bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishment and characterization of two novel patient-derived cell lines from giant cell tumor of bone: NCC-GCTB8-C1 and NCC-GCTB9-C1
Authors: Adachi Yuki , Noguchi Rei , Yoshimatsu Yuki , Sin Yooksil , Osaki Julia , Ono Takuya , Iwata Shuhei , Akiyama Taro , Tsuchiya Ryuto , Toda Yu , Ishihara Shin , Ogura Koichi , Kobayashi Eisuke , Kojima Naoki , Yoshida Akihiko , Yokoo Hideki , Kawai Akira , Kondo Tadashi
Published: November 2023

Giant cell tumor of bone (GCTB) is a rare osteolytic bone tumor consisting of mononuclear stromal cells, macrophages, and osteoclast-like giant cells. Although GCTB predominantly exhibits benign behavior, the tumor carries a significant risk of high local recurrence. Furthermore, GCTB can occasionally undergo malignant transformation and distal metastasis, making it potentially fatal. The standard treatment is complete surgical resection; nonetheless, an optimal treatment strategy for advanced GCTB remains unestablished, necessitating expanded preclinical research to identify appropriate therapeutic options. However, only one GCTB cell line is publicly available from a cell bank for research use worldwide. The present study reports the establishment of two novel cell lines, NCC-GCTB8-C1 and NCC-GCTB9-C1, derived from the primary tumor tissues of two patients with GCTB. Both cell lines maintained the hallmark mutation in the H3-3A gene, which is associated with tumor formation and development in GCTB. Characterization of these cell lines revealed their steady growth, spheroid-formation capability, and invasive traits. Potential therapeutic agents were identified via extensive drug screening of the two cell lines and seven previously established GCTB cell lines. Among the 214 antitumor agents tested, romidepsin, a histone deacetylase inhibitor, and mitoxantrone, a topoisomerase inhibitor, were identified as potential therapeutic agents against GCTB. Conclusively, the establishment of NCC-GCTB8-C1 and NCC-GCTB9-C1 provides novel and crucial resources that are expected to advance GCTB research and potentially revolutionize treatment strategies.
CXCL9 recombinant adeno-associated virus (AAV) virotherapy sensitizes glioblastoma (GBM) to anti-PD-1 immune checkpoint blockade
Authors: von Roemeling Christina , Yegorov Oleg , Yang Changlin , Klippel Kelena , Russell Rylynn , Trivedi Vrunda , Bhatia Alisha , Doonan Bently , Carpenter Savannah , Ryu Daniel , Grippen Adam , Futch Hunter , Ran Yong , Hoang-Minh Lan , Weidert Frances , Golde Todd , Mitchell Duane
Published: November 2023

The promise of immunotherapy to induce long-term durable responses in conventionally treatment resistant tumors like glioblastoma (GBM) has given hope for patients with a dismal prognosis. Yet, few patients have demonstrated a significant survival benefit despite multiple clinical trials designed to invigorate immune recognition and tumor eradication. Insights gathered over the last two decades have revealed numerous mechanisms by which glioma cells resist conventional therapy and evade immunological detection, underscoring the need for strategic combinatorial treatments as necessary to achieve appreciable therapeutic effects. However, new combination therapies are inherently difficult to develop as a result of dose-limiting toxicities, the constraints of the blood-brain barrier, and the suppressive nature of the GBM tumor microenvironment (TME). GBM is notoriously devoid of lymphocytes driven in part by a paucity of lymphocyte trafficking factors necessary to prompt their recruitment, infiltration, and activation. We have developed a novel recombinant adeno-associated virus (AAV) gene therapy strategy that enables focal and stable reconstitution of the GBM TME with C-X-C motif ligand 9 (CXCL9), a powerful call-and-receive chemokine for cytotoxic T lymphocytes (CTLs). By precisely manipulating local chemokine directional guidance, AAV-CXCL9 increases tumor infiltration by CD8-postive cytotoxic lymphocytes, sensitizing GBM to anti-PD-1 immune checkpoint blockade (ICB). These effects are accompanied by immunologic signatures evocative of an inflamed and responsive TME. These findings support targeted AAV gene therapy as a promising adjuvant strategy for reconditioning GBM immunogenicity given its excellent safety profile, TME-tropism, modularity, and off-the-shelf capability, where focal delivery bypasses the constrains of the blood-brain barrier, further mitigating risks observed with high-dose systemic therapy.
A dual-crosslinking electroactive hydrogel based on gelatin methacrylate and dibenzaldehyde-terminated telechelic polyethylene glycol for 3D bio-printing
Authors: Wang Yulong , Yang Songsong , Cai Heqing , Hu Hailong , Hu Kun , Liu Ruping , Sun Zhicheng , Wei Yen , Han Lu
Published: November 2023

