bluuebunny/crossref_metadata_2025 huggingface dataset:
Managing customer-to-customer interactions: revisiting older models for a fresh perspective
Authors: Furrer Olivier , Landry Mikèle , Baillod Chloé
Published: November 2023

Purpose

This study aims to develop a comprehensive, theoretically grounded framework of customer-to-customer interaction (CCI) management, by revisiting three older services marketing models: the servuction model, the services marketing triangle and the services marketing pyramid.

Design/methodology/approach

Noting the lack of theoretical frameworks of CCI management, this study adopts a problematization approach to identify foundational services marketing models, question their underlying assumptions, develop an alternative conceptual framework and evaluate its adequacy for CCI management, on the basis of a systematic literature review and content analyses.

Findings

By revisiting the assumptions underlying three relevant models in the light of the present-day, technology-infused service environment, this study proposes a four-triangle CCI management framework encompassing four specific modes of CCI management: managerial decisions by the firm; frontline employees; the design of the physical environment; and technology. Furthermore, this study emphasizes the triadic relationships involving the focal customer, other customers and the four modes of CCI management. Building on these findings, this study concludes with an extensive research agenda.

Originality/value

To the best of the authors’ knowledge, this study represents the first scholarly effort in services marketing literature to provide a comprehensive, theoretically grounded framework of CCI management. With its basis in foundational models, the new framework is well-suited to address future challenges to service marketplaces too.
Heat‐evolved algal symbionts enhance bleaching tolerance of adult corals without trade‐off against growth
Authors: Chan Wing Yan , Meyers Luka , Rudd David , Topa Sanjida H. , van Oppen Madeleine J. H.
Published: November 2023

Ocean warming has caused coral mass bleaching and mortality worldwide and the persistence of symbiotic reef‐building corals requires rapid acclimation or adaptation. Experimental evolution of the coral's microalgal symbionts followed by their introduction into coral is one potential method to enhance coral thermotolerance. Heat‐evolved microalgal symbionts of the generalist species, Cladocopium proliferum (strain SS8), were exposed to elevated temperature (31°C) for ~10 years, and were introduced into four genotypes of chemically bleached adult fragments of the scleractinian coral, Galaxea fascicularis. Two of the four coral genotypes acquired SS8. The new symbionts persisted for the 5 months of the experiment and enhanced adult coral thermotolerance, compared with corals that were inoculated with the wild‐type C. proliferum strain. Thermotolerance of SS8‐corals was similar to that of coral fragments from the same colony hosting the homologous symbiont, Durusdinium sp., which is naturally heat tolerant. However, SS8‐coral fragments exhibited faster growth and recovered cell density and photochemical efficiency more quickly following chemical bleaching and inoculation under ambient temperature relative to Durusdinium‐corals. Mass spectrometry imaging suggests that algal pigments involved in photobiology and oxidative stress were the greatest contributors to the thermotolerance differences between coral hosting heat‐evolved versus wild‐type C. proliferum. These pigments may have increased photoprotection in the heat‐evolved symbionts. This is the first laboratory study to show that thermotolerance of adult corals (G. fascicularis) can be enhanced via the uptake of exogenously supplied, heat‐evolved symbionts, without a trade‐off against growth under ambient temperature. Importantly, heat‐evolved C. proliferum remained in the corals in moderate abundance 2 years after first inoculation, suggesting long‐term stability of this novel symbiosis and potential long‐term benefits to coral thermotolerance.
Corrosion mechanism of reactive MgO‐bonded Cr2O3‐bearing castables in CaO–Al2O3–Fe2O3–SiO2‐based steel‐making slag
Authors: Zhang Hongrui , Wang Mengqiang , Jia Quanli , Zhang Zheng , Lei Lei , Chen Liugang
Published: November 2023

To assess the feasibility of the reactive MgO (RM) binder in preparing Cr2O3‐bearing castables, the degradation behavior of RM‐bonded Cr2O3‐bearing castables in CaO–Al2O3–Fe2O3–SiO2‐based steel‐making slag was investigated at 1600°C via refractory cup testing. The corrosion resistance and infiltration resistance of RM‐bonded castables were compared with hydratable alumina (HA)‐bonded and calcium aluminate cement (CAC)‐bonded castables with respect to the differences in phase composition and microstructure. Al2O3 grains in RM‐bonded castable were preferentially attacked by the slag compared with Mg(Al, Cr)2O4 spinel‐based matrix. The formation of spinel‐based and CaO·6Al2O3‐based solid solutions with volume expansion from slag/castable interactions suppressed slag infiltration into RM‐bonded castable matrix. Both experimental observations and thermodynamic calculations indicated that the in situ formed Mg(Al, Cr)2O4 spinel in RM‐bonded castables was the predominant reason leading to the superior slag corrosion resistance and infiltration resistance compared with HA‐bonded and CAC‐bonded Cr2O3‐bearing castables.
Fear of recurrence in postoperative lung cancer patients: Trajectories, influencing factors and impacts on quality of life
Authors: Yang Xiaoyan , Li Yonglin , Lin Jialing , Zheng Jianqing , Xiao Huimin , Chen Weiti , Huang Feifei
Published: November 2023

Aims

To investigate the trajectory, influencing factors and dynamic relationships between fear of cancer recurrence (FCR) and quality of life (QOL) in lung cancer patients.

Design

Prospective longitudinal study.

