bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid evolution of promoters from germline-specifically expressed genes including transposon silencing factors
Authors: McQuarrie David W. J. , Alizada Azad , Czech Nicholson Benjamin , Soller Matthias
Published: November 2023

Background

The piRNA pathway in animal gonads functions as an ‘RNA-based immune system’, serving to silence transposable elements and prevent inheritance of novel invaders. InDrosophila, this pathway relies on three gonad-specific Argonaute proteins (Argonaute-3, Aubergine and Piwi) that associate with 23-28 nucleotide piRNAs, directing the silencing of transposon-derived transcripts. Transposons constitute a primary driver of genome evolution, yet the evolution of piRNA pathway factors has not received in-depth exploration. Specifically, channel nuclear pore proteins, which impact piRNA processing, exhibit regions of rapid evolution in their promoters. Consequently, the question arises whether such a mode of evolution is a general feature of transposon silencing pathways.

Results

By employing genomic analysis of coding and promoter regions within genes that function in transposon silencing inDrosophila, we demonstrate that the promoters of germ cell-specific piRNA factors are undergoing rapid evolution. Our findings indicate that rapid promoter evolution is a common trait among piRNA factors engaged in germline silencing across insect species, potentially contributing to gene expression divergence in closely related taxa. Furthermore, we observe that the promoters of genes exclusively expressed in germ cells generally exhibit rapid evolution, with some divergence in gene expression.

Conclusion

Our results suggest that increased germline promoter evolution, in partnership with other factors, could contribute to transposon silencing and evolution of species through differential expression of genes driven by invading transposons.
Diffusion of DNA on Atomically Flat 2D Material Surfaces
Authors: Shin Dong Hoon , Kim Sung Hyun , Coshic Kush , Watanabe Kenji , Taniguchi Takashi , Verbiest Gerard , Caneva Sabina , Aksimentiev Aleksei , Steeneken Peter G. , Joo Chirlmin
Published: November 2023

Accurate localization of biomolecules is pivotal for understanding biological processes. Utilizing the atomically flat surface of 2D materials offers a promising route to achieve this without the need for tethering or constraining. Here we comprehensively investigate the binding and diffusion of DNA on hexagonal boron nitride (hBN) surfaces. Our findings reveal non-specific binding of DNA to pristine hBN, with subsequent diffusion and confinement within the 2D plane. Through single-molecule experiments and computational techniques, we explore DNA dynamics, and the effects of defects, step edges and domain boundaries on the motion, which gives insights on the interactions between solid-state surfaces and biomolecules. By engineering a narrow hBN ribbon structure, we enhance confinement, demonstrating its potential in nanofluidic guiding of biomolecules. Our 2D platform serves as a proving ground for next generation high-throughput single-molecule manipulation techniques for enabling applications in biotechnology and nanotechnology.
The genome and transcriptome of the snailBiomphalaria sudanica s.l.: Immune gene diversification and highly polymorphic genomic regions in an important African vector ofSchistosoma mansoni
Authors: Pennance Tom , Calvelo Javier , Tennessen Jacob A. , Burd Ryan , Cayton Jared , Bollmann Stephanie R. , Blouin Michael S. , Spaan Johannie M. , Hoffmann Federico G , Ogara George , Rawago Fredrick , Andiego Kennedy , Mulonga Boaz , Odhiambo Meredith , Loker Eric S. , Laidemitt Martina R. , Lu Lijun , Iriarte Andrés , Odiere Maurice , Steinauer Michelle L.
Published: November 2023

Background

Control and elimination of schistosomiasis is an arduous task, with current strategies proving inadequate to break transmission. Exploration of genetic approaches to interruptSchistosoma mansonitransmission, the causative agent for human intestinal schistosomiasis in sub-Saharan Africa and South America, has led to genomic research of the snail vector hosts of the genusBiomphalaria. Few complete genomic resources exist, with AfricanBiomphalariaspecies being particularly underrepresented despite this being where the majority ofS. mansoniinfections occur. Here we generate and annotate the first genome assembly ofBiomphalaria sudanicasensu lato, a species responsible forS. mansonitransmission in lake and marsh habitats of the African Rift Valley. Supported by whole-genome diversity data among five inbred lines, we describe orthologs of immune-relevant gene regions in the South American vectorB. glabrataand present a bioinformatic pipeline to identify candidate novel pathogen recognition receptors (PRRs).

Results

De novogenome and transcriptome assembly of inbredB. sudanicaoriginating from the shoreline of Lake Victoria (Kisumu, Kenya) resulted in a haploid genome size of ∼944.2 Mb (6732 fragments, N50=1.067 Mb), comprising 23,598 genes (BUSCO=93.6% complete). TheB. sudanicagenome contains orthologues to all described immune genes/regions tied to protection againstS. mansoniinB. glabrata. TheB. sudanica PTC2candidate immune genomic region contained many PRR-like genes across a much wider genomic region than has been shown inB. glabrata, as well as a large inversion between species. High levels of intra-species nucleotide diversity were seen inPTC2, as well as in regions linked toPTC1andRADresorthologues. Immune related and putative PRR gene families were significantly over-represented in the sub-set ofB. sudanicagenes determined as hyperdiverse, including high extracellular diversity in transmembrane genes, which could be under pathogen-mediated balancing selection. However, no overall expansion in immunity related genes were seen in African compared to South American lineages.

