bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental investigation and development of Artificial neural network modeling of 3D printed PEEK bio implants and its optimization
Authors: Borah Jyotisman , Chandrasekaran Muthumari
Published: September 2023

Additive manufacturing (AM) initially used as validation tool and now growing rapidly with promising results and challenges. Three-dimensional (3 D) printing is sub set of AM and it develops 3D parts from digital model data by adding materials ‘layer by layer’; it found applications in automotive, aerospace and medical sectors with a competitive advantage of reducing in product development cycle. Fused deposition modeling (FDM) is of the popular 3D printing approach used to fabricate polyether ether ketone (PEEK) parts being used as biomedical implants. In this work, an experimental investigation on PEEK 3D printing, artificial neural network (ANN) modeling and parametric optimization for obtaining improved 3D prints are investigated. Four process parameters viz., infill density (ID), layer height (LH), printing speed (PS) and infill pattern (IP) that affect the surface roughness (SR) and mechanical strength (UTS) of the prints produced. An ANN model having 4-12-2 network architecture found optimum with an average prediction error of 2.98% for SR and 1.92% for UTS. The developed ANN model is compared with response surface methodology (RSM) modeling and it exhibits excellent agreement with ANN. Higher ID and lower PS is required for producing better surface quality with improved strength so as to have regular grains with less irregularities. The microstructural study is carried out by obtaining SEM images. The Multi objective optimization results using desirability analysis (DA) obtain SR value of 4.80 µm and UTS of 61.90 MPa for ID = 79.4%, LH = 0.14 mm, PS = 25 mm/s with octet pattern is the best combined quality characteristics having composite desirability of 0.8221.
Assessment of Right Ventricular Function in Patients undergoing Coronary Artery Bypass Graft : a single center study
Authors: Taha Salma , Taha Ahmed , Refaat Maria , ElKhayat Hussein , Atta Salah , Mandour Ahmed , Abdel-Galeel Ahmed
Published: September 2023

Background:
Right ventricular dysfunction (RVD) is a major risk factor in coronary artery disease (CAD). In patients undergoing revascularization for left ventricular ischaemia, the incidence of RVD is reported in about 20%.
Aim:
this study aimed to assess right ventricular function as a possible risk factor in patients undergoing coronary artery bypass graft.
Patients and methods:
This prospective study was conducted on 77 patients underwent coronary artery bypass grafting. All cases were subjected to detailed medical history, full physical examination, electrocardiogram, routine laboratory tests including echocardiography or STE, all parameters obtained before, within 1 week and 6 months after surgery.
Result:
Though, LVEF preoperatively was insignificantly higher in RVD group compared to non RVD (P=0.84), LVEF 1 week postoperatively was significantly lower in RVD group compared to non RVD group (p=0.03) at the same time there was significant reduction in LVEF in both groups 1 week postoperatively compared to preoperatively and this was more obvious in RVD group compared to non RVD group (p=0.001). In addition, the diastolic function (E/A ratio) preoperatively was significantly lower in RVD group compared to non RVD group (p=0.03). Moreover, the mean longitudinal strain was significantly higher in non RVD group compared to RVD group preoperatively (p=0.012).
Conclusion:
It is suggested that at the early days after the CABG surgery there is a decline in right ventricle function which is relatively reversible at longer intervals (6 months after surgery). Hence, it is recommended to conduct longer studies to evaluate right ventricular function after CABG surgery.
Meso-scale geoacoustic seabed quantification
Authors: Sonnemann Tim , Dettmer Jan , Holland Charles , Dosso Stan
Published: September 2023

We present an automated geoacoustic inversion method for novel autonomous underwater vehicle data that adapts model inference to seabed structure. Through parallelized trans-dimensional Bayesian inference, we infer seabed properties along a 12 km survey track on the scale of about 10 cm and 50 m in the vertical and horizontal, respectively. Using acoustic reflection coefficient data, the inferred physical parameters as a function of depth include sound speed, attenuation, density, and porosity. Parameter uncertainties are quantified, and the seabed properties agree closely with core samples at two control points and the layering structure with an independent sub-bottom seismic survey. Recovering high resolution seabed properties over large areas is shown to be feasible, which could become an important tool for marine industries, navies and oceanic research organizations.
Illuminating the Function of the Orphan Transporter, SLC22A10 in Humans and Other Primates
Authors: Giacomini Kathleen , Yee Sook Wah , Ferrández-Peral Luis , Alentorn Pol , Fontsere Claudia , Ceylan Merve , Koleske Megan , Handin Niklas , Artegoitia Virginia , Lara Giovanni , Chien Huan-Chieh , Zhou Xujia , Dainat Jacques , Zalevsky Arthur , Sali Andrej , Brand Colin , Capra John , Artursson Per , Newman John , Marques-Bonet Tomas
Published: September 2023