Methods

Longitudinal data from 310 lung cancer patients across three hospitals in China were assessed at 1, 3, 6 and 12 months postoperatively (T1–T4). Descriptive statistics characterised patient demographics, clinical characteristics, levels of FCR and QOL. A linear mixed‐effects model was employed to analyse FCR trajectories, identify influencing factors on these trajectories, and predict the impact of FCR on QOL.

Results

FCR changed significantly over time, with a slight decrease during T1–T2, an increase at T3 and gradual decline at T4. Higher fear levels were associated with female sex, suburban or rural residency, being a family breadwinner, presence of comorbidities and negative coping behaviours, and low family resilience. QOL negatively correlated with FCR, and FCR predicted lower QOL.

Conclusions

At 3 and 6 months postoperatively, lung cancer patients, especially women, suburban or rural residents, family breadwinners, those with comorbidities, negative coping behaviours and low family resilience, reported high levels of FCR. Healthcare providers should pay special attention to lung cancer patients especially during the period of 3–6 months post‐surgery and offer tailored interventions to improve their QOL.

Implications for the Profession and Patient Care

Understanding the FCR trajectories, its influencing factors and its negative impacts on QOL can guide the development of targeted interventions to reduce fear and enhance well‐being in patients with cancer.

Impact

Identifying the trajectories and influencing factors of fear of lung cancer recurrence in patients at different time points informs future research on targeted interventions to improve QOL.

Reporting Method

The study adhered to the guidelines outlined in the Statement on Reporting Observational Longitudinal Research.
Efficacy of a mitral regurgitation severity index to predict long‐term outcome in dogs with myxomatous mitral valve disease
Authors: Vereb Michelle , Atkins Clarke E. , Adin Darcy , Blondel Thomas , Coffman Melissa , Lee Seunggon , Guillot Emilie , Ward Jessica L.
Published: November 2023

Background

Predicting progression of myxomatous mitral valve disease (MMVD) in dogs can be challenging.

Hypothesis/Objectives

The mitral regurgitation severity index (MRSI) will predict time to congestive heart failure (CHF) and all‐cause death in dogs with MMVD.

Animals

Eight hundred sixty‐nine client‐owned dogs.

Methods

Retrospective study pooling data from 4 previous samples including dogs with MMVD stage B2 or C. MRSI was calculated as: (heart rate [HR]/120) × left atrium‐to‐aorta ratio (LA:Ao) × (age in years/10) × 100. Alternative MRSI formulas substituting radiographic measures of left atrial size were also calculated. Cox proportional hazard modeling and time‐dependent receiver‐operator characteristic curves quantified prognostic performance.

Results

For Stage B2 pooled samples, MRSI > 156 was predictive of time to CHF (median 407 vs 1404 days; area under the curve [AUC] 0.68; hazard ratio 3.02 [95% CI 1.9‐4.9]; P < .001). MRSI > 173 was predictive of all‐cause death (median survival 868 vs 1843 days; AUC 0.64; hazard ratio 4.26 [95% CI 2.4‐7.5]; P < .001). MRSI showed superior predictive value compared to the individual variables of HR, LA:Ao, and age. Variations of the MRSI equation substituting radiographic vertebral left atrial size for LA:Ao were also significantly predictive of outcome in stage B2. MRSI was not consistently predictive of outcome in Stage C.

Conclusions and Clinical Importance

MRSI was predictive of outcome (onset of CHF and all‐cause death) in MMVD Stage B2, demonstrating utility as a useful prognostic tool. Echocardiographic LA:Ao can be effectively replaced by radiographically determined LA size in the MRSI formula.
The “practical mode of teaching” and the state of English studies in the United States
Authors: Denisoff Dennis , Stevens Laura M.
Published: November 2023

In the United States, student eagerness to pursue concentrated study in English literature as well as in other humanities fields has plummeted after the financial crisis of 2008. Envisioned strong career demand and high wages upon graduation are major drivers of program choices, and such demand is articulated through wealthy industries that can also offer funding to universities. That said, it becomes self‐fulfilling to contribute to the cliché of the humanities perpetually being in crisis, which occurs when humanities specialists begin valuing their own fields by the measures celebrated by other programs. Is it possible to take the current situation and leverage our strengths toward constructive innovations in English studies that remain true to our own values? To address this question, we first summarize three key ways in which the situation in the United States is distinct from, yet connected to, that of most other countries: extensive decentralization of education policy and funding; high student debt; and opposition to education in Diversity, Equity, and Inclusion and the humanities in general. After reflecting on the opportunities for greater global connection posed by the pandemic‐driven shift to online learning, we discuss some of our own efforts to build a sense of local and international responsibility in our students. The skills, knowledge, and openness to other cultures and identities that we nurture through the literature we teach and the socially invested pedagogy we practice allow us to incorporate ethics and empathy into the design of international economics and to help ensure that a sense of local and global responsibility is part of its operation.
Hospitalization for permanent pacemaker implantation in the context of isolated sinus node dysfunction is associated with increased mortality compared with an outpatient strategy
Authors: Sharp Alexander , Matthews Gareth , Papageorgiou Nikolaos , Till Richard , Raine Daniel , Williams Ian , Grahame‐Clarke Cairistine , Nair Santosh , Abdul‐Samad Omar , Vassiliou Vassilios , Garg Pankaj , Lim Wei Yao
Published: November 2023

Background

Permanent pacemaker (PPM) implantation is a well‐established treatment for symptomatic sinus node dysfunction (SND). The optimal timing of this intervention is unclear, with atrioventricular blocks often prioritized in resource stressed waiting lists due to mortality concerns.

