bluuebunny/crossref_metadata_2025 huggingface dataset:
Ancient Demographics Determine the Effectiveness of Genetic Purging in Endangered Lizards
Authors: Xie Hong-Xin , Liang Xi-Xi , Chen Zhi-Qiang , Li Wei-Ming , Mi Chun-Rong , Li Ming , Wu Zheng-Jun , Zhou Xu-Ming , Du Wei-Guo
Published: December 2021

The purging of deleterious alleles has been hypothesized to mitigate inbreeding depression, but its effectiveness in endangered species remains debatable. To understand how deleterious alleles are purged during population contractions, we analyzed genomes of the endangered Chinese crocodile lizard (Shinisaurus crocodilurus), which is the only surviving species of its family and currently isolated into small populations. Population genomic analyses revealed four genetically distinct conservation units and sharp declines in both effective population size and genetic diversity. By comparing the relative genetic load across populations and conducting genomic simulations, we discovered that seriously deleterious alleles were effectively purged during population contractions in this relict species, although inbreeding generally enhanced the genetic burden. However, despite with the initial purging, our simulations also predicted that seriously deleterious alleles will gradually accumulate under prolonged bottlenecking. Therefore, we emphasize the importance of maintaining a minimum population capacity and increasing the functional genetic diversity in conservation efforts to preserve populations of the crocodile lizard and other endangered species.
Adult-onset Still’s disease during pregnancy that delivered a neonate with haemophagocytic lymphohistiocytosis and severe liver failure requiring liver transplantation: A case report and literature review
Authors: Watanabe Eri , Sugiyama Yohei , Sato Hiroaki , Imanishi Toshiyuki , Fukuda Akinari , Takagi Kenjiro , Asano Tomoyuki , Migita Kiyoshi , Nanki Toshihiro , Kotake Shigeru
Published: December 2021

Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disorder of unknown aetiology that is categorised as a non-hereditary disease. Neonatal haemophagocytic lymphohistiocytosis (HLH) is also a rare, but potentially fatal condition. Neonatal HLH is one of the causes of neonatal acute liver failure that often requires urgent liver transplantation. The relationship between AOSD during pregnancy and neonatal HLH currently remains unclear. We encountered a case of AOSD that developed during pregnancy, and an offspring was born with neonatal HLH resulting in severe liver failure. The mother with AOSD only presented with liver dysfunction during pregnancy; however, disease activity was exacerbated after delivery. The maternal clinical course was quite severe and refractory that she required biological therapy in addition to high-dose corticosteroids and immunosuppressants. Additionally, the severe condition of the neonate with HLH and acute liver failure required intensive care with the administration of steroids and intravenous immunoglobulin treatments and ultimately liver transplantation. This is the first case that severe maternal AOSD associated with a neonatal HLH resulted in severe clinical courses. Physicians need to be aware of the risk of a mother with AOSD delivering an offspring with neonatal HLH with potentially acute liver failure.
Digital gangrene and pulmonary consolidation in a young girl with Takayasu arteritis
Authors: Bhatt Kamal , Jindal Parveen , Gupta Sudesh , Suri Shalini
Published: December 2021

Takayasu arteritis (TA) is a large-vessel vasculitis most commonly affecting women of childbearing age. The disease process is usually slow and smoldering, presenting over months to years. Digital gangrene is an uncommon manifestation of TA because of the formation of good collateral circulation. Similarly, although pulmonary artery involvement is well described, pulmonary parenchymal involvement is very rare. We are reporting a case of a young girl with TA presenting with digital gangrene and pulmonary consolidation, which was treated successfully with a combination of aggressive systemic immunosuppression and anti-coagulants. The possible mechanism for gangrene along with the confounding diagnostic possibility of co-existing tuberculosis have been discussed.
Interest in Electronic Cigarettes for Smoking Cessation Among Adults With Opioid Use Disorder in Buprenorphine Treatment: A Mixed-Methods Investigation
Authors: Streck Joanna M , Regan Susan , Neil Jordan , Kalkhoran Sara , Gupta Priya S , Bearnot Benjamin , Coker Faith K , Kalagher Kelly M , Park Elyse R , Wakeman Sarah , Rigotti Nancy A
Published: December 2021

Introduction

Individuals in treatment for opioid use disorder (OUD) have high smoking rates and limited success with Food and Drug Administration (FDA)-approved cessation aids, suggesting need for novel approaches. Electronic cigarettes (e-cigarettes) might benefit this population, but e-cigarettes’ acceptability for tobacco reduction or cessation among smokers in OUD treatment is not known.

Methods

A cross-sectional mixed-methods study of 222 adults in OUD treatment with buprenorphine in the Boston, Massachusetts metropolitan area was conducted in 2020. We used quantitative and qualitative data to investigate individuals’ experience with and interest in e-cigarettes and other methods for smoking cessation and assessed factors associated with interest in e-cigarette use.