Gelatin was widely used as scaffold materials in 3D bio-printing due to its excellent bioactivity and availability and especially that their arginine-glycine-aspartic acid (RGD) sequences could efficiently promote cell adhesion and proliferation. In this study, physical-chemical double crosslinked gelatin methacrylate-based electroactive hydrogel was prepared via Schiff-base reaction between the free amino groups of gelatin methacrylate (GelMA) and the aldehyde groups of dibenzaldehyde-terminated telechelic polyethylene glycol (DF-PEG), and meanwhile multi-walled carbon nanotubes (MWCNTs) were homogeneously distributed into GelMA solution. The optimized GelMA/DF-PEG composite hydrogel, i.e., 30% GelMA and 25% DF-PEG (G30D25-CNTs), exhibited superior bio-printability. When the content of CNTs was above 4%, the conductivity of G30D25-CNTs hydrogel exceeded 10− 2 S/m, which satisfied the needs of cells for micro-current stimulation. Furthermore, the swelling behavior and degradation ability of G30D25-CNTs electroactive hydrogels were thoroughly evaluated. Thus, the G30D25-CNTs hydrogel with 4% MWCNTs could be considered for further application in electrical stimulation of tissue regeneration such as muscle and cardiac nerve tissue repair.
The microalga Volvox carteri as a cell supportive building block for tissue engineering
Authors: STRICHER Mathilde , Vigneron Pascale , Delbecq Frédéric , Sarde Claude-Olivier , Egles Christophe
Published: November 2023

Background V. carteri f. nagariensis constitutes, in its most simplified form, a cellularized spheroid built around and stabilised by a form of primitive extracellular matrix (ECM).Methods Based on its structure and its ability to support surface cell adhesion most likely induced by the composition of its algal ECM, we have developed a modular approach to soft tissue engineering by compact-stacking of V. carteri–based living building blocks.Results A primary biocompatibility assessment demonstrated the algal suspension cytocompatibility, its histogenesis promoting properties, and that it did not induce an inflammatory response in vitro. These results allowed us to consider the use of such algal suspension for soft tissue augmentation and to initiate the study of its in vivo biocompatibility. V. carteri exhibited cellular fate-directing properties, causing fibroblasts to take on an alkaline phosphatase+ stem-cell-like phenotype and both human adipose-derived stem cells and mouse embryonic stem cells to differentiate into preadipocytes to adipocytes. The ability of V. carteri to support histogenesis and adipogenesis was also observed in vivo by subcutaneous tissue augmentation of athymic mice, highlighting the potential of V. carteri to support or influence tissue regeneration.Conclusions Our conclusion present for the first time V. carteri as an innovative and inspiring biomaterial for tissue engineering and soft tissue regeneration. Its strategies in terms of shape, structure and composition can be central in the design of a new generation of bio-inspired heterogeneous biomaterials recapitulating more appropriately the complexity of the body tissues when guiding their regeneration.
Risk assessment of antimony-arsenic contaminated soil remediated using zero-valent iron at different pH values combined with freeze-thaw cycles
Authors: Hei Erping , He Mingjiang , Zhang Enze , Yu Hua Yu , Chen Kun Chen , Qin Yusheng Qin , Zeng Xiangzhong , Zhou Zijun , Fan Hongzhu , Yuxian Shangguan , Wang Luying
Published: November 2023

Soil in mining wastelands is seriously polluted with heavy metals. Zero-valent iron (ZVI) is widely used for remediation of heavy metal-polluted soil because of its excellent adsorption properties; however, the remediation process is affected by complex environmental conditions, such as acid rain and freeze-thaw cycles. In this study, the effects of different pH values and freeze-thaw cycles on remediation of antimony (Sb)- and arsenic (As)-contaminated soil by ZVI were investigated in laboratory simulation experiments. The stability and human health risk of the remediated soil were evaluated. The results showed that different pH values coupled with freeze-thaw cycles could promote stabilization remediation of Sb- and As-contaminated soil by ZVI. Among them, ZVI significantly reduced the leaching toxicity and bioavailability of Sb and As in soil (both about 60.00%) after 32 rounds of freeze-thaw cycle treatment under water sample conditions of pH=1 (F1). However, Compared with soil not treated with freeze-thaw cycles, freeze-thaw cycles increased the leaching concentration of unstable forms of As. Bioavailability calculations based on Sb and As in remediated soil that alkaline soil there were no health or carcinogenic risks for children and adults, but the health risks and carcinogenic risks of Sb in acidic soil remained high for children. These findings provide a theoretical basis for the remediation of Sb- and As-contaminated soil using ZVI, and also highlight the importance of considering pH and freeze-thaw conditions in the remediation process to ensure effective and safe treatment.
Data-driven prediction of continuous renal replacement therapy survival
Authors: Bui Alex , Zamanzadeh Davina , Feng Jeffrey , Petousis Panayiotis , Vepa Arvind , Sarrafzadeh Majid , Karumanchi S. , Kurtz Ira
Published: November 2023

Continuous renal replacement therapy (CRRT) is a form of dialysis prescribed to severely ill patients who cannot tolerate regular hemodialysis. However, as the patients are typically very ill to begin with, there is always uncertainty as to whether they will survive during or after CRRT treatment. Because of outcome uncertainty, a large percentage of patients treated with CRRT do not survive, utilizing scarce resources and raising false hope in patients and their families. To address these issues, we present a machine-learning-based algorithm to predict if patients will survive after being treated with CRRT. We use information
extracted from electronic health records from patients who were placed on CRRT at multiple institutions to train a model that predicts CRRT survival outcome; on a held-out test set, the model achieved an area under the receiver operating curve of 0.929 (CI=0.917-0.942). Feature importance, error, and subgroup
analyses identified consistently, mean corpuscular volume as a driving feature for model predictions. Overall, we demonstrate the potential for predictive machine-learning models to assist clinicians in alleviating the uncertainty of CRRT patient survival outcomes, with opportunities for future improvement through further data collection and advanced modeling.
Optimum design parameters for double concave friction pendulum system considering ground motion characteristics and friction heating
Authors: Li Jiaxi , Tan Ping , Yang Kui , Liu Jingjing , Yamazaki Shinsuke , Yamada Satoshi
Published: November 2023

