bluuebunny/crossref_metadata_2025 huggingface dataset:
Design as the basis for integrated STEM education: A philosophical framework
Authors: Hallström Jonas , Ankiewicz Piet
Published: February 2023

STEM—science, technology, engineering, and mathematics—has become important as an educational construct and phenomenon in recent years. However, it is only just recently that STEM education has begun to be examined from a philosophical point of view. There is therefore a need for further investigation of its philosophical basis, particularly in relation to integrated STEM education (iSTEM). Recent conceptual and empirical studies emphasize the crucial role of design in achieving successful STEM integration, and design thinking has also lately gained traction in such integration. The aim of this study is to investigate an integrated philosophy of STEM education, based on the methodological backbone of design. The research methodology consisted of a critical review of the literature regarding the philosophy of STEM (education), science, technology, engineering, mathematics, and STEM education research, related to the current issues of integrating the various STEM subjects. We thus base the philosophical framework on philosophy and studies from/on the STEM subjects in education. It is concluded that from a methodological point of view, design holds promising affordances for unifying the STEM subjects through “pure STEM problems”. Design as part of, for instance, particular engineering design projects may consequently require the “design” of applicable scientific experiments as well as mathematics expressions and formulae specifically when engaging in technological modeling.
Short-term prediction for distributed photovoltaic power based on improved similar time period
Authors: Wu Zhihan , Zhang Yi , Liu Bijie , Zhang Minghui
Published: February 2023

A short-term prediction method for distributed PV power based on an improved selection of similar time periods (ISTP) is proposed, to address the problem of low output power prediction accuracy due to a large number of influencing factors and the large difference in the degree of influence of various factors. First, the simple correlation coefficient (SCC) based on path analysis is used to screen the main influencing factors with stronger correlation with PV output power, and these factors are classified into three categories. Second, correlations of the three dimensions are calculated, respectively: (i) TOPSIS (with weights optimized by the SCC) determines meteorological correlation, (ii) linear weighting (based on the fuzzy ranking) obtains time correlation, and (iii) load correlation is quantified with existing current parameters. Third, the combined impact correlation (CIC) is obtained by weighting the three correlations above to establish criteria for the selection of similar periods, and a short-term PV power prediction model is established. Finally, experimental results based on real data of Australian Yulara Solar System PV plant demonstrate that errors of proposed ISTP method are respectively improved by 47.06% and 46.09% compared with the traditional ELMAN and similar day method.
A community-informed transdisciplinary approach to coastal restoration planning: Maximizing the social and ecological co-benefits of wetland creation in Port Fourchon, Louisiana, USA
Authors: Hemmerling Scott A. , DeMyers Christine , Parfait Jessica , Piñero Edwin , Baustian Melissa M. , Bregman Martijn , Di Leonardo Diana , Esposito Christopher , Georgiou Ioannis Y. , Grismore Audrey , Jung Hoonshin , McMann Brett , Miner Michael D.
Published: February 2023

Port Fourchon is a vital staging area for Gulf of Mexico energy production and is strategically located in the Barataria-Terrebonne Estuary System, a biologically and economically productive ecosystem bounded by the Atchafalaya and Mississippi Rivers. This is also one of the most fragile and rapidly evolving landscapes in the United States, making the port and surrounding communities highly vulnerable to natural hazards and the impacts of climate change. Building resilience to climate-based disruptions is vital to Port Fourchon and other businesses operating in this dynamic landscape. The port plans to deepen its channel to 50 feet (15 m) to service larger vessels, generating millions of cubic yards of sediment and seeks to beneficially utilize this sediment to develop natural and nature-based solutions to help prepare for future challenges. To accomplish this goal, an Environmental Competency Group consisting of residents, coastal scientists, and key stakeholders was convened to co-develop and evaluate a series of marsh creation projects utilizing this sediment that will maximize social and ecological co-benefits and enhance the resilience of Port Fourchon and the surrounding communities. The group utilized participatory modeling and social return on investment methods to model long-term changes to the landscape and wetland vegetation communities resulting from the co-developed restoration strategies and assess the social value of these strategies. Residents who live and work around Port Fourchon were included in all stages of this research, including development and prioritization of potential restoration areas, identifying important physical and ecological parameters that should be modeled, evaluation of model results, and assessment of the social values expected to be generated by each restoration alternative under consideration. The transdisciplinary approach used in this research highlights the effectiveness of a community-informed, systematic approach to coastal restoration planning in building community resilience and ecosystem sustainability. This study provides approaches and tools that can be adapted for use elsewhere to develop holistic solutions that maximize the social, ecological, and economic co-benefits of coastal restoration.
Clustered tree size analysis of bio-productivity of Dinghushan National Nature Reserve in China
Authors: Li Yuelin , Nyongesah Maina John , Deng Libin , Haider Fasih Ullah , Liu Shizhong , Mwangi Brian Njoroge , Zhang Qianmei , Chu Guowei , Zhang Deqiang , Liu Juxiu , Meng Ze
Published: February 2023

