bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of contact correction on the state of accommodation in patients with keratoconus
Authors: Averich V. V. , Abugova T. D. , Aslamazova A. E.
Published: July 2023

Introduction. Keratoconus (KC) is a disease belonging to the group of primary keratectasias, characterized by pronounced irregularity of corneal topography and accompanied by irregular astigmatism, myopic refraction and higher order aberrations. It is established that accommodation in cases of ametropia is strongly influenced by the wave front of eye, but the influence of aberrations on ciliary muscle work in KC remains unstudied. The aim was to study the correlation of accommodation in KC with the ectasia-induced aberrations before and after optical correction with scleral rigid contact lenses (SRCL).

Materials and methods. Thirty people (60 eyes) with newly diagnosed bilateral KC, were included in the study: 26 eyes – stage I, 29 eyes – stage II, 5 eyes – stage III. Mean age of the patients was 26,2 ± 4,3 years. The clinical recruitment period was from January to September 2022. All patients were additionally evaluated for keratometric and aberration parameters of the cornea using a Scheimpflug camera besides a standard ophthalmological examination. Objective evaluation of accommodation was performed on the Righton Speedy-I device with determination of qualitative and quantitative indices. All investigations were performed before and after one month of wearing individual SRCL.

Results. According to the data of objective accomodography a state of spasmodic accommodation asthenopia was observed in 71% of cases before started wearing pressure lenses. There was a tendency to improvement of ciliary muscle function and a “stepped” course of the accommodative curve while wearing SRCL a month later. High values of corneal aberrations decreased by 4.5 times in the course of SRCL. Correlation analysis revealed a significant trend between the state of accommodation and the corneal wavefront.

Conclusion. Objective examination of the accommodation state in KC proves the signs presence of accommodative asthenopia mediated by irregular astigmatism. The revealed correlations between the indices of induced KC aberrations and accommodation state confirm the fact of ectasia negative influence on ciliary muscle work. It was proved that optical correction with SRCL in KC reduces corneal aberrations and significantly improves the state of accommodation.
Investigating the Causal Relationship between Renewable Energy Consumption and Life Expectancy in Turkey: A Toda-Yamamoto Causality Test
Authors: YILMAZ Ekrem , ŞENSOY Fatma
Published: July 2023

This study examines the causal relationship between renewable energy consumption and life expectancy in Turkiye using the Toda-Yamamoto causality test. By analyzing data from 1990 to 2019, the study explores the relationship between these variables. The results of the Toda-Yamamoto causality test indicate that there is no Granger causality relationship from renewable energy consumption to life expectancy, indicating that renewable energy consumption does not have a significant impact on life expectancy in Turkiye. However, the study found a Granger causality relationship from life expectancy to renewable energy consumption, suggesting that improving life expectancy could lead to an increase in renewable energy consumption in Turkiye. This study is significant as it provides insights into the relationship between renewable energy consumption and life expectancy in Turkiye. The results highlight the importance of considering factors other than renewable energy consumption when examining public health outcomes. The study's findings can inform policymakers in developing energy policies that prioritize public health outcomes and promote sustainable energy practices.
Survey of farm management and biosecurity practices on shrimp farms on Java Island, Indonesia
Authors: Patanasatienkul Thitiwan , Gautam Milan , Hammell K. Larry , Gilang Dimas , Delphino Marina K. V. C. , Burnley Holly , Salsabila Nikmatun Aliyah , Thakur Krishna K.
Published: July 2023

Current information on biosecurity measures implemented by shrimp farmers in Indonesia is limited. This study describes farmer demographic characteristics, on-farm biosecurity practices, farm production and disease status, among small and medium holder shrimp farms on Java Island, Indonesia. A questionnaire-based survey was conducted from November 2019 to May 2020 to collect data from shrimp farms operating in various regions of the Java Island. A numerical score was assigned for each of the assessed biosecurity practices, based on whether it was a conventional risk factor or a protective factor. Based on responses from 90 shrimp farmers, who volunteered to participate in the study, mean overall biosecurity scores ranged from 32 to 54 (out of a maximum score of 100). Most farms (88.9%) either shared common water sources with other aquaculture farms or were connected to other farms via water channel. Farm equipment sharing was common both within (91.1%) and between (41%) farms. Water pre-treatment was common (99%), but approximately a third of the farms did not practice any routine quality assessment for post larvae before stocking. On average, farms produced 1.6 kg/m2 (95% CI: 1.2, 2.0) of shrimp with a harvest size of 43 shrimp/kg (95% CI: 37, 49) or an average weight of 23.3 g at time of harvest. An increasing trend in harvest weight per pond area and shrimp size at harvest was noted with increasing overall biosecurity score. These results indicated that farms with better biosecurity practices tended to have a higher production yield.
The influence of early environment and micronutrient availability on developmental epigenetic programming: lessons from the placenta
Authors: Sainty Rebecca , Silver Matt J. , Prentice Andrew M. , Monk David
Published: July 2023