This paper addresses effectiveness limitations in the design of double concave friction pendulum systems (DCFPS) due to the absence of considering the interrelation between design parameters, ground motions (GM) characteristics, friction heating and seismic responses. By systematically evaluating the optimum design parameters for DCFPS under different strong GM classifications considering the effect of friction heating, it contributes a comprehensive understanding of the efficacy of DCFPS in vibration control. In this study, an analytical model for DCFPS in the SDOF structure is established, providing a precise characterization of the effect of friction heating and loading conditions on the responses. Based on this, the friction coefficient considering the influence of friction heating under strong GMs is applied in the seismic design. Subsequently, from the perspective of GM generation, strong GM records are categorized based on earthquake magnitude, distance-to-fault and soil conditions to indicate their magnitudes and spectral attributes. Then, the optimal design parameters are investigated for different GM classifications considering the effect of friction heating and response restrictions using response magnitude as criterion, and the effect of GM characteristics on the response and design parameters of DCFPS is investigated. It was found that, the consideration of residual displacement restriction and friction heating shows critical influence on the optimum selection of design parameters. Furthermore, the optimum friction coefficient is highly related to distance-to-fault, while the optimum range of isolation period is minimally influenced by GM characteristics. On top of these, a performance-based design method of FPS considering three performance criteria corresponding to three GM intensity levels is proposed, providing an effective method for mitigating the vibration of FPS under GMs.
Flight test results for the Microgravity Active Vibration Isolation System employed in the Fluid Physics Research Rack on-board the Chinese Space Station
Authors: Liu Wei , Gao Yang , Zhang Long , Zou Tianji , Yu Mengxi , Zheng Tuo
Published: November 2023

The Fluid Physics Research Rack (FPR) is a research platform employed on-board the Chinese Space Station for conducting microgravity fluid physics experiments. The research platform includes the Microgravity Active Vibration Isolation System (MAVIS) for isolating the FPR from disturbances arising from the space station itself. In addition, the MAVIS includes a microgravity operating mode that provides an environment with a controllable acceleration on the order of one millionth of the gravitational acceleration of the earth at sea level (i.e., µg0, where g0 = 9.80665 m/s2), and a vibration excitation operating mode that provides an environment with controllable vibrational acceleration signals of specific amplitudes in the frequency range of 0.01–10 Hz. The MAVIS is a structural platform consisting of a stator and floater that are monitored and controlled with non-contact electromagnetic actuators, high-precision accelerometers, and displacement transducers. The stator is fixed to the FPR, while the floater serves as a vibration isolation platform supporting payloads, and is connected with the stator only with umbilicals that mainly comprise power and data cables. However, the umbilicals have some stiffness that provides pathways for the transfer of disturbances from the stator to the floater. Therefore, the controller was designed with a correction for the umbilical stiffness to minimize the effect of the umbilicals on the vibration isolation performance of the MAVIS. In-orbit test results of the FPR demonstrate that the MAVIS was able to achieve a microgravity level of 1–30 µg0 in the frequency range of 0.01–125 Hz under the microgravity mode, and disturbances with a frequency greater than 2 Hz are attenuated by more than 10-fold. Under the vibration excitation mode, the MAVIS generated a minimum vibration acceleration of 0.4091 µg0 at a frequency of 0.00995 Hz and a maximum acceleration of 6253 µg0 at a frequency of 9.999 Hz. Therefore, the MAVIS provides a highly stable environment for conducting microgravity experiments, and promotes the development of microgravity fluid physics.
Ion Mobility-Tandem Mass Spectrometry of Mucin-type O-Glycans
Authors: Pagel Kevin , Bechtella Leïla , Chunsheng Jin , Fentker Kerstin , Ertürk Güney , Safferthal Marc , Polewski Łukasz , Götze Michael , Graeber Simon , Struwe Weston , Mall Marcus , Mertins Philipp , Karlsson Niclas
Published: November 2023

The dense O-glycosylation of mucins plays an important role in the defensive properties of the mucus hydrogel. Aberrant glycosylation is often correlated with inflammation and pathology such as COPD, cancer, and Crohn’s disease. The inherent complexity of glycans and the diversity in the O-core structure constitute fundamental challenges for the analysis of mucin-type O-glycans. Due to coexistence of multiple isomers, multidimensional workflows such as LC-MS are required. To separate the highly polar carbohydrates, porous graphitized carbon is often used as a stationary phase. However, LC-MS workflows are time-consuming and lack reproducibility. Here we present a rapid alternative for separating and identifying O-glycans released from mucins based on trapped ion mobility mass spectrometry. Compared to established LC-MS, the acquisition time is drastically reduced from an hour to two minutes. To test the validity, the developed workflow was applied to sputum samples from cystic fibrosis patients to map O-glycosylation features associated with disease.
How many blood pressure measurements should we take in the office?
Authors: Ozkan Gulsum , Ulusoy Sukru , Yılmaz Rahmi , Değer Müge , Derici Ülver , Arınsoy Turgay , Erdem Yunus
Published: November 2023