Conclusions

TheB. sudanicagenome and analyses presented here will facilitate future research in vector immune defense mechanisms against pathogens. This genomic/transcriptomic resource provides necessary data for the future development of molecular snail vector control/surveillance tools, facilitating schistosome transmission interruption mechanisms in Africa.
Structural basis of saccharine derivative inhibition of carbonic anhydrase IX
Authors: Leitans Janis , Kazaks Andris , Bogans Janis , Supuran Claudiu T. , Akopjana Inara , Ivanova Jekaterina , Zalubovskis Raivis , Tars Kaspars
Published: November 2023

This scientific study explores the binding mechanisms of saccharine derivatives with human carbonic anhydrase IX (hCA IX), an antitumor drug target, with the aim of facilitating the design of potent and selective inhibitors. Through the use of crystallographic analysis, we investigate the structures of hCA IX - saccharine derivative complexes, unveiling their unique binding modes that exhibit both similarities to sulfonamides and distinct orientations of the ligand tail. Our comprehensive structural insights provide information regarding the crucial interactions between the ligands and the protein, shedding light on interactions that dictate inhibitor binding and selectivity. Through a comparative analysis of the binding modes observed in hCA II and hCA IX, isoform-specific interactions are identified, offering promising strategies for the development of isoform-selective inhibitors that specifically target tumor-associated hCA IX. The findings of this study significantly deepen our understanding of the binding mechanisms of hCA inhibitors, laying a solid foundation for the rational design of more effective inhibitors.
Social health and subsequent cognitive functioning in people aged 50 years and above: examining the mediating roles of depressive symptoms and inflammatory biomarkers
Authors: Stafford Jean , Dekhtyar Serhiy , Welmer Anna-Karin , Vetrano Davide L , Grande Giulia , Marseglia Anna , Moulton Vanessa G , Mansfield Rosie , Liu Yiwen , Ning Ke , Wolf-Ostermann Karin , Brodaty Henry , Samtani Suraj , Ikram Mohammad Arfan , Melis René , Rymaszewska Joanna , Szcześniak Dorota , Gessa Giorgio Di , Richards Marcus , Davis Daniel , Patalay Praveetha , Maddock Jane
Published: November 2023

Background

Social health markers, including marital status, contact frequency, network size, and social support, have shown associations with cognition. However, the underlying mechanisms remain poorly understood. We investigated whether depressive symptoms and inflammation mediated associations between social health and subsequent cognition.

Methods

In the English Longitudinal Study of Ageing (ELSA; n=7,136; aged 50+), we used four-way decomposition to examine to what extent depressive symptoms, C-reactive protein (CRP) and fibrinogen (assessed at an intermediate time point) mediated associations between social health and subsequent standardised cognition (verbal fluency, delayed and immediate recall) including cognitive change, with slopes derived from multilevel models (ELSA: 12-year slope). We examined whether findings replicated in the Swedish National Study of Aging and Care in Kungsholmen (SNAC-K; n=2,846; aged 60+; 6-year slope).

Findings

We found indirect effects via depressive symptoms of network size, positive support and less negative support on subsequent verbal fluency, and positive support on subsequent immediate recall (pure indirect effect (PIE)=0.002 [0.000-0.003]). The positive support-verbal fluency mediation finding replicated in SNAC-K. Depressive symptoms partially mediated associations between less negative support and slower immediate (PIE=0.001 [0.000-0.002]) and delayed recall decline (PIE=0.001 [0.000-0.002]), and between positive support and slower immediate recall decline (PIE=0.001, [0.000-0.001]), which replicated in SNAC-K. We did not observe mediation by inflammatory biomarkers.

Interpretation

Findings provide new insights into mechanisms linking social health with cognition, suggesting that associations between cognition and interactional aspects of social health in particular, such as social support, are partly underpinned by depressive symptoms.
Sustainable strategies and firm performance in manufacturing industry of Coahuila, Mexico
Authors: Lara-Pérez Jorge Alfonso , Aguilera-Tovar Alberto , Hernandez-Rodriguez Alejandra
Published: November 2023

Purpose

Adoption and implementation of sustainable strategies (SS) in firms have been widely studied; however, there is scarce evidence of factors that affect the overall firm performance (FP). Therefore, in this research the variables knowledge management (KM) and professionalization (PR) toward the adoption of SS and their impact on FP are promoted.

Design/methodology/approach

Data from 120 firms in manufacturing industry in Coahuila, Mexico, were collected, and the study is based on the PLS-SEM technique.

Findings

The results revealed that (1) KM and PR present a positive impact on SS and (2) SS are positively related to FP.

Practical implications

For manufacturing managers, it is necessary to implement SS that meet the expectations of stakeholders, in addition to training human resources with the ability to achieve the aims of the firm and at the same time take care of the environment. As for corporate policymakers, it is essential that they promote global environmental care strategies based on collaborative business.

