bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of host biomarkers from dried blood spots for monitoring treatment response in extrapulmonary tuberculosis
Authors: Khalid Shizza , Ambreen Atiqa , Khaliq Aasia , Ullah Hafeez , Mustafa Manal , Mustafa Tehmina 
Published: January 2023

AbstractThere is a lack of objective tools for monitoring treatment response in extrapulmonary tuberculosis (EPTB). This study aimed to explore the utility of inflammatory biomarkers from the dry blood spots (DBS) as a tool for monitoring treatment response in EPTB. In a prospective cohort study, 40 inflammatory biomarkers were investigated in DBS samples from 105 EPTB cases using a Luminex platform. The samples were taken before, and, at the end of the 2nd and 6th months of treatment. A total of 11 inflammatory host biomarkers changed significantly with treatment in all EPTB patients. CXCL9/MIG, CCL20, CCL23, CXCL10/IP-10, CXCL1, CXCL2, and CXCL8 significantly declined in our cohort of EPTB (48 TB pleuritis and 57 TB lymphadenitis) patients at both time points. A biosignature consisting of MIG, CCL23, and CXCL2, corresponded with the treatment response in 81% of patients in the 2nd month and 79% of patients at the end of treatment. MIG, CCL23, IP-10, and CXCL2 changed significantly with treatment in all patients including those showing partial clinical response at the 2nd month of treatment. The changes in the levels of inflammatory biomarkers in the DBS correspond with the treatment success and can be developed as a routine test in low-resource settings.
Salivary peptidome analysis and protease prediction during orthodontic treatment with fixed appliances
Authors: Wazwaz Fidaa , Saloom Hayder , Houghton Jack W. , Cobourne Martyn T. , Carpenter Guy H. 
Published: January 2023

AbstractOrthodontic tooth movement (OTM) occurs through proteolytic remodelling within the periodontium following the application of external force to the tooth. This study describes the first characterization of the salivary peptidome and protease profile during the alignment stage of fixed appliance orthodontic treatment. Unstimulated whole mouth saliva from 16 orthodontic patients (10 males, 6 females, mean (SD) age 15.2 (1.6) years) was collected prior to fixed appliance placement (T1), 1-h (T2), 1-week (T3) following fixed appliance placement and on completion of mandibular arch alignment (T4). Salivary peptides were extracted using filtration followed by mass spectrometry to identify amino acid sequences. Protease prediction was carried out in silico using Proteasix and validated with gelatin zymography and enzyme-linked immunosorbent assay. A total of 2852 naturally-occurring peptides were detected, originating from 436 different proteins. Both collagen and statherin-derived peptide levels were increased at T2. Proteasix predicted 73 proteases potentially involved in generating these peptides, including metalloproteinases, calpains and cathepsins. Changes in predicted activity of proteases over time were also observed, with most metalloproteinases showing increased predicted activity at T2–T3. Increased gelatinolytic activity and MMP8/MMP9 levels were detected at T3. Collectively, multiple protein targets and changes in protease-predicted activity during OTM have been identified.
Vascular impulse technology versus elevation for reducing the swelling of upper and lower extremity joint fractures
Authors: El Barbari Jan S. , Schnetzke Marc , Bergmann Moritz B. , Baumann Lukas , Vetter Sven Y. , Swartman Benedict , Grützner Paul A. , Franke Jochen 
Published: January 2023

