bluuebunny/crossref_metadata_2025 huggingface dataset:
The End of Animal Welfare Labelling as We Know It? Persisting Problems at the Consumer Level and PLF-Based Solutions
Authors: Ingenbleek Paul T. M. , Krampe Caspar
Published: June 2022

Over the last few decades, animal welfare (AW) labels have become permanent factors in consumer markets for animal-based food products across Europe. During this time, scholarly thinking about consumer perspectives on AW labelling has identified problems that hinder the effectiveness of labels, pertaining to (i) consumers’ trust in labels, (ii) the number of labels present in the market, (iii) confusion about the meaning of labels, (iv) trade-offs between AW labels and price, (v) consistency between the AW standards and consumers’ individual opinions about AW and (vi) the ability of animal-based sectors to innovate in AW labelling. Based on these insights, this study explores the current state of these problems by questioning 2.433 consumers from four countries in the European Union (Finland, the Netherlands, Spain, and Italy) about these issues. The results show that, while opinions differ between countries and cross-border consumer segments, these issues persist for many consumers. These results cast doubt on the idea that AW labels in their traditional form can substantially increase their effect on the market. The study therefore explores potential data-based solutions to persistent consumer problems by drawing on precision livestock and e-commerce technologies. It extends current data use, which is often limited to farms and value chain actors but rarely reaches consumers. We argue that innovative technologies create opportunities to influence consumers in the often neglected pre- and post-purchase stages, through a selection system where consumers can indicate their AW preferences, receive feedback, and transparently provide insight into their preferences to other value chain actors.
Model-Based Fluid-Structure Interaction Approach for Evaluation of Thoracic Endovascular Aortic Repair Endograft Length in Type B Aortic Dissection
Authors: Aghilinejad Arian , Wei Heng , Magee Gregory A. , Pahlevan Niema M.
Published: June 2022

Thoracic endovascular aortic repair (TEVAR) is a commonly performed operation for patients with type B aortic dissection (TBAD). The goal of TEVAR is to cover the proximal entry tear between the true lumen (TL) and the false lumen (FL) with an endograft to induce FL thrombosis, allow for aortic healing, and decrease the risk of aortic aneurysm and rupture. While TEVAR has shown promising outcomes, it can also result in devastating complications including stroke, spinal cord ischemia resulting in paralysis, as well as long-term heart failure, so treatment remains controversial. Similarly, the biomechanical impact of aortic endograft implantation and the hemodynamic impact of endograft design parameters such as length are not well-understood. In this study, a fluid-structure interaction (FSI) computational fluid dynamics (CFD) approach was used based on the immersed boundary and Lattice–Boltzmann method to investigate the association between the endograft length and hemodynamic variables inside the TL and FL. The physiological accuracy of the model was evaluated by comparing simulation results with the true pressure waveform measurements taken during a live TEVAR operation for TBAD. The results demonstrate a non-linear trend towards increased FL flow reversal as the endograft length increases but also increased left ventricular pulsatile workload. These findings suggest a medium-length endograft may be optimal by achieving FL flow reversal and thus FL thrombosis, while minimizing the extra load on the left ventricle. These results also verify that a reduction in heart rate with medical therapy contributes favorably to FL flow reversal.
Significance of Liver Zonation in Hepatocellular Carcinoma
Authors: Yu Shizhe , Gao Jie , Wang Haoren , Liu Long , Liu Xudong , Xu Yuantong , Shi Jihua , Guo Wenzhi , Zhang Shuijun
Published: June 2022

Liver zonation is fundamental to normal liver function, and numerous studies have investigated the microstructure of normal liver lobules. However, only a few studies have explored the zonation signature in hepatocellular carcinoma (HCC). In this study, we investigated the significance of liver zonation in HCC with the help of single-cell RNA sequencing (scRNA-seq) and multicolor immunofluorescence staining. Liver zonation-related genes were extracted from the literature, and a three-gene model was established for HCC prognosis. The model reliability was validated using bulk RNA and single-cell RNA-level data, and the underlying biological mechanism was revealed by a functional enrichment analysis. The results showed that the signaling pathways of high-risk groups were similar to those of perivenous zones in the normal liver, indicating the possible regulating role of hypoxia in HCC zonation. Furthermore, the co-staining results showed that the low-grade tumors lost their zonation features whereas the high-grade tumors lost the expression of zonation-related genes, which supported the results obtained from the sequencing data.
dmrt2 and myf5 Link Early Somitogenesis to Left-Right Axis Determination in Xenopus laevis
Authors: Tingler Melanie , Brugger Amelie , Feistel Kerstin , Schweickert Axel
Published: June 2022

The vertebrate left-right axis is specified during neurulation by events occurring in a transient ciliated epithelium termed left-right organizer (LRO), which is made up of two distinct cell types. In the axial midline, central LRO (cLRO) cells project motile monocilia and generate a leftward fluid flow, which represents the mechanism of symmetry breakage. This directional fluid flow is perceived by laterally positioned sensory LRO (sLRO) cells, which harbor non-motile cilia. In sLRO cells on the left side, flow-induced signaling triggers post-transcriptional repression of the multi-pathway antagonist dand5. Subsequently, the co-expressed Tgf-β growth factor Nodal1 is released from Dand5-mediated repression to induce left-sided gene expression. Interestingly, Xenopus sLRO cells have somitic fate, suggesting a connection between LR determination and somitogenesis. Here, we show that doublesex and mab3-related transcription factor 2 (Dmrt2), known to be involved in vertebrate somitogenesis, is required for LRO ciliogenesis and sLRO specification. In dmrt2 morphants, misexpression of the myogenic transcription factors tbx6 and myf5 at early gastrula stages preceded the misspecification of sLRO cells at neurula stages. myf5 morphant tadpoles also showed LR defects due to a failure of sLRO development. The gain of myf5 function reintroduced sLRO cells in dmrt2 morphants, demonstrating that paraxial patterning and somitogenesis are functionally linked to LR axis formation in Xenopus.
Effects of Heavy Metals on the Performance and Mechanism of Anaerobic Ammonium Oxidation for Treating Wastewater
Authors: Ren Qiang , Gao Junling , Wang Chenfeng
Published: June 2022

