bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bank vole prion protein extends the use of RT-QuIC assays to detect prions in a range of inherited prion diseases
Authors: Mok Tze How , Nihat Akin , Luk Connie , Sequeira Danielle , Batchelor Mark , Mead Simon , Collinge John , Jackson Graham S. 
Published: March 2021

AbstractThe cerebrospinal fluid (CSF) real-time quaking-induced conversion assay (RT-QuIC) is an ultrasensitive prion amyloid seeding assay for diagnosis of sporadic Creutzfeldt–Jakob disease (CJD) but several prion strains remain unexplored or resistant to conversion with commonly used recombinant prion protein (rPrP) substrates. Here, bank vole (BV) rPrP was used to study seeding by a wide range of archived post-mortem human CSF samples from cases of sporadic, acquired and various inherited prion diseases in high throughput 384-well format. BV rPrP substrate yielded positive reactions in 70/79 cases of sporadic CJD [Sensitivity 88.6% (95% CI 79.5–94.7%)], 1/2 variant CJD samples, and 9/20 samples from various inherited prion diseases; 5/57 non-prion disease control CSFs had positive reactions, yielding an overall specificity of 91.2% (95% CI 80.1–97.1%). Despite limitations of using post-mortem samples and our results’ discrepancy with other studies, we demonstrated for the first time that BV rPrP is susceptible to conversion by human CSF samples containing certain prion strains not previously responsive in conventional rPrPs, thus justifying further optimisation for wider diagnostic and prognostic use.
Machine learning-based classification of mitochondrial morphology in primary neurons and brain
Authors: Fogo Garrett M. , Anzell Anthony R. , Maheras Kathleen J. , Raghunayakula Sarita , Wider Joseph M. , Emaus Katlynn J. , Bryson Timothy D. , Bukowski Melissa J. , Neumar Robert W. , Przyklenk Karin , Sanderson Thomas H. 
Published: March 2021

AbstractThe mitochondrial network continually undergoes events of fission and fusion. Under physiologic conditions, the network is in equilibrium and is characterized by the presence of both elongated and punctate mitochondria. However, this balanced, homeostatic mitochondrial profile can change morphologic distribution in response to various stressors. Therefore, it is imperative to develop a method that robustly measures mitochondrial morphology with high accuracy. Here, we developed a semi-automated image analysis pipeline for the quantitation of mitochondrial morphology for both in vitro and in vivo applications. The image analysis pipeline was generated and validated utilizing images of primary cortical neurons from transgenic mice, allowing genetic ablation of key components of mitochondrial dynamics. This analysis pipeline was further extended to evaluate mitochondrial morphology in vivo through immunolabeling of brain sections as well as serial block-face scanning electron microscopy. These data demonstrate a highly specific and sensitive method that accurately classifies distinct physiological and pathological mitochondrial morphologies. Furthermore, this workflow employs the use of readily available, free open-source software designed for high throughput image processing, segmentation, and analysis that is customizable to various biological models.
Pharmacological inhibition of tumor anabolism and host catabolism as a cancer therapy
Authors: Schcolnik-Cabrera Alejandro , Chavez-Blanco Alma , Dominguez-Gomez Guadalupe , Juarez Mandy , Vargas-Castillo Ariana , Ponce-Toledo Rafael Isaac , Lai Donna , Hua Sheng , Tovar Armando R. , Torres Nimbe , Perez-Montiel Delia , Diaz-Chavez Jose , Duenas-Gonzalez Alfonso 
Published: March 2021

AbstractThe malignant energetic demands are satisfied through glycolysis, glutaminolysis and de novo synthesis of fatty acids, while the host curses with a state of catabolism and systemic inflammation. The concurrent inhibition of both, tumor anabolism and host catabolism, and their effect upon tumor growth and whole animal metabolism, have not been evaluated. We aimed to evaluate in colon cancer cells a combination of six agents directed to block the tumor anabolism (orlistat + lonidamine + DON) and the host catabolism (growth hormone + insulin + indomethacin). Treatment reduced cellular viability, clonogenic capacity and cell cycle progression. These effects were associated with decreased glycolysis and oxidative phosphorylation, leading to a quiescent energetic phenotype, and with an aberrant transcriptomic landscape showing dysregulation in multiple metabolic pathways. The in vivo evaluation revealed a significant tumor volume inhibition, without damage to normal tissues. The six-drug combination preserved lean tissue and decreased fat loss, while the energy expenditure got decreased. Finally, a reduction in gene expression associated with thermogenesis was observed. Our findings demonstrate that the simultaneous use of this six-drug combination has anticancer effects by inducing a quiescent energetic phenotype of cultured cancer cells. Besides, the treatment is well-tolerated in mice and reduces whole animal energetic expenditure and fat loss.
Structure-guided selection of puromycin N-acetyltransferase mutants with enhanced selection stringency for deriving mammalian cell lines expressing recombinant proteins
Authors: Caputo Alessandro T. , Eder Oliver M. , Bereznakova Hana , Pothuis Heleen , Ardevol Albert , Newman Janet , Nuttall Stewart , Peat Thomas S. , Adams Timothy E. 
Published: March 2021

