bluuebunny/crossref_metadata_2025 huggingface dataset:
¿Influye la comunicación sobre asuntos sociales y políticos en la eficacia política interna y en las expectativas de participación sociopolítica de los adolescentes españoles?
Authors: Salado Vanesa , Moreno- Maldonado Concepción , Gaspar Tânia , Rivera Francisco
Published: May 2023

La participación de los estudiantes en debates, búsqueda de información, etc., sobre asuntos sociopolíticos, la eficacia política interna y las expectativas sociopolíticas de participación son indicadores de compromiso cívico adolescente. El objetivo de este estudio fue analizar la influencia de la Participación comunicativa sociopolítica de los adolescentes de España en las Expectativas de participación sociopolítica, de forma directa y a través de la Eficacia política interna según el género. Esta investigación basada en el proyecto “Barómetro OPINA” fué transversal y participaron 4711 adolescentes con edades comprendidas entre los 13 y los 18 años. Los instrumentos utilizados fueron tres escalas que medían los indicadores de compromiso cívico propuestos. Se realizaron comparaciones de media, un modelo de ecuaciones estructurales y un análisis de invarianza según el sexo. Los resultados obtenidos mostraron diferencias significativas en las puntuaciones de Expectativas de participación sociopolítica y Eficacia política interna. El modelo mostró buenos indicadores de ajuste sin efectos de mediación e invarianza según el sexo. Establecer debates sociopolíticos con familiares y amigos o ver noticias explica las creencias que tienen los jóvenes sobre cómo influir en la política y cómo intervenir en un futuro en situaciones que beneficien a su comunidad.
A graph-based machine learning framework identifies critical properties of FVIII that lead to hemophilia A
Authors: Ferreira Marcos V. , Nogueira Tatiane , Rios Ricardo A. , Lopes Tiago J. S.
Published: May 2023

Introduction: Blood coagulation is an essential process to cease bleeding in humans and other species. This mechanism is characterized by a molecular cascade of more than a dozen components activated after an injury to a blood vessel. In this process, the coagulation factor VIII (FVIII) is a master regulator, enhancing the activity of other components by thousands of times. In this sense, it is unsurprising that even single amino acid substitutions result in hemophilia A (HA)—a disease marked by uncontrolled bleeding and that leaves patients at permanent risk of hemorrhagic complications.

Methods: Despite recent advances in the diagnosis and treatment of HA, the precise role of each residue of the FVIII protein remains unclear. In this study, we developed a graph-based machine learning framework that explores in detail the network formed by the residues of the FVIII protein, where each residue is a node, and two nodes are connected if they are in close proximity on the FVIII 3D structure.

Results: Using this system, we identified the properties that lead to severe and mild forms of the disease. Finally, in an effort to advance the development of novel recombinant therapeutic FVIII proteins, we adapted our framework to predict the activity and expression of more than 300 in vitro alanine mutations, once more observing a close agreement between the in silico and the in vitro results.

Discussion: Together, the results derived from this study demonstrate how graph-based classifiers can leverage the diagnostic and treatment of a rare disease.
Role of nano-hydrogels coated exosomes in bone tissue repair
Authors: Pan Yuqi , Li Yige , Dong Wenjun , Jiang Bowei , Yu Yuhao , Chen Yunsu
Published: May 2023

With the development of nanotechnology, nanomaterials are widely applied in different areas. Some nanomaterials are designed to be biocompatible and can be used in the medical field, playing an important role in disease treatment. Exosomes are nanoscale vesicles with a diameter of 30–200 nm. Studies have shown that exosomes have the effect of angiogenesis, tissue (skin, tendon, cartilage, et al.) repair and reconstruction. Nano-hydrogels are hydrogels with a diameter of 200 nm or less and can be used as the carrier to transport the exosomes into the body. Some orthopedic diseases, such as bone defects and bone infections, are difficult to handle. The emergence of nano-hydrogels coated exosomes may provide a new idea to solve these problems, improving the prognosis of patients. This review summarizes the function of nano-hydrogels coated exosomes in bone tissue repair, intending to illustrate the potential use and application of nano-hydrogels coated exosomes in bone disease.
Synthesis and anticancer activity of podophyllotoxin derivatives with nitrogen-containing heterocycles
Authors: Yin Meng , Fang Yongsheng , Sun Xiaotong , Xue Minggao , Zhang Caimei , Zhu Zhiyun , Meng Yamiao , Kong Lingmei , Myint Yi Yi , Li Yan , Zhao Jingfeng , Yang Xiaodong
Published: May 2023

Three series of podophyllotoxin derivatives with various nitrogen-containing heterocycles were designed and synthesized. The antitumor activity of these podophyllotoxin derivatives was evaluated in vitro against a panel of human tumor cell lines. The results showed that podophyllotoxin-imidazolium salts and podophyllotoxin-1,2,4-triazolium salts a1–a20 exhibited excellent cytotoxic activity. Among them, a6 was the most potent cytotoxic compound with IC50 values of 0.04–0.29 μM. Podophyllotoxin-1,2,3-triazole derivatives b1–b5 displayed medium cytotoxic activity, and podophyllotoxin-amine compounds c1–c3 has good cytotoxic activity with IC50 value of 0.04–0.58 μM. Furthermore, cell cycle and apoptosis experiments of compound a6 were carried out and the results exhibited that a6 could induce G2/M cell cycle arrest and apoptosis in HCT-116 cells.
Immunosuppressive cells in oncolytic virotherapy for glioma: challenges and solutions
Authors: Liu Junfeng , Piranlioglu Raziye , Ye Fei , Shu Kai , Lei Ting , Nakashima Hiroshi
Published: May 2023

