bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-dimensional models of the cervicovaginal epithelia to study host-microbiome interactions and sexually transmitted infections
Authors: Edwards Vonetta L. , McComb Elias , Gleghorn Jason P. , Forney Larry , Bavoil Patrik M. , Ravel Jacques
Published: November 2021

Two-dimensional (2D) cell culture systems have provided controlled, reproducible means to analyze host-pathogen interactions. Although inexpensive, straightforward, and requiring very short time commitment, these models recapitulate neither the functionality of multi-layered cell types nor the microbial diversity of an infected human. Animal models have commonly been used to recreate the complexity of human infections. However, extensive modifications are commonly required to recreate interactions that resemble those in the human reproductive tract microbiologically and physiologically. Three-dimensional (3D) cell culture models have emerged as alternative means of reproducing key elements of human infections at a fraction of the cost of animal models and on a scale that allows for replicative experiments to be readily performed. Here we describe a new 3D model that utilizes transwells with epithelial cells seeded apically and a basolateral extra cellular matrix (ECM)-like layer containing collagen and fibroblasts. In this system, basal feeding creates a liquid/air interface on the apical side. The model produced tissues with close morphologic and physiological resemblance to human cervical and vaginal epithelia, including observable levels of mucus produced by cervical cells. Infection by both Chlamydia trachomatis and Neisseria gonorrhoeae was demonstrated as well as the growth of bacterial species observed in the human vaginal microbiota, enabling controlled mechanistic analyses of the interactions between host cells, vaginal microbiota and STI pathogens. Future experiments may include immune cells to mimic more closely the genital environment. Finally, the modular set up of the model makes it fully applicable to the analysis of non-genital host-microbiome-pathogen interactions.

IMPORTANCE

Infected sites in humans are a complex mix of host and microbial cell types interacting with each other to perform specific and necessary functions. The ability to understand the mechanism(s) that facilitate these interactions, and interactions with external factors is paramount to being able to develop preventative therapies. Models that attempt to faithfully replicate the complexity of these interactions are time intensive, costly, and not conducive to high throughput analysis. Two-dimensional (2D) models that have been used as a platform to understand these interactions, while cost effective, are generally limiting in experimental flexibility and structural/physiological relevance. Our three-dimensional (3D) models of the cervicovaginal epithelium can facilitate analysis of interactions between the host epithelium, sexually transmitted pathogens and bacteria present in the vaginal microbiota. Due to the modular design, additional cell types and environmental modulators can be introduced to the system to provide added complexity, approaching conditions in the infected human host.
A temporally resolved, multiplex molecular recorder based on sequential genome editing
Authors: Choi Junhong , Chen Wei , Minkina Anna , Chardon Florence M. , Suiter Chase C. , Regalado Samuel G. , Domcke Silvia , Hamazaki Nobuhiko , Lee Choli , Martin Beth , Daza Riza M. , Shendure Jay
Published: November 2021

DNA is naturally well-suited to serve as a digital medium for in vivo molecular recording. However, DNA-based memory devices described to date are constrained in terms of the number of distinct signals that can be concurrently recorded and/or by a failure to capture the precise order of recorded events1. Here we describe DNA Ticker Tape, a general system for in vivo molecular recording that largely overcomes these limitations. Blank DNA Ticker Tape consists of a tandem array of partial CRISPR-Cas9 target sites, with all but the first site truncated at their 5’ ends, and therefore inactive. Signals of interest are coupled to the expression of specific prime editing guide RNAs2. Editing events are insertional, and record the identity of the guide RNA mediating the insertion while also shifting the position of the “write head” by one unit along the tandem array, i.e. sequential genome editing. In this proof-of-concept of DNA Ticker Tape, we demonstrate the recording and decoding of complex event histories or short text messages; evaluate the performance of dozens of orthogonal tapes; and construct “long tape” potentially capable of recording the order of as many as 20 serial events. Finally, we demonstrate how DNA Ticker Tape simplifies the decoding of cell lineage histories.
Linking host plants to damage types in the fossil record of insect herbivory
Authors: Schachat Sandra R. , Payne Jonathan L. , Boyce C. Kevin
Published: November 2021

Studies of insect herbivory on fossilized leaves tend to focus on a few, relatively simple metrics that are agnostic to the distribution of insect damage types among host plants. More complex metrics that link particular damage types to particular host plants have the potential to address additional ecological questions, but such metrics can be biased by sampling incompleteness due to the difficulty of distinguishing the true absence of a particular interaction from the failure to detect it—a challenge that has been raised in the ecological literature. We evaluate a range of methods for characterizing the relationships between damage types and host plants by performing resampling and subsampling exercises on a variety of datasets. We found that the components of beta diversity provide a more valid, reliable, and interpretable method for comparing component communities than do bipartite network metrics. We found the rarefaction of interactions to be a valid, reliable, and interpretable method for comparing compound communities. Both beta diversity and rarefaction of interactions avoid the potential pitfalls of multiple comparisons. Lastly, we found that the host specificity of individual damage types is challenging to assess. Whereas some previously used methods are sufficiently biased by sampling incompleteness to be inappropriate for fossil herbivory data, alternatives exist that are perfectly suitable for fossil datasets with sufficient sample coverage.
Label-Free Prediction of Cell Painting from Brightfield Images
Authors: Cross-Zamirski Jan , Mouchet Elizabeth , Williams Guy , Schönlieb Carola-Bibiane , Turkki Riku , Wang Yinhai
Published: November 2021

