bluuebunny/crossref_metadata_2025 huggingface dataset:
Tantangan dan Dukungan dalam Kesiapan Penerapan Rekam Medis Elektronik di Rumah Sakit
Authors: Wulansari Inda , Purnami Cahya Tri , Prasetijo Agung Budi
Published: May 2023

The use of paper-based medical records requires a time-consuming process and had a relatively high risk of data loss compared to electronic-based medical records. This literature review aims to analyze the readiness of electronic medical records in hospitals. The search for journal references was carried out through several sources, namely Pubmed, Google Schoolar, and ScienceDirect with material inclusion criteria according to keywords, namely challenges and support in the readiness of implementing electronic medical records and exclusion criteria, namely the journal was a review article. Based on the search results, 963 articles were obtained which were then selected for up to 10 articles that were included in the discussion. The results showed that the readiness of health workers for the implementation of electronic medical records is still low and appropriate considerations and steps are needed to increase readiness in implementing electronic medical records in hospitals.
PENERAPAN METODE DOUBLE EXPONENTIAL SMOOTHING UNTUK MEMPREDIKSI JUMLAH PENJUALAN SPRINGBED DI PT. MASINDO KARYA PRIMA
Authors: Tarigan Victor
Published: May 2023

PT. Masindo Karya adalah salah satu perusahaan yang mendistribusi springbed dengan berbagai macam merek ke toko-toko yang ada di kota Indonesia, khususnya kota Medan. Pada saat ini proses peramalan jumlah springbed di perusaah ini masih dilakukan secara manual berdasarkan insting dari manajer perusahaan tersebut serta perhitungan sederhana dengan merata-ratakan jumlah penjualan berdasarkan periode tertentu. Pada saat ini proses peramalan jumlah springbed di perusaahan ini masih dilakukan secara manual berdasarkan insting dari manajer perusahaan tersebut serta perhitungan sederhana dengan merata-ratakan jumlah penjualan berdasarkan periode tertentu. Untuk memprediksi jumlah penjualan springbed di masa depan, data jumlah penjualan yang akan digunakan dari bulan agustus 2021 sampai dengan Maret 2023. Salah satu metode yang dapat digunakan untuk melakukan prediksi adalah dengan menggunakan metode double exponential smoothing. Metode Double Exponential Smoothing adalah metode peramalan untuk data time series yang digunakan untuk menghitung tren dan level data pada seri waktu Pada proses prediksi dengan metode ini harus memberikan parameter nilai alpha. Untuk mengukur nilai margin error metode double exponential smothing, metode MAPE akan digunakan untuk menghitung nilai margin error. Hasil dari penelitian dapat ditarik kesimpulan metode double exponential smoothing dapat membantu pihak perusahaan dalam menentukan jumlah stok penjualan springbed berdasarkan merek tertentu. Selain itu nilai input parameter alpha yang akan diberikan adalah 0.3, 0.5, dan 0.7 dan dari nilai inputan-inputan tersebut berdasarkan pengujian, bahwa nilai nilai margin error dengan menggunakan metode MAPE nilai MAPE terkecil yatu sebesar 15.07 % dengan nilai parameter alpha 0.5. Hasil prediksi yang didapatkan dengan nilai alpha tersebut adalah sebesar 664 stok penjualan.
A new portable toluidine blue/aptamer complex-on-polyethyleneimine-coated gold nanoparticles-based sensor for label-free electrochemical detection of alpha-fetoprotein
Authors: Yaiwong Patrawadee , Anuthum Siriporn , Sangthong Padchanee , Jakmunee Jaroon , Bamrungsap Suwussa , Ounnunkad Kontad
Published: May 2023

The quantification of alpha-fetoprotein (AFP) as a potential liver cancer biomarker which is generally found in ultratrace level is of significance in biomedical diagnostics. Therefore, it is challenging to find a strategy to fabricate a highly sensitive electrochemical device towards AFP detection through electrode modification for signal generation and amplification. This work shows the construction of a simple, reliable, highly sensitive, and label-free aptasensor based on polyethyleneimine-coated gold nanoparticles (PEI-AuNPs). A disposable ItalSens screen-printed electrode (SPE) is employed for fabricating the sensor by successive modifying with PEI-AuNPs, aptamer, bovine serum albumin (BSA), and toluidine blue (TB), respectively. The AFP assay is easily performed when the electrode is inserted into a small Sensit/Smart potentiostat connected to a smartphone. The readout signal of the aptasensor derives from the electrochemical response of TB intercalating into the aptamer-modified electrode after binding with the target. The decrease in current response of the proposed sensor is proportional to the AFP concentration due to the restriction of the electron transfer pathway of TB by a number of insulating AFP/aptamer complexes on the electrode surface. PEI-AuNPs improve SPE’s reactivity and provide a large surface area for aptamer immobilization whereas aptamer provides selectivity to the target AFP. Consequently, this electrochemical biosensor is highly sensitive and selective for AFP analysis. The developed assay reveals a linear range of detection from 10 to 50000 pg mL−1 with R2 = 0.9977 and provided a limit of detection (LOD) of 9.5 pg mL−1 in human serum. With its simplicity and robustness, it is anticipated that this electrochemical-based aptasensor will be a benefit for the clinical diagnosis of liver cancer and further developed for other biomarkers analysis.
Encapsulation of β-NGF in injectable microrods for localized delivery accelerates endochondral fracture repair
Authors: Rivera Kevin O. , Cuylear Darnell L. , Duke Victoria R. , O’Hara Kelsey M. , Zhong Justin X. , Elghazali Nafisa A. , Finbloom Joel A. , Kharbikar Bhushan N. , Kryger Alex N. , Miclau Theodore , Marcucio Ralph S. , Bahney Chelsea S. , Desai Tejal A.
Published: May 2023

