bluuebunny/crossref_metadata_2025 huggingface dataset:
TLR4 regulation in human fetal membranes as an explicative mechanism of a pathological preterm case
Authors: Belville Corinne , Ponelle-Chachuat Flora , Rouzaire Marion , Gross Christelle , Pereira Bruno , Gallot Denis , Sapin Vincent , Blanchon Loïc
Published: June 2021

The integrity of human fetal membranes is crucial for harmonious fetal development throughout pregnancy. Their premature rupture is often the consequence of a physiological phenomenon previously exacerbated. Beyond all biological processes implied, inflammation is of primary importance and is qualified as “sterile” at the end of pregnancy. Complementary methylomic and transcriptomic strategies on amnion and choriodecidua explants taken from the altered (cervix zone) and intact fetal membranes at term and before labor were used in this study. By cross-analyzing genome-wide studies strengthened byin vitroexperiments, we deciphered how the expression of Toll-like receptor 4 (TLR4), a well-known actor of pathological fetal membrane rupture, is controlled. Indeed, it is differentially regulated in the altered zone and between both layers by a dual mechanism: 1) the methylation of TLR4 and miRNA promoters and 2) targeting by miRNA (let-7a-2 and miR-125b-1) acting on the 3’-UTR of TLR4. Consequently, this study demonstrates that a fine regulation of TLR4 is required for sterile inflammation establishment at the end of pregnancy and that it may be dysregulated in the pathological premature rupture of membranes.
DeepMP: a deep learning tool to detect DNA base modifications on Nanopore sequencing data
Authors: Bonet Jose , Chen Mandi , Dabad Marc , Heath Simon , Gonzalez-Perez Abel , Lopez-Bigas Nuria , Lagergren Jens
Published: June 2021

Motivation

DNA Methylation plays a key role in a variety of biological processes. Recently, Nanopore long-read sequencing has enabled direct detection of these modifications. As a consequence, a range of computational methods have been developed to exploit Nanopore data for methylation detection. However, current approaches rely on a human-defined threshold to detect the methylation status of a genomic position and are not optimized to detect sites methylated at low frequency. Furthermore, most methods employ either the Nanopore signals or the basecalling errors as the model input and do not take advantage of their combination.

Results

Here we present DeepMP, a convolutional neural network (CNN)-based model that takes information from Nanopore signals and basecalling errors to detect whether a given motif in a read is methylated or not. Besides, DeepMP introduces a threshold-free position modification calling model sensitive to sites methylated at low frequency across cells. We comprehensively benchmarked DeepMP against state-of-the-art methods on E. coli, human and pUC19 datasets. DeepMP outperforms current approaches at read-based and position-based methylation detection across sites methylated at different frequencies in the three datasets.

Availability

DeepMP is implemented and freely available under MIT license at github.com/pepebonet/DeepMP

Contact

jose.bonet@irbbarcelona.org — mandiche@kth.se
Chemical unfolding of protein domains induces shape change in programmed
protein hydrogels
Authors: Khoury Luai R. , Popa Ionel
Published: June 2021

Programmable behavior combined with tailored stiffness and tunable
biomechanical response are key requirements for developing successful materials.
However, these properties are still an elusive goal for protein-based
biomaterials. Here, we present a new method based on protein-polymer
interactions, to manipulate the stiffness of protein-based hydrogels made from
bovine serum albumin (BSA) by using polyelectrolytes such as poly(Ethelene)imine
(PEI) and poly-L-lysine (PLL) at various concentrations. This approach confers
protein-hydrogels tunable wide-range stiffness, from ~ 10 - 60 kPa when treated
with PEI, without affecting the protein mechanics and nanostructure. We ascribe
the increase in stiffness to the synergistic effect of the non-covalent
electrostatic polymer-protein interaction, as well as the polymer-shell that
stabilizes the protein domains nanomechanics. We use the 6-fold increase in
stiffness induced by PEI to program BSA-hydrogels in various shapes. By
utilizing the characteristic protein unfolding we can induce reversible
shape-memory behavior of these composite materials using chemical denaturing
solutions. We anticipate this novel approach based on protein engineering and
polymer reinforcing will enable the development and investigation of new smart
biomaterials and extend protein hydrogel capabilities beyond their conventional
applications.
A systematic literature review of lean manufacturing implementation in manufacturing-based sectors of the developing and developed countries
Authors: Maware Catherine , Okwu Modestus Okechukwu , Adetunji Olufemi
Published: June 2021

Purpose

This study aims to comparatively discuss the effect of lean manufacturing (LM) implementation in the manufacturing sectors of developing and developed countries.

Design/methodology/approach

An in-depth literature review focused on previous research published between 2015 and March 2020. The papers published by the databases such as Google Scholar, Scopus, ProQuest and Web of Science were used in the study. A total of 63 studies that focused on LM application in manufacturing industries in developing and developed countries were used in the research.

Findings

It was observed that LM improves operational performance for manufacturing organizations in developing and developed countries. Small and medium-sized enterprises in both developed and developing countries have difficulties transforming their organizations into lean organizations compared to large enterprises. Furthermore, the review also found that there seems to have been no paper had reported the negative impact of implementing LM in manufacturing industries in developing and developed countries from 2015 to March 2020.