Cell Painting is a high-content image-based assay which can reveal rich cellular morphology and is applied in drug discovery to predict bioactivity, assess toxicity and understand diverse mechanisms of action of chemical and genetic perturbations. In this study, we investigate label-free Cell Painting by predicting the five fluorescent Cell Painting channels from paired brightfield z-stacks using deep learning models. We train and validate the models with a dataset representing 1000s of pan-assay interference compounds sampled from 17 unique batches. The model predictions are evaluated using a test set from two additional batches, treated with compounds comprised from a publicly available phenotypic set. In addition to pixel-level evaluation, we process the label-free Cell Painting images with a segmentation-based feature-extraction pipeline to understand whether the generated images are useful in downstream analysis. The mean Pearson correlation coefficient (PCC) of the images across all five channels is 0.84. Without actually incorporating these features into the model training we achieved a mean correlation of 0.45 from the features extracted from the images. Additionally we identified 30 features which correlated greater than 0.8 to the ground truth. Toxicity analysis on the label-free Cell Painting resulted a sensitivity of 62.5% and specificity of 99.3% on images from unseen batches. Additionally, we provide a breakdown of the feature profiles by channel and feature type to understand the potential and limitation of the approach in morphological profiling. Our findings demonstrate that label-free Cell Painting has potential above the improved visualization of cellular components, and it can be used for downstream analysis. The findings also suggest that label-free Cell Painting could allow for repurposing the imaging channels for other non-generic fluorescent stains of more targeted biological interest, thus increasing the information content of the assay.
3CAC: improving the classification of phages and plasmids in metagenomic assemblies using assembly graphs
Authors: Pu Lianrong , Shamir Ron
Published: November 2021

Motivation

Bacteriophages and plasmids usually coexist with their host bacteria in microbial communities and play important roles in microbial evolution. Accurately identifying sequence contigs as phages, plasmids, and bacterial chromosomes in mixed metagenomic assemblies is critical for further unravelling their functions. Many classification tools have been developed for identifying either phages or plasmids in metagenomic assemblies. However, only two classifiers, PPR-Meta and viralVerify, were proposed to simultaneously identify phages and plasmids in mixed metagenomic assemblies. Due to the very high fraction of chromosome contigs in the assemblies, both tools achieve high precision in the classification of chromosomes but perform poorly in classifying phages and plasmids. Short contigs in these assemblies are often wrongly classified or classified as uncertain.

Results

Here we present 3CAC, a new three-class classifier that improves the precision of phage and plasmid classification. 3CAC starts with an initial three-class classification generated by existing classifiers and improves the classification of short contigs and contigs with low confidence classification by using proximity in the assembly graph. Evaluation on simulated metagenomes and on real human gut microbiome samples showed that 3CAC outperformed PPR-Meta and viralVerify in both precision and recall, and increased F1-score by 10-60 percentage points.

Availability

The 3CAC software is available on https://github.com/Shamir-Lab/3CAC.

Contact

rshamir@tau.ac.il

Supplementary information

Supplementary data are available at Bioinformatics online.
Diversity of N-triphenylacetyl-L-tyrosine solvates with halogenated solvents
Authors: Czapik Agnieszka , Kwit Marcin
Published: November 2021

The structure of N-triphenylacetyl-L-tyrosine (C29H25NO4, L-TrCOTyr) is characterized by the presence of both donors and acceptors of classical hydrogen bonds. At the same time, the molecule contains a sterically demanding and hydrophobic trityl group capable of participating in π-electron interactions. Due to its large volume, the trityl group may favour the formation of structural voids in the crystals, which can be filled with guest molecules. In this article, we present the crystal structures of a series of N-triphenylacetyl-L-tyrosine solvates with chloroform, namely, L-TrCOTyr·CHCl3 (I) and L-TrCOTyr·1.5CHCl3 (III), and dichloromethane, namely, L-TrCOTyr·CH2Cl2 (II) and L-TrCOTyr·0.1CH2Cl2 (IV). To complement the topic, we also decided to use the racemic amide N-triphenylacetyl-DL-tyrosine (rac-TrCOTyr) and recrystallized it from a mixture of chloroform and dichloromethane. As a result, rac-TrCOTyr·1.5CHCl3 (V) was obtained. In the crystal structures, the amide molecules interact with each other via O—H...O hydrogen bonds. Noticeably, the amide N—H group does not participate in the formation of intermolecular hydrogen bonds. Channels are formed between the TrCOTyr molecules and these are filled with solvent molecules. Additionally, in the crystals of III and V, there are structural voids that are occupied by chloroform molecules. Structure analysis has shown that solvates I and II are isostructural. Upon loss of solvent, the solvates transform into the solvent-free form of TrCOTyr, as confirmed by thermogravimetric analysis, differential scanning calorimetry and powder X-ray diffraction.
Numerical investigation of heat transfer effects on combustion in a generic gas turbine burner
Authors: Hepkaya Ender , Yucel Nuri
Published: November 2021

Purpose

This study aims to methodologically investigate heat transfer effects on reacting flow inside a liquid-fueled, swirl-stabilized burner. Furthermore, particular attention is paid to turbulence modeling and the results of Reynolds-averaged Navier–Stokes and large eddy simulation approaches are compared in terms of velocity field and flame temperature.