SLC22A10 is classified as an orphan transporter with unknown substrates and function. Here we describe the discovery of the substrate specificity and functional characteristics of SLC22A10. The human SLC22A10 tagged with green fluorescent protein was found to be absent from the plasma membrane, in contrast to the SLC22A10 orthologs found in great apes. Estradiol-17β-glucuronide accumulated in cells expressing great ape SLC22A10 orthologs (over 4-fold, p<0.001). In contrast, human SLC22A10 displayed no uptake function. Sequence alignments revealed two amino acid differences including a proline at position 220 of the human SLC22A10 and a leucine at the same position of great ape orthologs. Site-directed mutagenesis yielding the human SLC22A10-P220L produced a protein with excellent plasma membrane localization and associated uptake function. Neanderthal and Denisovan genomes show human-like sequences at proline 220 position, corroborating that SLC22A10 were rendered nonfunctional during hominin evolution after the divergence from the pan lineage (chimpanzees and bonobos). These findings demonstrate that human SLC22A10 is a unitary pseudogene and was inactivated by a missense mutation that is fixed in humans, whereas orthologs in great apes transport sex steroid conjugates.
Meiotic recombination dynamics in plants with repeat-based holocentromeres shed light on the primary drivers of crossover patterning
Authors: Marques André , Castellani Marco , Zhang Meng , Thangavel Gokilavani , Sucre Yennifer Mata , Lux Thomas , Campoy José , Marek Magdalena , Hüttel Bruno , Sun Hequan , Mayer Klaus , Schneeberger Korbinian
Published: September 2023

Centromeres strongly affect (epi)genomic architecture and meiotic recombination dynamics influencing the overall distribution and frequency of crossovers. Here, we studied how recombination is regulated and distributed in the holocentric plant Rhynchospora breviuscula, a species lacking localised centromeres. Combining immunocytochemistry, chromatin analysis and high-throughput single-pollen sequencing, we discovered that crossover frequency is distally-biased, in sharp contrast with the diffused distribution of hundreds of centromeric units and (epi)genomic features. Remarkably, we found that crossovers were abolished inside centromeric units but not in their proximity indicating the absence of a canonical centromere effect. We further show that telomere-led synapsis of homologs is the feature that best explains the observed recombination landscape. Our results hint at the primary influence of mechanistic features of meiotic pairing and synapsis rather than (epi)genomic features and centromere organisation in determining the distally biased crossover distribution in R. breviuscula. While centromeres and (epi)genetic properties only affect crossover positioning locally.
Shaping Medical Assessment with Expert Consensus: A Theory-Based Summative Evaluation Blueprint for Community Medicine.
Authors: Kumar Pragya , Chaudhary Neha , Kokane Arun Mahadeo , Zaman Forhad , Kamble Bhushan , Yadav Kishore , Kalidoss Vinoth Kumar , Kusneniwar Govindrao , T Prasanna , Gupta Manoj , Kumar Sanjeev , Richa Richa , Biswas Bijit , Dabar Deepti , Giri Anjan , Naik Bijaya Nanda , Nirala Santosh , Kumar Santosh , Aravindakshan Rajeev , Pandey Sanjay , S. Sathiyanarayan , Parida Swayam Pragyan , Ranjan Alok , Mishra Abhishek , Shekhar Saket , Kumar Abhishek , Lohani Pallavi , Ayub Arshad , Shikha Swati , Singh Geetika , Agrawal Deepika , Ahmad Shamshad
Published: September 2023

Background
Many authors have proposed summative evaluation blueprints for cognitive domain levels. But the process of calculating the overall weight was not clear, and it was done at the chapter level. This study sought to create a theory-based summative evaluation blueprint by involving experts from the All-India Institute of Medical Sciences.
Methods
Twenty-five experts from 10 All India Institutes of Medical Science were invited via email and contributed for summative assessment for a theory paper. Each week, the study lead team sent an online form containing 25 topics. A total of 269 topics were selected to be included in the blueprint development. An Impact and Frequency score was obtained for each topic, with a score between 1 and 3 for both its "Impact (I)" and "Frequency" (F).
Results
The overall response rate was 71%. "Principle of epidemiology" (14.7%) had the most weight, followed by "Epidemiology of communicable disease" (13.4%) and "National Health Program" (10%). These three chapters constituted more than one-third of the total weight of the summative assessment (theory). 20 out of 24 (83%) chapters have moderate-to-good interrater reliability.
Conclusions
The proposed blueprint will serve as a reference for setting the question paper and will impart objectivity, uniformity, and validity to the construction of the written assessment tool.
Synthesis, swelling and water-retention behaviors of phytic acid-modified corn stalk-composite superabsorbents
Authors: Liu Bingjun , Wan Tao , Li Dongmei , Huang Zhenggen , Xu Hao , Zhao Yang
Published: September 2023

A novel phytic acid-modified corn stalk-composite superabsorbent (PACS-g-p(AA-AM-VP)) with water absorbency of 391g/g, water retention around 30% at 200min under 90°C, adsorption capacities of 284mg/g and 448 mg/g for Ni(II) and Cu (II), respectively, was synthesized by graft copolymerization of acrylamide(AM), vinyl pyrrolidone(VP) and itaconic acid(IA) with phytic acid-modified corn stalk (PACS) in aqueous solution, using N,N-methylenebisacrylamide (MBA) as a crosslinker and ammonium persulfate(APS) and sodium bisulfite(SBS) as redox initiator. Factors influencing water absorbency and water retention of PACS-g-p(AA-AM-VP), such as PACS amount, initiator amount, crosslinker amount, neutralization degree of IA, IA/VP mass ratio and IA/AM mass ratio, were investigated. Morphologies and structure of PACS-g-p(AA-AM-VP) were characterized by FTIR and SEM. FTIR spectra indicate the structure of phytic acid-modified corn stalk graft-copolymer. SEM data shows that fiber structure of corn stalk is partially destroyed after phytic acid modification under ultrasonic wave. PACS-g-p(AA-AM-VP) has a coarse, fluffy and porous structure, facilitating the permeation of water and heavy metal ions into the polymeric network. Given these properties, PACS-g-p(AA-AM-VP) can be extensively applied in agriculture and horticulture as a water-retaining and soil remediation material which increases agricultural irrigation efficiency and remediates heavy metal-contaminated soil due to its low cost, environmental friendliness, high water retention and good adsorption for heavy metal ions.
Exploring high-quality microbial genomes by assembling short-reads with long-range connectivity
Authors: Zhang Lu , Zhang Zhenmiao , Xiao Jin , Wang Hongbo , Yang Chao , Huang Yufen , Yue Zhen , Chen Yang , Han Lijuan , Yin Kejing , Lyu Aiping , Fang Xiaodong
Published: September 2023