AbstractPuromycin and the Streptomyces alboniger-derived puromycin N-acetyltransferase (PAC) enzyme form a commonly used system for selecting stably transfected cultured cells. The crystal structure of PAC has been solved using X-ray crystallography, revealing it to be a member of the GCN5-related N-acetyltransferase (GNAT) family of acetyltransferases. Based on structures in complex with acetyl-CoA or the reaction products CoA and acetylated puromycin, four classes of mutations in and around the catalytic site were designed and tested for activity. Single-residue mutations were identified that displayed a range of enzymatic activities, from complete ablation to enhanced activity relative to wild-type (WT) PAC. Cell pools of stably transfected HEK293 cells derived using two PAC mutants with attenuated activity, Y30F and A142D, were found to secrete up to three-fold higher levels of a soluble, recombinant target protein than corresponding pools derived with the WT enzyme. A third mutant, Y171F, appeared to stabilise the intracellular turnover of PAC, resulting in an apparent loss of selection stringency. Our results indicate that the structure-guided manipulation of PAC function can be utilised to enhance selection stringency for the derivation of mammalian cell lines secreting elevated levels of recombinant proteins.
Quantitative and semi-quantitative CT assessments of lung lesion burden in COVID-19 pneumonia
Authors: Guan Xiaojun , Yao Liding , Tan Yanbin , Shen Zhujing , Zheng Hanpeng , Zhou Haisheng , Gao Yuantong , Li Yongchou , Ji Wenbin , Zhang Huangqi , Wang Jun , Zhang Minming , Xu Xiaojun 
Published: March 2021

AbstractThis study aimed to clarify and provide clinical evidence for which computed tomography (CT) assessment method can more appropriately reflect lung lesion burden of the COVID-19 pneumonia. A total of 244 COVID-19 patients were recruited from three local hospitals. All the patients were assigned to mild, common and severe types. Semi-quantitative assessment methods, e.g., lobar-, segmental-based CT scores and opacity-weighted score, and quantitative assessment method, i.e., lesion volume quantification, were applied to quantify the lung lesions. All four assessment methods had high inter-rater agreements. At the group level, the lesion load in severe type patients was consistently observed to be significantly higher than that in common type in the applications of four assessment methods (all the p < 0.001). In discriminating severe from common patients at the individual level, results for lobe-based, segment-based and opacity-weighted assessments had high true positives while the quantitative lesion volume had high true negatives. In conclusion, both semi-quantitative and quantitative methods have excellent repeatability in measuring inflammatory lesions, and can well distinguish between common type and severe type patients. Lobe-based CT score is fast, readily clinically available, and has a high sensitivity in identifying severe type patients. It is suggested to be a prioritized method for assessing the burden of lung lesions in COVID-19 patients.
The magnetic resonance imaging evaluation of condylar new bone remodeling after Yang’s TMJ arthroscopic surgery
Authors: Dong Minjun , Jiao Zixian , Sun Qi , Tao Xiaofeng , Yang Chi , Qiu Weiliu 
Published: March 2021

AbstractTo evaluate the post-operative condylar bone remodeling after the treatment of Yang’s arthroscopic surgery. Consecutive cases from Jan 2017 to May 2018 that received Yang’s arthroscopic surgery were included in this study, the TMJ MRI examinations were performed preoperatively and postoperatively (follow up for 1 year or more), and condylar bone remodeling was estimated. A total of 229 patients (29 male and 200 female) were included in the study, 161 patients had new bone formation, and the average age was 17.5 ± 2.1a. There was no new bone formation in 68 patients with an average age of 24.5 ± 0.7a. The percentage of new bone formation patients in 10–15 years of age was 94.33% and decreases as the age increases. In the position of new bone formation, the posterior slope of condyle was the most (129 joints), the second was the top of condyle (54 joints), the third was around condyle (33 joints), only 25 joints had new bone on the anterior slope of condyle. After TMJ arthroscopic surgery, the condyle has the ability to form new bone, and the younger the age, the stronger the ability of new bone formation. The formation of new bone was most in posterior slope and least in anterior slope of condyle.
Performance of the hematology analyzer XN-31 prototype in the detection of Plasmodium infections in an endemic region of Colombia
Authors: Zuluaga-Idárraga Lina , Rios Alexandra , Sierra-Cifuentes Verónica , Garzón Edwar , Tobón-Castaño Alberto , Takehara Ikki , Toya Yuji , Izuka Munehisa , Uchihashi Kinya , Lopera-Mesa Tatiana M. 
Published: March 2021