Background: No consensus has emerged among different guidelines concerning how many blood pressure (BP) measurements should be performed at office visits in the diagnosis of hypertension (HT). The purpose of this study was to examine the compatibility of various multiple average office BP measurements and 24-h BP monitoring (ABPM) in patients follow-up in the Cappadocia HT cohort.
Methods: 1158 office BP measurements by 207 patients were examined. Five BP measurements were taken at each office visit. The results were then classified as G1 (average of the 1st and 2nd BP measurements), G2 (average of the 2nd and 3rd), G3 (average of the 2nd, 3rd, and 4th), G4 (average of the 2nd, 3rd, 4th, and 5th), and G5 (average of five measurements). Compatibility between the average values in the groups and concomitant 24-h ABPM data was examined.
Results: While a significant difference was observed between daytime 24-h ABPM SBP and G1 (p=0.002), no difference was found the other groups. Office DBP approached the daytime 24-h ABPM values as the number of measurements in the five groups increased, although average office DBP data in all groups were higher than daytime 24-h ABPM DBP (p 0.000 for all).
Conclusion:In the light of our study results, we recommend that three office BP measurements be performed and that the average of the 2nd and 3rd measurements be used for SBP, while in terms of DBP, we recommend that as many measurements as possible be taken without the 1st value being included in the average.
The effect of discordance between embryologist and pathologist on sperm retrieval rates in patients with non-obstructive azoospermia undergoing mTESE
Authors: Sahin Mehmet , CAN OSMAN , Keskin Emin , Filtekin Yigit , Canat Lutfi
Published: November 2023

This study investigates predictive factors, specifically the consistency between embryologist and pathologist, influencing sperm retrieval rates in microdissection testicular sperm extraction for non-obstructive azoospermia. The research involved 91 patients aged 20 to 47, who applied to our Reproductive Technology center from July 2020 to June 2023. Patient data, including demographics, physical exams, lab tests, radiological assessments, genetic analyses, medical histories, and histopathological results, were retrospectively collected. Different than literature findings, cases were identified where histopathology showed spermatozoa, yet microdissection testicular sperm extraction yielded unsuccessful sperm retrieval. The Johnsen score was categorized into three groups: spermatozoa found (Group I), maturation arrest (Group II), and no spermatogenesis (Group III). In Group I, despite pathologist-identified spermatozoa, only 66.6% were deemed successful sperm retrieval by the embryologist. Overall sperm retrieval rates were lower than expected at 39.56%. A logistic regression model was employed to determine the independent predictors of positive sperm retrieval. In this analysis, FSH levels, testicular volume, histopathological findings, and alcohol consumption emerged as significant predictive factors for the outcome of sperm retrieval. As a result, in addition to these patient-related factors, the consistency between the pathologist and histologist is also important.
The mechanism of element inhomogeneity in TW-DED-arc fabricated γ-TiAl Alloy
Authors: Xin Jianwen , Li Fang , Wu Dongsheng , Shen Chen , Komen Hisaya , Tanaka Manabu , Hua Xueming
Published: November 2023

The twin-wire directed energy deposition-arc (TW-DED-arc) method is a low-cost and efficient in-situ alloying process for producing γ-TiAl alloy, a new generation material for aero-engine blades. Its characteristic of “twin-wire-one-drop” can successfully avoid the phenomenon of discordant melting and ineffective mixing. In this study, the mixing effect of “twin-wire-one-drop” was analysed, and droplets of different diameters were used for fabricating Ti52Al48 walls. It was found that the mixing effect in the droplet was great, but there were still local unmixed areas, and a completely uniform Ti52Al48 wall could be obtained by using small droplets mode. Meanwhile, incompletely mixing regions with composition difference greater than 5% appeared in many places on the sides of the Ti48Al wall in huge droplet mode. A numerical model is established to simulate the mixing process after the droplet enters the molten pool. It is found that the secondary droplets generated in huge droplet mode is the main reason for the element inhomogeneity phenomenon. Therefore, keeping the droplet interval short and uniform is beneficial to the element in-situ alloying.
Phytochemical analysis of Stevia rebaudiana using HPLC and GC-MS
Authors: Gunasena M.D.K.M. , Senarath W.T.P.S.K.
Published: November 2023

Stevia rebaudiana is a medicinal plant rich in important phytochemicals including steviol glycosides. Its’ leaves are the source of non-caloric sweet steviol glycosides and stevioside is the main type. In this study leaves of naturally grown, tissue cultured plants and callus extracts of S. rebaudiana were analyzed using HPLC and GC-MS to determine the possibility of obtaining stevioside and other important phytochemicals through in vitro technology. Phytochemical extraction was done using methanol, evaporated using a rotary evaporator and re-dissolved in acetonitrile: deionized water (3:7) ratio solvent mixture. Stevioside contents were analyzed using HPLC system with C18 column. Methanolic extracts of naturally grown plants, tissue cultured plants and calli were screened using GC-MS and compared. According to HPLC analysis, leaves of tissue cultured plants contained highest amount of stevioside content (11.462 ± 0.03 mg/mL) followed by naturally grown plants and calli. Twenty seven important phytochemicals were identified by GC-MS analysis and out of those fourteen compounds were found to be common in all three samples. Results revealed that in vitro cultures can be used as the better alternative to overcome limitations in conventional propagation and can be used to obtain stevioside and other important phytochemicals instead of natural plants. GC-MS analysis of Stevia extracts revealed the presence of terpenes, fatty acids, aldehydes with biological activities such as antimicrobial, anticancer, anti-inflamatory, antioxidant, antimalarial and etc. Bioactivity of those phytochemicals showed the possible use of Stevia extracts in pharmaceutical, food and perfume industries.
Exploring patient-related factors behind racial inequities in buprenorphine treatment for opioid use disorder in primary care
Authors: Kung Sunny , Casey Sarah , Regan Susan , McGovern Sydney , Sawyer Samantha M. , Wakeman Sarah E.
Published: November 2023