Originality/value

This research contributes to literature on business management, mainly to the incorporation of SS that allow boosting the economic aspect, but without neglecting social and environmental part.
Model predictive control for smart buildings: a simulation approach within Indian context
Authors: Pandey Kamal , Basu Bhaskar
Published: November 2023

Purpose

In the context of a developing country, Indian buildings need further research to channelize energy needs optimally to reduce energy wastage, thereby reducing carbon emissions. Also, reduction in smart devices’ costs with sequential advancements in Information and Communication Technology have resulted in an environment where model predictive control (MPC) strategies can be easily implemented. This study aims to propose certain preemptive measures to minimize the energy costs, while ensuring the thermal comfort for occupants, resulting in better greener solutions for building structures.

Design/methodology/approach

A simulation-based multi-input multi-output MPC strategy has been proposed. A dual objective function involving optimized energy consumption with acceptable thermal comfort has been achieved through simultaneous control of indoor temperature, humidity and illumination using various control variables. A regression-based lighting model and seasonal auto-regressive moving average with exogenous inputs (SARMAX) based temperature and humidity models have been chosen as predictor models along with four different control levels incorporated.

Findings

The mathematical approach in this study maintains an optimum tradeoff between energy cost savings and satisfactory occupants’ comfort levels. The proposed control mechanism establishes the relationships of output variables with respect to control and disturbance variables. The SARMAX and regression-based predictor models are found to be the best fit models in terms of accuracy, stability and superior performance. By adopting the proposed methodology, significant energy savings can be accomplished during certain hours of the day.

Research limitations/implications

This study has been done on a specific corporate entity and future analysis can be done on other corporate or residential buildings and in other geographical settings within India. Inclusion of sensitivity analysis and non-linear predictor models is another area of future scope.

Originality/value

This study presents a dynamic MPC strategy, using five disturbance variables which further improves the overall performance and accuracy. In contrast to previous studies on MPC, SARMAX model has been used in this study, which is a novel contribution to the theoretical literature. Four levels of control zones: pre-cooling, strict, mild and loose zones have been used in the calculations to keep the Predictive Mean Vote index within acceptable threshold limits.
Silent alliances and shifting tides: unveiling the hidden pathways to resolving interstate rivalries – the UAE-Israel case
Authors: Schiff Amira , Kertcher Chen
Published: November 2023

Purpose

This study delves into the transformation of UAE-Israel relations, which transitioned from a long-term rivalry to a formal peace agreement in 2020. It aims to uncover the multifaceted elements that influenced both nations’ pursuit of bilateral negotiations, with a special emphasis on the role of unofficial collaboration.

Design/methodology/approach

Employing a case study approach, the research traces the evolution of the UAE-Israel ties, mapping their progression from covert collaborations to public accords. This exploration is set against a backdrop of political, economic, and societal factors that have historically characterized the broader Israel-Arab conflict. Real-world dynamics and theoretical constructs are analyzed in tandem to derive comprehensive insights.

Findings

Key drivers for the transformation of UAE-Israel relations included the threat from Iran, internal disturbances, economic stresses, and the strategic advantages of discreet diplomacy. Exogenous catalysts like the Covid-19 pandemic and Israel's annexation plans in 2019-2020 played pivotal roles, capitalizing on pre-existing covert collaborations and shared regional interests. Constructive strategies, notably inducements, effectively reshaped their adversarial relationship. The resultant U.S.-mediated agreement conferred strategic, security, economic, and diplomatic benefits to both parties. Importantly, the potency of conengagement conflict management strategy, especially when bolstered by exogenous factors and growing mutual interest, emerged as a game-changer in terminating longstanding rivalries.

Originality/value

This study offers a unique perspective on Israel-UAE relations, emphasizing the significance of covert engagements, inducements, and the innovative conengagement strategy in conflict resolution. By examining a relationship devoid of direct armed conflict, the research underscores the interplay of economic, political, and societal factors in reshaping rivalries. This case study serves as a testament to the potential for transformative change in enduring disputes when the right conditions and strategies align, supplementing conventional perspectives and offering valuable implications for policy and mediation initiatives in the Middle East.
Advancing social procurement: an institutional work perspective
Authors: Razmdoost Kamran , Alinaghian Leila
Published: November 2023

Purpose

The adoption of social procurement, the emerging practice of using a firm's spending power to generate social value, requires buying firms to navigate conflicts of institutional logics. Adopting an institutional work perspective, this study aims to investigate how buying firms change their existing procurement institutions to adopt and advance social procurement.

Design/methodology/approach

The authors conducted an in-depth case study of a social procurement initiative in the UK. This case study comprised of 16 buying firms that were actively participating in the social procurement initiative at the time of data collection (2020–2021). The data were largely captured through a set of 41 semi-structured interviews.

Findings

Four types of institutional work were observed: reducing institutional conflicts, crossing institutional boundaries, legitimising institutional change and spreading the new institutional logic. These different types of institutional work appeared in a sequential way.

