein; increased the levels of high‐density lipoprotein; and reduced the levels of serum TMAO when compared to the model group (P < 0.05); especially the GS polysaccharides (DT) and GS lipophilic components (XF) exhibited decreases in serum TMAO compared to TMAO‐induced control. The results of 16S rRNA sequencing showed that GS could change the gut microbiota, increasing the abundance of Firmicutes and Proteobacteria in the DT‐treated group and XF‐treated group, while reducing the abundance of Actinobacteria and Tenericutes. Quantitative proteomics analysis showed that GS extracts (DT and XF) could regulate the expression of some related proteins, such as Ucp1 (XF‐TMAO/M‐TMAO ratio is 2.76), Mpz (8.52), Fasn (2.39), Nefl (1.85), Mtnd5 (0.83), Mtnd2 (0.36), S100a8 (0.69), S100a9 (0.70), and Bdh1 (0.72). The results showed that XF can maintain the metabolic balance and function of the heart by regulating the expression of some proteins related to cardiovascular disease, and DT can reduce the risk of cardiovascular diseases by targeting gut microbiota.
Influence of cellulose nanocrystals gellan gum‐based coating on color and respiration rate of Agaricus bisporus mushrooms
Authors: Criado Paula , Fraschini Carole , Shankar Shiv , Salmieri Stephane , Lacroix Monique
Published: January 2021

The edible coating has been used for covering fruits and vegetables, bringing surface protection, and extending product shelf‐life. Due to the outstanding properties, nanomaterials have become a part of the packaging/coating new generation, demonstrating improvements in the barrier capacity of materials starting from construction products to the food industry. In the food industry, on the other hand, Agaricus bisporus mushrooms have a limited shelf‐life from 1 to 3 days because of their high respiration rate and enzymatic browning. With the aim to reduce these two parameters and prevent rapid senescence, the objective of this study was to incorporate a natural source of nanomaterials (cellulose nanocrystals (CNCs) into a gellan gum‐based coating and sprayed the surface of the mushrooms with the coating material. To evaluate the effect of CNCs, oxygen consumption, carbon dioxide production rate, and color change were recorded during the mushroom storage at 4 ± 1 °C. Results showed that all coatings were able to decrease total color change (ΔE) of mushrooms from 12 to 8 at day 10 when the coating was applied in all samples compared to control. In addition, significant differences were observed in the respiration rate when CNCs were added to the mushrooms. Oxygen consumption results exhibited a 44 mL O2/kg · day production at day 5 with 20% CNCs compared to 269 mL O2/kg · day observed in noncoated samples. This trend was similarly observed in the carbon dioxide production rate.

Practical Application

With this research, it was remarkable to see the presence of CNCs in the coating solution reduced the respiration rate and increased the shelf‐life of mushrooms. Similar applications can be industrially scaled‐up to protect fruits and vegetables by CNCs‐based coating or packaging materials. A variety of sustainable materials are available nowadays that serve as packaging matrix, and scientists are working on expanding the compatibility of these nanomaterials. In addition, it has been studied that CNCs enhance the degradation of polymers, an effort that many companies are making to reduce the environmental impact in their products.
The Ocean barcode atlas: A web service to explore the biodiversity and biogeography of marine organisms
Authors: Vernette Caroline , Henry Nicolas , Lecubin Julien , de Vargas Colomban , Hingamp Pascal , Lescot Magali
Published: January 2021

The Ocean Barcode Atlas (OBA) is a user friendly web service designed for biologists who wish to explore the biodiversity and biogeography of marine organisms locked in otherwise difficult to mine planetary scale DNA metabarcode data sets. Using just a web browser, a comprehensive picture of the diversity of a taxon or a barcode sequence is visualized graphically on world maps and interactive charts. Interactive results panels allow dynamic threshold adjustments and the display of diversity results in their environmental context measured at the time of sampling (temperature, oxygen, latitude, etc). Ecological analyses such as alpha and beta‐diversity plots are produced via publication quality vector graphics representations. Currently, the Ocean Barcode Altas is deployed online with the (i) Tara Oceans eukaryotic 18S‐V9 rDNA metabarcodes; (ii) Tara Oceans 16S/18S rRNA miTags; and (iii) 16S‐V4 V5 metabarcodes collected during the Malaspina‐2010 expedition. Additional prokaryotic or eukaryotic plankton barcode data sets will be added upon availability, given they provide the required complement of barcodes (including raw reads to compute barcode abundance) associated with their contextual environmental variables. Ocean Barcode Atlas is a freely‐available web service at: http://oba.mio.osupytheas.fr/ocean‐atlas/.
Ruptured pseudoaneurysm of the thoracic aorta mimicking lung cancer: A case report
Authors: Takahara Yutaka , Nishiki Kazuaki , Nakase Keisuke , Mizuno Shiro
Published: January 2021

