bluuebunny/crossref_metadata_2025 huggingface dataset:
Global trends and current status of distraction osteogenesis: Bibliometric analysis of publications from 1980 to 2021
Authors: Liu Qi , Liang Jieyu , Liu Ze , Guo Hongbin , Wang Min , Zhang Yi
Published: November 2022

Introduction: Distraction osteogenesis (DO) has become an important technology for the correction of various congenital and acquired skeletal ridge deformities. It is widely used in oral and maxillofacial surgery, orthopedics, and other disciplines. From 1980 to 2021, the cutting-edge research of DO has been continuously promoted, and the interaction between disciplines has also been deepening. However, the analysis on the global trend and status of DO is relatively rare. Therefore, the aim of our study was to summarize the global trends and current status of DO through bibliometrics.

Materials and methods: Web of Science (WOS) core collection database and Medline were used to search DO-related literatures published during 1980–2021. The collected data are imported into Microsoft Excel, Microsoft Word, VOSviewer software for analysis and drawing figure/table.

Results: A total of 7,721 publications were included in this study. The United States is the main contributing country to DO (ranking first in terms of total publications, sum of times cited and H-index). Harvard University was the main contributing institution to DO. Journal of Craniofacial Surgery is the main contributing journal of DO related articles. Buchman, SR is the main contributing author to DO related articles. DO related publications can be summarized into 7 clusters: 1) “mechanism study”, 2) “limb bone distraction study”, 3) “alveolar bone distraction study”, 4) “temporomandibular joint ankylosis study”, 5) “maxillofacial surgery study”, 6) “skull distraction study” and 7) “mandible distraction study”. Mandible distraction study has been a hot topic in recent years. In addition, the “management”, “osteogenesis” and “reconstruction” of DO have been the research hotspots from 1980 to 2021.

Conclusion: From 1980 to 2021, the total number of DO articles has increased rapidly and maintained a steady trend. The United States is the predominant country in the field. Surgery, dental, and oral surgery and orthopaedics are hot fields of DO research. The study of mandible distraction has been paid more and more attention and will become a hotspot in the future. Our study is beneficial for scientists to specify the research hotspot and development direction of DO.
MSCs vs. iPSCs: Potential in therapeutic applications
Authors: Thanaskody Kalaiselvaan , Jusop Amirah Syamimi , Tye Gee Jun , Wan Kamarul Zaman Wan Safwani , Dass Sylvia Annabel , Nordin Fazlina
Published: November 2022

Over the past 2 decades, mesenchymal stem cells (MSCs) have attracted a lot of interest as a unique therapeutic approach for a variety of diseases. MSCs are capable of self-renewal and multilineage differentiation capacity, immunomodulatory, and anti-inflammatory properties allowing it to play a role in regenerative medicine. Furthermore, MSCs are low in tumorigenicity and immune privileged, which permits the use of allogeneic MSCs for therapies that eliminate the need to collect MSCs directly from patients. Induced pluripotent stem cells (iPSCs) can be generated from adult cells through gene reprogramming with ectopic expression of specific pluripotency factors. Advancement in iPS technology avoids the destruction of embryos to make pluripotent cells, making it free of ethical concerns. iPSCs can self-renew and develop into a plethora of specialized cells making it a useful resource for regenerative medicine as they may be created from any human source. MSCs have also been used to treat individuals infected with the SARS-CoV-2 virus. MSCs have undergone more clinical trials than iPSCs due to high tumorigenicity, which can trigger oncogenic transformation. In this review, we discussed the overview of mesenchymal stem cells and induced pluripotent stem cells. We briefly present therapeutic approaches and COVID-19-related diseases using MSCs and iPSCs.
Synthesis of 14H-dibenzoxanthenes in green media using Sn(II)/nano silica as an efficient catalyst
Authors: Tavakol Hossein , Firouzi Mahdieh
Published: November 2022

In this project, Sn(II)/nano silica has been prepared using a simple deposition of SnCl2.2.H2O on nano-silica. The prepared catalyst has been used as a green and reusable catalyst for synthesis of 14H-dibenzoxanthenes through a one-pot condensation reaction of β-naphthol with various aliphatic and aromatic aldehydes. Several xanthene derivatives have been synthesized using ethanol as the solvent, 10 mol percent of the catalyst, at reflux condition, in 3 h, and by 48%–94% yield. The structures of the synthesized derivatives are confirmed by melting point, FT-IR, 13C-NMR, and 1H-NMR analyses. Additionally, the nanocatalyst composition was confirmed by SEM, EDX, FT-IR, and XRD.
Pyridinic nitrogen dominated doping on Pd/carbon catalysts for enhanced hydrogenation performance
Authors: He Limin , Wang Yangdong , Wang Can , Liu Zhicheng , Xie Zaiku
Published: November 2022

The hydrogenation of 4-carboxylbenzaldehyde over Pd catalysts is a crucial process during the production of pure terephthalic acid. Herein, ZIF-8 derived carbon materials (NC) with adjustable N types were synthesized and used as the supports of Pd catalysts. Pd supported on NC with 50.5% of pyridinic N exhibited best hydrogenation activity with a TOF value of 4.1 min−1. The microstructures of NC support and electronic structures of Pd in Pd/NC were investigated by techniques such as XRD, N2 physisorption, XPS, H2-O2 titration and TEM. The nitrogen species in CN surface not only can adjust chemical state and dispersion of Pd nanoparticles (NPs), but also promote the adsorption and activation capability of H2 molecular. Besides, the ratio of Pd0/Pd2+ and Pd dispersion were closely correlated with pyridinic nitrogen content. The improvement in hydrogenation activity and stability of Pd/CN catalyst in relative to Pd/C were ascribed to the synergistic effect of pyridinic nitrogen and active site Pd0.
Evaluation of the consistence between the results of immunoinformatics predictions and real-world animal experiments of a new tuberculosis vaccine MP3RT
Authors: Cheng Peng , Xue Yong , Wang Jie , Jia Zaixing , Wang Liang , Gong Wenping
Published: November 2022

Background

Our previous study developed a novel peptide-based vaccine, MP3RT, to fight against tuberculosis (TB) infection in a mouse model. However, the consistency between the immunoinformatics predictions and the results of real-world animal experiments on the MP3RT vaccine remains unclear.