Glioblastoma is a highly aggressive form of brain cancer characterized by the abundance of myeloid lineage cells in the tumor microenvironment. Tumor-associated macrophages and microglia (TAM) and myeloid-derived suppressor cells (MDSCs), play a pivotal role in promoting immune suppression and tumor progression. Oncolytic viruses (OVs) are self-amplifying cytotoxic agents that can stimulate local anti-tumor immune responses and have the potential to suppress immunosuppressive myeloid cells and recruit tumor-infiltrating T lymphocytes (TILs) to the tumor site, leading to an adaptive immune response against tumors. However, the impact of OV therapy on the tumor-resident myeloid population and the subsequent immune responses are not yet fully understood. This review provides an overview of how TAM and MDSC respond to different types of OVs, and combination therapeutics that target the myeloid population to promote anti-tumor immune responses in the glioma microenvironment.
Carrier bag storytelling with coastal Kenyan families: sharing food, illustrations, and knowledge for tangible environmental justice impacts
Authors: Cohn Rachel M. , Mbeyu Ruth , Sarange Catherine , Mbogholi Francis , Cheupe Christopher , Cheupe Joaquim , Wamukota Andrew , Kamau Elizabeth , Treviño Melva
Published: May 2023

The small-scale fisheries food system, in which individuals achieve food security independently or in small groups through fishing livelihoods and/or subsistence activities, provides food sovereignty for millions globally. However, this arrangement has inequitable engagement due to strictly enforced gendered roles in many communities, including coastal Kenya. Recently, critics across environmental research disciplines have called for social justice in science through anticolonial, feminist methodologies and interdisciplinary praxis. This resistance may take form through the “carrier bag” ability of fiction: an allusion to Le Guin's visionary analysis of containers as the first cultural device and evidence of the power of a story or personal sovereignty to tell one's story. Drawing from creative, service-driven methodologies emerging from collaboration among international research team members and Indigenous research participants, this project uses the “carrier bag” framework to support local environmental justice and food sovereignty goals through a science storybook resource created and shared with fishing families in Kilifi County, Kenya. We investigate how stories shape interpersonal relations in the context of this collaboration and how health knowledge, environmental science, and representational imagery can be tools for justice by examining the connections between social identity, family values, and social-ecological change in this food system. Having a deeper understanding of the experiences, changing ecosystems, and research feedback of these families allows this work to support fisheries management and nutrition interventions in Kenya and communities elsewhere.
Outcomes of catheter ablation vs. medical treatment for atrial fibrillation and heart failure: a meta-analysis
Authors: Lee Wei-Chieh , Fang Hsiu-Yu , Wu Po-Jui , Chen Huang-Chung , Fang Yen-Nan , Chen Mien-Cheng
Published: May 2023

Background

The benefit of catheter ablation vs. medical treatment has been reported to be inconsistent in randomized controlled trials (RCTs) for patients with atrial fibrillation (AF) and heart failure (HF) due to different enrollment criteria. This meta-analysis aimed to decipher the differential outcomes stratified by different left ventricular ejection fractions (LVEFs) and AF types.

Methods

We searched PubMed, Embase, ProQuest, ScienceDirect, Cochrane Library, ClinicalKey, Web of Science, and ClinicalTrials.gov databases for RCTs comparing medical treatment and catheter ablation in patients with AF and HF published before March 31, 2023. Nine studies were included.

Results

When patients were stratified by LVEF, improved LVEF and 6-min walk distance, less AF recurrence, and lower all-cause mortality in favor of catheter ablation were observed in patients with LVEF ≤50% but not in patients with LVEF ≤35%, and short HF hospitalization was observed in patients with LVEF ≤50% and LVEF ≤35%. When patients were stratified by AF types, improved LVEF and 6-min walk distance, better HF questionnaire score, and short HF hospitalization in favor of catheter ablation were observed both in patients with nonparoxysmal AF and mixed AF (paroxysmal and persistent) and less AF recurrence and lower all-cause mortality in favor of catheter ablation were observed in only patients with mixed AF.

Conclusions

This meta-analysis showed improved LVEF and 6-min walk distance, less AF recurrence, and lower all-cause mortality in favor of catheter ablation vs. medical treatment in AF patients with HF and LVEF of 36%–50%. Compared with medical treatment, catheter ablation improved LVEF and had better HF status in patients with nonparoxysmal AF and mixed AF; however, AF recurrence and all-cause mortality in favor of catheter ablation were observed in only HF patients with mixed AF.
A review on individual and multistakeholder fairness in tourism recommender systems
Authors: Banerjee Ashmi , Banik Paromita , Wörndl Wolfgang
Published: May 2023

The growing use of Recommender Systems (RS) across various industries, including e-commerce, social media, news, travel, and tourism, has prompted researchers to examine these systems for any biases or fairness concerns. Fairness in RS is a multi-faceted concept ensuring fair outcomes for all stakeholders involved in the recommendation process, and its definition can vary based on the context and domain. This paper highlights the importance of evaluating RS from multiple stakeholders' perspectives, specifically focusing on Tourism Recommender Systems (TRS). Stakeholders in TRS are categorized based on their main fairness criteria, and the paper reviews state-of-the-art research on TRS fairness from various viewpoints. It also outlines the challenges, potential solutions, and research gaps in developing fair TRS. The paper concludes that designing fair TRS is a multi-dimensional process that requires consideration not only of the other stakeholders but also of the environmental impact and effects of overtourism and undertourism.
Accessibility in assessment for learning: sharing criteria for success
Authors: Willis Jill , Arnold Julie , DeLuca Christopher
Published: May 2023