Persistence of ammonium nitrogen and heavy metals in wastewater still remains a challenge, and many wastewater treatment plants face the challenge of removing nitrogen under heavy metal stresses. There is no preferred method for the biological treatment of wastewater containing nitrogen and heavy metals with the possible exception of the anaerobic ammonium oxidation (anammox), since it has shown promise for removing nitrogen under heavy metal stresses. This article reviews the recent research results of the nitrogen-removal performance and mechanism by the anammox process under heavy metal stresses, mainly discussing the enhancing and inhibition effects of heavy metals on the performance of the Anammox reactor. The influencing mechanism of heavy metals on the microbial community and extracellular polymeric substances is also presented, and examples are given for explanation. The main problems of the present research are pointed out, and it is proposed that unifying the metal ion concentrations of inhibiting or promoting anammox activity is necessary for the development and industrial application of the anammox process. The information of this review can offer a great possibility for achieving desired nitrogen removal in wastewater treatment under heavy metal stresses and with significant energy savings.
Synthesis and Biological Evaluation of 5-Fluoro-2-Oxindole Derivatives as Potential α-Glucosidase Inhibitors
Authors: Lin Jing , Liang Qi-Ming , Ye Yuan-Na , Xiao Di , Lu Li , Li Meng-Yue , Li Jian-Ping , Zhang Yu-Fei , Xiong Zhuang , Feng Na , Li Chen
Published: June 2022

α-Glucosidase inhibitors are known to prevent the digestion of carbohydrates and reduce the impact of carbohydrates on blood glucose. To develop novel α-glucosidase inhibitors, a series of 5-fluoro-2-oxindole derivatives (3a ∼ 3v) were synthesized, and their α-glucosidase inhibitory activities were investigated. Biological assessment results showed that most synthesized compounds presented potential inhibition on α-glucosidase. Among them, compounds 3d, 3f, and 3i exhibited much better inhibitory activity with IC50 values of 49.89 ± 1.16 μM, 35.83 ± 0.98 μM, and 56.87 ± 0.42 μM, respectively, which were about 10 ∼ 15 folds higher than acarbose (IC50 = 569.43 ± 43.72 μM). A kinetic mechanism study revealed that compounds 3d, 3f, and 3i inhibited the α-glucosidase in a reversible and mixed manner. Molecular docking was carried out to simulate the affinity between the compound and α-glucosidase.
Cytokines as Potential Biomarkers for Differential Diagnosis of Sepsis and Other Non-Septic Disease Conditions
Authors: Frimpong Augustina , Owusu Ewurama D. A. , Amponsah Jones Amo , Obeng-Aboagye Elizabeth , Puije William van der , Frempong Abena Fremaah , Kusi Kwadwo Asamoah , Ofori Michael Fokuo
Published: June 2022

Sepsis defined as a dysregulated immune response is a major cause of morbidity in children. In sub-Saharan Africa, the clinical features of sepsis overlap with other frequent infections such as malaria, thus sepsis is usually misdiagnosed in the absence of confirmatory tests. Therefore, it becomes necessary to identify biomarkers that can be used to distinguish sepsis from other infectious diseases. We measured and compared the plasma levels of 18 cytokines (Th1 [GM-CSF, IFN-γ, TNF-α, IL-1β, 1L-2, IL-6, IL-8, IL-12/IL-23p40, IL-15], Th2[IL-4, IL-5, IL-13), Th17 [IL17A], Regulatory cytokine (IL-10) and 7 chemokines (MCP-1/CCL2, MIP-1α/CCL3, MIP-1β/CCL4, RANTES/CCL5, Eotaxin/CCL11, MIG/CXCL9 and IP-10/CXCL10 using the Human Cytokine Magnetic 25-Plex Panel in plasma samples obtained from children with sepsis, clinical malaria and other febrile conditions. Children with sepsis had significantly higher levels of IL-1β, IL-12 and IL-17A compared to febrile controls but lower levels of MIP1-β/CCL4, RANTES/CCL5 and IP10/CXCL10 when compared to children with malaria and febrile controls. Even though levels of most inflammatory responses were higher in malaria compared to sepsis, children with sepsis had a higher pro-inflammatory to anti-inflammatory ratio which seemed to be mediated by mostly monocytes. A principal component analysis and a receiver operator characteristic curve analysis, identified seven potential biomarkers; IL-1β, IL-7, IL-12, IL-1RA, RANTES/CCL5, MIP1β/CCL4 and IP10/CXCL10 that could discriminate children with sepsis from clinical malaria and other febrile conditions. The data suggests that sepsis is associated with a higher pro-inflammatory environment. These pro-inflammatory cytokines/chemokines could further be evaluated for their diagnostic potential to differentiate sepsis from malaria and other febrile conditions in areas burdened with infectious diseases.
Protein S Deficiency and the Risk of Venous Thromboembolism in the Han Chinese Population
Authors: Wu Yingying , Liu Jingdi , Zeng Wei , Hu Bei , Hu Yu , Tang Liang V.
Published: June 2022