Methods

Mortality data was compared between patients receiving elective outpatient (OP) PPM implantation, and those presenting to hospital for urgent inpatient (IP) management for symptomatic SND. Survival analysis was conducted using Kaplan‐Meier plots and compared using the log‐rank test. Univariable and multivariable Cox regression, as well as propensity score matching analyses were performed to assess the prognostic effect on 30‐day and 1‐year all‐cause mortality of inpatient implant.

Results

Of the 1269 patients identified with isolated SND, 740 (58%) had PPMs implanted on an OP and 529 (42%) on an IP basis. Mortality was significantly worse in patients where management was driven by hospital admission on an urgent basis (Log‐Rank χ2 = 21.6, p < 0.001) and remained an independent predictor of 1‐year all‐cause mortality (HR 3.40, 95% CI 1.97–5.86, p < 0.001) on multivariable analysis.

Conclusions

SND is predominantly a disease associated with ageing and comorbid populations, where avoidance of deconditioning, hospitalization acquired infections, and polypharmacy is advantageous. Admission avoidance is therefore the preferable strategy.
Misplacement of pacemaker leads: How to avoid and how to approach?
Authors: Erdem Almina , Torun Akin
Published: November 2023

The use of cardiac implantable electronic devices has increased in recent years due to factors such as a growing population, increased life expectancy, and improved access to healthcare services. In parallel with this trend, complications related to pacemakers have also increased. One of the most important and preventable complications among these is lead misplacement. Misplacement of a permanent pacemaker lead in the LV can lead to a variety of complications, including damage to the heart muscle, arrhythmias, blood clotes and cerebrovascular events. It is recommended to use the fluoroscopic 40° LAO view during implantation. That view clearly defines the interatrial and interventricular septum. Right bundle branch block pattern on ECG is an important clue to suspected misplaced lead. In addition to the postero‐anterior (PA) projection of x‐ray, the latero‐lateral (LL) projection provides a clearer view of lead malposition. In the LL view, the tip of an incorrectly positioned LV lead is characteristically directed toward the spine. If diagnosed soon after implantation, percutaneous lead extraction can reduce the risk of future thromboembolic events without the need for lifelong anticoagulation. It should be noted that in cases with a lead in the LV for a long time, lead removal is not the primary recommendation. Patient‐based approach should be fundamental.
Donor call simulation: A novel medical education tool to evaluate trainees’ clinical decision‐making in transplant infectious disease
Authors: Sigler Rachel , Wooten Darcy , Kumar Rebecca N. , Hand Jonathan , Marschalk Nicholas , Go Roderick , Prakash Katya , Stohs Erica , Schaenman Joanna , Law Nancy
Published: November 2023

Background

Evaluating organ suitability for transplantation based on infection risk is a core competency in transplant infectious disease (TID). It is unclear if trainees have opportunities to practice during training. We created a simulation curriculum to develop and evaluate this skill among infectious disease (ID) trainees.

Methods

We created six simulation questions about organ suitability for transplant based on infection risk. During trainees’ TID rotations, faculty texted or paged the simulation cases posing as the transplant coordinator. Trainees had 15 min to ask questions before deciding the suitability of the organ and explained their clinical reasoning in a survey. Trainees completed a post‐simulation survey to evaluate its effectiveness.

Results

ID trainees, including residents and fellows on rotation, from seven centers participated. Eighty‐seven percent (13/15) of trainees felt the simulation was effective in teaching them this concept, and 80% (12/15) felt prepared for clinical practice. The proportion of correct responses was generally high among the six different cases (43%–100%); correct responses increased for some cases in the post‐activity survey. Of the 100 clinical reasoning decisions made during the activity, 19% were discordant, where the trainee correctly identified suitable organs for incorrect reasons.

Conclusion

Our simulation was effective in teaching when to accept or reject an organ for transplant and was a valuable educational tool. By evaluating clinical reasoning for decisions our simulation provides educators with nuanced insight and allows for targeted coaching. This study demonstrates a critical need for further educational tools in TID.

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O Trabalho Escravo Contemporâneo na Ótica do Ministério Público do Trabalho e do Tribunal Regional do Trabalho da 3ª Região (Minas Gerais)
Authors: Barros de Freitas Lígia
Published: November 2023

O artigo analisa as Ações Civis Públicas propostas pela Procuradoria do Trabalho de Uberlândia, no período de 2002 a 2022, com o objetivo de apontar a base legal e principalmente o conceito de trabalho análogo à condição de escravo que embasa os pedidos de prevenção e repressão ao trabalho realizado nessas situações, bem como a resposta do Poder Judiciário Trabalhista e o seu conceito de escravidão contemporânea. Metodologicamente, foram analisadas as mencionadas ações e as Notas Técnicas emitidas pelo Ministério Público do Trabalho, através da Coordenadoria Nacional de Erradicação do Trabalho Escravo e Enfrentamento ao Tráfico de Pessoas (CONAETE). Conclui-se que com os retrocessos sociais acontecidos a partir de 2016, há uma mobilização institucional convergente do Ministério Público do Trabalho e do Ministério do Trabalho em uma clara resistência às restrições de direitos sociais impostas pelo governo federal, ampliando o conceito de trabalho análogo ao de escravo, assim como o reforço por parte do Poder Judiciário Trabalhista de seu posicionamento ampliado.
A LIiberdade Religiosa e o Uso de Véu no Ambiente Laboral:
Authors: Marques de Lima Francisco Meton , Meneses Brandão Zoraíma , Araújo Oliveira Élvio
Published: November 2023

