bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting the deNEDDylating enzyme NEDP1 to ameliorate ALS phenotypes through Stress Granules dissolution
Authors: Kassouf Toufic , Shrivastava Rohit , Meszka Igor , Bailly Aymeric , Polanowska Jolanta , Trauchessec Helene , Mandrioli Jessica , Carra Serena , Xirodimas Dimitris P.
Published: January 2023

In Amyotrophic Lateral Sclerosis (ALS) motor neuron disease, mutations in proteins that upon stress localize within cytoplasmic protein inclusions called Stress Granules (SGs), are linked to the formation of aberrant inclusions, which are related to neuronal cell death. By combining studies in human cells andC. elegansincluding the use of Nanobodies, we found that inhibition of NEDP1, the enzyme responsible for the processing and deconjugation of the Ubiquitin-like molecule NEDD8 from substrates, promotes the elimination both of physiological and pathological SGs. The hyper-NEDDylation of Poly-(ADP-ribose) polymerase-1 enzyme upon NEDP1 inhibition compromises PAR production and is a key mechanism for the observed SG phenotype. Importantly, the above-described effects are related to improved cell survival in human cells, and inC. elegans, NEDP1 deletion ameliorates ALS-phenotypes related to animal motility. Our studies reveal NEDP1 as potential therapeutic target for ALS, based on the elimination of aberrant SGs.
Thyroid hormone-dependent apoptosis during metamorphosis inCiona robustainvolves both bilaterian-ancestral and vertebrate-derived processes
Authors: Nelly Godefroy , Emilie Le Goff , Qiaowei Pan , Stephen Baghdiguian , Mélanie Debiais-Thibaud , Camille Martinand-Mari
Published: January 2023

Chordate metamorphosis is a postembryonic larva-to-juvenile transition triggered by thyroid hormones and their specific receptors (TR). This crucial developmental event shows a wide morphological diversity among different chordate lineages and is characterized by ecological, morphological, metabolic and behavioral changes that can be drastic. One of the most studied models is the amphibian Xenopus, whose tadpole metamorphosis includes apoptosis-induced tail regression dependent on the thyroid hormone pathway. In an evolutionary context, we used the ascidian model, the extant closest group to vertebrates, in which the swimming larva transforms to a sessile filter-feeding juvenile during metamorphosis, to study the role of thyroid hormones in this transformation. The ascidian metamorphosis is also characterized by an apoptosis-driven tail regression as in Xenopus. However, whether this apoptosis-driven process is dependent on the thyroid hormone has not yet been elucidated.

In this study, we interfered with thyroid hormone signaling during tail regression of the ascidianCiona robustato investigate whether (i) thyroid hormone is involved in the regulation of developmental apoptosis, and (ii) apoptosis leading to tail regression involves its classical molecular pathways. We described specific gene expression landmarks as well as apoptosis dynamics during larva metamorphosis under thyroid hormone exposure and thyroid hormone inhibition treatments. We provide evidence thatCiona robustametamorphosis involves thyroid hormone-dependent apoptosis, similar to other studied chordates. However, the mode of action of thyroid hormone shows great variation compared to the classically described scheme in chordates, both in thyroid hormone/TR interactions and in the apoptotic pathway.
CoVAMPnet: Comparative Markov State Analysis for Studying Effects of Drug Candidates on Disordered Biomolecules
Authors: Marques Sérgio M. , Kouba Petr , Legrand Anthony , Sedlar Jiri , Disson Lucas , Planas-Iglesias Joan , Sanusi Zainab , Kunka Antonin , Damborsky Jiri , Pajdla Tomas , Prokop Zbynek , Mazurenko Stanislav , Sivic Josef , Bednar David
Published: January 2023

Computational study of the effect of drug candidates on intrinsically disordered biomolecules is challenging due to their vast and complex conformational space. Here we developed a Comparative Markov State Analysis (CoVAMPnet) framework to quantify changes in the conformational distribution and dynamics of a disordered biomolecule in the presence and absence of small organic drug candidate molecules. First, molecular dynamics trajectories are generated using enhanced sampling, in the presence and absence of small molecule drug candidates, and ensembles of soft Markov state models (MSMs) are learned for each system using unsupervised machine learning. Second, these ensembles of learned MSMs are aligned across different systems based on a solution to an optimal transport problem. Third, the directional importance of inter-residue distances for the assignment to different conformational states is assessed by a discriminative analysis of aggregated neural network gradients. This final step provides interpretability and biophysical context to the learned MSMs. We applied this novel computational framework to assess the effects of ongoing phase 3 therapeutics tramiprosate (TMP) and its metabolite 3-sulfopropanoic acid (SPA) on the disordered Aβ42 peptide involved in Alzheimer’s disease. Based on adaptive sampling molecular dynamics and CoVAMPnet analysis, we observed that both TMP and SPA preserved more structured conformations of Aβ42 by interacting non-specifically with charged residues. SPA impacted Aβ42 more than TMP, protecting α-helices and suppressing the formation of aggregation-prone β-strands. Experimental biophysical analyses showed only mild effects of TMP/SPA on Aβ42, and activity enhancement by the endogenous metabolization of TMP into SPA. Our data suggest that TMP/SPA may also target other biomolecules than Aβ peptides. The CoVAMPnet method is broadly applicable to study the effects of drug candidates on the conformational behavior of intrinsically disordered biomolecules.