Plasma levels of the anticoagulant cofactor protein S and PROS1 mutation are reported to impart increased risk of thromboembolism in European and south east Asian populations, but the relationship is not yet documented in Han Chinese in population-based study. Therefore, we undertook a case-control study of this relationship among patients with venous thromboembolism, and probed the genetic factors contributing to low protein S deficiency. Among the 603 consecutively recruited venous thromboembolism patients, 51 (8.5%) proved to be deficient in free protein S antigen (lower than 38.6 U/dl), among whom 30 cases were identified to have a causative mutation by direct sequencing. In contrast, six cases (1.0%) of the 584 healthy controls had low free antigen levels, among whom direct sequencing confirmed disease-causing gene mutations in four controls (0.7%). After adjusting for age and gender, the odds ratio of developing venous thromboembolism in individuals with protein S deficiency based on free protein S tests was 8.1 (95% CI = 3.6–19.9,P< 0.001). Gene sequencing yielded 24 different heterozygous mutations in the 34 participants, of which 13 were newly described. 17 (50%) of the 34 mutations in our study cohort occurred in exons 12 and 13, indicating the LGR2 domain to be a hotspot mutation region for the protein. These findings are conducive to the clinical application of protein S assays for the molecular diagnosis of thrombophilia.
The German EMPATHIC-30 Questionnaire Showed Reliability and Convergent Validity for Use in an Intermediary/General Pediatric Cardiology Unit: A Psychometric Evaluation
Authors: Girch Alona , Rippe Ralph C. A. , Latour Jos M. , Jönebratt Stocker Michaela , Blendermann Magdalena , Hoffmann Katharina , Heppner Hannes , Berger Felix , Schmitt Katharina R. L. , Ferentzi Hannah
Published: June 2022

Background

Family-Centered Care is a useful framework for improving care for hospitalized children with congenital heart disease. The EMpowerment of PArents in THe Intensive Care-30 (EMPATHIC-30) questionnaire is a widely accepted tool to measure parental satisfaction with Family-Centered Care. Psychometric properties of the EMPATHIC-30 have been evaluated in neonatal and pediatric intensive care units, but not in pediatric cardiac care units. Therefore, our aim was to assess the psychometric properties of the German EMPATHIC-30 in an intermediary/general pediatric cardiology unit.

Methods

We used data from a quality management survey comprising the German EMPATHIC-30, a sociodemographic questionnaire and four general satisfaction items. Data were collected at the intermediary/general pediatric cardiology unit of a specialized heart center in Germany (n = 366). We split the data randomly into two subsets. In the first subset, we assessed internal consistency reliability with McDonald's omega and Cronbach's alpha, and convergent validity using Spearman's rank correlation. Furthermore, we explored the internal structure with Principal Component Analysis (PCA). In the second subset, we validated the resulting structure using Confirmatory Factor Analysis (CFA).

Results

The reliability estimates exceeded 0.70 for all five domain scores and 0.90 for the full-scale score. Convergent validity between EMPATHIC-30 domain scores/ the full-scale score and the four general satisfaction items was adequate (rs = 0.40–0.74). The PCA suggested three components, accounting for 56.8% of the total variance. Cross-validation via CFA showed poor model fit (χ2 = 1545.78, χ2/df = 3.85, CFI = 0.70, TLI = 0.66, RMSEA = 0.13), indicating that the EMPATHIC-30 shows no clear and generalizable factor structure in this sample.

Discussion

The German version of the EMPATHIC-30 exhibited reasonable psychometric properties in an intermediary/general pediatric cardiology unit. Follow-up studies should investigate the factor structure of the EMPATHIC-30 in other pediatric inpatient care settings.
A Self-Supervised Deep Learning Reconstruction for Shortening the Breathhold and Acquisition Window in Cardiac Magnetic Resonance Fingerprinting
Authors: Hamilton Jesse I.
Published: June 2022

The aim of this study is to shorten the breathhold and diastolic acquisition window in cardiac magnetic resonance fingerprinting (MRF) for simultaneous T1, T2, and proton spin density (M0) mapping to improve scan efficiency and reduce motion artifacts. To this end, a novel reconstruction was developed that combines low-rank subspace modeling with a deep image prior, termed DIP-MRF. A system of neural networks is used to generate spatial basis images and quantitative tissue property maps, with training performed using only the undersampled k-space measurements from the current scan. This approach avoids difficulties with obtaining in vivo MRF training data, as training is performed de novo for each acquisition. Calculation of the forward model during training is accelerated by using GRAPPA operator gridding to shift spiral k-space data to Cartesian grid points, and by using a neural network to rapidly generate fingerprints in place of a Bloch equation simulation. DIP-MRF was evaluated in simulations and at 1.5 T in a standardized phantom, 18 healthy subjects, and 10 patients with suspected cardiomyopathy. In addition to conventional mapping, two cardiac MRF sequences were acquired, one with a 15-heartbeat(HB) breathhold and 254 ms acquisition window, and one with a 5HB breathhold and 150 ms acquisition window. In simulations, DIP-MRF yielded decreased nRMSE compared to dictionary matching and a sparse and locally low rank (SLLR-MRF) reconstruction. Strong correlation (R2 > 0.999) with T1 and T2 reference values was observed in the phantom using the 5HB/150 ms scan with DIP-MRF. DIP-MRF provided better suppression of noise and aliasing artifacts in vivo, especially for the 5HB/150 ms scan, and lower intersubject and intrasubject variability compared to dictionary matching and SLLR-MRF. Furthermore, it yielded a better agreement between myocardial T1 and T2 from 15HB/254 ms and 5HB/150 ms MRF scans, with a bias of −9 ms for T1 and 2 ms for T2. In summary, this study introduces an extension of the deep image prior framework for cardiac MRF tissue property mapping, which does not require pre-training with in vivo scans, and has the potential to reduce motion artifacts by enabling a shortened breathhold and acquisition window.
Duct Stenting vs. Modified Blalock-Taussig Shunt: New Insights Learned From High-Risk Patients With Duct-Dependent Pulmonary Circulation
Authors: Mini Nathalie , Schneider Martin B. E. , Asfour Boulos , Mikus Marian , Zartner Peter A.
Published: June 2022