DNA methylation is the most commonly studied epigenetic mark in humans, as it is well recognised as a stable, heritable mark that can affect genome function and influence gene expression. Somatic DNA methylation patterns that can persist throughout life are established shortly after fertilisation when the majority of epigenetic marks, including DNA methylation, are erased from the pre-implantation embryo. Therefore, the period around conception is potentially critical for influencing DNA methylation, including methylation at imprinted alleles and metastable epialleles (MEs), loci where methylation varies between individuals but is correlated across tissues. Exposures before and during conception can affect pregnancy outcomes and health throughout life. Retrospective studies of the survivors of famines, such as those exposed to the Dutch Hunger Winter of 1944-45, have linked exposures around conception to later disease outcomes, some of which correlate with DNA methylation changes at certain genes. Animal models have shown more directly that DNA methylation can be affected by dietary supplements that act as cofactors in one-carbon metabolism, and in humans, methylation at birth has been associated with peri-conceptional micronutrient supplementation. However, directly showing a role of micronutrients in shaping the epigenome has proven difficult. Recently, the placenta, a tissue with a unique hypomethylated methylome, has been shown to possess great inter-individual variability, which we highlight as a promising target tissue for studying MEs and mixed environmental exposures. The placenta has a critical role shaping the health of the fetus. Placenta-associated pregnancy complications, such as preeclampsia and intrauterine growth restriction, are all associated with aberrant patterns of DNA methylation and expression which are only now being linked to disease risk later in life.
Nanoplasmonic biosensors for precision medicine
Authors: Xiao Yiran , Zhang Zongming , Yin Shi , Ma Xingyi
Published: July 2023

Nanoplasmonic biosensors have a huge boost for precision medicine, which allows doctors to better understand diseases at the molecular level and to improve the earlier diagnosis and develop treatment programs. Unlike traditional biosensors, nanoplasmonic biosensors meet the global health industry’s need for low-cost, rapid and portable aspects, while offering multiplexing, high sensitivity and real-time detection. In this review, we describe the common detection schemes used based on localized plasmon resonance (LSPR) and highlight three sensing classes based on LSPR. Then, we present the recent applications of nanoplasmonic in other sensing methods such as isothermal amplification, CRISPR/Cas systems, lab on a chip and enzyme-linked immunosorbent assay. The advantages of nanoplasmonic-based integrated sensing for multiple methods are discussed. Finally, we review the current applications of nanoplasmonic biosensors in precision medicine, such as DNA mutation, vaccine evaluation and drug delivery. The obstacles faced by nanoplasmonic biosensors and the current countermeasures are discussed.
Deep sea nature-based solutions to climate change
Authors: Hilmi Nathalie , Sutherland Michael , Farahmand Shekoofeh , Haraldsson Gunnar , van Doorn Erik , Ernst Ekkehard , Wisz Mary S. , Claudel Rusin Astrid , Elsler Laura G. , Levin Lisa A.
Published: July 2023

The deep sea (below 200 m depth) is the largest carbon sink on Earth. It hosts abundant biodiversity that underpins the carbon cycle and provides provisioning, supporting, regulating and cultural ecosystem services. There is growing attention to climate-regulating ocean ecosystem services from the scientific, business and political sectors. In this essay we synthesize the unique biophysical, socioeconomic and governance characteristics of the deep sea to critically assess opportunities for deep-sea blue carbon to mitigate climate change. Deep-sea blue carbon consists of carbon fluxes and storage including carbon transferred from the atmosphere by the inorganic and organic carbon pumps to deep water, carbon sequestered in the skeletons and bodies of deep-sea organisms, carbon buried within sediments or captured in carbonate rock. However, mitigating climate change through deep-sea blue carbon enhancement suffers from lack of scientific knowledge and verification, technological limitations, potential environmental impacts, a lack of cooperation and collaboration, and underdeveloped governance. Together, these issues suggest that deep-sea climate change mitigation is limited. Thus, we suggest that a strong focus on blue carbon is too limited a framework for managing the deep sea to contribute to international goals, including the Sustainable Development Goals (SDGs), the Paris Agreement and the post-2020 Biodiversity Goals. Instead, the deep sea can be viewed as a more holistic nature-based solution, including many ecosystem services and biodiversity in addition to climate. Environmental impact assessments (EIAs), area-based management, pollution reduction, moratoria, carbon accounting and fisheries management are tools in international treaties that could help realize benefits from deep-sea, nature-based solutions.
How convincing are AI-generated moral arguments for climate action?
Authors: Nisbett Nicole , Spaiser Viktoria
Published: July 2023

Mobilizing broad support for climate action is paramount for solving the climate crisis. Research suggests that people can be persuaded to support climate action when presented with certain moral arguments, but which moral arguments are most convincing across the population? With this pilot study, we aim to understand which types of moral arguments based on an extended Moral Foundation Theory are most effective at convincing people to support climate action. Additionally, we explore to what extent Generative Pre-trained Transformer 3 (GPT-3) models can be employed to generate bespoke moral statements. We find statements appealing to compassion, fairness and good ancestors are the most convincing to participants across the population, including to participants, who identify as politically right-leaning and who otherwise respond least to moral arguments. Negative statements appear to be more convincing than positive ones. Statements appealing to other moral foundations can be convincing, but only to specific social groups. GPT-3-generated statements are generally more convincing than human-generated statements, but the large language model struggles with creating novel arguments.
Communicating carbon removal
Authors: Bellamy Rob , Raimi Kaitlin T.
Published: July 2023