Results

One hundred sixty (72%) of the 222 participants were past 30-day cigarette smokers. They most frequently reported having ever used nicotine replacement therapy (NRT; 83%) and e-cigarettes (71%) for smoking cessation and most often indicated interest in using NRT (71%) and e-cigarettes (44%) for future smoking cessation. In multiple logistic regression analysis, interest in using e-cigarettes for future smoking cessation was independently associated with having ever used e-cigarettes for smoking cessation, current e-cigarette use, and perceiving e-cigarettes to be less harmful than cigarettes (ps < .05). In qualitative data, many current vapers/former smokers reported that e-cigarettes had been helpful for quitting cigarettes. For current smokers who currently or formerly vaped, frequently reported challenges in switching to e-cigarettes were concerns about replacing one addiction with another and e-cigarettes not adequately substituting for cigarettes.

Conclusions

E-cigarettes had a moderate level of acceptability for smoking cessation among cigarette smokers in OUD treatment. More research is warranted to test the efficacy of this approach.

Implications

Individuals in treatment for opioid use disorder (OUD) have high smoking rates and limited success with existing smoking cessation tools, suggesting a need for novel cessation treatment approaches. In this mixed-methods study of individuals receiving medication treatment for OUD with buprenorphine in Massachusetts in 2020, we found a moderate level of acceptability of e-cigarettes for smoking cessation.
An equity-oriented systematic review of online grocery shopping among low-income populations: implications for policy and research
Authors: Trude Angela C B , Lowery Caitlin M , Ali Shahmir H , Vedovato Gabriela M
Published: December 2021

Context

Online grocery services are an emerging component of the food system with the potential to address disparities in access to healthy food.

Objective

We assessed the barriers and facilitators of equitable access to healthy foods in the online grocery environment, and the psychosocial, purchasing, and dietary behaviors related to its use among low-income, diverse populations.

Data Sources

Four electronic databases were searched to identify relevant literature; 16 studies were identified.

Results

Barriers to equitable access to healthy food included cost and limited availability of online grocery services in food deserts and rural areas. The expansion of online grocery services and the ability to use nutrition assistance benefits online were equity-promoting factors. Perceived low control over food selection was a psychosocial factor that discouraged online grocery use, whereas convenience and lower perceived stress were facilitators. Findings were mixed regarding healthfulness of foods purchased online. Although few studies assessed diet, healthy food consumption was associated with online grocery use.

Conclusion

Researchers should assess the impact of online grocery shopping on low-income families’ food purchases and diet.

Systematic Review Registration

PROSPERO registration no. CRD: 42021240277
Police Labor and Exploitation: Case Study of North India
Authors: Jauregui Beatrice
Published: December 2021

This chapter analyzes data collected over more than two years of ethnographic fieldwork with police in north India. It argues that subordinate police personnel in this decolonizing world region often experience exploitation as laborers, even as they routinely deploy excessive force and sometimes misuse their authority to intervene in everyday life. The analysis reveals an imbrication of official police rank hierarchies with broader forms of social inequality (especially socioeconomic class, religion, and caste) through observations of interactions among police personnel of various ranks and interviews with current and former officers in Uttar Pradesh, India’s most populous state. It also develops methodological concepts of “strategic complicity” and “critical empathy,” and suggests directions for future ethnographic research on policing that may help us discern the complexities of both local and global social justice movements and power relations.
Agriculture in South Africa
Authors: Sihlobo Wandile , Kirsten Johann
Published: December 2021

South Africa is a semi-arid country with a weak resource base for agriculture which is also threatened by climate change and sporadic droughts. Through the adoption of modern technology, increased productivity growth and new export markets, South African commercial agriculture has shown dramatic growth over the last three decades. At the same time, the sector continues to be characterized by an extreme dualism between predominantly white commercial farmers and mainly black smallholder farmers, and many failed efforts to grow the sector in an inclusive and transformed manner. As a result, the country still has ‘two agricultures’. This chapter unpacks the structural characteristics of South African commercial agriculture based on a freighter-relation of the official statistics. This incomplete picture of the structural and geospatial dimensions of agriculture constrain any sensible policy design and support programmes to bring about a sustainable and transformed sector.
Agro-processing Industries in the South AfricaN Economy
Authors: Chitonge Horman
Published: December 2021

This chapter provides an overview of the agro-processing sector in the South African economy, focusing on the sector’s potential to contribute to inclusive growth through high value-added activities. The chapter shows that agro-processing industries have been the largest subsector of the manufacturing sector in the country since the 1970s, accounting for the largest share of both manufacturing output and employment. Apart from being the largest segment of the manufacturing sector, agro-processing industries have the potential to contribute to the broader national objective of transforming the structure of the economy through the creation of jobs and business opportunities for new small and medium enterprises on both sides of the agro-processing value chains. Employment creation potential lies in the fact that most agro-processing industries are labour intensive. Agro-processing industries, on average, use 40 per cent more labour per unit of capital relative to the manufacturing sector as a whole. However, the challenge is that several of the most labour-intensive agro-processing industries are experiencing declining or stagnating value-added, investment, and, most importantly, employment levels. Consistent and coordinated implementation of strategies which revive dynamism in labour-intensive industries is required to overcome this challenge.
Climate Change and the Green Transition in South Africa
Authors: Arndt Channing , Gabriel Sherwin , Hartley Faaiqa , Strzepek Kenneth Marc , Thomas Timothy S.
Published: December 2021