Background

As no data were available on the comparison of outcomes between modified Blalock-Taussig shunts (MBTs) vs. duct-stenting (DS) in patients with pulmonary atresia (PA) and an increased ductal tortuosity and in patients with pulmonary atresia and intact septum (PA-IVS) with right ventricle-dependent coronary circulation (RVDCC), we aimed to perform a single-center retrospective evaluation.

Methods

Between 2010 and 2019, 127 patients with duct-dependent pulmonary circulation (DDPC) underwent either MBTs (without additional repairs) (n = 56) or DS (n = 71). The primary endpoint was defined as arriving at the next planned surgery (Glenn or biventricular repair) avoiding one of the following: (1) unplanned surgery or unplanned perforation of the pulmonary valve (PVP) with a stent, (2) procedure-related permanent complications, and (3) death. Two subgroups were considered: (1) patients who had a ductal curvature index (DCI) >0.45 (n = 32) and (2) patients with PA-IVS and RVDCC (n = 13). Ductal curvature index (DCI) was measured in all the patients to assess the tortuosity of the ducts. Patients with DCI >0.45 were considered as being in a high-risk group for the duct-stenting; a previous study showed that the patients with a DCI < 0.45 had a better outcome when compared with those with a DCI> 0.45.

Results

The primary outcome was achieved equally in the two groups (77.5% in DS, 75% in MBTs). Hospital deaths, need for ECMO, and the occurrence of major complications was more frequent in the group with MBTs with an Odds Ratio (OR) of 5, 0.8, and 4, respectively, and a 95% Confidence Interval (CI) 1.1–22.6, 0.7–0.9, and 1.6–10.3, respectively, and a P-value < 0.05. For the two subgroups, the primary outcome was achieved in 64% of patients with a DCI >0.45 who received MBTs compared to 20% in those with DS (OR 3.5, 95% CI 1.2–10, P 0.005). While 74.1% of the patients with PA-IVS and RVDCC after DS had achieved the primary outcome, all patients with MBTs had an impaired outcome (OR 3.5, 95%CI 1–11.2, P 0.004).

Conclusion

MBTs showed a better outcome in patients with tortuous ducts compared to DS. DS seems to be superior in patients with DDPC with DCI <0.45 and patients with PA-IVS with RVDCC.
Patient Work Personas of Type 2 Diabetes—A Data-Driven Approach to Persona Development and Validation
Authors: Galliford Natasha , Yin Kathleen , Blandford Ann , Jung Joshua , Lau Annie Y. S.
Published: June 2022

Introduction

Many have argued that a “one-size-fits-all” approach to designing digital health is not optimal and that personalisation is essential to achieve targeted outcomes. Yet, most digital health practitioners struggle to identify which design aspect require personalisation. Personas are commonly used to communicate patient needs in consumer-oriented digital health design, however there is often a lack of reproducible clarity on development process and few attempts to assess their accuracy against the targeted population. In this study, we present a transparent approach to designing and validating personas, as well as identifying aspects of “patient work,” defined as the combined total of work tasks required to manage one's health and the contextual factors influencing such tasks, that are sensitive to an individual's context and may require personalisation.

Methods

A data-driven approach was used to develop and validate personas for people with Type 2 diabetes mellitus (T2DM), focusing on patient work. Eight different personas of T2DM patient work were constructed based physical activity, dietary control and contextual influences of 26 elderly Australian participants (median age = 72 years) via wearable camera footage, interviews, and self-reported diaries. These personas were validated for accuracy and perceived usefulness for design, both by the original participants and a younger (median age bracket = 45–54 years) independent online cohort f 131 T2DM patients from the United Kingdom and the United States.

Results

Both the original participants and the independent online cohort reported the personas to be accurate representations of their patient work routines. For the independent online cohort, 74% (97/131) indicated personas stratified to their levels of exercise and diet control were similar to their patient work routines. Findings from both cohorts highlight aspects that may require personalisation include daily routine, use of time, and social context.