Despite long-read sequencing enables to generate complete genomes of unculturable microbes, its high cost hinders its widespread application in large cohorts. An alternative method is to assemble short-reads with long-range connectivity, which can be a cost-effective way to generate high-quality microbial genomes. We developed Pangaea to improve metagenome assembly using short-reads with physical or virtual barcodes. It adopts a deep-learning-based binning algorithm to assemble the co-barcoded reads with similar sequence contexts and abundances to improve assemblies of high- and medium-abundance microbes. Pangaea also leverages a multi-thresholding reassembly strategy to refine assembly for low-abundance microbes. We benchmarked Pangaea with linked-reads and a combination of short- and long-reads from mock communities and human gut metagenomes. Pangaea achieved significantly higher contig continuity as well as more near-complete metagenome-assembled genomes (NCMAGs) than the existing assemblers. Pangaea was also observed to generate three complete and circular NCMAGs on the human gut microbiomes.
Large-scale green grabbing for wind and solar PV development in Brazil
Authors: Klingler Michael , Ameli Nadia , Rickman Jamie , Schmidt Johannes
Published: September 2023

Large-scale wind and solar photovoltaic (PV) infrastructures are expanding rapidly in Brazil. These projects can exacerbate struggles for land rooted in weak land governance, with negative impacts for traditional populations due to loss of access to common lands. Here, we trace how green grabbing, i.e. the large-scale appropriation and control of (undesignated) public lands, both formally legal and illicit, for low-carbon technologies, has developed in Brazil throughout 2000 to 2021. We find that global investors and owners, mainly from Europe, are involved in 78% of wind and 96% of solar PV parks, occupying 2,148 km2 and 102 km2 of land, respectively. We also show that land privatization is the prevalent land tenure regime for securing access to and control over land, indicating significant transformations of prior (undesignated) public land. We conclude that green grabbing is a persistent, critical phenomenon in Brazil, requiring transparency and close monitoring of land tenure modifications.
Residual networks without pooling layers improve the accuracy of genomic predictions
Authors: Xie Zhengchao , Xu Xiaogang , Li Ling , Wu Cuiling , Ma Yinxing , He Jingjing , Wei Sidi , Wang Jun , Feng Xianzhong
Published: September 2023

With the decrease in gene sequencing cost and the development of deep learning, phenotype prediction accuracy by genomic selection (GS) has been continuously improved. Residual networks, a widely validated deep learning technique, are introduced to deep learning for GS. Since each locus has a different weighted impact on the phenotype, strided convolutions are more suitable for GS problems than pooling layers. Through the above technological innovations, we propose a deep learning algorithm for GS, residual neural network genomic selection (ResGS). ResGS is the first neural network to reach 50 layers in GS. In 15 cases with four public data, the prediction accuracy of ResGS is higher than that of ridge-regression best linear unbiased prediction, support vector regression, random forest, gradient boosting regressor, and deep neural network genomic prediction in most cases. ResGS performs well in dealing with gene-environment interaction. Phenotypes from other environments are imported into ResGS along with genetic data. The prediction results are much better than just providing genetic data as input, which demonstrates the effectiveness of GS multi-modal learning. Standard deviation is recommended as an auxiliary GS evaluation metric, which could improve the distribution of predicted results. Deep learning for GS, such as ResGS, has increasingly apparent advantages compared with traditional GS algorithms.
Characterization of Xanthomonas isolates causal of citrus canker type A in Tucumán, Argentina, and biocontrol strategies using olive and wine-derived agro-industrial wastes.
Authors: Aguirre Constanza María , Viola Carolina , Salazar Sergio Miguel , Haelterman Raquel Mercedes , Arena Mario Eduardo
Published: September 2023

Argentina ranks fourth as a lemon producer worldwide and first in lemon industrialization. At the same time, Tucumán (NW region of Argentina) is the leading national producer and exporter of lemons and the fourth largest exporter of fresh lemons worldwide. Citrus canker is one of the major diseases that threaten citrus production, and its causal agent, Xanthomonas citri subsp. citri is present in all citrus-growing areas worldwide, including Tucumán. Due to the current global awareness of environmental care and the demand for organic food, the present study aims to characterize Xanthomonas strains in Tucumán and further evaluate the potential of wine-derived agro-industrial wastes as a natural alternative to control citrus canker. In this vein, we focused on those by-products derived from the olive (‘Alperujo’) and wine (‘Orujo’) industries. The current study provides an updated characterization of the Xanthomonas species isolated in Tucumán and confirms that all the isolates pertained to citrus canker type A. Such strains were clustered into four groups according to their distinctive features: in vitro growth, biofilm formation, metabolic activity, exopolysaccharide content, swarming mobility, and pathogenicity. We further demonstrated that ‘Alperujo’ extracts mainly inhibited bacterial growth, while ‘Orujo’ extracts were most active against biofilm production and bacterial motility, with evident antibacterial activity. Overall, this study confirms the presence of pathotype A of X. citri subsp. citri strains in Tucumán, Argentina, and proposes to use olive and wine agro-industrial sub-products as an efficient bio-input to control the causal agent of citrus canker in lemons.
Ecological consequences of low ampicillin concentrations on an ex-vivo biofilm model of the human oral microbiome
Authors: Petersen Fernanda C. , Brar Navdeep Kaur , Dhariwal Achal , Aar Heidi , Junges Roger , Salvadori Gabriela , Baker Jonathon , Edlund Anna
Published: September 2023