Over various terrain types, natural forests exhibit tree size and biomass variation. We started long- term research that consists of forest vegetation surveys in the Dinghushan National Nature Reserve to comprehensively investigate productivity based on the structure and species composition of China’s forest communities. We grouped the trees into three categories, i.e., as large or mature (DBH > 30 cm), medium-sized or growing (DBH 10–30 cm), and small-sized or regenerating seedlings (DBH < 10 cm). Forest data observations, i.e., species DBH, height, and biomass components (trunk, leaves, branches, above-ground dry weight, and below-ground dry weight) were recorded by use of standard protocols. All recorded observations were statistically analyzed by use of SPSS version 25. To comprehend the connections between the many elements of forest bio-productivity, linear regression analysis was utilized. Total above-ground biomass was 34.19 ± 5.75Kg/tree, but varied results were obtained when the forest was clustered based on DBH. Large-sized trees contributed an average of 2400.54 ± 510.4 kg/tree (93.24%), while medium-sized trees contributed 171.61 ± 25.06 kg/tree, and the least was regenerating seedlings which contributed 3.013 ± 0.07 kg/tree. There were positive linear relationships for all life forms between biomass and DHB, as well as DBH and height. The evergreen broadleaved shrubs were shorter in height (3.06 ± 0.99 m) than palm-leaved life forms (19.29 ± 5.39 m). Height influenced biomass accumulation and hence C gain, where life forms with tall stands had higher biomass. Generalized biomass estimation without clustering based on life forms or size class underestimates biomass components and hence lower C stocks for most forests worldwide. It’s also crucial to remember that trees with big DBH have tall, broad, well-lit crowns, which raise the primary productivity of forests and increase carbon storage. Besides natural disturbance (Typhoon) and climate change, it could be interesting to understand the relationship between soil resources such as nutrient and soil moisture content. These are factors that have direct impact on growth and biomass accumulation.
Incidents of snake fungal disease caused by the fungal pathogen Ophidiomyces ophidiicola in Texas
Authors: Lizarraga Alan J. , Hart Lezley , Wright R. Michele , Williams Lance R. , Glavy Joseph S.
Published: February 2023

The pathogen Ophidiomyces ophidiicola, widely known as the primary cause of snake fungal disease (SFD) has been detected in Texas’s naïve snakes. Our team set out to characterize O. ophidiicola’s spread in eastern Texas. From December 2018 until November 2021, we sampled and screened with ultraviolet (UV) light, 176 snakes across eastern Texas and detected 27. O. ophidiicola’s positive snakes using qPCR and one snake in which SFD was confirmed via additional histological examination. Upon finding the ribbon snake with clear clinical display, we isolated and cultured what we believe to be the first culture from Texas. This cultured O. ophidiicola TX displays a ring halo formation when grown on a solid medium as well as cellular autofluorescence as expected. Imaging reveals individual cells within the septated hyphae branches contain a distinct nucleus separation from neighboring cells. Overall, we have found over 1/10 snakes that may be infected in East Texas, gives credence to the onset of SFD in Texas. These results add to the progress of the disease across the continental United States.
Correlation of GDFT combined with rehabilitation therapy in DNA damage repair of esophageal cancer cells
Authors: Yan Lihua , Ji Yajun
Published: February 2023

Esophageal cancer is a common malignant tumor with a high incidence and a serious threat to human health. The treatment of esophageal cancer is a complex process, which requires the comprehensive use of a variety of treatment methods. At present, the treatment of esophageal cancer mainly includes surgery, radiotherapy, chemotherapy and immunotherapy. The research on the treatment of cancer cells based on Goal directed fluid therapy (GDFT) combined with rehabilitation therapy is the focus of the current society. This paper proposed a study on DNA damage repair of cancer cells based on goal directed fluid therapy combined with rehabilitation therapy, aiming to optimize the traditional treatment of esophageal cancer by using goal directed fluid therapy technology. The algorithm proposed in this paper was an electroencephalogram (EEG) signal optimization algorithm based on combined rehabilitation therapy. Through this algorithm, the electroencephalogram signal could be optimized. The algorithm could speed up signal processing, and improve signal reliability and stability by reducing the influence of interference signals and improving the signal to noise ratio. These optimization measures could better help researchers analyze and understand electroencephalogram signals, so as to help better study brain functions and diseases. Through the test and investigation on the treatment of cancer cells based on goal directed fluid therapy combined with rehabilitation therapy, the results showed that the blood transfusion volume of goal directed fluid therapy treatment and conventional treatment was 251.5 mL and 288.3 mL respectively. This showed that after goal directed fluid therapy treatment, the input amount of various medical fluids was relatively reduced, and the use of medical fluids was more economical. In addition, their bleeding volumes were 295.2 mL and 324.4 mL, respectively. Urine volume was 382.3 mL and 418.1 mL respectively. This showed that after goal directed fluid therapy treatment, the patient’s blood loss and urine volume were relatively reduced, which has improved the patient’s health. This experiment has proved the excellent ability of goal directed fluid therapy combined with rehabilitation therapy in the treatment of esophageal cancer, and this research result has also proved the excellent medical effect of goal directed fluid therapy technology. Similarly, this paper also provided valuable reference information for the treatment of esophageal cancer.
Identification of hsa_circRNA_100632 as a novel molecular biomarker for fulminant type 1 diabetes
Authors: Yin Wenfeng , Luo Shuoming , Qiu Junlin , Xiao Zilin , Zhang Ziwei , Xie Zhiguo , Li Xia , Zhou Zhiguang
Published: February 2023

Objective

Circular RNAs (circRNAs) are associated with diabetes, but their role in fulminant type 1 diabetes (FT1D) is unclear. Thus, we characterized the role of circRNAs in FT1D.