Conclusion

Personas made for a specific purpose can be very accurate if developed from real-life data. Our personas retained their accuracy even when tested against an independent cohort, demonstrating their generalisability. Our data-driven approach clarified the often non-transparent process of persona development and validation, suggesting it is possible to systematically identify whether persona components are accurate or. and which aspects require more personalisation and tailoring.
Ambulatory Assessment in Concussion Clinical Care and Rehabilitation
Authors: Elbin R. J. , Womble Melissa N. , Elbich Daniel B. , Dollar Christina , Fedor Sheri , Hakun Jonathan G.
Published: June 2022

Concussion is a mild traumatic brain injury that is characterized by a wide range of physical, emotional, and cognitive symptoms as well as neurocognitive, vestibular, and ocular impairments that can negatively affect daily functioning and quality of life. Clinical consensus statements recommend a targeted, clinical profile-based approach for management and treatment. This approach requires that clinicians utilize information obtained via a clinical interview and a multi-domain assessment battery to identify clinical profile(s) (e.g., vestibular, mood/anxiety, ocular, migraine, cognitive fatigue) and prescribe a corresponding treatment/rehabilitation program. Despite this comprehensive approach, the clinical picture can be limited by the accuracy and specificity of patient reports (which often conflate timing and severity of symptomology), as well as frequency and duration of exposure to symptom exacerbating environments (e.g., busy hallways, sitting in the back seat of a car). Given that modern rehabilitation programs leverage the natural environment as a tool to promote recovery (e.g., expose-recover approach), accurate characterization of the patient clinical profile is essential to improving recovery outcomes. Ambulatory assessment methodology could greatly benefit concussion clinical care by providing a window into the symptoms and impairments experienced by patients over the course of their daily lives. Moreover, by evaluating the timing, onset, and severity of symptoms and impairments in response to changes in a patient's natural environment, ambulatory assessments can provide clinicians with a tool to confirm clinical profiles and gauge effectiveness of the rehabilitation program. In this perspective report, we review the motivations for utilizing ambulatory assessment methodology in concussion clinical care and report on data from a pilot project utilizing smart phone-based, ambulatory assessments to capture patient reports of symptom severity, environmental exposures, and performance-based assessments of cognition for 7 days following their initial evaluation.
A Scoping Review of Internationalization of Dental Education—Identifying Formats and Motivations in Dental Education
Authors: Wu Anette , Shamim Abrar , Rahhal Zacharie , Kieff Monica , Lalla Evanthia , Torre Lynda , Zubiaurre Bitzer Laureen , Kunzel Carol
Published: June 2022

Background

Internationalization efforts, including global health activities, in dental education can play an important role in preparing future oral healthcare professionals. To date, in the available literature, there is no common understanding of what internationalization of dental education might mean, and there are no agreed-upon standards relating to, or a common definition of, the term internationalization of dental education. Here, the authors investigate what has been published in the above area from 01/01/2000 to 12/31/2020, identifying perceived motivations and formats. A proposed definition and connection to the field of international higher education are provided.

Methods

A scoping review of published literature was performed and identified 47 relevant articles. The articles were thematically sorted based on educational formats and concepts (previously established in international higher education) and motivations.

Results

Despite the paucity of articles directly addressing internationalization of dental education, there was a large variety of articles on topics that were identified to correlate with international higher education, ranging from international partnerships, student mobility, and language, to international curriculum at home—with different perceived motivations, including competition, international understanding, and social transformation.

Discussion

More research on internationalization of dental education is needed to provide guidelines and formalize standards for international educational goals to better align formats and motivations for international efforts in dental education.
Thyroid Inconveniences With Vaccination Against SARS-CoV-2: The Size of the Matter. A Systematic Review
Authors: Caironi Verdiana , Pitoia Fabián , Trimboli Pierpaolo
Published: June 2022

After the beginning of COVID-19 vaccination campaigns, several reports of thyroid disease possibly related to the COVID-19 vaccination progressively appeared in the literature, raising the question of whether the thyroid disorder might be a SARS-CoV-2 vaccine complication. The aim of this study was to analyze the data about COVID-19 vaccination and thyroid disease, evaluate the size and quality of related literature, assess the type of these events, and investigate their timing of onset with respect the vaccination. Pubmed/MEDLINE and Cochrane were systematically reviewed until February 2022 to retrieve the largest number of original papers, case reports, and case series articles reporting thyroid disease after SARS-CoV-2 vaccination. Forty-six articles were included with a total of 99 patients aged from 26 to 73 years were described, of whom 74.75% female. Regarding the vaccination received, 49.49% of patients received Comirnaty (Pfizer/BioNTech), 14.14% CoronaVac (Sinovac), 12.12% Vaxzevria (Oxford/Astrazeneca), 11.11% Spikevax (Moderna), 3.03% Ad26.COV2.S (Janssen, Johnson & Johnson), one patient Covaxin (Bharat Biotech) and one patient Convidecia (Cansino). In 7 cases the thyroid disorder developed after the third dose with a combination of different vaccines. Regarding the type of thyroid disorder, 59 were subacute thyroiditis (SAT), 29 Graves’ disease (GD), 2 co-occurrence of SAT and GD, 6 painless thyroiditis (PT), and single cases of thyroid eye disease and hypothyroidism associated with mixedema. The timeline between vaccination and thyroid disorder ranged between 0.5 to 60 days, with an average of 10.96 days. Considering the limited follow-up time, a complete remission was reported in most of SAT and PT cases while a persistence was observed in GD. In conclusion, both size and quality of published data about thyroid inconveniences after COVID-19 vaccination are limited; thyroid disorders may occur within 2 months after COVID-19 vaccination; among all thyroid diseases after COVID-19 vaccination, GD and SAT seem to be more frequent.
Comparative Evaluation of the Effects of Legacy and New Generation Perfluoralkyl Substances (PFAS) on Thyroid Cells In Vitro
Authors: De Toni Luca , Di Nisio Andrea , Rocca Maria Santa , Pedrucci Federica , Garolla Andrea , Dall’Acqua Stefano , Guidolin Diego , Ferlin Alberto , Foresta Carlo
Published: June 2022

Background

Per- and poly-fluorinated alkyl substances (PFAS) are environment-persitent emerging endocrine disrupting chemicals raising health concerns worldwide. Exposure to PFAS has been associated with the imbalance of thyroid hormones. However, available studies addressing the cell mechanism underlying thyroid disrupting feature of legacy PFAS, such as perfluoro-octanoic acid (PFOA), perfluoro-octane-sulfonic acid (PFOS), and the new generation substitutes, such as C6O4, are still lacking. In this study the potential disrupting effect of PFOA, PFOS, and C6O4 on a murine thyroid cell model was assessed.