Antibiotics at low concentration can promote processes such as biofilm formation, virulence and antibiotic resistance. This can be of high relevance in microbial communities like the oral microbiome, where commensals and pathogens share a common habitat and where the abundance of antibiotic resistance genes surpasses the abundance in the gut. Here, we used an ex vivo model of human oral biofilms to investigate the impact of ampicillin on biofilm viability. Further, the ecological impact on the microbiome and resistomes was investigated using shotgun metagenomics. The results showed that low concentrations promoted significant shifts in microbial taxonomic profile and could enhance biofilm viability by up to 1 to 2-log. For the resistome, low concentrations had no significant impact on antibiotic resistance gene (ARG) diversity, while ARG abundance decreased by up to 84%. A positive correlation was observed between reduced microbial diversity and reduced ARG abundance. The WHO priority pathogens Streptococcus pneumoniae and Staphylococcus aureus were identified in some of the samples, but their abundance was not significantly altered by ampicillin. Yet, most of the antibiotic resistance genes that increased in abundance in the ampicillin group were associated with streptococci, including Streptococcus mitis, a well-known potential donor of ARGs to S. pneumoniae. To our knowledge, this is the first report on antibiotic effects on oral microbial communities using an ex-vivo human microbiome model combining biofilms and shotgun metagenomics. Overall, the results highlight the potential of using the model to further our understanding of ecological and evolutionary forces driving antimicrobial resistance in oral microbiomes.
Leveraging sampling schemes on skewed class distribution to enhance male fertility detection with ensemble AI learners
Authors: GhoshRoy Debasmita , Alvi P. A. , Santosh KC
Published: September 2023

Designing effective AI models becomes a challenge when dealing with imbalanced/skewed class distributions in datasets. Addressing this, re-sampling techniques often come into play as potential solutions. In this investigation, we delve into the male fertility dataset, exploring fifteen re-sampling approaches to understand their impact on enhancing predictive model performance. The research employs conventional AI learners to gauge male fertility potential. Notably, five ensemble AI learners are studied, their performances compared, and their results are evaluated using four measurement indices. Through comprehensive comparative analysis, we identify substantial enhancement in model effectiveness. Our findings showcase that the LightGBM model with SMOTE-ENN re-sampling stands out, achieving an efficacy of 96.66% and an F1-score of 95.60% through 5-fold cross-validation. Interestingly, the CatBoost model, without re-sampling, exhibits strong performance, achieving an efficacy of 86.99% and an F1-score of 93.02%. Furthermore, we benchmark our approach against state-of-the-art methods in male fertility prediction, particularly highlighting the use of re-sampling techniques like SMOTE and ESLSMOTE. Consequently, our proposed model emerges as a robust and efficient computational framework, promising accurate male fertility prediction.
Efficient ring-opening polymerization of epsilon-caprolactone catalyzed by iron(III) chloride under mild reaction conditions
Authors: Wu Hai-Bo , Zhou Xiantai , Zhou Xiao-Wu , Fang Yan-Xiong
Published: September 2023

As a biodegradable polyester, the commercialized synthesis protocol of poly(ε-caprolactone) (PCL) under mild conditions is of great significance and attractive. Herein, the ring-opening polymerization (ROP) of ε-caprolactone (ε-CL) using FeCl3 catalyst and benzyl alcohol (BnOH) as the initiator was developed. FeCl3 has been proved to be an efficient catalyst for the ROP of ε-CL under mild conditions. The conversion of ε-CL to PCL was 98.8% at 60 oC within 4 h, with number-average molecular weight (Mn) and dispersity (PDI) of 16500 g/mol and 1.28, respectively. Moreover, a coordination-insertion ring-opening polymerization mechanism mediated by FeCl3 was proposed. Overall, this work is expected to provide a feasible industrial method for the preparation of PCL from the direct aerobic oxidation of cyclohexanone.
The Safety and Efficacy of Systemic Delivery of a New Liver-de-targeted TGFβ Signaling Inhibiting Adenovirus in an Immunocompetent Triple Negative Mouse Mammary Tumor Model
Authors: Xu Weidong , Shin Soon Cheon , Vickman Renee , Filimon Beniamin , Yang Yuefeng , Hu Zebin , Mangold Kathy , Prabhakar Bellur , Schreiber Hans
Published: September 2023