Method

In this study, we predicted the antigenicity, immunogenicity, physicochemical parameters, secondary structure, and tertiary structure of MP3RT using bioinformatics technologies. The immune response properties of the MP3RT vaccine were then predicted using the C-ImmSim server. Finally, humanized mice were used to verify the characteristics of the humoral and cellular immune responses induced by the MP3RT vaccine.

Results

MP3RT is a non-toxic and non-allergenic vaccine with an antigenicity index of 0.88 and an immunogenicity index of 0.61, respectively. Our results showed that the MP3RT vaccine contained 53.36% α-helix in the secondary structure, and the favored region accounted for 98.22% in the optimized tertiary structure. The binding affinities of the MP3RT vaccine to the human leukocyte antigen (HLA)-DRB1*01:01 allele, toll-like receptor-2 (TLR-2), and TLR-4 receptors were -1234.1 kcal/mol, -1066.4 kcal/mol, and -1250.4 kcal/mol, respectively. The results of the C-ImmSim server showed that the MP3RT vaccine could stimulate T and B cells to produce immune responses, such as high levels of IgM and IgG antibodies, IFN-γ, TNF-α, and IL-2 cytokines. Results from real-world animal experiments showed that the MP3RT vaccine could stimulate the humanized mice to produce high levels of IgG and IgG2a antibodies and IFN-γ+ T lymphocytes. Furthermore, the levels of IFN-γ, IL-2, and IL-6 cytokines in mice immunized with the MP3RT vaccine were significantly higher than those in the control group.

Conclusion

MP3RT is a highly antigenic and immunogenic potential vaccine that can effectively induce Th1-type immune responses in silico analysis and animal experiments. This study lays the foundation for evaluating the value of computational tools and immunoinformatic techniques in reverse vaccinology research.
Cost analysis of chronic heart failure management in Malaysia: A multi-centred retrospective study
Authors: Ong Siew Chin , Low Joo Zheng , Yew Wing Yee , Yen Chia How , Abdul Kader Muhamad Ali S. K. , Liew Houng Bang , Abdul Ghapar Abdul Kahar
Published: November 2022

Background

Estimation of the economic burden of heart failure (HF) through a complete evaluation is essential for improved treatment planning in the future. This estimation also helps in reimbursement decisions for newer HF treatments. This study aims to estimate the cost of HF treatment in Malaysia from the Ministry of Health’s perspective.

Materials and methods

A prevalence-based, bottom-up cost analysis study was conducted in three tertiary hospitals in Malaysia. Chronic HF patients who received treatment between 1 January 2016 and 31 December 2018 were included in the study. The direct cost of HF was estimated from the patients’ healthcare resource utilisation throughout a one-year follow-up period extracted from patients’ medical records. The total costs consisted of outpatient, hospitalisation, medications, laboratory tests and procedure costs, categorised according to ejection fraction (EF) and the New York Heart Association (NYHA) functional classification.

Results

A total of 329 patients were included in the study. The mean ± standard deviation of total cost per HF patient per-year (PPPY) was USD 1,971 ± USD 1,255, of which inpatient cost accounted for 74.7% of the total cost. Medication costs (42.0%) and procedure cost (40.8%) contributed to the largest proportion of outpatient and inpatient costs. HF patients with preserved EF had the highest mean total cost of PPPY, at USD 2,410 ± USD 1,226. The mean cost PPPY of NYHA class II was USD 2,044 ± USD 1,528, the highest among all the functional classes. Patients with underlying coronary artery disease had the highest mean total cost, at USD 2,438 ± USD 1,456, compared to other comorbidities. HF patients receiving angiotensin-receptor neprilysin-inhibitor (ARNi) had significantly higher total cost of HF PPPY in comparison to patients without ARNi consumption (USD 2,439 vs. USD 1,933, p < 0.001). Hospitalisation, percutaneous coronary intervention, coronary angiogram, and comorbidities were the cost predictors of HF.

Conclusion

Inpatient cost was the main driver of healthcare cost for HF. Efficient strategies for preventing HF-related hospitalisation and improving HF management may potentially reduce the healthcare cost for HF treatment in Malaysia.
Artificial intelligence for antiviral drug discovery in low resourced settings: A perspective
Authors: Namba-Nzanguim Cyril T. , Turon Gemma , Simoben Conrad V. , Tietjen Ian , Montaner Luis J. , Efange Simon M. N. , Duran-Frigola Miquel , Ntie-Kang Fidele
Published: November 2022

