bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of a liquid chromatography–tandem mass spectrometry method for the simultaneous analysis of androgens, estrogens, glucocorticoids and progestagens in human serum
Authors: Iannone Michele , Dima Anna Pia , Sciarra Francesca , Botrè Francesco , Isidori Andrea M. 
Published: January 2022

AbstractWe present a liquid chromatography tandem mass spectrometry method for the simultaneous analysis of 16 endogenous steroids (androgens, estrogens, glucocorticoids and progestogens) in human serum. Samples (250 μl of matrix) were extracted with t‐butylmethyl ether prior to LC–MS/MS analysis. The chromatographic separation was achieved on a reversed‐phase column using a methanol–water gradient. The HPLC was coupled to a triple quadrupole mass spectrometer equipped with an electrospray ionization source with acquisition in multiple reaction monitoring mode. The method was validated using surrogate matrices and human serum samples. The specificity of the method was confirmed for all of the considered steroids; linearity was also assessed (R2 > 0.99, lack‐of‐fit test) in the ranges of concentrations investigated. The lower limits of quantification were in the range 10–400 pg/ml depending on the target steroid. Accuracy was in the range 85–115% for all target steroids except for the lower limit of quantitation levels where it was 80–120%. The extraction recovery was always >65%. No significant matrix effects were observed. To test the reliability of the method, the analysis of serum samples collected from 10 healthy subjects (5 M/5F) was performed. The present method can be used to identify the trajectories of deviation from the concentration normality ranges applied to disorders of the gonadal and adrenal axes.
The occurrence and risk factors associated with post‐traumatic stress disorder among discharged COVID‐19 patients in Tianjin, China
Authors: Mei Zaoxian , Wu Xiaohui , Zhang Xueli , Zheng Xingjie , Li Wenxin , Fan Rui , Yu Hongwei , Zhang Shunming , Gu Yeqing , Wang Xuena , Xia Yang , Meng Ge , Shen Jun , Niu Kaijun 
Published: January 2022

BackgroundPost‐traumatic stress disorder (PTSD) is a serious mental health condition that is triggered by a terrifying event. We aimed to investigate the occurrence and risk factors of PTSD among discharged COVID‐19 patients.MethodsThis study included 144 discharged COVID‐19 patients. PTSD was assessed by using validated cut‐offs of the impact of event scale‐revised (IES‐R, score ≥25). All patients completed a detailed questionnaire survey, and clinical parameters were routinely measured in the hospital. Binary logistic regression models were applied to identify factors associated with PTSD.ResultsOf the 144 participants with laboratory‐confirmed COVID‐19, the occurrence of PTSD was 16.0%. In multivariable analyses, age above 40 years (adjusted OR [95% CI], 5.19 [2.17–12.32]), female sex (adjusted OR [95% CI], 7.82 [3.18–18.21]), current smoker (adjusted OR [95% CI], 6.72 [3.23–15.26]), and ≥3 involved pulmonary lobes (adjusted OR [95% CI], 5.76 [1.19–15.71]) were significantly associated with a higher risk of PTSD. Conversely, history of hypertension and serum hemoglobin levels were significantly associated with a lower risk of PTSD with adjusted ORs (95% CI) of 0.37 (0.12–0.87) and 0.91 (0.82–0.96), respectively.ConclusionOld age, gender (being female), current smoking, bacterial pneumonia, and ≥3 involved pulmonary lobes were associated with an increased occurrence of PTSD among discharged COVID‐19 patients.
Application of inline variable pathlength technology for rapid determination of dynamic binding capacity in downstream process development of biopharmaceuticals
Authors: Bhangale Rashmi P. , Ye Rui , Lindsey Thomas B. , Wolfe Leslie S. 
Published: January 2022

AbstractDetermination of dynamic binding capacity (DBC) for capture purification chromatographic step is usually the first experiment to be performed during downstream process development of biopharmaceuticals. In this work, we investigated the application of inline variable pathlength technology using FlowVPE for rapid determination of DBC on affinity resins for protein capture and proved its comparability with offline titer methods. This work also demonstrated that variable pathlength technology for DBC determination can be successfully applied to different classes of monoclonal antibodies and fusion proteins. This enabled rapid screening of affinity resins and optimization of the capture chromatography step. Hence, use of inline variable pathlength technology eliminated the dependency on offline titer data, traditionally used for DBC determination and accelerated overall process development timelines with less cost.
Particle‐based analysis elucidates the real retention capacities of virus filters and enables optimal virus clearance study design with evaluation systems of diverse virological characteristics
Authors: Kayukawa Taiki , Yanagibashi Akiyo , Hongo‐Hirasaki Tomoko , Yanagida Koichiro 
Published: January 2022