Research limitations/implications

The study used research papers written between January 2015 and March 2020 and only considered manufacturing organizations from developed and developing nations.

Practical implications

The study provides more insight into LM implementation in developing and developed countries. It gives the LM practices and the implications of applying these practices in manufacturing organizations for developing and developed countries.

Originality/value

A preliminary review of papers indicated that this seems to be the first paper that comparatively studies how LM implementation has affected manufacturing organizations in developed and developing countries. The study also assessed the LM practices commonly used by the manufacturing industries in developing and developed countries.
Industry 4.0: technology spillover impact on digital manufacturing industry
Authors: Miao Zeyi
Published: June 2021

Purpose

Under the guidance of the concept of openness and development, the paper grasps the mechanism of technology spillover in developed countries and analyzes how to better absorb advanced manufacturing technology based on empirical analysis so as to point out the path for the transformation and development of China’s digital manufacturing industry.

Design/methodology/approach

The paper constructs the panel data model and further analyzes the impact of international technology spillovers on the transformation and development of the digital manufacturing industry.

Findings

This paper measures the level of technology spillover in the Yangtze River Delta region and finds that foreign direct investment (FDI) technology spillover and import trade technology spillover among four provinces and cities show a growth trend from 2010 to 2017. But after 2017, there is a certain degree of decline.

Originality/value

With the advent of industry 4.0, the digital manufacturing industry of all countries in the world is developing with a new attitude, the global technology spillover methods are diverse and the spillover channels have changed greatly, which will affect the transformation and upgrading of China's digital manufacturing industry.
Modeling the enablers of sourcing risks faced by startups in COVID-19 era
Authors: Sreenivasan Aswathy , Suresh M.
Published: June 2021

Purpose

Startups across all sectors are affected by the COVID-19 pandemic and are facing a formidable challenge in terms of marketing and operations. Most of the startups have experienced a downturn in demand and supply due to COVID-19 led disturbances in sourcing networks. This paper aims to identify, analyze and categorize the significant risks influencing sourcing operations in startups during the COVID-19 era in India, using the total interpretive structural modeling (TISM) approach.

Design/methodology/approach

Eight enablers were identified through literature review and expert opinions from various startups in India. This study adopted the TISM approach to analyze the inter-relationships between the enablers. Multiplication Applied to Classification (MICMAC) analysis was used to rank the sourcing risk enablers and classify them as autonomous, independent, linkage and dependent enablers.

Findings

The results indicate “insufficient fund” as the most critical enabler. Network issues and employee flexibility risk were among the other critical enablers that have a high driving power. Supplier risk, quality risk and demand risk were found to have highly dependent on other enablers for implementation.

Research limitations/implications

This study mainly focuses on the sourcing risks in startup operations in India. This study can be extended to many other countries.

Practical implications

This study will help startup industry managers and practitioners understand the interactions of enablers and identify critical enablers to mitigate risks in startup sourcing operations in the COVID-19 era.

Originality/value

The present study identifies the sourcing risk enablers in the COVID-19 era. It is the first attempt to analyze the interrelationship among sourcing risks in startups using the TISM approach.
A meta-analysis of the variables related to turnover intention among IT personnel
Authors: Özkan Ahmet Hakan
Published: June 2021

Purpose

This study aims to investigate the relationships between job satisfaction, organizational commitment and turnover intention of information technology (IT) personnel.

Design/methodology/approach

3,844 studies which are published between 1998 and 2019 are screened on ScienceDirect, Scopus and ProQuest databases. 10,523 subjects formed the first data set regarding the relationship between job satisfaction and turnover intention, 7,903 subjects formed the second data set regarding the relationship between organizational commitment and turnover intention, 843 subjects formed the third data set regarding the relationship between empowerment and turnover intention, and 3,430 subjects formed the fourth data set regarding the relationship between job satisfaction and organizational commitment.

Findings

Results showed that the effect size of the relationship between job satisfaction and organizational commitment is the strongest (r = 0.59). The effect size of the relationship between job satisfaction and turnover intention (r = −0.50), and the effect size of the relationship between organizational commitment and turnover intentionr = −0.51) were also large. But the effect size of the relationship between empowerment and turnover intention was medium (r = −0.34).

Originality/value

This study is rare, and it can be used by the managers working in the IT industry.
The confluence approach – a theoretical proposition for effective structuring of architecture studio pedagogy in e-learning mode
Authors: Khan Asif R. , Thilagam N. Lakshmi
Published: June 2021

Purpose

The Covid-19 crisis has inflicted a disruptive impact on the conventional institutional format of architecture studio pedagogy. As a result, there is a critical suddenness for an alternative approach to ensure continuity. The research pursues is to pursue a multidisciplinary study with a focus on the following domains: architecture, the science of learning and e-learning architecture. Inference from the study would become the basis for a theoretical proposition for improvement of the existing pedagogical framework. Moreover, the literature would add valuable insights to the knowledge base.