Current antiviral drug discovery efforts face many challenges, including development of new drugs during an outbreak and coping with drug resistance due to rapidly accumulating viral mutations. Emerging artificial intelligence and machine learning (AI/ML) methods can accelerate anti-infective drug discovery and have the potential to reduce overall development costs in Low and Middle-Income Countries (LMIC), which in turn may help to develop new and/or accessible therapies against communicable diseases within these countries. While the marketplace currently offers a plethora of data-driven AI/ML tools, most to date have been developed within the context of non-communicable diseases like cancer, and several barriers have limited the translation of existing tools to the discovery of drugs against infectious diseases. Here, we provide a perspective on the benefits, limitations, and pitfalls of AI/ML tools in the discovery of novel therapeutics with a focus on antivirals. We also discuss available and emerging data sharing models including intellectual property-preserving AI/ML. In addition, we review available data sources and platforms and provide examples for low-cost and accessible screening methods and other virus-based bioassays suitable for implementation of AI/ML-based programs in LMICs. Finally, we introduce an emerging AI/ML-based Center in Cameroon (Central Africa) which is currently developing methods and tools to promote local, independent drug discovery and represents a model that could be replicated among LMIC globally.
Test-Retest reliability and preliminary reliable change estimates for Sway Balance tests administered remotely in community-dwelling adults
Authors: Caccese Jaclyn B. , Teel Elizabeth , Van Patten Ryan , Muzeau Mélissa A. , Iverson Grant L. , VanRavenhorst-Bell Heidi A.
Published: November 2022

Objective

Impaired balance and postural stability can occur with advanced age, following traumatic brain injury, in association with neurological disorders and diseases, and as the result of acute or chronic orthopedic problems. The remote assessment of balance and postural stability could be of value in clinical practice and research. We examined the test-retest reliability and reliable change estimates for Sway Balance Mobile Application tests (Sway Medical, Tulsa OK, USA) administered remotely from the participant's home.

Method

Primarily young, healthy community-dwelling adults completed Sway Balance Mobile Application tests remotely on their personal mobile devices once per week for three consecutive weeks while being supervised with a video-based virtual connection. Sway Balance tests include five stances (i.e., feet together, tandem right foot forward, tandem left foot forward, single leg right foot, single leg left foot), which are averaged to compute a Sway Balance composite score from 0 to 100, with higher scores indicating better postural stability. We examined test-retest reliability (measured with intraclass correlation coefficients, ICCs) and preliminary reliable change estimates for 70%, 80%, and 90% confidence intervals.

Results

Participants included 55 healthy adults (ages = 26.7 ± 9.9 years, interquartile range = 20–30, range = 18–58; 38 [69%] women). Test-retest reliability for the Sway Balance composite score across three weeks was.88. Test-retest reliability for individual stances ranged from 62 to 83 (all ps < 0.001). At the 80% confidence interval, preliminary reliable changes estimates were 9 points for the Sway Balance composite score.

Conclusions

For a remote administration, test–retest reliability was moderate-to-good for all Sway Balance stances, as well as for the Sway Balance composite score. Reliable change estimates may allow clinicians to determine whether an improvement or decline in performance is greater than the expected improvement or decline due to measurement error in young adults.
The hypoglycaemia error grid: A UK-wide consensus on CGM accuracy assessment in hyperinsulinism
Authors: Worth Chris , Dunne Mark J. , Salomon-Estebanez Maria , Harper Simon , Nutter Paul W. , Dastamani Antonia , Senniappan Senthil , Banerjee Indraneel
Published: November 2022

Objective

Continuous Glucose Monitoring (CGM) is gaining in popularity for patients with paediatric hypoglycaemia disorders such as Congenital Hyperinsulinism (CHI), but no standard measures of accuracy or associated clinical risk are available. The small number of prior assessments of CGM accuracy in CHI have thus been incomplete. We aimed to develop a novel Hypoglycaemia Error Grid (HEG) for CGM assessment for those with CHI based on expert consensus opinion applied to a large paired (CGM/blood glucose) dataset.

Design and methods

Paediatric endocrinology consultants regularly managing CHI in the two UK centres of excellence were asked to complete a questionnaire regarding glucose cutoffs and associated anticipated risks of CGM errors in a hypothetical model. Collated information was utilised to mathematically generate the HEG which was then approved by expert, consensus opinion. Ten patients with CHI underwent 12 weeks of monitoring with a Dexcom G6 CGM and self-monitored blood glucose (SMBG) with a Contour Next One glucometer to test application of the HEG and provide an assessment of accuracy for those with CHI.

Results

CGM performance was suboptimal, based on 1441 paired values of CGM and SMBG showing Mean Absolute Relative Difference (MARD) of 19.3% and hypoglycaemia (glucose <3.5mmol/L (63mg/dL)) sensitivity of only 45%. The HEG provided clinical context to CGM errors with 15% classified as moderate risk by expert consensus when data was restricted to that of practical use. This provides a contrasting risk profile from existing diabetes error grids, reinforcing its utility in the clinical assessment of CGM accuracy in hypoglycaemia.

Conclusions

The Hypoglycaemia Error Grid, based on UK expert consensus opinion has demonstrated inadequate accuracy of CGM to recommend as a standalone tool for routine clinical use. However, suboptimal accuracy of CGM relative to SMBG does not detract from alternative uses of CGM in this patient group, such as use as a digital phenotyping tool. The HEG is freely available on GitHub for use by other researchers to assess accuracy in their patient populations and validate these findings.
Clinical value of FNA puncture feeling in the diagnosis of non-diagnostic and indeterminate thyroid nodules
Authors: Wu Jintao , Li Yingying , Zhang Mingbo
Published: November 2022

Objective

The aim of this study was to explore the clinical diagnostic value of puncture feeling during fine-needle aspiration (FNA) for non-diagnostic and indeterminate thyroid nodules.