A 70‐year‐old woman was admitted to a local hospital with a five‐day history of back pain. She had been referred to our hospital after an abnormal chest shadow was identified on chest X‐ray. Chest computed tomography (CT) revealed an anterior mediastinal mass in the upper lobe of the left lung. Her general condition was good. She was diagnosed with lung cancer, and examination was planned. However, respiratory failure rapidly worsened on hospital day 2, and a ruptured pseudoaneurysm of the thoracic aorta (PTA) was diagnosed from contrast‐enhanced CT. Emergency thoracic endovascular aortic repair was successfully performed, and her postoperative course was uneventful. The hemodynamics of the PTA were stable in the case of this patient, but the risk of rupture is extremely high and frequently fatal. PTA should therefore be included among the differential diagnoses of mediastinal tumor.

Key points

Significant findings of the study

Pseudoaneurysm of the thoracic aorta (PTA) may present on imaging findings that resemble lung cancer.

What this study adds

PTA should be included among the differential diagnoses of mediastinal tumor. Clinicians therefore need to be familiar with the imaging findings of PTA.
Increased Synaptic Strength and mGlu2/3 Receptor Plasticity on Mouse Prefrontal Cortex Intratelencephalic Pyramidal Cells Following Intermittent Access to Ethanol
Authors: Joffe Max E. , Winder Danny G. , Conn P Jeffrey
Published: January 2021

Background

The medial prefrontal cortex (PFC) is crucial for regulating craving and alcohol seeking in alcohol use disorder (AUD) patients and alcohol seeking in animal models. Maladaptive changes in volitional ethanol (EtOH) intake have been associated with PFC function, yet synaptic adaptations within PFC have not been consistently detected in voluntary drinking rodent models. At least 80% of the neurons in PFC are glutamatergic pyramidal cells. Pyramidal cells provide the predominant cortical output to several brain regions relevant to AUD, including structures within the telencephalon (IT: e.g., basal ganglia, amygdala, other neocortical regions) and outside the telencephalon (ET: e.g., lateral hypothalamus, midbrain monoaminergic structures, thalamus).

Methods

In addition to their anatomical distinctions, studies from several laboratories have revealed that prefrontal cortical IT and ET pyramidal cells may be differentiated by specific electrophysiological parameters. These distinguishable parameters make it possible to readily classify pyramidal cells into separable subtypes. Here, we employed and validated the hyperpolarization sag ratio as a diagnostic proxy for separating ET (type A) and IT (type B) neurons. We recorded from deep‐layer prelimbic PFC pyramidal cells of mice 1 day after 4 to 5 weeks of intermittent access (IA) EtOH exposure.

Results

Membrane properties were not altered by IA EtOH, but excitatory postsynaptic strength onto IT type B neurons was selectively enhanced in slices from IA EtOH mice. The increased excitatory drive was accompanied by enhanced mGlu2/3 receptor plasticity on IT type B neurons, providing a potential translational approach to mitigate cognitive and motivational changes to PFC function related to binge drinking.

Conclusions

Together, these studies provide insight into the specific PFC neurocircuits altered by voluntary drinking. In addition, the findings provide an additional rationale for developing compounds that potentiate mGlu2 and/or mGlu3 receptor function as potential treatments for AUD.
Early Identification of Alcohol Use Disorder Patients at Risk of Developing Korsakoff’s Syndrome
Authors: Ritz Ludivine , Laniepce Alice , Cabé Nicolas , Lannuzel Coralie , Boudehent Céline , Urso Laurent , Segobin Shailendra , Vabret François , Beaunieux Hélène , Pitel Anne‐Lise
Published: January 2021

Background

The aim of the present study was to determine whether the Brief Evaluation of Alcohol‐Related Neuropsychological Impairments (BEARNI), a screening tool developed to identify neuropsychological deficits in alcohol use disorder (AUD) patients, can also be used for the early identification of AUD patients at risk of developing Korsakoff’s syndrome (KS).

Methods

Eighteen KS patients, 47 AUD patients and 27 healthy controls underwent BEARNI testing (including 5 subtests targeting episodic memory, working memory, executive function, visuospatial abilities, and ataxia) and a comprehensive neuropsychological examination.