AbstractIn virus clearance study (VCS) design, the amount of virus loaded onto the virus filters (VF) must be carefully controlled. A large amount of virus is required to demonstrate sufficient virus removal capability; however, too high a viral load causes virus breakthrough and reduces log reduction values. We have seen marked variation in the virus removal performance for VFs even with identical VCS design. Understanding how identical virus infectivity, materials and operating conditions can yield such different results is key to optimizing VCS design. The present study developed a particle number‐based method for VCS and investigated the effects on VF performance of discrepancies between apparent virus amount and total particle number of minute virus of mice. Co‐spiking of empty and genome‐containing particles resulted in a decrease in the virus removal performance proportional to the co‐spike ratio. This suggests that empty particles are captured in the same way as genome‐containing particles, competing for retention capacity. In addition, between virus titration methods with about 2.0 Log10 difference in particle‐to‐infectivity ratios, there was a 20‐fold decrease in virus retention capacity limiting the throughput that maintains the required LRV (e.g., 4.0), calculated using infectivity titers. These findings suggest that ignoring virus particle number in VCS design can cause virus overloading and accelerate filter breakthrough. This article asserts the importance of focusing on virus particle number and discusses optimization of VCS design that is unaffected by virological characteristics of evaluation systems and adequately reflect the VF retention capacity.
A tutorial on the analysis of multifactorial designs from one or more data sources using AComDim
Authors: de Figueiredo Miguel , Giannoukos Stamatios , Wüthrich Cedric , Zenobi Renato , Rutledge Douglas N. 
Published: January 2022

AbstractTo analyze data acquired from experiments based on multifactorial designs, approaches able to decompose and model the main sources of variation in the measurements are particularly useful. Although methods combining analysis of variance (ANOVA) with principal components analysis (PCA) or simultaneous components analysis (SCA), namely, ANOVA‐PCA (APCA) and ANOVA‐SCA (ASCA), have proven to be efficient to tackle such data structures, they require the construction and interpretation of a model for each experimental factor and interaction. Other methods like parallel factor analysis‐SCA (PARAFASCA), ANOVA multiblock orthogonal partial least squares (AMOPLS) and ANOVA‐Common Dimensions (AComDim) offer the possibility to have an overall picture of all the sources of variation by means of a single model. Moreover, acquiring data from one or multiple data sources through the same experimental design is becoming more common, and approaches able to cope with such complex data structures are needed. In this tutorial, an explanation of the theory and software implementation of AComDim as well as its usage for the analysis of data acquired from experimental designs is provided. Relying on the multiblock nature of AComDim, an extension to cases where data from multiple sources are acquired on the same samples is proposed.
Cuckoo search optimization‐based image color and detail enhancement for contrast distorted images
Authors: Subramani Bharath , Veluchamy Magudeeswaran 
Published: January 2022

AbstractResearchers have developed various contrast enhancement techniques to provide perceptually good quality images for many vision‐based applications. An exposure‐based optimally weighted gamma correction framework is proposed in this work to overcome the drawback of low contrast and unclear detail in contrast distorted image. At first, the intensities of the input image are expanded and compressed to increase the fine details and reduce the viewable artifacts. The gamma correction and weighted sum approach are then introduced to provide good contrast and natural‐looking images with optimal gamma values. Besides, the cuckoo search algorithm is employed to calculate the optimum value of the gamma function. In this work, the mean squared error is used as the objective function to maximize the information content of the enhanced image. The simulation results reveal the efficiency of the proposed method in enhancing the image for various levels of contrast distortion. Besides, quantitative and qualitative comparisons with the recently published methods demonstrate the superiority of the proposed algorithm in improving details and natural color of the contrast distorted images.
Hybrid zone of a tree in a Cerrado/Atlantic Forest ecotone as a hotspot of genetic diversity and conservation
Authors: Muniz André Carneiro , Pimenta Ricardo José Gonzaga , Cruz Mariana Vargas , Rodrigues Jacqueline Gomes , Buzatti Renata Santiago de Oliveira , Heuertz Myriam , Lemos‐Filho José P. , Lovato Maria Bernadete 
Published: January 2022