Design/methodology/approach

Simulations consist liquid fuel distribution using Eulerian–Lagrangian approach. Flamelet-Generated Manifold combustion model, which is a mixture fraction-progress variable formulation, is used to obtain reacting flow field. Discrete ordinates method is also added for modeling radiation heat transfer effect inside the burner. As a parametric study, different thermal boundary conditions namely: adiabatic wall, constant temperature and heat transfer coefficient are applied. Because of the fact that the burner is designed for operating with different materials, the effects of burner material on heat transfer and combustion processes are investigated. Additionally, material temperatures have been calculated using 1 D method. Finally, soot particles, which are source of luminous radiation in gas turbine combustors, are calculated using Moss-Brookes model.

Findings

The results show that the flow behavior is obviously different in recirculation region for both turbulence modeling approach, and this difference causes change on flame temperature distribution, particularly in the outer recirculation zone and region close to swirler. In thermal assessment of the burner, it is predicted that material of the burner walls and the applied thermal boundary conditions have significant influence on flame temperature, wall temperature and flow field. The radiation heat transfer also makes a strong impact on combustion inside the burner; however, luminous radiation arising from soot particles is negligible for the current case.

Originality/value

These types of burners are widely used in research of gas turbine combustion, and it can be seen that the heat transfer effects are generally neglected or oversimplified in the literature. This parametric study provides a basic understanding and methodology of the heat transfer effects on combustion to the researchers.
Usage of mobile phones to support management of agribusiness activities in Indonesia
Authors: Mariyono Joko , Santoso Siswanto Imam , Waskito Jaka , Utomo Akbar Ario Satrio
Published: November 2021

Purpose

The purpose of this study is to assess the impact of mobile phone usage on sales and profit as the indicator of business performance, to analyse the facilitating roles of mobile phones and factors affecting farmers' decision to use the mobile phone in agribusiness activities.

Design/methodology/approach

Intensive farming was selected in this study due to its higher profitability than other crops. Data were compiled from field surveys of 1,040 farmer households in vegetable production regions of Indonesia. This study employed structural equation modelling, identifying mediating variables and quantifying multiple endogenous variables' direct and indirect effects in simultaneous regression equations.

Findings

The results indicate that mobile phone usage enabled farmers to increase sales, obtain market information, acquire improved agronomic technology, access credit and contact customers. The device enhanced profit through mediations of high sales, reasonable prices and access to credit and market information. The personal attributes of farmers determined the adoption of mobile phones to support agribusiness activities.

Research limitations/implications

This study paid attention to the use of mobile phones, which was considered an integral technology of information and communication. Other components, such as personal computers and other Internet-based devices, need further study.

Practical implications

As the rate of mobile phone use was still low, farmers should be encouraged to utilise the device. Socialisation and specially designed training workshops on agribusiness information systems using mobile phones are of the best ways.

Originality/value

Using structural equation modelling enables to analyse of multi-dependent variables in one model. Farm-level data provide a real situation, and policy implications should address the right target. The subject of this investigation is a semi-subsistence farm household that lacked access to information and communication technology.
Inducing organizational resilience through collective mindfulness: A path towards an uninterrupted metamorphosis
Authors: Shela V. , Ramayah T. , Ahmad Noor Hazlina
Published: November 2021

Purpose

This paper aims to highlight the potential role of collective mindfulness as a key success factor for organizational resilience. It also outlines the processes and essential contexts that support the cultivation of collective mindfulness capability in organizations.

Design/methodology/approach

A review of the relevant articles and current development in the area of organizational resilience and collective mindfulness provided an in-depth understanding and valuable insights into how collective mindfulness can be utilized to engender organizational resilience in the challenging business world.

Findings

This paper provides a brief overview over the crucial role of collective mindfulness capability in augmenting organizational resilience. Additionally, the processes of collective mindfulness and the essential contexts for developing and sustaining this capability is also unveiled.

Originality/value

The paper offers practical solutions for the anxiety faced by many organizations around the globe due to the relentless disruptions by highlighting on the potential role of collective mindfulness. It reveals the way that organizations can undertake to wade through the waves imposed by the current volatile environment by leveraging on collective mindfulness capability.
Indigenous heritage in diplomacy: repositioning Taiwan in the Austronesian network and its cultural implications
Authors: Huang Shu-Mei
Published: November 2021

Purpose

This paper illustrates how Taiwan has tried to mobilize its prehistory Austronesian linguistic heritage and indigenous cultural memories to reposition itself in the Asia-Pacific. It examines how the attempt has gradually evolved into cross-border exchange and partnership based on the interconnectivity across the Pacific on different levels.