Results

Performance of AUD and KS patients on BEARNI subtests was consistent with the results on the standardized neuropsychological assessment. On BEARNI, ataxia and working memory deficits observed in AUD were as severe as those exhibited by KS patients, whereas for visuospatial abilities, a graded effect of performance was found. In contrast, the subtests involving long‐term memory abilities (episodic memory and fluency) were impaired in KS patients only. AUD patients with a score lower than 1.5 points (out of 6) on the episodic memory subtest of BEARNI exhibited the lowest episodic memory performance on the neuropsychological battery and could be considered at risk of developing KS.

Conclusions

These findings suggest that BEARNI is a useful tool for detecting severe memory impairments, suggesting that it could be used for the early identification of AUD patients at high risk of developing KS.
What should every dental health professional know about electronic cigarettes?
Authors: Briggs K , Bell C , Breik O
Published: January 2021

Electronic cigarettes (E‐cigarettes) have become increasingly popular around the world. Currently, dental professionals’ knowledge and attitudes are varied with many clinicians unclear regarding the impact of E‐cigarette products on the oral and general health of their patients. With developing social and health‐related challenges, advice of dental and medical associations and other regulatory bodies on E‐cigarette use is changing. Growing evidence demonstrating the risks of E‐cigarette usage has prompted a review of legislation in the United Kingdom (UK), United States of America (USA), Australia and Canada to include the sale and availability of E‐cigarettes, particularly those containing nicotine. Further consideration within the scientific and public health community is being given to assessing demographic usage patterns particularly uptake by non‐smokers and adolescents, efficacy as a cessation tool, the impact of vapour on bystanders and direct injuries via explosions as well as emerging lung injuries. This article aims to provide a summary of the most up to date evidence relating to E‐cigarette use, the latest position of dental associations and the oral health implications of E‐cigarettes compared to conventional smoking. The article also aims to collate this information in order to provide dental clinicians with guidance on how to advise patients, specifically in answering common questions posed regarding E‐cigarette use.
Dental professionals’ perspectives working with Aboriginal children in Western Australia: a qualitative study
Authors: Durey A , Hearn L , Lund S , O’Grady M , Slack‐Smith L
Published: January 2021

Background

The disproportionate burden of oral disease in Aboriginal children and the issues in accessing mainstream dental services are well documented. Yet little is known about dental professionals’ perspectives in providing oral care for Aboriginal children. This paper presents findings from a study exploring such perspectives.

Methods

Semi‐structured interviews were carried out in Western Australia following purposive sampling of non‐Aboriginal dentists, dental clinic assistants (dental nurses) and oral health therapists/dental hygienists. Interviews were recorded, transcribed and analysed guided by grounded theory for key themes related to the topic.

Results

Findings included a service delivery model sometimes unresponsive to Aboriginal families’ needs; dental professionals’ limited education and training to work with confidence and cultural sensitivity with Aboriginal patients and socioeconomic influences on Aboriginal children’s poor oral health considered outside dental professionals’ remit of care.

Discussion

Findings suggest oral health policies and practices and dental professionals’ education and training need reviewing for how well such policies support dental professionals in an Aboriginal context. This includes engaging with Aboriginal stakeholders, working effectively with Aboriginal families, and developing shared understandings about what is needed to increase access to care and improve oral health outcomes for Aboriginal children.
Understanding valvular heart disease in the dental setting
Authors: Truong T , Koh Y , Yosufi R , Marangou J , Slack‐Smith L , Katzenellenbogen JM
Published: January 2021

Background

Limited evidence is available regarding dentists’ knowledge and interpretation of infective endocarditis (IE) prophylaxis guidelines. The aim of this study was to determine understanding and management of rheumatic and non‐rheumatic valvular heart disease (VHD) in the dental setting in Western Australia (WA).

Methods

A cross‐sectional survey of dentists within Perth utilized an online Qualtrics questionnaire developed after consultation with stakeholders. A sampling frame was compiled from the Australian Health Practitioner Regulation Agency with contact details obtained from the White Pages (online), using five quintiles of Socio‐Economic Indexes for Areas according to dentist’s place of practice.

Results

Of 41 (13.7% of 300 approached) dentists completing the survey (95.1% general dentists, mean years of practice = 15.6), 90.2% reported following the Australian Therapeutic Guidelines (ATG) regarding IE antibiotic prophylaxis in VHD. Most (92.7%) were unaware of the rheumatic heart disease (RHD) control program. Nearly all participants indicated prophylaxis for clearly invasive procedures such as tooth extraction (100.0%) and periodontal surgery (95.1%). Many dentists made the decision to prescribe antibiotics themselves (36.6%).