AbstractThe Cerrado, the largest Neotropical savanna, and the Brazilian Atlantic Forest form large ecotonal areas where savanna and forest habitats occupy adjacent patches with closely related species occurring side by side, providing opportunities for hybridization. Here, we investigated the evolutionary divergence between the savanna and forest ecotypes of the widely distributed tree Plathymenia reticulata (n = 233 individuals). Genetic structure analysis of P. reticulata was congruent with the recognition of two ecotypes, whose divergence captured the largest proportion of genetic variance in the data (FCT = 0.222 and FST = 0.307). The ecotonal areas between the Cerrado and the Atlantic Forest constitute a hybrid zone in which a diversity of hybrid classes was observed, most of them corresponding to second‐generation hybrids (F2) or backcrosses. Gene flow occurred mainly toward the forest ecotype. The genetic structure was congruent with isolation by environment, and environmental correlates of divergence were identified. The observed pattern of high genetic divergence between ecotypes may reflect an incipient speciation process in P. reticulata. The low genetic diversity of the P. reticulata forest ecotype indicate that it is threatened in areas with high habitat loss on Atlantic Forest. In addition, the high divergence from the savanna ecotype suggests it should be treated as a different unit of management. The high genetic diversity found in the ecotonal hybrid zone supports the view of ecotones as important areas for the origin and conservation of biodiversity in the Neotropics.
Infection by dsRNA viruses is associated with enhanced sporulation efficiency in Saccharomyces cerevisiae
Authors: Travers Cook Thomas J. , Skirgaila Christina , Martin Oliver Y. , Buser Claudia C. 
Published: January 2022

AbstractUpon starvation diploid cells of the facultative sexual yeast Saccharomyces cerevisiae undergo sporulation, forming four metabolically quiescent and robust haploid spores encased in a degradable ascus. All endosymbionts, whether they provide net benefits or costs, utilize host resources; in yeast, this should induce an earlier onset of sporulation. Here, we tested whether the presence of endosymbiotic dsRNA viruses (M satellite and L‐A helper) correspond with higher sporulation rate of their host, S. cerevisiae. We find that S. cerevisiae hosting both the M and L‐A viruses (so‐called “killer yeasts”) have significantly higher sporulation efficiency than those without. We also found that the removal of the M virus did not reduce sporulation frequency, possibly because the L‐A virus still utilizes host resources with and without the M virus. Our findings indicate that either virulent resource use by endosymbionts induces sporulation, or that viruses are spread more frequently to sporulating strains. Further exploration is required to distinguish cause from effect.
Nomogram predicting death and heart transplantation before appropriate ICD shock in dilated cardiomyopathy
Authors: Deng Yu , Zhang Nixiao , Hua Wei , Cheng Sijing , Niu Hongxia , Chen Xuhua , Gu Min , Cai Chi , Liu Xi , Huang Hao , Cai Minsi , Zhang Shu 
Published: January 2022

