bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell uptake and intracellular trafficking of bioreducible poly(amidoamine) nanoparticles for efficient mRNA translation in chondrocytes
Authors: Pontes Adriano P. , van der Wal Steffen , Ranamalla Saketh R. , Roelofs Karin , Tomuta Ioan , Creemers Laura B. , Rip Jaap
Published: November 2023

Disulfide-containing poly(amidoamine) (PAA) is a cationic and bioreducible polymer, with potential use as a nanocarrier for mRNA delivery in the treatment of several diseases including osteoarthritis (OA). Successful transfection of joint cells with PAA-based nanoparticles (NPs) was shown previously, but cell uptake, endosomal escape and nanoparticle biodegradation were not studied in detail. In this study, C28/I2 human chondrocytes were transfected with NPs co-formulated with a PEG-polymer coating and loaded with EGFP mRNA for confocal imaging of intracellular trafficking and evaluation of transfection efficiency. Compared with uncoated NPs, PEG-coated NPs showed smaller particle size, neutral surface charge, higher colloidal stability and superior transfection efficiency. Furthermore, endosomal entrapment of these PEG-coated NPs decreased over time and mRNA release could be visualized both in vitro and in live cells. Importantly, cell treatment with modulators of the intracellular reducing environment showed that glutathione (GSH) concentrations affect translation of the mRNA payload. Finally, we applied a D-optimal experimental design to test different polymer-to-RNA loading ratios and dosages, thus obtaining an optimal formulation with up to ≈80% of GFP-positive cells and without toxic effects. Together, the biocompatibility and high transfection efficiency of this system may be a promising tool for intra-articular delivery of therapeutical mRNA in OA treatment.
Hedgehog signaling and the glioma-associated oncogene in cancer radioresistance
Authors: Zhang Li , Zhang Yuhan , Li Kaixuan , Xue Shuai
Published: November 2023

Tumor radioresistance remains a key clinical challenge. The Hedgehog (HH) signaling pathway and glioma-associated oncogene (GLI) are aberrantly activated in several cancers and are thought to contribute to cancer radioresistance by influencing DNA repair, reactive oxygen species production, apoptosis, autophagy, cancer stem cells, the cell cycle, and the tumor microenvironment. GLI is reported to activate the main DNA repair pathways, to interact with cell cycle regulators like Cyclin D and Cyclin E, to inhibit apoptosis via the activation of B-cell lymphoma-2, Forkhead Box M1, and the MYC proto-oncogene, to upregulate cell stemness related genes (Nanog, POU class 5 homeobox 1, SRY-box transcription factor 2, and the BMI1 proto-oncogene), and to promote cancer stem cell transformation. The inactivation of Patched, the receptor of HH, prevents caspase-mediated apoptosis. This causes some cancer cells to survive while others become cancer stem cells, resulting in cancer recurrence. Combination treatment using HH inhibitors (including GLI inhibitors) and conventional therapies may enhance treatment efficacy. However, the clinical use of HH signaling inhibitors is associated with toxic side effects and drug resistance. Nevertheless, selective HH agonists, which may relieve the adverse effects of inhibitors, have been developed in mouse models. Combination therapy with other pathway inhibitors or immunotherapy may effectively overcome resistance to HH inhibitors. A comprehensive cancer radiotherapy with HH or GLI inhibitor is more likely to enhance cancer treatment efficacy while further studies are still needed to overcome its adverse effects and drug resistance.
Lipid rafts mediate multilineage differentiation of human dental pulp-derived stem cells (DPSCs)
Authors: Santilli Francesca , Fabrizi Jessica , Martellucci Stefano , Santacroce Costantino , Iorio Egidio , Pisanu Maria Elena , Chirico Mattea , Lancia Loreto , Pulcini Fanny , Manganelli Valeria , Sorice Maurizio , Delle Monache Simona , Mattei Vincenzo
Published: November 2023

Cell outer membranes contain glycosphingolipids and protein receptors, which are integrated into glycoprotein domains, known as lipid rafts, which are involved in a variety of cellular processes, including receptor-mediated signal transduction and cellular differentiation process. In this study, we analyzed the lipidic composition of human Dental Pulp-Derived Stem Cells (DPSCs), and the role of lipid rafts during the multilineage differentiation process. The relative quantification of lipid metabolites in the organic fraction of DPSCs, performed by Nuclear Magnetic Resonance (NMR) spectroscopy, showed that mono-unsaturated fatty acids (MUFAs) were the most representative species in the total pool of acyl chains, compared to polyunsatured fatty acids (PUFAs). In addition, the stimulation of DPSCs with different culture media induces a multilineage differentiation process, determining changes in the gangliosides pattern. To understand the functional role of lipid rafts during multilineage differentiation, DPSCs were pretreated with a typical lipid raft affecting agent (MβCD). Subsequently, DPSCs were inducted to differentiate into osteoblast, chondroblast and adipoblast cells with specific media. We observed that raft-affecting agent MβCD prevented AKT activation and the expression of lineage-specific mRNA such as OSX, PPARγ2, and SOX9 during multilineage differentiation. Moreover, this compound significantly prevented the tri-lineage differentiation induced by specific stimuli, indicating that lipid raft integrity is essential for DPSCs differentiation. These results suggest that lipid rafts alteration may affect the signaling pathway activated, preventing multilineage differentiation.
Graphene quantum dots promote migration and differentiation of periodontal ligament stem cells
Authors: Liang Yan , Gao Wanshan , Deng Sicheng , Wu Dongyan , Jiang Yiling , Zhang Yishan , Qiu Rongmin
Published: November 2023