Abstract: Climate change is one of the most complex challenges facing South Africa as the country designs plans and policies for future economic growth and development. Higher temperatures and more variable rainfall are already affecting the economy and are expected to continue for decades. The degree to which climate change affects different regions in South Africa is likely to vary significantly, characterized by wide ranges in the direction and magnitude of change in key climate variables, especially precipitation. These uncertainties interact with South Africa’s growth and development challenges and complicate planning and policy formation in support national development objectives. This chapter presents key research on changes in climate experienced in South Africa in recent years, along with projected changes in years to come. It illustrates the uncertainties related to climate change and the key channels through which climate change affects the economy. The economic and developmental impacts of such changes are presented along with the lessons for adaptation policy. As energy will be a key focus area for mitigation efforts in the country, this chapter also outlines the implications of such a transition and the factors that need to be accounted for in limiting the impacts on vulnerable populations.
Inequality in South Africa
Authors: Leibbrandt Murray , Díaz Pabón Fabio Andrés
Published: December 2021

Post-apartheid South Africa inherited one of the most unequal societies in the world in 1994 and inequality has featured prominently as a key socio-economic and policy challenge over the post-apartheid period. Yet, despite policy interventions aimed at reducing inequality, these high levels of inequality remain in place. Such persistence demands a better understanding of the mechanisms that reproduce and create inequalities. We start by consolidating the extensive research on South Africa’s income inequality and the emerging literature on wealth inequality. We go on to explore the interactions between these economic inequalities, spatial inequality and two key categorical inequalities, gender and race. These inequalities work collectively to stifle opportunity and agency in contemporary South Africa. We show this through the lens of recent work on social mobility that highlights very low levels of social mobility and the precariousness of upward mobility. We conclude by reviewing policies to overcome inequality against this prevailing reality. Some of these policies have addressed important drivers of inequality, but in isolation. This chapter has shown that such an approach will have limited effectiveness. A coherent, integrated approach is required. Derivatively, there is an urgent need for further interdisciplinary research on how to break these inequality traps.
Cyber Espionage
Authors: Lindsay Jon R.
Published: December 2021

The ubiquity of information technology augurs a new golden age of espionage. Intelligence is the use of deceptive means for strategic ends. It encompasses the collection of secrets, analysis and decision support, covert action and influence, and counterintelligence. Modern computational networks expand the opportunities for all these types of intelligence, for new types of actors to engage in intelligence activities, and for almost anyone or anything to become intelligence targets. Yet large-scale information systems also amplify the classic ethical, operational, and strategic challenges associated with intelligence. Many of the policy controversies associated with cybersecurity, for instance, are not simply novelties of the Internet age, but rather are symptomatic of the uneasy relationship between counterintelligence and democracy. Understanding the technology used for cyber intrusion may be necessary for understanding cyber conflict, but it is not sufficient for comprehending its strategic ends and limits: it is further necessary to understand the political logic of intelligence.
Toward a Vulnerability Mitigation Model
Authors: Brandão José Eduardo Malta de Sá
Published: December 2021

This chapter demonstrates how the elements of a cybersecurity incident can be analysed systematically, and suggests an alternative way to mitigate the causes and consequences of such incidents. Cybersecurity incidents can be explained in terms of a sequence of elements linking the attacking agents to their objectives: the attacking agent uses tools to exploit vulnerabilities, causing actions on a specific target to obtain unauthorized results, achieving their objectives. Cyber security can be improved by stopping the flow of the attack by mitigating one or more elements that make up the process. Unfortunately, most of these elements have characteristics that limit the opportunities for mitigation. The least difficult element to mitigate is vulnerability. The current model of vulnerability mitigation has behaved for the corporate environment, which can pay for specialized tools and consulting. This is an excellent business model but inaccessible to the public. A new model is necessary to prevent cybersecurity incidents on a broader, more inclusive level. The main proposal for vulnerability mitigation is multisector cooperation to create an independent, trustworthy, and secure vulnerability database, based on a new vulnerability report protocol developed in accordance with researchers, companies, governments, and society. However, this proposal creates some social, political, and technical challenges.
Assessing Harm from Cyber Crime
Authors: Ignatuschtschenko Eva
Published: December 2021

This chapter discusses a harm concept that enables a more comprehensive assessment of the consequences of cyber crime. Even though harm resulting from cyber crime is not fundamentally different from harm that is caused by other forms of crime or crime in general, the reach, scope, and volume of crime facilitated by information and communications technology have transformed risks posed to individuals, organizations, and nations, and challenge conventional approaches of crime detection and prevention. Assessments of the impact of cyber crime have been focusing on estimating the cost in monetary value. However, most significant harm might not be experienced as a loss of money, but as a disruption or destabilization of systems that are built on trust. This article advocates for a human-centric approach to cyber security, which emphasizes harm mitigation strategies.
Mali
Authors: Whitehouse Bruce
Published: December 2021