Conclusions

The majority of dentists followed the ATG’s IE prophylaxis recommendations for cardiac lesions and dental procedures. There was limited knowledge of the national RHD guidelines and the WA RHD control program.
New evidence regarding the effects of contract farming on agricultural labor use
Authors: Ruml Anette , Qaim Matin
Published: January 2021

Contractual agreements between smallholder farmers and agribusiness companies have gained in importance in many developing countries. While productivity and income effects of contracting in the small farm sector were analyzed in many previous studies, labor market and employment effects are not yet well understood. This is an important research gap, especially against the background of continued population growth and structural transformation. Here, we investigate the effects of two types of contractual agreements between large international processing companies and smallholder farmers on agricultural labor use, household labor allocation, and hired labor demand in Ghana's palm oil sector. We use cross‐sectional survey data and a willingness‐to‐pay approach to control for unobserved heterogeneity between farmers with and without contracts. We find that agricultural labor intensity is substantially reduced through the contracts, because contracting in Ghana is associated with the adoption of labor‐saving procedures and technologies. Simple marketing contracts lead to reallocation of the saved household labor to off‐farm employment, whereas resource‐providing contracts lead to a stronger reallocation of labor within the farming enterprise. Household labor is more affected by labor savings than hired labor.
Letter: hidden costs in healthcare use for incident and prevalent Crohn's disease and ulcerative colitis
Authors: Lord Anton , Radford‐Smith Graham
Published: January 2021

LINKED CONTENT

This article is linked to Khalili et al paper. To view this article, visit https://doi.org/10.1111/apt.15889
Two‐stage penalized regression screening to detect biomarker–treatment interactions in randomized clinical trials
Authors: Wang Jixiong , Patel Ashish , Wason James M.S. , Newcombe Paul J.
Published: January 2021

High‐dimensional biomarkers such as genomics are increasingly being measured in randomized clinical trials. Consequently, there is a growing interest in developing methods that improve the power to detect biomarker–treatment interactions. We adapt recently proposed two‐stage interaction detecting procedures in the setting of randomized clinical trials. We also propose a new stage 1 multivariate screening strategy using ridge regression to account for correlations among biomarkers. For this multivariate screening, we prove the asymptotic between‐stage independence, required for familywise error rate control, under biomarker–treatment independence. Simulation results show that in various scenarios, the ridge regression screening procedure can provide substantially greater power than the traditional one‐biomarker‐at‐a‐time screening procedure in highly correlated data. We also exemplify our approach in two real clinical trial data applications.
What influences adherence to guidance for postoperative instillation of intravesical chemotherapy to patients with bladder cancer?
Authors: Dunsmore Jennifer , Duncan Eilidh , Mariappan Paramananthan , de Bruin Marijn , MacLennan Sara , Dimitropoulos Konstantinos , Kasivisvanathan Veeru , Mostafid Hugh , Briganti Alberto , N’Dow James , MacLennan Steven
Published: January 2021

Objective

To understand the barriers and facilitators to single instillation of intravesical chemotherapy (SI‐IVC) use after resection of non‐muscle‐invasive bladder cancer (NMIBC) in Scotland and England using a behavioural theory‐informed approach.

Subjects and Methods

In a cross‐sectional descriptive study of practices at seven hospitals, we investigated care pathways, policies, and interviewed 30 urology staff responsible for SI‐IVC. We used the Theoretical Domains Framework (TDF) to organise our investigation and conducted deductive thematic analyses, while inductively coding emergent beliefs.

Results

Barriers to SI‐IVC were present at different organisational levels and professional roles. In four hospitals, there was a policy to not instil SI‐IVC in theatre. Six hospitals’ staff reported delays in mitomycin C (MMC) ordering and/or local storage. Lack of training, skills and perceived workload affected motivation. Facilitators included access to modern instilling devices (four hospitals) and incorporating reminders in operation proforma (four hospitals). Performance targets (with audit and feedback) within a national governance framework were present in Scotland but not England. Differences in coordinated leadership, sharing best practices, and disliking being perceived as underperforming, were evident in Scotland.