Research design and methods

CircRNA expression profiles were detected in peripheral blood mononuclear cells (PBMCs) of five FT1D patients and five controls using a circRNA microarray. An independent cohort comprised of 40 FT1D cases, 75 type 1 diabetes (T1D) cases, and 115 controls was used to verify the circRNAs using quantitative real-time polymerase chain reaction (qRT-PCR). Spearman’s correlation analysis and receiver operating characteristic (ROC) curve analysis were performed to determine the clinical diagnostic capability of circRNAs. Bioinformatics was used to identify potential biological functions and circRNA–miRNA–mRNA interactions.

Results

There were 13 upregulated and 13 downregulated circRNAs in PBMCs of patients with FT1D. Five circRNAs were further verified in a second cohort. Hsa_circRNA_100632 was significantly upregulated in the FT1D and T1D groups. Hsa_circRNA_100632 was differentiated between patients with FT1D and controls [area under the curve (AUC) 0.846; 95% CI 0.776–0.916; P<0.0001] as well as between patients with FT1D and patients with T1D (AUC 0.726; 95% CI 0.633–0.820; P<0.0001). Bioinformatics analysis showed that hsa_circRNA_100632 may be involved in 47 circRNA–miRNA–mRNA signaling pathways associated with diabetes.

Conclusions

CircRNAs were aberrantly expressed in PBMCs of patients with FT1D, and hsa_circRNA_100632 may be a diagnostic marker of FT1D.
The role of HLA antigens in recurrent primary focal segmental glomerulosclerosis
Authors: Batal Ibrahim , Khairallah Pascale , Weins Astrid , Andeen Nicole K. , Stokes Michael B.
Published: February 2023

Primary focal segmental glomerulosclerosis (FSGS), typically characterized by diffuse podocyte foot process effacement and nephrotic syndrome (diffuse podocytopathy), is generally attributed to a circulating permeability factor. Primary FSGS can recur after transplantation where it manifests as diffuse foot process effacement in the early stages, with subsequent evolution of segmental sclerotic lesions. Previous published literature has been limited by the lack of stringent selection criteria to define primary FSGS. Although immunogenetic factors play an important role in many glomerular diseases, their role in recurrent primary FSGS post-transplantation has not been systematically investigated. To address this, we retrospectively studied a multicenter cohort of 74 kidney allograft recipients with end stage kidney disease due to primary FSGS, confirmed by clinical and histologic parameters. After adjusting for race/ethnicity, there was a numeric higher frequency of HLA-A30 antigen in primary FSGS (19%) compared to each of 22,490 healthy controls (7%, adjusted OR=2.0, P=0.04) and 296 deceased kidney donors (10%, OR=2.1, P=0.03). Within the group of transplant patients with end stage kidney disease due to primary FSGS, donor HLA-A30 was associated with recurrent disease (OR=9.1, P=0.02). Multivariable time-to-event analyses revealed that recipients who self-identified as Black people had lower risk of recurrent disease, probably reflecting enrichment of these recipients with APOL1 high-risk genotypes. These findings suggest a role for recipient and donor immunogenetic makeup in recurrent primary FSGS post-transplantation. Further larger studies in well-defined cohorts of primary FSGS that include high-resolution HLA typing and genome-wide association are necessary to refine these hereditary signals.
Histone deacetylase 8 inhibition prevents the progression of peritoneal fibrosis by counteracting the epithelial-mesenchymal transition and blockade of M2 macrophage polarization
Authors: Zhou Xun , Chen Hui , Shi Yingfeng , Li Jinqing , Ma Xiaoyan , Du Lin , Hu Yan , Tao Min , Zhong Qin , Yan Danying , Zhuang Shougang , Liu Na
Published: February 2023

Background

Peritoneal dialysis (PD) is an effective replacement therapy for end-stage renal disease patients. However, long-term exposure to peritoneal dialysate will lead to the development of peritoneal fibrosis. Epigenetics has been shown to play an important role in peritoneal fibrosis, but the role of histone deacetylases 8 (HDAC8) in peritoneal fibrosis have not been elucidated. In this research, we focused on the role and mechanisms of HDAC8 in peritoneal fibrosis and discussed the mechanisms involved.

Methods

We examined the expression of HDAC8 in the peritoneum and dialysis effluent of continuous PD patients. Then we assessed the role and mechanism of HDAC8 in peritoneal fibrosis progression in mouse model of peritoneal fibrosis induced by high glucose peritoneal dialysis fluid by using PCI-34051. In vitro, TGF-β1 or IL-4 were used to stimulate human peritoneal mesothelial cells (HPMCs) or RAW264.7 cells to establish two cell injury models to further explore the role and mechanism of HDAC8 in epithelial-mesenchymal transition (EMT) and macrophage polarization.

Results

We found that HDAC8 expressed highly in the peritoneum from patients with PD-related peritonitis. We further revealed that the level of HDAC8 in the dialysate increased over time, and HDAC8 was positively correlated with TGF-β1 and vascular endothelial growth factor (VEGF), and negatively correlated with cancer antigen 125. In mouse model of peritoneal fibrosis induced by high glucose dialysate, administration of PCI-34051 (a selective HDAC8 inhibitor) significantly prevented the progression of peritoneal fibrosis. Treatment with PCI-34051 blocked the phosphorylation of epidermal growth factor receptor (EGFR) and the activation of its downstream signaling pathways ERK1/2 and STAT3/HIF-1α. Inhibition of HDAC8 also reduced apoptosis. In vitro, HDAC8 silencing with PCI-34051 or siRNA inhibited TGF-β1-induced EMT and apoptosis in HPMCs. In addition, continuous high glucose dialysate or IL-4 stimulation induced M2 macrophage polarization. Blockade of HDAC8 reduced M2 macrophage polarization by inhibiting the activation of STAT6 and PI3K/Akt signaling pathways.

