bluuebunny/crossref_metadata_2025 huggingface dataset:
From “punks” at school to “superstars” at work: Social capital and educators’ asset-based perspectives of students in high school internships
Authors: Kundu Anindya , McLeod Scott , Piedrahita-Guzmán Yuly
Published: June 2024

High school internships provide students with valuable work-based learning experiences, career-oriented networking, and in-demand professional skills. In this study of high school principals, internship coordinators (“institutional agents”), and student interns, we highlight data from interviews and focus groups that substantiate the idea that internships can showcase students’ more diverse and latent aptitudes but are more effective when building upon students’ existing interests and abilities. Given the opportunity-focused goals of these programs, we recommend that school-based professionals adopt the language of social capital (or similar frameworks) to develop shared understandings between stakeholders and also critique existing conceptualizations to approach the work from asset-based and equity lenses.
Evaluating the effect of the accountability audit of natural resources on carbon emissions reduction in China
Authors: Xiong Liyang , Shu Yiyi , Li Xuefeng
Published: June 2024

The accountability audit of natural resources (AANR) is a major institutional arrangement for advancing the construction of an ecological civilization in China. Based on the panel data of 271 cities in China from 2005 to 2017, this paper investigates the relationship between the AANR and carbon dioxide (CO2) emissions using a multi-period difference-in-differences (DID) model. The results show that AANR significantly increases the CO2 emission reduction rate by 0.009 units at the 5% significance level. The results still hold after a series of robustness tests. Given all else being equal, this significant effect is 0.001. Further analyses show that AANR improves pilot cities’ CO2 emission reduction rates mainly by enhancing their green innovation capability. The mediating effect of cities’ green technology innovation capability accounts for 96.00%, while the AANR’s direct effect only accounts for 4.00%. The AANR has significantly positive effects of 0.017% and 0.029% for western cities and cities with high fiscal pressure at the 5% and 1% significance levels, respectively. Therefore, strengthening AANR implementation by enhancing the mediating efficiency of cities’ green technology innovations and implementing dynamically differentiated AANR policies in Chinese meso-cities will contribute to the achievement of China’s carbon peaking and carbon neutrality targets.
Long-term organic farming impact on soil nutrient status and grain yield at the foothill of Himalayas
Authors: Singh Pranjali , Suyal Deep Chandra , Kumar Saurabh , Singh Dhananjay Kumar , Goel Reeta
Published: June 2024

This study aimed to document the effects of the long-term organic farming (OF) on soil quality, agronomical parameters, crop productivity, and food grain yield compared to the conventional farming (CF) system. The crop used in this study is chickpea (Cicer arietinum), and the field was located at Pantnagar, India, in the foothills of Himalayas. The organic farming approach involved utilizing a blend of farmyard manure and vermicompost, combined with a biopesticide comprising neem oil and cow urine. Chickpea grain micronutrient analysis was done via atomic absorption spectrophotometry. It was found that the physicochemical properties of soil in the organic plot were improved compared to the conventional counterpart. At the post-harvesting stage, the organically managed field had higher soil organic carbon than the conventional field (OF-0.93± 0.05%, CF-0.75 ± 0.12%), higher available nitrogen (OF-317 ± 11 kg/ha, CF-240 ± 22 kg/ha), and more available phosphorus (OF-37.4 ± 1.3 kg/ha, CF-25.2 ± 2.5 kg/ha). The agronomical parameters of the chickpea crop were better under organic cultivation, with a significantly high nodule number, nodule dry weight, and grains per pod. Hence, the grain yield of the crop was better under organic cultivation, with the yield of 1,048 kg ha−1, whereas it was 896.5 kg ha−1 for conventional cultivation. The Fe and Zn contents of organically produced chickpea grains were almost double of their conventional counterpart. Therefore, organic cultivation led to better soil fertility, chickpea grain yield, and nutrient status of the crop. It will be beneficial for the nutritious and sustainable production of chickpeas in Himalayan regions.
Meta-analysis compares the effectiveness of modified biochar on cadmium availability
Authors: Liu Hanyi , Chen Chuntan , Li Xue , Yang Peng
Published: June 2024

This study aims to quantitatively evaluate the effectiveness of modified biochar in reducing soil Cd availability and Cd content in plants by performing a meta-analysis using data from 58 papers. Modified biochar enhances the surface function and adsorption efficiency of biochar, making it a cost-effective modifier for immobilizing heavy metals. Various factors influence the cadmium (Cd) passivation effect of modified biochar, including the materials used, modification methods, and specific modified materials, warranting further research and clarification. On average, the application of modified biochar results in a significant reduction in soil Cd availability by 65.01% and Cd content in plants by 70.72%. Notably, biochar made from lignocellulose as a raw material exhibits an impressive reduction effect of 96.34% on soil Cd availability. Furthermore, organic modified biochar and acid-base modified biochar demonstrate reduction effects of 119.53% and 112.03%, respectively, for soil Cd availability. When considering plant uptake, modified biochar composed of herbs and combined modified biochar show better Cd reduction effects, with respective reductions of 100.53% and 88.87%. The optimal application rate of modified biochar falls within the range of 2%–3%, leading to a reduction of effective Cd in soil by 76.94% and Cd content in plants by 88.88%. This meta-analysis underscores the potential of modified biochar in remediating Cd-contaminated soil, offering valuable insights for the preparation and application of this material.
Turning setbacks into stepping-stones for growth in conservation paleobiology
Authors: Wingard G. Lynn , Schneider Chris L. , Dietl Gregory P. , Fordham Damien A.
Published: June 2024