Graphene and its derivatives have attracted much attention as nanomaterials in bone tissue engineering because of their remarkable ability to induce cell osteogenic differentiation. However, graphene quantum dots (GQDs), as graphene derivatives, little is known about their osteodifferentiation- and osteoinduction-promoting capabilities, especially in the restoration of bone defect caused by periodontitis. Therefore, there is a growing need to investigate the effect of GQDs on periodontal ligament stem cells (PDLSCs). Here, we postulated that GQDs are a promising biocompatible nanomaterial that facilitated the migration and differentiation of PDLSCs, and use laboratory methods like CCK-8, transwell experiments, qRT-PCR, Alizarin red staining and immunofluorescence staining to evaluate. Our experiments confirmed that GQDs did not inhibit cell viability, with most cells remaining viable even at GQDs concentrations of up to 30 μg mL-1. Moreover, GQDs were found to significantly enhance PDLSC migration, with the peak effect observed at concentrations of 5 and 10 μg mL-1. Furthermore, GQDs accelerated osteoblastic differentiation in PDLSCs and induced the mineralization of calcium nodules. Additionally, GQDs were shown to promote fibroblast differentiation in PDLSCs compared to the control group. Thus, GQDs not only possessed low cytotoxicity and good biocompatibility, but also displayed the beneficial capability to migration and differentiation of PDLSCs, which indicated GQDs might be a potential nanomaterial for bone regeneration.
When do tripdoublet states fluoresce? A theoretical study of copper(II) porphyrin
Authors: Wang Xingwen , Wu Chenyu , Wang Zikuan , Liu Wenjian
Published: November 2023

Open-shell molecules rarely fluoresce, due to their typically faster non-radiative relaxation rates compared to closed-shell ones. Even rarer is the fluorescence from states that have two more unpaired electrons than the open-shell ground state, since they involve excitations from closed-shell orbitals to vacant-shell orbitals, which are typically higher in energy compared to excitations from or out of open-shell orbitals. States that are dominated by the former type of excitations are known as tripdoublet states when they can be described as a triplet excitation antiferromagnetically coupled to a doublet state, and their description by unrestricted single-reference methods (e.g., U-TDDFT) is notoriously inaccurate due to large spin contamination. In this work, we applied our spin-adapted TDDFT method, X-TDDFT, and the efficient and accurate static-dynamic-static second order perturbation theory (SDSPT2), to the study of the excited states as well as their relaxation pathways of copper(II) porphyrin; previous experimental works suggested that the photoluminescence of some substituted copper(II) porphyrins originate from a tripdoublet state, formed by a triplet ligand π → π* excitation antiferromagnetically coupled with the unpaired d electron. Our results demonstrated favorable agreement between the X-TDDFT, SDSPT2 and experimental excitation energies, and revealed noticeable improvements of X-TDDFT compared to U-TDDFT, not only for vertical excitation energies but also for adiabatic energy differences. These suggest that X-TDDFT is a reliable tool for the study of tripdoublet state fluorescence. Intriguingly, we showed that the aforementioned tripdoublet state is only slightly above the lowest doublet excited state and lies only slightly higher than the lowest quartet state, which suggests that the tripdoublet of copper(II) porphyrin is long-lived enough to fluoresce due to a lack of efficient non-radiative relaxation pathways; an explanation for this unusual state ordering is given. Indeed, thermal vibration correlation function (TVCF)-based calculations of internal conversion, intersystem crossing, and radiative transition rates confirm that copper(II) porphyrin emits thermally activated delayed fluorescence (TADF) and a small amount of phosphorescence at low temperature (83 K), in accordance with experiment. The present contribution is concluded by a few possible approaches of designing new molecules that fluoresce from tripdoublet states.
Hemoglobin albumin lymphocyte and platelet score and all-cause mortality in coronary heart disease: a retrospective cohort study of NHANES database
Authors: Zheng Yang , Huang Yubing , Li Haitao
Published: November 2023

Aim

Anemia, inflammatory status, and malnutrition are all important factors in the prognosis of cardiovascular disease (CVD), and their interactions are also noteworthy. A recent scoring system, the hemoglobin albumin lymphocyte and platelet (HALP) score, combining multi-dimensional metrics, has been used in the prognoses of many diseases except coronary heart disease (CHD). Herein, this study aims to explore the association between HALP score and all-cause mortality in patients with CHD.

Methods

Demographic and clinical data of adult patients with CHD were extracted from the National Health and Nutrition Examination Surveys (NHANES) database from 2003 to 2018 in this retrospective cohort study. Weighted univariate and multivariate COX proportional hazard models were used for covariates screening and exploration of the association between HALP score and all-cause mortality. The evaluation indexes were hazard ratios (ORs) and 95% confidence intervals (CIs). Kaplan-Meier (KM) curve and the receiver operator characteristic (ROC) curve were used to assess the predictive performance of HALP on CHD prognosis. In addition, subgroup analyses of age and congestive heart failure (CHF) were also performed.