In 2012, Mali began a long slide into insecurity and political instability. This chapter reviews the historical roots of that crisis, beginning in the waning days of French colonialism and continuing through periods of socialist nationalism, military rule, and liberal democracy. Mali’s postcolonial state has faced numerous internal and external threats. Some stemmed from hierarchical structures within the country’s heterogeneous population and the conflicts these structures engendered. Others emanated from heavy-handed government attempts to impose order and national identity on this population. Some were posed by other states in the Sahel and beyond. Still others came in the form of non-state actors exploiting state weakness to advance their own political and social agendas. Critically examining the competing narratives about Mali’s ongoing crisis, which focus on neocolonialism, geopolitics, and political institutions, this chapter demonstrates that the origins of the crisis are neither simple nor monocausal.
European and National Social Policy
Authors: Schmidt Manfred G.
Published: December 2021

This chapter portrays the development of social policy managed by the European Union, focuses on principles of steering in the EU’s social policy, and explores the distribution of power between national social political action in the member states and European social policy since 1957. The data show that the EU has been able to gain influence through regulatory social policies and soft governance instruments. As pertaining to social services, social expenditure, and redistributive concepts, however, the EU only plays a marginal role. The predominance of national social policy and the limited role of European social policy have been largely due to socio-economic diversity of the EU’s member state, heterogeneous welfare states, institutional obstacles of policymaking in the EU, and powerful national constraints.
Family Benefits and Services
Authors: Finch Naomi , Bradshaw Jonathan
Published: December 2021

This chapter examines welfare-state support for families with children in the context of low fertility, increasing rates of childlessness, and a general move away from the breadwinner model of the family. Welfare-state spending on families is explored, and, although most countries, with few exceptions, spend more on older people, spending on children varies between countries, as does spending to encourage mothers into employment. Adopting the model family method to compare the package of policies to support families with children at different earning levels, the chapter shows varying results of generosity, depending on whether we compare low or average earners. The chapter also provides evidence that family policies matter for outcomes—with stronger spending on services increasing both fertility and maternal employment, spending on both services and benefits increasing child well-being, and generosity of transfers lowering child poverty rates.
Inequality and Poverty
Authors: Saunders Peter
Published: December 2021

A key goal of any welfare state is to promote social justice by tackling inequality and poverty. This chapter reviews some of the ideas and evidence that have informed the debate about the causes of differences in inequality and poverty, including alternative interpretations of the meaning of both as policy objectives and how each can be measured. Although the two concepts are often related, they are conceptually distinct: inequality captures differences in economic outcomes, while poverty covers those with inadequate economic resources. Estimating the impact of policy on either variable is difficult because of the many other factors involved. Examining cross-country differences provides an insight into the impacts of different policies introduced in otherwise broadly similar countries. These studies have shown that transfers and taxes reduce inequality and poverty, and also that those countries that spend more on social programmes have less inequality and lower poverty rates, but the relationship is weak and there are many exceptions. While considerable progress has been made in understanding the role of the welfare state in accounting for these differences, we are a long way from fully understanding the many complex interactions that are the drivers of inequality and poverty.
From Welfare States to Planetary Well-Being
Authors: Gough Ian
Published: December 2021

This final chapter concentrates on global environmental challenges to rich-country welfare states: climate breakdown and associated ecological disasters. These common threats add two new raison d’êtres for welfare states: first, that the security and equity they seek should be sustainable through time; second, that their scope is broadened to take account of global equity and well-being. With a few notable exceptions, these fundamental questions have been ignored in the social policy community. I argue here that we need to transform our understanding of social policy in four ways, each more difficult than the previous one. First, we need to develop novel eco-social programmes to tap synergies between well-being and sustainability via transformative investment programmes such as a Green New Deal. Second, we need to recompose consumption in rich countries in two ways: to realize the best principles of the welfare state by extending the range of universal basic services and to work towards a private ‘consumption corridor’ to end waste, meet basic needs, and reduce inequality. Third, we must develop strategies of ‘reduce and redistribute’ to adapt welfare systems for a future of slower, if not negative, economic growth. And finally, we need to develop a global equity framework to meet climatic and ecological threats in a globally just way that recognizes current international inequalities.
Shadow Insurance? Money Market Fund Investors and Bank Sponsorship
Authors: Jacewitz Stefan , Unal Haluk , Wu Chengjun
Published: December 2021

We argue that bank holding companies (BHCs) extend shadow insurance to the prime institutional money market funds (PI-MMFs) they sponsor and that PI-MMFs price this shadow insurance by charging investors significantly higher expense ratios and paying lower net yields. We provide evidence that after September 2008, expense ratios at BHC-sponsored PI-MMFs increased more than at non-BHC-sponsored PI-MMFs. Despite higher expense ratios, BHC-sponsored PI-MMFs did not experience larger redemptions than non-BHC-sponsored PI-MMFs. In addition, we show that expense ratios increased with BHCs’ financial strength and the likelihood of their support; however, this expense ratio differential disappeared after the 2016 MMF reform. (JEL G2, G21, G23, G28, H12, H81)
ESTIMATION OF SCATTERED NEUTRONS CONTRIBUTION IN A NEUTRON CALIBRATION BUNKER USING A MONTE CARLO SIMULATION
Authors: Obeid M H , Ismail A , Bitar A , Shweikani R
Published: December 2021