Removing carbon dioxide from the atmosphere is “unavoidable” if net zero emissions are to be achieved, and is fast rising up the climate policy agenda. Research, development, demonstration, and deployment of various methods has begun, but technical advances alone will not guarantee a role for them in tackling climate change. For those engrossed in carbon removal debates, it is easy to forget that most people have never heard of these strategies. Public perception of carbon removal is therefore particularly sensitive to framings—the ways in which scientists, entrepreneurs, activists, politicians, the media, and others choose to organize and communicate it. In this perspective, we highlight four aspects of carbon removal for which their framing will play a decisive role in whether—and how—different methods are taken forward. First, the use of analogies can be helpful in guiding mental models, but can also inadvertently imply processes or outcomes that do not apply in the new example. Second, a taxonomic split between “nature-based” and “technological” methods threatens to divert attention from the actual qualities of different methods and constrain our policy options. Third, people are likely to overestimate the emissions-reduction potential of carbon removal, but this misperception can be corrected. Fourth, communications overlook the social arrangements for carbon removal and the alternative trajectories that implementation may take. We end by offering key recommendations for how we can communicate carbon removal more responsibly.
Successful clusters through successful communication: why clusters should be managed by Place Leaders
Authors: Ganske Patricia , Carbon Claus-Christian
Published: July 2023

Communication is critical in a wide variety of fields. Successful intra-organizational communication plays a significant role in building trust by creating an environment that empowers leaders to lead effectively, motivates employees to work, and thus contributes to organizational performance. In the context of cluster management, communication within the cluster, especially between the cluster leadership and the often vast number of cluster members, plays a pivotal role in successful and effective cluster development. A cluster typically operates in a regional context characterized by multi-agent, multi-objective, multi-vision, and pluralistic processes, methods, competencies, expertise, and aims. Cluster leadership is usually associated with particular difficulties in addressing these challenges. The primary needs and demands to fulfill such a role are to bring together a large number of partly competing actors involved in a cluster, to build up a trustful and open network, to include different cultures, and to harmonize institutional agendas. The main aim is to develop and establish a common ground to communicate and coordinate joint work efforts, which can mutually benefit and create synergies. The present article conceptualizes Effective internal Cluster Communication and Place Leadership as determinants for successful cluster developments. Despite the multiplicity of actors and sometimes even competing interest groups, Effective Place Leader Cluster Communication (EPLCC) enables clusters to inspire common, cooperative, collaborative and synergetic ways of working together. This is key to cluster development, successful and goal-directed cluster operation, and a sustainable operation of the cluster.
Markerless human pose estimation for biomedical applications: a survey
Authors: Avogaro Andrea , Cunico Federico , Rosenhahn Bodo , Setti Francesco
Published: July 2023

Markerless Human Pose Estimation (HPE) proved its potential to support decision making and assessment in many fields of application. HPE is often preferred to traditional marker-based Motion Capture systems due to the ease of setup, portability, and affordable cost of the technology. However, the exploitation of HPE in biomedical applications is still under investigation. This review aims to provide an overview of current biomedical applications of HPE. In this paper, we examine the main features of HPE approaches and discuss whether or not those features are of interest to biomedical applications. We also identify those areas where HPE is already in use and present peculiarities and trends followed by researchers and practitioners. We include here 25 approaches to HPE and more than 40 studies of HPE applied to motor development assessment, neuromuscolar rehabilitation, and gait & posture analysis. We conclude that markerless HPE offers great potential for extending diagnosis and rehabilitation outside hospitals and clinics, toward the paradigm of remote medical care.
Alarm reduction and root cause inference based on association mining in communication network
Authors: Li Min , Yang Mengyuan , Chen Pengfei
Published: July 2023

With the growing demand for data computation and communication, the size and complexity of communication networks have grown significantly. However, due to hardware and software problems, in a large-scale communication network (e.g., telecommunication network), the daily alarm events are massive, e.g., millions of alarms occur in a serious failure, which contains crucial information such as the time, content, and device of exceptions. With the expansion of the communication network, the number of components and their interactions become more complex, leading to numerous alarm events and complex alarm propagation. Moreover, these alarm events are redundant and consume much effort to resolve. To reduce alarms and pinpoint root causes from them, we propose a data-driven and unsupervised alarm analysis framework, which can effectively compress massive alarm events and improve the efficiency of root cause localization. In our framework, an offline learning procedure obtains results of association reduction based on a period of historical alarms. Then, an online analysis procedure matches and compresses real-time alarms and generates root cause groups. The evaluation is based on real communication network alarms from telecom operators, and the results show that our method can associate and reduce communication network alarms with an accuracy of more than 91%, reducing more than 62% of redundant alarms. In addition, we validate it on fault data coming from a microservices system, and it achieves an accuracy of 95% in root cause location. Compared with existing methods, the proposed method is more suitable for operation and maintenance analysis in communication networks.
Case report: Repeat coronary function testing in women with ischemia and no obstructive coronary artery disease
Authors: Suppogu Nissi , Tjoe Benita , Wei Janet , Maughan Jenna , Joung Sandy , Quesada Odayme , Shufelt Chrisandra L. , Samuels Bruce , Azarbal Babak , Bairey Merz C. Noel
Published: July 2023