From 2019 to 2020, overdose death rates increased 39% among Black Americans nationally. The goal of this study is to understand patient-related etiologies behind racial inequities in buprenorphine treatment for opioid use disorder (OUD) in primary care patients. We surveyed adults with primary care providers (PCPs) in practices at an integrated healthcare system in Massachusetts where buprenorphine was prescribed. 428 adults were randomly sampled, 278 confirmed to have OUD via chart review, and 33 patients completed the survey. 36.4% (n=12) identified as LatinX, 33.3% (n=11) identified as Black, 27.3% (n=9) as white. 82% (n=27) reported having ever been prescribed buprenorphine for OUD [100% (n=9) of white respondents, 75% (n=9) of Latinx respondents, 73% (n=8) of Black respondents]. A majority (n=23) of respondents preferred to get their OUD treatment at their PCP’s office [82% (n=9) of Black respondents, 75% (n=9) of LatinX respondents, and 56% (n=5) of white respondents]. Most Black and Latinx patients preferred to get their OUD treatment at their PCP’s office although only half have ever discussed buprenorphine with their PCP. Black and Latinx patients placed more importance on having healthcare staff who are from and know about different racial/ethnic backgrounds compared to white patients. None of the respondents reported that having their PCP share or understand their racial/ethnic background would improve buprenorphine access. Respondents suggested that hiring more staff and clinicians who are Black and/or Latinx, treating people with SUD compassionately, and offering financial assistance would better meet the needs of Black and Latinx patients.
Use of cold plasma treatment to improve banana tolerance against Fusarium wilt disease
Authors: Rejab Nur Ardiyana binti , Rajakumar Priya , Baharum Nadiya Akmal , Lutfi Afiqah Insyirah , Sadali Najiah Mohd , Mispan Muhamad Shakirin , Kuang Lim Liang , Ling Yap Seong , Khalid Norzulaani
Published: November 2023

Bananas (Musaspp.), which serves millions of people worldwide, face a serious threat from Fusarium wilt (FW) disease caused by Fusarium oxysporum f. sp.cubense (Foc). Developing disease-resistant varieties particularly through breeding is challenging due to bananas' seedless nature (parthenocarpic). As an alternative, cold plasma (CP) technology, has the potential to be used for crop improvement. Our study demonstrates a favourable impact of CP on the growth performance of banana (Berangan cultivar) in terms of height, leaf number and stem diameter. Plasma treated plants also displayed delayed disease progression as well as lower disease severity indicated by slightly lower value of leaf symptoms index (LSI) and rhizome discoloration index (RDI) compared to controls. Additionally, quantitative polymerase chain reaction (qPCR) analysis revealed upregulation of several defence (PR1, WRKY22, PAL, CEBiP) and growth (Cytochrome P450, NAC68, and CAT) related genes in CP treated plants, particularly in conjunction with Foc infection. These findings shed highlight the potential use of CP in managing FW in banana and offer insights into possible mechanism behind improved traits.
Growth of Fatty Acid Vesicles Coupled with Amino Acid Sequences of Peptides: Toward Evolvable Protocells
Authors: Imai Masayuki , Baba Akiko , Yokoyama Kazuki , Sato Keidai , Asanuma Shuna , Olsson Ulf
Published: November 2023

How sequence of information polymer and reproduction (growth and division) of vesicles were linked is a fundamental question about the emergence of the living systems. To address the origin of this linkage, we have investigated the relationship between amino acid sequence and vesicle growth using short peptides and fatty acid vesicles. The growth of fatty acid vesicles was measured by a dynamic light scattering technique when fatty acid molecules and peptides were fed into a fatty acid vesicle suspension. The obtained relationship between amino acid sequences of peptides and vesicle growth rate (fitness) was visualized as the fitness landscape. The growth rate of fatty acid vesicles depends on the amino acid sequence, and specific amino acid sequences significantly promote vesicle growth. Furthermore, when amino acids in a peptide are replaced by other amino acids, the change in fitness depends on the remaining amino acid sequence, so-called epistasis, which guarantees the diversity of peptide-fatty acid vesicle systems (protocell). The observed linkage between amino acid sequence and vesicle growth indicates that the peptide-fatty acid vesicle systems can lead to primitive evolution. Finally, we demonstrate that the promotion of vesicle growth by peptides is driven by the modulation of the chemical potential of fatty acid molecules. Thus, the vesicle growth promoted by peptides is a spontaneous process that is thermodynamically driven.
Molecular mechanism of flower color formation in Rhododendron simsii Planchon revealed by integration of microRNAome and RNAomics
Authors: Wu Wei , Wan Xuchun , Huang Wendong , Hu Ruibin , Dong Hongjin , Zhang Jialiang , Wang Shuzhen
Published: November 2023

Background

Systems-wide understanding of gene regulatory networks underlying flower color formation in Rhododendron simsii is insufficient. In this research, integration analysis of microRNAome and RNAomics were performed to reveal the molecular mechanism of flower color formation in three R. simsii varieties with red, pink, and crimson flowers, respectively.