Design/methodology/approach

An exploratory research approach is used for this study. The inquiry-based approach enlightens on the role of the architect in society. Also, the nature of architectural design education that existed prior to the Covid-19 outbreak is examined. Further, the paper explores the impact of the paradigm shift from institutional mode to e-learning mode overnight. Purposefully multi-disciplinary studies are pursued to develop a broad understanding of the associated domains. This could effectively contribute to developing an effective pedagogical framework. This would facilitate the conduct of architecture studio discourse in a structured manner during the current scenario.

Findings

The confluence approach – a theoretical proposition for effective structuring of architecture studio pedagogy has evolved as part of the research. Further, the proposed virtual learning pyramid enlightens on the drive to continue on with augmentation of students existing creative acumen. Which is one of the universally sought-after goals of studio pedagogy even during times of uncertainties.

Research limitations/implications

Pedagogues would find the study very meaningful for the conduct of architecture design studio in e-learning mode. They would also acquire a broad understanding of factors to be considered. The research would pave way for future studies in this area from a multi-disciplinary perspective.

Social implications

The current Covid-19 crisis deters architecture studio discourse from being conducted in an accustomed institutional format. Therefore, it becomes important for institutions to ensure continuity of architectural education with the help of new measures. In concurrence, the research envisions an alternative approach: virtual design studio using e-learning mode. This would ensure continuity of architectural education even when the instructor and students are separated in either time or place.

Originality/value

The study presents a unique contribution to the limited literature available on architecture studio pedagogy during the e-learning scenario.
Supply chain sustainability learning: the COVID-19 impact on emerging economy suppliers
Authors: Pereira Michele Morais Oliveira , Silva Minelle E. , Hendry Linda C.
Published: June 2021

Purpose

This paper aims to investigate the impact of the COVID-19 pandemic on supply chain (SC) sustainability learning. In particular, it focuses on the learning associated with changes in the sustainability initiatives of emerging economy suppliers.

Design/methodology/approach

Through studying three scenarios (pre-outbreak, buyer-centred peak and supplier-centred peak) over a nine-month period, a multi-case study strategy was used to gain an understanding of the learning of export-oriented Brazilian coffee producers, using both exploitation and exploration capabilities. Content analysis was developed after each data collection phase to investigate how sustainability initiatives had changed.

Findings

Social sustainability was observed to be the main priority by suppliers facing this unprecedented outbreak, in ways that go beyond expected sustainability certification requirements. For instance, there was evidence of outstanding contributions to the local community. Suppliers initially developed their sustainability initiatives during the outbreak without any support from global buyers, certification bodies or government. In spite of this, stronger relationships with buyers ultimately emerged facilitating greater SC sustainability. Consequently, by using both exploitation and exploration learning capabilities, multiple levels of learning were observed (i.e. individual, organisational and SC) as related to planning, new procedures and social awareness.

Practical implications

A greater awareness of supplier learning processes will aid buyers in developing recovery plans that are appropriate for their global SC partners.

Originality/value

This paper provides an understanding of how emerging economy suppliers of global SCs are coping with this unprecedented outbreak in regard to sustainability management. Moving the spotlight from buyers to suppliers, the research demonstrates that supplier learning is central to global SC sustainability.
Identity/Alterity Re‐De‐Constructed in Repetition and Difference
Authors: Deepwell Katy
Published: June 2021

This essay offers a close reading of Verdi Yahooda's work Photo Booth Classic (1974–present), its presentation as artists’ pages in n.paradoxa: international feminist art journal, 17, January 2006, and in the exhibitions Said (London: Camberwell Space, 2008) and Now! Now! In more than one place (London: Cookhouse and Triangle Space, Chelsea College of Art and Design, 2016) organized by the Black Arts and Modernism project. The differences in format and presentation over time, as well as the making of this work, as an action performed by the artist in monthly cycles over forty years, are considered in relation to other artworks, the use of documentation as medium, and questions about feminism, ethnicity and Jewishness. The aim is to move beyond the ready identification of this work as simply another example of a woman artist's performance made as if self‐to‐camera, or as identity politics.
Vong Phaophanit and Claire Oboussier: Three Decades, Four Moments
Authors: san lok susan pui
Published: June 2021

‘Three Decades, Four Moments’ is based on two interviews that took place in 2016 and 2017 with the artists Vong Phaophanit and Claire Oboussier in their studio in London. The text foregrounds a number of works by Phaophanit/Oboussier, signalling four ‘moments’ in their artistic practice over several decades, at turns identified (and resisted) as individual, collective and collaborative. In these, we may find coincidences, correspondences and divergences from the three (or four) ‘moments’ in Stuart Hall's essay: moments that interrogate the space of the ‘international’; that complicate the ‘problem space’ of the 1980s; and that inhabit what Zeigam Azizov, cited by Hall, calls ‘“the migration paradigm” – boundaries and border crossings, liminal and disrupted places, voyaging and displacement, fault lines’. Works discussed include: Neon Rice Field (1993); Line Writing (1994); Atopia (1997 and 2003); All That's Solid Melts into Air (Karl Marx) (2005–6); and It Is As If (2015).
Brexit, Covid‐19, and Possible Frameworks for Future UK/EU Financial Governance Cooperation
Authors: Howell Elizabeth
Published: June 2021