Design/methodology/approach

The research is based on policy review of the Taiwan government's growing focus on indigenous culture in strategizing diplomacy and cultural policy from 2000 through 2021 and the researcher's participant observation in expert cultural heritage meetings (2018–2021). It is also complemented by semi-structured interviews with both selected state actors and civil actors.

Findings

The past connection among indigenous communities in Taiwan and the Austronesian peoples contributes to building up new cultural circuits across-borders based upon shared indigenous heritage and demonstrates the extraterritorial role of heritage, which can be the potential base for developing diplomacy.

Research limitations/implications

The research is limited in not directly engaging with actors in the Pacific given limited time, budget and mobility under the coronavirus disease (COVID) pandemic. The author would like to follow on that in her future research.

Originality/value

The paper sheds light on the uneasy relationship between indigenous heritage making and nation building and its cultural implications. This study demonstrates that the state framework of heritage is not necessarily appropriate to deal with these complicated historical matters, especially when the notion of heritage per se is not decolonised in a settler state.
Heritage making and interpretation in postcolonial Harbin: contemporary urban memory of the Russian-built Harbin Railway Station and beyond
Authors: Zhang Wenzhuo
Published: November 2021

Purpose

This paper critically analyses the urban memory and heritage interpretation of postcolonial Harbin, a city in China that was founded by the Russians in 1898. It investigates the role and making of Russian colonial heritage in contemporary Harbin with a detailed case study of the Harbin Railway Station

Design/methodology/approach

Research methods include archival analysis, observation and semi-structured interview. In-depth interviews were conducted with local people, architect/urban planners and officials.

Findings

Local people of different generations with different backgrounds have different interpretations of the recently made colonial heritage of the Harbin Railway Station. The urban memory of Harbin has been consistently re-forming with both nostalgia and amnesia. Younger generations tend to regard the colonial heritage as their own heritage and a symbol of Harbin's cultural character without considering much about its related colonial history. In today's Harbin, colonial heritage as the “colonial past presencing” is more about a feel of the Europeanised space rather than the actual historical events of the period, and colonial heritage making becomes a tool for urban development and revitalisation at the institutional level. However, due to the paradigm shift in China's urban development, Harbin is facing new challenges in dealing with its colonial heritage.

Originality/value

Harbin is an under-researched case in terms of urban heritage studies. This paper offers a new entry point for understanding the westernisation and colonial heritage making in the contemporary China more deeply and thoroughly and helps to see the trend of China's urban development more clearly.
Asymmetric impact of tourism on the balance of payments in Pakistan: evidence from non-linear ARDL
Authors: Rafiq Asim , Aamir Ameer Muhammad , Nadeem Muhammad
Published: November 2021

Purpose

The aim of the paper is to determine the asymmetric impact of tourism on the deficit in the balance of payments (BOPs).

Design/methodology/approach

The research uses the non-linear autoregressive distributed lag (ARDL) model to investigate the asymmetric impact of tourism on Pakistan's BOPs deficit using quarterly data from 1995 to 2019.

Findings

The finding reveals that due to the positive change in tourism, the BOPs deficit decreases by 27%, although due to the negative change in tourism, the BOPs deficit rises by 2.3%. In addition, the significance of F-statistics (10.609) confirms the existence of co-integration between tourism and the deficit in the BOPs. The Wald test confirms the asymmetric association between tourism and the deficit in the BOPs over the long term.

Research limitations/implications

In order to improve tourism in Pakistan, policymakers must consider the following implications. First, there is a need for an adequate infrastructure that can help the tourist. Second, the Government must maintain a stable law and order situation as a whole and particularly at tourist destinations. Finally, the Government should develop tourism-friendly policies in order to boost tourism in Pakistan.

Originality/value

The research provides new evidence of the impact of tourism on the BOPs using the novel non-linear ARDL (NARDL) technique. The evidence will help policymakers to develop policies to improve tourism in order to reduce the BOPs deficit.
Testing interaction effects of intellectual capital and burnout on innovative work behaviour of professional nurses
Authors: Narzary Genuine , Palo Sasmita
Published: November 2021

Purpose

The present study aims to examine the moderating effect of burnout between intellectual capital and innovative work behaviour of professional nurses.

Design/methodology/approach

Mixed-method approach was followed that involves conducting both quantitative surveys and qualitative semi-structured interviews. Quantitative data was collected from 844 staff nurses. Interviews were conducted with a total of 20 participants including director of nursing, chief nursing officer, general manager operation, professor cum principal, doctors, nurse educators, ward in charges and staff nurses working with multi, super speciality private and charitable trust hospitals in Mumbai (India).