Results

A total of 213 miRNAs, containing 151 known miRNAs belonging to 55 families and 62 novel miRNA, were identified. In particular, 53 miRNAs were significantly differently expressed. The top significant enriched GO terms were mainly “meristem maintenance”, “carbohydrate metabolic process”, and “signal transduction”. The main KEGG pathways were “Monobactam biosynthesis”, “Plant-pathogen interaction”, and “MAPK signaling pathway-plant”. The miRNA–mRNA regulatory network construction showed that key genes and pathways were mainly associated with synthesis of secondary metabolites. In particular, ath-miR5658 could affect the synthesis of pelargonidin, cyanidin, and delphinidin through downregulating expression of anthocyanidin 3-O-glucosyltransferase; ath-miR868-3p could regulate isoflavonoid biosynthesis through downregulating expression of CYP81E1/E7; ath-miR156g regulated the expression of flavonoid 3',5'-hydroxylase; ath-miR829-5p regulated flavonol synthase in flavonoid biosynthesis process.

Conclusion

This research will provide critical clues of flower color formation, and provide novel insights into the breeding of new varieties with rich flower color.
Hepatitis E outbreak in the health district of Bocaranga-Koui, Central African Republic, 2018-2019
Authors: Nombot-Yazenguet Marina Prisca Marguerite , Doté Joël Wilfried , Koyaweda Giscard Wilfried , Zemingui-Bembete Philippe Armand , Selekon Benjamin , Vickos Ulrich , Manirakiza Alexandre , Nakoune Emmanuel , Gouandjika-Vasilache Ionela , Komas Narcisse Patrice Joseph
Published: November 2023

Background:Hepatitis E virus (HEV) is one of major public health diseases causing large outbreaks and sporadic cases of acute hepatitis. We investigated an outbreak of HEV infection that occured in september 2018 in the health district (HD) of Bocaranga-Koui in the northwestern part of Central African Republic (CAR).Methods:Blood samples were collected from 352 patients aged 0-85 years suspected for yellow fever (YF) according to the World Health Organization YF case definition. The notification forms from cases recorded were used. Water sources consumed in the areas were also collected. Human samples found negative for anti-YF IgM were then ELISA-tested for anti-HEV IgM and IgG antibodies. Positive anti-HEV (IgM and/or IgG) samples and collected water were subjected to molecular biology tests.Results:Of the 352 icterus patients included, anti-HEV IgM was found in 142 people (40.3%) and anti-HEV IgG in 175 (49.7%). Although HEV infection was detected in all age groups, there was significant difference between age groups (P= 0.001). Elevated levels of serum aminotransferase were observed in anti-HEV IgM-positive persons. Phylogenetic analysis showed HEV genotype 1e in infected patients and also in the contaminated water.Conclusion:This epidemic showed that CAR remains an HEV-endemic area. The genotype 1e strain is responsible for the HEV outbreak in Bocaranga-Koui health district. It is necessary to implement basic conditions of hygiene and sanitation to prevent the outbreak of an hepatitis E epidemic, by facilitating access to clean drinking water for the population, by launching intensive work to raise awareness for basic hygiene measures, by setting up targeted hygiene promotion activities and, finally, by making a care service available.
Alcohol and e-cigarette damage alveolar-epithelial barrier by activation of P2X7r and provoke brain endothelial injury via extracellular vesicles
Authors: Mekala Naveen , Trivedi Jayshil , Bhoj Priyanka , Togre Namdev , Rom Slava , Sri Uma , Persidsky Yuri
Published: November 2023

Background
Use of nicotine containing products like electronic cigarettes (e-Cig) and alcohol are associated with mitochondrial membrane depolarization, resulting in the extracellular release of ATP, and mitochondrial DNA (mtDNA), mediating inflammatory responses. While nicotine effects on lungs is well-known, chronic alcohol (ETH) exposure also weakens lung immune responses and cause inflammation. Extracellular ATP (eATP) released by inflammatory/stressed cells stimulate purinergic P2X7 receptors (P2X7r) activation in adjacent cells. We hypothesized that injury caused by alcohol and e-Cig to pulmonary alveolar epithelial cells (hPAEpiC) promote the release of eATP, mtDNA and P2X7r in circulation. This induces a paracrine signaling communication either directly or via EVs to affect brain cells (human brain endothelial cells - hBMVEC).
Methods
We used a model of primary human pulmonary alveolar epithelial cells (hPAEpiC) and exposed the cells to 100 mM ethanol (ETH), 100 µM acetaldehyde (ALD), or e-Cig (1.75µg/mL of 1.8% or 0% nicotine) conditioned media, and measured the mitochondrial efficiency using Agilent Seahorse machine. Gene expression was measured by Taqman RT-qPCR and digital PCR. hPAEpiC-EVs were extracted from culture supernatant and characterized by flow cytometric analysis. Calcium (Ca2+) and eATP levels were quantified using commercial kits. To study intercellular communication via paracrine signaling or by EVs, we stimulated hBMVECs with hPAEpiC cell culture medium conditioned with ETH, ALD or e-cig or hPAEpiC-EVs and measured Ca2+ levels.
Results
ETH, ALD, or e-Cig (1.8% nicotine) stimulation depleted the mitochondrial spare respiration capacity in hPAEpiC. We observed increased expression of P2X7r and TRPV1 genes (3-6-fold) and increased intracellular Ca2+ accumulation (20-30-fold increase) in hPAEpiC, resulting in greater expression of endoplasmic reticulum (ER) stress markers. hPAEpiC stimulated by ETH, ALD, and e-Cig conditioned media shed more EVs with larger particle sizes, carrying higher amounts of eATP and mtDNA. ETH, ALD and e-Cig (1.8% nicotine) exposure also increased the P2X7r shedding in media and via EVs. hPAEpiC-EVs carrying P2X7r and eATP cargo triggered paracrine signaling in human brain microvascular endothelial cells (BMVECs) and increased Ca2+ levels. P2X7r inhibition by A804598 compound normalized mitochondrial spare respiration, reduced ER stress and diminished EV release, thus protecting the BBB function.
Conclusion
Abusive drugs like ETH and e-Cig promote mitochondrial and endoplasmic reticulum stress in hPAEpiC and disrupts the cell functions via P2X7 receptor signaling. EVs released by lung epithelial cells against ETH/e-cig insults, carry a cargo of secondary messengers that stimulate brain cells via paracrine signals.
The Study of Genetic Diversity and Structure of Extremely Endangered Manglietia longipedunculata and Endangered Manglietia insignis
Authors: Qin Qiaomei , Yang Yishan , Wei Xiao , Pan Lipo , Zhu Xianliang , Wu Linfang , Liu Shunlai , Zhong Qifeng , Zhong Wenchao , Tang Jianmin
Published: November 2023