Methods

A rat FRTL-5 cell line was used as the normal thyroid follicular cell model. Cell iodide-uptake, induced by thyroid stimulating hormone (TSH), was used to assess the functional impact of PFAS exposure on cell function. Tetrazolium salt-based cell viability assay and merocyanine 540-based cell staining were used to address the possible involvement of cell toxicity and membrane biophysical properties on altered cell function. The possible direct interaction of PFAS with TSH-receptor (TSH-R) was investigated by computer-based molecular docking and analysis of molecular dynamics. Evaluation of intracellular cAMP levels and gene expression analysis were used to validate the direct impairment of TSH-R-mediated downstream events upon PFAS exposure.

Results

Different from PFOS or C6O4, exposure to PFOA at a concentration ≥ 10 ng/mL was associated with significant impairment of the iodide uptake upon TSH stimulation (respectively: basal 100.0 ± 19.0%, CTRL + TSH 188.9 ± 7.8%, PFOA 10 ng/mL + TSH 120.4 ± 20.9%, p= 0.030 vs CTRL + TSH; PFOA 100 ng/mL + TSH 115,6 ± 12,3% p= 0.017 vs CTRL + TSH). No impairment of cell viability or membrane stability was observed. Computational analysis showed a possible direct differential interaction of C6O4, PFOA, and PFOS on a same binding site of the extracellular domain of TSH-R. Finally, exposure to PFOA was associated with a significant reduction of downstream intracellular cAMP levels and both sodium-iodide transporter and thyroperoxidase gene expression upon TSH-R stimulation.

Conclusions

Our data suggest that legacy and new generation PFAS can differentially influence TSH dependent signaling pathways through the direct interaction with TSH-R.
Prediction of Remaining Useful Life of the Lithium-Ion Battery Based on Improved Particle Filtering
Authors: Wu Tiezhou , Zhao Tong , Xu Siyun
Published: June 2022

Remaining useful life (RUL) prediction of lithium-ion batteries plays an important role in battery failure prediction and health management (PHM). By accurately predicting the RUL of the battery, the battery can be replaced accordingly, thereby effectively avoiding the occurrence of an accident and ensuring the normal operation of the entire system. In the prediction of the remaining service life of lithium-ion batteries, it is difficult to ensure accuracy due to the problem of particle degradation and the influence of singular values in the particle filter algorithm. In view of these problems, this article introduces the unscented Kalman algorithm to improve the particle filter algorithm from the perspective of re-weighting the particles, so as to improve the accuracy of the prediction results of the remaining service life of lithium-ion batteries. The improved particle filter is simulated and verified using the battery sample data in the Arbin experimental test platform. Comparing the simulation results with the traditional particle filter method, when the number of reference samples is the same, the PDF width of the prediction results of the improved particle filter algorithm is slightly smaller than that of the particle filter algorithm, indicating that the fluctuation of the prediction result is more accurate. It is proved that the improved particle filter method proposed in this article can provide more accurate battery RUL prediction results and can effectively improve the accuracy and robustness of the remaining service life prediction of lithium-ion batteries.
Fish Parasites and Heavy Metals Relationship in Wild and Cultivated Fish as Potential Health Risk Assessment in Egypt
Authors: Radwan Mahmoud , Abbas Mahmoud Mahrous M. , Afifi Moharam Adel Mohamed , Mohammadein Amaal , Al Malki Jamila S.
Published: June 2022

Despite wide studies of biomonitoring aquatic environment through dynamics of host–parasite interaction, bio-indicators to track the influence and accumulation of heavy metals on fish are still few. The present study sheds light on the relation between fish parasites and heavy metals as it threatens fish’s health and, as a consequence, that of humans after fish consumption. Samples of Nile tilapia (Oreochromis niloticus) were collected in Burullus Lake, a wild fish source, and from a private fish farm in Kafr El-Sheikh Governorate, in Egypt. They were exposed to various pollutants associated with anthropogenic activities to determine the levels of accumulation of Fe, Zn, and Cu, along with the top three most toxic metals (As, Cd, and Pb) in water and fish tissues of gills, intestine, liver, and muscles in both wild and farmedO. niloticus. The results showed the order of abundance: Fe < Zn < Pb < Cu < As < Cd. In waters of both farmed and wild fish, there was a significant negative relation between parasite prevalence and heavy metals, including Zn, Pb, and As. Also, there was a significant positive relation between parasite prevalence with Cu while no significant relation was found with Fe and Cd. Heavy metal content was significantly higher (p> 0.05) in non-infected than infected farmed and wildO. niloticus. In addition, a significantly decreased concentration (p> 0.05) of essential heavy metal was recorded in wild fish compared to farmed specimens, while non-essential heavy metal was significantly higher (p> 0.05) in wild compared to farmed fish. Bioaccumulation factors (BAF) of different organs ofO. niloticuswere ranked in ascending order: Liver > Gills > Intestine > Muscles. In general, the risk assessment showed safe human consumption of farmed and wild fish under the reported environmental conditions in this study. Moreover, the parasite's presence can be adopted as a surrogate indicator to estimate the potential impact of heavy metal pollution and accumulation.
The Domestication of the Seasons: The Exploitation of Variations in Crop Seasonality Responses by Later Prehistoric Farmers
Authors: Jones Martin K. , Lister Diane L.
Published: June 2022