Conclusions

We demonstrated that HDAC8 promoted the EMT of HPMCs via EGFR/ERK1/2/STAT3/HIF-1α, induced M2 macrophage polarization via STAT6 and PI3K/Akt signaling pathways, and ultimately accelerated the process of peritoneal fibrosis.
Single-cell RNA-seq analysis identifies distinct myeloid cells in a case with encephalitis temporally associated with COVID-19 vaccination
Authors: Ishikawa Masakazu , Shimada Yuki , Ozono Tatsuhiko , Matsumoto Hisatake , Ogura Hiroshi , Kihara Keigo , Mochizuki Hideki , Okuno Tatsusada , Sakakibara Shuhei , Kinoshita Makoto , Okuzaki Daisuke
Published: February 2023

Recently accumulating evidence has highlighted the rare occurrence of COVID-19 vaccination-induced inflammation in the central nervous system. However, the precise information on immune dysregulation related to the COVID-19 vaccination-associated autoimmunity remains elusive. Here we report a case of encephalitis temporally associated with COVID-19 vaccination, where single-cell RNA sequencing (scRNA-seq) analysis was applied to elucidate the distinct immune signature in the peripheral immune system. Peripheral blood mononuclear cells (PBMCs) were analyzed using scRNA-seq to clarify the cellular components of the patients in the acute and remission phases of the disease. The data obtained were compared to those acquired from a healthy cohort. The scRNA-seq analysis identified a distinct myeloid cell population in PBMCs during the acute phase of encephalitis. This specific myeloid population was detected neither in the remission phase of the disease nor in the healthy cohort. Our findings illustrate induction of a unique myeloid subset in encephalitis temporally associated with COVID-19 vaccination. Further research into the dysregulated immune signature of COVID-19 vaccination-associated autoimmunity including the cerebrospinal fluid (CSF) cells of central nervous system (CNS) is warranted to clarify the pathogenic role of the myeloid subset observed in our study.
Assessing the effects of heavy metals and polycyclic aromatic hydrocarbons on benthic foraminifera: The case of Houshui and Yangpu Bays, Hainan Island, China
Authors: Zhang Muhui , Yang Chupeng , Cai Guanqiang , Li Shun , Nie Xin , Zhou Shuqin
Published: February 2023

This work aimed to investigate the distribution of benthic foraminiferal assemblages in Houshui and Yangpu Bays, Hainan Island, and assess the relative effects of heavy metals, total organic carbon (TOC), and polycyclic aromatic hydrocarbons (PAHs) on foraminiferal assemblages. A total of 30 sites were sampled and analyzed for benthic foraminiferal assemblages, heavy metals, TOC, and PAHs. The organic matter in the study was derived primarily from algae according to the C/N ratios, and PAHs were generated by petroleum and combustion of petroleum products, as inferred from the diagnostic ratios of PAH isomers. Two-way hierarchical cluster analysis was used to classify the 35 common species into two species groups, and the 30 sites were classified based on their geographical location. CCA was used to investigate the effects of pollution on foraminiferal assemblages. The results showed that the effects of pollution on foraminiferal assemblages were in the order of heavy metals > TOC > PAHs. Furthermore, the species group I, which consisted of agglutinated taxa including Bigenerina nodosaria, Ammobaculites agglutinans, Textularia spp., T. foliacea, Haplophragmoides canariensis, and several tolerant species of hyaline forms, including Ammonia beccarii, Elphidium advenum, E. hispidulum, Quinqueloculina laevigata, and Q. seminula, was found to be positively influenced by heavy metals. In contrast, species group II, primarily composed of porcelaneous taxa such as Massilina laevigata, Spiroloculina communis, and some hyaline taxa including E. crispum and Elphidium spp., was found to be positively influenced by TOC and PAHs. This work suggest that heavy metal pollution is the main factor influencing foraminiferal assemblages in the study area. The observed positive effect of heavy metals on species group I may indicate the presence of metal-tolerant taxa, whereas the positive effect of TOC and PAHs on species group II suggests that these taxa may be more tolerant of organic pollution. The study highlights the potential of specific foraminiferal assemblages as bioindicators for assessing the impact of different types of pollution on marine ecosystems.
Distribution and sources of macrolitter on the seafloor in Belgian fisheries areas
Authors: Vanavermaete David , Verlé Katrien , Devriese Lisa I. , De Cauwer Karien , De Schrijver Coline , Torreele Els , Vandecasteele Loes , Velimirovic Milica , Tirez Kristof , Hostens Kris , De Witte Bavo
Published: February 2023