AbstractEarly and accurate diagnosis is critical in reducing the morbidity and mortality associated with malaria. Microscopy (MI) is the current diagnostic gold standard in the field; however, it requires expert personnel, is time-consuming, and has limited sensitivity. Although rapid diagnostic tests for antigen detection (RDTs) are an alternative to diagnosis, they also have limited sensitivity and produce false positive results in detecting recent past infection. The automated hematology analyzer XN-31 prototype (XN-31p) (Sysmex Corporation, Kobe, Japan) is able to identify plasmodium-infected erythrocytes, count parasitemia and perform complete blood-cell counts within one minute. The performance of the XN-31p in diagnosing malaria was evaluated and compared with real-time polymerase chain reaction (qPCR), MI and RDT in an endemic area of Colombia wherePlasmodium falciparumandPlasmodium vivaxare present. Acute febrile patients were enrolled from July 2018 to April 2019 in Quibdó, Colombia. Malaria diagnoses were obtained from MI and RDT in the field and later confirmed by qPCR. Venous blood samples in EDTA were processed with an XN-31p in the field. Sensitivity, specificity, positive/negative predictive values, and the likelihood ratios of positive and negative tests were calculated with respect to the results from qPCR, MI and RDT. The intraclass correlation coefficient (ICC) and Bland–Altman plot were used to evaluate the concordance in the parasitemia with respect to MI. A total of 1,754 subjects were enrolled. The mean age was 27.0 years (IQR 14–44); 89.6% were Afro-Colombians, 94.3% lived in urban areas and 0.91% were pregnant. With respect to qPCR, the XN-31p showed a sensitivity of 90% (95% CI 87.24–92.34) and a specificity of 99.83% (95% CI 99.38–99.98) in detectingPlasmodiumspp.; both parameters were equivalent to those for MI and RDT. Using MI as the reference, the XN-31p showed a sensitivity of 98.09% (95% CI 96.51–99.08), a specificity of 99.83% (95% CI 99.4–99.98), an ICC of 0.85 (95% CI 0.83–0.87) and an average difference of − 3096 parasites/µL when compared with thick-smear MI and an ICC of 0.98 (95% CI 0.97–0.98) and an average difference of − 0.0013% when compared with thin-smear MI. The XN-31p offers a rapid and accurate alternative method for diagnosing malaria in clinical laboratories in areas whereP. falciparumandP. vivaxcocirculate.
Spectroscopic characterization of electronic structures of ultra-thin single crystal La0.7Sr0.3MnO3
Authors: Chiu Chun-Chien , Chang Yao-Wen , Shao Yu-Cheng , Liu Yu-Chen , Lee Jenn-Min , Huang Shih-Wen , Yang Wanli , Guo Jinghua , de Groot Frank M. F. , Yang Jan-Chi , Chuang Yi-De 
Published: March 2021

AbstractWe have successfully fabricated high quality single crystalline La0.7Sr0.3MnO3 (LSMO) film in the freestanding form that can be transferred onto silicon wafer and copper mesh support. Using soft x-ray absorption (XAS) and resonant inelastic x-ray scattering (RIXS) spectroscopy in transmission and reflection geometries, we demonstrate that the x-ray emission from Mn 3s-2p core-to-core transition (3sPFY) seen in the RIXS maps can represent the bulk-like absorption signal with minimal self-absorption effect around the Mn L3-edge. Similar measurements were also performed on a reference LSMO film grown on the SrTiO3 substrate and the agreement between measurements substantiates the claim that the bulk electronic structures can be preserved even after the freestanding treatment process. The 3sPFY spectrum obtained from analyzing the RIXS maps offers a powerful way to probe the bulk electronic structures in thin films and heterostructures when recording the XAS spectra in the transmission mode is not available.
Your verbal questions beginning with 'what' will rapidly deactivate the left prefrontal cortex of listeners
Authors: Iwaki Hirotaka , Sonoda Masaki , Osawa Shin-ichiro , Silverstein Brian H. , Mitsuhashi Takumi , Ukishiro Kazushi , Takayama Yutaro , Kambara Toshimune , Kakinuma Kazuo , Suzuki Kyoko , Tominaga Teiji , Nakasato Nobukazu , Iwasaki Masaki , Asano Eishi 
Published: March 2021