AbstractSoft-tissue conditioning due to posttraumatic oedema after complicated joint fractures is a central therapeutic aspect both pre- and postoperatively. On average, 6–10 days pass until the patient is suitable for surgery. This study compares the decongestant effect of vascular impulse technology (VIT) with that of conventional elevation. In this monocentric RCT, 68 patients with joint fractures of the upper (n = 36) and lower (n = 32) extremity were included and randomized after consent in a 1:1 ratio. Variables were evaluated for all fractures together and additionally subdivided into upper or lower extremity for better clinical comparability. Primary endpoint was the time in days from hospital admission to operability. Secondary endpoints were total length of stay, oedema reduction, pain intensity, complications, and revisions. The time from admission until operability was reduced by 1.4 (95% CI − 0.4; 3.1) days in the mITT analysis (p = 0.120) and was statistically significant with 1.7 (95% CI 0.1; 3.3) days in the as-treated sensitivity analysis (pAT = 0.038). Significantly less pain and a faster oedema reduction were found in the intervention group. Due to rare occurrences, nothing can be concluded regarding complications and revisions. Administration of VIT therapy did not lead to a significant reduction in time until operability in the whole population but was superior to elevation for soft-tissue conditioning and pain reduction. However, there was a significant reduction by 2.5 days (95% CI 0.7; 4.3) in the subgroup of lower extremity fractures. VIT therapy therefore seems to be a helpful tool in the treatment of posttraumatic oedema after complex joint fractures of the lower and upper extremity, especially in tibial head and lower leg fractures.
Complex multiple introductions drive fall armyworm invasions into Asia and Australia
Authors: Rane Rahul , Walsh Thomas K. , Lenancker Pauline , Gock Andrew , Dao Thi Hang , Nguyen Van Liem , Khin Thein Nyunt , Amalin Divina , Chittarath Khonesavanh , Faheem Muhammad , Annamalai Sivapragasam , Thanarajoo Sathis Sri , Trisyono Y. Andi , Khay Sathya , Kim Juil , Kuniata Lastus , Powell Kevin , Kalyebi Andrew , Otim Michael H. , Nam Kiwoong , d’Alençon Emmanuelle , Gordon Karl H. J. , Tay Wee Tek 
Published: January 2023

AbstractThe fall armyworm (FAW)Spodoptera frugiperdais thought to have undergone a rapid ‘west-to-east’ spread since 2016 when it was first identified in western Africa. Between 2018 and 2020, it was recorded from South Asia (SA), Southeast Asia (SEA), East Asia (EA), and Pacific/Australia (PA). Population genomic analyses enabled the understanding of pathways, population sources, and gene flow in this notorious agricultural pest species. Using neutral single nucleotide polymorphic (SNP) DNA markers, we detected genome introgression that suggested most populations in this study were overwhelmingly C- and R-strain hybrids (n = 252/262). SNP and mitochondrial DNA markers identified multiple introductions that were most parsimoniously explained by anthropogenic-assisted spread, i.e., associated with international trade of live/fresh plants and plant products, and involved ‘bridgehead populations’ in countries to enable successful pest establishment in neighbouring countries. Distinct population genomic signatures between Myanmar and China do not support the ‘African origin spread’ nor the ‘Myanmar source population to China’ hypotheses. Significant genetic differentiation between populations from different Australian states supported multiple pathways involving distinct SEA populations. Our study identified Asia as a biosecurity hotspot and a FAW genetic melting pot, and demonstrated the use of genome analysis to disentangle preventable human-assisted pest introductions from unpreventable natural pest spread.
Altered gut microbiota in individuals with episodic and chronic migraine
Authors: Yong Dongeun , Lee Hakbae , Min Hyung-Gyu , Kim Kyungnam , Oh Hyun-Seok , Chu Min Kyung 
Published: January 2023

AbstractEmerging evidence reveals a close association between gut microbiota and human neurological disorders. The present study aimed to assess whether the composition of gut microbiota in participants with episodic migraine (EM) and chronic migraine (CM) was altered in comparison to that of the controls. This study was a cross-sectional, case–control study. The gut microbiota were evaluated by the partial, targeted sequencing of the 16S rRNA V3–V4 region. This study enrolled 42 and 45 participants with EM and CM, respectively, and 43 controls. Alpha and beta diversities revealed no significant difference among the three groups; however, the microbiota composition at the class, order, family, and genus levels differed significantly between EM and the control, CM and the control, and the EM and CM groups. Moreover, higher composition of PAC000195_g was significantly associated with a lower headache frequency among the five genera that exhibited significantly different microbiota composition in EM and CM. Agathobacter revealed a significant negative association with severe headache intensity. The findings of the present study provide evidence of altered gut microbiota in EM and CM. These findings will help in understanding the course and treatment of migraine.
Linagliptin treatment is associated with altered cobalamin (VitB12) homeostasis in mice and humans
Authors: Tammen Harald , Kömhoff Martin , Delić Denis , Lund Søren S. , Hocher Berthold , Frankenreiter Sandra , Hess Rüdiger , von Eynatten Maximilian , Mark Michael , Klein Thomas 
Published: January 2023

AbstractLinagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor used for the treatment of type 2 diabetes, with additional beneficial effects for the kidney. Treatment of mice with linagliptin revealed increased storage of cobalamin (Cbl, Vitamin B12) in organs if a standard Cbl diet (30 µg Cbl/kg chow) is given. In order to translate these findings to humans, we determined methylmalonic acid (MMA), a surrogate marker of functional Cbl homeostasis, in human plasma and urine samples (n = 1092) from baseline and end of trial (6 months after baseline) of the previously completed MARLINA-T2D clinical trial. We found that individuals with medium Cbl levels (MMA between 50 and 270 nmol/L for plasma, 0.4 and 3.5 µmol/mmol creatinine for urine, at baseline and end of trial) exhibited higher MMA values at the end of study in placebo compared with linagliptin. Linagliptin might inhibit the N-terminal degradation of the transcobalamin receptor CD320, which is necessary for uptake of Cbl into endothelial cells. Because we demonstrate that linagliptin led to increased organ levels of Cbl in mice, sustained constant medium MMA levels in humans, and inhibited CD320 processing by DPP-4 in-vitro, we speculate that linagliptin promotes intra-cellular uptake of Cbl by prolonging half-life of CD320.
PIK3CA is recurrently mutated in canine mammary tumors, similarly to in human mammary neoplasia
Authors: Arendt Maja Louise , Sakthikumar Sharadha , Melin Malin , Elvers Ingegerd , Rivera Patricio , Larsen Majbritt , Saellström Sara , Lingaas Frode , Rönnberg Henrik , Lindblad-Toh Kerstin 
Published: January 2023

AbstractBiological features of neoplastic disease affecting mammary gland tissue are shared between canines and humans. Research performed in either species has translational value and early phase clinical trials performed in canines with spontaneous disease could be informative for human trials. The purpose of this study was to investigate the somatic genetic aberrations occurring in canine mammary neoplasia by exome capture and next generation sequencing. Based on 55 tumor-normal pairs we identified the PIK3CA gene as the most commonly mutated gene in canine mammary tumors, with 25% of samples carrying mutations in this gene. A recurrent missense mutation was identified, p.H1047R, which is homologous to the human PIK3CA hotspot mutation found in different types of breast neoplasia. Mutations homologous to other known human mutation hotspots such as the PIK3CA p.E545K and the KRAS p.G12V/D were also identified. We identified copy number aberrations affecting important tumor suppressor and oncogenic pathways including deletions affecting the PTEN tumor suppressor gene. We suggest that activation of the KRAS or PIK3CA oncogenes or loss of the PTEN suppressor gene may be important for mammary tumor development in dogs. This data endorses the conservation of cancer across species and the validity of studying cancer in non-human species.
Secretory leukocyte protease inhibitor and risk of heart failure in the Multi-Ethnic Study of Atherosclerosis
Authors: Sawicki Konrad Teodor , Nannini Drew R. , Bielinski Suzette J. , Larson Nicholas B. , Lloyd-Jones Donald M. , Psaty Bruce , Taylor Kent D. , Shah Sanjiv J. , Rasmussen-Torvik Laura J. , Wilkins John T. , McNally Elizabeth M. , Patel Ravi B. 
Published: January 2023

AbstractCirculating protease inhibitors are important regulators of inflammation that are implicated in the pathophysiology of heart failure (HF). Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor which protects pulmonary tissues against inflammatory damage; however, its role in HF is not well understood. We sought to evaluate associations of circulating SLPI and genetically-mediated serum SLPI with incident HF and its subtypes in a multi-ethnic cohort of adults using clinical and genetic epidemiological approaches. Among 2,297 participants in the Multi-Ethnic Study of Atherosclerosis (MESA), each doubling of serum SLPI was independently associated with incident HF (HR 1.77; 95% CI 1.02–3.02; P = 0.04), particularly incident HF with preserved ejection fraction (HFpEF; HR 2.44; 95% CI 1.23–4.84; P = 0.01) but not HF with reduced ejection fraction (HFrEF; HR 0.95; 95% CI 0.36–2.46; P = 0.91). Previously reported circulating SLPI protein quantitative trait loci (pQTLs) were not associated with serum SLPI levels or incident HF among MESA participants. In conclusion, baseline serum SLPI levels, but not genetically-determined serum SLPI, were significantly associated with incident HF and HFpEF over long-term follow-up in a multi-ethnic cohort. Serum circulating SLPI may be a correlate of inflammation that sheds insight on the pathobiology of HFpEF.
Traffic flow digital twin generation for highway scenario based on radar-camera paired fusion
Authors: Li Yanbing , Zhang Weichuan 
Published: January 2023