Originality/value

This study contributes to various strands of literature investigating the role of procurement in generating value and benefits within societies, adopting an institutional lens to investigate the buying firms' purposeful actions to change procurement institutions. Secondly, this study complements the existing literature investigating the conflicts of institutional logics by illustrating the ways firms address such institutional conflicts when adopting and advancing social procurement. Finally, this work contributes to the recently emerging research on institutional work that examines the creation and establishment of new institutions by considering the existing procurement institutions in the examination of institutional work.
Best practice in sexual offender rehabilitation and reintegration programs
Authors: Prenzler Tim , McKillop Nadine , Rayment-McHugh Sue , Christensen Lara
Published: November 2023

Purpose

This paper aims to report on the results of a global search to identify the characteristics of successful sexual offender treatment programs, with a view to providing guidance for program development.

Design/methodology/approach

A keyword search was conducted of criminology and social science databases. Successful programs were selected on evaluations that used standard scientific designs.

Findings

This study identified 18 evaluations of 16 programs showing significant reductions in reconvictions. Most programs used cognitive behavioural therapy (CBT), with both group and individual sessions; and many evidenced multisystemic therapy (MST) approaches involving families and/or local communities. CBT-based approaches were also common in the 20 unsuccessful programs identified in the study, although fewer MST-oriented features were in evidence. Noncustodial settings, and combined custodial-noncustodial settings, were also more prominent in the successful programs.

Research limitations/implications

There is a shortage of studies focused on the specific components of successful treatment programs for sexual offenders, including for subsets of offenders, such as ethnic minority groups and women.

Practical implications

The findings demonstrate the need for more investment in treatment programs with strict evaluation processes. New and modified programs are likely to benefit from the application of CBT, MST and a community-based reintegration component. More research is needed on effective elements of sexual offender treatment programs.

Originality/value

To the best of the authors’ knowledge, this appears to be the first study that examines features of successful sexual offender treatment programs, compared to unsuccessful programs, using a case-study approach. The findings reinforce the known value of CBT and systemic approaches as core features of programs but raise important questions about what other components are key to activating success.
A count model of financial inclusion in Ghana: evidence from living standards surveys
Authors: Issahaku Haruna , Muhammed Munira Alhassan , Abu Benjamin Musah
Published: November 2023

Purpose

This paper aims to estimate the determinants of the intensity of use of financial inclusion by households in Ghana.

Design/methodology/approach

Due to the reality of a household using one or more financial products or services, this study uses the generalised Poisson model applied to GLSS6 and GLSS7 data collected in 2012/2013 and 2016/2017 respectively, to estimate the determinants of the intensity of use of financial inclusion. To deepen the analysis, a multinomial probit model is also applied.

Findings

Results show that infrastructural variables such as roads, public transport and banks stimulate the intensity of financial inclusion. In addition, agricultural development characteristics such as markets and cooperatives are essential for the intensity of inclusion.

Research limitations/implications

There is a need to incorporate how many services or depth of services that people use as part of the conceptualisation of financial inclusion, as this can provide more policy-relevant evidence to enhance priority setting in financial inclusion policies. Also, micro-level financial inclusion studies in agrarian economies should consider exploring agricultural development and infrastructure variables in the modelling framework. As lead to further studies, count models of financial inclusion should consider exploring cross-country analysis, the use of panel data, or other methodological approaches to provide more robust evidence.

Originality/value

Previous studies have not modelled financial inclusion based on a count model as a means of measuring intensity though conceptualisations highlight the fact that people use varied financial products or services. Following from this angle, to the best of the authors’ knowledge, this study provides the first attempt at analysing the underlying determinants of the number of financial products or services used by households.
Types of organizational culture and sustainability in ecotourism businesses in southern Mexico
Authors: Medina-Álvarez Efraín , Sánchez-Medina Patricia S.
Published: November 2023

Purpose

The purpose of this paper is to contribute to the understanding of the relationship between different types of organizational culture (hierarchical, clan or group, market or rational and adhocratic) and sustainability through three dimensions (economic, environmental and social) in ecotourism businesses in Oaxaca and Chiapas, Mexico.

Design/methodology/approach

In this research 80 questionnaires were administered in the form of face-to-face interviews to ecotourism business owners'. Through a discriminant analysis and the theoretical support of the competing values framework (CVF), the prevailing types of culture were identified, and their influence was analysed through a regression analysis.

Findings

The results show that ecotourism businesses which are driven by hierarchical culture tend to have a greater focus on economic sustainability, while those businesses with a market or rational culture show a positive and significant influence on environmental sustainability. Likewise, businesses with adhocratic culture achieve sustainability holistically; however, the data reveal that clan or group culture is not associated with social sustainability.

Originality/value

This study offers empirical research that explains the relationship between organizational culture and sustainability. Additionally, it contributes to the study of environmental management issues in the ecotourism sector.
Suspicious activity reporting in the United Kingdom and the United States: statutory obligations of auditors and optimal harvesting of information
Authors: Norton Simon D.
Published: November 2023

Purpose

This study aims to evaluate the advantages and disadvantages of auditor mandatory suspicious activity reporting versus the exercise of professional judgement in the anti-money laundering regimes of the UK and the USA.