Introduction: Currently, there are no non-surgical FDA-approved biological approaches to accelerate fracture repair. Injectable therapies designed to stimulate bone healing represent an exciting alternative to surgically implanted biologics, however, the translation of effective osteoinductive therapies remains challenging due to the need for safe and effective drug delivery. Hydrogel-based microparticle platforms may be a clinically relevant solution to create controlled and localized drug delivery to treat bone fractures. Here, we describe poly (ethylene glycol) dimethacrylate (PEGDMA)-based microparticles, in the shape of microrods, loaded with beta nerve growth factor (β-NGF) for the purpose of promoting fracture repair.

Methods: Herein, PEGDMA microrods were fabricated through photolithography. PEGDMA microrods were loaded with β-NGF and in vitro release was examined. Subsequently, bioactivity assays were evaluated in vitro using the TF-1 tyrosine receptor kinase A (Trk-A) expressing cell line. Finally, in vivo studies using our well-established murine tibia fracture model were performed and a single injection of the β-NGF loaded PEGDMA microrods, non-loaded PEGDMA microrods, or soluble β-NGF was administered to assess the extent of fracture healing using Micro-computed tomography (µCT) and histomorphometry.

Results:In vitro release studies showed there is significant retention of protein within the polymer matrix over 168 hours through physiochemical interactions. Bioactivity of protein post-loading was confirmed with the TF-1 cell line. In vivo studies using our murine tibia fracture model show that PEGDMA microrods injected at the site of fracture remained adjacent to the callus for over 7 days. Importantly, a single injection of β-NGF loaded PEGDMA microrods resulted in improved fracture healing as indicated by a significant increase in the percent bone in the fracture callus, trabecular connective density, and bone mineral density relative to soluble β-NGF control indicating improved drug retention within the tissue. The concomitant decrease in cartilage fraction supports our prior work showing that β-NGF promotes endochondral conversion of cartilage to bone to accelerate healing.

Discussion: We demonstrate a novel and translational method wherein β-NGF can be encapsulated within PEGDMA microrods for local delivery and that β-NGF bioactivity is maintained resulting in improved bone fracture repair.
Patient-derived organoids as a platform for drug screening in metastatic colorectal cancer
Authors: He Xingfeng , Jiang Yan , Zhang Long , Li Yaqi , Hu Xiang , Hua Guoqiang , Cai Sanjun , Mo Shaobo , Peng Junjie
Published: May 2023

Introduction: Most advanced colorectal cancers are aggressive, and there is a lack of effective methods for selecting appropriate anticancer regimens. Patient-derived organoids (PDOs) have emerged as preclinical platforms for modeling clinical responses to cancer therapy.

Methods: In this study, we successfully constructed a living biobank with 42 organoids derived from primary and metastatic lesions of metastatic colorectal cancer patients. Tumor tissue was obtained from patients undergoing surgical resection of the primary or metastatic lesion and then used to establish PDOs. Immunohistochemistry (IHC) and drug sensitivity assays were performed to analyze the properties of these organoids.

Results: The mCRC organoids were successfully established with an 80% success rate. The PDOs maintained the genetic and phenotypic heterogeneity of their parental tumors. The IC50 values of5-fluorouracil (5-FU), oxaliplatin, and irinotecan (CPT11) were determined for mCRC organoids using drug sensitivity assays. The in vitro chemosensitivity data revealed the potential value of PDOs for clinical applications in predicting chemotherapy response and clinical outcomes in mCRC patients.

Discussion: In summary, the PDO model is an effective platform for in vitro assessment of patient-specific drug sensitivity, which can guide personalized treatment decisions for patients with end-stage CRC.
Technological advances for analyzing the content of organ-on-a-chip by mass spectrometry
Authors: Hadavi Darya , Tosheva Ilona , Siegel Tiffany Porta , Cuypers Eva , Honing Maarten
Published: May 2023

Three-dimensional (3D) cell cultures, including organ-on-a-chip (OOC) devices, offer the possibility to mimic human physiology conditions better than 2D models. The organ-on-a-chip devices have a wide range of applications, including mechanical studies, functional validation, and toxicology investigations. Despite many advances in this field, the major challenge with the use of organ-on-a-chips relies on the lack of online analysis methods preventing the real-time observation of cultured cells. Mass spectrometry is a promising analytical technique for real-time analysis of cell excretes from organ-on-a-chip models. This is due to its high sensitivity, selectivity, and ability to tentatively identify a large variety of unknown compounds, ranging from metabolites, lipids, and peptides to proteins. However, the hyphenation of organ-on-a-chip with MS is largely hampered by the nature of the media used, and the presence of nonvolatile buffers. This in turn stalls the straightforward and online connection of organ-on-a-chip outlet to MS. To overcome this challenge, multiple advances have been made to pre-treat samples right after organ-on-a-chip and just before MS. In this review, we summarised these technological advances and exhaustively evaluated their benefits and shortcomings for successful hyphenation of organ-on-a-chip with MS.
Material quantities and estimated construction costs for new elevated IRC 2015-compliant single-family home foundations
Authors: Kodavatiganti Yamini , Rahim Md Adilur , Friedland Carol J. , Mostafiz Rubayet Bin , Taghinezhad Arash , Heil Shandy
Published: May 2023