Conservation paleobiology is a cross-disciplinary field that utilizes the geohistorical record of past life on Earth to inform present-day decisions in conservation and restoration and assist in planning for future natural resource management. However, information on how past ecosystems and species responded to environmental change over decadal to millennial timescales is rarely incorporated into conservation and restoration decision-making. To heighten awareness among conservation and restoration practitioners of the relevance of geohistorical data and to bridge the gap between research and implementation in conservation paleobiology, we proposed a Research Topic titled “Integrating Conservation Biology and Paleobiology to Manage Biodiversity and Ecosystems in a Changing World”. The 21 articles subsequently published demonstrate the diversity and breadth of geohistorical information available to resource management and the challenges of translating these results into conservation practice and policy. Here we discuss the lessons we learned from editing the Research Topic and suggest a pathway forward for conservation paleobiologists who aspire to generate actionable research results to solve current problems in biodiversity conservation and ecological restoration.
Development and validation of novel keloid-derived immortalized fibroblast cell lines
Authors: Sadiq Alia , Khumalo Nonhlanhla P. , Bayat Ardeshir
Published: June 2024

Keloids are a common connective tissue disorder with an ill-understood etiopathogenesis and no effective treatment. This is exacerbated because of the absence of an animal model. Patient-derived primary keloid cells are insufficient as they age through passaging and have a limited supply. Therefore, there is an unmet need for development of a cellular model that can consistently and faithfully represent keloid’s pathognomic features. In view of this, we developed keloid-derived immortalized fibroblast (KDIF) cell lines from primary keloid fibroblasts (PKF) by transfecting the human telomerase reverse transcriptase (hTERT) gene. The TERT gene encodes the catalytic subunit of the telomerase enzyme, which is responsible for maintaining the cellular replicative potential (cellular immortalization). Primary fibroblasts from keloid-specific lesional (peripheral, middle, and top) as well as extralesional sites were isolated and evaluated for cell line development and comparative cellular characteristics by employing qRT-PCR and immunofluorescence staining. Moreover, the immortalized behavior of KDIF cell lines was evaluated by comparing with cutaneous fibrosarcoma and dermatofibrosarcoma protuberans cell lines. Stable KDIF cell lines with elevated expression of hTERT exhibited the cellular characteristics of site-specific keloid fibroblasts. Histochemical staining for β-galactosidase revealed a significantly lower number of β-gal–positive cells in all three KDIF cell lines compared with that in PKFs. The cell growth curve pattern was studied over 10 passages for all three KDIF cell lines and was compared with the control groups. The results showed that all three KDIF cell lines grew significantly faster and obtained a fast growing characteristic as compared to primary keloid and normal fibroblasts. Phenotypic behavior in growth potential is an indication of hTERT-mediated immortalized transformation. Cell migration analysis revealed that the top and middle KDIF cell lines exhibited similar migration trend as site-specific PKFs. Notably, peripheral KDIF cell line showed significantly enhanced cell migration in comparison to the primary peripheral fibroblasts. All KDIF cell lines expressed Collagen I protein as a keloid-associated fibrotic marker. Functional testing with triamcinolone inhibited cell migration in KDIF. ATCC short tandem repeat profiling validated the KDIF as keloid representative cell line. In summary, we provide the first novel KDIF cell lines. These cell lines overcome the limitations related to primary cell passaging and tissue supply due to immortalized features and present an accessible and consistent experimental model for keloid research.
The disruptive effects of COPD exacerbation-associated factors on epithelial repair responses
Authors: Kortekaas Rosa K. , Geillinger-Kästle Kerstin E. , Fuentes-Mateos Rocío , van Orsoy Roël , Al-Alyan Nakaa , Burgess Janette K. , Gosens Reinoud
Published: June 2024

Introduction

Exacerbations of chronic obstructive pulmonary disease (COPD) increase mortality risk and can lead to accelerated loss of lung function. The increased inflammatory response during exacerbations contributes to worsening of airflow limitation, but whether it also impacts epithelial repair is unclear. Therefore, we studied the effect of the soluble factor micro-environment during COPD exacerbations on epithelial repair using an exacerbation cocktail (EC), composed of four factors that are increased in COPD lungs during exacerbations (IL-1β, IL-6, IL-8, TNF-α).

Methods

Mouse organoids (primary CD31-CD45-Epcam+ cells co-cultured with CCL206 fibroblasts) were used to study epithelial progenitor behavior. Mature epithelial cell responses were evaluated using mouse precision cut lung slices (PCLS). The expression of epithelial supportive factors was assessed in CCL206 fibroblasts and primary human lung fibroblasts.

Results

EC exposure increased the number and size of organoids formed, and upregulated Lamp3, Muc5ac and Muc5b expression in day 14 organoids. In PCLS, EC imparted no effect on epithelial marker expression. Pre-treatment of CCL206 fibroblasts with EC was sufficient to increase organoid formation. Additionally, the expression of Il33, Tgfa and Areg was increased in CCL206 fibroblasts from EC treated organoids, but these factors individually did not affect organoid formation or size. However, TGF-α downregulated Foxj1 expression and upregulated Aqp5 expression in day 14 organoids.