Results

Among the eligible patients, 657 died of all-cause mortality. After adjusting for the covariates including age, education level, PIR, marital status, smoking, physical activity, total energy intake, CHF, stroke, hypertension, DM, CKD, cancer or malignancy, monocyte, drug for CVD, treatment for anemia, anticoagulants drug, and adrenal cortical steroids, we found that HALP score was negatively associated with the risk of all-cause mortality [HR = 0.83, 95% CI: (0.74–0.93)]. Compared with patients with high HALP scores, those who had lower HALP scores seemed to have a higher risk of all-cause mortality (all P < 0.05). HALP score has a potential predictive value on CHD prognosis with an area under the curve (AUC) of 0.61. Furthermore, in patients aged <65 years, with or without CHF, a lower HALP score was also associated with a higher risk of all-cause mortality (all P < 0.05).

Conclusions

HALP score has a potential predictive value on CHD prognosis; however, the causal association between HALP score and mortality in patients with CHD needs further exploration.
Lower ventricular and atrial strain in patients who recovered from COVID-19 assessed by cardiovascular magnetic resonance feature tracking
Authors: Mojica-Pisciotti Mary Luz , Panovský Roman , Holeček Tomáš , Opatřil Lukáš , Feitová Věra
Published: November 2023

Introduction

One of the most common complications of coronavirus disease 2019 (COVID-19) is myocardial injury, and although its cause is unclear, it can alter the heart's contractility. This study aimed to characterize the ventricular and atrial strain in patients who recovered from COVID-19 using cardiovascular magnetic resonance feature-tracking (CMR-FT).

Methods

In this single-center study, we assessed left ventricle (LV) and right ventricular (RV) global circumferential strain (GCS), global longitudinal strain (GLS), global radial strain (GRS), left atrial (LA) and right atrial (RA) longitudinal strain (LS) parameters by CMR-FT. The student's t-test and Wilcoxon rank-sum test were used to compare the variables.

Results

We compared seventy-two patients who recovered from COVID-19 (49 ± 16 years) to fifty-four controls (49 ± 12 years, p = 0.752). The patients received a CMR examination 48 (34 to 165) days after the COVID-19 diagnosis. 28% had LGE. Both groups had normal LV systolic function. Strain parameters were significantly lower in the COVID-19 survivors than in controls.

Discussion

Patients who recovered from COVID-19 exhibited significantly lower strain in the left ventricle (through LVGCS, LVGLS, LVGRS), right ventricle (through RVGLS and RVGRS), left atrium (through LALS), and right atrium (through RALS) than controls.
Sustainable development goals in teacher education: comparing syllabi in a Japanese and a Slovenian university
Authors: Fiel’ardh Khalifatulloh , Torkar Gregor , Rožman Hana , Fujii Hiroki
Published: November 2023

Introduction

This research aims to explore the integration of Sustainable Development Goals (SDGs) within teacher education programs, focusing on the Faculty of Education at Okayama University, Japan and the University of Ljubljana, Slovenia.

Methods

We employed a qualitative content analysis of the syllabi (n = 2,079 from Okayama University; n = 504 from University of Ljubljana) and combined it with insights from semi-structured interviews.

Results

The analysis illuminated a strong emphasis on Quality Education (SDG 4) in both institutions. However, certain SDGs, like Climate Action (SDG 13), were less represented, marking potential areas for enhancement. Differences were also identified in the distribution of SDGs-related content between compulsory and elective courses, indicating institutional priorities. Interview reflections emphasized the pivotal role of educators in realizing SDGs and highlighted the necessity of collaboration to achieve these global objectives.

Discussion

The insights from interviews and syllabi content analysis underscore the urgency to bridge the identified gaps in SDG coverage. Disparities in emphasis between the two Education for Sustainable Development (ESD)-committed universities were noted, suggesting the importance of fostering strategy exchange and partnerships across institutions.

Conclusion

Enhancing the alignment of teacher education programs with SDGs requires collective efforts. By addressing the gaps and promoting effective collaboration, these programs can achieve greater relevance and efficacy in promoting the SDGs.
Guiding pre-service teachers’ visual attention through instructional settings: an eye-tracking study
Authors: Gabel Sylvia , Keskin Özün , Kollar Ingo , Lewalter Doris , Gegenfurtner Andreas
Published: November 2023