Residential foundation selection is critical for the lifetime performance of the project, but the type of foundation selected can depend on cost. This study aims to compare the new construction costs of residential slab-on-fill and four types of crawl space foundations for residential projects by quantifying the material quantities for each and exploring the effect of building characteristics on material quantities and total costs. The building characteristics selected are size (139 m2, 186 m2, and 232 m2), footprint aspect ratio (1:1, 1:2.5, and 1:5) and first floor elevation (0 m–1.2 m in 0.3 m increments). We find that material quantities and total costs change not only with building size and elevation, but also with footprint aspect ratio. Applying 2022 RSMeans Building Construction Cost data, the results show that for any building size, aspect ratio, or elevation, raised wood flooring on pier foundations ($118–$180 per m2) and slab on fill ($103–$211 per m2) are the least expensive, while crawl space foundations with stemwalls are the most expensive ($147–$280 per m2). The results of this study can be used by residential builders, developers and designers in evaluating foundation costs and design alternatives. The methodology may also be adapted for use in other applications such as flood mitigation or energy efficiency projects or environmental sustainability assessments.
Comparative environmental footprint analysis of ultra-high-performance concrete using Portland cement and alkali-activated materials
Authors: Glanz Dilan , Sameer Husam , Göbel Daniela , Wetzel Alexander , Middendorf Bernhard , Mostert Clemens , Bringezu Stefan
Published: May 2023

Considering the ambitious greenhouse gas emission reduction and efficient use of resource targets set by the Sustainable Development Goals and the importance of concrete structures to achieve these goals, there is an increasing need to study the environmental performance of different concrete production alternatives. Cement is one of the main building materials that contribute significantly to global warming; therefore, studying the environmental performance of innovative binders that can substitute the use of cement is highly recommended. This article investigates the climate, material, energy, and water footprints of four innovative mixtures of ultra-high-performance concrete (UHPC) with a binder made of alkali-activated materials in comparison with the one made of Portland cement. Footprint analysis is carried out within cradle-to-grave life cycle assessment boundaries. Within the life cycle assessment, the functional unit defines the quantification of the final product or service. The functional units of the UHPC were adapted for the comparability of concrete mixtures with different compressive strengths. The results show that UHPC made with an alkali-activated material has 32%–45% better performance in terms of a climate footprint and 19%–33% better performance in terms of material footprints, whereas a trade-off can be seen regarding 44%–83% higher energy footprints and 75%–146% higher water footprints. The disadvantages in energy and water footprints are caused by waterglass. When allocation is considered, mixtures with high silica fume content have higher environmental footprints.
Single-cell analysis reveals dysregulated inflammatory response in peripheral blood immunity in patients with acute respiratory distress syndrome
Authors: Mo Jingjia , Yang Yanli , Feng Jihua , Lei Yanhua , Huang Suhong , Cen Weiluan , Wei Shanshan , Huang Hao , Lu Junyu , Zhang Jianfeng
Published: May 2023

Introduction: Acute respiratory distress syndrome (ARDS) remains a major clinical challenge for patients in intensive care units. Determining the differential mechanisms underlying ARDS with different etiologies is a key goal to improve the effectiveness of ARDS therapy. Despite growing evidence that different immune cell types are involved in ARDS, the role of altered immune cell subpopulations in disease progression is unelucidated.

Methods: In this study, we combined scRNA-seq and bulk-level sequencing to analyze the transcriptomes of peripheral blood mononuclear cells from healthy volunteers and patients with septic ARDS (sep-ARDS) and pneumonic ARDS (PNE-ARDS).

Results: Our data revealed differential alterations at the cellular and molecular levels and within biological signaling pathways in ARDS with different etiologies. The dynamics of neutrophils, macrophages (Macs), classical dendritic cells (cDCs), myeloid-derived suppressive cells (MDSCs), and CD8+ T cells varied significantly among groups of different samples, with neutrophils and cDCs at higher, and Macs at significantly lower, amounts in the patients with sep-ARDS. Furthermore, MDSCs were highly enriched only in the sep-ARDS patients, whereas a higher abundance of CD8+ T cells was observed in patients with PNE-ARDS. In addition, these cell subpopulations were found to be significantly involved in apoptosis, inflammatory, and immune-related pathways. In particular, a significant enhancement of the oxidative stress response was observed in the neutrophil subpopulation.

Conclusion: Our study shows that the composition of cells involved in the main peripheral circulation differs in patients with ARDS with different etiologies. Studying the role and mechanism of action of these cells during ARDS will provide new opportunities for the treatment of this condition.
Identifying promising GSK3β inhibitors for cancer management: a computational pipeline combining virtual screening and molecular dynamics simulations
Authors: Hua Libo , Anjum Farah , Shafie Alaa , Ashour Amal Adnan , Almalki Abdulraheem Ali , Alqarni Ali Abdullah , Banjer Hamsa Jameel , Almaghrabi Sarah Abdullah , He Shan , Xu Nenggui
Published: May 2023