Assessment for learning (AfL) practices in secondary schools are intended to help learners understand what expert performances in disciplines look like, and then apply this understanding to their own learning and assessment performances. Common AfL practices such as sharing criteria for success through rubrics and students using them to interrogate exemplars and give feedback rely heavily on the students’ language and attention. Students need to understand and draw on conceptual and collaborative language, and to make connections across several activity stages. Consequently, students with language and/or attentional difficulties and their teachers face a dilemma. On the one hand, AfL practices can provide access to developmentally appropriate curriculum. On the other, AfL practices may present additional barriers to learning. This article identifies some of the barriers students with language and/or attentional difficulties may encounter in common AfL practices, and how teachers adapted sharing of success criteria to design for greater accessibility. Access to learning is conceptualized by referring to Dewey’s principles of continuity and interaction. Interviews with 20 teachers were analyzed to find out how they adapted AfL to be more accessible in an 8 week AfL pedagogical intervention focused on success criteria. Ideas for designing accessible AfL practices from the outset are outlined as teachers realized the role of their language, small steps, visual tools, and regular opportunities for connection and interactions in making it more likely for students to benefit from AfL practices. Given that students with language and/or attentional difficulties represent some of the highest occurrences of disability in student populations, these ideas have immediate relevance for teachers and those who support AfL practices in educational policy and research.
Automatic item generation: foundations and machine learning-based approaches for assessments
Authors: Circi Ruhan , Hicks Juanita , Sikali Emmanuel
Published: May 2023

This mini review summarizes the current state of knowledge about automatic item generation in the context of educational assessment and discusses key points in the item generation pipeline. Assessment is critical in all learning systems and digitalized assessments have shown significant growth over the last decade. This leads to an urgent need to generate more items in a fast and efficient manner. Continuous improvements in computational power and advancements in methodological approaches, specifically in the field of natural language processing, provide new opportunities as well as new challenges in automatic generation of items for educational assessment. This mini review asserts the need for more work across a wide variety of areas for the scaled implementation of AIG.
Case Report: Giant insulinoma, a very rare tumor causing hypoglycemia
Authors: Tarris Georges , Rouland Alexia , Guillen Kévin , Loffroy Romaric , Lariotte Anne-Cécile , Rat Patrick , Bouillet Benjamin , Andrianiaina Haingo , Petit Jean-Michel , Martin Laurent
Published: May 2023

Insulinomas, with an incidence of 4 cases per million individuals per year, remain amongst the most frequent functional neuroendocrine tumors. The usual diameter of insulinomas usually remains under 3 cm of major axis. However, 44 exceptional cases of “giant insulinomas”, have been reported worldwide, generally exceeding 9 cm in major axis. In this article, we report the case of a 38-year-old woman whom suffered from chronic hypoglycemia despite treatment with diazoxide. Abdominal CT-scan revealed a 88 x 73 mm mass located at the tail of the pancreas. Following surgical excision, histopathological analysis confirmed G1 neuroendocrine tumor, with focal cytoplasmic expression of insulin in tumor cells. After a 16-month follow-up period, the patient didn’t address any specific complaint, and no disease recurrence and/or metastasis were observed. A 68Ga-DOTATATE-PET scan was performed 6 months after surgery, which came back normal. Genetic evaluation has not been performed in our patient. The physiopathology of giant insulinomas remain unexplained, however with possible relationship with type 1 multiple endocrine neoplasia, sporadic somatic YY1 mutations and possible transformation of bulky non-functional pancreatic neuroendocrine tumors to a functional phenotype, with slow insulin secretion. While giant insulinomas remain rare in the literature, multicentric genetic analysis of tumor samples might reveal unique features of this rare subtype of neuroendocrine pancreatic tumors. Insulinomas of large size tend to have greater malignancy and higher rates of invasiveness. Careful follow-up, especially for liver and lymph node metastases, must be performed using functional imaging techniques to avoid disease relapse.
Effect of gestational diabetes mellitus on pregnancy outcomes among younger and older women and its additive interaction with advanced maternal age
Authors: Li Jiangheng , Yan Jingli , Ma Linghua , Huang Yongquan , Zhu Maoling , Jiang Wu
Published: May 2023

Background

The prevalence of gestational diabetes mellitus (GDM) and advanced maternal age (AMA, ≥ 35 years) has shown an increasing trend worldwide. This study aimed to evaluate the risk of pregnancy outcomes among younger (20-34 years) and older (≥ 35 years) women with GDM and further analyze the epidemiologic interaction of GDM and AMA on these outcomes.

Methods

This historical cohort study included 105 683 singleton pregnant women aged 20 years or older between January 2012 and December 2015 in China. Stratified by maternal age, the associations between GDM and pregnancy outcomes were analyzed by performing logistic regression. Epidemiologic interactions were assessed by using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI) with their 95% confidence intervals (95%CIs).