Women with signs and symptoms of ischemia and no obstructive coronary artery disease (INOCA) often have coronary microvascular dysfunction (CMD). It can be diagnosed by coronary function testing (CFT), which is an invasive coronary angiogram procedure. Frequently, these women have persistent angina despite medical therapy, but it is not clear whether it is due to worsening or persistent CMD or inadequate therapy. In this brief report, we describe findings of repeat CFT in a case series of 12 women undergoing repeat CFT for the assessment of persistent angina in order to better understand the evolving pathology.
Human planting strategies and its relation to climate change during ∼4,800–3,900 BP in the mid-lower Hulu River Valley, northwest China
Authors: Wei Wenyu , Ma Minmin , Chen Guoke , Dong Jiajia , Wu Zekun , Li Haiming , Li Xiaobin
Published: July 2023

The response of agricultural societies to global climate events during the Neolithic (e.g., 4.2 ka event) is a scientific issue of general interest. In the mid-lower Hulu River Valley of northwest China, millet cultivation became the primary subsistence during the late Neolithic. Local paleoclimate studies have detected a notable decline in temperature and precipitation around 4,400 BP (Before Present), while the Qijia culture (4,200–3,600 BP) sites far outnumber those of the Lower Changshan culture (4,800–4,400 BP) in the area. Why the intensity of millet farming groups increased when climate was relatively cold and dry, however, has not been well understood. To explore the issue, we performed archaeobotanical analysis, grain size measurement, stable isotope analysis and radiocarbon dating in the excavated sites of the Zhongtianxingfucheng (ZTXFC) and Wangjiayangwan (WJYW), which were dated to between ∼4,800–4,400 BP and ∼4,200–3,900 BP, respectively. Our results demonstrate the overall declines in the proportion, grain sizes and carbon isotope values of millets from the WJYW site compared to ZTXFC. The nitrogen isotopes of millets from the two sites are similar [foxtail millet: 6.8‰ ± 1.9‰ (ZTXFC), 7.5‰ ± 1.5‰ (WJYW); broomcorn millet: 7.3‰ ± 2.0‰ (ZTXFC), 7.5‰ ± 1.2‰ (WJYW)]. These results suggest that the degree of field management during ∼4,200–3,900 BP was lower than ∼4,800–4,400 BP in the mid-lower Hulu River Valley. Instead of improving cultivation management or altering cropping patterns, Qijia millet farmers might have adopted a strategy of expanding cultivated lands to promote the social development under a relatively cold-dry climate.
Metabolite-sensing GPCRs controlling interactions between adipose tissue and inflammation
Authors: Duncan Elaine M. , Vita Luca , Dibnah Bethany , Hudson Brian D.
Published: July 2023

Metabolic disorders including obesity, diabetes and non-alcoholic steatohepatitis are a group of conditions characterised by chronic low-grade inflammation of metabolic tissues. There is now a growing appreciation that various metabolites released from adipose tissue serve as key signalling mediators, influencing this interaction with inflammation. G protein-coupled receptors (GPCRs) are the largest family of signal transduction proteins and most historically successful drug targets. The signalling pathways for several key adipose metabolites are mediated through GPCRs expressed both on the adipocytes themselves and on infiltrating macrophages. These include three main groups of GPCRs: the FFA4 receptor, which is activated by long chain free fatty acids; the HCA2 and HCA3 receptors, activated by hydroxy carboxylic acids; and the succinate receptor. Understanding the roles these metabolites and their receptors play in metabolic-immune interactions is critical to establishing how these GPCRs may be exploited for the treatment of metabolic disorders.
Preferences and adoption of improved cookstove from results-based financing program in Southeastern Ethiopia
Authors: Belachew Azmera , Melka Yoseph
Published: July 2023

Environment-friendly energy practices are essential for a sustainable and quality environment in most developing countries, like Ethiopia. To achieve this, results-based financing (RBF) was implemented to distribute improved cookstove with a demand and supply side management system. However, the success of RBF is not evaluated regarding households’ preferences and adoption of the stove. This study was conducted to evaluate households’ preference and adoption of improved Tikikil stove in the RBF implementation areas. Data were collected from 191 households using a household survey and 10 focus group discussions. The data were analyzed using descriptive statistics and a binary logit regression model using STATA 16 software. The result revealed that the cost of stove, stove holding, construction material, cooking time reduction, and smoke reduction were the top five attributes ranked by user households. The dissatisfied households have complained about durability, wood inlet size, stove cost, and suitability of pot size. Results also indicated that the success of RBF program showed moderately effective. The regression result revealed that education, family size, landholding size, livestock holding, fuel expenditure, awareness, and separate kitchen were significantly and positively associated while distance to nearest town is significantly and negatively related to the adoption of Tikikil stove. The findings suggest that households need Tikikil stove options to reduce the negative effect of traditional stoves but currently available stoves lack to address the preferences of the households. In addition, different socio-economic characteristics of households and stove attributes are important factors that need to consider for the wider adoption of ICS to meet the current demand of carbon credit by reducing emissions from traditional stove.
Genetically predicted ankylosing spondylitis is causally associated with psoriasis
Authors: Tian Di , Zhou Yuan , Chen Yuting , Wu Ye , Wang Heng , Jie Chunchun , Yang Yan , Liu Yaoyao , Wang Haoyu , Zhou Dian
Published: July 2023

Background

Previous observational studies have reported the striking association between ankylosing spondylitis (AS) and psoriasis, but the causal relationship between the two diseases remains unclear.