Glycogen synthase kinase-3 (GSK3β), a serine/threonine protein kinase, has been discovered as a novel target for anticancer drugs. Although GSK3β is involved in multiple pathways linked to the etiology of various cancers, no specific GSK3β inhibitor has been authorized for cancer therapy. Most of its inhibitors have toxicity effects therefore, there is a need to develop safe and more potent inhibitors. In this study, a library of 4,222 anti-cancer compounds underwent rigorous computational screening to identify potential candidates for targeting the binding pocket of GSK3β. The screening process involved various stages, including docking-based virtual screening, physicochemical and ADMET analysis, and molecular dynamics simulations. Ultimately, two hit compounds, BMS-754807 and GSK429286A, were identified as having high binding affinities to GSK3β. BMS-754807 and GSK429286A exhibited binding affinities of −11.9, and −9.8 kcal/mol, respectively, which were greater than that of the positive control (−7.6 kcal/mol). Further, molecular dynamics simulations for 100 ns were employed to optimize the interaction between the compounds and GSK3β, and the simulations demonstrated that the interaction was stable and consistent throughout the study. These hits were also anticipated to have good drug-like properties. Finally, this study suggests that BMS-754807 and GSK429286A may undergo experimental validation to evaluate their potential as cancer treatments in clinical settings.
Antibiotic susceptibility of Escherichia coli isolated from neonates admitted to neonatal intensive care units across China from 2015 to 2020
Authors: Xiao Ruiqi , Li Ying , Liu Xiaowei , Ding Yijun , Lai Jidong , Li Yangfang , Kang Wenqing , Zou Peicen , Wang Jie , Du Yue , Zhang Jinjing , Wang Yajuan
Published: May 2023

Background

Escherichia coli is one of the most common pathogens causing neonatal infections. Recently, the incidence and drug resistance of E. coli have increased, posing a major threat to neonatal health. The aim of this study was to describe and analyze the antibiotic resistance and multilocus sequence typing (MLST) characteristics of E. coli derived from infants admitted to neonatal intensive care units (NICUs) across China.

Methods

In this study, 370 strains of E. coli from neonates were collected. E. coli isolated from these specimens were subjected to antimicrobial susceptibility testing (by broth microdilution method) and MLST.

Results

The overall resistance rate was 82.68%, with the highest rate of methicillin/sulfamethoxazole (55.68%) followed by cefotaxime (46.22%). Multiple resistance rate was 36.74%, 132 strains (35.68%) had extended-spectrum β-lactamase (ESBL) phenotype and 5 strains (1.35%) had insensitivity to the tested carbapenem antibiotics. The resistance of E. coli isolated from different pathogenicity and different sites of infections varied, strains derived from sputum were significantly more resistant to β-lactams and tetracyclines. Currently, the prevalence spectrum in NICUs was dominated by ST1193, ST95, ST73, ST69 and ST131 across China. And the multidrug resistance of ST410 was the most severe. ST410 had the highest resistance rate to cefotaxime (86.67%), and its most common multidrug resistance pattern was β-lactams + aminoglycosides + quinolones + tetracyclines + sulfonamides.

Conclusions

Substantial proportions of neonatal E. coli isolates were severely resistant to commonly administered antibiotics. MLST results can suggest the prevalent characteristics of antibiotic resistance in E. coli with different ST types.
Perspectives on climate information use in the Caribbean
Authors: Dookie Denyse S. , Conway Declan , Dessai Suraje
Published: May 2023

Within research on climate information for decision-making, localized insights on the influences of climate information use remain limited in small and low-income countries. This paper offers an empirical contribution on Caribbean perspectives of climate information use considering current barriers and enablers in the region. We employ thematic analysis of 26 semi-structured interviews with region-focused sectoral experts (including end-users and decision-makers) drawn from climate adaptation, disaster risk reduction, and resilience focused initiatives and institutions. The results reaffirm presence of known barriers, such as the crucial role of finance, but notably we identify a range of interlinked enabling and catalyzing conditions necessary for the effective use of climate information. These conditions include the need for island- and sector- contextualized climate information, the role of international donors, the importance of adequate human resource capacity and presence of loud voices/climate champions, as well as the need for effective political and legislative mandates and for greater co-production. We construct a visualization of respondents' understanding of influencing factor interrelationships. This shows how their heuristics of climate information use for decision-making intricately link with roles for proactive climate champions, and that available finance often reflects donor interests. We end by discussing how these insights can contribute to strategies for more effective climate information use to promote resilience within the region.
Charismatic speech features in robot instructions enhance team creativity
Authors: Fucinato Karen , Niebuhr Oliver , Nørskov Sladjana , Fischer Kerstin
Published: May 2023

This study examines whether a social robot can enable team creativity and increase team performance depending on its speaking style. The aim is to provide insight into human teams' creativity and performance when exposed to different ways of speaking by a social robot, that is, when the robotic creativity facilitator is using different acoustic-prosodic features. In one condition, participants received their instructions from the robot in a “charismatic” speaking style, in the other, the robot used a less engaging way of speaking. The results show that when the robot's speech is based on charismatic speech characteristics, it is significantly better at enhancing team creativity and performance than when its speech uses fewer charismatic speech characteristics. The robot's speaking style thus influences its effectiveness as team creativity facilitator.
A fully-automated low-cost cardiac monolayer optical mapping robot
Authors: Lee Peter , Hou Luqia , Alibhai Faisal J. , Al-attar Rasha , Simón-Chica Ana , Redondo-Rodríguez Andrés , Nie Yilin , Mirotsou Maria , Laflamme Michael A. , Swaminath Gayathri , Filgueiras-Rama David
Published: May 2023