Design/methodology/approach

The research draws upon the following sources. Firstly, statistics provided by the UK National Crime Agency, 2019 (NCA) regarding suspicious activity report (SAR) filing rates. Secondly, anti-money laundering legislation in the USA and UK. Thirdly, statements made in the political domain in the USA, particularly those which raised constitutional concerns during the progress of the Patriot Act 2001. Finally, statements and recommendations by a UK Parliamentary Commission enquiring into the effectiveness of the suspicious activity reporting regime.

Findings

The UK reporting regime does not accommodate professional judgement, resulting in the filing of SARs with limited intelligence value. This contrasts with discretionary reporting in the USA: voluntary reporting guides and influences auditor behaviour rather than mandating it. Defensive filing by UK auditors (defence to anti-money launderings [DAMLs]) has increased in recent years but the number of SARs filed has declined.

Originality/value

The study evaluates auditor behavioural responses to legislative regimes which mandate or alternatively accommodate discretion in the reporting suspicion of money laundering. Consideration of constitutional and judicial activism in this context is a novel contribution to the literature. For its theoretical framework the study uses Foucault’s concept of discipline of the self to evaluate auditor behaviour under both regimes.
Fall seven times, stand up eight: the neuropsychological and managerial configurations of resilience Configurations of resilience
Authors: Brenes Esteban R. , Rodriguez Gabriel , Murillo-Rojas Jorge-Vinicio , Pichardo Caleb A.
Published: November 2023

Purpose

Resiliency is essential for achieving the necessary level of performance and ensuring the survival of a new business during difficult times. However, neither this characteristic nor its antecedents have been exhaustively studied. Using a configuration approach, this study aims to analyze the neuropsychological and business-related characteristics of entrepreneurs that may explain their resilience during the business development process.

Design/methodology/approach

Using the fuzzy set qualitative comparative analysis (fsQCA), the authors investigated distinct characteristics of Costa Rican agro-entrepreneurs with high levels of entrepreneurial resilience. The fsQCA methodology identifies combinations of causal measures that result in the outcome.

Findings

From the mixture of configurations, the authors found four combinations of individual’s characteristics that explain the profile of a resilient agro-entrepreneur.

Originality/value

This work contributes to the literature on agricultural entrepreneurship and entrepreneurial resilience. This study identifies four distinct combinations of entrepreneurs’ characteristics that produce entrepreneurial resilience in the agricultural industry. Moreover, it incorporates individuals’ business-related attributes into examining characteristics combinations that affect resilience. Also, this research offers agro-entrepreneurs’ stakeholders, valuable insights to develop more resilient entrepreneurs.
Effect of renin–angiotensin system inhibitors on cardiovascular events in hemodialysis patients with hyperphosphatemia: A post hoc analysis of the LANDMARK trial
Authors: Saito Yoshinori , Ito Hidetoshi , Fukagawa Masafumi , Akizawa Tadao , Kagimura Tatsuo , Yamamoto Masahiro , Kato Masanori , Ogata Hiroaki
Published: November 2023

Introduction

The clinical benefits of renin–angiotensin system inhibitors (RASi) in patients undergoing hemodialysis remain obscure.

Methods

This is a post hoc cohort analysis of the LANDMARK trial investigate whether RASi use was associated with cardiovascular events (CVEs) and all‐cause mortality. A total of 2135 patients at risk for vascular calcification were analyzed using a Cox proportional hazards model with propensity‐score matching.

Results

The risk of CVEs was similar between participants with RASi use at baseline and those without RASi use at baseline and between participants with RASi use during the study period and those without RASi use during the study period. No clinical benefits of RASi use on all‐cause mortality were observed. Serum phosphate levels were significantly associated with the effect of RASi on CVEs.

Conclusions

RASi use was not significantly associated with a lower risk of CVEs or all‐cause mortality in hemodialysis patients at risk of vascular calcification.
Bioaerosols in swine confinement buildings: A metaproteomic view
Authors: Meyer Susann , Hüttig Nicole , Zenk Marianne , Jäckel Udo , Pöther Dierk‐Christoph
Published: November 2023

Swine confinement buildings represent workplaces with high biological air pollution. It is suspected that individual components of inhalable air are causatives of chronic respiratory disease that are regularly detected among workers. In order to understand the relationship between exposure and stress, it is necessary to study the components of bioaerosols in more detail. For this purpose, bioaerosols from pig barns were collected on quartz filters and analysed via a combinatorial approach of 16S rRNA amplicon sequencing and metaproteomics. The study reveals the presence of peptides from pigs, their feed and microorganisms. The proportion of fungal peptides detected is considered to be underrepresented compared to bacterial peptides. In addition, the metaproteomic workflow enabled functional predictions about the discovered peptides. Housekeeping proteins were found in particular, but also evidence for the presence of bacterial virulence factors (e.g., serralysin‐like metalloprotease) as well as plant (e.g., chitinase) and fungal allergens (e.g., alt a10). Metaproteomic analyses can thus be used to identify factors that may be relevant to the health of pig farmers. Accordingly, such studies could be used in the future to assess the adverse health potential of an occupationally relevant bioaerosol and help consider defined protective strategies for workers.
The future(s) of global governance: A scenarios exercise
Authors: Saz‐Carranza Angel , Rueda‐Sabater Enrique , Vandendriessche Marie , Moreno Carlota , Jordana Jacint
Published: November 2023