Conclusions

EC exposure stimulates organoid formation and growth, but it alters epithelial differentiation. EC changes the epithelial progenitor support function of fibroblasts which contributes to observed effects on epithelial progenitors.
State-of-the-art diagnosis of autoimmune blistering diseases
Authors: van Beek Nina , Holtsche Maike M. , Atefi Ingeborg , Olbrich Henning , Schmitz Marie J. , Pruessmann Jasper , Vorobyev Artem , Schmidt Enno
Published: June 2024

Autoimmune blistering disorders (AIBDs) are a heterogeneous group of approximately a dozen entities comprising pemphigus and pemphigoid disorders and dermatitis herpetiformis. The exact diagnosis of AIBDs is critical for both prognosis and treatment and is based on the clinical appearance combined with the detection of tissue-bound and circulating autoantibodies. While blisters and erosions on the skin and/or inspectable mucosal surfaces are typical, lesions may be highly variable with erythematous, urticarial, prurigo-like, or eczematous manifestations. While direct immunofluorescence microscopy (IFM) of a perilesional biopsy is still the diagnostic gold standard, the molecular identification of the major target antigens opened novel therapeutic avenues. At present, most AIBDs can be diagnosed by the detection of autoantigen-specific serum antibodies by enzyme-linked immunosorbent assay (ELISA) or indirect IFM when the clinical picture is known. This is achieved by easily available and highly specific and sensitive assays employing recombinant immunodominant fragments of the major target antigens, i.e., desmoglein 1 (for pemphigus foliaceus), desmoglein 3 (for pemphigus vulgaris), envoplakin (for paraneoplastic pemphigus), BP180/type XVII collagen (for bullous pemphigoid, pemphigoid gestationis, and mucous membrane pemphigoid), laminin 332 (for mucous membrane pemphigoid), laminin β4 (for anti-p200 pemphigoid), type VII collagen (for epidermolysis bullosa acquisita and mucous membrane pemphigoid), and transglutaminase 3 (for dermatitis herpetiformis). Indirect IFM on tissue substrates and in-house ELISA and immunoblot tests are required to detect autoantibodies in some AIBD patients including those with linear IgA disease. Here, a straightforward modern approach to diagnosing AIBDs is presented including diagnostic criteria according to national and international guidelines supplemented by long-term in-house expertise.
Towards a survival risk prediction model for metastatic NSCLC patients on durvalumab using whole-lung CT radiomics
Authors: Patwardhan Kedar A. , RaviPrakash Harish , Nikolaou Nikolaos , Gonzalez-García Ignacio , Salazar José Domingo , Metcalfe Paul , Reischl Joachim
Published: June 2024

Background

Existing criteria for predicting patient survival from immunotherapy are primarily centered on the PD-L1 status of patients. We tested the hypothesis that noninvasively captured baseline whole-lung radiomics features from CT images, baseline clinical parameters, combined with advanced machine learning approaches, can help to build models of patient survival that compare favorably with PD-L1 status for predicting ‘less-than-median-survival risk’ in the metastatic NSCLC setting for patients on durvalumab. With a total of 1062 patients, inclusive of model training and validation, this is the largest such study yet.

Methods

To ensure a sufficient sample size, we combined data from treatment arms of three metastatic NSCLC studies. About 80% of this data was used for model training, and the remainder was held-out for validation. We first trained two independent models; Model-C trained to predict survival using clinical data; and Model-R trained to predict survival using whole-lung radiomics features. Finally, we created Model-C+R which leveraged both clinical and radiomics features.

Results

The classification accuracy (for median survival) of Model-C, Model-R, and Model-C+R was 63%, 55%, and 68% respectively. Sensitivity analysis of survival prediction across different training and validation cohorts showed concordance indices ([95 percentile]) of 0.64 ([0.63, 0.65]), 0.60 ([0.59, 0.60]), and 0.66 ([0.65,0.67]), respectively. We additionally evaluated generalization of these models on a comparable cohort of 144 patients from an independent study, demonstrating classification accuracies of 65%, 62%, and 72% respectively.

Conclusion

Machine Learning models combining baseline whole-lung CT radiomic and clinical features may be a useful tool for patient selection in immunotherapy. Further validation through prospective studies is needed.
A two-years real-word study with fingolimod: early predictors of efficacy and an association between EBNA-1 IgG titers and multiple sclerosis progression
Authors: Dominguez-Mozo Maria Inmaculada , Galán Victoria , Ramió-Torrentà Lluís , Quiroga Ana , Quintana E. , Villar Luisa María , Costa-Frossard Lucienne , Fernández-Velasco José Ignacio , Villarrubia Noelia , Garcia-Martinez María Angel , Arroyo Rafael , Alvarez-Lafuente Roberto
Published: June 2024

Background

Although fingolimod, a sphingosine 1-phosphate receptor agonist, has shown to be an effective treatment reducing relapse rate and also slowing down the disability progression in relapsing-remitting multiple sclerosis (RRMS) patients, it is important to quickly identify those suboptimal responders.