Scalable and high-throughput electrophysiological measurement systems are necessary to accelerate the elucidation of cardiac diseases in drug development. Optical mapping is the primary method of simultaneously measuring several key electrophysiological parameters, such as action potentials, intracellular free calcium and conduction velocity, at high spatiotemporal resolution. This tool has been applied to isolated whole-hearts, whole-hearts in-vivo, tissue-slices and cardiac monolayers/tissue-constructs. Although optical mapping of all of these substrates have contributed to our understanding of ion-channels and fibrillation dynamics, cardiac monolayers/tissue-constructs are scalable macroscopic substrates that are particularly amenable to high-throughput interrogation. Here, we describe and validate a scalable and fully-automated monolayer optical mapping robot that requires no human intervention and with reasonable costs. As a proof-of-principle demonstration, we performed parallelized macroscopic optical mapping of calcium dynamics in the well-established neonatal-rat-ventricular-myocyte monolayer plated on standard 35 mm dishes. Given the advancements in regenerative and personalized medicine, we also performed parallelized macroscopic optical mapping of voltage dynamics in human pluripotent stem cell-derived cardiomyocyte monolayers using a genetically encoded voltage indictor and a commonly-used voltage sensitive dye to demonstrate the versatility of our system.
A trading optimization model for virtual power plants in day-ahead power market considering uncertainties
Authors: Weishang Guo , Qiang Wang , Haiying Liu , Jing Wu
Published: May 2023

Background: The day-ahead power market is an important part of the spot market. In the day-ahead market, participants make short-term forecasts of the load and output to propose the bidding curve more precisely. As energy aggregators that have regulatory resources, virtual power plants (VPPs) need to consider the uncertainty of distributed renewable energy output when participating in power market transactions.

Methods: This paper analyzes the uncertainty and built an optimization model for VPP in day-ahead power market considering the uncertainty from both inner parts and the market environment. To verify the model, a simulation study is ran.

Results: And the study results show the following: 1) the forecasting model is more efficient than the traditional algorithm in terms of accuracy, and 2) the confidence levels are not fully positive with the benefit of VPPs.

Discussion: Improving the confidence level could reduce the uncertainty brought by renewable energy, but could also cause conservative trading behavior and affect the consumption of renewable energy.
From national monitoring to transnational indicators: reporting and processing of aquatic biology data under the European Environment Agency’s State of the Environment data flow
Authors: Moe S. Jannicke , Mentzel Sophie , Welch Samuel A. , Lyche Solheim Anne
Published: May 2023

Biological monitoring data from aquatic ecosystems are collected from European countries on a yearly basis by the European Environment Agency (EEA) through the Water Information System for Europe (WISE). The WISE-SoE (State of Environment) data flows provide indicators of pressures, states and impacts of surface waters and groundwaters on a pan-European scale. The WISE-2 Biology was established to obtain a harmonised flow of biology data reported annually as Ecological Quality Ratios (EQRs) from European surface waters, as a supplement to the mandatory 6-yearly reporting of ecological status of water bodies for the Water Framework Directive. The purposes of this paper are 1) to describe the compilation of national aquatic biology monitoring data indicators and to inform about the public availability of these data, 2) to give an overview of the reported data and indicate the potential for assessments based on these data, and 3) to illustrate the potential for further use of the underlying species abundance data in biodiversity research and assessment. WISE-2 data are reported for the following biological quality elements: phytoplankton, phytobenthos, macrophytes, macroalgae, angiosperms, benthic invertebrates and fish in rivers, lakes, transitional and/or coastal waters. The EQR values represent the deviation from reference conditions. The final processed and quality-checked data are published in EEA’s database Waterbase - Biology, which currently holds data from more than 13,000 waterbodies in 26 countries from the reporting years 2011–2021. Examples of time series aggregated by geographic regions give an indication of the type of trends that can be obtained from the reported data at the nEQR scale. However, the current results are representative only for certain geographic regions with high coverage of water bodies. Within the European research project EuropaBON (Europa Biodiversity Observation Network), the use of WISE-2 data can be leveraged to support biodiversity policy and conservation planning. EuropaBON’s online database provides an overview of how biodiversity monitoring schemes across Europe flows through different integration nodes, to produce Essential Biodiversity Variables and other policy-relevant indicators. Here, we use the EuropaBON visualisation tool to illustrate the WISE-2 as a European integration node for 157 biology datasets via the national integration nodes.
Acidification and hypoxia drive physiological trade-offs in oysters and partial loss of nutrient cycling capacity in oyster holobiont
Authors: Hemraj Deevesh Ashley , Falkenberg Laura J. , Cheung Khan , Man Lauren , Carini Alessia , Russell Bayden D.
Published: May 2023

Introduction

Reef building oysters provide vast ecological benefits and ecosystem services. A large part of their role in driving ecological processes is mediated by the microbial communities that are associated with the oysters; together forming the oyster holobiont. While changing environmental conditions are known to alter the physiological performance of oysters, it is unclear how multiple stressors may alter the ability of the oyster holobiont to maintain its functional role.

Methods

Here, we exposed oysters to acidification and hypoxia to examine their physiological responses (molecular defense and immune response), changes in community structure of their associated microbial community, and changes in water nutrient concentrations to evaluate how acidification and hypoxia will alter the oyster holobiont’s ecological role.