The EU project is at an inflection point. Intra‐EU alliances are altering following the UK's departure, the EU's financial markets remain segmented, and there is limited appetite for completing the Banking Union. The second stage of Brexit negotiations also collided with the Covid‐19 pandemic, which has strained economies around the world. These issues amount to a ‘polycrisis’ for the EU, raising existential questions about its future. This article focuses on one strand of the debates generated within this polycrisis: future UK/EU policy cooperation with respect to financial governance. The article discusses the importance of the financial services sector to the UK and the EU, and examines potential institutional options for future cooperation. In particular, it advocates harnessing dexterous aspects evident within precedents, including existing EU/third country association agreements, to develop a functional arrangement for future financial governance cooperation, which could also lead to closer UK/EU cooperation than currently appears likely.
A hierarchy of expert performance as applied to forensic anthropology
Authors: Hartley Stephanie , Winburn Allysha Powanda
Published: June 2021

Due to their medicolegal repercussions, forensic anthropology conclusions must be reliable, consistent, and minimally compromised by bias. Yet, a synthetic analysis of the reliability and biasability of the discipline's methods has not yet been conducted. To do so, this study utilized Dror's (2016) hierarchy of expert performance (HEP), an eight‐level model aimed at examining intra‐ and inter‐expert reliability and biasability (the potential for cognitive bias) within the literature of forensic science disciplines. A systematic review of the forensic anthropology literature was conducted (1972‐present), including papers published in the American Journal of Physical Anthropology, Forensic Anthropology, Forensic Science International, and the Journal of Forensic Sciences and Anthropology Section abstracts published in the Proceedings of the Annual Meeting of the AAFS which matched keywords such as “forensic anthropology,” “bias,” “reliability,” “cognition,” “cognitive,” or “error.” The resulting forensic anthropology HEP showcases areas that have ample research and areas where more research can be conducted. Specifically, statistically significant increases in reliability (p < 0.001) and biasability (p < 0.001) publications were found since 2009 (publication of the NAS report). Extensive research examined the reliability of forensic anthropological observations and conclusions (n = 744 publications). However, minimal research investigated the biasability of forensic anthropological observations and conclusions (n = 20 publications). Notably, while several studies demonstrated the biasing effect of extraneous information on anthropological morphological assessments, there was no research into these effects on anthropological metric assessments. The findings revealed by the forensic anthropology HEP can help to guide future research, ultimately informing the development and refinement of best‐practice standards for the discipline.
Magnetic Resonance Imaging evidence of Inflammation at Interphalangeal joint of Thumb — A distinct entity in psoriatic arthritis
Authors: Mathew Ashish J , Ganapati Arvind , Panwar Jyoti , Koshy Varghese , Desai Anu , Danda Debashish
Published: June 2021

Background

This study aimed to compare inflammation at the interphalangeal (IP) joint of thumb in patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), undifferentiated inflammatory arthritis (UIA), and in psoriasis patients without clinical arthritis (PsO) using low‐field magnetic resonance imaging (MRI).

Methods

Age‐matched and disease duration‐matched patients with inflammatory arthritis (RA, PsA, and UIA) and psoriasis patients without clinical arthritis (PsO), who had undergone MRI of hands were included in this study. The presence or absence of MRI inflammatory lesions including synovitis, tenosynovitis, and bone marrow edema was assessed by three independent readers. Agreement between the readers was assessed using the intraclass correlation coefficient. Risk ratio of MRI global inflammation around thumb IP joints among patients with PsA was compared with the other groups.

Results

Clinical parameters and MRI inflammation were studied in 161 patients (42 PsA, 28 RA, 29 UIA, and 62 PsO). Global MRI inflammation at the IP joint of the thumb was observed in 33.3% of PsA patients compared with 14.3% in RA, and 10.3% in UIA. Subclinical MRI inflammation was observed in 8.1% of patients with PsO. The risk ratios of MRI global inflammation at the IP joint of the thumb in PsA patients were 2.3 (95% confidence interval [CI] 0.86‐6.36) and 3.2 (95% CI 1.02‐10.21) compared with RA and UIA patients, respectively.

Conclusion

Global MRI inflammation around the IP joint of the thumb is significantly more common in patients with PsA as compared to individuals with UIA.
Hospitalizations in solid tumor phase I clinical trial patients: Incidence, pattern and clinical outcomes at an Australian phase I clinical trial unit
Authors: Ye Linda , Ariyapperuma Mihitha , Jacques Angela , Meniawy Tarek , Millward Michael
Published: June 2021

Background

Participation in early‐phase clinical trials has become a prominent part of medical oncology patient management. We examined the incidence and pattern of hospitalizations in early‐phase clinical trial patients and the associated clinical outcomes.

Method

We conducted a retrospective review of 194 patients with solid tumors treated on phase I clinical trials between July 2014 and October 2018 at a phase I trial unit. Unplanned hospitalizations occurring during the study period were characterized and correlated with treatment response and duration of trial participation.