In complex classroom situations, pre-service teachers often struggle to identify relevant information. Consequently, classroom videos are widely used to support pre-service teachers’ professional vision. However, pre-service teachers need instructional guidance to attend to relevant information in classroom videos. Previous studies identified a specific task instruction and prompts as promising instructions to enhance pre-service teachers’ professional vision. This mixed-methods eye-tracking study aimed to compare pre-service teachers’ visual attention to information relevant for classroom management in one of three instructional conditions. Participants viewed two classroom videos and clicked a button whenever they identified situations relevant to classroom management in the videos. They got either (1) a specific task instruction before video viewing (n = 45), (2) attention-guiding prompts during video viewing (n = 45), or (3) a general task instruction (n = 45) before video viewing as a control group. We expected a specific task instruction and prompts to better guide participants’ visual attention compared to a general task instruction before video viewing because both experimental conditions contained informational cues to focus on specific dimensions of classroom management. As both a specific task and prompts were assumed to activate cognitive schemata, resulting in knowledge-based processing of visual information, we expected the specific task instruction to have a similar attention-guiding effect as prompts during video viewing. Measurements were conducted on an outcome level (mouse clicks) and on a process level (eye tracking). Findings confirmed our hypotheses on an outcome level and in part on a process level regarding participants’ gaze relational index. Nevertheless, in a disruptive classroom situation, participants of the prompting condition showed better attentional performance than participants of the other conditions regarding a higher number of fixation and a shorter time to first fixation on disruptive students. Further qualitative analyses revealed that, when observing classroom videos without instructional guidance, pre-service teachers were less likely to identify disruptive situations in the video and more likely to attend to other situations of classroom management concerning the teachers’ action. We discuss advantages of both attention-guiding instructions for pre-service teacher education in terms of the economy of implementation and the salience of situations.
Association of Cutibacterium acnes with human thyroid cancer
Authors: Trivedi Vaishakhi , Noronha Vanita , Sreekanthreddy Peddagangannagari , Desai Sanket , Poojary Disha , Varghese Linu , Gowda Pooja , Butle Ashwin , Mishra Rohit , Bal Munita , Mittal Neha , Rane Swapnil , Kane Shubhada , Basu Sandip , Patil Vijay , Menon Nandini , Singh Ajay Kumar , Chaturvedi Pankaj , Chandrani Pratik , Choughule Anuradha , Veldore Vidya , Prabhash Kumar , Dutt Amit
Published: November 2023

Introduction

The diverse subtypes of thyroid carcinoma have distinct clinical outcomes despite a comparable spectrum of underlying genetic alterations. Beyond genetic alterations, sparse efforts have been made to characterize the microbes associated with thyroid cancer. In this study, we examine the microbial profile of thyroid cancer.

Methods

We sequenced the whole transcriptome of 70 thyroid cancers (40 papillary and 30 anaplastic). Using Infectious Pathogen Detector IPD 2.0, we analysed the relative abundance of 1060 microbes across 70 tumours from patients with thyroid cancer against 118 tumour samples from patients with breast, cervical, colorectal, and tongue cancer.

Results

Our analysis reveals a significant prevalence of Cutibacterium acnes in 58.6% thyroid cancer samples compared to other cancer types (p=0.00038). Immune cell fraction analysis between thyroid cancer samples with high and low Cutibacterium loads identify enrichment of immunosuppressive cells, including Tregs (p=0.015), and other anti-inflammatory cytokines in the tumour microenvironment, suggesting an immune evasion/immunosuppression milieu is associated with the infection. A higher burden of Cutibacterium acnes was also found to be associated with poor survival defining a distinct sub-group of thyroid cancer.

Conclusion

Cutibacterium acnes is associated with immune suppression and poor prognosis in a subpopulation of thyroid cancer. This study may help design novel therapeutic measures involving appropriate antibiotics to manage the disease better.
Knowledge, experiences, and perceptions relating to obesity management among primary care physicians in the Lazio Region, Italy
Authors: Guglielmi Valeria , Capoccia Danila , Russo Benedetta , Lubrano Carla , Mariani Stefania , Poggiogalle Eleonora , Furia Giuseppe , Alizadeh Aurora Heidar , Patrizi Cristina , Sapienza Martina , Damiani Gianfranco , Tarsitano Maria Grazia , Conte Caterina , Frontoni Simona
Published: November 2023

Background

Primary care providers (PCPs) play an essential role in obesity care as they represent the first contact for patients seeking weight loss interventions.

Objective

This study explored the knowledge, experiences, and perceptions of PCPs in the Lazio Region of Italy in the management of obesity.

Design and subjects

We conducted an anonymous survey delivered from March to July 2022 via the newsletter of Rome Provincial Order of Physicians and Dentists and at the annual meeting of the regional section of the Italian Obesity Society.

Approach

The survey consisted of 24 closed-ended questions grouped into 5 sections: sociodemographic and work information; assessment of obesity; management of obesity; connections with regional Centres for Obesity Management; attitudes towards obesity.

Key results

A total of 92 PCPs accessed the survey. Of those, 2.2% were excluded because they did not see any patients with obesity. A total of 68 PCPs (75.6%) had complete questionnaires and were included in this analysis. All participants reported asking their patients about their eating habits, lifestyle, and clinical complications at the first assessment. Body weight and blood pressure were measured by 98.5% of participants and 82% calculate body mass index (BMI), while a small proportion of PCPs analysed body composition and fat distribution. Over 80% prescribed laboratory tests and ECG. Approximately 40% of PCPs did not refer patients for nutritional counselling, and most prescribed a low-calorie diet. Sixty-three percent referred patients to an endocrinologist, 48.5% to a psychotherapist, and a minority to specialists for obesity complications. Twenty-three percent prescribed anti-obesity medications and 46.5% referred patients for bariatric surgery only in severe cases. Ninety-one percent stated that obesity is “a complex and multifactorial disease” and 7.4% considered obesity to be secondary to other conditions.