Methods

A retrospective analysis was performed on 176 patients (196 nodules) diagnosed with Bethesda I or III by FNA cytology at the ultrasound department of our hospital between January 2017 and January 2020. Comparisons were made on the differences in puncture feeling (including stiffness and grittiness) between benign and malignant thyroid nodules, and their diagnostic performance was analyzed.

Results

There were significant differences between benign and malignant nodules with respect to the puncture stiffness and puncture grittiness (P < 0.001). The presence of a hard stiffness and grittiness demonstrated comparable levels of diagnostic performance for malignant thyroid nodules, with sensitivities, specificities, accuracies, positive predictive values, and negative predicative values of 55.56% and 63.89%, 87.10% and 78.22%, 75.51% and 72.96%, 71.43% and 63.01%, and 77.14% and 78.86%, respectively. The diagnostic performance was most optimal in the presence of at least one puncture feeling (area under the receiver operating characteristic curve: 0.771), exhibiting a sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 79.17%, 75.00%, 76.53%, 64.77, and 86.11%%, respectively.

Conclusions

Puncture feeling adds clinical value in the diagnosis of thyroid nodules with indeterminate FNA findings.
Use of levothyroxine in the management of hypothyroidism: A historical perspective
Authors: Kahaly George J. , Gottwald-Hostalek Ulrike
Published: November 2022

The thyroid operates within a complex system of homeostatic regulation, where the level of thyrotropin (TSH) influences the rate of secretion of the principal thyroid hormones, thyroxine (T4) and triiodothyronine (T3). The devastating consequences of untreated thyroid dysfunction have been evident for centuries. Indeed, sources from antiquity described goitre and cretinism, two of the clinical sequelae of untreated overt thyroid disease. It was not until the first part of the 19th century that goitre and cretinism were first associated with iodine status; however, the endocrine function of the thyroid was not clearly identified until the early part of the 20th century. Three principal innovations in the 20th century supported the use of levothyroxine (LT4) replacement therapy for the management of hypothyroidism: a practical technique for the synthesis of LT4 suitable to support pharmaceutical use (late 1940s), the discovery that LT4 is converted to the active thyroid hormone, T3, in the peripheral tissues (1970), and the development of robust and sensitive assay methodology for measuring thyroid hormones in the blood (1960 onwards). Synthetic LT4, titrated to bring the level of TSH within a predefined “normal” reference range, is now established as the mainstay of treatment for hypothyroidism, and provides adequate restoration of thyroid hormone function for most people with this condition. Future research will explore further the nuances of the hypothalamic-pituitary-thyroid axis, and the place, if any, for T3 within the management of thyroid dysfunction.
Perceptions and attitudes toward blue energy and technologies in the Mediterranean area: ASKYOURCITIZENSONBE
Authors: Betti Gianni , Cervellera Gian Piero , Gagliardi Francesca , Gioia Carmela , Patrizi Nicoletta , Bastianoni Simone
Published: November 2022

An energy transition is needed in order to meet the European pledge of reaching climate neutrality by 2050. This transition cannot ignore the renewable resources available from 70% of the Earth (namely, the oceans and seas). This concept is fundamental for the planet, especially for the Mediterranean area. Marine renewable energies are still under-deployed in the Mediterranean area for many reasons, including legislative constraints, lower energy availability, and technological readiness. An appropriate participatory process including all actors (e.g., policymakers, firms, citizens, and researchers) is necessary for a correct path toward decarbonization. The BLUE DEAL project was conceived and implemented by 12 Mediterranean partners to tackle these issues and set the route for blue energy deployment in the Mediterranean area. Activities already conducted include a survey to probe the perceptions and attitudes of citizens toward blue energy. The survey targeted about 3,000 persons in 12 Mediterranean sites with the aim of bringing citizens into the discussion on future technologies. The results showed that although blue energy is still relatively unknown to the general public (only 42% of respondents were aware of these technologies), there was a general willingness (70%) to host one or more such installations in their areas. Here, we describe our survey method and some empirical results with suggestions for replicability and recommendations on how to use it for policymaking purposes.
Performance evaluation of the development of eco-cultural tourism in Fujian Province based on the method of fuzzy comprehensive evaluation
Authors: Zheng Qiuqin , Chen Qiuhua , Kong Deyi
Published: November 2022

The performance evaluation serves as a crucial means of examining the economic, ecological and social benefits of eco-cultural tourism in a holistic manner and a vital method of assessing the sustainable development of regional eco-cultural tourism. However, due to the non-profit features of public resources, it is hard to evaluate the performance of eco-cultural tourism in an objective manner through the conventional approach that depends on economic performance as the primary evaluation indicator. Therefore, based on the balanced score card, this paper aims to build a system of performance evaluation indicators custom-tailored to the eco-cultural tourism development in Fujian Province from four aspects, namely, financial performance, public benefits, internal process and learning and growth. By adopting the method of fuzzy comprehensive evaluation, the study intends to objectively assess the economic value, efficiency and public benefits of eco-cultural tourism in Fujian Province. In addition, by adopting the method of Analytic Hierarchy Process (AHP), the study has identified the weights of the performance evaluation indicators, namely, 0.558 for public benefits, 0.122 for financial performance, 0.057 for internal process and 0.263 for learning and growth. Judging from the fuzzy comprehensive evaluation, the effects are found to be at the average level for the eco-cultural tourism development in Fujian Province, scoring between 60 and 74. As shown by the research findings, although Fujian Province is endowed with optimal resources of eco-cultural tourism, further efforts need to be made in exploring and optimizing the building of eco-cultural tourism.
Biochar-compost amendment enhanced sorghum growth and yield by improving soil physicochemical properties and shifting soil bacterial community in a coastal soil
Authors: Yin Shaojing , Suo Fengyue , Zheng Ying , You Xiangwei , Li Hui , Wang Juying , Zhang Chengsheng , Li Yiqiang , Cheng Yadong
Published: November 2022