Methods

Two-sample Mendelian randomization (MR) analysis with methods of inverse-variance weighted, MR-Egger regression, weighted median, and weighted mode was conducted to evaluate the bidirectional causal associations between AS and psoriasis. Effective single-nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS) were selected as instrumental variables (IVs). Sensitivity analyses were also applied to verify whether heterogeneity and pleiotropy can bias the results.

Result

We found positive causal effects of genetically increased AS risk on psoriasis (IVW: OR = 1.009, 95% CI = 1.005–1.012, p = 8.07E-07). Comparable outcomes were acquired by MR-Egger regression, weighted median, and weighted mode approaches. Nevertheless, we did not find significant causal effects of psoriasis on AS (IVW: OR = 1.183, 95% CI = 0.137–10.199, p = 0.879). The sensitivity analyses showed that the horizontal pleiotropy was unlikely to skew the causality. The leave-one-out analysis demonstrated that no single SNP can drive the MR estimates. No evidence of heterogeneity was found between the selected IVs.

Conclusion

Our findings provide evidence that AS has positive causal effects on the risk of psoriasis in the European population.
Sirtuin family in autoimmune diseases
Authors: Tao Zhengjie , Jin Zihan , Wu Jiabiao , Cai Gaojun , Yu Xiaolong
Published: July 2023

In recent years, epigenetic modifications have been widely researched. As humans age, environmental and genetic factors may drive inflammation and immune responses by influencing the epigenome, which can lead to abnormal autoimmune responses in the body. Currently, an increasing number of studies have emphasized the important role of epigenetic modification in the progression of autoimmune diseases. Sirtuins (SIRTs) are class III nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases and SIRT-mediated deacetylation is an important epigenetic alteration. The SIRT family comprises seven protein members (namely, SIRT1–7). While the catalytic core domain contains amino acid residues that have remained stable throughout the entire evolutionary process, the N- and C-terminal regions are structurally divergent and contribute to differences in subcellular localization, enzymatic activity and substrate specificity. SIRT1 and SIRT2 are localized in the nucleus and cytoplasm. SIRT3, SIRT4, and SIRT5 are mitochondrial, and SIRT6 and SIRT7 are predominantly found in the nucleus. SIRTs are key regulators of various physiological processes such as cellular differentiation, apoptosis, metabolism, ageing, immune response, oxidative stress, and mitochondrial function. We discuss the association between SIRTs and common autoimmune diseases to facilitate the development of more effective therapeutic strategies.
E protein binding at the Tcra enhancer promotes Tcra repertoire diversity
Authors: Mihai Ariana , Roy Sumedha , Krangel Michael S. , Zhuang Yuan
Published: July 2023

V(D)J recombination of antigen receptor loci is a highly developmentally regulated process. During T lymphocyte development, recombination of the Tcra gene occurs in CD4+CD8+ double positive (DP) thymocytes and requires the Tcra enhancer (Eα). E proteins are known regulators of DP thymocyte development and have three identified binding sites in Eα. To understand the contribution of E proteins to Eα function, mutants lacking one or two of the respective binding sites were generated. The double-binding site mutant displayed a partial block at the positive selection stage of αβ T cell development. Further investigation revealed loss of germline transcription within the Tcra locus at the Jα array, along with dysregulated primary and impaired secondary Vα-Jα rearrangement. Eα E protein binding increases Tcra locus accessibility and regulates TCRα recombination, thus directly promoting Tcra repertoire diversity.
A new method for oral cancer biomarkers detection with a non-invasive cyto-salivary sampling and rapid-highly sensitive ELISA immunoassay: a pilot study in humans
Authors: Rebaudi Federico , De Rosa Alfredo , Greppi Marco , Pistilli Roberto , Pucci Resi , Govoni Flavio Andrea , Iacoviello Paolo , Broccolo Francesco , Tomasello Giuseppe , Pesce Silvia , Laganà Francesco , Bianchi Bernardo , Di Gaudio Francesca , Rebaudi Alberto , Marcenaro Emanuela
Published: July 2023

Introduction

Oral squamous cell carcinoma (OSCC) accounts for approximately 90% of oral malignancies and has a 5-year mortality rate close to 50%. A consistent part (70%) of all oral cancers is diagnosed at an advanced stage since available screening techniques are ineffective. Therefore, it would be urgent to improve them. The diagnostic gold standard is tissue biopsy with histological and immunohistochemical assessment. This method presents some limitations. Biopsy is invasive and the histopathological evaluation is semi-quantitative, and the absolute abundance of the target cannot be reliably determined. In addition, tissue is highly processed and may lead to loss of information of the natural state. The search for classical and new clinical biomarkers on fragments of tissue/cells collected with a cytobrush is a highly hopeful technique for early detection and diagnosis of OSCC, because of its non-invasive sampling and easy collection method.