Conclusions

Despite most PCPs adopt a correct approach to manage patients with obesity, many aspects could be improved to ensure optimal and multidisciplinary management.
Early detection of type 2 diabetes risk: limitations of current diagnostic criteria
Authors: Zhang Jiale , Zhang Zhuoya , Zhang Kaiqi , Ge Xiaolei , Sun Ranran , Zhai Xu
Published: November 2023

Type 2 diabetes (T2D) is the leading cause of diabetes worldwide and is increasing rapidly, especially in youth. It accounts for most diabetes deaths in adults ≥20 years old in the Americas, with type 2 diabetes responsible for most of the disease burden. The incidence and burden of type 2 diabetes in adolescents and young adults have risen in recent decades globally. Countries with lower socioeconomic status had the highest incidence and burden, and females generally had higher mortality and disease burden than males at ages <30 years. Early diagnosis and management are crucial to delaying progression, but current diagnostic criteria based on glucose thresholds and glycated hemoglobin have limitations. Recent analyses show that prediabetes increases cancer risk. Better diagnostic criteria are urgently needed to identify high-risk individuals earlier. This article discusses the limitations of current criteria and explores alternative approaches and future research directions.
Complex relationship between gut microbiota and thyroid dysfunction: a bidirectional two-sample Mendelian randomization study
Authors: Liu Xiao , Liu Jingyu , Zhang Tongxin , Wang Qian , Zhang Huawei
Published: November 2023

Background

Many studies have reported the link between gut microbiota and thyroid dysfunction. However, the causal effect of gut microbiota on thyroid dysfunction and the changes in gut microbiota after the onset of thyroid dysfunction are not clear.

Methods

A two-sample Mendelian randomization (MR) study was used to explore the complex relationship between gut microbiota and thyroid dysfunction. Data on 211 bacterial taxa were obtained from the MiBioGen consortium, and data on thyroid dysfunction, including hypothyroidism, thyroid-stimulating hormone alteration, thyroxine deficiency, and thyroid peroxidase antibodies positivity, were derived from several databases. Inverse variance weighting (IVW), weighted median, MR-Egger, weighted mode, and simple mode were applied to assess the causal effects of gut microbiota on thyroid dysfunction. Comprehensive sensitivity analyses were followed to validate the robustness of the results. Finally, a reverse MR study was conducted to explore the alteration of gut microbiota after hypothyroidism onset.

Results

Our bidirectional two-sample MR study revealed that the genera Intestinimonas, Eubacterium brachy group, Ruminiclostridium5, and Ruminococcaceae UCG004 were the risk factors for decreased thyroid function, whereas the genera Bifidobacterium and Lachnospiraceae UCG008 and phyla Actinobacteria and Verrucomicrobia were protective. The abundance of eight bacterial taxa varied after the onset of hypothyroidism. Sensitivity analysis showed that no heterogeneity or pleiotropy existed in the results of this study.

Conclusion

This novel MR study systematically demonstrated the complex relationship between gut microbiota and thyroid dysfunction, which supports the selection of more targeted probiotics to maintain thyroid–gut axis homeostasis and thus to prevent, control, and reverse the development of thyroid dysfunction.
Tri-ponderal mass index as a screening tool for obesity prediction in children aged 6–9 years
Authors: Niu Yang , Zhang Yajie , Sheng Jinye , Lu Wenyi , Li Ji , Mao Xiaomeng , Cai Wei , Tang Qingya , Shen Xiuhua , Feng Yi
Published: November 2023

Objective

This study aimed to evaluate the efficiency of tri-ponderal mass index (TMI) in determining obesity in Chinese children aged 6-9 years, using the criteria of percentage of body fat (PBF) and body mass index z-scores (BMI-Z).

Methods

The cross-sectional study included 5365 children, aged 6–9 years, who participated in the project survey “Group prevention and treatment of obesity among students and school health promotion in Shanghai” from September 2007 to September 2009. Height, weight, waist circumference, body mass index (BMI), TMI, waist-to-height ratio (WHtR), and PBF were recorded. Statistical analyses including Kolmogorov–Smirnov test, chi-square test, receiver operating characteristics curve, and kappa chi-square test were performed.

Results

TMI for both sexes was relatively constant with increasing age, and statistically significant differences were not observed at some ages (P > 0.05 at 6, 7, 8, and 9 years). WHtR showed subtle changes, while BMI and PBF increased significantly with age in boys and girls (P < 0.01). Using BMI-Z criteria as the measure of general obesity, the results indicated that TMI cutoff values for 6–9 years were 14.60 kg/m3 for boys and 14.84 kg/m3 for girls (P < 0.001). Analysis of the agreement between TMI and BMI-Z showed that the kappa statistic was 0.826 in boys and 0.709 in girls (P < 0.001).

Conclusion

TMI, as a constant tool, holds great potential as an alternative screening method for identifying children aged 6-9 years who may be at risk of obesity at an early stage.
How patients experience thyroid eye disease
Authors: Smith Terry J. , Hegedüs Laszlo , Lesser Ira , Perros Petros , Dorris Kimberly , Kinrade Michele , Troy-Ott Patti , Wuerth Laura , Nori Mukund
Published: November 2023

Objective

To determine the impact of thyroid eye disease (TED) on patients in various stages of the disease.

Background

TED is a debilitating and potentially sight-threatening inflammatory autoimmune disease that is frequently misdiagnosed. Challenging quality-of-life (QoL) issues can persist long after the active phase of disease has subsided.

Methods

A 62-question survey was designed as a hypothesis-generating instrument to identify key issues confronting patients ≥18 years old with physician-diagnosed TED. Questions focused primarily on physical and emotional status, and QoL experiences in the 2 months prior to the survey. Data for individual questions are presented as summary statistics. Correlations between questions were determined using χ2 analyses.