AbstractThe left prefrontal cortex is essential for verbal communication. It remains uncertain at what timing, to what extent, and what type of phrase initiates left-hemispheric dominant prefrontal activation during comprehension of spoken sentences. We clarified this issue by measuring event-related high-gamma activity during a task to respond to three-phrase questions configured in different orders. Questions beginning with a wh-interrogative deactivated the left posterior prefrontal cortex right after the 1st phrase offset and the anterior prefrontal cortex after the 2nd phrase offset. Left prefrontal high-gamma activity augmented subsequently and maximized around the 3rd phrase offset. Conversely, questions starting with a concrete phrase deactivated the right orbitofrontal region and then activated the left posterior prefrontal cortex after the 1st phrase offset. Regardless of sentence types, high-gamma activity emerged earlier, by one phrase, in the left posterior prefrontal than anterior prefrontal region. Sentences beginning with a wh-interrogative may initially deactivate the left prefrontal cortex to prioritize the bottom-up processing of upcoming auditory information. A concrete phrase may obliterate the inhibitory function of the right orbitofrontal region and facilitate top-down lexical prediction by the left prefrontal cortex. The left anterior prefrontal regions may be recruited for semantic integration of multiple concrete phrases.
Clinicopathological and radiological significance of the collateral vessels of renal cell carcinoma on preoperative computed tomography
Authors: Suo Xueling , Chen Junru , Zhao Yijun , Tang Qidun , Yang Xibiao , Yuan Yuan , Nie Ling , Chen Ni , Zeng Hao , Yao Jin 
Published: March 2021

AbstractThis study aimed to investigate the clinicopathological and radiological significance of the collateral vessel of renal cell carcinoma (RCC) on preoperative computed tomography (CT). Preoperative contrast-enhanced CT of 236 consecutive patients with pathological documented RCC were retrospectively reviewed during the period of 2014. The associations of the presence of collateral vessels with perioperative clinicopathological and radiological features, as well as long term survival outcomes were analyzed. Totally, collateral vessels were detected by contrast-enhanced CT in 110 of 236 patients. The presence of collateral vessels was significantly associated with higher pathologic T stage, higher Fuhrman grade, higher overall RENAL scores, greater tumor size and enhancement, and more tumor necrosis (all P < 0.05). In patients with clear cell RCC, those harboring collateral vessels had significantly higher SSIGN scores (P < 0.001) and shorter overall survival (P = 0.01) than those without collateral vessel. The incidence of intraoperative blood loss, blood transfusion, radical nephrectomy (RN) and open surgery were also significantly higher in patients with collateral vessels (all P < 0.05). In multivariate analysis, the presence of collateral vessels was significantly associated with RN (P = 0.021) and open surgery (P = 0.012). The presence of collateral vessels was significantly associated with aggressive clinicopathological parameters and worse prognosis. It is worth paying attention to its association with the choice of RN and open surgery in clinical practice.
Integrative network analysis reveals USP7 haploinsufficiency inhibits E-protein activity in pediatric T-lineage acute lymphoblastic leukemia (T-ALL)
Authors: Shaw Timothy I. , Dong Li , Tian Liqing , Qian Chenxi , Liu Yu , Ju Bensheng , High Anthony , Kavdia Kanisha , Pagala Vishwajeeth R. , Shaner Bridget , Pei Deqing , Easton John , Janke Laura J. , Porter Shaina N. , Ma Xiaotu , Cheng Cheng , Pruett-Miller Shondra M. , Choi John , Yu Jiyang , Peng Junmin , Gu Wei , Look A. Thomas , Downing James R. , Zhang Jinghui 
Published: March 2021

AbstractUSP7, which encodes a deubiquitylating enzyme, is among the most frequently mutated genes in pediatric T-ALL, with somatic heterozygous loss-of-function mutations (haploinsufficiency) predominantly affecting the subgroup that has aberrant TAL1 oncogene activation. Network analysis of > 200 T-ALL transcriptomes linked USP7 haploinsufficiency with decreased activities of E-proteins. E-proteins are also negatively regulated by TAL1, leading to concerted down-regulation of E-protein target genes involved in T-cell development. In T-ALL cell lines, we showed the physical interaction of USP7 with E-proteins and TAL1 by mass spectrometry and ChIP-seq. Haploinsufficient but not complete CRISPR knock-out of USP7 showed accelerated cell growth and validated transcriptional down-regulation of E-protein targets. Our study unveiled the synergistic effect of USP7 haploinsufficiency with aberrant TAL1 activation on T-ALL, implicating USP7 as a haploinsufficient tumor suppressor in T-ALL. Our findings caution against a universal oncogene designation for USP7 while emphasizing the dosage-dependent consequences of USP7 inhibitors currently under development as potential cancer therapeutics.
Development of in-airway laser absorption spectroscopy for respiratory based measurements of cardiac output
Authors: Smith Nicholas M. J. , Couper John , Richmond Graham , Sandhu Dominic , Hancock Gus , Robbins Peter A. , Ritchie Grant A. D. 
Published: March 2021