Objective

The main objective was to assess different clinical, radiological, genetic and environmental factors as possible early predictors of response in MS patients treated with fingolimod for 24 months. The secondary objective was to analyze the possible contribution of the environmental factors analyzed to the progression and activity of the disease along the 2-years of follow-up.

Methods

A retrospective study with 151 patients diagnosed with MS, under fingolimod treatment for 24 months, with serum samples at initiation and six months later, and with clinical and radiological data at initiation and 24 months later, were included in the study. Clinical and radiological variables were collected to establish NEDA-3 (no evidence of disease activity: patients without relapses, disability progression and new T2 lesions or Gd+ lesions) and EDA (evidence of disease activity: patients with relapses and/or progression and/or new T2 lesions or gadolinium-positive [Gd+] lesions) conditions. Human leukocyte antigen II (HLA-II), EBNA-1 IgG and VCA IgG from Epstein-Barr virus (EBV) and antibody titers against Human herpesvirus 6A/B (HHV-6A/B) were also analyzed.

Results

A total of 151 MS patients fulfilled the inclusion criteria: 27.8% was NEDA-3 (37.5% among those previously treated with high efficacy therapies >24 months). The following early predictors were statistically significantly associated with NEDA-3 condition: sex (male; p=0.002), age at baseline (older; p=0.009), relapses 2-years before fingolimod initiation ≤1 (p=0.010), and absence of Gd+ lesions at baseline (p=0.006). Regarding the possible contribution of the environmental factors included in the study to the activity or the progression of the disease, we only found that EBNA-1 IgG titers decreased in 20.0% of PIRA (progression independent from relapse activity) patients vs. 73.3% of RAW (relapse-associated worsening) patients (p=0.006; O.R. = 11.0).

Conclusion

MS patients that are male, older, and with a low clinical and radiological activity at fingolimod initiation have a greater probability to reach NEDA-3 condition after two years with this therapy. An intriguing association of EBV with the progression of the disease has also been described, but it should be further study in a larger cohort to confirm these results.
Insufficient PD-1 expression during active autoimmune responses: a deep single-cell proteomics analysis in inflammatory arthritis
Authors: Vetsika Eleni-Kyriaki , Fragoulis George E. , Kyriakidi Maria , Verrou Kleio-Maria , Tektonidou Maria G. , Alissafi Themis , Sfikakis Petros P.
Published: June 2024

Objectives

Programmed cell death protein-1 (PD-1) maintains peripheral immune tolerance by preventing T cell continuous activation. Aiming to understand the extent of PD-1 expression in inflammatory arthritis beyond its involvement with T cells, we assess its presence on various circulating single cells.

Methods

Mass cytometry analysis of patients with active seropositive/seronegative rheumatoid (RA; n=9/8) and psoriatic (PsA; n=9) arthritis versus healthy controls (HC; n=13), re-evaluating patients after 3 months of anti-rheumatic treatment.

Results

PD-1 was expressed in all leukocyte subpopulations, with the highest PD-1+ cell frequencies in eosinophils (59-73%) and T cells (50–60%), and the lowest in natural-killer cells (1–3%). PD-1+ cell frequencies and PD-1 median expression were comparable between patient subgroups and HC, in the majority of cell subsets. Exceptions included increases in certain T cell/B cell subsets of seropositive RA and specific monocyte subsets and dendritic cells of PsA; an expanded PD-1+CD4+CD45RA+CD27+CD28+ T subset, denoting exhausted T cells, was common across patient subgroups. Strikingly, significant inverse correlations between individual biomarkers of systemic inflammation (ESR and/or serum CRP) and PD-1+ cell frequencies and/or median expression were evident in several innate and adaptive immunity cell subsets of RA and PsA patients. Furthermore, all inverse correlations noted in individuals with active arthritis were no longer discernible in those who attained remission/low disease activity post-treatment.

Conclusion

PD-1 expression may be insufficient, relative to the magnitude of the concomitant systemic inflammatory response on distinct leukocyte subsets, varying between RA and PsA. Our results point to the potential therapeutic benefits of pharmacological PD-1 activation, to rebalance the autoimmune response and reduce inflammation.
From proteome to candidate vaccines: target discovery and molecular dynamics-guided multi-epitope vaccine engineering against kissing bug
Authors: Albaqami Faisal F. , Altharawi Ali , Althurwi Hassan N. , Alharthy Khalid M.
Published: June 2024

Introduction

Trypanosoma cruzi is a protozoan parasite that causes the tropical ailment known as Chagas disease, which has its origins in South America. Globally, it has a major impact on health and is transported by insect vector that serves as a parasite. Given the scarcity of vaccines and the limited treatment choices, we conducted a comprehensive investigation of core proteomics to explore a potential reverse vaccine candidate with high antigenicity.

Methods

To identify the immunodominant epitopes, T. cruzi core proteomics was initially explored. Consequently, the vaccine sequence was engineered to possess characteristics of non-allergenicity, antigenicity, immunogenicity, and enhanced solubility. After modeling the tertiary structure of the human TLR4 receptor, the binding affinities were assessed employing molecular docking and molecular dynamics simulations (MDS).