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Customer experiences in the era of artificial intelligence (AI) in context to FinTech: a fuzzy AHP approach
Authors: Arora Anchal , Gupta Sanjay , Devi Chandrika , Walia Nidhi
Published: January 2023

Purpose

The financial technology (FinTech) era has brought a revolutionary change in the financial sector’s customer experiences at the national and global levels. The importance of artificial intelligence (AI) in the context of FinTech services for enriching customer experiences has become a new norm in this modern era of technological advancement. So, it becomes crucial to understand the customer’s perspective. The current research ranks the factors and sub-factors influencing customers’ perceptions of AI-based FinTech services.

Design/methodology/approach

The sample size for this study was decided to be 970 respondents from four Indian cities: Mumbai, Delhi, Kolkata and Chennai. The Fuzzy-AHP technique was used to identify the primary factors and sub-factors influencing customers’ experiences with AI-enabled finance services. The factors considered in the study were service quality, trust commitment, personalization, perceived convenience, relationship commitment, perceived sacrifice, subjective norms, perceived usefulness, attitude and vulnerability. The current research is both empirical and descriptive.

Findings

The study’s three top factors are service quality, perceived usefulness and perceived convenience, all of which have a significant impact on customers’ experience with AI-enabled FinTech services discussing sub-criteria three primary criteria for customers’ experience for FinTech services include: “Using FinTech would increase my effectiveness in managing a portfolio (A2)”, “My peer groups and friends have an impact on using FinTech services (SN3)” and “Using FinTech would increase my efficacy in administering portfolio (PU2)”.

Research limitations/implications

The current study is limited to four Indian cities, with 10 factors to understand customers’ preferences in FinTech. Further research can focus on other dimensions like perceived ease of use, familiarity, etc. Future studies can have a broader view of different geographical locations and consider new tech to understand customer perceptions better.

Practical implications

The study’s findings will significantly assist businesses in determining the primary aspects influencing customers’ experiences with AI-enabled financial services. As a result, they will develop strategies and policies to entice clients to use AI-powered FinTech services.

Originality/value

Existing AI research investigated several vital topics in the context of FinTech services. On the other hand, the current study ranked the criteria in understanding customer experiences. The research will substantially assist marketers, business houses, academicians and practitioners in understanding essential facets influencing customer experience and contribute significantly to the literature.
Big data analytics capabilities and supply chain performance: testing a moderated mediation model using partial least squares approach
Authors: AL-Khatib Ayman Wael , Ramayah T.
Published: January 2023

Purpose

In this study, the authors investigate the effect of big data analytics capability (BDAC) on supply chain performance (SCP) to assess the mediating effect of supply chain innovation (SCI) and the moderating effect of a data-driven culture (DDC).

Design/methodology/approach

The authors collected the primary data through an online questionnaire survey from the manufacturing sector operating in Jordan. The authors used 420 samples for the final data analysis, which the authors performed via partial least squares structural equation modelling using SmartPLS 3.3.9 software.

Findings

The results indicate that BDAC has a strong relationship with SCI and SCP. SCI shows a positive relationship with SCP as well as a mediating effect on SCI. The authors confirmed that DDC moderated the relationship between SCI and SCP.

Originality/value

The authors developed a conceptual and empirical model to investigate the relationship between BDAC, SCI, DDC and SCP. The authors contributed new theoretical and managerial insights that add value to the supply chain management literature through testing the moderated-mediated model of these constructs in Jordan’s manufacturing sector.
The impact of brand origin and CSR actions on consumer perceptions in retail banking during a crisis
Authors: Tosun Petek , Köylüoğlu A. Selçuk
Published: January 2023

Purpose

Consumers’ corporate social responsibility (CSR) expectations have increased in the new coronavirus (COVID-19) pandemic, while many financial institutions have supported society with their health-related CSR actions. This study examines the impact of CSR actions and brand origin on consumer attitudes, CSR perceptions, customer-based brand equity (CBBE) and supportive communication intent in retail banking during the crisis from signaling and stakeholder theory perspectives.

Design/methodology/approach

A 2 (foreign vs. local brand) x 2 (COVID-19-related vs. another CSR action) between-subjects factorial design was used to analyze consumer data.

Findings

CSR actions of local brands created more positive attitudes, CSR perceptions and greater CBBE and supportive communication intent than foreign banks. However, CSR action (COVID-19-related vs. another) did not significantly influence consumer attitudes, CSR perceptions, CBBE and supportive communication intent.

Originality/value

This research has shown the significant impact of brand origin on consumer perceptions in response to CSR actions during the pandemic. It has suggested an original conceptual framework and presented timely empirical findings for retail banking in the pandemic period, which can exemplify a crisis period shaped by uncertainty. Besides, it extended the previous literature by focusing on the interaction between brand origin and CSR actions in shaping consumers’ CSR and brand perceptions. It is among the first studies examining brand origin’s impact on supportive communication intent.
Financial performance of firms with supply chains during the COVID-19 pandemic: the roles of dynamic capability and supply chain resilience
Authors: Juan Shih-Jung , Li Eldon Y.
Published: January 2023

Purpose

This study proposes an integrated model to explore the relationships between dynamic capability and supply chain resilience (SCRE) and the relationships' impacts on firms' financial performance with supply chains (FPwSC) during the coronavirus disease 2019 (COVID-19) pandemic.