Pervasive uncertainty has stretched the fabric of global governance to its limit. The shape and form of future global governance is far from clear – yet we need to explore how it may play out, so that we can not only prepare for it but also overcome possible pernicious trajectories. Scenario thinking can be used to rigorously explore different possible outcomes. In this article, we present an exercise applying scenario thinking to global governance. These scenarios should help policymakers to understand which policies may or may not work in the diverse possible futures. They may also help policymakers to consider how their organisation, state, or institution could be affected if the global governance of a specific issue evolves in one direction or another. Civil society members or private companies may want to probe how robust their strategies would be in different global governance configurations. The article synthetically presents key contextual premises and uncertainties which are given as follows: four broad scenarios for the world in 2035; four corresponding scenarios for global governance; and scenarios for the global governance of four macro‐sectors: trade, security, climate change, and finance.
Successful management of postoperative tracheal metastasis in small cell lung cancer with radiotherapy and durvalumab: A case report
Authors: Sugiura Yasoo , Fujimoto Hiroyuki , Hashizume Toshinori
Published: November 2023

The patient in this report was a 73‐year‐old male who was diagnosed with small cell lung cancer (T3N0M0 stage IIB) after presenting with a 5.5 cm tumor detected in the right lower lobe of the lung by radiography. After right lower lobectomy and lymphadenectomy, postoperative adjuvant chemotherapy was administered with cisplatin and etoposide. At 27 months after surgery, the patient complained of wheezing. Tracheal metastasis was identified through computed tomography and bronchoscopy. Biopsy confirmed metastasis of small cell lung cancer. Radiotherapy (60 Gy) was administered to the mediastinal lymph nodes, including the supraclavicular region. The patient then underwent four cycles of carboplatin‐etoposide‐durvalumab, followed by durvalumab maintenance therapy. At 49 months after surgery, the patient complained of discomfort while speaking, leading to the discovery of a nodule in the subglottic space, which confirmed small cell lung cancer metastasis. Radiotherapy (30 Gy) was administered to the larynx and mediastinum, and the patient continued with durvalumab monotherapy. As of 61 months after surgery, he remains recurrence‐free after the second course of radiotherapy. Our favorable outcome could be explained by the synergy between immunotherapy and radiotherapy. Here, we report a rare case of postoperative tracheal metastasis in small cell lung cancer successfully managed with radiotherapy and durvalumab. This shows promise in achieving local disease control and extending survival in postoperative metastatic lesions, highlighting a potential therapeutic approach.
Miliary brain metastases from lung adenocarcinoma with EGFR (L858R) and CTNNB1 mutations
Authors: Kunishige Michihiro , Takeuchi Eiji
Published: November 2023

A 76‐year‐old man was referred to our hospital with a cough. Chest computed tomography (CT) revealed a 45‐mm mass in the lingular segment of the left upper lobe. Transbronchial tumor biopsies showed adenocarcinoma. Contrast‐enhanced CT and bone scintigraphy revealed lung, pleura, and bone metastases. The patient was diagnosed with left upper lobe adenocarcinoma cT2bN3M1c stage IVB. A genetic analysis of the primary tumor using the Oncomine Dx Target Test Multi‐CDx system revealed positivity for epidermal growth factor receptor (EGFR) (L858R) and CTNNB1 mutations. Based on these findings, the patient was treated with osimertinib (80 mg/day) as first‐line therapy. Six months later, the tumor increased in size, indicating progressive disease. Osimertinib was stopped and second‐line therapy with carboplatin (area under the curve 5) and pemetrexed (500 mg/m2) was initiated. After three cycles of chemotherapy, the patient developed dementia and disorientation. Contrast‐enhanced magnetic resonance imaging of the head showed miliary brain metastases. Miliary dissemination is a rare form of brain metastasis. Miliary patterns of lung metastases have been strongly associated with the EGFR exon 19 deletion. The radiological features of miliary brain metastases of non‐small cell lung cancer with the exon 19 deletion have been reported. To the best of our knowledge, this is the first case report of lung cancer with miliary brain metastases and co‐mutations of EGFR (L858R) and CTNNB1. In conclusion, co‐mutations of EGFR (L858R) and CTNNB1 and the discontinuation of EGFR‐tyrosine kinase inhibitor may contribute to the development of miliary brain metastases. Further case studies are warranted.
MFSD2A frameshift variant in Kerry Hill sheep with microcephaly
Authors: Rudd Garces Gabriela , Letko Anna , Häfliger Irene M. , Müller Jana , Herden Christiane , Nesseler Anne , Wagner Henrik , Schmidt Martin J. , Drögemüller Cord , Lühken Gesine
Published: November 2023