AbstractRespiratory approaches to determining cardiac output in humans are securely rooted in mass balance and therefore potentially highly accurate. To address existing limitations in the gas analysis, we developed an in-airway analyser based on laser absorption spectroscopy to provide analyses every 10 ms. The technique for estimating cardiac output requires both a relatively soluble and insoluble tracer gas, and we employed acetylene and methane for these, respectively. A multipass cell was used to provide sufficient measurement sensitivity to enable analysis directly within the main gas stream, thus avoiding errors introduced by sidestream gas analysis. To assess performance, measurements of cardiac output were made during both rest and exercise on five successive days in each of six volunteers. The measurements were extremely repeatable (coefficient of variation ~ 7%). This new measurement technology provides a stable foundation against which the algorithm to calculate cardiac output can be further developed.
The significance of metalloproteinase 3 (MMP-3), chemokine CXC ligand 13 (CXCL-13) and complement component C5a in different stages of ANCA associated vasculitis
Authors: Rymarz Aleksandra , Mosakowska Magdalena , Niemczyk Stanisław 
Published: March 2021

AbstractThe aim of the study was to evaluate the significance of metalloproteinase 3 (MMP-3), chemokine CXC ligand 13 (CXCL-13) and complement component 5a (C5a) in different stages of ANCA associated vasculitis (AAV). 89 adults were included into the study. 28 patients with active AAV (Birmingham Vasculitis Activity Score, BVAS > 3) formed the Active Group. 24 individuals who were in remission after 6 months of induction therapy formed the Short R Group, while 34 patients with longitudinal remission formed the Long R Group. 28 patients without autoimmune diseases similar in terms of age, gender and stage of kidney disease formed the Control Group. Receiver operating characteristic curve analysis (ROC) was used to evaluate MMP-3, CXCL-13 and C5a as markers of the different phases of vasculitis. In ROC analysis, MMP-3, CXCL-13 and C5a presented a good ability in distinguishing active vasculitis (Active Group) from the Control Group (AUC > 0.8), whereas only CXCL-13 displayed potential ability in distinguishing active vasculitis (Active Group) from long term remission (Long R Group, AUC = 0.683). MMP-3 significantly and positively correlated with serum creatinine concentration (r = 0.51,p = 0.011; r = 0.44,p = 0.009; r =  −0.66,p < 0.001) and negatively with eGFR (r =  −0.5,p = 0.012; r =  −0.35,p = 0.039; r =  −0.63,p < 0.001) in the Short R, Long R and Control Groups. MMP-3, CXCL-13, C5a can be potential markers in differentiating an active phase of vasculitis from other pathologies. However they can be treated as complementary to the well-known markers. CXCL-13 seems to be a potential marker in distinguishing active vasculitis from long term remission. MMP-3 level can be related to kidney function expressed by eGFR, therefore its elevation should be interpreted with caution in patients with kidney failure.
Temporal stability of quality of life assessments in cancer patients
Authors: Hinz Andreas , Schulte Thomas , Rassler Jörg , Zenger Markus , Geue Kristina 
Published: March 2021

AbstractQuality of life (QoL) is an important outcome criterion in cancer research and practice. Multiple studies have been performed to test the short-term temporal stability (1 day–2 weeks) of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire EORTC QLQ-C30, but its stability over longer periods of time is largely unknown. The EORTC QLQ-C30 was administered at two time points between 3 and 12 months apart in six samples of cancer patients with varying characteristics (N between 298 and 923). Averaged across the six samples, the coefficients of temporal stability (intra-class correlation coefficients ICC) were between 0.31 and 0.59 for the single scales. The 2-item global health/QoL scale showed a mean coefficient of 0.44. When the stability coefficients were calculated separately for males and females and for younger vs. older patients, no systematic gender or age differences were found in the temporal stability of the QoL scales, though the stability was slightly higher in males (vs. females) and in older subgroups (vs. younger subgroups). It is nearly impossible to predict the course a cancer patients’ QoL will take over a several month period. Repeated measurements are necessary to track QoL developments.