Methods

Here we analyzed cytobrush biopsies samples collected from the oral cavity of 15 patients with already diagnosed OSCC by applying an innovative high-sensitivity ELISA technique, in order to verify if this approach may provide useful information for detection, diagnosis, and prognosis of OSCC. To this end, we selected six biomarkers, already used in clinical practice for the diagnosis of OSCC (EGFR, Ki67, p53) or selected based on recent scientific and clinical data which indicate their presence or over-expression in cells undergoing transformation and their role as possible molecular targets in immunecheckpoints blockade therapies (PD-L1, HLA-E, B7-H6).

Results

The selected tumor biomarkers were highly expressed in the tumor core, while were virtually negative in healthy tissue collected from the same patients. These differences were highly statistically significant and consistent with those obtained using the gold standard test clearly indicating that the proposed approach, i.e. analysis of biomarkers by a custom ELISA technique, is strongly reliable.

Discussion

These preliminary data suggest that this non-invasive rapid phenotyping technique could be useful as a screening tool for phenotyping oral lesions and support clinical practice by precise indications on the characteristics of the lesion, also with a view to the application of new anti-tumor treatments, such as immunotherapy, aimed at OSCC patients.
Engineering cytokines for cancer immunotherapy: a systematic review
Authors: Fu Yong , Tang Renhong , Zhao Xiaofeng
Published: July 2023

Cytokines are pivotal mediators of cell communication in the tumor microenvironment. Multiple cytokines are involved in the host antitumor response, but the production and function of these cytokines are usually dysregulated during malignant tumor progression. Considering their clinical potential and the early successful use of cytokines in cancer immunotherapy, such as interferon alpha-2b (IFNα-2b; IntronA®) and IL-2 (Proleukin®), cytokine-based therapeutics have been extensively evaluated in many follow-up clinical trials. Following these initial breakthroughs, however, clinical translation of these natural messenger molecules has been greatly limited owing to their high-degree pleiotropic features and complex biological properties in many cell types. These characteristics, coupled with poor pharmacokinetics (a short half-life), have hampered the delivery of cytokines via systemic administration, particularly because of severe dose-limiting toxicities. New engineering approaches have been developed to widen the therapeutic window, prolong pharmacokinetic effects, enhance tumor targeting and reduce adverse effects, thereby improving therapeutic efficacy. In this review, we focus on the recent progress and competitive landscape in cytokine engineering strategies and preclinical/clinical therapeutics for cancer. In addition, aiming to promote engineered cytokine-based cancer immunotherapy, we present a profound discussion about the feasibility of recently developed methods in clinical medicine translation.
Efficacy and safety of innate and adaptive immunotherapy combined with standard of care in high-grade gliomas: a systematic review and meta-analysis
Authors: Guo Baofeng , Zhang Shengnan , Xu Libo , Sun Jicheng , Chan Wai-Lun , Zheng Pengfei , Zhang Jinnan , Zhang Ling
Published: July 2023

Background

Malignant glioma is the most common intracranial malignant tumor with the highest mortality. In the era of immunotherapy, it is important to determine what type of immunotherapy provides the best chance of survival.

Method

Here, the efficacy and safety of immunotherapy in high-grade glioma (HGG) were evaluated by systematic review and meta-analysis. The differences between various types of immunotherapy were explored. Retrieved hits were screened for inclusion in 2,317 articles. We extracted the overall survival (OS) and progression-free survival (PFS) hazard ratios (HRs) as two key outcomes for examining the efficacy of immunotherapy. We also analyzed data on the reported corresponding adverse events to assess the safety of immunotherapy. This study was registered with PROSPERO (CRD42019112356).

Results

We included a total of 1,271 patients, of which 524 received a combination of immunotherapy and standard of care (SOC), while 747 received SOC alone. We found that immunotherapy extended the OS (HR = 0.74; 95% confidence interval [CI], 0.56−0.99; Z = −2.00, P = 0.0458 < 0.05) and PFS (HR = 0.67; 95% CI, 0.45−0.99; Z = −1.99, P = 0.0466 < 0.05), although certain adverse events occurred (proportion = 0.0773, 95% CI, 0.0589-0.1014). Our data have demonstrated the efficacy of the dendritic cell (DC) vaccine in prolonging the OS (HR = 0.38; 95% CI, 0.21−0.68; Z = −3.23; P = 0.0012 < 0.05) of glioma patients. Oncolytic viral therapy (VT) only extended patient survival in a subgroup analysis (HR = 0.60; 95% CI, 0.45−0.80; Z = −3.53; P = 0.0004 < 0.05). By contrast, immunopotentiation (IP) did not prolong OS (HR = 0.69; 95% CI, 0.50−0.96; Z = −2.23; P = 0.0256).