Marine litter is recognized as a global environmental concern. Seafloor litter can provide important information to help assess the status of the marine ecosystem and is relatively easy to collect on a regular basis. The Belgian fisheries area covers different parts of the OSPAR Greater North Sea region and the Celtic Seas. In these regions, seafloor litter data were gathered by quantifying the litter items caught in the trawl net during two different fisheries surveys to investigate litter distribution on both regional and local scales. In the international beam trawl survey (BTS), covering essentially the OSPAR Greater North Sea and Celtic Seas, an average of 2.2 ± 0.05 items.ha-1 were caught with a median of 1.4 items.ha-1. In the environmental monitoring survey (EMS) only the Belgian part of the North Sea was covered and a smaller cod-end mesh size was used, resulting in 12.7 ± 1.7 litter items.ha-1 in the coastal zone (< 12 nm) and 2.8 ± 0.2 items.ha-1 in the more offshore zone (> 12 nm). In both surveys plastic items were predominant, representing up to 88% of the collected litter in the Belgian part of the North Sea. The impact of human activities at sea such as fisheries, sand extraction, wind farms and dredge disposal was investigated. A significant correlation was found between fishing activities and the amount of litter registered in the Belgian part of the North Sea, but not for the OSPAR Greater North Sea and Celtic Seas.
Grain-boundary segregation and superior mechanical properties in a multicomponent L12 Ni46.5Co24Fe8Al12.5Ti9 superlattice alloy
Authors: Liu Weihong , Chen Keyu , Yu Chunyan
Published: February 2023

Ni3Al superlattice alloys with the L12 structure have garnered much attention due to their attractive high-temperature mechanical properties; however, their grain-boundary brittleness and low ductility in the ambient temperature range have greatly restricted their widespread application. In this study, we developed an L12 structure multicomponent Ni46.5Co24Fe8Al12.5Ti9 (at. %) superlattice alloy that notably suppressed the room-temperature intergranular brittleness and exhibited a large tensile elongation of 17.1% ± 5.2% together with a high ultimate tensile strength of 1,080.2 ± 57.4 MPa. Multiple microstructural examinations reveal an L12 equiaxed-grain microstructure, with the presence of a minor B2 phase. Moreover, the co-segregation of Fe and Co atoms, and the associated reduction or elimination of the L12 chemical order at the grain-boundary regions were characterized, which were proved to be the root cause of the suppression of intergranular brittleness and the high tensile ductility. Further theoretical calculations show that alloying of Fe and Co to binary Ni3Al reduced the ordering energy, which promoted intergranular segregation and associated disordering. This observation demonstrated that the elimination or reduction of interfacial chemical order is an effective ductilizing method for superlattice alloys.
The mast cell exosome-fibroblast connection: A novel pro-fibrotic pathway
Authors: Savage Alexandria , Risquez Cristobal , Gomi Kazunori , Schreiner Ryan , Borczuk Alain C. , Worgall Stefan , Silver Randi B.
Published: February 2023

Introduction

In addition to the traditional activation of resident receptors by release of local mediators, new evidence favors the existence of exosomes in cell-to-cell communication that mediates delivery of specific cargo to modulate recipient cell function. We report that mast cell exosomes are an additional source of pro-fibrotic substances and constitute a unique pathway for the generation of excess collagen.

Methods

We use primary human lung fibroblasts (HLFs) to demonstrate the uptake of labeled exosomes isolated from the human mast cell line HMC-1 (MC-EXOs), previously shown to contain protein cargo in common with human mast cell exosomes.

Results

The MC-EXO uptake by HLF is to the cytosol and increases both proline hydroxylation in HLF lysate and secreted collagen, within 24 h, which is sustained over 72 h, the same time required for transforming growth factor-β (TGF-β) to activate collagen synthesis in the HLFs. Unlike TGF-β, MC-EXO uptake does not induce fibrillar gene activation or invoke the Smad-nuclear transcription pathway. We show that MC-EXO uptake and TGF-β have an additive effect on collagen synthesis in HLF and postulate that MC-EXO uptake by HLFs is a contributing factor to excess collagen synthesis and represents a unique paradigm for understanding fibrosis.

Discussion

It is known that, in the lungs, mast cells are more activated and increase in number with inflammation, injury and viral infection associated with fibrosis. With the reported increased incidence of post-COVID-pulmonary fibrosis (PCPF), data from patients with severe COVID-19 are presented that show an increase in the mast cell number in lung parenchyma, the site of PCPF. Our findings provide a rationale for targeting multiple fibrogenic pathways in the management of lung fibrosis and the use of mast cell exosomes as a biomarker for the prognostic and diagnostic management of evolving fibrotic lung disease.
Thiostrepton, a resurging drug inhibiting the stringent response to counteract antibiotic-resistance and expression of virulence determinants in Neisseria gonorrhoeae
Authors: Talà Adelfia , Calcagnile Matteo , Resta Silvia Caterina , Pennetta Antonio , De Benedetto Giuseppe Egidio , Alifano Pietro
Published: February 2023

Due to the increased resistance to all available antibiotics and the lack of vaccines, Neisseria gonorrhoeae (the gonococcus) poses an urgent threat. Although the mechanisms of virulence and antibiotic resistance have been largely investigated in this bacterium, very few studies have addressed the stringent response (SR) that in pathogenic bacteria controls the expression of genes involved in host-pathogen interaction and tolerance and persistence toward antibiotics. In this study, the results of the transcriptome analysis of a clinical isolate of N. gonorrhoeae, after induction of the SR by serine hydroxamate, provided us with an accurate list of genes that are transcriptionally modulated during the SR. The list includes genes associated with metabolism, cellular machine functions, host-pathogen interaction, genome plasticity, and antibiotic tolerance and persistence. Moreover, we found that the artificial induction of the SR in N. gonorrhoeae by serine hydroxamate is prevented by thiostrepton, a thiopeptide antibiotic that is known to interact with ribosomal protein L11, thereby inhibiting functions of EF-Tu and EF-G, and binding of pppGpp synthase I (RelA) to ribosome upon entry of uncharged tRNA. We found that N. gonorrhoeae is highly sensitive to thiostrepton under in vitro conditions, and that thiostrepton, in contrast to other antibiotics, does not induce tolerance or persistence. Finally, we observed that thiostrepton attenuated the expression of key genes involved in the host-pathogen interaction. These properties make thiostrepton a good drug candidate for dampening bacterial virulence and preventing antibiotic tolerance and persistence. The ongoing challenge is to increase the bioavailability of thiostrepton through the use of chemistry and nanotechnology.
MCM10 expression is linked to cervical cancer aggressiveness
Authors: Ahmed Sumayyah M. Q. , Laha Suparna , Das Ranajit , Ifthikar Mariam Anjum , Das Shankar Prasad
Published: February 2023