Design/methodology/approach

Based on resource-based theory and knowledge-based theory, the dynamic capability is classified into resource-based dynamic capability (RBDC) and knowledge-based dynamic capability (KBDC). The study collects 158 useable survey samples from manufacturers in Taiwan and analyzes the samples with the structural equation model.

Findings

The results show that knowledge is power; KBDC is crucial for FPwSC, SCRE and RBDC. In addition, SCRE mediates the relationship between KBDC and FPwSC. Finally, RBDC significantly suppresses FPwSC.

Research limitations/implications

Future researchers could replicate this study in other industries and expand this to other countries to generalize the results.

Practical implications

A firm with KBDC can adopt and implement strategies that exploit its internal strengths to respond to environmental opportunities, overcome internal weaknesses and mitigate external threats. Furthermore, a firm should fully utilize SCRE with proactive and reactive strategies. Exercising a firm's KBDC could facilitate SC collective intelligence to handle the risk of SC disruption and vice versa.

Originality/value

The study is the first to combine KBDC, RBDC and SCRE into an integrated model for FPwSC. Moreover, this study reveals that resilience relies on knowledge, not resources, as evidenced by SCRE being affected significantly by KBDC but not RBDC.
Developing SME performance management practices: interventions for improving productivity
Authors: Jones Oliver William , Devins David , Barnes Greg
Published: January 2023

Purpose

The paper is a proof of concept (PoC) intervention study aimed for developing performance management (PM) practices in manufacturing small and medium-sized enterprises (SMEs) with the longer-term aim enabling the SMEs to improve their productivity. The intervention was designed and deployed by a collaborative quartet of academics, management consultants, accountancy firm and a commercial bank manager.

Design/methodology/approach

The paper firstly musters a set of initialising PM practices aligned to productivity improvement. These are utilised to design a knowledge transfer intervention for deployment with a set of manufacturing SMEs incorporating some associated productivity tools. The evaluation of the intervention utilised a case study approach founded on a logic model of the intervention to assess the development of the PM practices.

Findings

The intervention contributed to a partial development of the mustered practices and the productivity diagnostic based on the multi-factor productivity (MFP) abstraction and a data extraction protocol had the strongest impact. The study revealed the importance of the three interlaced factors: Depth of engagement, feedback opportunities and the intervention gradient (the increase of independent action from the participating SME's and the diminishment of the external intervention effort).

Research limitations/implications

The case study is based on a limited number of individual SME's, and within just the manufacturing sector.

Practical implications

SME businesses will require a more sustained programme of interventions than this pilot to develop PM capability, and depth of engagement within the SME is critical. Professional stakeholders can be utilised in recruitment of firms for intervention programmes. Business can start developing PM capability prior to PMS implementation using the tools from this programme.

Originality/value

The productivity diagnostic tool, based on a synthesis of MFP and the performance pyramid, an array of potential initialising practices for PM capability and discovery of potential mechanisms for PM practice development.
Do executive remuneration decision-makers know what's going on? The gap between independence and institutional contexts
Authors: Perkins Stephen J. , Shortland Susan
Published: January 2023

Purpose

Drawing on institutional theory, this study aims to analyse the regulation of executive remuneration as espoused in the United Kingdom (UK) codified corporate governance principles, focussing on sources of advice to decision-makers, the nature of the advice sought and given, and interaction of those involved in the process.

Design/methodology/approach

A qualitative research design was used. Data were assembled from interviewing non-executive board/remuneration committee members; institutional investors; external remuneration consultants and internal human resources (HR)/reward specialists. Results were analysed in accordance with the Gioia technique.

Findings

Tensions inherent in the interpretation of corporate governance codes are illustrated. Emphasis on independent advice combined with constraints on decision-makers' capacity to navigate the nuances of a complex field and reputational concerns risks standardised instead of bespoke remuneration approaches aligned with corporate contexts.

Practical implications

There is a role for internal HR advisors to add value through their potential to reduce the gap within remuneration committees between institutional contexts and independent decision-making, facilitating more strategic human resource management inspired executive remuneration.

Originality/value

Application of institutional theory indicates the relevance of balancing external with internal sources to secure advice that is horizontally and vertically aligned within an organisation to meet the letter and spirit of corporate governance norms. Extending the explanatory power of institutional theory, care is needed though not to overlook the normative underpinnings of professional advisors' own value sets.
Boosting propagule transport models with individual‐specific data from mobile apps
Authors: Fischer Samuel M. , Ramazi Pouria , Simmons Sean , Poesch Mark S. , Lewis Mark A.
Published: January 2023

Management of invasive species and pathogens requires information about the traffic of potential vectors. Such information is often taken from vector traffic models fitted to survey data. Here, user‐specific data collected via mobile apps offer new opportunities to obtain more accurate estimates and to analyse how vectors' individual preferences affect propagule flows. However, data voluntarily reported via apps may lack some trip records, adding a significant layer of uncertainty. We show how the benefits of app‐based data can be exploited despite this drawback.