Results

Among 194 patients, 104 hospitalizations were recorded involving 62 patients (31%). Nineteen percent of patients were hospitalized for cancer‐related complications and 8% for treatment toxicity. No significant correlation was seen between the hospitalization and age, sex, tumor type, or trial drug. Best response to trial therapy was complete response, partial response, stable disease, and progressive disease in 5%, 11%, 37%, and 47% of patients, respectively. Median duration on trial was 86 days (range 0–1,412). Twenty‐two patients (11%) remained on trial for more than 12 months. Overall, hospitalization did not impact treatment response or trial duration. However, cancer‐related hospitalization was associated with significantly lower response (p < 0.001) and early patient attrition (p < 0.001). Resolution of the hospitalization event was associated with improved response (p = 0.002) and longer duration on trial (p < 0.001). The treatment related mortality was 0.5% (n = 1).

Conclusion

Approximately one third of patients required hospitalization, most commonly for cancer‐related complications which correlated with poorer clinical outcomes. Hospitalizations related to treatment toxicity were infrequent. A significant proportion of patients derived significant therapeutic benefit. Phase I clinical trials provide a valuable treatment option for patients with cancer.
One Health: EAACI Position Paper on coronaviruses at the human‐animal interface, with a specific focus on comparative and zoonotic aspects of SARS‐CoV‐2
Authors: Korath Anna D. J. , Janda Jozef , Untersmayr Eva , Sokolowska Milena , Feleszko Wojciech , Agache Ioana , Adel Seida Ahmed , Hartmann Katrin , Jensen‐Jarolim Erika , Pali‐Schöll Isabella
Published: June 2021

The latest outbreak of a coronavirus disease in 2019 (COVID‐19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), evolved into a worldwide pandemic with massive effects on health, quality of life, and economy. Given the short period of time since the outbreak, there are several knowledge gaps on the comparative and zoonotic aspects of this new virus. Within the One Health concept, the current EAACI position paper dwells into the current knowledge on SARS‐CoV‐2’s receptors, symptoms, transmission routes for human and animals living in close vicinity to each other, usefulness of animal models to study this disease and management options to avoid intra‐ and interspecies transmission. Similar pandemics might appear unexpectedly and more frequently in the near future due to climate change, consumption of exotic foods and drinks, globe‐trotter travel possibilities, the growing world population, the decreasing production space, declining room for wildlife and free‐ranging animals, and the changed lifestyle including living very close to animals. Therefore, both the society and the health authorities need to be aware and well prepared for similar future situations, and research needs to focus on prevention and fast development of treatment options (medications, vaccines).
Endoscopic clips allow for accurate pre‐operative localisation of colorectal cancer
Authors: Parys Simon , Park Hyerin , Entriken Fiona , Ee Hooi C. , Hodder Rupert
Published: June 2021

Background

Colorectal cancer is a major cause of morbidity and mortality worldwide. Optimal management of this disease relies upon accurate pre‐operative localisation to allow multidisciplinary discussion and treatment planning. Current pre‐operative localisation methods consist of colonoscopy and computed tomography (CT), which are only 79%–85% accurate. To minimise this error, colonoscopy tattooing is a routine practice to facilitate operative localisation. The aim of this study is to investigate if endoscopic radiopaque clips can more accurately localise the lesions pre‐operatively.

Methods

A retrospective case–control study was conducted of patients diagnosed with colorectal cancer at a tertiary hospital between 2017 and 2019. Visualisation rates and accurate localisation rates were compared between patients receiving radiopaque clips and those who had colonoscopy alone. All patients received a tattoo distal to the tumour and a staging CT. Data on patient demographics, tumour demographics, post‐procedure complications and changes to surgical management were collected.

Results

Of 285 patients, 245 had tumour localisation with colonoscopy alone and 40 had additional clip localisation. Groups had comparable patient demographics. For patients receiving clips and follow‐up CTs within 14 days, 92% of lesions were visualised and 100% of these lesions were accurately localised. In contrast, colonoscopy only accurately localised 77% of lesions (p < 0.01). This resulted in 1.2% of patients requiring an altered operation due to incorrect localisation. No clip‐related complications were reported.

Conclusion

Radiopaque clips are a highly accurate and cost‐effective method for localising colorectal cancer with a pre‐operative accuracy rate over 92%.
Prevalence and incidence of diabetic retinopathy (DR) in the UK population of Gloucestershire
Authors: Scanlon Peter H. , Nevill Clareece R. , Stratton Irene M. , Maruti Sonia S. , Massó‐González Elvira L. , Sivaprasad Sobha , Bailey Clare , Ehrlich Michael , Chong Victor
Published: June 2021

Purpose

To estimate prevalence and incidence of diabetic retinopathy (DR) in a UK region by severity between 2012 and 2016 and risk factors for progression to proliferative DR (PDR).

Methods

Electronic medical records from people with diabetes (PWD) ≥18 years seen at the Gloucestershire Diabetic Eye Screening Programme (GDESP) and the hospital eye clinic were analysed (HEC). Prevalence and incidence of DR per 100 PWD (%) by calendar year, grade and diabetes type were estimated using log‐linear regression. Progression to PDR and associated risk factors were estimated using parametric survival analyses.