O presente artigo versa sobre o tema da liberdade religiosa e o uso de véu no ambiente de trabalho a partir da análise do acórdão do Tribunal de Justiça da União Europeia, de 15 de julho de 2021, nos processos apensos C‑804/18 e C‑341/19. A temática se apresenta nos holofotes das discussões em razão da sociedade europeia multiétnica, marcada pela diversidade de religiões em um mesmo espaço. Neste contexto, pretende-se com a investigação averiguar as controvérsias entre o direito à liberdade religiosa e o direito à liberdade de empresa, no caso centrando-se na questão do uso do véu. Para tal, utiliza-se o método qualitativo, buscando na doutrina e jurisprudência do TJUE elementos balizadores para a análise se a liberdade religiosa tem sido objeto de limitações desproporcionais no espaço comunitário europeu. Com uma análise resumida dos resultados, constata-se que a jurisprudência do TJUE tem caminhado no sentido de sedimentar parâmetros coesos e norteadores às cortes nacionais, por meio da tentativa de compatibilização prática do direito à liberdade religiosa e à liberdade de empresa.
PALAVRAS-CHAVE: Liberdade religiosa; Uso de véu; Ambiente de trabalho; Jurisprudência; TJUE
Ajustando as Lentes para Abusos de Posição Dominante Relacionados a Dados
Authors: Zingales Nicolo
Published: November 2023

Apesar da proliferação de debates sobre o papel dos dados na concorrência e, particularmente, seu impacto no poder de mercado, as empresas ainda carecem de uma estrutura orientadora para determinar quando o uso de um conjunto específico de dados pode dar origem a um abuso de posição dominante. Este artigo dá alguns passos para a definição desse quadro, utilizando como estudo de caso duas investigações abertas pela autoridade de concorrência brasileira relativas a fintech. Mostra que as autoridades de concorrência enfrentam dificuldades em analisar casos usando as lentes dos testes jurídicos tradicionais, e propõe conceitos e métodos alternativos que podem servir de inspiração para futuras avaliações de abusos relacionados a dados.
Le Trasformazioni Del Lavoro E La Tendenza Espansiva Delle Tutele Nel Diritto Del Lavoro Italiano
Authors: Nuzzo Valeria
Published: November 2023

l’A. parte dalle trasformazioni del lavoro, in particolare quelle determinate dall’uso di sistemi di I.A., che hanno determinato una “spazzamento” del diritto del lavoro e una riduzione dei confini della sua materia, per sottolineare come il legislatore italiano abbia reagito ad esse, recuperando (ed anzi ampliando) il campo di applicazione delle garanzie lavoristiche, oggi esteso a tutte quelle prestazioni prevalentemente personali funzionalmente inserite in una organizzazione altrui per il perseguimento del fine economico dell’imprenditore.

 

PAROLE CHIAVE: Subordinazione; Tutele del lavoro; Lavoro etero-organizzato; Riders.
Acordos De Distribuição Exclusiva No Contexto Da Economia Digital
Authors: Padilla Jorge , Sarmento Bernardo , Vasconcelos Helder
Published: November 2023

O presente artigo investiga os efeitos concorrenciais dos acordos de distribuição exclusiva no contexto da economia digital. Ao analisar as principais conclusões da literatura económica existente sobre o tema, bem como a jurisprudência relevante na União Europeia, concluímos que, embora este tipo de contratos possa conduzir ao encerramento do mercado, aumentando as barreiras à entrada e/ou contribuindo para aumentar os custos dos rivais, a exclusividade pode também criar importantes possibilidades de concorrência, o que complica a aplicação da política de concorrência. Em primeiro lugar, a concorrência pela exclusividade deve ser entendida um meio primordial de diferenciação entre as plataformas digitais, uma vez que leva as plataformas a competir entre si para criar uma oferta diferenciada, reforçando assim (em vez de reduzir) a concorrência inter-marcas e os esforços de inovação. Em segundo lugar, num cenário de ausência de contratos de exclusividade, os investimentos das plataformas estão potencialmente sujeitos efeito carona (free-riding effect) por parte de plataformas rivais não comprometidas com a realização de investimentos, o que implica que os acordos de negociação exclusiva podem servir objetivos de eficiência, protegendo os investimentos específicos do titular do direito exclusivo contra o comportamento oportunista dos concorrentes. Por conseguinte, a única forma sensata de abordar a avaliação concorrencial da adoção de contratos de exclusividade em mercados digitais é uma abordagem baseada numa análise caso a caso, concentrada em procurar o equilíbrio regulatório adequado entre a garantia de uma concorrência saudável, por um lado, e a proteção dos interesses dos consumidores, por outro, num ambiente cada vez mais digitalizado e dinâmico em que a inovação e a capacidade de diferenciar as ofertas desempenham um papel fundamental. O artigo também apresenta uma aplicação ao mercado brasileiro de entrega de comida online.