Based on data collected via an angler app, we built a stochastic model for angler traffic in the Canadian province Alberta. There, anglers facilitate the spread of whirling disease, a parasite‐induced fish disease. The model is temporally and spatially explicit and accounts for individual preferences and repeating behaviour of anglers, helping to address the problem of missing trip records.

We obtained estimates of angler traffic between all subbasins in Alberta. The model's accuracy exceeds that of direct empirical estimates even when fewer data were used to fit the model. The results indicate that anglers' local preferences and their tendency to revisit previous destinations reduce the number of long interwaterbody trips potentially dispersing whirling disease. According to our model, anglers revisit their previous destination in 64% of their trips, making these trips irrelevant for the spread of whirling disease. Furthermore, 54% of fishing trips end in individual‐specific spatially contained areas with mean radius of 54.7 km. Finally, although the fraction of trips that anglers report was unknown, we were able to estimate the total yearly number of fishing trips in Alberta, matching an independent empirical estimate.

Policy implications. We make two major contributions: (1) we provide a model that uses mobile app data to boost the mechanistic accuracy of classic propagule transport models, and (2) we demonstrate the importance of individual‐specific behaviour of vectors for propagule transport. Ignoring vectors' local preferences and their tendency to revisit previous destinations can lead to significant overestimates of vector traffic and biased estimates of propagule flows. This has clear implications for the management of invasive species and animal diseases.
Contrasting effects of vineyard type, soil and landscape factors on ground‐ versus above‐ground‐nesting bees
Authors: Wersebeckmann Vera , Warzecha Daniela , Entling Martin H. , Leyer Ilona
Published: January 2023

Agricultural intensification and abandonment of traditional agricultural practices are main drivers of current insect declines. The resulting loss of feeding and nesting opportunities has led to a decrease in pollinator populations like wild bees. While the restoration of floral resources has been widely implemented in wild bee conservation, nesting resources, particularly for ground‐nesting species, are barely considered.

We assessed wild bee diversity in a wine‐growing area in Germany in 15 study sites along a soil gradient and evaluated whether wild bees were distinctly affected by different vineyard types (vertically oriented, terraced, abandoned), local conditions (e.g. shrub and flower cover) and landscape factors in response to divergent nesting needs (above‐ground vs. ground‐nesting).

We found that wild bees responded more strongly to the availability of nesting sites than to flower resources. While ground‐nesting bees were determined by the suitability of soil aspects for nesting irrespective of vineyard management types, above‐ground‐nesting bees profited from vineyard abandonment and shrub encroachment in vineyard fallows and were enhanced by the availability of semi‐natural habitats (SNHs) in the surrounding landscape. In contrast, floral resource availability in managed vineyards had only marginal effects on above‐ground‐nesting bees.

Synthesis and applications: Life‐history traits like nesting strategies have long been neglected in wild bee conservation approaches, but proved to be highly relevant, especially for ground‐nesting bees. For this, agri‐environmental schemes can no longer solely focus on the restoration of floral resources, but should equally address nesting resources. Therefore, management efforts for enhancing wild bees in vineyard landscapes should aim at complementing nesting resources for ground‐nesting bees (e.g. exposed bare ground patches) and above‐ground‐nesting bees (e.g. woody elements, hedges) in addition to floral resources. At the landscape level, conserving heterogeneous landscapes at a mixture of actively managed vineyards and semi‐natural and woody elements is significant to maintain diverse bee communities.
Scalar properties of the transnational field of human rights: Field effects and human rights in Bahrain
Authors: Bhatia Luke G. G.
Published: January 2023

Whilst a body of work exists that has engaged with and conceptualised transnational fields, and in particular for this paper, the transnational field of human rights, more work needs to be done to elaborate on the effects of transnational fields, at the national level. Using Bourdieu's field theory, and more recent scholarship that focuses on scalar aspects of fields, this research focuses on a human rights field at the national level in Bahrain. The paper addresses two levels/dimensions of the transnational field of human rights: the transnational level and the national level, focussing on the field's vertical autonomy. Based upon nineteen in‐depth interviews, the research retrieves the biographical trajectories of Bahraini human rights activists and activists from iNGOs with a specific remit that includes Bahrain. The paper argues that the vertical autonomy of the transnational field of human rights has demonstrable field effects at the national level, and that this has a number of implications. First, where transnational fields have greater vertical autonomy, the national level can operate with varying hierarchies, with actors adopting practices that diverge from those acting transnationally. Second, as a result of these scalar differences and the vertical autonomy of the transnational field, actors at the national level may have to adapt their practices, others can be side‐lined as a result of ‘symbolic pollution.’ Third, in order for local actors to engage with transnational advocacy networks, they must be the right type of actor.
Insights into the divergent evolution of the oceanic squid Sthenoteuthis oualaniensis (Cephalopoda: Ommastrephidae) from the Indian Ocean
Authors: JEENA Nikarthil S. , SAJIKUMAR Kurichithara K. , RAHUMAN Summaya , RAGESH Nadakkal , KOYA K. P. Said , CHINNADURAI Shunmugavel , SASIKUMAR Geetha , MOHAMED Kolliyil S.
Published: January 2023