Results

Across the study period, 35 873 PWD had at least one DR assessment. They were aged 66 (56–75) years (median (interquartile range)), 57% male, 5 (1–10) years since diabetes diagnosis, 93% Type 2 diabetes. Prevalence of DR decreased from 38.9% (95% CI: 38.1%, 39.8%) in 2012 to 36.6% (95% CI: 35.9%, 37.3%) in 2016 (p < 0.001). Incidence of any DR decreased from 10.9% (95% CI: 10.4%, 11.5%) in 2013 to 8.5% (95% CI: 8.1%, 9.0%) in 2016 (p < 0.001). Prevalence of PDR decreased from 3.5% (95% CI: 3.3%, 3.8%) in 2012 to 3.1% (95% CI 2.9%, 3.3%) in 2016 (p = 0.008). Incidence of PDR did not change over time. HbA1c and bilateral moderate–severe NPDR were statistically significant risk factors associated with progression to PDR.

Conclusions

Incidence and prevalence of DR decreased between 2012 and 2016 in this well‐characterized population of the UK.
Recognizing heat‐treated chert: A comparison between infrared spectroscopy and fracture surface analysis
Authors: Bachellerie Julie , Schmidt Patrick
Published: June 2021

Heat treatment of lithic raw material is used for the first time in Europe in the Solutrean of the upper Paleolithic. The study of which heating technique was used by these groups requires analytical methods to understand and recognize the chemical and physical processes involved. Roughness measurements were tested as a tool for recognizing heat treatment and to compare them to infrared spectroscopy. We also measured the surface topography of geological samples to observe its evolution as a function of heating and then compare the results with those obtained on Solutrean artefacts. Near infrared analyses was carried out for comparing the effectiveness of surface roughness measurements. This work complements our knowledge about the heating environment used by Solutrean groups by confirming the use of controlled heating. In addition, our roughness measurements provide promising results for the recognition of heat treatment through the quantification of the surface luster.
Justifying the risks of COVID‐19 challenge trials: The analogy with organ donation
Authors: Jayaram Athmeya , Sparks Jacob , Callies Daniel
Published: June 2021

In the beginning of the COVID pandemic, researchers and bioethicists called for human challenge trials to hasten the development of a vaccine for COVID. However, the fact that we lacked a specific, highly effective treatment for COVID led many to argue that a COVID challenge trial would be unethical and we ought to pursue traditional phase III testing instead. These ethical objections to challenge trials may have slowed the progress of a COVID vaccine, so it is important to evaluate their merit. One common way of doing so is to make an analogy to other social practices that are relevantly similar and which we currently sanction. We submit that non‐directed live organ donation (NDLOD) is a promising analogy. After arguing that the risks to volunteers for each activity appear similar, we explore potential disanalogies that would undermine the comparison. We note that there are differences in both the kind and certainty of benefit secured by NDLOD compared to challenge trials. We conclude these differences are insufficient to make NDLOD permissible and challenge trials impermissible. Ultimately, if we think the risks associated with NDLOD are ethically permissible, then we should think the same of the risks associated with COVID challenge trials.
Australian women's experiences of receiving maternity care during the COVID‐19 pandemic: A cross‐sectional national survey
Authors: Wilson Alyce N. , Sweet Linda , Vasilevski Vidanka , Hauck Yvonne , Wynter Karen , Kuliukas Lesley , Szabo Rebecca A. , Homer Caroline S. E. , Bradfield Zoe
Published: June 2021

Background

The COVID‐19 pandemic has led to multiple changes in maternity services worldwide. Systems rapidly adapted to meet public health requirements aimed at preventing transmission of SARS‐CoV‐2, including quarantine procedures, travel restrictions, border closures, physical distancing and “stay‐at‐home” orders. Although these changes have impacted all stakeholders in maternity services, arguably the women at the center of this care have been most affected. This study aimed to explore women's experiences of receiving maternity care during the COVID‐19 pandemic in Australia.

Methods

A national cross‐sectional online survey, including fixed choice and open‐ended questions, was conducted during the first wave of the COVID‐19 pandemic in Australia; pregnant and postnatal women were recruited through social media networks.

Results

The survey was completed by 3364 women. Women felt distressed and alone due to rapid changes to their maternity care. Limited face‐to‐face contact with health practitioners and altered models of care often required women to accommodate significant changes and to coordinate their own care. Women felt that they were often “doing it alone,” due to public health restrictions on support people and visitors, both within and outside health services. Women described some benefits of visitor restrictions, such as, more time for rest, breastfeeding establishment, and bonding with their baby.

Conclusions

This large nationwide Australian study provides unique data on women's experiences of receiving maternity care during the COVID‐19 pandemic. Lessons learned provide an opportunity to rebuild and reshape the maternity sector to best meet the needs of women and their families during current and future public health crises.
Predictors of cardiovascular events and all‐cause of death in patients with transfusion‐dependent myelodysplastic syndrome
Authors: Alonso‐Fernandez‐Gatta Marta , Martin‐Garcia Ana , Martin‐Garcia Agustin C. , Lopez‐Cadenas Felix , Diaz‐Pelaez Elena , Jimenez‐Solas Tamara , Gonzalez‐Martinez Teresa , Sanchez‐Pablo Clara , Diez‐Campelo Maria , Sanchez Pedro L.
Published: June 2021