Findings

Intellectual capital and burnout (intellectual capital*burnout) interaction increased the proportion of innovative work behaviour from 0.09 to 0.15, an increase of 66.67%. The results also reveal a significant and negative (−0.09) moderating effect of burnout between intellectual capital and innovative work behaviour of nurses. Qualitative findings also could confirm and support that human, structural and relational capital help nurses to be innovative. However, whenever nurses feel a loss of energy, enthusiasm, motivation and exhaustion, they tend to become less innovative and continue only with the routine works.

Research limitations/implications

This study provides a new implication for multi, super speciality private and charitable trust hospitals management to relook at and reduce the level of burnout to mitigate its adverse effect.

Originality/value

To the best of the authors’ knowledge, this is the first study and findings related to professional nurses working in multi, super speciality private and charitable trust hospitals in India.
A tale of two frameworks: charting a path to lifelong learning for physician leaders through CanMEDS and LEADS
Authors: Chan Ming-Ka , Dickson Graham , Keegan David A. , Busari Jamiu O. , Matlow Anne , Van Aerde John
Published: November 2021

Purpose

The purpose of this paper was to determine the complementarity between the Canadian Medical Education Directions for Specialists (CanMEDS) physician competency and LEADS leadership capability frameworks from three perspectives: epistemological, philosophical and pragmatic. Based on those findings, the authors propose how the frameworks collectively layout pathways of lifelong learning for physician leadership.

Design/methodology/approach

Using a qualitative approach combining critical discourse analysis with a modified Delphi, the authors examined “How complementary the CanMEDS and LEADS frameworks are in guiding physician leadership development and practice” with the following sub-questions: What are the similarities and differences between CanMEDS and LEADS from: An epistemological and philosophical perspective? The perspective of guiding physician leadership training and practice? How can CanMEDS and LEADS guide physician leadership development from medical school to retirement?

Findings

Similarities and differences exist between the two frameworks from philosophical and epistemological perspectives with significant complementarity. Both frameworks are founded on a caring ethos and value physician leadership – CanMEDS (for physicians) and LEADS (physicians as one of many professions) define leadership similarly. The frameworks share beliefs in the function of leadership, embrace a belief in distributed leadership, and although having some philosophical differences, have a shared purpose (preparing for changing health systems). Practically, the frameworks are mutually supportive, addressing leadership action in different contexts and where there is overlap, complement one another in intent and purpose.

Originality/value

To the best of the authors’ knowledge, this is the first paper to map the CanMEDS (physician competency) and LEADS (leadership capabilities) frameworks. By determining the complementarity between the two, synergies can be used to influence physician leadership capacity needed for today and the future.
Effects of different colorants on service performance for colored asphalt pavement in cold regions
Authors: Fu Xinxin , Chen Yanjun , Sun Minggang , Yu Tengjiang
Published: November 2021

Purpose

The service performance for colored asphalt pavement is inevitably affected by the addition of different colorants, especially the challenge of low temperature environment in cold regions. Therefore, the purpose of study is to explore the effects of different colorants on the service performance for colored asphalt pavement and to provide a foundation for improving the applicability of colored asphalt pavement in cold regions.

Design/methodology/approach

In the study, three kinds of colorants (iron oxide red, iron oxide yellow, iron oxide green) were used to compare the influence of different colorants amounts and different colorants kinds on the service performance for colored asphalt pavement in cold regions. According to the characteristics of low temperature in cold regions, the effects of different colorants on the low temperature performance for colored asphalt pavement were studied.

Findings

The study shows that different colorants have different effects on the service performance of colored asphalt pavement. The high temperature performance increases with the increase of the colorants amount, but the low temperature performance is opposite. Additionally, the yellow colored asphalt pavement has more advantages of low temperature adaptation than the red and green colored asphalt pavement.

Originality/value

The study results provide a certain theoretical foundation for the application of colored asphalt pavement in cold regions and have certain value and significance for the further development of colored asphalt pavement.
Prothrombin induced by vitamin K absence or antagonist‐II and alpha foetoprotein to predict development of hepatocellular carcinoma in Caucasian patients with hepatitis C‐related cirrhosis treated with direct‐acting antiviral agents
Authors: Degasperi Elisabetta , Perbellini Riccardo , D’Ambrosio Roberta , Uceda Renteria Sara Colonia , Ceriotti Ferruccio , Perego Alberto , Orsini Corinna , Borghi Marta , Iavarone Massimo , Bruccoleri Mariangela , Rimondi Alessandro , De Silvestri Annalisa , Sangiovanni Angelo , Lampertico Pietro
Published: November 2021

Background

Prothrombin induced by vitamin K absence or antagonist‐II (PIVKA‐II) and alpha fetoprotein (AFP) are biomarkers for hepatocellular carcinoma (HCC). However, their performance in patients with cirrhosis related to hepatitis C virus (HCV) treated with direct‐acting antiviral agents (DAA) is unknown.

Aim

To evaluate PIVKA‐II and AFP as HCC predictors in DAA‐treated patients with HCV‐related cirrhosis

Methods

In this single centre study, patients with cirrhosis from chronic HCV infection and with a sustained virological response (SVR) to DAA were tested for PIVKA‐II and AFP (Fujirebio, Japan) at the start of DAA treatment (baseline), end of treatment (EOT) and at HCC diagnosis.