Sthenoteuthis oualaniensis is known for its complex population structure with three major transoceanic forms (viz. middle‐sized, dwarf, and giant forms) whose taxonomic status has been disputed for decades. This integrated taxonomic study examines these prevenient morphotypes gathered on cruises in the Indian Ocean to ascertain their status in the evolutionary history of the species. Molecular analyses employing mitochondrial (COI, ND2) and nuclear (H3) markers revealed four genetically distinct and novel lineages of the species in the Indian Ocean, representing three morphotypes from the Arabian Sea and one from the Southern Indian Ocean. The mitochondrial‐based phylograms revealed two distinct clades in the species: “dwarf forms + giant form” and “middle‐sized forms,” which further branch into geographically structured evolutionary units. Species delimitation analyses recovered five distinct clades, namely, the Arabian Sea giant and dwarf forms, Equatorial, Eastern Typical, and Other Middle‐sized forms, representing the consensus molecular operational taxonomic units. H3 being heterozygous could not resolve the phylogeny. Haplotype network and AMOVA analysis of mtDNA genes indicated explicit phylogeographic structuring of haplotypes, whereas these outputs and PCA results were incongruent with the morphological grouping. Phenetic features distinguishing the morphotypes were sometimes plastic and mismatched with the genotypes. The giant form was genetically close to the dwarf forms, contradicting the earlier notion that it descended from the middle‐sized form. It may be assumed that the dwarf form evolved following sympatric speciation and adaptation to warm equatorial waters, while the focal features of the Western Arabian Sea guide toward allopatric speciation of the giant form.
Flight performance and wing morphology in the bat Carollia perspicillata: biophysical models and energetics
Authors: CARNEIRO Lucas de Oliveira , MELLADO Breno , NOGUEIRA Marcelo Rodrigues , CRUZ‐NETO Ariovaldo Pereira da , MONTEIRO Leandro Rabello
Published: January 2023

Studies on functional performance are important to understand the processes responsible for the evolution of diversity. Morphological trait variation within species influences the energetic cost of locomotion and impacts life history traits, with ecological and evolutionary consequences. This study examined wing morphology correlates of flight performance measured by energetic expenditure in the Seba's short‐tailed bat, Carollia perspicillata. In the flight experiments, nature caught bats (59 females, 57 males) were allowed to fly for 3 min in a room. After each flight, thermographic images were taken to measure body temperature, and biophysical models were used to calculate sensible heat loss as a measure of energetic expenditure. Wing morphological traits were measured for each individual and associated with heat loss and power required to fly on performance surfaces. Wing morphological traits explained 7–10% of flight energetic cost, and morphologies with the best performance would save the energy equivalent to 9–30% of total daily requirements. The optimal performance areas within the C. perspicillata morphospace were consistent with predicted selection trends from the literature. A trade‐off between demands for flight speed and maneuverability was observed. Wing loading and camber presented sexual dimorphism. These morphological differences are likely associated with more economical but less maneuverable flight in females, leading them to fly more often in open areas along the forest edge. Our findings demonstrate how small scale changes in wing morphology can affect life history strategies and fitness.
Effect of sodium‐glucose cotransporter 2 inhibitors on the rate of decline in kidney function: A systematic review and meta‐analysis
Authors: Duo Yanbei , Gao Junxiang , Yuan Tao , Zhao Weigang
Published: January 2023

Aim

To investigate the influence of sodium/glucose cotransporter‐2 inhibitors (SGLT‐2i) on renal function during the course of its administration, particularly in the initial weeks.

Materials and Methods

Randomized controlled trials (RCTs) related to SGLT‐2i were searched in databases (MEDLINE, EMBASE, and Cochrane Central Register) from the database's inception to August 31, 2021. All RCTs reported the kidney outcomes of SGLT2i versus active or placebo control were included, regardless of the presence of diabetes in the patients and the baseline estimated glomerular filtration rate (eGFR). The Cochrane Collaboration risk of bias tool was used to assess the quality of the included studies. All outcome comparisons were performed using the RevMan 5.4 software.

Results

Eleven RCTs with 58 534 participants reporting prespecified renal outcomes were identified. There was no heterogeneity in the baseline eGFR and urine albumin‐to‐creatinine ratio in the included studies. In the initial 2–4 weeks, there was an acute decline of eGFR in the SGLT‐2i group compared with placebo group (weighted mean difference [WMD] −3.35 ml/min/1.73 m2; 95% CI, −3.81 to −2.90; I2 = 35%, p = .15); When compared to baseline eGFR in the SGLT‐2i group, the WMD was −4.02 ml/min/1.73 m2 (95% confidence interval [CI], −3.61 to −4.44; I2 = 0%, p = .45). The renoprotective effect gradually appeared, and the decline rate of eGFR in the SGLT‐2i group was sustained slower than placebo. However, the statistically significant benefit of SGLT‐2i did not appear until the 104th week (the second year) (WMD 0.35 ml/min/1.73 m2, 95% CI, 0.04 to 0.66; I2 = 45%, p = .08). Subgroup analysis showed SGLT‐2i had a similar benefit on renal function regardless of baseline eGFR values.