Results

We found clear physiological stress in oysters exposed to acidification, hypoxia, and their combination but low mortality. However, there were different physiological trade-offs in oysters exposed to acidification or hypoxia, and the combination of stressors incited greater physiological costs (i.e., >600% increase in protein damage and drastic decrease in haemocyte counts). The microbial communities differed depending on the environment, with microbial community structure partly readjusted based on the environmental conditions. Microbes also seemed to have lost some capacity in nutrient cycling under hypoxia and multi-stressor conditions (~50% less nitrification) but not acidification.

Discussion

We show that the microbiota associated to the oyster can be enriched differently under climate change depending on the type of environmental change that the oyster holobiont is exposed to. In addition, it may be the primary impacts to oyster physiology which then drives changes to the associated microbial community. Therefore, we suggest the oyster holobiont may lose some of its nutrient cycling properties under hypoxia and multi-stressor conditions although the oysters can regulate their physiological processes to maintain homeostasis on the short-term.
Expression quantitative trait locus studies in the era of single-cell omics
Authors: Luo Jie , Wu Xinyi , Cheng Yuan , Chen Guang , Wang Jian , Song Xijiao
Published: May 2023

Genome-wide association studies have revealed that the regulation of gene expression bridges genetic variants and complex phenotypes. Profiling of the bulk transcriptome coupled with linkage analysis (expression quantitative trait locus (eQTL) mapping) has advanced our understanding of the relationship between genetic variants and gene regulation in the context of complex phenotypes. However, bulk transcriptomics has inherited limitations as the regulation of gene expression tends to be cell-type-specific. The advent of single-cell RNA-seq technology now enables the identification of the cell-type-specific regulation of gene expression through a single-cell eQTL (sc-eQTL). In this review, we first provide an overview of sc-eQTL studies, including data processing and the mapping procedure of the sc-eQTL. We then discuss the benefits and limitations of sc-eQTL analyses. Finally, we present an overview of the current and future applications of sc-eQTL discoveries.
Toll-like receptors 2, 4, and 9 modulate promoting effect of COPD-like airway inflammation on K-ras-driven lung cancer through activation of the MyD88/NF-ĸB pathway in the airway epithelium
Authors: Velasco Walter V. , Khosravi Nasim , Castro-Pando Susana , Torres-Garza Nelly , Grimaldo Maria T. , Krishna Avantika , Clowers Michael J. , Umer Misha , Tariq Amir Sabah , Del Bosque Diana , Daliri Soudabeh , De La Garza Maria Miguelina , Ramos-Castaneda Marco , Evans Scott E. , Moghaddam Seyed Javad
Published: May 2023

Introduction

Toll-like receptors (TLRs) are an extensive group of proteins involved in host defense processes that express themselves upon the increased production of endogenous damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) due to the constant contact that airway epithelium may have with pathogenic foreign antigens. We have previously shown that COPD-like airway inflammation induced by exposure to an aerosolized lysate of nontypeable Haemophilus influenzae (NTHi) promotes tumorigenesis in a K-ras mutant mouse model of lung cancer, CCSPCre/LSL-K-rasG12D (CC-LR) mouse.

Methods

In the present study, we have dissected the role of TLRs in this process by knocking out TLR2, 4, and 9 and analyzing how these deletions affect the promoting effect of COPD-like airway inflammation on K-ras-driven lung adenocarcinoma.

Results

We found that knockout of TLR 2, 4, or 9 results in a lower tumor burden, reduced angiogenesis, and tumor cell proliferation, accompanied by increased tumor cell apoptosis and reprogramming of the tumor microenvironment to one that is antitumorigenic. Additionally, knocking out of downstream signaling pathways, MyD88/NF-κB in the airway epithelial cells further recapitulated this initial finding.

Discussion

Our study expands the current knowledge of the roles that TLR signaling plays in lung cancer, which we hope, can pave the way for more reliable and efficacious prevention and treatment modalities for lung cancer.
High immunogenicity of virus-like particles (VLPs) decorated with Aeromonas salmonicida VapA antigen in rainbow trout
Authors: Yang Jeong In , Sepúlveda Dagoberto , Vardia Irina , Skov Jakob , Goksøyr Louise , Sander Adam F. , Lorenzen Niels
Published: May 2023

The Gram-negative bacterium A. salmonicida is the causal agent of furunculosis and used to be one of the most loss-causing bacterial infections in the salmonid aquaculture industry with a mortality rate of about 90% until the 1990s, when an inactivated vaccine with mineral oil as adjuvant was successfully implemented to control the disease. However, the use of this vaccine is associated with inflammatory side effects in the peritoneal cavity as well as autoimmune reactions in Atlantic salmon, and incomplete protection has been reported in rainbow trout. We here aimed at developing and testing a recombinant alternative vaccine based on virus-like particles (VLPs) decorated with VapA, the key structural surface protein in the outer A-layer of A. salmonicida. The VLP carrier was based on either the capsid protein of a fish nodavirus, namely red grouper nervous necrotic virus (RGNNV) or the capsid protein of Acinetobacter phage AP205. The VapA and capsid proteins were expressed individually in E. coli and VapA was fused to auto-assembled VLPs using the SpyTag/SpyCatcher technology. Rainbow trout were vaccinated/immunized with the VapA-VLP vaccines by intraperitoneal injection and were challenged with A. salmonicida 7 weeks later. The VLP vaccines provided protection comparable to that of a bacterin-based vaccine and antibody response analysis demonstrated that vaccinated fish mounted a strong VapA-specific antibody response. To our knowledge, this is the first demonstration of the potential use of antigen-decorated VLPs for vaccination against a bacterial disease in salmonids.
Soluble biomarkers to predict clinical outcomes in non-small cell lung cancer treated by immune checkpoints inhibitors
Authors: Ancel Julien , Dormoy Valérian , Raby Béatrice Nawrocki , Dalstein Véronique , Durlach Anne , Dewolf Maxime , Gilles Christine , Polette Myriam , Deslée Gaëtan
Published: May 2023