Results

Among younger women, individuals with GDM had a higher risk of all maternal outcomes, preterm birth (relative risk [RR] 1.67, 95%CI 1.50–1.85), low birthweight (RR 1.24, 95%CI 1.09–1.41), large for gestational age (RR 1.51, 95%CI 1.40–1.63), macrosomia (RR 1.54, 95%CI 1.31–1.79), and fetal distress (RR 1.56, 95%CI 1.37–1.77) than those without GDM. Among older women, GDM increased the risk of gestational hypertension (RR 2.17, 95%CI 1.65–2.83), preeclampsia (RR 2.30, 95%CI 1.81–2.93), polyhydramnios (RR 3.46, 95%CI 2.01–5.96), cesarean delivery (RR 1.18, 95%CI 1.10–1.25), preterm birth (RR 1.35, 95%CI 1.14–1.60), large for gestational age (RR 1.40, 95%CI 1.23–1.60), macrosomia (RR 1.65, 95%CI 1.28–2.14) and fetal distress (RR 1.46, 95%CI 1.12–1.90). Additive interactions of GDM and AMA on polyhydramnios and preeclampsia were found, with RERI of 3.11 (95%CI 0.05-6.16) and 1.43 (95%CI 0.09-2.77), AP of 0.51 (95%CI 0.22-0.80) and 0.27 (95%CI 0.07-0.46), and SI of 2.59 (95%CI 1.17-5.77) and 1.49 (95%CI 1.07-2.07), respectively.

Conclusion

GDM is an independent risk factor for multiple adverse pregnancy outcomes, and may exert additive interactions with AMA on the risk of polyhydramnios and preeclampsia.
Associations between the serum triglyceride-glucose index and pericoronary adipose tissue attenuation and plaque features using dual-layer spectral detector computed tomography: a cross-sectional study
Authors: Ma Yue , Zhen Yanhua , Wang Min , Gao Lingfeng , Dang Yuxue , Shang Jin , Chen Xujiao , Ma Shaowei , Zhou Ke , Feng Kai , Xin Yang , Hou Yang , Guo Chuanji
Published: May 2023

Background and aims

The triglyceride-glucose (TyG) index is a reliable alternative marker for insulin resistance (IR). Pericoronary adipose tissue (PCAT) can indirectly reflect coronary inflammation. IR and coronary inflammation play a key role in the development and progression of coronary atherosclerosis. Therefore, this study investigated the relationships between the TyG index, PCAT and atherosclerotic plaque characteristics to explore whether IR might lead to coronary artery atherosclerosis progression by inducing coronary inflammation.

Methods

We retrospectively collected data on patients with chest pain who underwent coronary computed tomography angiography using spectral detector computed tomography at our institution from June to December 2021. The patients were grouped based on their TyG index levels: T1 (low), T2 (medium), and T3 (high). Each patient was assessed for total plaque volume, plaque load, maximum stenosis, the plaque component volume proportion, high-risk plaques(HRPs), and plaque characteristics (including low attenuation plaques, positive remodeling, a napkin ring sign, and spot calcification). PCAT quantification was performed on the proximal right coronary artery using the fat attenuation index (FAI) measured from a conventional multicolor computed tomography image (FAI120kVp), a spectral virtual single-energy image (FAI40keV), and the slope of the spectral HU curve (λHU).

Results

We enrolled 201 patients. The proportion of patients with maximum plaque stenosis, positive remodeling, low-density plaques, and HRPs increased as the TyG index level increased. Moreover, the FAI40keV and λHU significantly differed among the three groups, and we identified good positive correlations between FAI40keV and λHU and the TyG index (r = 0.319, P <0.01 and r = 0.325, P <0.01, respectively). FAI120kVp did not significantly differ among the groups. FAI40keV had the highest area under the curve, with an optimal cutoff value of −130.5 HU for predicting a TyG index value of ≥9.13. The multivariate linear regression analysis demonstrated that FAI40keV and λHU were independently positively related to a high TyG index level (standardized regression coefficients: 0.117 [P <0.001] and 0.134 [P <0.001], respectively).

Conclusions

Patients with chest pain and a higher TyG index level were more likely to have severe stenosis and HRPs. Moreover, FAI40keV and λHU had good correlations with the serum TyG index, which may noninvasively reflect PCAT inflammation under insulin resistance. These results could help explain the mechanism of plaque progression and instability in patients with insulin resistance might be related to IR-induced coronary inflammation.
Genetic testing for misclassified monogenic diabetes in Māori and Pacific peoples in Aōtearoa New Zealand with early-onset type 2 diabetes
Authors: Toomata Zanetta , Leask Megan , Krishnan Mohanraj , Cadzow Murray , Dalbeth Nicola , Stamp Lisa K. , de Zoysa Janak , Merriman Tony , Wilcox Phillip , Dewes Ofa , Murphy Rinki
Published: May 2023

Aims

Monogenic diabetes accounts for 1-2% of diabetes cases yet is often misdiagnosed as type 2 diabetes. The aim of this study was to examine in Māori and Pacific adults clinically diagnosed with type 2 diabetes within 40 years of age, (a) the prevalence of monogenic diabetes in this population (b) the prevalence of beta-cell autoantibodies and (c) the pre-test probability of monogenic diabetes.

Methods

Targeted sequencing data of 38 known monogenic diabetes genes was analyzed in 199 Māori and Pacific peoples with BMI of 37.9 ± 8.6 kg/m2 who had been diagnosed with type 2 diabetes between 3 and 40 years of age. A triple-screen combined autoantibody assay was used to test for GAD, IA-2, and ZnT8. MODY probability calculator score was generated in those with sufficient clinical information (55/199).

Results

No genetic variants curated as likely pathogenic or pathogenic were found. One individual (1/199) tested positive for GAD/IA-2/ZnT8 antibodies. The pre-test probability of monogenic diabetes was calculated in 55 individuals with 17/55 (31%) scoring above the 20% threshold considered for diagnostic testing referral.