 

PALAVRAS-CHAVE: Mercados e plataformas digitais; Cláusulas de exclusividade; Condutas unilaterais de caráter potencialmente exclusionário.
Para Além do Horizontal e do Vertical
Authors: Oliveira Fernandes Victor
Published: November 2023

O artigo analisa quatro novas teorias de dano concorrencial relacionadas a fusões de empresas de tecnologia discutidas recentemente em decisões do Conselho Administrativo de Defesa Econômica (CADE), quais sejam: (i) concentração de dados, (ii) degradação do acesso a dados; (iii) obtenção de informações concorrencialmente sensíveis de rivais e (iv) enclausuramento de ecossistemas digitais. Argumenta-se que, apesar de tangenciarem preocupações tradicionais com fusões verticais e conglomeradas, essas teorias podem ganhar autonomia conceitual. O CADE tem adaptado parcialmente suas metodologias para avaliar estratégias de fechamento de acesso por grandes plataformas digitais. À medida que fusões nesse setor se tornem mais comuns, espera-se um refinamento contínuo do arcabouço analítico antitruste para o controle de estruturas.

 

Palavras-chave: antitruste; fusões; economia digital; plataformas; teorias do dano
Open-Loop Control Co-Design of Semisubmersible Floating Offshore Wind Turbines Using Linear Parameter-Varying Models
Authors: Sundarrajan Athul K. , Hoon Lee Yong , Allison James T. , Zalkind Daniel S. , Herber Daniel R.
Published: November 2023

This paper discusses a framework to design elements of the plant and control systems for floating offshore wind turbines in an integrated manner using linear parameter-varying models. Multiple linearized models derived from aero-elastic simulation software in different operating regions characterized by the incoming wind speed are combined to construct an approximate low-fidelity model of the system. The combined model is then used to generate open-loop, optimal control trajectories as part of a nested control co-design strategy that explores the system’s power production and stability using the platform pitch tilt as a proxy in the context of crucial plant and control design decisions. The radial distance between the central and outer columns and the diameter of the outer columns of the semisubmersible platform are the plant design variables. The platform stability and power production are studied for different plant design decisions. The effect of plant decisions on subsequent power production and stability response of the floating wind turbine is quantified in terms of the levelized cost of energy. The results show that the inner-loop constraints and the plant design decisions affect the turbine’s power and, subsequently, the cost of the system.
Detecting intermediate-mass black hole binaries with atom interferometer observatories: Using the resonant mode for the merger phase
Authors: Torres-Orjuela Alejandro
Published: November 2023

Atom interferometry detectors like AION, ZAIGA, and AEDGE will be able to detect gravitational waves (GWs) at dHz covering the band between large space-based laser interferometers LISA/TianQin/Taiji and ground-based facilities LIGO/Virgo/KAGRA. They will detect the late inspiral and merger of GW sources containing intermediate-mass black holes (IMBHs) in the mass range 102−105 M⊙. We study how accurately the parameters of an IMBH binary can be measured using AION's power spectral density. Furthermore, we propose a detection scheme where the early inspiral of the binary is detected using the regular broadband mode while the merger is detected using the resonant mode. We find that using such a detection scheme, the signal-to-noise ratio of the detection and the detection accuracy of the parameters can be enhanced compared to the full detection of the signal using the broadband mode. We, further, assess the impact of the necessary detection gap while switching from broadband to resonant mode studying the case of a short (30  s) and a long (600  s) gap. We find that the improvement in the detection accuracy for both gaps is around 40% for the total mass and the spin of the heavier black hole. For the short gap, the accuracy always improves ranging between 2% and 31% for the other parameters. For the long gap, there is a decrease in the detection accuracy for the luminosity distance, the inclination, and the initial phase but only by 1%–6% while for the remaining parameters, we have improved accuracies of around 2%–20%.
A multicentennial mode of North Atlantic climate variability throughout the Last Glacial Maximum
Authors: Prange Matthias , Jonkers Lukas , Merkel Ute , Schulz Michael , Bakker Pepijn
Published: November 2023

Paleoclimate proxy records from the North Atlantic region reveal substantially greater multicentennial temperature variability during the Last Glacial Maximum (LGM) compared to the current interglacial. As there was no obvious change in external forcing, causes for the increased variability remain unknown. Exploiting LGM simulations with a comprehensive coupled climate model along with high-resolution proxy records, we introduce an oscillatory mode of multicentennial variability, which is associated with moderate variations in the Atlantic meridional overturning circulation and depends on the large-scale salinity distribution. This self-sustained mode is amplified by sea-ice feedbacks and induces maximum surface temperature variability in the subpolar North Atlantic region. Characterized by a distinct climatic imprint and different dynamics, the multicentennial oscillation has to be distinguished from Dansgaard-Oeschger variability and emerges only under full LGM climate forcing. The potential of multicentennial modes of variability to emerge or disappear in response to changing climate forcing may have implications for future climate change.
An immunotherapeutic artificial vitreous body hydrogel to control choroidal melanoma and preserve vision after vitrectomy
Authors: Chen Muchao , Hu Jiaying , Gao Huiqin , Shen Jingjing , Wei Ting , Yao Jing , Zhang Yan , Gu Ping , Liu Zhuang , Chen Qian
Published: November 2023