Conclusions

High‐certainty evidence shows that SI‐IVC, such as MMC, after NMIBC resection reduces recurrences. This evidence underpins international guidance. The number of eligible patients receiving SI‐IVC is variable indicating suboptimal practice. Improving SI‐IVC adherence requires modifications to theatre instilling policies, delivery and storage of MMC, staff training, and documentation. Centralising care, with bladder cancer expert leadership and best practices sharing with performance targets, likely led to improvements in Scotland. National quality improvement, incorporating audit and feedback, with additional implementation strategies targeted to professional role could improve adherence and patient outcomes elsewhere. This process should be controlled to clarify implementation intervention effectiveness.
Can foreign direct investment foster the manufacturing industries’ spatial total factor productivity convergence in a transition economy? An empirical approach from Vietnam
Authors: Pham Anh Tuan , Nguyen Minh Khac , Dang Hoang Linh , Nguyen Thi Xuan Thu
Published: January 2021

This study tries to examine the influence of foreign direct investment (FDI) on the total factor productivity (TFP) convergence of the manufacturing industries in Vietnamese provinces. We find that the convergence rates estimated using spatial lag and error models are larger than those implied by panel data models that do not consider spatial dependence. The spatial dependence of TFP growth in the provinces is due to geographical TFP and FDI spillovers. Our findings indicate that studies on the convergence rate of regions should check for spatial dependence.
STAT3/NF‐κB signalling disruption in M2 tumour‐associated macrophages is a major target of PLGA nanocarriers/PD‐L1 antibody immunomodulatory therapy in breast cancer
Authors: Cavalcante Rômulo S. , Ishikawa Uta , Silva Emanuell S. , Silva‐Júnior Arnóbio A. , Araújo Aurigena A. , Cruz Luis J. , Chan Alan B. , de Araújo Júnior Raimundo F.
Published: January 2021

Background and Purpose

Inflammation associated with the tumour microenvironment (TME) is critical for cancer development, and immunotherapeutic strategies modulating the immune response in cancer have been crucial. In this study, a methotrexate‐loaded (MTX) poly(lactic‐co‐glycolic acid)‐based (PLGA) drug nanocarrier covered with polyethyleneimine (Pei) and hyaluronic acid (HA) was developed and combined with an PD‐L1 antibody to investigate anti‐cancer and immunomodulatory effects in breast cancer TME.

Experimental Approach

Naked or HA‐coated PeiPLGA‐MTX nanoparticles (NPs) were assessed on 4T1 breast cancer cells grown in culture and in a mouse model of orthotopic tumour growth. Tumours were evaluated by qRT‐PCR and immunohistochemistry. The cell death profile and cell migration were analysed in vitro in 4T1 cells. Polarization of murine macrophages (RAW cells) was also carried out.

Key Results

Naked or HA‐coated PeiPLGA‐MTX NPs used alone or combined with PD‐L1 antibody modified the tumourigenic course by TME immunomodulation, leading to reduction of primary tumour size and metastases. STAT3 and NF‐κB were the major genes downregulated by NPs. In tumor‐associated macrophages (TAM) such regulation switched M2 phenotype (CD163) towards M1 (CD68) and reduced levels of IL‐10, TGF‐β and CCL22. Moreover, malignant cells showed overexpression of FADD, APAF‐1, caspase‐3 and E‐cadherin, and decreased expression of Bcl‐2, MDR‐1, survivin, vimentin, CXCR4 and PD‐L1 after treatment with NPs.

Conclusion and Implications

NPs‐mediated STAT3/NF‐κB signalling axis suppression disrupted crosstalk between immune and malignant cells, reducing immunosuppression and critical pro‐tumour events. These findings provide a promising therapeutic approach capable of guiding the immune TME to suppress the development of breast cancer.
KHDRBS3 promotes multi‐drug resistance and anchorage‐independent growth in colorectal cancer
Authors: Ukai Shoichi , Sakamoto Naoya , Taniyama Daiki , Harada Kenji , Honma Ririno , Maruyama Ryota , Naka Kazuhito , Hinoi Takao , Takakura Yuji , Shimizu Wataru , Ohdan Hideki , Yasui Wataru
Published: January 2021

5‐Fluorouracil (5‐FU) is one of the most frequently used pharmacological agents in the treatment of colorectal cancer (CRC). Resistance to chemotherapy is a major cause of treatment failure of CRC, and it is a well known fact that cancer stem cells play a significant role in the acquisition of drug resistance. In this study, we focused on the KHDRBS3 gene that encodes KH RNA Binding Domain Containing, Signal Transduction Associated 3. We first clarified the relationship between KHDRBS3 and 5‐FU resistance. We then observed higher expression levels of KHDRBS3 in KRAS‐mutant organoids and cell lines in comparison with KRAS wild‐type organoids and cell lines. Immunohistochemical analysis using CRC cases revealed that the prognosis of KHDRBS3‐positive patients was significantly worse compared with that of KHDRBS3‐negative patients. Univariate and multivariate Cox proportional hazards analyses showed that KHDRBS3 was an independent prognostic factor in patients with CRC. We determined that KHDRBS3 might play a crucial role in the acquisition of stem cell properties, such as drug resistance and spheroid/organoid formation, by regulating CD44 variant expression and the Wnt signaling pathway. In an immunodeficient mouse model, KHDRBS3‐positive cells showed efficient tumor formation and formed metastatic lesions in the lungs. These results indicated that KHDRBS3 plays a crucial role in drug resistance and anchorage‐independent growth by maintaining stem cell‐like features in CRC cells. KHDRBS3 could be a promising candidate marker for predicting chemotherapeutic effect and prognosis in CRC patients.
Assessment of soft and hard tissue dimensions following different treatment approaches of ligature‐induced peri‐implantitis defects
Authors: Ramanauskaite Ausra , Obreja Karina , Sader Robert , Becker Jürgen , Schwarz Frank
Published: January 2021