AbstractAimsThis study aimed to develop and validate a competing risk nomogram for predicting all‐cause mortality and heart transplantation (HT) before first appropriate shock in non‐ischaemic dilated cardiomyopathy (DCM) patients receiving implantable cardioverter‐defibrillators (ICD).Methods and resultsA total of 218 consecutive DCM patients implanted with ICD between 2010 and 2019 at our institution were retrospectively enrolled. Cox proportional hazards model was primarily built to identify variables associated with death and HT. Then, a Fine–Gray model, accounting for the appropriate shock as a competing risk, was constructed using these selected variables along with implantation indication (primary vs. secondary). Finally, a nomogram based on the Fine–Gray model was established to predict 1‐, 3‐, and 5‐year probabilities of all‐cause mortality and HT before first appropriate shock. The area under the receiver operating characteristic (ROC) curve (AUC), Harrell's C‐index, and calibration curves were used to evaluate and internally validate the performance of this model. The decision curve analysis was applied to assess its clinical utility. The 1‐, 3‐, and 5‐year cumulative incidence of all‐cause mortality and HT without former appropriate shock were 5.3% [95% confidence interval (CI) 2.9–9.9%], 16.6% (95% CI 11–25.0%), and 25.3% (95% CI 17.2–37.1%), respectively. Five variables including implantation indication, left ventricular end‐diastolic diameter, N‐terminal pro‐brain natriuretic peptide, angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker, and amiodarone treatment were independently associated with it (all P < 0.05) and were used for constructing the nomogram. The 1‐, 3‐, and 5‐year AUC of the nomogram were 0.83 (95% CI 0.73–0.94, P < 0.001), 0.84 (95% CI 0.75–0.93, P < 0.001), and 0.85 (95% CI 0.77–0.94, P < 0.001), respectively. The Harrell's C‐index was 0.788 (95% CI 0.697–0.877, P < 0.001; 0.762 for the optimism‐corrected C‐index), showing the good discriminative ability of the model. The calibration was acceptable (optimism‐corrected slope 0.896). Decision curve analysis identified our model was clinically useful within the entire range of potential treatment thresholds for ICD implantation. Three risk groups stratified by scores were significantly different between cumulative incidence curves (P < 0.001). The identified high‐risk group composed 17.9% of our population and did not derive long‐term benefit from ICD.ConclusionsThe proposed nomogram is a simple, useful risk stratification tool for selecting potential ICD recipients in DCM patients. It might facilitate the shared decision‐making between patients and clinicians.
Transapical mitral valve implantation for treatment of symptomatic mitral valve disease: a real‐world multicentre experience
Authors: Wild Mirjam G. , Kreidel Felix , Hell Michaela M. , Praz Fabien , Mach Markus , Adam Matti , Reineke David , Ruge Hendrik , Ludwig Sebastian , Conradi Lenard , Rudolph Tanja K. , Bleiziffer Sabine , Kellermair Jörg , Zierer Andreas , Nickenig Georg , Weber Marcel , Petronio Anna Sonia , Giannini Cristina , Dahle Gry , Rein Kjell A. , Coisne Augustin , Vincentelli André , Dubois Christophe , Duncan Alison , Quarto Cesare , Unbehaun Axel , Amat‐Santos Ignacio , Cobiella Javier , Dumonteil Nicolas , Estevez‐Loureiro Rodrigo , Fumero Andrea , Geisler Tobias , Lurz Philipp , Mangieri Antonio , Monivas Vanessa , Noack Thilo , Franco Luis Nombela , Pinon Miguel A. , Stolz Lukas , Tchétché Didier , Walter Thomas , Unsöld Bernhard , Baldus Stephan , Andreas Martin , Hausleiter Jörg , von Bardeleben Ralph S. ,   on behalf of the TENDER Investigators
Published: January 2022

AimsTranscatheter mitral valve implantation (TMVI) is a new treatment option for patients with symptomatic mitral valve (MV) disease. Real‐world data have not yet been reported. This study aimed to assess procedural and 30‐day outcomes of TMVI in a real‐world patient cohort.Method and resultsAll consecutive patients undergoing implantation of a transapically delivered self‐expanding valve at 26 European centres from January 2020 to April 2021 were included in this retrospective observational registry. Among 108 surgical high‐risk patients included (43% female, mean age 75 ± 7 years, mean STS‐PROM 7.2 ± 5.3%), 25% was treated for an off‐label indication (e.g. previous MV intervention or surgery, mitral stenosis, mitral annular calcification). Patients were highly symptomatic (New York Heart Association [NYHA] functional class III/IV in 86%) and mitral regurgitation (MR) was graded 3+/4+ in 95% (38% primary, 37% secondary, and 25% mixed aetiology). Technical success rate was 96%, and MR reduction to ≤1+ was achieved in all patients with successful implantation. There were two procedural deaths and 30‐day all‐cause mortality was 12%. At early clinical follow‐up, MR reduction was sustained and there were significant reductions of pulmonary pressure (systolic pulmonary artery pressure 52 vs. 42 mmHg, p < 0.001), and tricuspid regurgitation severity (p = 0.013). Heart failure symptoms improved significantly (73% in NYHA class I/II, p < 0.001). Procedural success rate according to MVARC criteria was 80% and was not different in patients treated for an off‐label indication (74% vs. 81% for off‐ vs. on‐label, p = 0.41).ConclusionIn a real‐world patient population, TMVI has a high technical and procedural success rate with efficient and durable MR reduction and symptomatic improvement.
8‐Prenylnaringenin tissue distribution and pharmacokinetics in mice and its binding to human serum albumin and cellular uptake in human embryonic kidney cells
Authors: Tanaka Yoshiaki , Okuyama Hitomi , Nishikawa Miyu , Ikushiro Shin‐ichi , Ikeda Mayumi , Ishima Yu , Ukawa Yuichi , Oe Kenichi , Terao Junji , Mukai Rie 
Published: January 2022