Results

The 443 respondents were 18 to >80 years old; >90% female, and >80% from the United States. Time since TED diagnosis ranged from <1 year to >10 years. Participants provided >500 free-form responses describing experiences of living with TED. Physical signs/symptoms were experienced by 307/443 (69%) patients. Of those responding to the QoL questions (N = 394), 53 (13%) reported symptoms improving, 73 (19%) reported symptoms worsening, and 255 (65%) reported no change in the 2 months prior to the survey. The most bothersome signs/symptoms were dry/gritty eyes, light sensitivity, bulging eyes, and pressure or pain behind the eyes. Respondents <60 years were significantly (p < 0.0001) more likely to report symptomatic TED than older patients. Of 394 respondents, 179 (45%) reported feeling depressed and/or anxious, 174 (44%) reported concern about their appearance, and 73 (19%) avoided public situations; 192 (49%) reported declines in confidence or feelings of general well-being, and 78 (20%) reported an inability to achieve goals. Activities limited by TED included reading, driving, and socializing. The proportion of respondents experiencing these negative QoL measures was higher when patients reported experiencing >5 symptoms, had been diagnosed within the last 5 years, or were <60 years of age.

Conclusions

Physical manifestations of TED impact QoL for patients through all phases of the disease. It is essential that physicians and healthcare professionals become more familiar with patient experiences such as those described here to better help patients manage their disease.
Compliance relationship analysis between environmental governance attention and environmental quality in the Beijing–Tianjin–Hebei region
Authors: Wang Lin , Pan Feng , Li Xiaojing
Published: November 2023

This study analyzes the changes and allocation characteristics of environmental governance attention in the Beijing–Tianjin–Hebei region based on the government work report from 2002 to 2020 and explores the compliance relationship between environmental governance attention and environmental quality. The results show that the allocation of local government environmental governance attention shows high consistency with that of the central government, and the overall environmental governance attention shows a fluctuating upward trend. There is a long-term stable co-integrated relationship between environmental governance attention and environmental quality in the Beijing–Tianjin–Hebei region, as well as a two-way Granger causality relationship in the short term. The non-linear influence of environmental governance attention on the environmental quality in the Beijing–Hebei–Tianjin region can be described using the LSTR2 model. During 2004–2016, environmental governance attention often had non-linear effects on the environmental quality. Since 2016, there has been a stable linear relationship between environmental governance attention and environmental quality. Finally, some policy suggestions on improving the local performance evaluation system and establishing a collaborative environment system for the Beijing–Tianjin–Hebei region have been put forward for the government.
Using riverscape genetics to investigate the genetic response of two species and their life-history forms to dam removal
Authors: Ledger Kimberly J. , Su Yingxin , Jeon Jong Yoon , Fullerton Aimee H. , Kuligowski David , Bennett Todd , Denton Keith , McHenry Michael , McMillan John H. , Anderson Joseph H. , Connor Heidi , Seamons Todd R. , Pess George , Nichols Krista M. , McKinney Garrett , Seaborn Travis , Fraik Alexandra K.
Published: November 2023

Barriers such as hydroelectric dams inhibit migratory pathways essential to many aquatic species, resulting in significant losses of species, their unique life-history forms, and genetic diversity. Understanding the impacts of dam removal to species recovery at these different biological levels is crucial to fully understand the restoration response. We used the removal of two large dams on the Elwha River as an opportunity to characterize how restored connectivity impacts the reestablishment of two fish species, Chinook salmon (Oncorhynchus tshawytscha) and Steelhead/rainbow trout (Oncorhynchus mykiss), and their unique ocean migration return-timing life-history forms. In this study, we employed riverscape genetics to understand how restoration and the environment influence the distribution of neutral and return-timing genetic variation underlying the migratory life-history forms and species at- and between- sampling sites. We genotyped fish sampled over time and space in the Elwha River using Genotyping-in-Thousands by sequencing (GTseq) loci for both species at neutral and putatively adaptive loci in and near the major effect genic region GREB1L/ROCK1 putatively associated with migration timing. We observed little evidence of genetic structure for either species, but a statistically significant increase in early return-timing alleles in upriver O. mykiss population post-dam removal. For O. tshawytscha, at-site genetic variation was shaped by river distance and a combination of environmental habitat differences, while between-site genetic variation was mainly shaped by river distance. For all O. mykiss, at- and between-site genetic variation is primarily explained by river distance. Genetic variation in juvenile and adult Steelhead, respectively, were influenced by at- and between-site environmental and habitat differences. Our study illustrates the power of using genetics to understand the implications of both demography and environment in facilitating the recovery of species and their diverse life-history forms following barrier removal.
Practitioner perspectives on the application of palaeoecology in nature conservation
Authors: Siggery Ben , Bennion Helen , Morse Stephen , Murphy Richard , Waite Mike
Published: November 2023