Conclusion

SGLT‐2i consistently slowed the deterioration of eGFR since the early stage of administration, even in patients with chronic kidney disease. However, there was an acute decline in eGFR in the initial 2–4 weeks; afterwards the renoprotective effect of SGLT‐2i gradually appeared and remained stable in the next few years.
Development and evaluation of a risk algorithm predicting alcohol dependence after early onset of regular alcohol use
Authors: Bharat Chrianna , Glantz Meyer D. , Aguilar‐Gaxiola Sergio , Alonso Jordi , Bruffaerts Ronny , Bunting Brendan , Caldas‐de‐Almeida José Miguel , Cardoso Graça , Chardoul Stephanie , de Jonge Peter , Gureje Oye , Haro Josep Maria , Harris Meredith G. , Karam Elie G. , Kawakami Norito , Kiejna Andrzej , Kovess‐Masfety Viviane , Lee Sing , McGrath John J. , Moskalewicz Jacek , Navarro‐Mateu Fernando , Rapsey Charlene , Sampson Nancy A. , Scott Kate M. , Tachimori Hisateru , ten Have Margreet , Vilagut Gemma , Wojtyniak Bogdan , Xavier Miguel , Kessler Ronald C. , Degenhardt Louisa
Published: January 2023

Aims

Likelihood of alcohol dependence (AD) is increased among people who transition to greater levels of alcohol involvement at a younger age. Indicated interventions delivered early may be effective in reducing risk, but could be costly. One way to increase cost‐effectiveness would be to develop a prediction model that targeted interventions to the subset of youth with early alcohol use who are at highest risk of subsequent AD.

Design

A prediction model was developed for DSM‐IV AD onset by age 25 years using an ensemble machine‐learning algorithm known as ‘Super Learner’. Shapley additive explanations (SHAP) assessed variable importance.

Setting and Participants

Respondents reporting early onset of regular alcohol use (i.e. by 17 years of age) who were aged 25 years or older at interview from 14 representative community surveys conducted in 13 countries as part of WHO's World Mental Health Surveys.

Measurements

The primary outcome to be predicted was onset of life‐time DSM‐IV AD by age 25 as measured using the Composite International Diagnostic Interview, a fully structured diagnostic interview.

Findings

AD prevalence by age 25 was 5.1% among the 10 687 individuals who reported drinking alcohol regularly by age 17. The prediction model achieved an external area under the curve [0.78; 95% confidence interval (CI) = 0.74–0.81] higher than any individual candidate risk model (0.73–0.77) and an area under the precision‐recall curve of 0.22. Overall calibration was good [integrated calibration index (ICI) = 1.05%]; however, miscalibration was observed at the extreme ends of the distribution of predicted probabilities. Interventions provided to the 20% of people with highest risk would identify 49% of AD cases and require treating four people without AD to reach one with AD. Important predictors of increased risk included younger onset of alcohol use, males, higher cohort alcohol use and more mental disorders.

Conclusions

A risk algorithm can be created using data collected at the onset of regular alcohol use to target youth at highest risk of alcohol dependence by early adulthood. Important considerations remain for advancing the development and practical implementation of such models.
Host selection behaviour of the banded pine weevil, Pissodes castaneus (Coleoptera: Curculionidae)
Authors: Germano Mónica D.
Published: January 2023

Pissodes castaneus represents an emerging pest species for Pinus spp. production in Latin America. This species attacks all the cultivated pine species in Patagonia Argentina causing wood damage and tree death. The objectives of this work were to describe the host preference behaviour of P. castaneus and the influence of wood damage by conspecifics on its host selection.

In two‐choice bioassays, P. castaneus showed a feeding preference for Pinus contorta over P. ponderosa. However, percent weight gain when feeding on either species was similar.

In other bioassays, P. castaneus spent more time in areas with twigs on which other conspecifics had recently fed, although they were able to successfully feed on twigs without previous damage.

These results show that while P. castaneus can successfully colonize different pine species, P. contorta may be more susceptible to attack than P. ponderosa. Silvicultural management should be prioritized considering the weevil's preference for attacking damaged hosts.
The positive effects of online group singing on psycho‐physiological variables during the COVID‐19 pandemic—A pilot randomized controlled trial
Authors: Schäfer Thomas
Published: January 2023

The psychological variables that were particularly influenced by social distancing during the COVID‐19 pandemic—stress, loneliness, social participation, and well‐being—correspond closely to variables that can also be influenced by music. The present study is a pilot randomized controlled trial examining the effects of online group singing on psycho‐physiological variables during the pandemic. Over 4 weeks, an online singing group sang together once a week, for 1 h, under the guidance of a professional voice coach. In a first control group, participants also met for 60 min per week but only discussed and exchanged personal experiences about music. A second control condition consisted of a waiting list group. Across all variables studied (positive and negative affect, life satisfaction, stress, loneliness, social participation, self‐efficacy, and body perception), positive effects were revealed in the singing group and in the discussion group, but not in the waiting list group. The effects of the variables self‐efficacy, social participation, loneliness, and life satisfaction were markedly stronger in the singing group than in the discussion group. The results demonstrate the effectiveness of group singing on a number of psycho‐physiological variables, which can be used profitably in and outside of times of crisis, in both clinical and non‐clinical settings.
Assessment of the influence of Fc‐γ receptor polymorphisms on biologics' pharmacokinetics in Tunisian rheumatoid arthritis patients
Authors: Mahmoud Ines , Moalla Myriam , Ben Tekaya Aicha , Charfi Rim , Rouached Leila , Bouden Selma , Tekaya Rawdha , Saidane Olfa , Abdelmoula Leila , Sfar Imen
Published: January 2023

Aims

This study aims to determine whether a modification in Fc‐γ receptors' (FcgRs) affinity to Fc portion, caused by single nucleotide polymorphisms such as rs1801274‐R131H FcgRIIa, rs396991‐F158V FcgRIIIa and NA1/NA2‐FcgRIIIb, might impact clearance of therapeutic monoclonal antibodies and thus serum drug levels and the development of anti‐drug antibodies.