Lung cancer remains the first cause of cancer-related death despite many therapeutic innovations, including immune checkpoint inhibitors (ICI). ICI are now well used in daily practice at late metastatic stages and locally advanced stages after a chemo-radiation. ICI are also emerging in the peri-operative context. However, all patients do not benefit from ICI and even suffer from additional immune side effects. A current challenge remains to identify patients eligible for ICI and benefiting from these drugs. Currently, the prediction of ICI response is only supported by Programmed death-ligand 1 (PD-L1) tumor expression with perfectible results and limitations inherent to tumor-biopsy specimen analysis. Here, we reviewed alternative markers based on liquid biopsy and focused on the most promising biomarkers to modify clinical practice, including non-tumoral blood cell count such as absolute neutrophil counts, platelet to lymphocyte ratio, neutrophil to lymphocyte ratio, and derived neutrophil to lymphocyte ratio. We also discussed soluble-derived immune checkpoint-related products such as sPD-L1, circulating tumor cells (detection, count, and marker expression), and circulating tumor DNA-related products. Finally, we explored perspectives for liquid biopsies in the immune landscape and discussed how they could be implemented into lung cancer management with a potential biological–driven decision.
Fusion of the molecular adjuvant C3d to cleavage-independent native-like HIV-1 Env trimers improves the elicited antibody response
Authors: Bale Shridhar , Yang Lifei , Alirezaei Mehrdad , Wilson Richard , Ota Takayuki , Doyle Esmeralda D. , Cottrell Christopher A. , Guenaga Javier , Tran Karen , Li Wenjuan , Stamatatos Leonidas , Nemazee David , Ward Andrew B. , Wyatt Richard T.
Published: May 2023

An effective HIV vaccine likely requires the elicitation of neutralizing antibodies (NAbs) against multiple HIV-1 clades. The recently developed cleavage-independent native flexibly linked (NFL) envelope (Env) trimers exhibit well-ordered conformation and elicit autologous tier 2 NAbs in multiple animal models. Here, we investigated whether the fusion of molecular adjuvant C3d to the Env trimers can improve B- cell germinal center (GC) formation and antibody responses. To generate Env-C3d trimers, we performed a glycine-serine- based (G4S) flexible peptide linker screening and identified a linker range that allowed native folding. A 30–60- amino- acid- long linker facilitates Env-to-C3d association and achieves the secretion of well-ordered trimers and the structural integrity and functional integrity of Env and C3d. The fusion of C3d did not dramatically affect the antigenicity of the Env trimers and enhanced the ability of the Env trimers to engage and activate B cells in vitro. In mice, the fusion of C3d enhanced germinal center formation, the magnitude of Env-specific binding antibodies, and the avidity of the antibodies in the presence of an adjuvant. The Sigma Adjuvant System (SAS) did not affect the trimer integrity in vitro but contributed to altered immunogenicity in vivo, resulting in increased tier 1 neutralization, likely by increased exposure of variable region 3 (V3). Taken together, the results indicate that the fusion of the molecular adjuvant, C3d, to the Env trimers improves antibody responses and could be useful for Env-based vaccines against HIV.
Monitoring islet specific immune responses in type 1 diabetes clinical immunotherapy trials
Authors: Arif Sefina , Domingo-Vila Clara , Pollock Emily , Christakou Eleni , Williams Evangelia , Tree Timothy I. M.
Published: May 2023

The number of immunotherapeutic clinical trials in type 1 diabetes currently being conducted is expanding, and thus there is a need for robust immune-monitoring assays which are capable of detecting and characterizing islet specific immune responses in peripheral blood. Islet- specific T cells can serve as biomarkers and as such can guide drug selection, dosing regimens and immunological efficacy. Furthermore, these biomarkers can be utilized in patient stratification which can then benchmark suitability for participation in future clinical trials. This review focusses on the commonly used immune-monitoring techniques including multimer and antigen induced marker assays and the potential to combine these with single cell transcriptional profiling which may provide a greater understanding of the mechanisms underlying immuno-intervention. Although challenges remain around some key areas such as the need for harmonizing assays, technological advances mean that multiparametric information derived from a single sample can be used in coordinated efforts to harmonize biomarker discovery and validation. Moreover, the technologies discussed here have the potential to provide a unique insight on the effect of therapies on key players in the pathogenesis of T1D that cannot be obtained using antigen agnostic approaches.
Transcriptome and network analyses reveal key pathways and genes involved in response to carotenoid deposition in scallop muscle
Authors: Li Tingting , Zhang Yihan , Liu Shiqi , Li Moli , Yao Ruixing , Niu Senyu , Yuan Jingyao , Wang Huizhen , Hu Jingjie , Bao Zhenmin , Hu Xiaoli
Published: May 2023