Aberrant TGFβ signaling is linked to metastasis and tumor immune escape of many cancers including metastatic triple negative breast cancer (mTNBC). Previously, we have found that oncolytic adenoviruses expressing a TGFβ signaling inhibitory protein (sTGFβRIIFc) induced immune activation in a mouse TNBC (4T1) immunocompetent subcutaneous model with intratumoral injection. Systemic administration of adenoviruses can be a superior route to treat mTNBC but faces the challenges of increased toxicity and viral clearance. Thus, we created a liver-de-targeted sTGFβRIIFc- and LyP-1 peptide-expressing adenovirus (mHAdLyp.sT) with enhanced breast cancer cell tropism. Its safety and immune response features were profiled in the 4T1 model. Our data showed that the systemic administration of mHAdLyp.sT resulted in reduced hepatic and systemic toxicity. mHAdLyp.sT was also effective in increasing Th1 cytokines and anti-tumor cell populations by cytokine analysis, spleen/tumor qRT-PCR, and flow cytometry. We further tested the therapeutic effects of mHAdLyp.sT alone and in combination with immune checkpoint inhibitors (ICIs). mHAdLyp.sT alone and with all ICI combinations elicited significant inhibition of lung metastasis by histological analysis. When mHAdLyp.sT was combined with both anti-PD-1 and anti-CTLA-4 antibodies, primary 4T1 tumor growth was also significantly inhibited. We are confident in advancing this new treatment option for mTNBC.
Proteinuria frequency and subsequent renal dysfunction in bevacizumab-treated patients: A single center, retrospective, observational study
Authors: Kataoka Shigeki , Nishikawa Yoshitaka , Funakoshi Taro , Horimatsu Takahiro , Sakuragi Minoru , Uchino Eiichiro , Hiragi Shusuke , Yamamoto Shinya , Sakai Kaoru , Matsubara Takeshi , Yanagita Motoko , Muto Manabu
Published: September 2023

Background
Proteinuria is a common adverse event observed during treatment with antivascular endothelial growth factor (VEGF) antibodies. Proteinuria is a risk factor for renal dysfunction and cardiovascular complications in patients with chronic kidney disease. However, the association between anti-VEGF antibody-induced proteinuria and renal dysfunction or cardiovascular complications remains unclear.
Methods
The medical records of patients treated with bevacizumab (BV) at Kyoto University Hospital (Kyoto, Japan) between January 2006 and March 2018 were retrospectively reviewed. Adverse event rates were compared between patients who developed qualitative ≥ 2 + proteinuria and those who developed < 1 + proteinuria. Adverse events were defined as renal dysfunction (i.e., ≥ 57% decrease in the eGFR, compared to the rate at the initial treatment) and hospitalization due to BV-associated cardiovascular complications and other adverse events.
Results
In total, 734 patients were included in this analysis. Renal dysfunction was more common in patients with ≥ 2 + proteinuria than in those with < 1 + proteinuria (13/199, 6.5% vs. 13/535, 2.4%). Seven of these 13 patients with ≥ 2 + proteinuria had transient reversible renal dysfunction. Only four (2.0%) patients had BV-associated renal dysfunction. Of the 734 patients, 6 patients, 16 patients, and 13 patients were hospitalized because of the adverse events of cardiovascular complications, thromboembolisms, and cerebrovascular complications, respectively. No relationship was observed between these adverse events and proteinuria.
Conclusion
BV treatment-induced proteinuria was not associated with renal dysfunction or other adverse events. Continuing BV with caution is a possible treatment option, even after proteinuria develops, in patients with cancer and a limited prognosis.
Structural basis for the dynamic chaperoning of disordered clients by Hsp90
Authors: Huang Chengdong , Qu Xiaozhan , Zhao Shuo , Wan Chanjuan , Zhu Lei , Rossi Paolo , Wang Junfeng , Kalodimos Charalampos , Wang Chao , Xu Weiya
Published: September 2023

Molecular chaperone Hsp90 is a ubiquitous regulator that fine-tunes and remodels diverse client proteins, exerting profound effects on normal biology and diseases. However, the atomic-level chaperoning mechanism of Hsp90 remains elusive. Here, using NMR spectroscopy in combination with other techniques, we determined the solution structure of the initial encounter complex in the chaperone cycle, wherein Hsp90 adopts an open conformation while engaging with a disordered client. Our structure reveals a dual-binding mechanism, as Hsp90 utilizes two distinct sites that synergistically capture hydrophobic segments within client proteins, forming a bipartite complex that enables rapid conformational samplings. Furthermore, we demonstrate that the chaperone cycle triggers significant conformational and dynamic transformations. Distant client binding effectively primes Hsp90's global dynamics and conformational equilibrium, ultimately unleashing its ATPase potential for efficient client remodeling. These findings offer fundamental insights into the dynamic machinery of Hsp90, contributing to a unified conceptual and mechanistic understanding of Hsp90-client interactions.
A large-scale, multi-centre, prospective observational study to treat hepatitis C in Pakistan and assess resistance to antiviral drugs (HepFREEPak): study protocol
Authors: Arif Ambreen , Hasnain Aliya , Chaudhry Auj , Asim Muhammad , Shafqat Muhammad Nabeel , Altaf Abeer , Saba Noor , Kemos Polychronis , Ansari M. Azim , Barnes Eleanor , Metcalfe Chris , Vickerman Peter , Qureshi Huma , Hamid Saeed , Choudhry Asad Ali , Niaz Saad Khalid , Foster Graham R , Choudhry Naheed
Published: September 2023