It is widely recognised that palaeoecology holds great potential to inform and support nature conservation, but that there are difficulties in knowledge exchange between academia and practitioners that inhibit the operationalisation of research. To facilitate the integration of palaeoecology into the conservation toolkit, it is essential to understand perspectives of the practitioners themselves and the contexts in which they work. This paper reports the results of a survey of 153 UK-based conservation practitioners, concerning their perceptions of palaeoecology, the barriers to its use and potential solutions for making palaeoecological insights more accessible in conservation practice. The survey was conducted online over a period of 3 months; closed question responses were analysed for statistical trends and thematic analysis was done on open question responses. The majority of respondents were strongly positive about the role palaeoecological research could play, though they also exhibited a limited understanding of how and why one might implement it. They identified time constraints as the biggest barrier to using palaeoecology within their work, and also flagged concerns around financial resources and the accessibility of the research. Access to applied case studies and a centralised database were the most favoured solutions among respondents. Respondents with prior experience of working with palaeoecology were generally more optimistic about its incorporation. This paper makes several key recommendations to progress the integration of palaeoecology into conservation, including improving data accessibility, aligning research design with conservation and policy drivers, and increasing both respective groups’ understanding of the other.
Characteristics of carbon sources and sinks and their relationships with climate factors during the desertification reversal process in Yulin, China
Authors: Feng Xiao , Fan Qingbin , Qu Jianjun , Ding Xinhui , Niu Ziru
Published: November 2023

Research on carbon sources/sinks in desert ecosystems is of great importance to understand the carbon cycle and its response to climate change. Net primary productivity (NPP) and net ecosystem productivity (NEP) are the two most important indictors for quantitatively evaluating carbon storage and can be used to indicate the response of terrestrial ecosystems to climate change. In this study, we used remote sensing data, meteorological data and vegetation type data to estimate the NPP and NEP using CASA model and soil respiration model from 2000 to 2020 in the region of Yulin, which is a typical desertification reversal region in the Mu Us Sandy Land. The spatial and temporal features of the NPP and NEP and their relationships with temperature and precipitation were determined. The results showed that both the annual NPP and NEP showed an increasing trend from 2000 to 2020 in the region of Yulin, where the terrestrial ecosystem acted as a carbon source until 2001 but turned into a sink thereafter. The carbon storage showed an increasing trend with a rate of 0.50 Tg C·a−1 from 2000 to 2020. Both the mean annual NPP and the total NEP increased from the west to the east of the region in spatial distribution. The total NEP indicated that the area with a carbon sink accounted for 89.22% of the total area, showing a carbon accumulation of 103.0 Tg C, and the carbon source area accounted for 10.78% of the total area with a carbon emission of 4.40 Tg C. The net carbon sequestration was 99.44 Tg C in the region of Yulin during the period from 2000 to 2020. Temperature had no significant effects on NPP and NEP for most areas of the region, while precipitation had a positive effect on the increasing NPP in 75.3% of areas and NEP in 30.07% of areas of the region. These results indicated that it is of utmost significance to protect terrestrial ecosystems from degradation, and ecological restoration projects are essential in combating desertification, which would be helpful for soil water conservation and could effectively increase carbon storage in desert ecosystems.
Genome-wide identification of the PFK gene family and their expression analysis in Quercus rubra
Authors: Kim Tae-Lim , Lim Hyemin , Denison Michael Immanuel Jesse , Natarajan Sathishkumar , Oh Changyoung
Published: November 2023

The glycolytic pathway involves phosphofructokinase (PFK), a rate-limiting enzyme that catalyzes the phosphorylation of fructose-6-phosphate. In plants, the two PFK members are ATP-dependent phosphofructokinase (PFK) and pyrophosphate-fructose-6-phosphate phosphotransferase (PFP). However, the functions of the PFK family members in Quercus rubra are not well understood. The purpose of this study was to investigate the genome-wide distribution of the PFK family members and their roles in Q. rubra by performing a systematic study of the phylogenetic relationships, molecular characteristics, motifs, chromosomal and subcellular locations, and cis-elements of QrPFKs. We identified 14 QrPFK genes in the genome of Q. rubra, followed by examining their expression in different tissues, including the roots, stems, and leaves. The phylogenetic tree divided the 14 QrPFK genes into two groups: 11 belonging to PFK and three belonging to PFP. The expression profiles of all 14 proteins were relatively the same in leaves but differed between stems and roots. Four genes (Qurub.02G189400.1, Qurub.02G189400.2, Qurub.09G134300.1, and Qurub.09G134300.2) were expressed at very low levels in both stems and roots, while two (Qurub.05G235500.1 and Qurub.05G235500.1) were expressed at low levels and the others showed relatively high expression in all tissues.
HIV-1 and opiates modulate miRNA profiles in extracellular vesicles
Authors: Caobi Allen , Bonilla Jesenia , Gomez Mario , Andre Mickensone , Yndart Adriana , Fernandez-Lima Francisco A. , Nair Madhavan P. , Raymond Andrea D.
Published: November 2023