Results

Docking of the final vaccine design with TLR4 receptors revealed substantial hydrogen bond interactions. A server-based methodology for immunological simulation was developed to forecast the effectiveness against antibodies (IgM + IgG) and interferons (IFN-g). The MDS analysis revealed notable levels of structural compactness and binding stability with average RMSD of 5.03 Aring;, beta-factor 1.09e+5 Å, Rg is 44.7 Aring; and RMSF of 49.50 Aring;. This is followed by binding free energies calculation. The system stability was compromised by the complexes, as evidenced by their corresponding Gibbs free energies of -54.6 kcal/mol.

Discussion

Subtractive proteomics approach was applied to determine the antigenic regions of the T cruzi. Our study utilized computational techniques to identify B- and T-cell epitopes in the T. cruzi core proteome. In current study the developed vaccine candidate exhibits immunodominant features. Our findings suggest that formulating a vaccine targeting the causative agent of Chagas disease should be the initial step in its development.
An evaluation tool for assessing coral restoration efforts
Authors: Schopmeyer Stephanie , Galvan Victor , Hernandez-Delgado Edwin A. , Nava Gabriela , D’Alessandro Martine , Carne Lisa , Goergen Elizabeth , Viehman Shay , Moulding Alison , Lirman Diego
Published: June 2024

The ever-increasing need for coral restoration as a tool available to mitigate reef declines and aid in the recovery of lost ecosystem services requires improving restoration performance over time through an adaptive management framework to evaluate the status of restoration programs using uniform, consistent metrics. An evaluation tool, presented herein, allows restoration practitioners and managers to self-evaluate the robustness of each project and identify successful metrics, those metrics that need special attention, and changes to restoration strategies that can improve performance and aid recovery. This tool is designed to allow programs to track the progress of each key metric over time to assist in improving upon successes and learning from failures. The metrics within this restoration evaluation tool focus on published best-management practices and have resulted from extensive research conducted by restoration experts over the past 20 years. Common metrics of growth and survival are included, in addition to parameters vital to the operational success of restoration programs, such as coral reproduction, recruitment of associated reef taxa, increasing habitat for reef fisheries, and improving overall reef habitat. Five Caribbean restoration programs, each with at least 15 years of restoration experience, are presented as case studies. Each program was evaluated based on six restoration categories including: field-based nurseries, outplantings, programmatic management, education and outreach, event-driven restoration, and socioeconomic restoration. Category-specific metrics were scored with a binary scoring system and summarized using a stop-light indicator framework, where the resulting color/score indicates the operations tatus of the different program components (Scores >75% = green/successful; 50–74.9% = light green > yellow > orange/intermediate; <49.9% = red/sub-optimal). Composite scores may be used to evaluate individual projects, overall restoration programs, or even large-scale state of regional restoration plans. Overall, four of the five programs scored >75% indicating most of these programs are performing well, are versatile, well managed, and sustainable. Outside of environmental factors and large-scale disturbance events, many programs described resource limitations, including funding and staffing, as reasons for scoring low on some metrics. A holistic evaluation rubric incorporated into programmatic self-assessment can ensure that restoration projects and programs are working towards success and sustainability.
The comparison of preoxygenation methods before endotracheal intubation: a network meta-analysis of randomized trials
Authors: Zhong Ming , Xia Rong , Zhou Junyu , Zhang Jing , Yi Xia , Yang Anbo
Published: June 2024

Background

Preoxygenation before endotracheal intubation (ETI) maintains asphyxiated oxygenation and reduces the risk of hypoxia-induced adverse events. Previous studies have compared various preoxygenation methods. However, network meta-analyses (NMAs) of the combined comparison of preoxygenation methods is still lacking.

Methods

We searched for studies published in PubMed, Embase, Web of Science, Scopus, and the Cochrane Library. Review Manager version 5.3 was used to evaluate the risk of bias. The primary outcome of this meta-analysis was low oxygen saturation (SpO2) during ETI. The secondary outcomes included SpO2 <80%, SpO2 <90%, and apnea time during ETI. NMA was performed using R 4.1.2 software gemtc packages in RStudio.

Results

A total of 15 randomized controlled trials were included in this study. Regarding the lowest SpO2, the noninvasive ventilation (NIV) with high-flow nasal cannula (HFNC) group performed better than the other groups. For SpO2 <80%, the NIV group (0.8603467) performed better than the HFNC (0.1373533) and conventional oxygen therapy (COT, 0.0023) groups, according to the surface under the cumulative ranking curve results. For SpO2 <90%, the NIV group (0.60932667) performed better than the HFNC (0.37888667) and COT (0.01178667) groups. With regard to apnea time, the HFNC group was superior to the COT group (mean difference: −50.05; 95% confidence interval: −90.01, −10.09; P = 0.01).

Conclusion

Network analysis revealed that NIV for preoxygenation achieved higher SpO2 levels than HFNC and COT and offered a more significant advantage in maintaining patient oxygenation during ETI. Patients experienced a longer apnea time after HFNC preoxygenation. The combination of NIV with HFNC proved to be significantly superior to other methods. Given the scarcity of such studies, further research is needed to evaluate its effectiveness.