Microcephaly is a rare neurodevelopmental disorder characterized by reduced skull circumference and brain volume that occurs sporadically in farm animals. We investigated an early‐onset neurodegenerative disorder observed in seven lambs of purebred Kerry Hill sheep. Clinical signs included inability to stand or severe ataxia, convulsions, and early death. Diagnostic imaging and brain necropsy confirmed microcephaly. The pedigree of the lambs suggested monogenic autosomal recessive inheritance. We sequenced the genome of one affected lamb, and comparison with 115 control genomes revealed a single private protein‐changing variant. This frameshift variant, MFSD2A: c.285dupA, p.(Asp96fs*9), represents a 1‐bp duplication predicted to truncate 80% of the open reading frame. MFSD2A is a transmembrane protein that is essential for maintaining blood–brain barrier homeostasis and plays a key role in regulating brain lipogenesis. Human MFSD2A pathogenic variants are associated with a neurodevelopmental disorder with progressive microcephaly, spasticity, and brain imaging abnormalities (NEDMISBA, OMIM 616486). Here we present evidence for the occurrence of a recessively inherited form of microcephaly in sheep due to a loss‐of‐function variant in MFSD2A (OMIA 002371‐9940). To the best of our knowledge, this is the first report of a spontaneous MFSD2A variant in domestic animals.
No trade‐off between growth and OsHV‐1 tolerance in Pacific oysters (Crassostrea gigas) farmed on the West Coast, USA
Authors: Divilov Konstantin , Schoolfield Blaine , Merz Noah , Langdon Chris
Published: November 2023

An important pathogen of concern for Pacific oyster growers in the USA is ostreid herpesvirus 1 (OsHV‐1). Currently, oyster stocks exist that are tolerant to OsHV‐1; however, it is uncertain if a trade‐off exists between their tolerance to OsHV‐1 and their growth in different environments. To investigate any potential trade‐offs, Pacific oyster families with varying levels of OsHV‐1 tolerance were grown in a bay where OsHV‐1 is endemic (Tomales Bay, CA) and in a bay where OsHV‐1 is absent (Willapa Bay, WA). In Tomales Bay, we found that oysters from OsHV‐1 tolerant families grew faster than oysters from OsHV‐1 susceptible families, while in Willapa Bay, no statistically significant difference in growth was found between oyster families with different levels of OsHV‐1 tolerance observed in Tomales Bay. These findings indicate that Pacific oysters bred to be tolerant to OsHV‐1 would not be expected to have a longer time‐to‐market regardless of the presence of OsHV‐1 in the growing environment.
Dermatological considerations for transgender and gender diverse patients: An Australian perspective
Authors: Gu Yaron , Tang Gia Toan , Cheung Ada Sau‐Zhuen , Sebaratnam Deshan Frank
Published: November 2023

Transgender and gender diverse (TGD) individuals are a group that experiences significant health disparities. In the multidisciplinary management of TGD patients, dermatologists may participate in managing skin‐ and hair‐related issues which contribute to gender affirmation and to the cutaneous sequelae of gender‐affirming hormone therapy. This review aims to highlight the unique needs of TGD patients, particularly from the perspective of Australian dermatologists. We review appropriate terminology critical for TGD care, gender affirmation in the Australian healthcare landscape, dermatological considerations for TGD patients and considerations for management.
Should the non‐canonical pathway of nitric oxide generation be targeted in hypertensive pregnancies?
Authors: Cottrell Elizabeth C.
Published: November 2023

Hypertension in pregnancy is prevalent, affecting around 10% of pregnancies worldwide, and significantly increases the risk of adverse outcomes for both mothers and their babies. Current treatment strategies for pregnant women with hypertension are limited, and new approaches for the management of hypertension in pregnancy are urgently needed. Substantial evidence from non‐pregnant subjects has demonstrated the potential for dietary nitrate supplementation to increase nitric oxide (NO) bioavailability and lower blood pressure, following bioactivation via the non‐canonical NO pathway. Emerging data suggest this approach may also be of benefit in pregnant women, although studies are limited. This review aims to summarise the current evidence from preclinical and clinical studies of nitrate supplementation in pregnancy, drawing on data from non‐pregnant populations where appropriate and highlighting key gaps in knowledge that remain to be addressed in future trials.
Sedimentary architecture of submarine lobes affected by bottom currents: Insights from the Rovuma Basin offshore East Africa
Authors: Chen Mei , Wu Shenghe , Wang Ruifeng , Zhang Jiajia , Xie Pengfei , Wang Min , Wang Xiaofeng , Xiong Qicong , Yu Jitao , Miramontes Elda
Published: November 2023