Discussion

Our findings suggest that monogenic diabetes is rare in Māori and Pacific people with clinical age, and the MODY probability calculator likely overestimates the likelihood of a monogenic cause for diabetes in this population.
Polluting our rivers in search of gold: how sustainable are reforms to stop informal miners from returning to mining sites in Ghana?
Authors: Mensah Albert Kobina , Tuokuu Francis Xavier Dery
Published: May 2023

Introduction: Although artisanal gold mining has contributed to livelihoods in many rural communities across the world, it has destroyed and polluted several water bodies.

Methods: Using Prestea in the southwestern region of Ghana, this paper demonstrates how artisanal gold mining has culminated in the pollution of freshwater bodies and the ecosystem. A non-probabilistic purposive sampling technique was used for the selection of twelve artisanal gold mining communities. We used participant observation, in-depth interviews with stakeholders, a review of policy and legal documents, reports from media websites, and site visits to various artisanal gold mining sites. We observed that artisanal gold mining has destroyed major rivers, which used to serve as major sources of water supply for domestic and irrigation purposes. To achieve benign production, the Ghanaian government over the years has made efforts to formalize the operations of galamsey activities through six main routes: policy intervention, a complete ban on their activities, military strategy, national dialogue, alternative livelihood programs, and community mining. We assessed the sustainability of three of these measures (i.e., policy intervention, a complete ban on ASM, and the military strategy).

Results: We found that none of these approaches is sustainable, as the miners continue to defy the orders and military brutalities and return to mining sites to continue their operations.

Conclusion: Therefore, acknowledging ASM as a significant tool for reducing poverty and its pertinent contribution to the larger economy, providing tax exemptions and incentives to informal miners to boost their production, involving local mining communities and subaltern miners in mineral governance and decision-making, removing bureaucracies and lowering costs to make the registration of new ASM businesses easier, and strengthening the mine regulatory infrastructure are necessary to formalize the sector.
Catalogue of super-trees in Istria (Croatia) created as a result of the citizen science action
Authors: Sladonja Barbara , Damijanić Danijela , Uzelac Mirela , Poljuha Danijela
Published: May 2023

Large and monumental trees are important elements of the ecosystem and represent valuable ecological, environmental, and historical heritage. Different countries have different strategies to protect such trees; most often, through the creation and reference to catalogues of the most valuable, old, big, or monumental trees on the territory. In Croatia, such an inventory has not yet been implemented. In order to create a database and catalogue of super-trees on the territory of Istria, in 2022, we launched a citizen science action to find out the locations of large, old, and valuable trees in Istria with the help of the public. The result of the action is a geo-referenced census of 64 ʻsuper-treesʼ in Istria in the form of an online Catalogue created in ArcGIS StoryMaps application. We proved that it is possible to efficiently and quickly create a catalogue that will serve to protect monumental trees. This Catalogue is the first step in creating a regional or national register.
Unlocking environmental archives in the Arctic—insights from modern diatom-environment relationships in lakes and ponds across Greenland
Authors: Weckström Kaarina , Weckström Jan , Wischnewski Juliane , Davidson Thomas A. , Lauridsen Torben L. , Landkildehus Frank , Christoffersen Kirsten S. , Jeppesen Erik
Published: May 2023

Given the current rate of Arctic warming, the associated ecological changes need to be put into a longer-term context of natural variability. Palaeolimnology offers tools to explore archives stored in the sediments of Arctic lakes and ponds. The interpretation of these archives requires a sound knowledge of the ecology and distribution of the sedimentary proxy organisms used. Here we explored the relationship between diatoms, a widely used proxy group of siliceous algae, and the environmental drivers defining their assemblages and diversity in 115 lakes and ponds in Greenland, a markedly understudied arctic region covering extensive climate and environmental gradients. The main environmental drivers of diatom communities were related to climate and lake ontogeny, including both measured and unmeasured (spatially structured) environmental variables. The lakes and ponds in the northern study regions showed a distinctive dominance of small benthic fragilarioid species, while diatom communities in the South(west) of Greenland were more varied, including many epiphytes, owing to the longer growing season and higher habitat diversity of these lakes and ponds. The newly established lakes in the Ilulissat region host markedly different communities compared to all other sites. Species diversity followed an overall clear latitudinal decline towards the North. Despite the large distances between our study regions, diatom dispersal appeared not to be limited. Based on our results, diatoms are an excellent proxy for climate-mediated lake ecosystem change in the Arctic and thus a valuable tool for climate reconstructions in the region. Particular consideration should be given to often unmeasured climate-related drivers, such as in-lake habitat availability, due to their apparent importance in defining Arctic diatom communities.
CD4+ T cells are the major predictor of HCMV control in allogeneic stem cell transplant recipients on letermovir prophylaxis
Authors: Lauruschkat Chris David , Muchsin Ihsan , Rein Alice , Erhard Florian , Grathwohl Denise , Dölken Lars , Köchel Carolin , Falk Christine Susanne , Einsele Hermann , Wurster Sebastian , Grigoleit Götz Ulrich , Kraus Sabrina
Published: May 2023

Introduction

Human cytomegalovirus (HCMV) causes significant morbidity and mortality in allogeneic stem cell transplant (alloSCT) recipients. Recently, antiviral letermovir prophylaxis during the first 100 days after alloSCT replaced PCR-guided preemptive therapy as the primary standard of care for HCMV reactivations. Here, we compared NK-cell and T-cell reconstitution in alloSCT recipients receiving preemptive therapy or letermovir prophylaxis in order to identify potential biomarkers predicting prolonged and symptomatic HCMV reactivation.