Objectives

To evaluate peri‐implant tissue dimensions following nonsurgical (NS) and surgical therapy (S) employing different decontamination protocols of advanced ligature‐induced peri‐implantitis in dogs.

Material & Methods

Peri‐implantitis defects (n = 5 dogs,n = 30 implants) were randomly and equally allocated in a split‐mouth design to NS or S treatment using either an Er:YAG laser (ERL), an ultrasonic device (VUS), or plastic curettes + local application of metronidazole gel (PCM), respectively. Horizontal bone thickness (hBT) and soft tissue thickness (hMT) were measured at different reference points: (v0) at the marginal portion of the peri‐implant mucosa (PM); (v1) at 50% of the distance from PM to bone crest (BC); (v2) at the BC; (v3) at the most coronal extension of the bone‐to‐implant contact. Vertical peri‐implant tissue height was calculated from PM to BC.

Results

All of the treatment groups showed a gradual hMT increase from v0 to the v2 reference point, followed by a reduction from v2 to the v3 region. The S‐VUS subgroup tended to be associated with higher hMT values at the v0 region than the NS‐VUS subgroup (0.44 mm versus 0.31 mm). PM‐BC distance varied from 2.22 to 2.83 mm in the NS group, and from 2.07 to 2.38 in the S group.

Conclusion

Vertical and horizontal peri‐implant tissue dimensions were similar in different treatment groups.
The lost lizards of Christmas Island: A retrospective assessment of factors driving the collapse of a native reptile community
Authors: Emery Jon‐Paul , Mitchell Nicola J. , Cogger Harold , Agius Jessica , Andrew Paul , Arnall Sophie , Detto Tanya , Driscoll Don A. , Flakus Samantha , Green Peter , Harlow Peter , McFadden Michael , Pink Caitlyn , Retallick Kent , Rose Karrie , Sleeth Matthew , Tiernan Brendan , Valentine Leonie E. , Woinarski John Z.
Published: January 2021

Until recently, the reptile fauna of Christmas Island in the Indian Ocean comprised five endemic species (two skinks, two geckos, and one snake) and one native, non‐endemic skink. Four of these species were common and widespread until at least 1979, but by 2012 had disappeared from the wild. During the years of decline, little research was undertaken to examine why the species were disappearing. Here, we use a retrospective expert elicitation to rank potential factors that contributed to the loss of Christmas Island's reptiles and to assess the likelihood of re‐establishing populations of two species now listed as Extinct in the Wild. We additionally considered why one endemic lizard, the Christmas Island giant gecko (Cyrtodactylus sadleiri), and three introduced lizards remain common. Experts considered that the introduced common wolf snake (Lycodon capucinus) was the most likely cause of decline, as its temporal and spatial spread across the island closely matched patterns of lizard disappearances. An Asian co‐occurrence in recent evolutionary timeframes of the common wolf snake with the Christmas Island giant gecko and three introduced reptiles was the most marked point of difference between the extant and lost lizard species. The demise in less than 20 years of 80% of Christmas Island's native lizard assemblage highlights the vulnerability of island fauna to invading species.
Association of British Clinical Diabetologists and Renal Association guidelines on the detection and management of diabetes post solid organ transplantation
Authors: Chowdhury Tahseen A. , Wahba Mona , Mallik Ritwika , Peracha Javeria , Patel Dipesh , De Parijat , Fogarty Damian , Frankel Andrew , Karalliedde Janaka , Mark Patrick B. , Montero Rosa M. , Pokrajac Ana , Zac‐Varghese Sagen , Bain Stephen C. , Dasgupta Indranil , Banerjee Debasish , Winocour Peter , Sharif Adnan
Published: January 2021