Methods

A cross sectional, multicentral and noninterventional study was conducted in Tunisian RA patients treated with rituximab (RTX), etanercept (ETA), infliximab (IFX) and adalimumab (ADL). Serum drug level (SDL) of the different biologics and ADA against them were measured. All patients were genotyped for the 3 FcgR single nucleotide polymorphisms.

Results

A total of 81 patients were included: 47 were under tumour necrosis factor inhibitors (18 ETA, 13 ADL and 16 IFX), and 34 were under RTX. Regardless of the type of biotherapy, SDL was in therapeutic range, in 35 patients (43.2%), of whom only 1 was treated with RTX. Fourteen patients (22.2%) developed ADA, but none of the patients treated with ETA had detectable ADA levels. There was no association between SDL positivity and FcgR polymorphisms. However, the high affinity FcgR2A 131 H/H receptor was statistically more prevalent in patients with detectable ADA treated with ADL, IFX and RTX (P = .018). The same result was obtained in the monoclonal antibody tumour necrosis factor inhibitor subgroup (n = 29, P = .022) as well as in patients treated only with IFX (n = 16, P = .029).

Conclusion

Our work supports the hypothesis of an impact of FcgR single nucleotide polymorphisms on biologics' immunogenicity, particularly FcgR R131H polymorphism, but further studies with larger cohorts need to be undertaken to confirm these results.
Equity and COVID‐19 treatment allocation: A questionable criterion
Authors: Vogelstein Eric , Krishnamurthi Guha
Published: January 2023

Since the onset of the COVID‐19 pandemic, a controversial criterion for allocating scarce medical treatment has been defended and incorporated into policy: the criterion of equity. Equity‐included allocation schemes prioritize, to some degree, patients from marginalized or historically disadvantaged racial/ethnic groups, or patients with low socioeconomic status, for scarce treatment. The use of such criteria has been most prominently defended in two ways: (1) as reflecting a risk factor for severe COVID‐19, and thus as a way of tracking medical need, and (2) as a form of remedial justice, viz. a way of redressing disparities in COVID outcomes that are caused by underlying unjust social conditions. Here, we delineate and critique those arguments. We argue that not only are such arguments unconvincing but also that there are compelling moral reasons to reject the sort of equity‐included allocation schemes at issue.
Incidence of self‐harm after bariatric surgery: A nationwide registry‐based matched cohort study
Authors: Dahlberg Karuna , Jaensson Maria , Cao Yang , Näslund Erik , Stenberg Erik
Published: January 2023

The aims of this study were to evaluate the longitudinal risk of self‐harm and the risk factors for self‐harm after bariatric surgery in patients and control subjects without prior self‐harm. This observational cohort study was based on prospectively registered data. Patients 18–70 years at time of surgery, body mass index (BMI) > 30 kg/m2, who underwent a primary Roux‐en‐Y gastric bypass (RYGB) procedure or a primary sleeve gastrectomy between 2007 and 2019 were considered for inclusion. All patients who met the inclusion criteria were matched 1:10 to the general population in Sweden (69 492 patients vs. 694 920 controls). After excluding patients and controls with previous self‐harm, a self‐harm event occurred in 1408 patients in the surgical group (incidence rate (IR) 3.54/1000 person‐years, 95% confidence interval (CI) 3.36–3.73) versus in 3162 patients in the control group (IR 0.81/1000 person‐years, 95% CI 0.78–0.84), with a hazard ratio (HR) of 4.38 (95% CI 4.11–4.66, p < .001). Median follow‐up time was 6.1 years. Risk factors were younger age, lower BMI, cardiovascular, and chronic obstructive pulmonary disease, all aspects of psychiatric comorbidities (except neuropsychiatric disorder), lower socioeconomic status, RYGB, lower health‐related quality of life, lower postoperative weight loss, and not attending postoperative follow‐up visits. Self‐harm is clearly higher after bariatric surgery than in the general population. A qualitative follow‐up may be particularly important for patients at increased risk.
COVID‐19 associated development of antibody mediated rejection in orthotopic heart transplantation patients
Authors: Marek‐Iannucci Stefanie , Rajapreyar Indranee N. , Huaman Maria Gamero , Uber Patricia , Alvarez Rene , Rame Eduardo J. , Brailovsky Yevgeniy
Published: January 2023