The contribution of scattered neutrons is inevitable in neutron calibration facilities. This contribution complicates the measurements of neutron radiation, therefore, it should be estimated to correct the response of neutron probe instruments. In the present work, Monte Carlo simulation was performed for a neutron calibration bunker using the MCNP-4C code. This simulation aimed to calculate the contribution ratio of scattered neutrons to the neutron field. To simulate the neutron field, 241Am-Be neutron source defined in the ISO 8529-1 was used. The results of the simulation reported in this work were found to be consistent with those found experimentally in previous work. Additionally, the distribution of both the ambient dose equivalent rate and the contribution ratio of scattered neutrons in the bunker were mapped using this simulation.
Socioeconomic and cognitive roots of trait anxiety in young adults
Authors: Cermakova Pavla , Chlapečka Adam , Andrýsková Lenka , Brázdil Milan , Marečková Klára
Published: December 2021

In 54 participants (41% women) from the Czech arm of the European Longitudinal Study of Pregnancy and Childhood, a national birth cohort with prospectively collected data from their birth until young adulthood, we aimed to study the association between early-life socioeconomic deprivation (ELSD), cognitive ability in adolescence, trait anxiety and resting state functional connectivity of the lateral prefrontal cortex (LPFC) in young adulthood. We found that ELSD was associated with lower cognitive ability in adolescence (at age 13) as well as higher trait anxiety in young adulthood (at age 23/24). Higher cognitive ability in adolescence predicted lower trait anxiety in young adulthood. Resting state functional connectivity between the right LPFC and a cluster of voxels including left precentral gyrus, left postcentral gyrus and superior frontal gyrus mediated the relationship between lower cognitive ability in adolescence and higher trait anxiety in young adulthood. These findings indicate that lower cognitive ability and higher trait anxiety may be both consequences of socioeconomic deprivation in early life. The recruitment of the right LPFC may be the underlying mechanism, through which higher cognitive ability may ameliorate trait anxiety.
Integrated Omic Analyses Identify Pathways and Transcriptomic Regulators Associated With Chemical Alterations ofIn VitroNeural Network Formation
Authors: Marable Carmen A , Frank Christopher L , Seim Roland F , Hester Susan , Henderson W Matthew , Chorley Brian , Shafer Timothy J
Published: December 2021

Development of in vitro new approach methodologies has been driven by the need for developmental neurotoxicity (DNT) hazard data on thousands of chemicals. The network formation assay characterizes DNT hazard based on changes in network formation but provides no mechanistic information. This study investigated nervous system signaling pathways and upstream physiological regulators underlying chemically induced neural network dysfunction. Rat primary cortical neural networks grown on microelectrode arrays were exposed for 12 days in vitro to cytosine arabinoside, 5-fluorouracil, domoic acid, cypermethrin, deltamethrin, or haloperidol as these exposures altered network formation in previous studies. RNA-seq from cells and gas chromatography/mass spectrometry analysis of media extracts collected on days in vitro 12 provided gene expression and metabolomic identification, respectively. The integration of differentially expressed genes and metabolites for each neurotoxicant was analyzed using ingenuity pathway analysis. All 6 compounds altered gene expression that linked to developmental disorders and neurological diseases. Other enriched canonical pathways overlapped among compounds of the same class; eg, genes and metabolites altered by both cytosine arabinoside and 5-fluorouracil exposures are enriched in axonal guidance pathways. Integrated analysis of upstream regulators was heterogeneous across compounds, but identified several transcriptomic regulators including CREB1, SOX2, NOTCH1, and PRODH. These results demonstrate that changes in network formation are accompanied by transcriptomic and metabolomic changes and that different classes of compounds produce differing responses. This approach can enhance information obtained from new approach methodologies and contribute to the identification and development of adverse outcome pathways associated with DNT.
Nonhepatic Cancer in the Pediatric Liver Transplant Population: Guidelines From the ILTS-SETH Consensus Conference
Authors: Rela Mohamed , Quintero Jesus , Kasahara Mureo , Muiesan Paolo , Hernández-Oliveros Francisco , Rajalingam Rajesh , Shankar Sadhana , Sayed Blayne Amir , di Sabato Diego , Rammohan Ashwin , Fung John , Bilbao Itxarone
Published: December 2021

The incidence and geographical distribution of cancers in children are dramatically different from the adult population. Consequent to improvements in postcancer survival, there is a progressive increase in the number of patients requiring liver transplantation (LT) who are in remission from pretransplant malignancy (PTM). Conventionally, however, PTM has been considered a relative contraindication to LT. Furthermore, with improving post-LT survival now extending beyond decades, the cumulative effect of immunosuppression and the increasing risk of de novo cancers need to be acknowledged. A working group was formed to evaluate, discuss, and retrieve all the evidence and provide guidelines with regards to best practices surrounding nonhepatic cancer in the pediatric LT (PLT) population. Further subsections of research included (a) extrahepatic solid tumors, leukemia, lymphoma, and other hematological disturbances before PLT and (b) malignancies following PLT (including posttransplant lymphoproliferative disorders). This guidance provides a collection of evidence-based expert opinions, consensus, and best practices on nonhepatic cancers in PLT.
Evaluation and Management of Liver Transplant Candidates With Prior Nonhepatic Cancer: Guidelines From the ILTS/SETH Consensus Conference
Authors: Salcedo Magdalena , Vinaixa Carmen , Javle Milind , Trapero-Marugán María , Bustamante Javier , Line Pål-Dag
Published: December 2021