Systematic review registration

identifier CRD42022346013
Phenotypic drug discovery: a case for thymosin alpha-1
Authors: Garaci Enrico , Paci Maurizio , Matteucci Claudia , Costantini Claudio , Puccetti Paolo , Romani Luigina
Published: June 2024

Phenotypic drug discovery (PDD) involves screening compounds for their effects on cells, tissues, or whole organisms without necessarily understanding the underlying molecular targets. PDD differs from target-based strategies as it does not require knowledge of a specific drug target or its role in the disease. This approach can lead to the discovery of drugs with unexpected therapeutic effects or applications and allows for the identification of drugs based on their functional effects, rather than through a predefined target-based approach. Ultimately, disease definitions are mostly symptom-based rather than mechanism-based, and the therapeutics should be likewise. In recent years, there has been a renewed interest in PDD due to its potential to address the complexity of human diseases, including the holistic picture of multiple metabolites engaging with multiple targets constituting the central hub of the metabolic host–microbe interactions. Although PDD presents challenges such as hit validation and target deconvolution, significant achievements have been reached in the era of big data. This article explores the experiences of researchers testing the effect of a thymic peptide hormone, thymosin alpha-1, in preclinical and clinical settings and discuss how its therapeutic utility in the precision medicine era can be accommodated within the PDD framework.
The other side of the mark sheet: lessons learnt when medical students assess peers in formative clinical examinations
Authors: Rienits Helen
Published: June 2024

This study aimed to investigate the experience of medical students assessing their cohort peers in formative clinical assessment. The exercise was designed to provide students with a formative experience prior to their summative assessment, and to determine what students could learn by being on the “other side of the mark sheet.” Students were grateful for the experience learning both from the assessment practice, and from the individual written feedback provided immediately afterwards. They also described how much they learnt from seeing the assessment from the assessor’s viewpoint, with many students commenting that they learnt more from being the “assessor” than from being the “student” in the process. Students were asked how they felt about being assessed by their peers, with some describing the experience as being more intimidating and stressful than when compared to assessment by clinicians. An interesting aspect of this study is that it also demonstrates some findings which suggest that the students’ current learning context appears to have an effect on their attitudes to their peers as assessors. It is possible the competitive cultural milieu of the teaching hospital environment may have a negative effect on medical student collegiality and peer support.
Microbiome and metabolome analyses of milk and feces from dairy cows with healthy, subclinical, and clinical mastitis
Authors: Zhu Chenglin , Zhao Yuxuan , Yang Falong , Zhang Qian , Zhao Xin , Yang Zhibo , Dao Xiaofang , Laghi Luca
Published: June 2024

Mastitis is commonly recognized as a localized inflammatory udder disease induced by the infiltration of exogenous pathogens. In the present study, our objective was to discern fecal and milk variations in both microbiota composition and metabolite profiles among three distinct groups of cows: healthy cows, cows with subclinical mastitis and cows with clinical mastitis. The fecal microbial community of cows with clinical mastitis was significantly less rich and diverse than the one harbored by healthy cows. In parallel, mastitis caused a strong disturbance in milk microbiota. Metabolomic profiles showed that eleven and twenty-eight molecules exhibited significant differences among the three groups in feces and milk, respectively. Similarly, to microbiota profile, milk metabolome was affected by mastitis more extensively than fecal metabolome, with particular reference to amino acids and sugars. Pathway analysis revealed that amino acids metabolism and energy metabolism could be considered as the main pathways altered by mastitis. These findings underscore the notable distinctions of fecal and milk samples among groups, from microbiome and metabolomic points of view. This observation stands to enhance our comprehension of mastitis in dairy cows.
Climate change induces shifts in coastal Baltic Sea surface water microorganism stress and photosynthesis gene expression
Authors: Seidel Laura , Broman Elias , Ståhle Magnus , Bergström Kristofer , Forsman Anders , Hylander Samuel , Ketzer Marcelo , Dopson Mark
Published: June 2024

The world’s oceans are challenged by climate change linked warming with typically highly populated coastal areas being particularly susceptible to these effects. Many studies of climate change on the marine environment use large, short-term temperature manipulations that neglect factors such as long-term adaptation and seasonal cycles. In this study, a Baltic Sea ‘heated’ bay influenced by thermal discharge since the 1970s from a nuclear reactor (in relation to an unaffected nearby ‘control’ bay) was used to investigate how elevated temperature impacts surface water microbial communities and activities. 16S rRNA gene amplicon based microbial diversity and population structure showed no difference in alpha diversity in surface water microbial communities, while the beta diversity showed a dissimilarity between the bays. Amplicon sequencing variant relative abundances between the bays showed statistically higher values for, e.g., Ilumatobacteraceae and Burkholderiaceae in the heated and control bays, respectively. RNA transcript-derived activities followed a similar pattern in alpha and beta diversity with no effect on Shannon’s H diversity but a significant difference in the beta diversity between the bays. The RNA data further showed more elevated transcript counts assigned to stress related genes in the heated bay that included heat shock protein genes dnaKJ, the co-chaperonin groS, and the nucleotide exchange factor heat shock protein grpE. The RNA data also showed elevated oxidative phosphorylation transcripts in the heated (e.g., atpHG) compared to control (e.g., atpAEFB) bay. Furthermore, genes related to photosynthesis had generally higher transcript numbers in the control bay, such as photosystem I (psaAC) and II genes (psbABCEH). These increased stress gene responses in the heated bay will likely have additional cascading effects on marine carbon cycling and ecosystem services.
ROS are required for the germinative cell proliferation and metacestode larval growth of Echinococcus multilocularis
Authors: Tian Ye , Cheng Zhe , Ge Defeng , Xu Zhijian , Wang Huijuan , Li Xiazhen , Tian Huimin , Liu Fan , Luo Damin , Wang Yanhai
Published: June 2024