Cervical cancer screening is a challenge mainly in developing countries. In developed countries, both incidence and mortality rates have been decreasing due to well organized screening programs. One of the potential biomarkers being exploited are the minichromosome maintenance proteins (MCMs), which show both specificity and sensitivity. MCM2-7 are involved in DNA replication initiation and elongation, and the MCM subunits are highly expressed in malignant tissues. Unlike other MCMs, MCM10, which is not part of the core helicase complex, is a critical determinant of origin activation and its levels are limiting in cancer cells. In this study, we performed bioinformatic analysis on the expression profile of all DNA replication associated MCM proteins in cervical cancer. MCM10 showed a relatively higher expression profile compared to the other MCMs. The mRNA expression levels of the MCMs were significantly increased in tumour tissues compared to normal, and MCM10 showed a fold change of 3.4. In order to understand if MCM10 is associated with the aggressiveness of cervical cancer, we looked into the mRNA expression pattern of MCM10 in three cervical cancer cell lines and one normal cervical cell line. MCM10 expression was significantly higher in the case of the more aggressive cancer cell line HeLa compared to controls. MCM10, therefore, can serve as a prominent biomarker for cancer progression and thus aid in early detection to control the spread of cancer cells. Our results show that MCM10 expression levels in cervical cancer cell lines are associated with cancer aggressiveness, demonstrating its clinical significance.
Naïve-memory regulatory T cells ratio is a prognostic biomarker for patients with acute ischemic stroke
Authors: Deng Gang , Tang Yue , Xiao Jun , Chen Xin , Chu Yun-Hui , Shang Ke , Zhou Luo-Qi , Qin Chuan , Wang Feng , Tian Dai-Shi
Published: February 2023

Background

Regulatory T cells (Treg) have been identified as a key modulator of neuroinflammation in stroke. However, little is known about the association of Treg subpopulations with clinical outcome in patients with acute ischemic stroke (AIS).

Methods

Patients within 1 week from stroke onset were prospectively enrolled in this study. Healthy controls were sex-and age-matched 1:1 to AIS patients. The frequencies of Treg and Treg subsets were analyzed by flow cytometry and compared with nonstroke control. Univariate and multivariate logistic regression analysis was performed to investigate the prognostic value of Treg subsets in stroke outcomes.

Results

A total of 328 patients and 328 controls were included in the study. Compared with controls, patients with AIS had higher levels of Treg frequency and memory Treg (mTreg) frequency, but lower levels of naïve Treg (nTreg) frequency and nTreg/mTreg ratio. One hundred twenty-six (38.4%) patients experienced unfavorable outcome (modified Rankin score 2–6). Multivariate regression analysis showed that nTreg/mTreg ratio was negatively associated with unfavorable 90-day outcome (the highest tertile versus the lowest tertile: odds ratio 0.13, 95% confidential interval [CI] 0.05–0.35). The risk estimation of unfavorable 90 day outcome can be significantly improved by adding nTreg/mTreg ratio to the conventional clinical parameters (continuous net reclassification improvement 91.26, 95% CI 69.04–113.5%, p < 0.001; integrated discrimination improvement 22.38, 95% CI 17.16–27.59%, p < 0.001).

Conclusion

This study showed that patients with AIS had elevated Treg frequency and mTreg frequency, but reduced nTreg frequency and nTreg/mTreg ratio. Admission nTreg/mTreg ratio was an independent predictor of unfavorable 90 day outcome in AIS. However, large sample-size cohort studies are needed to confirm our findings.
Behavioral and biochemical effects of alcohol withdrawal in female C3H/HeNRj and C57BL/6JRj mice
Authors: Tonetto Simone , Weikop Pia , Brudek Tomasz , Thomsen Morgane
Published: February 2023

Background

Alcohol use disorder (AUD) is a major problem of our society and is often characterized and worsened by relapse. Prolonged alcohol exposure leads to numerous biochemical alterations that, upon cessation of alcohol intake, cause an array of immediate and lasting withdrawal symptoms. Acute withdrawal and neuroinflammation can be harmful in themselves, and lasting withdrawal symptoms contribute to relapse. Here, we conducted an initial feasibility study assessing several behavioral and neurochemical factors in female C3H/HeNRj (C3H) and C57BL/6JRj (B6) mice to determine which strain showed the clearest alcohol withdrawal symptoms during long-term abstinence and neurochemical alterations following re-exposure.

Methods

Female C3H and B6 mice (n = 12 per group/strain) were intermittently exposed to alcohol-containing or control liquid diets for 3 weeks. Acute and prolonged withdrawal symptoms were assessed over a period of 3 weeks using a battery of behavioral test, comprised of alcohol self-administration, anhedonia, hyperalgesia, anxiety-like and depressive-like disturbances. Brain inflammation was measured by multiplex cytokine assay. Monoamine levels in the hippocampus and striatum, as well as exploratory analyses of cations levels in the cerebellum, were assessed by High-Performance Liquid Chromatography (HPLC).