Soil salinization, an important type of soil degradation, has become a problem restricting crop production and food quality. The remediation technologies by using compost and biochar were considered sustainable and environment friendly, but the sole application of compost or biochar hardly gets the satisfactory remediation effects. Until now, information about the effects of cocomposted biochar on soils is limited, especially in the coastal soil. This study investigated the impact and potential underlying mechanism of corn straw biochar (BC), seaweed compost (SC), and cocomposted BC and SC (BCSC) on the growth and yield of sorghum (Sorghum bicolor (L.) Moench) in the coastal soil of China in a pot experiment. BC and BCSC treatments increased the dry biomass and yield of the sorghum by 44.0–52.4% and 132.9–192.3%, respectively. Similarly, the root morphologies of sorghum, including surface area and average diameter, were also increased with BC and BCSC addition. Meanwhile, BCSC treatment showed a better performance than what the others did. The enhanced growth and yield of sorghum primarily resulted from the improvement of soil properties (WHC, SOM, and EC) and nutrient availability (Olsen-P and AK content). In addition, the increased diversity and shifted composition of soil bacteria with BC and BCSC addition might also account for the increased growth and yield of sorghum. Furthermore, the enhanced relative abundances of beneficial bacteria Vicinamibacteraceae (39.0%) and Sphingomonadaceae (41.5%) in the rhizosphere soil were positively correlated with the content of available nutrients (NH4+, Olsen-P, and available K) in the coastal soil, which might reveal the mechanism of enhancing growth under the established collaborative interactions of them. Our study provides the potential of using biochar-compost to ameliorate the degradation of coastal soils and improve crop yield.
Biochar enhanced phytostabilization of heavy metal contaminated mine tailings: A review
Authors: Shi Yanfeng , Zang Yufei , Yang Huanhuan , Zhang Xu , Shi Jinmiao , Zhang Jie , Liu Bing
Published: November 2022

Mining activities has generated large amounts of mine tailings each year, and these tailings usually contain high concentrations of heavy metal pollutants, which not only cause serious damage to the local and surrounding soil ecosystems, but also harm human health via the transmission of food chain. Phytoremediation is treated as environmentally friendly, long-term effective and low-cost restoration method. However, tailing soil acidification, low organic matter content, poor water holding capacity and compaction make plant struggle to survive. Biochar, a soil conditioner can promote plant growth by improving the physical, chemical and biological properties of soil, thus strengthening the ability of phytoremediation in the contaminated tailings. This review elaborates how the physicochemical properties of biochar affect phytoremediation; and summarized how the raw materials of biochar affect the physicochemical characteristics. Finally, the future research directions are prospected.
Conserving the unique aquatic ecosystem of the Jiuzhai National Heritage Site after the 2017 earthquake: Achievements and challenges
Authors: Xiong Yujiu , Du Jie , Qiu Gouyu
Published: November 2022

Water resources are the key link within the unique landscape of the Jiuzhaigou World Natural Heritage Site. However, the earthquake on 8 August 2017 induced serious damage to the ecosystem of the Jiuzhaigou region. Water resource quantity was threatened by the direct destruction of the connectivity between the upstream and downstream river systems, whereas water quality and the original aquatic ecosystem were worsened indirectly by secondary disasters, such as landslides and debris flows triggered by earthquakes. It is urgent to protect water resources to maintain a healthy aquatic ecosystem for the Jiuzhaigou World Natural Heritage Site. Therefore, water resource protection strategies are developed by collaboratively considering water quantity, quality and aquatic ecology, including 1) studying the relationship between upstream and downstream in terms of water supply and connectivity, 2) developing emergency plans for extreme precipitation disasters and ecological water regulation schemes for extreme drought, 3) clarifying the impact of vegetation management measures on water conservation, nutrient cycling and water quality, 4) separating the contributions of earthquakes from related disasters, hydrodynamic changes, and lake bank vegetation succession to lake swamping, 5) identifying the potential water pollution risk caused by ecological restoration projects, analyzing the sources of pollutants such as nitrogen, phosphorus and atmospheric acid deposits and developing control measures, and 6) systematically evaluating aquatic ecological health and determining water ecological protection and restoration measures. This review may provide critical viewpoints for conserving aquatic ecosystems, not only in the Jiuzhai World Natural Heritage Site but also in other global conserved aquatic parks.
Implications of m6A-associated snRNAs in the prognosis and immunotherapeutic responses of hepatocellular carcinoma
Authors: Zhang Cheng , Zhang Wangjian , Shui Yongjie , Li Ping , Tian Zhifeng , Duan Shiwei , Wei Qichun
Published: November 2022

Background

Hepatocellular carcinoma (HCC) is the most prevalent pathological type of liver cancer worldwide with high mortality and poor prognosis. N6-methyladenosine (m6A) can modify RNAs such as mRNA, lncRNA, miRNA, and tRNA, thereby playing a critical role in the pathogenesis of HCC. However, the role of m6A-associated small nuclear RNA (snRNA) in the prognostic value and immunotherapeutic response in HCC remains unclear.