The potentially lethal zoonotic disease alveolar echinococcosis (AE) is caused by the metacestode larval stages of the tapeworm Echinococcus multilocularis. Metacestode growth and proliferation occurs within the inner organs of mammalian hosts, which is associated with complex molecular parasite–host interactions. The host has developed various ways to resist a parasitic infection, and the production of reactive oxygen species (ROS) is one of the most important strategies. Here, we found that scavenging of ROS reduced metacestode larval growth and germinative cell proliferation in in vivo models. Furthermore, using in vitro-cultured metacestode vesicles, we found that increased ROS levels enhanced metacestode growth and germinative cell proliferation, which was achieved by positively activating the ROS-EmERK-EmHIF1α axis. These results indicate that, beside its capacity to damage the parasite, ROS also play critical roles in metacestode growth and germinative cell proliferation. This study suggests that the effects of ROS on parasite may be bidirectional during AE infection, reflecting the parasite’s adaptation to the oxidative stress microenvironment.
Effect of thermal treatment of illite on the bioavailability of copper and zinc in the aerobic composting of pig manure with corn straw
Authors: Escobar Maia , Ji Jiaoyang , Wang Yueru , Feng Meiqin , Bao Changjie , Ma Jianxun , Cui Shijia , Zang Sihan , Zhang Jinpeng , Zhang Wei , Chen Guang , Chen Huan
Published: June 2024

The large amount of various types of heavy metals in animal manure applied to agricultural field has caused severe threat to the ecosystems of soil environments. In this study, the effect of thermal treatment of illite on the bioavailability of copper (Cu) and zinc (Zn) in the aerobic composting of pig manure with corn straw biochar was investigated. The objectives of this study were to characterize the variations in the bioavailability of Cu and Zn in the aerobic composting of pig manure added with illite treated with high temperatures and to identify the relatively dominant microbes involved in the formation of humus and passivation of heavy metals in pig manure composting based on 16S rRNA high-throughput sequencing analysis. The results showed that in comparison with the raw materials of pig manure, the bioavailability of Zn and Cu in the control and three experimental composting groups, i.e., group I (with untreated illite), group I-2 (with illite treated under 200°C), and group I-5 (with illite treated under 500°C), was decreased by 27.66 and 71.54%, 47.05 and 79.80%, 51.56 and 81.93%, and 58.15 and 86.60%, respectively. The results of 16S rRNA sequencing analysis revealed that in the I-5 group, the highest relative abundance was detected in Fermentimonas, which was associated with the degradation of glucose and fructose, and the increased relative abundances were revealed in the microbes associated with the formation of humus, which chelated with Zn and Cu to ultimately reduce the bioavailability of heavy metals and their biotoxicity in the compost. This study provided strong experimental evidence to support the application of illite in pig manure composting and novel insights into the selection of appropriate additives (i.e., illite) to promote humification and passivation of different heavy metals in pig manure composting.
Short-chain fatty acids inhibit bacterial plasmid transfer through conjugation in vitro and in ex vivo chicken tissue explants
Authors: Ott Logan C. , Mellata Melha
Published: June 2024

The animal gut acts as a potent reservoir for spreading and maintaining conjugative plasmids that confer antimicrobial resistance (AMR), fitness, and virulence attributes. Interventions that inhibit the continued emergence and expansion of AMR and virulent strains in agricultural and clinical environments are greatly desired. This study aims to determine the presence and efficacy of short-chain fatty acids (SCFA) inhibitory effects on the conjugal transfer of AMR plasmids. In vitro broth conjugations were conducted between donor Escherichia coli strains carrying AMP plasmids and the plasmid-less Escherichia coli HS-4 recipient strain. Conjugations were supplemented with ddH2O or SCFAs at 1, 0.1, 0.01, or 0.001 molar final concentration. The addition of SCFAs completely inhibited plasmid transfer at 1 and 0.1 molar and significantly (p < 0.05) reduced transfer at 0.01 molar, regardless of SCFA tested. In explant models for the chicken ceca, either ddH2O or a final concentration of 0.025 M SCFAs were supplemented to the explants infected with donor and recipient E. coli. In every SCFA tested, significant decreases in transconjugant populations compared to ddH2O-treated control samples were observed with minimal effects on donor and recipient populations. Finally, significant reductions in transconjugants for plasmids of each incompatibility type (IncP1ε, IncFIβ, and IncI1) tested were detected. This study demonstrates for the first time the broad inhibition ability of SCFAs on bacterial plasmid transfer and eliminates AMR with minimal effect on bacteria. Implementing interventions that increase the concentrations of SCFAs in the gut may be a viable method to reduce the risk, incidence, and rate of AMR emergence in agricultural and human environments.
The potential protective role of peripheral immunophenotypes in Alzheimer’s disease: a Mendelian randomization study
Authors: Zuo Chun-yan , Hu Zhengwei , Hao Xiao-yan , Li Meng-jie , Shi Jing-jing , Guo Meng-nan , Ma Dong-rui , Li Shuang-jie , Liang Yuan-yuan , Zhang Chan , Mao Cheng-yuan , Xu Yuming , Shi Chang-he
Published: June 2024

Introduction

Alzheimer’s disease (AD) is the most widespread neurodegenerative disease in the world. Previous studies have shown that peripheral immune dysregulation plays a paramount role in AD, but whether there is a protective causal relationship between peripheral immunophenotypes and AD risk remains ambiguous.