Conclusion

Thus, DC vaccination significantly prolonged the OS of HGG patients, however, the efficacy of VT and IP should be explored in further studies. All the therapeutic schemes evaluated were associated with certain side effects.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=112356.
Synchronous spawning of nursery-raised elkhorn coral (Acropora palmata) outplanted to reefs in the Florida Keys (United States)
Authors: Williams Dana E. , Bright Allan J. , Williamson Olivia M. , Moura Amelia , Ladd Mark C.
Published: July 2023

Here, we provide the first reports of spawning activity by Acropora palmata colonies outplanted to reefs in Florida, USA. In 2020, we observed light spawning from A. palmata colonies five years after they had been outplanted on two Florida reefs. In 2021 and 2022, we observed outplanted A. palmata colonies spawning synchronously with other nearby (<3 m) outplants and wild colonies more than 100 m away. During the 2022 spawning event, some colonies spawned in as few as four years after they had been outplanted. Among all spawning seasons, gametes collected from the outplanted colonies yielded high fertilization rates and viable larvae. These observations are promising for A. palmata restoration as they indicate fragments of A. palmata can spawn four years after outplanting and that efforts to restore A. palmata may be close to achieving the first step towards self-sustaining populations that can produce viable larvae, resulting in an increase in the population’s genotypic diversity upon successful recruitment to the reef.
Offshore wind project-level monitoring in the Northeast U.S. continental shelf ecosystem: evaluating the potential to mitigate impacts to long-term scientific surveys
Authors: Methratta Elizabeth T. , Lipsky Andrew , Boucher Jason M.
Published: July 2023

Offshore wind will generate much needed renewable energy in the U.S. and worldwide, but this industry will also affect other ocean uses. In the Northeast U.S. continental shelf (NES) ecosystem, these effects include the impact that wind development will have on the design and execution of long running scientific surveys conducted by National Marine Fisheries Service of the National Oceanic and Atmospheric Administration (NOAA Fisheries) which play a critical role in the provision of scientific information for stock assessment and advice for fisheries management. Recognizing these impacts, the federal government has established a Survey Mitigation Strategy that identifies a need to evaluate whether the information yielded from project-level monitoring studies conducted by wind developers might be suitable for integration with data from NOAA Fisheries surveys, thereby ameliorating the impacts to the surveys. To address this need, we compiled and tabulated information from all currently available project-level monitoring studies and compared elements of the design and methodology of each study with that of the comparable NOAA Fisheries survey. Based on this information, we evaluated their suitability for filling expected gaps in long term surveys, for addressing impacts at the population level, and for understanding interactions between fish stocks and habitat alterations. We found that project-level monitoring studies as currently designed for the NES ecosystem will not yield information that can mitigate impacts to NOAA Fisheries scientific survey time series from offshore wind development. We provide recommendations on how to enhance the ability of project-level monitoring studies to mitigate impacts to long term scientific surveys.
Numerical simulation of the effect of geometric parameters on silicone airway stent migration
Authors: Farahani Maryam Mazraehei , Bakhtiyari Arman , Beshkoofe Saed , Kajbafzadeh Abdolmohammad , Kiani Arda , Eskandari Amir Hossein , Baniassadi Majid , Baghani Mostafa
Published: July 2023

Recently, endotracheal stenting has become critical in treating respiratory diseases. Due to the COVID-19 pandemic in recent years, many patients had stenosis because of long-term intubation, and silicone stents can be used to treat tracheal stenosis in these patients. Standard airway stents are silicone tubes that provide immediate relief but are prone to migration. In this work, we design different silicone stents and analyze them in the trachea to evaluate silicone airway stents’ performance to overcome undesired migration. A finite-element model of the trachea was employed to evaluate anti-migration forces in each stent. The geometry of the trachea is brought from a computerized tomography scan of the chest of a 68-year-old healthy man. The results are shown based on the least migration of stents based on anti-migration forces. Also, the conditions of stent placement have been considered based on two different assumed friction factors, and the importance of choosing the type of silicone for stent construction has been analyzed. The results show that increasing the diameter of the stent reduces the displacement and migration of it in the trachea. Furthermore, the 23 mm stent with a 45° angle revealed the best implementation against compression under the impact of respiratory pressure differences.
Validation of metagenomic next-generation sequencing of bronchoalveolar lavage fluid for diagnosis of suspected pulmonary infections in patients with systemic autoimmune rheumatic diseases receiving immunosuppressant therapy
Authors: Wen Sichun , Peng Siqi , Hu Xuejiao , Jiang Nan , Li Bohou , Chen Boxi , Deng Shuting , Yuan Ye , Wu Qiong , Tao Yiming , Ma Jianchao , Li Sijia , Lin Ting , Wen Feng , Li Zhuo , Huang Renwei , Feng Zhonglin , He Chaosheng , Wang Wenjian , Liang Xinling , Shi Wei , Xu Lixia , Liu Shuangxin
Published: July 2023

Background

The accuracy and sensitivity of conventional microbiological tests (CMTs) are insufficient to identify opportunistic pathogens in patients with systemic autoimmune rheumatic diseases (SARDs). The study aimed to assess the usefulness of metagenomic next-generation sequencing (mNGS) vs. CMTs for the diagnosis of pulmonary infections in patients with SARDs receiving immunosuppressant therapy.

Methods

The medical records of 40 patients with pulmonary infections and SARDs treated with immunosuppressants or corticosteroids were reviewed retrospectively. Bronchoalveolar lavage fluid (BALF) samples were collected from all patients and examined by mNGS and CMTs. Diagnostic values of the CMTs and mNGS were compared with the clinical composite diagnosis as the reference standard.