Materials and methods

In this study, snRNA expression data, gene mutation data, and clinical data of HCC patients were acquired from The Cancer Genome Atlas (TCGA) database. We used the least absolute shrinkage and selection operator (LASSO) Cox regression analysis to identify significant prognostic m6A-associated snRNAs, and then developed a multivariate Cox model based on the selected snRNAs. HCC patients were split into low- and high-risk groups based on the median risk score. We subsequently performed Kaplan-Meier curve analysis to estimate overall survival (OS) by clinicopathological characteristics and tumor mutational burden (TMB) status in low- and high-risk HCC patients. Finally, we compared the immunotherapeutic response as represented by tumor immune dysfunction and exclusion (TIDE) scores between the two risk groups.

Results

Eight m6A-associated snRNAs were selected as independent predictors to develop the risk model. Our results revealed that the OS of HCC patients in the high-risk group was significantly worse than that in the low-risk group on clinicopathologic characteristics, including age (≤65 years and >65 years), gender (male), grade (G I-II and G III-IV) and TNM staging (Stage I-II and Stage III-IV). In addition, the OS of low-TMB and low-risk group was longer than that of high-TMB and high-risk group. The TIDE score indicated that HCC patients in the high-risk group were more susceptible to immunotherapy.

Conclusion

Our study suggests that m6A-associated snRNAs may be useful biomarkers for the prognosis of HCC and that m6A-associated snRNA models can predict the effect of immunotherapy in HCC patients.
Dynamic changes in kynurenine pathway metabolites in multiple sclerosis: A systematic review
Authors: Fathi Mobina , Vakili Kimia , Yaghoobpoor Shirin , Tavasol Arian , Jazi Kimia , Mohamadkhani Ashraf , Klegeris Andis , McElhinney Alyssa , Mafi Zahedeh , Hajiesmaeili Mohammadreza , Sayehmiri Fatemeh
Published: November 2022

Background

Multiple sclerosis (MS) is a debilitating neurodegenerative disorder characterized by axonal damage, demyelination, and perivascular inflammatory lesions in the white matter of the central nervous system (CNS). Kynurenine pathway (KP), which is the major route of tryptophan (TRP) metabolism, generates a variety of neurotoxic as well as neuroprotective compounds, affecting MS pathology and the severity of impairments. Alterations in KP have been described not only in MS, but also in various psychiatric and neurodegenerative diseases. The purpose of this systematic review is to investigate the previously reported dysregulation of KP and differences in its metabolites and enzymes in patients with MS compared to healthy control subjects.

Method

Electronic databases of PubMed, Scopus, Cochrane Database of Systematic Reviews, and Web of Science were searched to identify studies measuring concentrations of KP metabolites and enzymes in MS patients and control subjects. The following metabolites and enzymes implicated in the KP were investigated: TRP, kynurenine (KYN), kynurenic acid (KYNA), quinolinic acid (QUIN), picolinic acid (PIC), hydroxyindoleacetic acid (HIAA), indoleamine 2,3-dioxygenase (IDO), kynurenine aminotransferase (KAT), and their related ratios.

Result

Ten studies were included in our systematic review. Our review demonstrates that IDO expression is reduced in the peripheral blood mononuclear cells (PBMCs) of MS patients compared to healthy controls. Also, increased levels of QUIN and QUIN/KYNA in the serum and cerebrospinal fluid (CSF) of MS patients is observed. Differences in levels of other metabolites and enzymes of KP are also reported in some of the reviewed studies, however there are discrepancies among the included reports.

Conclusion

The results of this investigation suggest a possible connection between alterations in the levels of KP metabolite or enzymes and MS. QUIN levels in CSF were higher in MS patients than in healthy controls, suggesting that QUIN may be involved in the pathogenesis of MS. The data indicate that differences in the serum/blood or CSF levels of certain KP metabolites and enzymes could potentially be used to differentiate between MS patients and control subjects.
Roles and crosstalks of macrophages in diabetic nephropathy
Authors: Li Hai-Di , You Yong-Ke , Shao Bao-Yi , Wu Wei-Feng , Wang Yi-Fan , Guo Jian-Bo , Meng Xiao-Ming , Chen Haiyong
Published: November 2022

Diabetic nephropathy (DN) is the most common chronic kidney disease. Accumulation of glucose and metabolites activates resident macrophages in kidneys. Resident macrophages play diverse roles on diabetic kidney injuries by releasing cytokines/chemokines, recruiting peripheral monocytes/macrophages, enhancing renal cell injuries (podocytes, mesangial cells, endothelial cells and tubular epithelial cells), and macrophage-myofibroblast transition. The differentiation and cross-talks of macrophages ultimately result renal inflammation and fibrosis in DN. Emerging evidence shows that targeting macrophages by suppressing macrophage activation/transition, and macrophages-cell interactions may be a promising approach to attenuate DN. In the review, we summarized the diverse roles of macrophages and the cross-talks to other cells in DN, and highlighted the therapeutic potentials by targeting macrophages.
Immuno-informatics profiling of monkeypox virus cell surface binding protein for designing a next generation multi-valent peptide-based vaccine
Authors: Yousaf Maha , Ismail Saba , Ullah Asad , Bibi Shabana
Published: November 2022