Results

Both C3H and B6 alcohol-exposed mice displayed decreased saccharin intake or preference and higher stress levels assessed by ultrasonic vocalizations (USVs) recordings. B6 but not C3H alcohol-exposed mice also exhibited a slower decline of alcohol oral self-administration (OSA), hyperalgesia, elevated brain TNF-α and elevated serotonin turnover.

Conclusion

Our findings highlight the suitability of the B6 strain to study the behavioral and neurochemical alterations caused by alcohol withdrawal and the potential efficacy of experimental treatments, not only in early detoxification, but also in prolonged abstinence. The feasibility of these assays is important because long-lasting withdrawal symptoms are often the main cause of relapse in alcohol-dependent patients.
Machine learning segmentation of core and penumbra from acute stroke CT perfusion data
Authors: Werdiger Freda , Parsons Mark W. , Visser Milanka , Levi Christopher , Spratt Neil , Kleinig Tim , Lin Longting , Bivard Andrew
Published: February 2023

Introduction

Computed tomography perfusion (CTP) imaging is widely used in cases of suspected acute ischemic stroke to positively identify ischemia and assess suitability for treatment through identification of reversible and irreversible tissue injury. Traditionally, this has been done via setting single perfusion thresholds on two or four CTP parameter maps. We present an alternative model for the estimation of tissue fate using multiple perfusion measures simultaneously.

Methods

We used machine learning (ML) models based on four different algorithms, combining four CTP measures (cerebral blood flow, cerebral blood volume, mean transit time and delay time) plus 3D-neighborhood (patch) analysis to predict the acute ischemic core and perfusion lesion volumes. The model was developed using 86 patient images, and then tested further on 22 images.

Results

XGBoost was the highest-performing algorithm. With standard threshold-based core and penumbra measures as the reference, the model demonstrated moderate agreement in segmenting core and penumbra on test images. Dice similarity coefficients for core and penumbra were 0.38 ± 0.26 and 0.50 ± 0.21, respectively, demonstrating moderate agreement. Skull-related image artefacts contributed to lower accuracy.

Discussion

Further development may enable us to move beyond the current overly simplistic core and penumbra definitions using single thresholds where a single error or artefact may lead to substantial error.
Tui Na for painful peripheral neuropathy in people with human immunodeficiency virus: A randomized, double-blind, placebo-controlled trial protocol
Authors: Zhu Xingmei , Ge Song , Dune Linda , Yang Chao , Tian Chong , Wang Yong
Published: February 2023

Background

Peripheral neuropathy (PN), including numbness, loss of sensation, paresthesia, a burning sensation, and stabbing pain in extremities, is a common complication in people with human immunodeficiency virus (PHIV). Medications commonly used to treat HIV-related PN are not effective and lead to many side effects. HIV-related PN symptoms may be alleviated or treated with a series of therapeutic Chinese foot massages (TCFM), which are non-invasive and relatively safe. However, relevant studies are lacking.

Study design

This proposed trial is a prospective, two-arm, parallel, double-blinded, randomized controlled trial.

Aim

This proposed trial aims to assess the effectiveness of TCFM on HIV-related PN in people with HIV (PHIV).

Outcomes

The primary outcomes, measured at baseline, end of TCFM/placebo, and twelve weeks after, include (1), lower extremity pain, (2) lower extremity functioning, and (3) health-related quality of life. The secondary outcomes, measured throughout the trial process, include (1) recruitment and completion rate (No. of referred, No. of eligible, No. of enrolled, No. of withdrawals, trial recruitment rate, and trial completion rate), (2) participants' safety (No. and severity of adverse events), (3) treatment adherence (average time of each message session, No. of completed sessions, and No. of missed sessions), and (4) compliance (No. of participants completing the trial following the initial group assignment).

Sample size

An estimated 142 participants in total, or 71 participants in each arm, will be needed for this trial.

Trial status

This trial was registered at ClinicalTrials.gov of the National Institute of Health on Oct 26, 2022 (ClinicalTrials.gov Identifier: NCT05596123). The researchers expect to recruit participants starting in Feb. 2023 and ending in Feb 2025.
Intraoperative microelectrode recording under general anesthesia guided subthalamic nucleus deep brain stimulation for Parkinson's disease: One institution's experience
Authors: Qian Kang , Wang Jiajing , Rao Jing , Zhang Peng , Sun Yaqiang , Hu Wenqing , Hao Jie , Jiang Xiaobing , Fu Peng
Published: February 2023

Objective

Microelectrode recording (MER) guided subthalamic nucleus deep brain stimulation (STN-DBS) under local anesthesia (LA) is widely applied in the management of advanced Parkinson's disease (PD). Whereas, awake DBS under LA is painful and burdensome for PD patients. We analyzed the influence of general anesthesia (GA) on intraoperative MER, to assess the feasibility and effectiveness of GA in MER guided STN-DBS.

Methods

Retrospective analysis was performed on the PD patients, who underwent bilateral MER guided STN-DBS in Wuhan Union Hospital from July 2019 to December 2021. The patients were assigned to LA or GA group according to the anesthetic methods implemented. Multidimensional parameters, including MER signals, electrode implantation accuracy, clinical outcome and adverse events, were analyzed.