To strengthen the protection of Manglietia insignis and Manglietia longipedunculata germplasm resources, the endangered mechanism and scientific protection strategies of these two species were investigated. A novel, effective, and flexible DNA sequencing library construction approach-Hyper-seq was used in this study to develop large-scale genomic single nucleotide polymorphism (SNP) and to evaluate the genetic diversity and population structure of M. insignis and M. longipedunculata. Genetic diversity analysis demonstrated that the genetic diversity of M. insignis, which expected heterozygosity (He) was 0.1435 and nucleotide diversity (π) was 0.1541.M. longipedunculata, lower than in M. longipedunculata (He= 0.1793, π = 0.1916) with narrow distribution. The genetic diversity of the two ex-situ conservation populations (He=0.1797, 0.1990, π = 0.1894, 0.2121 ) was higher than the wild populations (He=0.1591, π = 0.1733), suggesting that the artificial ex-situ conservation population can effectively protect its genetic diversity and the genetic breeding in future studies. The mean inbreeding coefficient (FIS) in the M. longipedunculata and M. insignis populations were − 0.0141 and − 0.0176, respectively, indicating that the two populations were largely outcrossing in the natural state. The frequency of rare alleles in M. insignis (Tajima's D = 0.3436 > 0) and M. longipedunculata (Tajima's D = 0.2119 > 0) populations was low, which may be under balanced selection pressure or experienced population shrinkage. A high degree of genetic differentiation between the two species was detected, but moderate among the populations of the same species. The results of cluster analysis demonstrated a obvious separation between the two species with all individuals clustering according to species differences. It is worth noting that individuals 7, 8, and 9 in the ML-CW M. insignis population first clustered with M. longipedunculata. Furthermore, these individuals also contained a small genetic component from M. longipedunculata. Principal component and genetic relationship analysis also demonstrated that some M. insignis individuals exhibited an evident genetic relationship with M. longipedunculata. These populations can therefore be preferentially selected in the further cross-breeding experiments of the two species. The genetic diversity and structure of M. insignis and M. longipedunculata were compared in this study. Not only were the genetic characteristics of the two species explored for the first time, but the genetic relationship between the two species was also preliminarily explored. This study provides a scientific basis for the development of future protection strategies at the molecular level.
Vision-related quality of life and its related factors among older adults
Authors: Morowatisharifabad Mohammad Ali , Zough Leila Jafari , Babaei Esmail , Behrevar Vali , Rezaeipandari Hassan
Published: November 2023

Purpose
This study aimed to determine the vision-related quality of life (VRQoL) status and its related factors among older adults in Yazd city, Iran.
Methods
This cross-sectional study was conducted in 2023 with the participation of 250 elderly people ≥ 60 years of age covered by comprehensive health centers in Yazd city in central Iran, who were selected by multi-stage random sampling. The data collection tool included demographic information and the National Eye Institute-Visual Function Questionnaire (NEI VFQ-25) which was completed by interview. Data analysis was done using independent T-tests, one-way analysis of variance and hierarchical regression analysis using SPSS software.
Results
The most common visual impairment (VI) in the participants were hyperopia (38.2%), cataract (35.5%) and myopia (31.3%), respectively. Their average VRQoL score was 85.37 ± 15.24 from the range of 0 to 100. In univariate analysis, VRQoL score was significantly related to age, marital status, use of glasses, suffering from some diseases and VI (p < 0.05). In the multivariate analysis, diabetes (β = -0.15), hypertension (β = -0.20) and VI (β = -0.62) remained as significant predictors of VRQoL in the regression model.
Conclusion
The level of VRQoL in the studied elderly is favorable, and in the meantime, the dimensions of social functioning, driving and color vision are at the highest level, and the dimensions of general health and general vision are unfavorable and should be given special attention. VRQoL is influenced by various factors, of which diabetes, high blood pressure and VI were identified as the most important predictors.
Crucial role of TFAP2B in the nervous system for regulating NREM sleep
Authors: Nakai Ayaka , Kashiwagi Mitsuaki , Fujiyama Tomoyuki , Iwasaki Kanako , Hirano Arisa , Funato Hiromasa , Yanagisawa Masashi , Sakurai Takeshi , Hayashi Yu
Published: November 2023