Background: Pakistan has one of the highest burdens of Hepatitis C virus (HCV) infection globally. To achieve the World Health Organization’s goals for HCV elimination, there is a need for substantial scale-up in testing, treatment, and a reduction in new infections. Data on the population impact of scaling up treatment is not available in Pakistan, nor is there reliable data on the incidence of infection/reinfection. This project will fill this gap by providing important empirical data on the incidence of infection (primary and reinfection) in Pakistan. Then, by using this data in epidemic models, the study will determine whether response rates achieved with affordable therapies (sofosbuvir plus daclatasvir) will be sufficient to eliminate HCV in Pakistan.Methods: This prospective multi-centre cohort study will screen 25,000 individuals for HCV antibody (Ab) and RNA (if Ab-positive) at various centers in Pakistan - Karachi (Sindh) and Punjab, providing estimates of the disease prevalence. HCV positive patients will be treated with sofosbuvir and daclatasvir for 12-weeks, (extended to 24-weeks in those with cirrhosis) and the proportion responding to this first-line treatment estimated. Patients who test HCV Ab negative will be recalled 12 months later to test for new HCV infections, providing estimates of the incidence rate. Patients diagnosed with HCV (~ 4,000) will be treated and tested for Sustained Virological Response (SVR). Questionnaires to assess risk factors, productivity, health care usage and quality of life will be completed at both the initial screening and at 12-month follow-up, allowing mathematical modelling and economic analysis to assess the current treatment strategies. Viral resistance will be analysed and patients who have successfully completed treatment will be retested 12 months later to estimate the rate of re-infection.Conclusion The HepFREEPak study will provide evidence on the efficacy of available and widely used treatment options in Pakistan. It will also provide data on the incidence rate of primary infections and re-infections. Data on incidence risk factors will allow us to model and incorporate heterogeneity of risk and how that affects screening and treatment strategies. These data will identify any gaps in current test-and-treat programs to achieve HCV elimination in Pakistan.Study registration This study was registered on clinicaltrials.gov (NCT04943588) on June 29, 2021.
Seed hydropriming to alleviate drought stress in germination of two cotton (Gossypium hirsutum L.) varieties
Authors: BOKOBANA Atalaèsso , GNOFAM Nambou , KOFFI Zovodu Kokou , ASSIH Alèdi , AKANTETOU Komlan Pikassalé , BASSAROU Ayeva , TOZO Koffi
Published: September 2023

Background Drought is a serious threat to the farming community, biasing the crop productivity in arid and semi-arid regions of the world. This study aims to evaluate effect of hydropriming on seed germination of two varieties of cotton, STAM 129A and STAM 190, under drought stress. The seed imbibition kinetics allowed to fix various hydropriming delays (3, 6, 9, 12, 15 and 18 hours). The germination test was conducted in four completely randomized repetitions of 25 seeds for each of the four induced osmotic water stress modalities (0 bar, -3bar, -6 bar, -9 bar), which required the use of PEG-6000 for adjustment. Calculus of germination percentage (GP), mean germination time (MGT), germination index (GI) and the relative PEG injury rate (RPIR) made it possible to evaluate the germinative behavior of the seeds following the different treatments. Results Drought stress-induced damage to seed germination was significantly reduced by priming seeds for 12 hours for both cotton varieties. Under drought stress (average of values measured at -3 bar, -6 bar and − 9 bar), 12H-hydropriming increased the GP by 206.25% for STAM 190 and 179.26% for STAM 190. Germination, previously nil at -6 bar and − 9 bar for unprimed seeds, becomes possible with priming and better with 12H-hydropriming. Increases of 250.76% and 289.55% of GI for respectively STAM 129A and STAM 190 are noted under drought stress. In general, primed seeds germinated one day earlier than unprimed seeds under normal hydrous conditions. Under drought conditions, however, MGT did not vary significantly from the control, approximately 4.56–4.77 days. Longer priming (18H-hydropriming) had a repressive effect on seed germination with total PEG damage, the few seeds that germinated doing so earlier than all the other treatments, at around 3.83–4.02 days under normal hydrous conditions, and 4.33–4.46 days under drought conditions. RPIR was reduced 35.89% (for STAM 129A) and 27.10% (for STAM 190) with 12H-hydropriming. Conclusions Thus, for growing cotton varieties STAM 129A and STAM 190, hydropriming seeds for 12 hours can be recommended to maintain germinative vigor whatever rainfall conditions may arise.
Transfer of heavy metals in topsoils, based on sequential extraction and statistical tools in Northeast Brazil
Authors: Fernández Zahily Herrero , Júnior José Araújo dos Santos , Amaral Romilton dos Santos , Coutinho Artur Paiva , Bezerra Mariana Brayner Cavalcanti Freire , Santos Josineide Marques do Nascimento , Milan Marvic Ortueta , Rojas Lino Angel Valcarcel , Yinusa Taiwo Saheed , Melo Robert Fernandes , de Oliveira Marcela Ferreira Marques , Santos Yasmin Marques dos
Published: September 2023

Trace metals are associated with various organic and inorganic components, appearing in different chemical forms, which regulate their solubility, mobility, and availability to biological systems. Given this, it is necessary to know the chemical form in which these elements are found since this defines their potential for remobilization. Thus, this work aimed to evaluate the distribution and mobility of Pb, Cu, Cd, Cr, Ni, and Zn in eight types of soils from Northeast Brazil. The concentration in the fractions was determined through sequential extraction using the procedure outlined by the Community Bureau of Reference (BCR). Cu was extracted using oxidizing conditions and in the residual fraction. The Principal Component Analysis (PCA) and Pearson correlation matrix were used in fifty topsoil samples to investigate the relationship between metals and physical-chemical parameters. The results revealed that metals were prevalent in the residual fraction. Cd, Ni, and Zn were primarily detected in the mobile fraction. Cd and Pb were associated with Fe and Mn oxides, suggesting the mobility of these metals within the environment. The organic matter and texture influenced the mobility of metals in the soil. The PCA analysis shows that the pH correlates positively with Ni, Cu, and Cr and negatively with Zn, Cd, and Pb. The parameters analyzed showed significant variations across different soil classes, highlighting their diverse nature. The findings highlighted the significance of sequential metal extraction in soil and the utilization of PCA to predict changes in solubility and determine its availability to plants.
An automated tool to classify and transform unstructured MRI data into BIDS datasets
Authors: Bartnik Alexander , Singh Sujal , Sum Conan , Smith Mackenzie , Bergsland Niels , Zivadinov Robert , Dwyer Michael
Published: September 2023