Liver transplant in patients with prior nonhepatic cancer is a matter of concern, needing further research, development, and consensus guidelines. This International Liver Transplantation Society/Sociedad Española De Trasplante Hepático consensus conference document focuses on the role of liver transplantation in patients with a prior history of nonhepatic cancer. This document addresses (1) the evaluation of transplant candidates with prior cancers based on the assessment of prognosis, the natural history of individual cancers, and the emerging role for circulating DNA and minimal residual disease in these patients; (2) the impact of prior treatments, including immunotherapy for prior malignancies; and (3) the surveillance of posttransplant cancer recurrence. The consensus statement is based on previously published guidelines, as well as a review of the current, relevant, published literature.
De Novo Malignancy After Liver Transplantation: Risk Assessment, Prevention, and Management—Guidelines From the ILTS-SETH Consensus Conference
Authors: Colmenero Jordi , Tabrizian Parissa , Bhangui Prashant , Pinato David James , Rodríguez-Perálvarez Manuel L. , Sapisochin Gonzalo , Bhoori Sherrie , Pascual Sonia , Senzolo Marco , Al-Adra David , Herrero J. Ignacio , Petrowsky Henrik , Dawson Laura A. , Hosni Ali , Kutzke Jade L. , Gastaca Mikel , Watt Kymberly D.
Published: December 2021

De novo malignancies (DNMs) following liver transplantation (LT) have been reported as 1 of the major causes of late mortality, being the most common cause of death in the second decade after LT. The overall incidence of DNMs is reported to be in the range of 3.1% to 14.4%, and the incidence is 2- to 3-fold higher in transplant recipients than in age- and sex-matched healthy controls. Long-term immunosuppressive therapy, which is the key in maintaining host tolerance and achieving good long-term outcomes, is known to contribute to a higher risk of DNMs. However, the incidence and type of DNM also depends on different risk factors, including patient demographics, cause of the underlying chronic liver disease, behavior (smoking and alcohol abuse), and pre-existing premalignant conditions. The estimated standardized incidence ratio for different DNMs is also variable. The International Liver Transplantation Society–Spanish Society of Liver Transplantation Consensus Conference working group on DNM has summarized and discussed the current available literature on epidemiology, risk factors, management, and survival after DNMs. Recommendations for screening and surveillance for specific tumors, as well as immunosuppression and cancer-specific management in patients with DNM, are summarized.
Evaluation of Early Markers of Ischemia-reperfusion Injury and Preservation Solutions in a Modified Hindlimb Model of Vascularized Composite Allotransplantation
Authors: Rostami Sara , Xu Michael , Datta Shaishav , Haykal Siba
Published: December 2021

Background.

Ischemia-reperfusion injury plays an important role in vascularized composite allotransplantation (VCA). Currently, there is no ideal preservation solution for VCA. In this study, we investigated the effects of 4 different preservation solutions on different tissues within an allogeneic hindlimb rat model.

Methods.

Sprague Dawley rat hindlimbs were flushed and placed at 4°C for 6 h in heparinized saline, histidine-tryptophan-ketoglutarate, University of Wisconsin (UW), and Perfadex and heterotopically transplanted for ease of ambulation. Apoptosis, necrosis, and the extracellular matrix of the tissues within the allograft were analyzed 2 h posttransplantation using immunohistochemistry, terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick-end labeling (TUNEL) assay, and enzyme-linked immunoassay.

Results.

Higher expression of cleaved caspase 3, a significant increase of high-mobility group box 1 and TUNEL-positive apoptotic cells were observed in the muscle and vessels preserved with heparinized saline compared with UW and Perfadex following reperfusion. Higher expression of TUNEL-positive apoptotic cells was observed in the skin at 12 h of ischemia and in the nerve following reperfusion with histidine-tryptophan-ketoglutarate as a preservation solution.

Conclusions.

Our data suggest that UW and Perfadex are preferred solutions in VCA. The vessels within the allografts appear to be very susceptible, with laminins and CD31 playing a role in ischemia-reperfusion injury.
Porcine Liver Normothermic Machine Perfusion: Methodological Framework and Potential Pitfalls
Authors: Gilbo Nicholas , Wylin Tine , Heedfeld Veerle , Jochmans Ina , Pirenne Jacques , Friend Peter , Monbaliu Diethard
Published: December 2021