Monkeypox is a viral etiological agent with hallmarks analogous to those observed in smallpox cases in the past. The ongoing outbreak of Monkeypox viral infection is becoming a global health problem. Multi-valent peptide based next generation vaccines provides us a promising solution to combat these emerging infectious diseases by eliciting cell-mediated and humoral immune response. Considering the success rate of subtractive proteomics pipeline and reverse vaccinology approach, in this study, we have developed a novel, next-generation, multi-valent, in silico peptide based vaccine construct by employing cell surface binding protein. After analyzing physiochemical and biological properties of the selected target, the protein was subjected to B cell derived T cell epitope mapping. Iterative scrutinization lead to the identification of two highly antigenic, virulent, non-allergic, non-toxic, water soluble, and Interferon-gamma inducer epitopes i.e. HYITENYRN and TTSPVRENY. We estimated that the shortlisted epitopes for vaccine construction, roughly correspond to 99.74% of the world’s population. UK, Finland and Sweden had the highest overall population coverage at 100% which is followed by Austria (99.99%), Germany (99.99%), France (99.98%), Poland (99.96), Croatia (99.93), Czech Republic (99.87%), Belgium (99.87), Italy (99.86%), China (97.83%), India (97.35%) and Pakistan (97.13%). The designed vaccine construct comprises of 150 amino acids with a molecular weight of 16.97242 kDa. Molecular docking studies of the modelled MEMPV (Multi-epitope Monkeypox Vaccine) with MHC I (PDB ID: 1I1Y), MHC II (PDB ID: 1KG0), and other immune mediators i.e. toll like receptors TLR3 (PDB ID: 2A0Z), and TLR4 (PDB ID: 4G8A) revealed strong binding affinity with immune receptors. Host immune simulation results predicted that the designed vaccine has strong potency to induce immune responses against target pathogen in the form of cellular and antibody-dependent immunity. Our findings suggest that the hypothesized vaccine candidate can be utilized as a potential therapeutic against Monkeypox however experimental study is required to validate the results and safe immunogenicity.
Membranous nephropathy: Clearer pathology and mechanisms identify potential strategies for treatment
Authors: Chung Edmund Y. M. , Wang Yuan M. , Keung Karen , Hu Min , McCarthy Hugh , Wong Germaine , Kairaitis Lukas , Bose Bhadran , Harris David C. H. , Alexander Stephen I.
Published: November 2022

Primary membranous nephropathy (PMN) is one of the common causes of adult-onset nephrotic syndrome and is characterized by autoantibodies against podocyte antigens causingin situimmune complex deposition. Much of our understanding of the disease mechanisms underpinning this kidney-limited autoimmune disease originally came from studies of Heymann nephritis, a rat model of PMN, where autoantibodies against megalin produced a similar disease phenotype though megalin is not implicated in human disease. In PMN, the major target antigen was identified to be M-type phospholipase A2 receptor 1 (PLA2R) in 2009. Further utilization of mass spectrometry on immunoprecipitated glomerular extracts and laser micro dissected glomeruli has allowed the rapid discovery of other antigens (thrombospondin type-1 domain-containing protein 7A, neural epidermal growth factor-like 1 protein, semaphorin 3B, protocadherin 7, high temperature requirement A serine peptidase 1, netrin G1) targeted by autoantibodies in PMN. Despite these major advances in our understanding of the pathophysiology of PMN, treatments remain non-specific, often ineffective, or toxic. In this review, we summarize our current understanding of the immune mechanisms driving PMN from animal models and clinical studies, and the implications on the development of future targeted therapeutic strategies.
Untargeted metabolomics identified kynurenine as a predictive prognostic biomarker in acute myocardial infarction
Authors: Zhang Xiaolin , Cai Yi , Su Xu , Jing Quanmin , Liu Haiwei , Na Kun , Qiu Miaohan , Tian Xiaoxiang , Liu Dan , Wu Tianxiao , Yan Chenghui , Han Yaling
Published: November 2022

Objective

The occurrence of cardiovascular adverse events in the first year after ST-acute myocardial infarction (STEMI) remains high; therefore, identification of patients with poor prognosis is essential for early intervention. This study aimed to evaluate the prognostic value of metabolomics-based biomarkers in STEMI patients and explore their functional mechanisms.

Methods

Metabolite profiling was performed using nuclear magnetic resonance. The plasma concentration of Kynurenine (Kyn) was measured using ultraperformance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry. Major adverse cardiac and cerebral events were assessed for 1 year. A functional metabolomics strategy was proposed for investigating the role of Kyn in both vitro and vivo models.

Results

The adjusted hazard ratios in STEMI patients for Kyn in the 4th quartile 7.12(5.71-10.82) was significantly higher than that in the 3rd quartile 3.03(2.62-3.74), 2nd quartile 1.86(1.70-2.03), and 1st quartile 1.20(0.93-1.39).The incidence of MACCE was significantly different among Kyn quartiles and the highest incidence of MACCE was observed in the 4th quartile when compared with the 1st quartile (9.84% vs.2.85%, P<0.001).Immunofluorescence staining indicated that indoleamine-pyrrole 2,3-dioxygenase (IDO1) was located in the CD68 positive staining area of thrombi from STEMI patients and Kyn was induced in the early phase after myocardial infarction. Kyn could trigger inflammation and oxidative stress of macrophage cells by activation of the Sirt3-acSOD2/IL-1β signaling pathway in vitro.