Results

A total of 40 PD patients were enrolled in this study, including 18 in LA group and 22 in GA group. There were no statistically significant differences in patient demographics and baseline characteristics between two groups. Although, the parameters of MER signal, including frequency, inter-spike interval (ISI) and amplitude, were obviously interfered under GA, the waveforms of MER signals were recognizable and shared similar characteristics with LA group. Both LA and GA could achieve effective electrode implantation accuracy and clinical outcome. They also shared similar adverse events postoperatively.

Conclusion

GA is viable and comparable to LA in MER guided STN-DBS for PD, regarding electrode implantation accuracy, clinical outcome and adverse events. Notably, GA is more friendly and acceptable to the patients who are incapable of enduring intraoperative MER under LA.
Linking resting-state network fluctuations with systems of coherent synaptic density: A multimodal fMRI and 11C-UCB-J PET study
Authors: Fang Xiaotian T. , Volpi Tommaso , Holmes Sophie E. , Esterlis Irina , Carson Richard E. , Worhunsky Patrick D.
Published: February 2023

Introduction: Resting-state network (RSN) connectivity is a widely used measure of the brain’s functional organization in health and disease; however, little is known regarding the underlying neurophysiology of RSNs. The aim of the current study was to investigate associations between RSN connectivity and synaptic density assessed using the synaptic vesicle glycoprotein 2A radioligand 11C-UCB-J PET.

Methods: Independent component analyses (ICA) were performed on resting-state fMRI and PET data from 34 healthy adult participants (16F, mean age: 46 ± 15 years) to identify a priori RSNs of interest (default-mode, right frontoparietal executive-control, salience, and sensorimotor networks) and select sources of 11C-UCB-J variability (medial prefrontal, striatal, and medial parietal). Pairwise correlations were performed to examine potential intermodal associations between the fractional amplitude of low-frequency fluctuations (fALFF) of RSNs and subject loadings of 11C-UCB-J source networks both locally and along known anatomical and functional pathways.

Results: Greater medial prefrontal synaptic density was associated with greater fALFF of the anterior default-mode, posterior default-mode, and executive-control networks. Greater striatal synaptic density was associated with greater fALFF of the anterior default-mode and salience networks. Post-hoc mediation analyses exploring relationships between aging, synaptic density, and RSN activity revealed a significant indirect effect of greater age on fALFF of the anterior default-mode network mediated by the medial prefrontal 11C-UCB-J source.

Discussion: RSN functional connectivity may be linked to synaptic architecture through multiple local and circuit-based associations. Findings regarding healthy aging, lower prefrontal synaptic density, and lower default-mode activity provide initial evidence of a neurophysiological link between RSN activity and local synaptic density, which may have relevance in neurodegenerative and psychiatric disorders.
A narrative review of the interconnection between pilot acute stress, startle, and surprise effects in the aviation context: Contribution of physiological measurements
Authors: Diarra Moussa , Marchitto Mauro , Bressolle Marie-Christine , Baccino Thierry , Drai-Zerbib Véronique
Published: February 2023

Aviation remains one of the safest modes of transportation. However, an inappropriate response to an unexpected event can lead to flight incidents and accidents. Among several contributory factors, startle and surprise, which can lead to or exacerbate the pilot's state of stress, are often cited. Unlike stress, which has been the subject of much study in the context of driving and piloting, studies on startle and surprise are less numerous and these concepts are sometimes used interchangeably. Thus, the definitions of stress, startle, and surprise are reviewed, and related differences are put in evidence. Furthermore, it is proposed to distinguish these notions in the evaluation and to add physiological measures to subjective measures in their study. Indeed, Landman's theoretical model makes it possible to show the links between these concepts and studies using physiological parameters show that they would make it possible to disentangle the links between stress, startle and surprise in the context of aviation. Finally, we draw some perspectives to set up further studies focusing specifically on these concepts and their measurement.
Global research trends in palliative care for breast cancer from 2012 to 2022: A scientometric analysis
Authors: Sun Yixian , Wu Jinyao , Tian Huiting , Qiu Xiuhua , Fang Ying , Xiao Yingjie , Zheng Jiehua , Zhou Yanqiong
Published: February 2023

Purpose

We used bibliometric methods to evaluate the global scientific output of palliative care breast cancer research and to explore the current status and further research directions in the field over the past decade.

Methods

All relevant publications from the year 2012 to 2022 were retrieved from Web of Science. We applied VOSviewer and Bibliometrix R v4.2.1 to obtain information on subject domains, annual publication output and citations, countries and authors with the highest productivity, influential journals and articles, and popular keywords.

Results

In total, 1529 publications were included in the final analysis. Health services and supportive care, pain and symptom management were the focus of the research in the field. From the year 2017 to 2021, the annual publication output was abundant and peaked in 2018. The systematic review by Fitzmaurice et al. in 2017 was the most-cited publication. The United States was the leading country with the maximum number of publications, citations, and link strengths with other countries. The most contributing institution was University of Toronto. E. Bruera was the most prolific author, ranking first among the authors in both the H and M index. The journal with the most publications was Palliative & Supportive Care. Keywords analysis indicated that exploring the significant degree of palliative care to reduce anxiety and depression in breast cancer patients may be a good research direction. In addition, how to assess the optimal timing of palliative care interventions and further exploring the specific contradiction between insufficient medical resources and palliative care are also possible research directions.

Conclusion

Palliative care plays an important role in the treatment of breast cancer. With the help of a scientometric analysis in this field, researchers can clarify the current research status and hotspots worth fully exploring.