Methods

To that end, the NK-cell and T-cell repertoire of alloSCT recipients managed with preemptive therapy (n=32) or letermovir prophylaxis (n=24) was characterized by flow cytometry on days +30, +60, +90 and +120 after alloSCT. Additionally, background-corrected HCMV-specific T-helper (CD4+IFNγ+) and cytotoxic (CD8+IFNγ+CD107a+) T cells were quantified after pp65 stimulation.

Results

Compared to preemptive therapy, letermovir prophylaxis prevented HCMV reactivation and decreased HCMV peak viral loads until days +120 and +365. Letermovir prophylaxis resulted in decreased T-cell numbers but increased NK-cell numbers. Interestingly, despite the inhibition of HCMV, we found high numbers of “memory-like” (CD56dimFcεRIγ- and/or CD159c+) NK cells and an expansion of HCMV-specific CD4+ and CD8+ T cells in letermovir recipients. We further compared immunological readouts in patients on letermovir prophylaxis with non/short-term HCMV reactivation (NSTR) and prolonged/symptomatic HCMV reactivation (long-term HCMV reactivation, LTR). Median HCMV-specific CD4+ T-cell frequencies were significantly higher in NSTR patients (day +60, 0.35 % vs. 0.00 % CD4+IFNγ+/CD4+ cells, p=0.018) than in patients with LTR, whereas patients with LTR had significantly higher median regulatory T-cell (Treg) frequencies (day +90, 2.2 % vs. 6.2 % CD4+CD25+CD127dim/CD4+ cells, p=0.019). ROC analysis confirmed low HCMV specific CD4+ (AUC on day +60: 0.813, p=0.019) and high Treg frequencies (AUC on day +90: 0.847, p=0.021) as significant predictors of prolonged and symptomatic HCMV reactivation.

Discussion

Taken together, letermovir prophylaxis delays HCMV reactivation and alters NK- and T-cell reconstitution. High numbers of HCMV-specific CD4+ T cells and low numbers of Tregs seem to be pivotal to suppress post-alloSCT HCMV reactivation during letermovir prophylaxis. Administration of more advanced immunoassays that include Treg signature cytokines might contribute to the identification of patients at high-risk for long-term and symptomatic HCMV reactivation who might benefit from prolonged administration of letermovir.
Impact of SARS-CoV2 infection on anti-apolipoprotein A-1 IgG response in inflammatory rheumatic diseases
Authors: Lamacchia Celine , Mongin Denis , Juillard Catherine , Antinori-Malaspina Paola , Gabay Cem , Finckh Axel , Pagano Sabrina , Vuilleumier Nicolas
Published: May 2023

Objectives

To investigate the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection on anti-apolipoprotein A-1 IgG (AAA1) humoral response in immunosuppressed inflammatory rheumatic diseases (IRD) patients.

Methods

This is a nested cohort study from the prospective Swiss Clinical Quality Management registry. A total of 368 IRD patients for which serum samples were available before and after the SARS-CoV2 pandemic were included. Autoantibodies against ApoA-1 (AAA1) and its c-terminal region (AF3L1) were measured in both samples. The exposure of interest was anti-SARS-CoV2 spike subunit 1 (S1) seropositivity measured in the second sample. The effect of SARS-CoV2 infection (anti-S1 seropositivity) on becoming AAA1 or AF3L1 positive and on the change of AAA1 or AF3L1 optical density (OD) between the two samples was tested with multivariable regressions.

Results

There were 12 out of 368 IRD patients who were seroconverted against S1. The proportion of patients becoming AF3L1 seropositive was significantly higher in anti-S1-positive patients, compared with anti-S1-negative patients (66.7% versus 21.6%, p = 0.001). Adjusted logistic regression analyses indicated that anti-S1 seroconversion was associated with a sevenfold increased risk of AFL1 seropositivity (odds ratio: 7.4, 95% confidence interval (95% CI): 2.1–25.9) and predicted median increase in AF3L1 OD values (+0.17, 95% CI: 0.08–0.26).

Conclusions

SARS-CoV2 infection is associated with a marked humoral response against the immunodominant c-terminal region of ApoA-1 in IRD patients. The possible clinical impact of AAA1 and AF3L1 antibodies on disease progression, cardiovascular complications, or long COVID syndrome deserves future investigations.
Dynamic change in Siglec-15 expression in peritumoral macrophages confers an immunosuppressive microenvironment and poor outcome in glioma
Authors: Chen Quan , Chen Bingkun , Wang Chunhua , Hu Li , Wu Qiongwen , Zhu Yanyang , Zhang Qiuyu
Published: May 2023

Background

Sialic acid-binding immunoglobulin-like lectin-15 (Siglec-15) was reported to be a novel immune checkpoint molecule comparable to programmed cell death 1 ligand 1 (PD-L1). However, its expression profile and immunosuppressive mechanisms in the glioma tumor microenvironment have not yet been fully explored.

Objectives

To identify the expression profile and potential function of Siglec-15 in glioma tumor microenvironment.

Methods

We investigated Siglec-15 and PD-L1 expression in tumor tissues from 60 human glioma patients and GL261 tumor models. Next, Siglec-15 knockout macrophages and mice were used to elucidate the immunosuppressive mechanism of Siglec-15 impacting macrophage function.