Post‐transplant diabetes mellitus (PTDM) is common after solid organ transplantation (SOT) and associated with increased morbidity and mortality for allograft recipients. Despite the significant burden of disease, there is a paucity of literature with regards to detection, prevention and management. Evidence from the general population with diabetes may not be translatable to the unique context of SOT. In light of emerging clinical evidence and novel anti‐diabetic agents, there is an urgent need for updated guidance and recommendations in this high‐risk cohort. The Association of British Clinical Diabetologists (ABCD) and Renal Association (RA) Diabetic Kidney Disease Clinical Speciality Group has undertaken a systematic review and critical appraisal of the available evidence. Areas of focus are; (1) epidemiology, (2) pathogenesis, (3) detection, (4) management, (5) modification of immunosuppression, (6) prevention, and (7) PTDM in the non‐renal setting. Evidence‐graded recommendations are provided for the detection, management and prevention of PTDM, with suggested areas for future research and potential audit standards. The guidelines are endorsed by Diabetes UK, the British Transplantation Society and the Royal College of Physicians of London. The full guidelines are available freely online for the diabetes, renal and transplantation community using the link below. The aim of this review article is to introduce an abridged version of this new clinical guideline ( https://abcd.care/sites/abcd.care/files/site_uploads/Resources/Position‐Papers/ABCD‐RA%20PTDM%20v14.pdf).
Sperm, metabolic memory and echoes from Lamarck
Authors: Crisóstomo Luís , Oliveira Pedro F. , Alves Marco G.
Published: January 2021

There is a widespread misconception that only maternal variables affect in utero development.

Epigenetic markers carried by the spermatozoon are transmitted to the zygote.

Sperm‐born epigenetic factors influence in utero development, for various generations.

Acquired traits of metabolic disease can be inherited by the offspring via the male gamete.

Health assessment of future fathers is essential to predict the offspring's health.
Clinical effectiveness of early treatment with paliperidone palmitate in schizophrenia: A retrospective real‐world study in South Korea
Authors: Shin Wonsuk , Lee Dong Hyeon , Kim Min‐Kyoung , Lee Sang‐Hyuk , Cho Doo‐Yeoun , Bang Minji
Published: January 2021

Aim

Long‐acting injectable antipsychotic agents (LAIs) including paliperidone palmitate (PP) have shown promising results in preventing relapse and rehospitalization in schizophrenia. This study aimed to ascertain the comparative real‐world effectiveness between the early and late administration of PP and oral formulations of risperidone and paliperidone (ORPs) in patients experiencing a first episode or relapse of schizophrenia.

Methods

We identified patients with schizophrenia admitted to a psychiatric ward at least once and treated with ORPs or PP using the Korea National Insurance Claims Database. Patients were divided into three groups based on the clinical data: (1) patients treated with PP within 30 days of the initiation of treatment (early‐PP), (2) patients treated with PP after 30 days of the initiation of therapy (late‐PP) and (3) patients treated with only ORPs and not received PP (only‐ORP). The primary outcomes were determined as psychiatric rehospitalization during the entire duration of treatment after the first discharge.

Results

A total of 3790 patients (1096 early‐PP, 799 late‐PP and 1895 only‐ORP) were finally included in the analysis. The mean of number and total length of rehospitalization stays during the entire duration in early‐PP group were significantly lower than those of late‐PP group and only‐ORP group (number: 2.32 stays/year, 3.24 stays/year and 4.23 stays/year, p < .001; total length: 50.34 days/year, 72.26 days/year and 105.14 days/year, p < .001).

Conclusions

Early treatment with PP was associated with a greater reduction in psychiatric rehospitalization during the treatment period than late treatment with PP and ORP in schizophrenia.
Refined hepatic grading system in chronic graft‐versus‐host disease improves prognostic risk stratification of long‐term outcomes
Authors: Novitzky‐Basso Igor , AlHayli Saud , Shin Elizabeth , Pasic Ivan , Al‐Shaibani Zeyad , Lam Wilson , Law Arjun , Michelis Fotios V. , Gerbitz Armin , Viswabandya Auro , Lipton Jeffrey H. , Kumar Rajat , Mattsson Jonas , Kim Dennis Dong Hwan
Published: January 2021

Objectives

Hepatic grading systems for categorizing severity in chronic graft‐versus‐host disease (cGvHD) were determined arbitrarily, leading us to initiate the present study to provide objective evidence for the determination of optimal cutoff values and devise a hepatic grading system to predict prognosis.