Results

We included 400 patients with mean age 65 (24‐92); 56% were men. From baseline to EOT, PIVKA‐II did not change (35 vs 35 mAU/mL, P = 0.43) while AFP significantly decreased (12 vs 6 ng/mL, P < 0.0001). After 52 (3‐66) months from baseline, 34 (8.5%) patients developed de novo HCC; median AFP 9 (2‐12 868) ng/mL and PIVKA‐II 80 (22‐1813) mAU/mL. EOT‐PIVKA‐II (HR 3.05, P < 0.0001) and AFP (HR 2.77, P = 0.001) independently predicted HCC together with diabetes (HR 6.12, P < 0.001) and GGT (HR 1.01, P = 0.03). The 4‐year cumulative probability of HCC was 24% vs 2% in patients with EOT‐PIVKA‐II > or ≤41 mAU/mL (P < 0.0001), and 26% vs 9% for EOT‐AFP > or ≤15 ng/mL (P = 0.02). By combining EOT‐PIVKA‐II and AFP, the 4‐year probabilities of HCC were 3% in patients testing negative for both markers, 18% in patients positive for both, and 38% in patients positive for at least one (P < 0.0001).

Conclusions

In patients with HCV‐related cirrhosis treated with DAA, PIVKA‐II and AFP independently predicted HCC, while their combination improved risk stratification.
Conditional relative survival in Waldenström’s macroglobulinaemia: a population‐based study in The Netherlands
Authors: Amaador Karima , Kersten Marie José , Visser Otto , Posthuma Eduardus F. M. , Minnema Monique C. , Vos Josephine M. I. , Dinmohamed Avinash G.
Published: November 2021

Contemporary diagnosed WM patients, compared to the general population, continue to experience excess mortality regardless of having survived up to 15 years post‐diagnosis. This gradual increase in excess mortality might result from the incurable nature of this disease characterized by multiple relapses throughout the disease course with limited efficacious treatment options in the released/refractory setting.
Understanding the needs of low‐income countries: how urologists can help
Authors: Payne Stephen R. , Chalwe Mumba
Published: November 2021

Delivering urological humanitarian aid to countries with greater need has been provided by urologists associated with British Association of Urological Surgeons (BAUS) Urolink over the last 30 years. Urolink has realised the need to understand where that need is geographically, what tangible help is required, and how assistance can be delivered in the most ethically appropriate way. The World Bank stratification of countries by per capita gross national income has helped in the identification of low‐come countries or lower‐middle‐income countries (LMICs), the vast majority of which are in sub‐Saharan Africa. The medical and socioeconomic needs of those country’s populations, which constitute 17% of the global community, are substantially different from that required in higher income countries. More than 40% of sub‐Saharan Africa’s population is aged <14 years, it has a substantially reduced life expectancy, which influences the type of pathologies seen, and perinatal complications are a major cause of morbidity for both mother and child. There is a significant problem with the availability of medical care in these countries and almost a third of global deaths have been attributed to the lack of access to emergency and elective surgery. Urologically, the main conditions demanding the attention of the very few available urologists are congenital anomalies, benign prostatic hypertrophy, urolithiasis, urethral stricture, and pelvic cancer. The management of these conditions is often substantially different from that in the UK, being limited by a lack of personnel, equipment, and access to geographically relevant guidelines appropriate to the healthcare environment. Assisting LMICs to develop sustainable urological services can be helped by understanding the local needs of linked institutions, establishing trusting and durable relationships with partner centres and by providing appropriate education that can be perpetuated, and disseminated, across a region of need.
Metformin versus insulin therapy for gestational diabetes: Effects on offspring anthropometrics and metabolism at the age of 9 years: A follow‐up study of two open‐label, randomized controlled trials
Authors: Paavilainen Elisa , Tertti Kristiina , Nikkinen Hilkka , Veijola Riitta , Vääräsmäki Marja , Loo Britt‐Marie , Tossavainen Päivi , Rönnemaa Tapani , Niinikoski Harri
Published: November 2021

Aims

To compare anthropometrics, and lipid and glucose metabolism in the 9‐year‐old offspring of mothers treated with metformin or insulin for gestational diabetes mellitus (GDM).

Materials and Methods

This was a Finnish two‐centre, 9‐year follow‐up study of two open‐label, randomized controlled trials comparing the effects observed in the offspring of mothers who received metformin and insulin treatment for GDM. Measurements included anthropometrics, blood pressure, lipoproteins, and oral glucose tolerance tests. This study was registered with ClinicalTrials.gov, number NCT02417090.

Results

At the age of 9 years 172 children (55% of the original study cohort, 82 from the metformin and 90 from the insulin group) participated in the study. No differences were found between the 9‐year‐old offspring groups in anthropometric variables, including body mass index and waist‐to‐height ratio. The offspring in the metformin group had higher high‐density lipoprotein (HDL) cholesterol concentrations (1.72 vs. 1.54 mmol/L; P = 0.039) but lower low‐density lipoprotein cholesterol (2.39 vs. 2.58 mmol/L; P = 0.046) and apolipoprotein B concentrations (0.63 vs. 0.67 g/L; P = 0.043) than the offspring in the insulin group. The difference in HDL cholesterol concentration was found to be significant only in boys (P = 0.003). The 2‐hour glucose value in the oral glucose tolerance test was 0.6‐mmol/L lower in boys from the metformin group than in those from the insulin group (P = 0.015).