Porcine models of liver normothermic machine perfusion (NMP) are increasingly used in transplant research, although known to be challenging because of their complex methodology and their scarcely documented operational aspects. Here, we aimed to provide a methodological framework for researchers looking to adopt NMP technology in research setting by giving an in-detail account of the implementation of a previously validated porcine liver NMP model. We subjected groups of 3–5 porcine livers to 24 h NMP and, using a trial-and-error principle, introduced stepwise changes in the NMP setting with the objective to obtain stable preservation of liver function and histology for 24 h. Female porcine livers were procured, and packed red-blood-cell perfusate was prepared. Perfusate oxygenation, hemodynamics, markers of hepatic injury (aspartate transaminase [AST]), function (lactate, perfusate pH, bile production), and histology were analyzed. Intermediate analysis was performed within groups and a minimum of 3 (out of 5) failed experiments prompted methodological reevaluation. Overall, 13 liver NMP experiments were needed in 3 phases. In phase 1, loss of oxygenator performance occurred from 6 h onward in 3 consecutive experiments because of perfusate leakage. In phase 2, a plasma-tight hollow fiber oxygenator ensured adequate perfusate oxygenation in 5 experiments. However, portal vein resistance increased during all liver NMP, associated with high perfusate AST levels (range, 106–322 IU/L/100 g) and pan-lobular sinusoidal dilation and hemorrhage, suggesting liver outflow impairment. In phase 3, an improved inferior vena cava cannulation technique avoided liver outflow impairment, resulting in lower AST release (range, 29–101 IU/L/100 g), improved lactate clearance, preserved biliary excretion, and normal histology in 5 experiments. This study underscores the critical importance of auditing all equipment and operational components of NMP circuits to obtain successful and reproducible perfusion setup and advocates for in-detail reporting of methodological aspects and potential pitfalls.
Physiological magnesium concentrations increase fidelity of diverse reverse transcriptases from HIV-1, HIV-2, and foamy virus, but not MuLV or AMV
Authors: Wang Ruofan , Belew Ashton T. , Achuthan Vasudevan , El Sayed Najib , DeStefano Jeffrey J.
Published: December 2021

Reverse transcriptases (RTs) are typically assayed using optimized Mg2+ concentrations (~5–10 mM) several-fold higher than physiological cellular free Mg2+ (~0.5 mM). Recent analyses demonstrated that HIV-1, but not Moloney murine leukaemia (MuLV) or avain myeloblastosis (AMV) virus RTs has higher fidelity in low Mg2+. In the current report, lacZα-based α-complementation assays were used to measure the fidelity of several RTs including HIV-1 (subtype B and A/E), several drug-resistant HIV-1 derivatives, HIV-2, and prototype foamy virus (PFV), all which showed higher fidelity using physiological Mg2+, while MuLV and AMV RTs demonstrated equivalent fidelity in low and high Mg2+. In 0.5 mM Mg2+, all RTs demonstrated approximately equal fidelity, except for PFV which showed higher fidelity. A Next Generation Sequencing (NGS) approach that used barcoding to determine mutation profiles was used to examine the types of mutations made by HIV-1 RT (type B) in low (0.5 mM) and high (6 mM) Mg2+ on a lacZα template. Unlike α-complementation assays which are dependent on LacZα activity, the NGS assay scores mutations at all positions and of every type. Consistent with α-complementation assays, a ~four-fold increase in mutations was observed in high Mg2+. These findings help explain why HIV-1 RT displays lower fidelity in vitro (with high Mg2+ concentrations) than other RTs (e.g. MuLV and AMV), yet cellular fidelity for these viruses is comparable. Establishing in vitro conditions that accurately represent RT’s activity in cells is pivotal to determining the contribution of RT and other factors to the mutation profile observed with HIV-1.
Genomic insights into the circulation of pandemic fluoroquinolone-resistant extra-intestinal pathogenic Escherichia coli ST1193 in Vietnam
Authors: Nguyen Quynh , Nguyen To Thi Nguyen , Pham Phuong , Chau Vinh , Nguyen Lan Phu Huong , Nguyen Toan Duc , Ha Tuyen Thanh , Le Nhi Thi Quynh , Vu Duong Thuy , Baker Stephen , Thwaites Guy E. , Rabaa Maia A. , Pham Duy Thanh
Published: December 2021

Extra-intestinal pathogenic

Escherichia coli

(ExPEC) ST1193, a globally emergent fluoroquinolone-resistant clone, has become an important cause of bloodstream infections (BSIs) associated with significant morbidity and mortality. Previous studies have reported the emergence of fluoroquinolone-resistant ExPEC ST1193 in Vietnam; however, limited data exist regarding the genetic structure, antimicrobial resistance (AMR) determinants and transmission dynamics of this pandemic clone. Here, we performed genomic and phylogenetic analyses of 46 ST1193 isolates obtained from BSIs and healthy individuals in Ho Chi Minh City, Vietnam, to investigate the pathogen population structure, molecular mechanisms of AMR and potential transmission patterns. We further examined the phylogenetic structure of ST1193 isolates in a global context. We found that the endemic