Choroidal melanoma, a common intraocular malignant tumor, relies on local radiotherapy and enucleation for treatment. However, cancer recurrence and visual impairment remain important challenges. Here, a therapeutic artificial vitreous body (AVB) hydrogel based on tetra-armed poly(ethylene glycol) was developed to control the recurrence of choroidal melanoma and preserve vision after vitrectomy. AVB loaded with melphalan (Mel) and anti–programmed cell death ligand-1 (αPDL1), was injected after surgical resection in the choroidal melanoma mouse model. Afterwards, the sequentially released Mel and αPDL1 from AVB could achieve a synergistic antitumor effect to inhibit tumor recurrence. AVB with similar physical properties to native vitreous body could maintain the normal structure and visual function of eye after vitrectomy, which has been evidenced by standard examinations of ophthalmology in the mouse model. Thus, the immunotherapeutic AVB may be a promising candidate as an infill biomaterial to assist surgical treatment of intraocular malignant tumors.
Neural adaption in midbrain GABAergic cells contributes to high-fat diet–induced obesity
Authors: Wang Xiaomeng , Wu Xiaotong , Wu Hao , Xiao Hanyang , Hao Sijia , Wang Bingwei , Li Chen , Bleymehl Katherin , Kauschke Stefan G. , Mack Volker , Ferger Boris , Klein Holger , Zheng Ruimao , Duan Shumin , Wang Hao
Published: November 2023

Overeating disorders largely contribute to worldwide incidences of obesity. Available treatments are limited. Here, we discovered that long-term chemogenetic activation of ventrolateral periaqueductal gray (vlPAG) GABAergic cells rescue obesity of high-fat diet–induced obesity (DIO) mice. This was associated with the recovery of enhanced mIPSCs, decreased food intake, increased energy expenditure, and inguinal white adipose tissue (iWAT) browning. In vivo calcium imaging confirmed vlPAG GABAergic suppression for DIO mice, with corresponding reduction in intrinsic excitability. Single-nucleus RNA sequencing identified transcriptional expression changes in GABAergic cell subtypes in DIO mice, highlighting
Cacna2d1
as of potential importance. Overexpressing CACNA2D1 in vlPAG GABAergic cells of DIO mice rescued enhanced mIPSCs and calcium response, reversed obesity, and therefore presented here as a potential target for obesity treatment.
A telencephalon cell type atlas for goldfish reveals diversity in the evolution of spatial structure and cell types
Authors: Tibi Muhammad , Biton Hayun Stav , Hochgerner Hannah , Lin Zhige , Givon Shachar , Ophir Osnat , Shay Tal , Mueller Thomas , Segev Ronen , Zeisel Amit
Published: November 2023

Teleost fish form the largest group of vertebrates and show a tremendous variety of adaptive behaviors, making them critically important for the study of brain evolution and cognition. The neural basis mediating these behaviors remains elusive. We performed a systematic comparative survey of the goldfish telencephalon. We mapped cell types using single-cell RNA sequencing and spatial transcriptomics, resulting in de novo molecular neuroanatomy parcellation. Glial cells were highly conserved across 450 million years of evolution separating mouse and goldfish, while neurons showed diversity and modularity in gene expression. Specifically, somatostatin interneurons, famously interspersed in the mammalian isocortex for local inhibitory input, were curiously aggregated in a single goldfish telencephalon nucleus but molecularly conserved. Cerebral nuclei including the striatum, a hub for motivated behavior in amniotes, had molecularly conserved goldfish homologs. We suggest elements of a hippocampal formation across the goldfish pallium. Last, aiding study of the teleostan everted telencephalon, we describe substantial molecular similarities between goldfish and zebrafish neuronal taxonomies.
MicroRNA-146b protects kidney injury during urinary tract infections by modulating macrophage polarization
Authors: Wang Changying , Cheng Hongyan , Yan Fenglian , Zhang Hui , Zhang Junfeng , Li Chunxia , Zhao Mingsheng , Shi Dongmei , Xiong Huabao
Published: November 2023

Urinary tract infections (UTIs) caused by uropathogenic
Escherichia coli
(UPEC) can lead to severe kidney injury. However, the molecular mechanisms underlying the pathological process of kidney injury are still incompletely understood. In the present study, we demonstrate that microRNA-146b (miR-146b) deficiency aggravates kidney injury during UTIs caused by UPEC. In a mouse kidney infection model utilizing urosepsis isolate CFT073, we found that miR-146b expression significantly increased in the early stages of UPEC infection. Also, miR-146b-deficient mice displayed exacerbated inflammation in the kidney injury with severe M1 macrophage infiltration. Additionally, the results showed that miR-146b targeted interferon regulatory factor 5-regulated M1 macrophage polarization during UTIs. The results suggested that miR-146b contributed significantly to the control of kidney damage during UTIs, highlighting that miR-146b might be used as a novel therapeutic target for treating kidney injury during UTIs.