Conclusions

Metformin treatment for GDM is associated with similar offspring growth and glucose metabolism but a more favourable lipid profile at the age of 9 years as compared to insulin treatment.
Molecular characterization of substrate‐induced ubiquitin transfer by UBR7‐PHD finger, a newly identified histone H2BK120 ubiquitin ligase
Authors: Dasgupta Anirban , Mondal Payel , Dalui Sambit , Das Chandrima , Roy Siddhartha
Published: November 2021

Monoubiquitination of histone H2B at lysine 120 plays a vital role in active transcription and DNA damage response pathways. Ubiquitin protein ligase E3 component N‐recognin 7 (UBR7) has been recently identified as an H2BK120 monoubiquitin ligase. However, the molecular details of its ubiquitin transfer mechanism are not well understood. Here, we report that the plant homeodomain (PHD) finger of UBR7 is essential for its association with E2 UbcH6 and consequent ubiquitin transfer to its substrate histone H2B. We also identified the critical region of UbcH6 involved in this function and shown that the residues stretching from 114 to 125 of histone H2B C‐terminal tail are sufficient for UBR7/UbcH6‐mediated ubiquitin transfer. We also employed antibody‐independent mass spectrometry to confirm UBR7‐mediated ubiquitination of the H2B C‐terminal tail. We demonstrated that the PHD finger of UBR7 forms a dimer and this dimerization is essential for ubiquitination of histone H2B. We mapped the critical residues involved in the dimerization and mutation of these residues that abrogate E3 ligase activity and are associated with cancer. Furthermore, we compared the mode of ubiquitin discharge from UbcH6 mediated by UBR7 and RING finger protein 20 (RNF20) through a thioester hydrolysis assay. Interestingly, binding of substrate H2B to UBR7 induces a conformational change in the PHD finger, which triggers ubiquitin transfer from UbcH6. However, the RNF20 RING finger alone is sufficient to promote the release of ubiquitin from UbcH6. Overall, the mechanism of ubiquitin transfer by the newly identified E3 ubiquitin ligase UBR7 is markedly different from that of RNF20.
Data‐driven estimates of fertilizer‐induced soil NH3, NO and N2O emissions from croplands in China and their climate change impacts
Authors: Ma Ruoya , Yu Kai , Xiao Shuqi , Liu Shuwei , Ciais Philippe , Zou Jianwen
Published: November 2021

Gaseous reactive nitrogen (Nr) emissions from agricultural soils to the atmosphere constitute an integral part of global N cycle, directly or indirectly causing climate change impacts. The extensive use of N fertilizer in crop production will compromise our efforts to reduce agricultural Nr emissions in China. A national inventory of fertilizer N‐induced gaseous Nr emissions from croplands in China remains to be developed to reveal its role in shaping climate change. Here we present a data‐driven estimate of fertilizer N‐induced soil Nr emissions based on regional and crop‐specific emission factors (EFs) compiled from 379 manipulative studies. In China, agricultural soil Nr emissions from the use of synthetic N fertilizer and manure in 2018 are estimated to be 3.81 and 0.73 Tg N yr−1, with a combined contribution of 23%, 20% and 15% to the global agricultural emission total of ammonia (NH3), nitrous oxide (N2O) and nitric oxide (NO), respectively. Over the past three decades, NH3 volatilization from croplands has experienced a shift from a rapid increase to a decline trend, whereas N2O and NO emissions always maintain a strong growth momentum due to a robust and continuous rise of EFs. Regionally, croplands in Central south (1.51 Tg N yr−1) and East (0.99 Tg N yr−1) of China exhibit as hotspots of soil Nr emissions. In terms of crop‐specific emissions, rice, maize and vegetable show as three leading Nr emitters, together accounting for 61% of synthetic N fertilizer‐induced Nr emissions from croplands. The global warming effect derived from cropland N2O emissions in China was found to dominate over the local cooling effects of NH3 and NO emissions. Our established regional and crop‐specific EFs for gaseous Nr forms provide a new benchmark for constraining the IPCC Tier 1 default EF values. The spatio‐temporal insight into soil Nr emission data from N fertilizer application in our estimate is expected to advance our efforts towards more accurate global or regional cropland Nr emission inventories and effective mitigation strategies.
Listening to the archive: Historical geographies of sound
Authors: della Dora Veronica
Published: November 2021