The AP-2 transcription factors are crucial for regulating sleep in both vertebrate and invertebrate animals. In mice, loss of function of the transcription factor AP-2β (TFAP2B) reduces non-rapid eye movement (NREM) sleep. When and where TFAP2B functions, however, is unclear. Here, we used the Cre-loxP system to generate mice in which Tfap2b was specifically deleted in the nervous system during development and mice in which neuronal Tfap2b was specifically deleted postnatally. Both types of mice exhibited reduced NREM sleep, but the nervous system-specific deletion of Tfap2b resulted in more severe sleep phenotypes accompanied by defective light entrainment of the circadian clock and stereotypic jumping behavior. These findings indicate that TFAP2B in postnatal neurons functions at least partly in sleep regulation and imply that TFAP2B also functions either at earlier stages or in additional cell types within the nervous system.
Machine Learning with Multiparametric MRI-based Radiomics Models for Preoperative Prediction of Ki-67 Status in Luminal Breast Cancer
Authors: Gao Qian , Lu Meixiu , Xie Xiaojie , Luo Chunyan , Gao Chao , Han Zhiquan , Lu Yanhui , Zhao Ruixue , Fang Linlin , Han Dan , Li Jun
Published: November 2023

Background
The main objective of the study was to determine whether multiparametric MRI (mpMRI) radiomics models supported by machine learning could preoperatively predict Ki-67 status in luminalbreast carcinoma.
Methods
Between 2018 and 2021, patients with luminal breast cancer who underwent mpMRI in our institution were retrospectively enrolled. The Ki-67 status was analyzed by biopsy preoperatively. Radiomics features were extracted from the T2WI, DCE, DWI, and ADC images, and mpMRI features were derived from four MRI sequences. A prediction model was developed by training the logistic regression (LR), multilayer perceptron (MLP), random forest (RF), and support vector machine (SVM) machine learning classifiersaccording to the radiomic characteristics. A clinical-radiomic nomogram was constructed by integrating mpMRI radiomic features and routine clinical MRI variables, followed by calibration and decision curve analyses.
Results
A total of 140 patients (85 with high and 55 with low Ki-67 expression) were enrolled. Compared to the DCE-, DWI-, and ADC-based radiomic signatures, the T2WI-based radiomic signature exhibited high prediction quality with AUCs of 0.87, 0.92, 0.92, and 0.89 for the four classification algorithms (LG, RF, MLP, SVM), respectively (all p<0.05). The mpMRI radiomic signature also showed high quality with AUCs of 0.92, 0.89, 0.92, and 0.92 for the four algorithms (all p<0.05). A prediction clinical-radiomicnomogram was constructed with training and validation set AUCs of 0.93 (0.90-0.96) and 0.92 (0.89-0.95), respectively.
Conclusion
T2-based and mpMRI-based radiomics models combined with advanced machine learning classifiers could assist in the preoperative individual-specific prediction of Ki-67 status in luminalbreast carcinoma.
Computational Simulation of Blood Flow in the Right Coronary Artery and its Interaction Between the Blood Flow and the Arterial Wall
Authors: Chinè Bruno , Campos Manuel A. Molina , Granados Benito A. Stradi
Published: November 2023

Flow through a heart artery is modeled using computational fluid dynamics with and without a more detailed fluid-solid interaction model. The study describes the interactions between the blood flow and the arterial wall. Blood rheological properties are modeled using the Bird-Carreau model under steady state conditions. The flow path is comprised by the right coronary artery and two branches (bifurcations) namely the acute marginal and the posterior descending sections. Inlet velocity values of a typical cardiac cycle are used in the model. The differences between the solutions from the FSI model and the CFD model were determined by comparing the wall shear stress and the first principal stress. Wall shear stresses and first principal stresses for four separate times (0.05, 0.14, 0.44 and 0.96 s) are reported. At 0.14 s and at 0.96 s, the values of the WSS maximum are greater than those previously computed using FSI by 10.8 Pa and 7.5 Pa. Similarly at 0.44 s, significant differences were obtained in the WSS distributions between both solutions. The highest magnitudes of first principal stresses were of 552 kPa in the bifurcation of the PDA at a time of 0.44 s.
Etiology, clinical manifestations, and management methods of cryptitis beside the preputial frenulum in men
Authors: Fan Wenge , Zhang Qingsong , Fan Zhijiang , Wei Mei , Zhu Yuan
Published: November 2023

Background: To understand the etiology, clinical manifestations, and management methods of cryptitis beside the preputial frenulum in men.
Methods: The demographic data; shortest distance between the opening edges of the left and right crypts beside the preputial frenulum; and presence, shape, opening diameter, and depth of a blind cavity-like structure at the crypt were compared between the observation group and control group. The clinical manifestations were also recorded. Pathogen testing was performed on secretions from skin lesions, and antibiotic treatment was conducted.
Results: Thirteen patients treated for cryptitis beside the preputial frenulum served as the observation group, and 40 healthy individuals served as the control group. The patients’ clinical manifestation was the presence of a yellowish oily substance embedded in the crypt. Wiping off the substance revealed a conical blind cavity-like structure with an opening diameter of 1 to 5mm (2.8±1.3mm) and depth of 1 to 4mm (2.5±1.1mm). No blind cavity-like structures in the crypt were found in the control group. The shortest distance between the opening edges of the bilateral crypts in the observation and control groups was 6 to 14mm (10.3±2.4mm) and 2 to 10mm (3.9±1.9mm), respectively, with a statistically significant difference. The three most common pathogens were Candida albicans, Staphylococcus aureus, and Escherichia coli. All patients recovered after treatment.
Conclusion: A blind cavity-like structure in the crypt may be related to the excessive width of the preputial frenulum. Cryptitis may be a secondary infection caused by smegma trapped in the blind cavity-like structure. Antibiotic treatment is effective.