E. coli

ST1193 population was heterogeneous and highly dynamic, largely driven by multiple strain importations. Several well-supported phylogenetic clusters (C1–C6) were identified and associated with distinct bla
CTX-M variants, including bla
CTXM-27 (C1–C3, C5), bla
CTXM-55 (C4) and bla
CTXM-15 (C6). Most ST1193 isolates were multidrug-resistant and carried an extensive array of AMR genes. ST1193 isolates also exhibited the ability to acquire further resistance while circulating in Vietnam. There were phylogenetic links between ST1193 isolates from BSIs and healthy individuals, suggesting these organisms may both establish long-term colonization in the human intestinal tract and induce infections. Our study uncovers factors shaping the population structure and transmission dynamics of multidrug-resistant ST1193 in Vietnam, and highlights the urgent need for local One Health genomic surveillance to capture new emerging ExPEC clones and to better understand the origins and transmission patterns of these pathogens.
Introduction and adaptation of an emerging pathogen to olive trees in Italy
Authors: Sicard Anne , Saponari Maria , Vanhove Mathieu , Castillo Andreina I. , Giampetruzzi Annalisa , Loconsole Giuliana , Saldarelli Pasquale , Boscia Donato , Neema Claire , Almeida Rodrigo P. P.
Published: December 2021

The invasive plant pathogen

Xylella fastidiosa

currently threatens European flora through the loss of economically and culturally important host plants. This emerging vector-borne bacterium, native to the Americas, causes several important diseases in a wide range of plants including crops, ornamentals, and trees. Previously absent from Europe, and considered a quarantine pathogen,

X. fastidiosa

was first detected in Apulia, Italy in 2013 associated with a devastating disease of olive trees (Olive Quick Decline Syndrome, OQDS). OQDS has led to significant economic, environmental, cultural, as well as political crises. Although the biology of

X. fastidiosa

diseases have been studied for over a century, there is still no information on the determinants of specificity between bacterial genotypes and host plant species, which is particularly relevant today as

X. fastidiosa

is expanding in the naive European landscape. We analysed the genomes of 79

X

.

fastidiosa

samples from diseased olive trees across the affected area in Italy as well as genomes of the most genetically closely related strains from Central America. We provided insights into the ecological and evolutionary emergence of this pathogen in Italy. We first showed that the outbreak in Apulia is due to a single introduction from Central America that we estimated to have occurred in 2008 [95 % HPD: 1930–2016]. By using a combination of population genomic approaches and evolutionary genomics methods, we further identified a short list of genes that could play a major role in the adaptation of

X. fastidiosa

to this new environment. We finally provided experimental evidence for the adaptation of the strain to this new environment.
The evolutionary history of Shigella flexneri serotype 6 in Asia
Authors: Mai Si-Nguyen T. , Bodhidatta Ladaporn , Turner Paul , Wangchuk Sonam , Ha Thanh Tuyen , Voong Vinh Phat , Pham Duy Thanh , Rabaa Maia A. , Thwaites Guy E. , Thomson Nicholas R. , Baker Stephen , Chung The Hao
Published: December 2021

Shigella flexneri

serotype 6 is an understudied cause of diarrhoeal diseases in developing countries, and has been proposed as one of the major targets for vaccine development against shigellosis. Despite being named as

S. flexneri

,

Shigella flexneri

serotype 6 is phylogenetically distinct from other

S. flexneri

serotypes and more closely related to

S. boydii

. This unique phylogenetic relationship and its low sampling frequency have hampered genomic research on this pathogen. Herein, by utilizing whole genome sequencing (WGS) and analyses of

Shigella flexneri

serotype 6 collected from epidemiological studies (1987–2013) in four Asian countries, we revealed its population structure and evolutionary history in the region. Phylogenetic analyses supported the delineation of Asian

Shigella flexneri

serotype 6 into two phylogenetic groups (PG-1 and −2). Notably, temporal phylogenetic approaches showed that extant Asian

S. flexneri

serotype 6 could be traced back to an inferred common ancestor arising in the 18th century. The dominant lineage PG-1 likely emerged in the 1970s, which coincided with the times to most recent common ancestors (tMRCAs) inferred from other major Southeast Asian

S. flexneri

serotypes. Similar to other

S. flexneri

serotypes in the same period in Asia, genomic analyses showed that resistance to first-generation antimicrobials was widespread, while resistance to more recent first-line antimicrobials was rare. These data also showed a number of gene inactivation and gene loss events, particularly on genes related to metabolism and synthesis of cellular appendages, emphasizing the continuing role of reductive evolution in the adaptation of the pathogen to an intracellular lifestyle. Together, our findings reveal insights into the genomic evolution of the understudied

Shigella flexneri

serotype 6, providing a new piece in the puzzle of

Shigella

epidemiology and evolution.
Analytical evaluation of thirty-two SARS-CoV-2 lateral flow antigen tests demonstrates sensitivity remains with the SARS-CoV-2 Gamma lineage
Authors: Kontogianni Konstantina , Bengey Daisy , Wooding Dominic , Buist Kate , Greenland-Bews Caitlin , Williams Christopher T. , de Vos Margaretha , Escadafal Camille , Adams Emily R. , Edwards Thomas , Cubas-Atienzar Ana I.
Published: December 2021

The limit of detection (LOD) of thirty-two antigen lateral flow tests (Ag-RDT) were evaluated with the SARS-CoV-2 Gamma variant. Twenty-eight of thirty-two Ag-RDTs exceeded the World Health Organization criteria of an LOD of 1.0×106 genome copy numbers/ml and performance was equivalent as with the 2020 B.1 lineage and Alpha variant.