Sound is a fundamental dimension of human experience. However, its ephemeral nature poses specific challenges to historical geographers and other scholars concerned with the study of the past. The last two decades have nonetheless witnessed an increased interest in the spatialities of historical sounds and acoustic environments in geography and across the humanities by large. This article offers a brief overview of some of this work. In particular, it traces a cross‐disciplinary move from the study and preservation of past soundscapes to the study of their shifting perceptions, as well as increased attention to the aesthetic and affective qualities of past sounds and their complex poetics and politics. Rather than another subfield to be reinvented by geographers, I suggest that sonic geographies of the past are to be better understood and approached as a dynamic platform for interdisciplinary dialogue and exchange.
The effects of financial statement disaggregation on audit pricing
Authors: Koh Kevin , Tong Yen H. , Zhu Zinan
Published: November 2021

We examine whether the extent of financial statement disaggregation affects the pricing of audit engagements in the United States. We hypothesize and find that auditors assess higher engagement risk and charge higher audit fees for clients with more disaggregated financial statements. We also find that these higher audit fees are not the result of either increased auditor effort to mitigate detection risk or heightened inherent and control risks reflected in lower financial reporting quality. Instead, we document that greater financial statement disaggregation is positively associated with litigation risk. This result suggests that higher audit fees arise out of auditors' assessments of heightened client and auditor business risks associated with litigation. While financial statement disaggregation may have beneficial effects on the quality of financial information, we document that financial statement disaggregation can impose costs on firms in terms of higher audit fees and a higher likelihood of litigation. Our study informs standard setters, firms and auditors as they debate the costs, benefits and extent of disaggregation to be presented in financial statements.
German‐style dual apprenticeship training in the Greater Shanghai Area‐ Spatial Agglomeration Dynamics
Authors: Wiemann Judith
Published: November 2021

A considerable number of German multinational enterprises (MNE) are located in the Greater Shanghai Area. German MNE in the industrial sector show an inclination to export German forms of technical training—more specifically German‐style dual apprenticeship training—to their worldwide subsidiaries. Within China, this is especially the case for the Greater Shanghai Area, which has established itself as a ‘hotspot’ for dual apprenticeship training in the last 15 years. This paper explores what makes the Greater Shanghai Area such a ‘hotspot’ for dual apprenticeship training—in international comparison—by focusing on factors influencing the spatial agglomeration of dual apprenticeship training activities in this region. The paper finds unevenly distributed institutional resources regarding the attraction of German Foreign Direct Investment as well as unevenly distributed resources at the skill formation system level as important influencing factors. Both factors show ‘self‐reinforcing’ dynamics strengthening already existing spatial agglomeration of dual apprenticeship training activities.
The DOMON domain protein LmKnk contributes to correct chitin content, pore canal formation and lipid deposition in the cuticle of Locusta migratoria during moulting
Authors: Yu R. R. , Zhang R. , Liu W. M. , Zhao X. M. , Zhu K. Y. , Moussian B. , Zhang J. Z.
Published: November 2021

Insects prevent uncontrolled penetration of water and xenobiotics by producing an impermeable cuticle. The major component of the cuticle is chitin that adopts a crystalline structure thereby contributing to cuticle stability. Our understanding of the contribution of chitin to the cuticle barrier function is limited. Here, we studied the role of the DOMON domain protein Knickkopf (LmKnk) that is involved in chitin organization and cuticle permeability in the migratory locust Locusta migratoria. We show that LmKnk localizes to the chitin layer in the newly produced cuticle. Injection of double‐stranded RNA targeting LmKnk (dsLmKnk) in locust nymphs caused failure of moulting to the next stage. Histological experiments revealed that apolysis, i.e., the detachment of the old cuticle from the body surface, was normal; however, the newly synthesized cuticle was thinner than the cuticle of the control insects. Indeed, chitin content dropped after suppression of LmKnk expression. As seen by transmission electron microscopy, crystalline chitin organization was lost in dsLmKnk‐treated insects. In addition, the structure of pore canals, which are lipid transporting routes in the cuticle, was abnormal. Consistently, their content was reduced and, probably by consequence, lipid deposition on the cuticle was decreased after injection of dsLmKnk. Suppression of LmKnk transcript levels rendered L. migratoria more susceptible to each of four selected insecticides including malathion, chlorpyrifos, carbaryl and deltamethrin. Overall, our data show that LmKnk is needed for correct chitin amounts and organization, and their changes ultimately affect cuticular permeability in L. migratoria.
Assessing subsidy policies for green products: operational and environmental perspectives
Authors: Zhang Linghong , Xue Bowen , Li Kevin W.
Published: November 2021

This paper studies the impacts of two government subsidy policies, a fixed amount subsidy and discount subsidy, on the environment and operations of a two‐echelon supply chain, where the supply chain serves the market with either a marginal cost intensive green product (MIGP) or development‐intensive green product (DIGP). We first derive the equilibrium unit greenness level, pricing decisions, and the resulting economic and aggregate environmental performances. Then, we compare the effects of the two subsidy policies for the MIGP and DIGP with and without a total subsidy budget constraint. The main results are as follows: (1) We identify the congruence regions (conflict regions) within which one subsidy policy dominates the other according to all (some) criteria. (2) With the budget constraint, the fixed amount subsidy outperforms the discount subsidy for both MIGP and DIGP in terms of the unit and aggregate greenness levels.