IMPORTANCE

Kidney injury during acute urinary tract infections (UTIs) caused by uropathogenic
Escherichia coli
(UPEC) is an important public health problem. However, how kidney injury develops during UPEC infection is still unclear. Although antibiotic therapy is currently an effective treatment for UTI, it cannot avoid kidney injury. MicroRNAs have gained extensive attention as essential molecules capable of regulating the autoimmune response. Among these, microRNA-146b (miR-146b) is involved in regulating inflammatory responses. In the present study, we demonstrated that miR-146b played an essential role in the development of kidney injury during UTIs caused by UPEC. The results showed that miR-146b may suppress M1 macrophage polarization and alleviate acute kidney injury. Furthermore, the miR-146b activator, agomir, in order to upregulate miR-146b, was effective in treating kidney damage by inhibiting the activation of M1 macrophages. In conclusion, our findings elucidated the mechanisms by which miR-146b alleviated kidney injury induced by UTIs, shed new light on the relationship between microRNA and bacterial infection, and provided a novel therapeutic target for treating this common bacterial infection.
Mesenchymal stem cells of the bone marrow raise infectivity of
Plasmodium falciparum
gametocytes
Authors: Suresh Ragavan Varadharajan , Deng Bingbing , Gebremicale Yonas , Roche Kyle , Miura Kazutoyo , Long Carole
Published: November 2023

Plasmodium falciparum
is a parasite that causes the deadly human disease, malaria, and exhibits a complex life cycle in human and mosquito hosts. In the sexual stages of the parasite, gametocytes mature in the human body and propagate malaria when they are picked up by mosquitoes to infect new hosts. Previous research has shown that gametocytes home to the bone marrow of the host, where they complete their maturation and alter the behavior of resident mesenchymal stem cells (MSCs). In this study, we investigated the alternate side of this host-pathogen interaction, whether MSCs could alter the behavior of gametocytes. Gametocytes were co-cultured with MSCs until maturity and subsequently fed to mosquitoes to measure the oocysts produced. Here, we report, for the first time, that MSCs co-culture significantly elevated oocyst numbers in the infected mosquito compared to conventional culture medium. This enhancement appeared to be most effective during the early stages of gametocyte development and was not replicated by other cell types. MSC co-culture also increased the infectivity of field isolated
P. falciparum
parasites. This effect was partially mediated by soluble factor(s) as conditioned medium harvested from MSCs could also partially raise infectivity of gametocytes to nearly half compared to MSC co-culture. Together, this study reveals novel host-pathogen interactions, where the human MSCs are elevating the infectivity of malaria gametocytes.

IMPORTANCE

While prior research has established that
Plasmodium
gametocytes sequester in the bone marrow and can influence resident stem cells, the question of why they would choose this compartment and these cells remained a mystery. This study, for the first time, shows that being in the presence of mesenchymal stem cells (MSCs) alters the biology of the
P. falciparum
parasite and makes it more infectious to mosquitoes, hinting at novel mechanisms in its life cycle. This method also facilitates mosquito infections with field isolated parasites, affording research teams new infection models with parasites, which are challenging to infect into mosquitos using conventional culture methods. Finally, our findings that MSC-conditioned medium can also raise infectivity open avenues of investigation into mechanisms involved but can also serve as a practical tool for researchers hoping to increase oocyst yields.
An unexpected, pH-sensitive step of the enterovirus D68 lifecycle
Authors: Aponte-Diaz David , Vogt Matthew R. , Cameron Craig E.
Published: November 2023

Enterovirus D68 (EV-D68) contributes significantly to pathogen-induced respiratory illnesses and severe neurological disorders like acute flaccid myelitis. We lack EV-D68 preventive measures, and knowledge of its molecular and cellular biology is incomplete. Multiple studies have highlighted the role of membrane compartments and autophagy during picornavirus multiplication. Galitska et al. found that EV-D68 also exploits cellular autophagic compartments and relies on autophagic machinery as pro-viral factors (G. Galitska, A. Jassey, M. A. Wagner, N. Pollack, et al., mBio e02141-23, 2023,
https://doi.org/10.1128/mbio.02141-23
). Surprisingly, failure of the autophagic compartment to acidify early during EV-D68 infection causes a delay in RNA synthesis that has not been reported for other enteroviruses. This delay appears to reflect the inability of viral proteins 2B and 3A to engage membranes stably, leading to their degradation in the cytoplasm. Observations like this underscore the importance of studying individual members of the virus genus. It will be interesting to understand how this phenomenon connects to EV-D68 pathogenesis, if at all.
Mechanosensation induces persistent bacterial growth during bacteriophage predation
Authors: Mason Guy , Footer Matthew J. , Rojas Enrique R.
Published: November 2023

Although the relationship between bacteria and lytic bacteriophage is fundamentally antagonistic, these microbes not only coexist but thrive side by side in myriad ecological environments. The mechanisms by which coexistence is achieved, however, are not fully understood. By examining
Escherichia coli
and bacteriophage T7 population dynamics at the single-cell and single-virion level using a novel microfluidics assay, we observed bacteria growing “persistently” when perfused with high-titer bacteriophage. Bacteriophage persistence occurred at a frequency five orders of magnitude higher than is expected from the natural selection of bacteriophage-resistant mutants. Rather, the frequency of persistence was correlated with the degree to which the bacteria were mechanically compressed by the microfluidic perfusion chamber. Using a combination of mutagenesis and fluorescent imaging techniques, we discovered that compression induces persistence by activating the Rcs phosphorelay pathway, which results in the synthesis of extracellular capsule that sterically blocks bacteriophage adsorption. Other forms of mechanical perturbation also promoted Rcs activity and persistence. These findings have important implications for our understanding of microbial ecology in many important environments, including the gut and the soil, where bacteria grow in confinement.