The increasing use of neuroimaging in clinical research has driven the creation of many large imaging datasets. However, these datasets often rely on inconsistent naming conventions in image file headers to describe acquisition, and time-consuming manual curation is necessary. Therefore, we sought to automate the process of classifying and organizing magnetic resonance imaging (MRI) data according to acquisition types common to the clinical routine, as well as automate the transformation of raw, unstructured images into Brain Imaging Data Structure (BIDS) datasets. To do this, we trained an XGBoost model to classify MRI acquisition types using relatively few acquisition parameters that are automatically stored by the MRI scanner in image file metadata, which are then mapped to the naming conventions prescribed by BIDS to transform the input images to the BIDS structure. The model recognizes MRI types with 99.475% accuracy, as well as a micro/macro-averaged precision of 0.9995/0.994, a micro/macro-averaged recall of 0.9995/0.989, and a micro/macro-averaged F1 of 0.9995/0.991. Our approach accurately and quickly classifies MRI types and transforms unstructured data into standardized structures with little-to-no user intervention, reducing the barrier of entry for clinical scientists and increasing the accessibility of existing neuroimaging data.
LoGD-ai: An Efficient Network Intrusion Detection System Using a Soft Voting-Based Ensemble Learner
Authors: Agyapong Isaac , Boateng Samuel , Prempeh Isaac , Acheampong Rebecca
Published: September 2023

Network attacks detection is still a difficult task because of the large data volumes needed for training a cutting-edge machine learning algorithms to unearth network invasions. Recently, a number of data mining methods have been put out for network intrusion detection. Meanwhile, each of them encounters certain difficulties resulting from the sophisticated nature of threats the existing models cannot detect. The NSL-KDD dataset containing four different form of attacks was employed in this paper. In this paper, we demonstrate the efficiency of LoGD-ai, a soft voting-based ensemble learner as network intrusion detection system to classify network data to normal and malicious. This soft-voting based ensemble classifier employs logistic regression, gradient boosting and decision tree algorithms for intrusion detection. Finally, the performance of the LoGD-ai classifier is compared to the popular gradient boosting machine (GBM), random forests (RF), and AdaBoost. Scoring 98.05% on accuracy, the LoGD-ai classifier performs better than GBM, RF and AdaBoost classifiers, efficiently detecting and classifying network traffic as normal or malicious. Compared to gradient boosting, our proposed methodology increases accuracy by 0.52%, which is critical for network intrusion detection.
Safety and health economic evaluation of different materials of peripheral intravenous catheters
Authors: Liang Shanshan , Zhou Zhaoju , Jiang Liping , Ding Huirong
Published: September 2023

Background
To explore the safety and economics of two materials of peripheral intravenous catheters based on propensity score matching.
Methods
A multi-center prospective survey on inpatients in 5 hospitals in Shanghai, Sichuan, and Shandong. Propensity score matching (PSM) was used to analyze the complications, indwelling time, comfort, and economic comparison.
Results
The data of 3,245 patients were matched by PSM. There were 1812 patients with two different materials, 906 cases in each group. The complication rate in the Vialon group (22.4% vs 29.5%) was lower than that in the Teflon group, and its average indwelling time was significantly longer than that of the Teflon material group (0.13 days) (p < 0.05). The comfort evaluation of patients in the Vialon group was 5.5% higher than that in the Teflon group. The additional cost of unplanned extubation of Vialon material was lower than that of Teflon material.
Conclusions
The peripheral intravenous catheters made of Vialon material can reduce complications and the total cost.
Unleashing Nature's Defense: Potent Antimicrobial Power of Mediterranean Ethyl Acetate Extracts against Oral Pathogens and Streptococcus mutans Biofilms
Authors: Hickl Joachim , Argyropoulou Aikaterini , Al-Ahmad Ali , Hellwig Elmar , Skaltsounis Alexios Leandros , Wittmer Annette , Vach Kirstin , Karygianni Lamprini
Published: September 2023