Solid organ transplant candidates encountered increased wait times and mortality rates during the coronavirus 2019 (COVID‐19) pandemic. Despite improvement in medical management and vaccination efficacy, this patient population remains at increased risk for complications post COVID‐19 including organ rejection. We describe the development of antibody mediated rejection with or without cellular rejection in heart transplant (HT) recipients and previous COVID‐19 infection or vaccination. Although centers have changed their management of outpatient follow‐up for orthotopic heart transplant patients, little is known on surveillance of rejection and management of HT recipients after COVID‐19 infection. We recommend frequent surveillance for rejection or allograft dysfunction after COVID‐19 infection. We have adopted a transplant surveillance protocol for HT recipients with COVID‐19 infection, given our recent experience with transplanted patients affected of COVID‐19.
Molecular characteristics of low‐grade serous carcinoma in effusions
Authors: Doutel Delfim , Davidson Ben , Nitschke Pettersen Ina Kathrine , Torgunrud Annette
Published: January 2023

Objective

The molecular characteristics of low‐grade serous carcinoma (LGSC) in serous effusions have not been studied previously. The present study analysed the molecular profile of LGSC at this anatomical site.

Methods

Specimens consisted of a series of 17 serous effusions (15 peritoneal, 2 pleural) from 16 patients, of which 15 were LGSC and 2 serous borderline tumour (SBT) who later progressed to LGSC. For comparative purposes, 9 surgical specimens from 6 patients with LGSC were analysed. Fresh‐frozen cell pellets and surgical specimens underwent targeted next‐generation sequencing covering 50 unique genes.

Results

Mutations were found in tumours from 14 of the 22 patients, of whom 4 had 2 different mutations and 10 had a single mutation. Overall, the most common mutations were in KRAS (n = 3) and BRAF (n = 3), followed by NRAS (n = 2), CDK2NA (n = 2), TP53 (n = 2), ATM (n = 2). Mutations in MET, STK11, ERBB2 and FLT3 were found in one case each. Patient‐matched specimens had the same molecular profile. Both effusions with TP53 mutation had concomitant ATM mutation, and both stained immunohistochemically with a wild‐type pattern. The absence of mutations was associated with a trend for shorter overall survival in univariate analysis (p = 0.072).

Conclusions

The molecular alterations in LGSCs in serous effusions are consistent with those found in solid tumours, with frequent alterations in the mitogen‐activated protein kinase pathway. Mutations in LGSC may be a marker of better outcomes.
Effects of developmental alcohol exposure on cortical multisensory integration
Authors: Keum Dongil , Pultorak Katie , Meredith M. Alex , Medina Alexandre E.
Published: January 2023

Fetal alcohol spectrum disorder (FASD) is one of the most common causes of mental disabilities in the world with a prevalence of 1%–6% of all births. Sensory processing deficits and cognitive problems are a major feature in this condition. Because developmental alcohol exposure can impair neuronal plasticity, and neuronal plasticity is crucial for the establishment of neuronal circuits in sensory areas, we predicted that exposure to alcohol during the third trimester equivalent of human gestation would disrupt the development of multisensory integration (MSI) in the rostral portion of the posterior parietal cortex (PPr), an integrative visual–tactile area. We conducted in vivo electrophysiology in 17 ferrets from four groups (saline/alcohol; infancy/adolescence). A total of 1157 neurons were recorded after visual, tactile and combined visual–tactile stimulation. A multisensory (MS) enhancement or suppression is characterized by a significantly increased or decreased number of elicited spikes after combined visual–tactile stimulation compared to the strongest unimodal (visual or tactile) response. At the neuronal level, those in infant animals were more prone to show MS suppression whereas adolescents were more prone to show MS enhancement. Although alcohol‐treated animals showed similar developmental changes between infancy and adolescence, they always ‘lagged behind’ controls showing more MS suppression and less enhancement. Our findings suggest that alcohol exposure during the last months of human gestation would stunt the development of MSI, which could underlie sensory problems seen in FASD.
Ligand‐dependent protein interactions of the juvenile hormone receptor captured in real time
Authors: Tumova Sarka , Jindra Marek
Published: January 2023

Juvenile hormone (JH) signalling provides vital regulatory functions during insect development via transcriptional regulation of genes critical for the progression of metamorphosis and oogenesis. Despite the importance of JH signalling, the underlying molecular mechanisms remain largely unknown. Our current understanding of the pathway depends on static end‐point information and suffers from the lack of time‐resolved data. Here, we have addressed the dynamic aspect of JH signalling by monitoring in real time the interactions of insect JH receptor proteins. Use of two tags that reconstitute a functional luciferase when in proximity enabled us to follow the rapid assembly of a JH receptor heterodimer from basic helix–loop–helix/Per‐Arnt‐SIM (bHLH‐PAS) proteins, methoprene‐tolerant (Met) and taiman (Tai), upon specific JH binding to Met. On a similar timescale (minutes), the dissociation of Met‐Met complexes occurred, again strictly dependent on Met interaction with specific agonist ligands. To resolve questions regarding the regulatory role of the chaperone Hsp90/83 in the JHR complex formation, we used the same technique to demonstrate that the Met‐Hsp83 complex persisted in the agonist absence but readily dissociated upon specific binding of JH to Met. Preincubation with the Hsp90 inhibitor geldanamycin showed that the chaperone interaction protected Met from degradation and was critical for Met to produce the active signalling dimer with Tai. Thus, the JH receptor functions appear to be governed by principles similar to those regulating the aryl hydrocarbon receptor, the closest vertebrate homologue of the arthropod JH receptor.