Methods

Of 842 patients who received allogeneic hematopoietic stem transplant (HCT), 336 patients diagnosed with cGvHD were evaluated for overall survival (OS) and non‐relapse mortality (NRM) after cGVHD development. Multiple statistical parameters were evaluated to define optimal cutoff values of liver profile, including negative predictive value (NPV), positive predictive value (PPV), accuracy, and p‐values as measures of risk stratification power.

Results

We found that alkaline phosphatase (ALP) ≥ 146 IU/L (NPV: 83.4%; PPV: 32.8%; accuracy: 52.7%) and bilirubin ≥ 14 µmol/L (NPV: 81.8%; PPV: 39.4%; accuracy 68.1%) significantly correlated with OS. We developed a refined hepatic cGvHD grading score (RHS), stratifying patients into a low‐RHS group with RHS score 0, OS at 3 years (n = 162) to 80.5%, compared to high‐RHS group with score 1‐2 (n = 172) 62.7%. Regarding NRM, score 0 segregated NRM at 3 years to 11.9%, compared with score 1‐2 19.6%, P = .1.

Conclusions

Refined hepatic score is promising for stratifying patients with cGVHD and liver involvement according to long‐term outcomes.
Investigation of the soil properties that affect Olsen P critical values in different soil types and impact on P fertiliser recommendations
Authors: Tandy Susan , Hawkins Jane M. B. , Dunham Sarah J. , Hernandez‐Allica Javier , Granger Steve J. , Yuan Huimin , McGrath Steve P. , Blackwell Martin S. A.
Published: January 2021

Optimization of phosphorus (P) fertiliser use is desired to ensure more sustainable use of fertiliser, economic food production and reduction of eutrophication of water bodies. Presently, the Olsen P values on which fertiliser recommendations are based to achieve optimum yield are frequently the same for all soils. The aim of this study was to identify the properties of different soils that affect their critical Olsen P values in order to develop better, soil‐specific P fertiliser recommendations. A pot experiment using 10 soils with low available P with different P additions was carried out to investigate the impact of wide‐ranging soil properties on the relationship between P addition, resultant Olsen P values and yield response of ryegrass to Olsen P values. The relationship between added P and Olsen P varied greatly between the individual soils. These relationships were affected by pH, manganese oxide, crystalline aluminium oxide and amorphous iron oxide contents of the soil. Different soils had widely varying critical Olsen P values for ryegrass. However, these could not be related to the measured soil properties. Fertiliser recommendations and critical values for optimum yield of ryegrass based on the Olsen P test should be soil specific. The complexity and lack of clarity over which combination of soil properties governs critical Olsen P values calls for further investigation with more soil types and additional soil property measurements to elucidate the different factors controlling critical Olsen P values in different soils.

Highlights

Soil‐specific P fertiliser recommendations are needed for sustainable fertiliser use

We investigated soil properties affecting critical Olsen P values and added P fertiliser availability

Fertiliser P availability was affected by pH and metal (hydr)oxide contents of the soil

Critical Olsen P values varied with soil, but measured soil properties could not explain this variation
Controls on variation of soil organic carbon concentration in the shrublands of the north‐eastern Tibetan Plateau
Authors: Nie Xiuqing , Wang Dong , Yang Lucun , Zhou Guoying
Published: January 2021

Assessment of soil organic carbon (SOC) concentration in high‐altitude shrublands is essential for understanding C dynamics in terrestrial ecosystems. Hence, we investigated the SOC concentration and its influencing factors using 198 soil profiles (0–100 cm) from 66 sites between 2011 and 2013 in the north‐eastern Tibetan Plateau shrublands. SOC concentration was different under different shrubland types, with SOC concentration significantly greater in the alpine shrublands relative to the desert shrublands, whereas SOC concentration showed limited increases with altitude. Both mean annual temperature (MAT) and mean annual precipitation (MAP) have positive relationships with SOC concentration, and their relationships are moderate. Compared with MAT, a correlation between MAP and variation in SOC concentration was larger. Meanwhile, with increasing soil depth, a correlation between variation in SOC concentration and climatic factors was smaller. Soil pH seems to be a robust factor that not only had a significant negative correlation with SOC, but also played an important role in regulating a correlation between climatic condition and variation in SOC concentration. Controls on variation of SOC concentration on the Tibetan Plateau help to understand soil C dynamics in terrestrial ecosystems.

Highlights

SOC concentration was different under different shrubland types, whereas SOC concentration showed limited increases with altitude.

Compared with MAT, a correlation between MAP and variation in SOC concentration was larger.

Soil pH seems to be a robust factor that had a significant negative correlation with SOC concentration

Soil pH was also important for regulating a correlation between climatic condition and variation in SOC concentration.