Results

Our results demonstrated that high levels of Siglec-15 in tumor tissues was positively correlated with poor survival in glioma patients. Siglec-15 was predominantly expressed on peritumoral CD68+ tumor-associated macrophages, which accumulated to the highest level in grade II glioma and then declined as grade increased. The Siglec-15 expression pattern was mutually exclusive with that of PD-L1 in glioma tissues, and the number of Siglec-15+PD-L1- samples (n = 45) was greater than the number of Siglec-15-PD-L1+ samples (n = 4). The dynamic change in and tissue localization of Siglec-15 expression were confirmed in GL261 tumor models. Importantly, after Siglec15 gene knockout, macrophages exhibited enhanced capacities for phagocytosis, antigen cross-presentation and initiation of antigen-specific CD8+ T-lymphocyte responses.

Conclusion

Our findings suggested that Siglec-15 could be a valuable prognostic factor and potential target for glioma patients. In addition, our data first identified dynamic changes in Siglec-15 expression and distribution in human glioma tissues, indicating that the timing of Siglec-15 blockade is critical to achieve an effective combination with other immune checkpoint inhibitors in clinical practice.
Characterization of RBD-specific cross-neutralizing antibodies responses against SARS-CoV-2 variants from COVID-19 convalescents
Authors: Wang Zheng , Li Dan , Chen Yulu , Sun Yeping , Jin Changzhong , Hu Caiqin , Feng Yi , Su Junwei , Ren Li , Hao Yanling , Wang Shuo , Zhu Meiling , Liu Ying , Qi Jianxun , Zhu Biao , Shao Yiming
Published: May 2023

Introduction

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been posing a severe threat to global public health. Although broadly neutralizing antibodies have been used to prevent or treat corona virus disease 2019 (COVID-19), new emerging variants have been proven resistant to these antibodies.

Methods

In this study, we isolated receptor binding domain (RBD)-specific memory B cells using single-cell sorting method from two COVID-19 convalescents and expressed the antibody to test their neutralizing activity against diverse SARS-CoV-2 variants. Then, we resolved antibody-RBD complex structures of potent RBD-specific neutralizing antibodies by X-ray diffraction method. Finally, we analyzed the whole antibody repertoires of the two donors and studied the evolutionary pathway of potent neutralizing antibodies.

Results and discussion

We identified three potent RBD-specific neutralizing antibodies (1D7, 3G10 and 3C11) from two COVID-19 convalescents that neutralized authentic SARS-CoV-2 WH-1 and Delta variant, and one of them, 1D7, presented broadly neutralizing activity against WH-1, Beta, Gamma, Delta and Omicron authentic viruses. The resolved antibody-RBD complex structures of two antibodies, 3G10 and 3C11, indicate that both of them interact with the external subdomain of the RBD and that they belong to the RBD-1 and RBD-4 communities, respectively. From the antibody repertoire analysis, we found that the CDR3 frequencies of the light chain, which shared high degrees of amino acid identity with these three antibodies, were higher than those of the heavy chain. This research will contribute to the development of RBD-specific antibody-based drugs and immunogens against multiple variants.
TLR4-mediated release of heparin-binding protein in human airways: a co-stimulatory role for IL-26
Authors: Paulsson Magnus , Cardenas Eduardo I. , Che Karlhans F. , Brundin Bettina , Smith Margaretha , Qvarfordt Ingemar , Lindén Anders
Published: May 2023

Background

Bacterial infection causes accumulation of neutrophils that release antimicrobial proteins including heparin-binding protein (HBP). In human airways, this neutrophil accumulation can be re-capitulated via intrabronchial exposure to lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR4) agonist, that also causes a local increase in the neutrophil-mobilizing cytokine IL-26. Although LPS is considered a weak stimulus for HBP release ex vivo, its effect on HBP release in human airways in vivo has not been characterized.

Methods

We determined whether intrabronchial exposure to LPS causes concomitant release of HBP and IL-26 in human airways, and whether IL-26 can enhance LPS-induced release of HBP in isolated human neutrophils.

Results

We found that the concentration of HBP was markedly increased in bronchoalveolar lavage (BAL) fluid 12, 24, and 48 hours after LPS exposure, and that it displayed a strong and positive correlation with that of IL-26. Moreover, the concentration of HBP in conditioned media from isolated neutrophils was enhanced only after co-stimulation with LPS and IL-26.

Conclusions

Taken together, our findings indicate that TLR4 stimulation causes concomitant release of HBP and IL-26 in human airways, and that IL-26 may constitute a required co-stimulant for HBP release in neutrophils, thus enabling the concerted action of HBP and IL-26 in local host defense.
Ecomorphology of a predatory deep-sea fish family: does trophic specialization drive hyperspeciation?
Authors: McGonagle Ryan P. , Kerstetter David W. , Fenolio Danté , Sutton Tracey T.
Published: May 2023