Cardiovascular disease (CVD) involves the second cause of death in low‐risk myelodysplastic syndrome (MDS) population. Prospective study to characterise the CVD and to identify predictors for the combined event (CE) cardiovascular event and/or all‐cause mortality in transfusion dependent low‐risk MDS patients. Thirty‐one patients underwent a cardiac assessment including biomarkers and cardiac magnetic resonance (cMR) with parametric sequences (T1, T2 and T2* mapping) and myocardial deformation by feature tracking (FT) and were analysed for clonal hematopoiesis of indeterminate potential mutations. Cardiac assessment revealed high prevalence of unknown structural heart disease (51% cMR pathological findings). After 2·2 [0·44] years follow‐up, 35·5% of patients suffered the CE: 16% death, 29% cardiovascular event. At multivariate analysis elevated NT‐proBNP ≥ 486pg/ml (HR 96·7; 95%‐CI 1·135–8243; P = 0·044), reduced native T1 time < 983ms (HR 44·8; 95%‐CI 1·235–1623; P = 0·038) and higher left ventricular global longitudinal strain (LV‐GLS) (HR 0·4; 95%‐CI 0·196–0·973; P = 0·043) showed an independent prognostic value. These variables, together with the myocardial T2* time < 20ms, showed an additive prognostic value (Log Rank: 12·4; P = 0·001). In conclusion, low‐risk MDS patients frequently suffer CVD. NT‐proBNP value, native T1 relaxation time and longitudinal strain by FT are independent predictors of poor cardiovascular prognosis, thus, their determination would identify high‐risk patients who could benefit from a cardiac treatment and follow‐up.
The Inter‐American Court of Human Rights and Indigenous Rights in Nicaragua: From Land to Empowerment?
Authors: Koper Natalia
Published: June 2021

Through fieldwork conducted among Mayangna and Miskito indigenous peoples in Nicaragua I examine the capacity of the judgments of the Inter‐American Court of Human Rights to build political agency. I observe that Miskito and Mayangna communities struggle to advance their agenda, as they remain entangled in inter‐ethnic resentments and a culture of corruption. I conclude that the language of rights promoted by the Court and embraced by the communities is insufficient to politicise the right to indigenous land effectively as long as that demand does not align with the interests of other political groups in Nicaragua.
Grassland trees and the common bulbul Pycnonotus barbatus promote Afromontane forest restoration
Authors: Jaafar Ridwan , Yadok Biplang G. , Elisha Emmanuel B. , Chapman Hazel M.
Published: June 2021

Restoration of Afromontane forests is critical because of their biodiversity richness and ecosystem service provision. With an evolutionary history of rapid forest migration into grassland in response to shifting climate, traits of Afromontane forests such as a high frequency of light tolerant, small fruited, and bird dispersed species may pre‐adapt them to relatively rapid recolonization of grassland protected from fire. Here, we test this hypothesis with a focus on the role of isolated grassland tree species in promoting forest regeneration. Through seed, seedling, and frugivore surveys, we found that seed rain below small, isolated grassland trees was almost 300 times that in open grassland, with 30 times more seedlings established under trees. However, these seedlings were mostly grassland or forest edge woody shrubs or small trees. Dispersal limitation was moderate to high and establishment limitation high for all other species. Ecological filtering of seed species favored some over others, which needs further exploration. Key tree traits attracting frugivore visits were distance from forest edge, height, and “leaflessness.” Across a year of sampling almost 90% of frugivore visits to isolated trees were by just two grassland / forest edge species, the common bulbul Pycnonotus barbatus (71%) and the speckled mouse bird Colius striatus (17%). Overall, our results suggest that while anthropogenic changes within Afromontane systems render any pre‐adaption Afromontane forests may have to rapid reestablishment of forest into grassland ineffectual, small, isolated grassland trees are nevertheless critical for the first stage of succession.
Ca2+‐activated K+ channel KCa1.1 as a therapeutic target to overcome chemoresistance in three‐dimensional sarcoma spheroid models
Authors: Ohya Susumu , Kajikuri Junko , Endo Kyoko , Kito Hiroaki , Elboray Elghareeb E. , Suzuki Takayoshi
Published: June 2021

The large‐conductance Ca2+‐activated K+ channel KCa1.1 plays a pivotal role in tumor development and progression in several solid cancers. The three‐dimensional (3D) in vitro cell culture system is a powerful tool for cancer spheroid formation, and mimics in vivo solid tumor resistance to chemotherapy in the tumor microenvironment (TME). KCa1.1 is functionally expressed in osteosarcoma and chondrosarcoma cell lines. KCa1.1 activator‐induced hyperpolarizing responses were significantly larger in human osteosarcoma MG‐63 cells isolated from 3D spheroid models compared with in those from adherent 2D monolayer cells. The present study investigated the mechanisms underlying the upregulation of KCa1.1 and its role in chemoresistance using a 3D spheroid model. KCa1.1 protein expression levels were significantly elevated in the lipid‐raft‐enriched compartments of MG‐63 spheroids without changes in its transcriptional level. 3D spheroid formation downregulated the expression of the ubiquitin E3 ligase FBXW7, which is an essential contributor to KCa1.1 protein degradation in breast cancer. The siRNA‐mediated inhibition of FBXW7 in MG‐63 cells from 2D monolayers upregulated KCa1.1 protein expression. Furthermore, a treatment with a potent and selective KCa1.1 inhibitor overcame the chemoresistance of the MG‐63 and human chondrosarcoma SW‐1353 spheroid models to paclitaxel, doxorubicin, and cisplatin. Among several multidrug resistance ATP‐binding cassette transporters, the expression of the multidrug resistance‐associated protein MRP1 was upregulated in both spheroids and restored by the inhibition of KCa1.1. Therefore, the pharmacological inhibition of KCa1.1 may be an attractive new strategy for acquiring resistance to chemotherapeutic drugs in the TME of KCa1.1‐positive sarcomas.
The Warburg effect as a therapeutic target for bladder cancers and intratumoral heterogeneity in associated molecular targets
Authors: Burns Julie E. , Hurst Carolyn D. , Knowles Margaret A. , Phillips Roger M. , Allison Simon J.
Published: June 2021