Carotenoids are essential nutrients for humans and animals, and carotenoid content has become an important trait to evaluate the nutritional value of many cultured animals. Marine animals provide humans with diverse carotenoids, and developing carotenoid-enriched varieties has been the focus of marine animal breeding. Understanding the molecular mechanism of carotenoid deposition could benefit marine animal breeding for carotenoid content improvement. In the present study, transcriptomic analysis of adductor muscle was performed between Yesso scallop (Patinopecten yessoensis) with white muscle (WM) and carotenoid-enriched orange muscle (OM). A total of 683 differentially expressed genes (DEGs) were identified, with 302 and 381 genes being up- and down-regulated in OM scallop. Gene co-expression network analysis identified four carotenoid accumulation−related modules, including three up-regulated modules and one down-regulated module. The genes in up-regulated modules mainly participate in the pathways of translation and transcription (MEgreen), immune system (MElightyellow), and lipid metabolism (MEpink), while the down-regulated module is mainly enriched with genes involved in various metabolic pathways (MEturquoise). As the causal gene responsible for muscle coloration in scallop, PyBCO-like 1 is the hub gene of MEturquoise and showed strong connectivity with NR2F1A, a transcriptional factor involved in the regulation of retinoic acid. In addition, the up-regulated DEGs, including WDR3, RPP29, TBL3, RIOK2, and NOB1 from “ribosome biogenesis”, HSP70s and HSP702Bs from “antigen processing and presentation”, and ACOX1 from “PPAR signaling pathway” were identified as hub genes, indicating the potential regulatory role of these genes and pathways in response to carotenoid accumulation. Our data contribute to a deeper understanding of the regulatory and response mechanisms of carotenoid accumulation in marine animals.
The effect of an information intervention on the career commitment of medical students: evidence from a randomized experiment
Authors: Li Chunqing , Ye Xiaoyang , Yu Chen , Wu Hongbin
Published: May 2023

Introduction

The needs-based shortage of healthcare workers is severe worldwide and it would be exacerbated if many medical students switch to other careers after graduation. Maintaining and improving the career commitment of medical students, which could be a feasible, effective, and scalable way to reduce the attrition rate, is essential in medical education. We designed a randomized experiment to test whether an information intervention based on role modeling could enhance medical students’ career commitment.

Methods

In the randomized experiment, the sample (N = 36,482) was divided into the treatment group (N = 18,070) and the control group (N = 18,412). The intervention information consisted of image-text messages on Zhong Nanshan, who is an inspiring role model for he went to the frontline of COVID-19 in the most critical circumstances and received praise and affirmation from the public. Α difference-in-differences model was employed to identify the effect of the information intervention. Heterogeneous treatment effects were identified using sub-sample analyses.

Results

The results showed that the information intervention statistically significantly reduced medical students’ dropout intention by 2.7 percentage points (95% CI: −0.037 to −0.016, t = −4.95, p < 0.001), equivalent to 14.6% of the control group mean. This estimate indicates that the information intervention could significantly increase the career commitment of medical students. Finally, male and senior students were influenced more than their female and junior counterparts, which can be explained by their relatively high dropout intention.

Conclusion

Role model-based information intervention improves the career commitment of medical students. The underlying behavioral model is that, when students use a role model as their reference point, they consider dropout as a substantial welfare loss. Role modeling is an effective way to improve the career commitment of medical students, especially for males and senior students.
Efficacy and safety of single-dose ivermectin in mild-to-moderate COVID-19: the double-blind, randomized, placebo-controlled CORVETTE-01 trial
Authors: Wada Tatsuhiko , Hibino Makoto , Aono Hiromi , Kyoda Shunsuke , Iwadate Yosuke , Shishido Eri , Ikeda Keisuke , Kinoshita Nana , Matsuda Yasuki , Otani Sakiko , Kameda Ryo , Matoba Kenta , Nonaka Miwa , Maeda Mika , Kumagai Yuji , Ako Junya , Shichiri Masayoshi , Naoki Katsuhiko , Katagiri Masato , Takaso Masashi , Iwamura Masatsugu , Katayama Kazuhiko , Miyatsuka Takeshi , Orihashi Yasushi , Yamaoka Kunihiro ,   for the CORVETTE-01 Study Group
Published: May 2023

Background

To investigate whether ivermectin inhibits SARS-CoV-2 proliferation in patients with mild-to-moderate COVID-19 using time to a negative COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) test.

Methods

CORVETTE-01 was a double-blind, randomized, placebo-controlled study (August 2020–October 2021) conducted in Japan. Overall, 248 patients diagnosed with COVID-19 using RT-PCR were assessed for eligibility. A single oral dose of ivermectin (200  μg/kg) or placebo was administered under fasting. The primary outcome was time to a negative COVID-19 RT-PCR test result for SARS-CoV-2 nucleic acid, assessed using stratified log-rank test and Cox regression models.

Results

Overall, 112 and 109 patients were randomized to ivermectin and placebo, respectively; 106 patients from each group were included in the full analysis set (male [%], mean age: 68.9%, 47.9 years [ivermectin]; 62.3%, 47.5 years [placebo]). No significant difference was observed in the occurrence of negative RT-PCR tests between the groups (hazard ratio, 0.96; 95% confidence interval [CI] 0.70–1.32; p = 0.785). Median (95% CI) time to a negative RT-PCR test was 14.0 (13.0–16.0) and 14.0 (12.0–16.0) days for ivermectin and placebo, respectively; 82.1% and 84% of patients achieved negative RT-PCR tests, respectively.

Conclusion

In patients with COVID-19, single-dose ivermectin was ineffective in decreasing the time to a negative RT-PCR test.

Clinical Trial Registration

ClinicalTrials.gov, NCT04703205.