Results

Of the 40 patients included for analysis, 37 (92.5%) were diagnosed with pulmonary infections and 3 (7.5%) with non-infectious diseases, of which two were considered primary diseases and one an asthma attack. In total, 15 pathogens (7 bacteria, 5 fungi, and 3 viruses) were detected by CMTs as compared to 58 (36 bacteria, 12 fungi, and 10 viruses) by mNGS. Diagnostic accuracy of mNGS was superior to that of the CMTs for the detection of co-infections with bacteria and fungi (95 vs. 53%, respectively, p < 0.01), and for the detection of single infections with fungi (97.5 vs. 55%, respectively, p < 0.01). Of the 31 patients diagnosed with co-infections, 4 (12.9%) were positive for two pathogens and 27 (87.1%) for three or more. The detection rate of co-infection was significantly higher for mNGS than CMTs (95 vs. 16%, respectively, p < 0.01).

Conclusion

The accuracy of mNGS was superior to that of the CMTs for the diagnosis of pulmonary infections in patients with SARDs treated with immunosuppressants. The rapid diagnosis by mNGS can ensure timely adjustment of treatment regimens to improve diagnosis and outcomes.
Prevalence of geriatric syndromes in frail patients and mortality risks
Authors: Tkacheva O. N. , Sharashkina N. V. , Eruslanova K. A. , Lysenkov S. N. , Reshetova A. A. , Matchekhina L. V. , Ilyushchenko A. K. , Runikhina N. K.
Published: July 2023

The prevalence of older people in Russian population increases rapidly. Therefore, the concept of healthy aging is becoming crucial in Russia and all over the world, and thus disability prevention is one aspect of this issue.

Aim

To assess a possible association between geriatric syndromes, comorbidities, and mortality rate among frail patients who receive home medical care in Moscow.

Materials and methods

The study included 450 patients with home medical care provided by the State Budgetary Healthcare Institution “Diagnostic Center No. 3 of the Moscow Health Department” from June 2019 to April 2021. Physical health, functional, cognitive, social and emotional statuses were evaluated by comprehensive geriatric assessment (CGA). The mortality rate after 1 year was assessed.

Results

The all-cause case mortality rate in patients during the observation period was 22.4%. There was no difference in age and comorbidities in survivors and deceased patients, but the latter group had more geriatric syndromes. The association between risks of mortality and anemia and some geriatric syndromes, such as malnutrition and hearing impairment, total dependence (Barthel index less than 60) was observed.
Effects of grain-based diets on the rumen and fecal bacterial communities of the North American bison (Bison bison)
Authors: Fresno Rueda Anlly , Griffith Jason Eric , Kruse Carter , St-Pierre Benoit
Published: July 2023

To overcome the challenges of pasture-finishing of bison, producers commonly feed them with higher energy, grain-based diets to reach the desired market weight. However, decades of research on domesticated ruminants have shown that such diets can have profound effects on the composition of gut microbial communities. To gain further insight, the 16S rRNA gene-based study described in this report aimed to compare the composition of ruminal and fecal bacterial communities from two herds of bison heifers (n = 20/herd) raised on different ranches that were both transitioned from native pasture to a grain-based, free-choice diet for ~100 days prior to slaughter. Comparative analyses of operational taxonomic unit (OTU) composition, either by alpha diversity indices, principal coordinate analysis (PCoA), or on the most abundant individual OTUs, showed the dramatic effect of a diet on the composition of both rumen and fecal bacterial communities in bison. Indeed, feeding a grain-based diet resulted in a lower number of rumen and fecal bacterial OTUs, respectively, compared to grazing on pasture (p < 0.05). PCoA revealed that the composition of the rumen and fecal bacterial communities from the two herds was more similar when they were grazing on native pastures compared to when they were fed a grain-based, free-choice diet. Finally, a comparative analysis of the 20 most abundant OTUs from the rumen and fecal communities further showed that the representation of all these species-level bacterial groups differed (p < 0.05) between the two dietary treatments. Together, these results provide further insights into the rumen and fecal microbiomes of grazing bison and their response to grain-based diet regimens commonly used in intensive ruminant production systems.
The stability and composition of the gut and skin microbiota of Atlantic salmon throughout the yolk sac stage
Authors: Fiedler Alexander W. , Drågen Martha K. R. , Lorentsen Eirik D. , Vadstein Olav , Bakke Ingrid
Published: July 2023

The bacterial colonization of newly hatched fish is important for the larval development and health. Still, little is known about the ontogeny of the early microbiota of fish. Here, we conducted two independent experiments with yolk sac fry of Atlantic salmon that were (1) either reared conventionally, with the eggs as the only source for bacteria (egg-derived microbiota; EDM) or (2) hatched germ-free and re-colonized using lake water (lake-derived microbiota; LDM). First, we characterized the gut and skin microbiota at 6, 9, and 13 weeks post hatching based on extracted RNA. In the second experiment, we exposed fry to high doses of either a fish pathogen or a commensal bacterial isolate and sampled the microbiota based on extracted DNA. The fish microbiota differed strongly between EDM and LDM treatments. The phyla Proteobacteria, Bacteroidetes, and Actinobacteria dominated the fry microbiota, which was found temporarily dynamic. Interestingly, the microbiota of EDM fry was more stable, both between replicate rearing flasks, and over time. Although similar, the skin and gut microbiota started to differentiate during the yolk sac stage, several weeks before the yolk was consumed. Addition of high doses of bacterial isolates to fish flasks had only minor effects on the microbiota.