Objectives
The increasing demand for alternatives to antibiotics against resistant bacteria has led to research on natural products. The aim of this study was to analyze the antimicrobial and antibiofilm activity of 16 Mediterranean herb extracts.
Materials and Methods
The extracts were analyzed using High Performance Thin Layer Chromatography. The minimum inhibitory concentration and minimum bactericidal concentration of the extracts from Achillea taygetea, Cistus creticus ssp. creticus, Cistus monspeliensis, Lavandula stoechas, Mentha aquatica, Mentha longifolia, Origanum vulgare, Phlomis cretica, Rosmarinus officinalis, Salvia sclarea, Satureja parnassica, Satureja thymbra, Sideritis euboea, Sideritis syriaca, Stachys spinosa, and Thymus longicaulis were determined against eight oral bacteria and fungus Candida albicans. Microtiter plate test was conducted to evaluate the antibiofilm activity against Streptococcus mutans.
Results
Overall, all tested extracts efficiently suppressed the growth of obligate anaerobic bacteria. When applied at concentrations ≥ 0.15 mg / ml, the extracts exhibited moderate to high antibiofilm activity comparable to that of chlorhexidine (CHX) against S. mutans. Interestingly, R. officinalis (MIC: 0.01–0.06 mg / ml) and O. vulgare (MIC: 0.04–1.25 mg / ml) demonstrated the highest antibacterial activity against oral bacteria. Additionally, R. officinalis and L. stoechas significantly inhibited S. mutans biofilm formation at 0.15 mg / ml.
Conclusions
The tested plant extracts can be considered as alternative natural antimicrobial and antibiofilm agents.
Clinical Relevance:
Mediterranean herb extracts show promise as natural alternatives to combat oral bacteria and biofilm formation, offering potential new therapies for infectious oral diseases in the context of antibiotic resistance.
Multi-silicone Bilateral Soft Physical Twin as an Alternative to Traditional User Interfaces for Remote Palpation: a Comparative Study
Authors: Costi Leone , Iida Fumiya
Published: September 2023

Teleoperated medical technologies are a fundamental part of the healthcare system. From telemedicine to remote surgery, they allow remote diagnosis and treatment. However, the absence of any interface able to effectively reproduce the sense of touch and interaction with the patient prevents the implementation of teleoperated systems for primary care examinations, such as palpation. In this paper, we propose the first reported case of a soft robotic bilateral physical twin for remote palpation. By creating an entirely soft interface that can be used both to control the robot and receive feedback, the proposed device allows the user to achieve remote palpation by simply palpating the soft physical twin. This is achieved through a compact design showcasing 9 pneumatic chambers and exploiting multi-silicone casting to minimize cross-noise and allow teleoperation. A comparative study has been run against a traditional setup, and both the control and feedback of the physical twin are carefully analyzed. Despite distributed tactile feedback not achieving the same performance as the visual map, the soft control and visual feedback combination showcases a 5.1% higher accuracy. Moreover, the bilateral soft physical twin results always in a less invasive procedure, with 41% lower mechanical work exchanged with the remote phantom.
TRIM58 downregulation maintains stemness via MYH9-GRK3-Hippo/YAP axis activation in triple-negative breast cancer stem cells
Authors: Li Xujun , Cai Ting , Wu Qian , Jiang Jing , You Tianzi , Guo Linyan , Liu Huina , Yang Fan
Published: September 2023

Background
TRIM58 is, a member of the TRIM protein family, which possess with E3 ubiquitin ligase activities. Studies have revealed that weak expression of TRIM58 plays key roles, has been implicated in the tumor progression of tumor formation due to its reduced expression. However, its role in regulating the stemness of breast cancer stem cells (CSCs) remains unexplored.
Methods
The expression of TRIM58 was examined in breast cancer cells and triple-negative breast cancer (TNBC) patient specimens. Human TNBC CSCs were enriched from TNBC patient cancer tissues using serum-free medium. Stemness functions of TRIM58 in CSCs were assessed using western blot, cell viability analysis, tumorsphere formation assay, and subcutaneous tumorigenesis assays. Mechanistic investigations of TRIM58 on stemness and differentiation were conducted using co-immunoprecipitation, mass spectrometry, q-PCR, ubiquitination detection, label-free quantitative proteomics, and dual luciferase reporter assays.
Results
TRIM58 was underexpressed in TNBC tissues and cells compared to adjacent mucosa tissue, and its downregulation was significantly associated with shorter survival. Overexpression of TRIM58 reduced the proportion of CD44+/CD24- cells, upregulated differentiation genes, and inhibited stemness-related gene expression in TNBC CSCs. In vitro and in vivo experiments revealed that TRIM58 overexpression in CSCs suppressed tumor sphere formation and tumorigenic capacity. Co-IP results indicated direct interaction between TRIM58 and MYH9, with TRIM58 inducing MYH9 degradation via ubiquitination in differentiated cells. Label-free quantitative proteomics identified GRK3 and Hippo-YAP as downstream targets and signaling pathways of MYH9. TIMER database analysis, immunohistochemistry, western blotting, DNA-protein pulldown experiments, and dual luciferase reporter assays demonstrated that MYH9 regulated GRK3 transcriptional activation in CSCs.
Conclusions
This study highlights the negative impact of TRIM58 on the stemness of triple-negative breast CSCs. Elevated TRIM58 expression in CSCs downregulates MYH9 protein levels by promoting ubiquitin-mediated degradation, thereby inhibiting downstream GRK3 transcription, inactivating the Hippo-YAP stemness pathway, and ultimately promoting CSC differentiation.
The Diagnostic Degree and Diagnostic Algorithmfor t/s in Hierarchical Star Graphs
Authors: Gao Yangyang
Published: September 2023

This article establishes the kn −k(k+1)2 + 1/kn −k(k+1)2 + k − 1-diagnosability of n-dimensional hierarchical star graphs HSn (n ≥ 4) underthe PMC model and the MM* model, where 2 ≤ k ≤ n − 2. Moreover, novelt/s diagnostic algorithms are proposed for the rapid localization of faulty processors within both the PMC model and the MM* model. These algorithms exhibita time complexity of O(N log2 N), where N represents the total number ofprocessors in the system.