AbstractAutonomous driving is gradually moving from single-vehicle intelligence to internet of vehicles, where traffic participants can share the traffic flow information perceived by each other. When the sensing technology is combined with the internet of vehicles, a sensor network all over the road can provide a large-scale of traffic flow data, thus providing a basis for building a traffic digital twin model. The digital twin can enable the traffic system not only to use past and present information, but also to predict traffic conditions, providing more effective optimization for autonomous driving and intelligent transportation, so as to make long-term rational planning of the overall traffic state and enhance the level of traffic intelligence. The current mainstream traffic sensors, namely radar and camera, have their own advantages, and the fusion of these two sensors can provide more accurate traffic flow data for the generation of digital twin model. In this paper, an end-to-end digital twin system implementation approach is proposed for highway scenarios. Starting from a paired radar-camera sensing system, a single-site radar-camera fusion framework is proposed, and then using the definition of a unified coordinate system, the traffic flow data between multiple sites is combined to form a dynamic real-time traffic flow digital twin model. The effectiveness of the digital twin building is verified based on the real-world traffic data.
Modelling altered signalling of G-protein coupled receptors in inflamed environment to advance drug design
Authors: Thies Arne , Sunkara Vikram , Ray Sourav , Wulkow Hanna , Celik M. Özgür , Yergöz Fatih , Schütte Christof , Stein Christoph , Weber Marcus , Winkelmann Stefanie 
Published: January 2023

AbstractWe previously reported the successful design, synthesis and testing of the prototype opioid painkiller NFEPP that does not elicit adverse side effects. The design process of NFEPP was based on mathematical modelling of extracellular interactions between G-protein coupled receptors (GPCRs) and ligands, recognizing that GPCRs function differently under pathological versus healthy conditions. We now present an additional and novel stochastic model of GPCR function that includes intracellular dissociation of G-protein subunits and modulation of plasma membrane calcium channels and their dependence on parameters of inflamed and healthy tissue (pH, radicals). The model is validated against in vitro experimental data for the ligands NFEPP and fentanyl at different pH values and radical concentrations. We observe markedly reduced binding affinity and calcium channel inhibition for NFEPP at normal pH compared to lower pH, in contrast to the effect of fentanyl. For increasing radical concentrations, we find enhanced constitutive G-protein activation but reduced ligand binding affinity. Assessing the different effects, the results suggest that, compared to radicals, low pH is a more important determinant of overall GPCR function in an inflamed environment. Future drug design efforts should take this into account.
Assessment of diffusion-weighted MRI in predicting response to neoadjuvant chemotherapy in breast cancer patients
Authors: Hottat Nathalie A. , Badr Dominique A. , Lecomte Sophie , Besse-Hammer Tatiana , Jani Jacques C. , Cannie Mieke M. 
Published: January 2023

AbstractTo compare region of interest (ROI)-apparent diffusion coefficient (ADC) on diffusion-weighted imaging (DWI) measurements and Ki-67 proliferation index before and after neoadjuvant chemotherapy (NACT) for breast cancer. 55 women were enrolled in this prospective single-center study, with a final population of 47 women (49 cases of invasive breast cancer). ROI-ADC measurements were obtained on MRI before and after NACT and were compared to histological findings, including the Ki-67 index in the whole study population and in subgroups of “pathologic complete response” (pCR) and non-pCR. Nineteen percent of women experienced pCR. There was a significant inverse correlation between Ki-67 index and ROI-ADC before NACT (r = − 0.443, p = 0.001) and after NACT (r = − 0.614, p < 0.001). The mean Ki-67 index decreased from 45.8% before NACT to 18.0% after NACT (p < 0.001), whereas the mean ROI-ADC increased from 0.883 × 10–3 mm2/s before NACT to 1.533 × 10–3 mm2/s after NACT (p < 0.001). The model for the prediction of Ki67 index variations included patient age, hormonal receptor status, human epidermal growth factor receptor 2 status, Scarff-Bloom-Richardson grade 2, and ROI-ADC variations (p = 0.006). After NACT, a significant increase in breast cancer ROI-ADC on diffusion-weighted imaging was observed and a significant decrease in the Ki-67 index was predicted. Clinical trial registration number: clinicaltrial.gov NCT02798484, date: 14/06/2016.
Technological properties and composition of volatile compounds in winter wheat malts grown with addition of seed meals into soil
Authors: Gasiński Alan , Pytlarz Elżbieta , Hamkało Oliwia , Kawa-Rygielska Joanna 
Published: January 2023