IMPORTANCE

Bacteria and bacteriophage form one of the most important predator-prey relationships on earth, yet how the long-term stability of this ecological interaction is achieved is unclear. Here, we demonstrate that
Escherichia coli
can rapidly grow during bacteriophage predation if they are doing so in spatially confined environments. This discovery revises our understanding of bacteria-bacteriophage population dynamics in many real-world environments where bacteria grow in confinement, such as the gut and the soil. Additionally, this result has clear implications for the potential of bacteriophage therapy and the role of mechanosensation during bacterial pathogenesis.
Transcriptome data sets of free-living diplomonads,
Trepomonas
sp. and
Hexamita
sp.
Authors: Kume Keitaro , Gen Tsubasa , Abe Kazutaka , Komatsuzaki Hiroshi , Yazaki Euki , Tanifuji Goro , Kamikawa Ryoma , Inagaki Yuji , Hashimoto Tetsuo
Published: November 2023

Most species belonging to the diplomonad genera,
Trepomonas
and
Hexamita
, are considered to have secondarily adapted to free-living lifestyles from the parasitic ancestor. Here, we report the annotated transcriptome data of
Trepomonas
sp. NIES-1444 and
Hexamita
sp. NIES-1440, the analysis of which will provide insights into the lifestyle transitions.
Complete genome sequencing and annotation of
Rhodomicrobium vannielii
strain DSM166 suggest affiliation to
Rhodomicrobium lacus
Authors: Müller Frank D. , Schüler Dirk , Weig Alfons
Published: November 2023

Rhodomicrobium vannielii
is a multicellular and differentiating member of the order Hyphomicrobiales in the class Alphaproteobacteria. Here, we report the complete genome of strain DSM166 obtained by PacBio SMRT sequencing. The results suggest that this strain is closely related to
Rhodomicrobium lacus
.
Multifocal choroidal melanoma: a clinicohistopathological correlation
Authors: Ketkar Manasi , Jakati Saumya , Raval Vishal
Published: November 2023

A woman in her late 50s presented with on-and-off redness and diminution of vision in her left eye for 6 months. Her best corrected visual acuity was 20/40 in the right eye and hand motion in the left eye. Anterior segment examination revealed a greyish-white lesion extending from 3 to 6 o’clock hours posterior to the iris and protruding into the anterior chamber. Left eye B-scan ultrasonography showed a multifocal choroidal lesion, a smaller one involving the posterior pole, and a larger lesion involving the complete nasal quadrant and anteriorly extending to the ciliary body and iris. Fine-needle aspiration biopsy performed from the anterior lesion showed a possible neoplastic aetiology of melanocytic origin of the cells. Finally, the patient underwent left eye enucleation with a ball implant. Histopathological examination of the enucleated eye confirmed the final diagnosis of multifocal choroidal melanoma involving the adjacent ciliary body and iris.
Embolic myocardial infarction with cardiac arrest as an initial manifestation of non-bacterial thrombotic endocarditis
Authors: Hansen Anna C , Piranavan Paramarajan , Kundu Amartya , A El-Dalati Sami , Ahmed Taha
Published: November 2023

Non-bacterial thrombotic endocarditis, characterised by sterile vegetations, is commonly caused by systemic lupus erythematosus and is known to be complicated with embolic cerebrovascular disease. Embolic myocardial infarction with non-bacterial thrombotic endocarditis is extremely rare. We report a case of ventricular fibrillation arrest from presumed coronary embolisation in non-bacterial thrombotic endocarditis. While there are no standardised guidelines on the management of embolic myocardial infarction in endocarditis, it requires a multidisciplinary approach unique for every encountered clinical scenario.
Research priorities for the primordial prevention of acute rheumatic fever and rheumatic heart disease by modifying the social determinants of health
Authors: Baker Michael G , Masterson Mary Y , Shung-King Maylene , Beaton Andrea , Bowen Asha C , Bansal Geetha P , Carapetis Jonathan R
Published: November 2023

The social determinants of health (SDH), such as access to income, education, housing and healthcare, strongly shape the occurrence of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) at the household, community and national levels. The SDH are systemic factors that privilege some more than others and result in poverty and inequitable access to resources to support health and well-being. Primordial prevention is the modification of SDH to improve health and reduce the risk of disease acquisition and the subsequent progression to RHD. Modifying these determinants using primordial prevention strategies can reduce the risk of exposure to Group A Streptococcus, a causative agent of throat and skin infections, thereby lowering the risk of initiating ARF and its subsequent progression to RHD.

This report summarises the findings of the Primordial Prevention Working Group-SDH, which was convened in November 2021 by the National Heart, Lung, and Blood Institute to assess how SDH influence the risk of developing RHD. Working group members identified a series of knowledge gaps and proposed research priorities, while recognising that community engagement and partnerships with those with lived experience will be integral to the success of these activities. Specifically, members emphasised the need for: (1) global analysis of disease incidence, prevalence and SDH characteristics concurrently to inform policy and interventions, (2) global assessment of legacy primordial prevention programmes to help inform the co-design of interventions alongside affected communities, (3) research to develop, implement and evaluate scalable primordial prevention interventions in diverse settings and (4) research to improve access to and equity of services across the RHD continuum. Addressing SDH, through the implementation of primordial prevention strategies, could have broader implications, not only improving RHD-related health outcomes but also impacting other neglected diseases in low-resource settings.