Abstract8‐Prenylnaringenin (8‐PN), a hop flavonoid, is a promising food substance with health benefits. Compared with nonprenylated naringenin, 8‐PN exhibits stronger estrogenic activity and prevents muscle atrophy. Moreover, 8‐PN prevents hot flushes and bone loss. Considering that prenylation reportedly improves the bioavailability of flavonoids, we compared the parameters related to the bioavailability [pharmacokinetics and tissue distribution in C57/BL6 mice, binding affinity to human serum albumin (HSA), and cellular uptake in HEK293 cells] of 8‐PN and its mother (non‐prenylated) compound naringenin. C57/BL6 mice were fed an 8‐PN or naringenin mixed diet for 22 days. The amount of 8‐PN (nmol/g tissue) in the kidneys (16.8 ± 9.20), liver (14.8 ± 2.58), muscles (3.33 ± 0.60), lungs (2.07 ± 0.68), pancreas (1.80 ± 0.38), heart (1.71 ± 0.27), spleen (1.36 ± 0.29), and brain (0.31 ± 0.09) was higher than that of naringenin. A pharmacokinetic study in mice demonstrated that the Cmax of 8‐PN (50 mg/kg body weight) was lower than that of naringenin; however, the plasma concentration of 8‐PN 8 h after ingestion was higher than that of naringenin. The binding affinity of 8‐PN to HSA and cellular uptake in HEK293 cells were higher than those of naringenin. 8‐PN bioavailability features assessed in mouse or human model experiments were obviously different from those of naringenin.
The novel finding of an FGFR1::TACC1 fusion in an undifferentiated spindle cell sarcoma of soft tissue with aggressive clinical course
Authors: Yau Derek Tsz‐Wai , Lacambra Maribel D. , Chow Chit , To Ka‐Fai 
Published: January 2022

AbstractWe report an aggressive soft tissue sarcoma with FGFR1‐TACC1 fusion occurring in the thigh of an 83‐year‐old man. Microscopically, the tumor was composed of monomorphic spindle cells arranged in intersecting fascicles. The tumor cells showed ovoid nuclei, fine chromatin, indistinct nucleoli, and elongated eosinophilic cytoplasm. Focal increase in nuclear atypia was noted. Immunohistochemistry showed only focal rare positivity to S100, but negative to SOX10, CD34, STAT6, TLE‐1, SMA, and other myogenic markers. An extensive panel of immunostains did not reveal a definite lineage of cellular differentiation. The fusion junction of the chimeric transcript involved FGFR1 exon 16 and TACC1 exon 7, which was similar to those reported in other types of neoplasms such as glioblastomas and epithelial cancers. The transcript was predicted to be in‐frame and confirmed by Sanger sequencing after reverse transcriptase‐polymerase chain reaction. The patient was treated by marginal excision of tumor without receiving adjuvant therapy. He experienced rapid tumor recurrence with distant metastases and succumbed at 3.5 months after presentation. The finding of FGFR1‐TACC1 fusion in a high‐grade, undifferentiated spindle cell sarcoma of soft tissue is novel and may offer a potential therapeutic target in the near future.
Astrocytic p75NTR expression provoked by ischemic stroke exacerbates the blood–brain barrier disruption
Authors: Qin Xiaoying , Wang Jianing , Chen Shujian , Liu Gang , Wu Chaoran , Lv Qunyu , He Xinran , Bai Xianshu , Huang Wenhui , Liao Hong 
Published: January 2022

AbstractThe disruption of the blood–brain barrier (BBB) plays a critical role in the pathology of ischemic stroke. p75 neurotrophin receptor (p75NTR) contributes to the disruption of the blood‐retinal barrier in retinal ischemia. However, whether p75NTR influences the BBB permeability after acute cerebral ischemia remains unknown. The present study investigated the role and underlying mechanism of p75NTR on BBB integrity in an ischemic stroke mouse model, middle cerebral artery occlusion (MCAO). After 24 h of MCAO, astrocytes and endothelial cells in the infarct‐affected brain area up‐regulated p75NTR. Genetic p75NTR knockdown (p75NTR+/−) or pharmacological inhibition of p75NTR using LM11A‐31, a selective inhibitor of p75NTR, both attenuated brain damage and BBB leakage in MCAO mice. Astrocyte‐specific conditional knockdown of p75NTR mediated with an adeno‐associated virus significantly ameliorated BBB disruption and brain tissue damage, as well as the neurological functions after stroke. Further molecular biological examinations indicated that astrocytic p75NTR activated NF‐κB and HIF‐1α signals, which upregulated the expression of MMP‐9 and vascular endothelial growth factor (VEGF), subsequently leading to tight junction degradation after ischemia. As a result, increased leukocyte infiltration and microglia activation exacerbated brain injury after stroke. Overall, our results provide novel insight into the role of astrocytic p75NTR in BBB disruption after acute cerebral ischemia. The p75NTR may therefore be a potential therapeutic target for the treatment of ischemic stroke.