AbstractWheat malts are necessary to produce wheat beers. In this study, wheat was grown with addition of seed meals into the soil, to determine whether such agricultural practice could improve the quality of the grain and, therefore, improve the quality of wheat malt produced from these grains. It was determined, that malt produced from the grains of the winter wheat cultivated with the use of seed meals is characterised with improved technological properties, such as saccharification time, filtration time and extract content and some of the seed meals had a positive impact on the content of various volatile compounds present in the produced malts.
Overexpression of soybean microRNA156b enhanced tolerance to phosphorus deficiency and seed yield in Arabidopsis
Authors: Lu Guangyuan , Tian Zhitao , Hao Yifan , Xu Meihua , Lin Yongxin , Wei Jinxing , Zhao Yongguo 
Published: January 2023

AbstractmicroRNAs (miRNAs) are endogenous small RNAs that are key regulatory factors participating in various biological activities such as the signaling of phosphorus deficiency in the plant. Previous studies have shown that miR156 expression was modulated by phosphorus starvation in Arabidopsis and soybean. However, it is not clear whether the over-expression of soybean miR156b (GmmiR156b) can improve a plant’s tolerance to phosphorus deficiency and affect yield component traits. In this study, we generated Arabidopsis transgenic lines overexpressing GmmiR156b and investigated the plant’s response to phosphorus deficiency. Compared with the wild type, the transgenic Arabidopsis seedlings had longer primary roots and higher phosphorus contents in roots under phosphorus-deficit conditions, but lower fresh weight root/shoot ratios under either phosphorus-deficient or sufficient conditions. Moreover, the GmmiR156b overexpression transgenic lines had higher phosphorus content in shoots of adult plants and grew better than the wide type under phosphorus-deficient conditions, and exhibited increased seed yields as well as strong pleiotropic developmental morphology such as dwarfness, prolonged growth period, bushy shoot/branching, and shorter silique length, suggesting that the transgenic lines were more tolerant to phosphorus deficiency. In addition, the expression level of four SQUAMOSA PROMOTER BINDING PROTEIN LIKE (SPL) genes (i.e., AtSPL4/5/6/15) were markedly suppressed in transgenic plants, indicating that they were the main targets negatively regulated by GmmiR156b (especially AtSPL15) and that the enhanced tolerance to phosphorus deficiency and seed yield is conferred mainly by the miR156-mediated downregulation of AtSPL15.
Optimization of injection molding process parameters for the lining of IV hydrogen storage cylinder
Authors: Li Jin , Zhao Chunjiang , Jia Fuliang , Li Shunyang , Ma Shaohua , Liang Jianguo 
Published: January 2023

AbstractThe hydrogen storage cylinder lining was taken as the research object. The injection model of the cylinder liner was developed employing 3D software, a two-cavity injection molding system was built, and Moldflow was utilized for analysis to determine the best combination of injection molding process parameters. The effects of injection process parameters (melt temperature, mold temperature, holding pressure, holding time and cooling time) on the evaluation index were analyzed by orthogonal experiment L16(45). The prediction data of IV hydrogen storage cylinder lining under different parameters were obtained by the range analysis method. The multi-objective optimization problem of injection molding process was transformed into a single-objective optimization problem by using the grey correlation analysis method. The optimal parameters such as melt temperature 270 °C, mold temperature 80 °C, packing pressure 55 MPa, packing time 20 s and cooling time 13 s were obtained. Taguchi method was adopted to obtain SNR (signal-to-noise ratio), while range and variance methods were used for analysis. The results showed that warpage was 0.4892 mm, the volume shrinkage was 12.31%, the residual stress in the first direction was 98.13 MPa, and the residual stress in the second direction was 108.1 MPa. The comprehensive index was simultaneously most impacted by the melt temperature.