Conclusions

Plasma Kyn levels were positively associated with the occurrence of STEMI. Kyn could induce macrophage cells inflammation and oxidative stress by activating the Sirt3-acSOD2/IL-1β pathway following myocardial ischemia injury. Kyn could be a robust biomarker for STEMI prognosis and reduction of Kyn could be beneficial in STEMI patients.
Vessel state and immune infiltration of the angiogenesis subgroup and construction of a prediction model in osteosarcoma
Authors: Wu Jintao , Jin Zhijian , Lin Jianwei , Fu Yucheng , Wang Jun , Shen Yuhui
Published: November 2022

Angiogenesis has been recognized as a pivotal contributor to tumorigenesis and progression. However, the role of angiogenesis-related genes (ARGs) in vessel state, immune infiltration, and prognosis remains unknown in osteosarcoma (OS). Bulk RNA sequencing data of osteosarcoma patients were obtained from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database, and patients were divided into two angiogenesis subgroups according to the expression of ARGs. We compared their vessel state and used two independent algorithms to evaluate the tumor microenvironment (TME) in the two subgroups. Furthermore, hub genes of differentially expressed genes (DEGs) in the two subgroups were selected to perform LASSO regression and multivariate Cox stepwise regression, and two prognostic hub genes were found. An ARG_score based on prognostic hub genes was calculated and proved to be reliable in the overall survival prediction in OS patients. Furthermore, the ARG_score was significantly associated with ARGs, immune infiltration, response to immunotherapy, and drug sensitivity. To make our prediction model perform well, clinical features were added and a highly accurate interactive nomogram was constructed. Immunohistochemistry and qRT-PCR were utilized to verify the expression of prognostic hub genes. GSE21257 from the Gene Expression Omnibus (GEO) database was used as a validation dataset to verify its robustness. In conclusion, our comprehensive analysis of angiogenesis subgroups in OS illustrated that angiogenesis may lead to different vessel states and further affect immune infiltration and prognosis of OS patients. Our findings may bring a novel perspective for the immunotherapy strategies for OS patients.
Climate and fishing simultaneously impact small pelagic fish in the oceans around the southernmost tip of Africa
Authors: Ramírez Francisco , Shannon Lynne J. , van der Lingen Carl D. , Julià Laura , Steenbeek Jeroen , Coll Marta
Published: November 2022

Climate and fisheries interact, often synergistically, and may challenge marine ecosystem functioning and, ultimately, seafood provision and human wellbeing that depend on them. Holistic and integrative approaches aiming at evaluating the spatial overlap between these major stressors are crucial for identifying marine regions and key fish species that require conservation priority to prevent possible future collapses. Based on highly resolved information on environmental conditions and fishing pressure from the Southern Benguela and the Agulhas Bank ecosystems off South Africa, we identified the main areas where small pelagic fish species (European anchovy Engraulis encrasicolus, Pacific sardine Sardinops sagax, and West Coast round herring Etrumeus whiteheadi) have been highly impacted in terms of unfavourable environmental conditions and fishing pressure over the period 1993-2018. We termed these areas cumulative “hotspots” of climate change and fishing impact. We also identified fishing grounds where environmental conditions are now more favourable for these pelagic fish species, terming these “bright spots” of climate change. Environmental conditions and fishing intensity show contrasting patterns between the Southern Benguela and the Agulhas Bank ecosystems, with the Southern Benguela region accumulating most of the cumulative hotspots and showing the most negative trends in CPUE (a proxy for local fish abundance). Contrastingly, bright spots, identified on the south coast but also south of Cape Town, showed more positive trends in CPUE, suggesting that they may support sustainable growth of the small pelagic fishery in the medium term. Focussing future fishing effort on these bright spots may serve to alleviate pressure on the doubly and highly impacted cumulative hotspots from the western side of the southernmost tip of Africa.
Impacts of nighttime hypoxia on the physiological performance of Red Sea macroalgae under peak summer temperature
Authors: Alamoudi Taiba , Steckbauer Alexandra , Klein Shannon G. , Alva García Jacqueline V. , Arossa Silvia , Parry Anieka J. , Duarte Carlos M.
Published: November 2022

Eutrophication-induced hypoxic sites are increasingly reported in coastal regions. At the same time, ocean warming, water column stratification, and changing circulation lead to open-ocean deoxygenation. In coastal areas and reefs with dense vegetation, aquatic organisms can be exposed to oxygen limitation stress where oxygen concentration reaches extremely low levels, particularly during nighttime once photosynthetic O2 production has ceased. Despite scientists being aware of this for decades, little is known about the impact of deoxygenation on the physiology of marine primary producers, such as macroalgae. In the Red Sea, in particular, the physiological adaptations of macroalgae under future climate scenarios are nonexistent. Here, we investigate the impact of different oxygen levels (6.5, 2.5, and 1.3 mg O2 L-1) at night for three conspicuous Red Sea macroalgae species Halimeda opuntia and Padina boryana (calcareous) and the brown algae Sargassum latifolium (noncalcifying). We monitored algal physiological responses during a 12-hour nighttime (dark) period at 32°C by measuring photochemical efficiency (Fv/Fm), respiration rates, and cellular viability. No lethal thresholds were detected. However, both deoxygenation treatments decreased respiration rates and induced changes in cellular activity, and only under severe hypoxia was a decrease in photochemical efficiency observed in all species. We calculated sublethal O2 thresholds SLC(50) of 1.2 ± 0.1, 1.5 ± 0.1, and 1.7 ± 0.1 mg O2 L-1 for H. opuntia, P. boryana, and S. latifolium, respectively. Therefore, the effects of nighttime hypoxia are evident over short timescales and may impact ecosystems via reduced primary production. Future consequences of persistent hypoxia and subsequent performance in multifaceted stressor exposures will provide a fundamental understanding of hypoxia’s threat to biodiversity and ecosystems.