Bladder cancer is the 10th most common cancer worldwide. For muscle‐invasive bladder cancer (MIBC), treatment includes radical cystectomy, radiotherapy, and chemotherapy; however, the outcome is generally poor. For non–muscle‐invasive bladder cancer (NMIBC), tumor recurrence is common. There is an urgent need for more effective and less harmful therapeutic approaches. Here, bladder cancer cell metabolic reprogramming to rely on aerobic glycolysis (the Warburg effect) and expression of associated molecular therapeutic targets by bladder cancer cells of different stages and grades, and in freshly resected clinical tissue, is investigated. Importantly, analyses indicate that the Warburg effect is a feature of both NMIBCs and MIBCs. In two in vitro inducible epithelial‐mesenchymal transition (EMT) bladder cancer models, EMT stimulation correlated with increased lactate production, the end product of aerobic glycolysis. Protein levels of lactate dehydrogenase A (LDH‐A), which promotes pyruvate enzymatic reduction to lactate, were higher in most bladder cancer cell lines (compared with LDH‐B, which catalyzes the reverse reaction), but the levels did not closely correlate with aerobic glycolysis rates. Although LDH‐A is expressed in normal urothelial cells, LDH‐A knockdown by RNAi selectively induced urothelial cancer cell apoptotic death, whereas normal cells were unaffected—identifying LDH‐A as a cancer‐selective therapeutic target for bladder cancers. LDH‐A and other potential therapeutic targets (MCT4 and GLUT1) were expressed in patient clinical specimens; however, positive staining varied in different areas of sections and with distance from a blood vessel. This intratumoral heterogeneity has important therapeutic implications and indicates the possibility of tumor cell metabolic coupling.
‘We are Hungry but We Won’t Eat the Food’: Schoolchildren’s ‘Thin’ agency and its impacts on the implementation of Ghana’s School Feeding Programme
Authors: Mohammed Abdul‐Rahim
Published: June 2021

Following the introduction of the concept of agency by the New Sociology of Childhood, the concept has dominated discourses about children's everyday lives. Nevertheless, little is known about schoolchildren's agency in their daily interactions with the service providers of Ghana's school feeding programme. Through this qualitative study, the paper provides empirical evidence to show how children in restrictive contexts exercise ‘thin’ agency in their interactions with frontline service providers, leading to significant improvements in the quality of services delivered to them. Consequently, the article questions Michael Lipsky's assumption that clients have minimal effect on the services delivered to them.
Disclosures of harming others during their most recent drinking session: Findings from a large national study of heavy‐drinking adolescents
Authors: Lam Tina , Laslett Anne‐Marie , Fischer Jane , Salom Caroline , Ogeil Rowan P. , Lubman Dan I. , Aiken Alexandra , Mattick Richard , Gilmore William , Allsop Steve
Published: June 2021

Introduction

The extant Alcohol's Harms to Others (AHTO) literature is largely comprised of reports from victims. We investigated AHTO from perpetrators' perspectives, including how harms were associated with individual characteristics, and alcohol quantities consumed during the perpetration incident.

Methods

Participants (N = 2932) were 14–19 years old, recruited primarily through social media and screened as risky drinkers. They completed face‐to‐face (n = 594) or self‐administered (n = 2338) surveys. They self‐reported whether during their last risky drinking session (LRDS) they had perpetrated any verbal abuse, physical abuse or property damage. A multinomial logistic regression examined whether nine factors were associated with perpetrating zero, one or 2+ categories of AHTO.

Results

Eleven percent (n = 323) reported perpetrating at least one form of AHTO (7.5% verbal, 1.9% physical and 4.6% property). Perpetration of AHTO at LRDS was uniquely associated with: younger age, male gender, experiences of childhood physical punishment, greater perpetration incident‐specific drinking, concurrent illicit drug use, and less frequent use of safety strategies while drinking in the past 12 months. Controlling for the other variables, an increase of six Australian standard drinks (60 g of alcohol) increased the odds of perpetration by 15% [95% confidence interval (CI) adjusted odds ratio (AOR) 1.08, 1.23], and an increase of 15 Australian standard drinks increased the odds by 42% (95% CI AOR 1.20, 1.69).

Discussion and Conclusions

Individual characteristics, larger quantities of alcohol consumed, and a disinclination to practice harm reduction amplified risk of AHTO perpetration. This has implications for health promotion and risk prevention/reduction strategies.