Discussions of domestication and its associated genetic traits has focused upon dispersal mechanisms, for example in the rachis structure of cereals. Here we consider another trait of importance to domesticated crops – their seasonality response. We particularly consider flowering response to changing daylength, and how that relates to domesticated species that are carried by farmers considerable distances from their regions of origin. We consider the implications of cultivating crops in regions whose seasonality patterns contrast with those of the crop’s region of origin, and consider the consequent genetic changes. Reference is made to the particular case of barley, and a discussion of archaeogenetic research into its photoperiod response mechanism is provided.
Integrating Transcriptomic and Metabolomic Analyses to Explore the Effect of Color Under Fruit Calyx on That of Fruit Apex in Eggplant (Solanum melongena L.)
Authors: Zhang Jingjing , Li Bing , Gao Xiurui , Pan Xiuqing , Wu Yanrong
Published: June 2022

Fruit color is an important commercial characteristic of eggplant (Solanum melongena L.), which affects both the profits of growers and consumer choice. Two eggplant inbred lines were discovered: “Z,” which is a light purple color under the fruit calyx, with purple on the fruit apex; and “L,” fruits of which are green under the calyx and at the apex. To determine the molecular mechanisms underlying the effect of fruit peel color under the calyx on that at the fruit apex, we conducted a combined transcriptomic and metabolomic analyses of the Z and L inbred eggplant lines. Transcriptome analysis of peel samples from three fruit regions (under the calyx, the apex, and the middle surface) of each line was conducted by RNA sequencing, and generated a total of 791,512,404 clean reads from 18 samples (three biological replicates). Differentially expressed genes (DEGs; n = 424) were identified in comparisons of peel samples from the three sites of L line fruits. Gene ontology analysis showed that “catalytic activity” was extremely significantly enriched. Further, DEGs (n = 8) were enriched in the Kyoto Encyclopedia of Genes and Genomes pathway “flavonoid biosynthesis.” Levels of CHI, LDOX, F3′5′H, and dihydroflavonol reductase were higher in the Z line than the L line. In addition, metabolome analysis showed that, 10 differentially accumulated metabolites were detected between peel samples from the apex of L and Z line fruit. The most significant DAM was delphinidin-3-O-rutinoside (Z line content, 34.89 μg/g vs. L line content 0.01 μg/g). Combined transcriptomic and metabolomic analyses indicated that DFR and F3′5′H were closely related to content of the metabolites, cyanidin and delphinidin, and that some downstream metabolites differed significantly between the L and Z lines. Content levels of delphinidin-3-O-rutinoside, delphinidin-3-O-glucoside, cyanidin-3-O-glucoside, and cyanidin-3-O-rutinoside were markedly down-regulated in the L line. Altogether, increased CHI levels could up-regulate the downstream genes, LDOX, F3′5′H, and DFR, which further lead to increasing the content of delphindin. Thus, the uniform purple color was presented at the apex of fruits in Z plants. These findings not only identify key candidate genes, but will also improve understanding of the genetics and the efficiency of breeding for eggplant fruit color.
Role of the PD-1/PD-L1 Pathway in Experimental Trypanosoma cruzi Infection and Potential Therapeutic Options
Authors: Arana Yanina , Gálvez Rosa Isela , Jacobs Thomas
Published: June 2022

Chagas disease (CD) is a neglected chronic infection caused by the protozoan parasiteTrypanosoma cruzi(T. cruzi). A significant portion of infected people develops cardiac or digestive alterations over a lifetime. Since several chronic infections associated with antigen persistence and inflammation have been shown to lead to T cell exhaustion, new therapies targeting co-inhibitory receptors to regain T cell activity are under consideration. This study explored immune therapeutic approaches targeting the inhibitory PD-1/PD-L pathway in an experimental model for CD. Infected PD-L1 knockout mice (PD-L1 KO) showed increased systemic parasitemia in blood although no significant differences in parasite load were observed in different organs. Furthermore, we found no significant differences in the frequency of activated T cells or proinflammatory cytokine production when compared to WT counterparts. PD-L1 deficiency led to the production of IL-10 by CD8+T cells and an upregulation of Tim-3 and CD244 (2B4). Unexpectedly, the lack of PD-L1 did not contribute to a significantly improved T cell response to infection. Single blockade and combined blockade of PD-1 and Tim-3 using monoclonal antibodies confirmed the results observed in infected. PD-L1 KO mice. Our results describe for the first time that the interruption of the PD-1/PD-L1 axis during acuteT. cruziinfection does not necessarily enhance the immune response against this parasite. Its interruption favors increased levels of parasitemia and sustained upregulation of other co-inhibitory receptors as well as the production of regulatory cytokines. These results suggest that the clinical application of immune therapeutic approaches targeting thePD-1/PD-L1axis in CD might be risky and associated with adverse events. It highlights that more research is urgently needed to better understand the immune regulation of T cells in CD before designing immune therapeutic approaches for a clinical context.
Identification of Highly Cross-Reactive Mimotopes for a Public T Cell Response in Murine Melanoma
Authors: Grace Beth E. , Backlund Coralie M. , Morgan Duncan M. , Kang Byong H. , Singh Nishant K. , Huisman Brooke D. , Rappazzo C. Garrett , Moynihan Kelly D. , Maiorino Laura , Dobson Connor S. , Kyung Taeyoon , Gordon Khloe S. , Holec Patrick V. , Mbah Overbeck C. Takou , Garafola Daniel , Wu Shengwei , Love J. Christopher , Wittrup K. Dane , Irvine Darrell J. , Birnbaum Michael E.
Published: June 2022