Two of the main drivers of speciation among aquatic vertebrates are physical isolation (e.g., lakes and streams) and micro-niche availability (e.g., tropical reefs). In both regards, the mesopelagic domain of the open ocean, Earth’s second largest cumulative ecosystem (behind only the bathypelagic domain), would seem retardant. Ocean circulation makes isolation rare on both contemporary and geological time/space scales, and the lack of substrate precludes stable micro-niches. Paradoxically, some pelagic taxa demonstrate much higher-than-expected species richness on regional scales. A prime example is the dragonfish family Stomiidae, the most speciose family of mesopelagic fishes, owing largely to the subfamily Melanostomiinae (scaleless black dragonfishes), which contributes 222 of the 320 described species. Within genera, species are differentiated almost solely by form of the jugular-positioned, bioluminescent barbel, a structure putatively linked to feeding (via prey luring). The relationship between diversity (both systematic and morphological) and diet within the Melanostomiinae has not been previously examined, primarily due to sample size limitation. Herein, the diet and morphology of 16 species of melanostomiine dragonfishes from the Gulf of Mexico were examined to ascertain whether the diversification in this fish clade is based on prey specialization, as is the case with many other speciose fish families (e.g., Cichlidae). Gut content analysis revealed a rather small spectrum of prey taxa across a wide spectrum of predators, with most species exhibiting piscivory centered on the most regionally abundant lanternfishes (Myctophidae). Lesser numbers of species preyed upon bristlemouths (Gonostomatidae), oceanic basslets (Howellidae), bigscales (Melamphaidae), and other dragonfishes, while three species selected for cephalopod prey. No dragonfish species consumed macrocrustaceans (e.g., decapod shrimps), despite their numerical prevalence as potential prey. Regarding functional morphology, dissimilarity was driven mostly by barbel length, vertical oral gape, and horizontal maxillary oral gape. There were no robust morphological-dietary relationships amongst melanostomiines, with dietary diversity much lower than morphological diversity. These results suggest that other factors, perhaps conspecific recognition and/or sexual selection related to spawning, may be primary drivers of hyperspeciation in the micro-habitat-poor pelagic environment.
Levels of autotrophy and heterotrophy in mesophotic corals near the end photic zone
Authors: Carmignani Amy , Radice Veronica Z. , McMahon Kathryn M. , Holman Alex I. , Miller Karen , Grice Kliti , Richards Zoe
Published: May 2023

Mesophotic corals live at ~30-150 m depth and can sustain metabolic processes under light-limited conditions by enhancing autotrophy through specialized photoadaptations or increasing heterotrophic nutrient acquisition. These acclimatory processes are often species-specific, however mesophotic ecosystems are largely unexplored and acclimation limits for most species are unknown. This study examined mesophotic coral ecosystems using a remotely operated vehicle (Ashmore Reef, Western Australia at 40–75m depth) to investigate the trophic ecology of five species of scleractinian coral (from genera Leptoseris, Pachyseris, and Craterastrea) using stable isotope analyses (δ13C and δ15N) of host and symbiont tissues and protein concentration. Trophic strategies were analyzed between species and between overall corals sampled above and below the end-photic point, where light is only 1% of surface irradiance. Results showed species-specific differences in resource use. Leptoseris hawaiiensis, L. scabra, and P. speciosa had similar Δ13C values (δ13C host - δ13C symbiont) approaching zero (< 0.5 ‰) which indicated greater dependence on symbiont autotrophy. In contrast, Leptoseris glabra and Craterastrea levis had higher Δ13C values (1.4 to 3.5 ‰) which indicated a greater reliance on external carbon sources. The latter two species also demonstrated tight nitrogen recycling within the holobiont, exhibiting low Δ15N values (host δ15N - symbiont δ15N =< 0.5 ‰), compared to more autotrophic species (Δ15N = >1.2 ‰). Some species demonstrated the ability to maintain metabolic processes despite substantially reduced light availability (0.5 – 2% of surface irradiance). This research challenges our knowledge of acclimation limits for many scleractinian corals and contributes novel information for Ashmore Reef, the Western Australia region and mesophotic ecosystems in general, and critically examines common methods used to interpretate trophic ecology with bulk stable isotopes δ13C and δ15N.
PUFA and carotenoid producing thraustochytrids and their anti-microbial and antioxidant activities
Authors: Kaliyamoorthy Kalidasan , Chavanich Suchana , Kandasamy Kathiresan , Ponnuvel Mohanchander , Kamlangdee Niyom , Taoka Yousuke , Viyakarn Voranop
Published: May 2023

Thraustochytrids contribute to the microbiota of mangrove ecosystem, and they hold promise as a potential source of polyunsaturated fatty acids (PUFAs), antimicrobials and antioxidants for their application in pharmaceutical, aquaculture, and human health sectors. However, the thraustochytrids have not been properly studied in Indian mangrove ecosystems for their PUFAs and biological activities, and hence, the present study was carried to isolate the PUFAs-rich thraustochytrids for their pigments, antimicrobial and antioxidant properties. This work isolated and identified the thraustochytrids that are capable of producing PUFAs from decomposing leaves of mangroves at Pichavaram, southeast coast of India. Two predominant isolates were identified as Thraustochytrium sp. and Aurantiochytrium mangrovei based on morphological and molecular characteristics. Thraustochytrium sp., produced the biomass of 4.72 g L-1, containing total lipids of 42.36% and docosahexaenoic acid (DHA) of 32.69% of total lipids, whereas, A. mangrovei produced the biomass of 6.25 g L-1 containing total lipids of 49.81% and DHA of 44.71% of total lipids. Astaxanthin pigment accumulated up to 3.2 µg L-1 in A. mangrovei, whereas the pigment was not detected in Thraustochytrium sp. Further, the biomass extracted in organic solvents was tested for antibacterial activity against seven clinical pathogens along with positive control of ampicillin. Thraustochytrium sp., exhibited the highest antibacterial activity with the zone of inhibition of 78.77% against Staphylococcus aureus and the lowest (20.95%) against Klebsiella pneumonia. Thraustochytrium sp., also showed minimum inhibitory concentration (MIC) of 40 µg L-1 inhibiting the growth of S. aureus. The antioxidant activity of A. mangrovei was tested by using six assays and noted the highest free radical scavenging (87.37 ± 1.22%) and the lowest nitric oxide radical scavenging (75.12 ± 2.22%) activities. Hence, it is clear that the extracts of Thraustochytrium sp., and A. mangrovei are promising sources of lead compounds for biopharma and food industries.