Opiate abuse increases the risk of HIV transmission and exacerbates HIV neuropathology by increasing inflammation and modulating immune cell function. Exosomal EVs(xEV) contain miRNAs that may be differentially expressed due to HIV infection or opiate abuse. Here we develop a preliminary exosomal-miRNA biomarker profile of HIV-infected PBMCs in the context of opiate use. PBMCs infected with HIV were treated with increasing dosages of morphine for 72 hours, the culture supernatants were collected, and the exosomes isolated using differential centrifugation. Exosomal miRNAs were extracted, expression levels determined via Nanostring multiplexed microRNA arrays, and analyzed with Webgestalt. The effect of the exosomes on neuronal function was determined by measuring calcium. Preliminary findings show that HIV-1 infection altered the miRNA profile of PBMC-derived EVs concurrently with opiate exposure. MicroRNA, hsa-miR-1246 was up-regulated 12-fold in the presence of morphine, relative to uninfected control. PBMCs infected with HIV-1 MN, an X4-tropic HIV-1 strain and exposed to morphine, displayed a trend which suggests potential synergistic effects between HIV-1 infection and morphine exposure promoting an increase in viral replication. Dose-dependent differences were observed in miRNA expression as a result of opiate exposure. The xEVs derived from PBMCs exposed to morphine or HIV modulated neuronal cell function. SH-SY5Y cells, treated with xEVs derived from ART-treated PBMCs, exhibited increased viability while for SH-SY5Ys exposed to xEVs derived from HIV-1 infected PBMCs viability was decreased compared to the untreated control. Exposing SH-SY5Y to xEVs derived from HIV-infected PBMCs resulted in significant decrease in calcium signaling, relative to treatment with xEVs derived from uninfected PBMCs. Overall, HIV-1 and morphine induced differential miRNA expression in PBMC-derived exosomes, potentially identifying mechanisms of action or novel therapeutic targets involved in opiate use disorder, HIV neuropathology, TNF signaling pathway, NF-κB signaling pathway, autophagy, and apoptosis in context of HIV infection.
Heterologous booster with a novel formulation containing glycosylated trimeric S protein is effective against Omicron
Authors: Bottero Daniela , Rudi Erika , Martin Aispuro Pablo , Zurita Eugenia , Gaillard Emilia , Gonzalez Lopez Ledesma Maria M. , Malito Juan , Stuible Matthew , Ambrosis Nicolas , Durocher Yves , Gamarnik Andrea V. , Wigdorovitz Andrés , Hozbor Daniela
Published: November 2023

In this study, we evaluated the efficacy of a heterologous three-dose vaccination schedule against the Omicron BA.1 SARS-CoV-2 variant infection using a mouse intranasal challenge model. The vaccination schedules tested in this study consisted of a primary series of 2 doses covered by two commercial vaccines: an mRNA-based vaccine (mRNA1273) or a non-replicative vector-based vaccine (AZD1222/ChAdOx1, hereafter referred to as AZD1222). These were followed by a heterologous booster dose using one of the two vaccine candidates previously designed by us: one containing the glycosylated and trimeric spike protein (S) from the ancestral virus (SW-Vac 2µg), and the other from the Delta variant of SARS-CoV-2 (SD-Vac 2µg), both formulated with Alhydrogel as an adjuvant. For comparison purposes, homologous three-dose schedules of the commercial vaccines were used. The mRNA-based vaccine, whether used in heterologous or homologous schedules, demonstrated the best performance, significantly increasing both humoral and cellular immune responses. In contrast, for the schedules that included the AZD1222 vaccine as the primary series, the heterologous schemes showed superior immunological outcomes compared to the homologous 3-dose AZD1222 regimen. For these schemes no differences were observed in the immune response obtained when SW-Vac 2µg or SD-Vac 2µg were used as a booster dose. Neutralizing antibody levels against Omicron BA.1 were low, especially for the schedules using AZD1222. However, a robust Th1 profile, known to be crucial for protection, was observed, particularly for the heterologous schemes that included AZD1222. All the tested schedules were capable of inducing populations of CD4 T effector, memory, and follicular helper T lymphocytes. It is important to highlight that all the evaluated schedules demonstrated a satisfactory safety profile and induced multiple immunological markers of protection. Although the levels of these markers were different among the tested schedules, they appear to complement each other in conferring protection against intranasal challenge with Omicron BA.1 in K18-hACE2 mice. In summary, the results highlight the potential of using the S protein (either ancestral Wuhan or Delta variant)-based vaccine formulation as heterologous boosters in the management of COVID-19, particularly for certain commercial vaccines currently in use.
Targeting tumor-associated macrophage: an adjuvant strategy for lung cancer therapy
Authors: Liu Lei , Chen Genwang , Gong Sisi , Huang Rongfu , Fan Chunmei
Published: November 2023

The emergence of immunotherapy has revolutionized the treatment landscape for various types of cancer. Nevertheless, lung cancer remains one of the leading causes of cancer-related mortality worldwide due to the development of resistance in most patients. As one of the most abundant groups of immune cells in the tumor microenvironment (TME), tumor-associated macrophages (TAMs) play crucial and complex roles in the development of lung cancer, including the regulation of immunosuppressive TME remodeling, metabolic reprogramming, neoangiogenesis, metastasis, and promotion of tumoral neurogenesis. Hence, relevant strategies for lung cancer therapy, such as inhibition of macrophage recruitment, TAM reprograming, depletion of TAMs, and engineering of TAMs for drug delivery, have been developed. Based on the satisfactory treatment effect of TAM-targeted therapy, recent studies also investigated its synergistic effect with current therapies for lung cancer, including immunotherapy, radiotherapy, chemotherapy, anti-epidermal growth factor receptor (anti-EGFR) treatment, or photodynamic therapy. Thus, in this article, we summarized the key mechanisms of TAMs contributing to lung cancer progression and elaborated on the novel therapeutic strategies against TAMs. We also discussed the therapeutic potential of TAM targeting as adjuvant therapy in the current treatment of lung cancer, particularly highlighting the TAM-centered strategies for improving the efficacy of anti-programmed cell death-1/programmed cell death-ligand 1 (anti-PD-1/PD-L1) treatment.