While immune checkpoint blockade results in durable responses for some patients, many others have not experienced such benefits. These treatments rely upon reinvigorating specific T cell-antigen interactions. However, it is often unknown what antigens are being recognized by T cells or how to potently induce antigen-specific responses in a broadly applicable manner. Here, we characterized the CD8+T cell response to a murine model of melanoma following combination immunotherapy to determine the basis of tumor recognition. Sequencing of tumor-infiltrating T cells revealed a repertoire of highly homologous TCR sequences that were particularly expanded in treated mice and which recognized an antigen from an endogenous retrovirus. While vaccination against this peptide failed to raise a protective T cell responsein vivo, engineered antigen mimotopes induced a significant expansion of CD8+T cells cross-reactive to the original antigen. Vaccination with mimotopes resulted in killing of antigen-loaded cellsin vivoyet showed modest survival benefit in a prophylactic vaccine paradigm. Together, this work demonstrates the identification of a dominant tumor-associated antigen and generation of mimotopes which can induce robust functional T cell responses that are cross-reactive to the endogenous antigen across multiple individuals.
Humoral and Cellular Immune Response After a 3-Dose Heterologous SARS-CoV-2 Vaccination Using the mRNA-BNT162b2 and Viral Vector Ad26COVS1 Vaccine in Hemodialysis Patients
Authors: Davidovic Tamara , Schimpf Judith , Abbassi-Nik Armin , Stockinger Richard , Sprenger-Mähr Hannelore , Lhotta Karl , Zitt Emanuel
Published: June 2022

Background

Due to the waning humoral response after a two-dose SARS-CoV-2 mRNA vaccination, a third booster was recommended in hemodialyis patients. Data on a heterologous mRNA-vector regimen, which might improve immunogenicity, are very limited.

Methods

In this observational study 36 chronic hemodialysis patients (mean (SD) age 66.9 (15.9) years, 33.3% females) were followed up for 13 months. All patients were vaccinated twice using the mRNA-BNT162b2 vaccine, followed by a 3rd dose of the vector vaccine Ad26COVS1 eight months later. We assessed the humoral response by quantifying the anti-SARS-CoV-2 spike IgG antibody and neutralizing antibody concentrations. The cellular immune response was evaluated via SARS-CoV-2 spike protein-specific interferon-γ release assay.

Results

The seroconversion rate was 47.2%, 100%, 69.4% and 100% one month after the 1st dose, one and six months after the 2nd dose and four months after the heterologous 3rd dose. The median (Q1, Q3) anti-SARS-CoV-2 spike IgG concentrations at the same time were 28.7 (13.2, 69.4) BAU/ml, 1130.0 (594.5, 1735.0) BAU/ml, 89.7 (26.4, 203.8) BAU/ml, and 2080.0 (1062.5, 2080.0) BAU/ml. The percentage of patients with neutralizing antibodies was 58.3% after the 2nd dose and improved to 100% after the 3rd dose (P <0.001). A positive T-cell response was found in 50% of patients after the 3rd dose.

Conclusions

A third heterologous booster dose helped to sustain humoral immunity in almost all hemodialysis patients and induced a significant T-cellular response in half of them. Stimulating the immune response against SARS-CoV-2 by two different vaccine platforms seems to be a promising approach.
Relationship Between Anemia and Systemic Inflammation in People Living With HIV and Tuberculosis: A Sub-Analysis of the CADIRIS Clinical Trial
Authors: Araújo-Pereira Mariana , Barreto-Duarte Beatriz , Arriaga María B. , Musselwhite Laura W. , Vinhaes Caian L. , Belaunzaran-Zamudio Pablo F. , Rupert Adam , Montaner Luis J. , Lederman Michael M. , Sereti Irini , Madero Juan G. Sierra , Andrade Bruno B.
Published: June 2022

People with HIV (PWH) are at increased risk of developing active tuberculosis (TB), and anemia is a common complication in both conditions. Anemia in TB patients has been linked to immune activation, levels of inflammatory biomarkers in blood, and risk for HIV disease progression and death. In this study we show that anemia was associated with a more pronounced inflammatory profile in HIV-TB coinfected persons in a cohort of 159 individuals with advanced HIV disease (CD4 count < 100 cells/µL) recruited as part of a randomized clinical trial (NCT00988780). A panel of plasma biomarkers was assessed on plasma obtained prior to combination antiretroviral therapy (cART) initiation. We performed a series of multidimensional analyses including clinical variables and concentrations of inflammatory biomarkers to profile systemic inflammation of PWH with and without anemia. We observed that TB participants presented with moderately lower levels of hemoglobin than non-TB participants. These participants also presented a higher Degree of Inflammatory Perturbation (DIP) score, related to increased levels of IFN-γ and TNF. The DIP was associated with TB coinfection and anemia before cART initiation. Future mechanistic studies are warranted to assess the determinants of such associations and the implications on treatment outcomes.