The influence of bottom currents on submarine channels has been widely recognized, for instance, by the formation of asymmetric channel‐levee systems and drifts. In contrast, it is often considered that submarine lobes can be only reworked by strong bottom currents and are not affected by bottom currents during their deposition. In this study, we analyse the potential effect of bottom currents on different hierarchical lobe architectures that formed during the lower Oligocene in the Rovuma Basin offshore East Africa. We characterize the stacking patterns, morphology and connectivity of different hierarchy lobes using well data and three‐dimensional seismic data. We found no direct influence of bottom currents on the lobe complexes and single lobes that show a unidirectional stacking pattern that is opposite to the direction of bottom currents. Lobe elements in single lobes display vertical accretion with no obvious relationship with bottom currents. Additionally, the first deposited single lobe morphology presents an asymmetric shape, with a thicker lobe margin on the downstream side of the bottom currents, but this is due to an initial low topography on the downstream side rather than bottom currents. The architectural distribution reflects that the topography present before the depositions of the submarine lobes was controlled by previous asymmetrical channel‐levee systems formed by the synchronous interaction of bottom currents and gravity flows. This asymmetric topography controls the subsequent deposition of lobes and results in the migration of single lobes in the upstream direction of bottom currents. Although weak to moderate bottom currents may not be able to substantially rework submarine lobes, our results demonstrate that they may control the geometry and evolution of submarine channels and thus indirectly affect the thickness and migration of lobes in more environments than previously thought.
Breast cancer and its therapeutic targets: A comprehensive review
Authors: Singh Ayushi , Mishra Rakhi , Mazumder Avijit
Published: November 2023

Breast cancer is a common and deadly disease, so there is a constant need for research to find efficient targets and therapeutic approaches. Breast cancer can be classified on a molecular and histological base. Breast cancer can be divided into ER (estrogen receptor)‐positive and ER‐negative, HER2 (human epidermal growth factor receptor2)‐positive and HER2‐negative subtypes based on the presence of specific biomarkers. Targeting hormone receptors, such as the HER2, progesterone receptor (PR), and ER, is very significant and plays a vital role in the onset and progression of breast cancer. Endocrine treatments and HER2‐targeted drugs are examples of targeted therapies now being used against these receptors. Emerging immune‐based medicines with promising outcomes in the treatment of breast cancer include immune checkpoint inhibitors, cancer vaccines, and adoptive T‐cell therapy. It is also explored how immune cells and the tumor microenvironment affect breast cancer development and treatment response. The major biochemical pathways, signaling cascades, and DNA repair mechanisms that are involved in the development and progression of breast cancer, include the PI3K/AKT/mTOR system, the MAPK pathway, and others. These pathways are intended to be inhibited by a variety of targeted drugs, which are then delivered with the goal of restoring normal cellular function. This review aims to shed light on types of breast cancer with the summarization of different therapeutic approaches which can target different pathways for tailored medicines and better patient outcomes.
What starts with laughter ends in tears: Invasive alien species regulations should not hinder scientific research
Authors: Pietrzyk‐Kaszyńska Agata , Olszańska Agnieszka , Najberek Kamil , Maciaszek Rafał , Solarz Wojciech
Published: November 2023

Biological invasions represent one of the major threats to the world's biodiversity. National and international efforts are taken to address the complexity and dynamic of invasions in legislation. However, based on the Polish experience of implementing the European Union's regulation on invasive alien species (IAS), we suggest that an unclear and disorganized process of law implementation results in the regulations being counterproductive. We describe how a well‐planned policy can become a burden impeding effective research and, consequently, scientific feedback to improve the policy. The results of our study suggest that there is a large scale of scientists' noncompliance with new legal requirements. For many researchers, the implementation of the new IAS regulation was changing the rules in the middle of the game. Researchers strictly following the new regulations must wait for the relevant permits and may risk the successful completion of their projects. Conversely, researchers who prioritize project completion may be forced to continue their research violating the law. We argue that this example of implementing the new IAS regulation illustrates the need to include some intermediate solutions providing more flexibility and time for researchers to adjust to policy change, thus minimizing the negative impacts of the new legislature on scientific progress.
Wild sea cucumber trade in rural Madagascar: Consequences for conservation and human welfare
Authors: Rothamel Emily , Borgerson Cortni , Rajaona Delox , Razafindrapaoly Be Noel , Rasolofoniaina Be Jean Rodolph , Feehan Colette
Published: November 2023

Overexploitation of fisheries is a challenge to both marine conservation and human welfare. The trade of sea cucumbers is a multi‐billion‐dollar market, spanning over 70 countries. Global concern over unsustainable sea cucumber trade led to the inclusion of three species in CITES Appendix II, two of which are found in Madagascar (Holothuria fuscogilva and Holothuria nobilis). We used 792 structured interviews (2015–2020) to study the intensity of wild sea cucumber collection and exportation in rural northeastern Madagascar, where 30% of all (terrestrial and aquatic) native species are threatened with extinction. Wild sea cucumber collection was common and increased tenfold during the study; one in five coastal households caught and sold wild sea cucumbers. Furthermore, trade relied on threatened species; half of collected sea cucumbers are threatened, including CITES II‐restricted H. nobilis (Endangered) and H. fuscogilva (Vulnerable). While such collection threatens conservation, it improved the welfare of rural collectors. Sea cucumber collectors were significantly wealthier and more food secure than other community members. Given both the high collection of threatened and regulated species and high regional food insecurity (58% of households), the current regulation of threatened species alone is not reducing levels of unsustainable catch.