Methods

Two-sample Mendelian randomization (MR) was performed using large genome-wide association study (GWAS) genetic data to assess causal effects between peripheral immunophenotypes and AD risk. Utilizing the genetic associations of 731 immune cell traits as exposures. We adopted the inverse variance weighted method as the primary approach. The Weighted median and MR-Egger regression methods were employed as supplements. Various sensitivity analyses were performed to assess the robustness of the outcomes.

Results

Based on the IVW method, we identified 14 immune cell traits that significantly reduced the risk of AD, of which six demonstrated statistical significance in both IVW and Weighted median methods. Among the seven immune traits, four were related to regulatory T (Treg) cells : (1) CD25++ CD45RA- CD4 not regulatory T cell % T cell (odds ratio (OR) [95% confidence interval (CI)] = 0.96 [0.95, 0.98], adjusted P = 1.17E−02), (2) CD25++ CD45RA- CD4 not regulatory T cell % CD4+ T cell (OR [95% CI] = 0.97 [0.96, 0.99], adjusted P = 3.77E−02), (3) Secreting CD4 regulatory T cell % CD4 regulatory T cell (OR [95% CI] = 0.98 [0.97, 0.99], adjusted P = 7.10E−03), (4) Activated & secreting CD4 regulatory T cell % CD4 regulatory T cell(OR [95% CI] = 0.98 [0.97, 0.99], adjusted P = 7.10E−03). In addition, HLA DR++ monocyte % monocyte (OR [95% CI] = 0.93 [0.89, 0.98], adjusted P = 4.87E−02) was associated with monocytes, and HLA DR on myeloid Dendritic Cell (OR [95% CI] = 0.93 [0.89, 0.97], adjusted P = 1.17E−02) was related to dendritic cells (DCs).

Conclusion

These findings enhance the comprehension of the protective role of peripheral immunity in AD and provide further support for Treg and monocyte as potential targets for immunotherapy in AD.
A novel Gaussian sum quaternion constrained cubature Kalman filter algorithm for GNSS/SINS integrated attitude determination and positioning system
Authors: Dai Qing , Xiao Guo-Rui , Zhou Guo-Hua , Ye Qian-Qian , Han Shao-Yong
Published: June 2024

The quaternion cubature Kalman filter (QCKF) algorithm has emerged as a prominent nonlinear filter algorithm and has found extensive applications in the field of GNSS/SINS integrated attitude determination and positioning system (GNSS/SINS-IADPS) data processing for unmanned aerial vehicles (UAV). However, on one hand, the QCKF algorithm is predicated on the assumption that the random model of filter algorithm, which follows a white Gaussian noise distribution. The noise in actual GNSS/SINS-IADPS is not the white Gaussian noise but rather a ubiquitous non-Gaussian noise. On the other hand, the use of quaternions as state variables is bound by normalization constraints. When applied directly in nonlinear non-Gaussian system without considering normalization constraints, the QCKF algorithm may result in a mismatch phenomenon in the filtering random model, potentially resulting in a decline in estimation accuracy. To address this issue, we propose a novel Gaussian sum quaternion constrained cubature Kalman filter (GSQCCKF) algorithm. This algorithm refines the random model of the QCKF by approximating non-Gaussian noise with a Gaussian mixture model. Meanwhile, to account for quaternion normalization in attitude determination, a two-step projection method is employed to constrain the quaternion, which consequently enhances the filtering estimation accuracy. Simulation and experimental analyses demonstrate that the proposed GSQCCKF algorithm significantly improves accuracy and adaptability in GNSS/SINS-IADPS data processing under non-Gaussian noise conditions for Unmanned Aerial Vehicles (UAVs).
Case report: A case of pseudo-acute kidney injury due to cyclin-dependent kinase inhibitor
Authors: Errabelli Praveen , Lathiya Maulik , Singh Devender
Published: June 2024

Various classes of targeted therapies have emerged in the last few years, which have revolutionized cancer treatment, and improved the prognosis and survival of cancer patients. Unfortunately, these agents have serious toxic effects on the kidneys. Some of the toxic effects are hypertension, acute kidney injury (AKI), and proteinuria. One interesting phenomenon that has emerged recently is pseudo-acute kidney injury due to the interference with the tubular secretion of creatinine by some of the targeted therapeutic agents. Understanding this physiology is needed to avoid unnecessary investigation and withholding of lifesaving chemo regimen. Alternative methods to assess renal function such as cystatin C-based estimated glomerular filtration rate (eGFR) can differentiate true AKI from pseudo-AKI. Here, we describe one such case of pseudo-AKI from cyclin-dependent kinase (CDK) 4/6 inhibitor, abemaciclib, which inhibits tubular secretion of creatinine. Using cystatin-C-based eGFR revealed pseudo-AKI in this case.