bluuebunny/crossref_metadata_2025 huggingface dataset:
Color and cellular selectivity of retinal ganglion cell subtypes through frequency modulation of electrical stimulation
Authors: Paknahad Javad , Loizos Kyle , Yue Lan , Humayun Mark S. , Lazzi Gianluca
Published: March 2021

Epiretinal prostheses aim at electrically stimulating the inner most surviving retinal cells—retinal ganglion cells (RGCs)—to restore partial sight to the blind. Recent tests in patients with epiretinal implants have revealed that electrical stimulation of the retina results in the percept of color of the elicited phosphenes, which depends on the frequency of stimulation. This paper presents computational results that are predictive of this finding and further support our understanding of the mechanisms of color encoding in electrical stimulation of retina, which could prove pivotal for the design of advanced retinal prosthetics that elicit both percept and color. This provides, for the first time, a directly applicable “amplitude-frequency” stimulation strategy to “encode color” in future retinal prosthetics through a predictive computational tool to selectively target small bistratified cells, which have been shown to contribute to “blue-yellow” color opponency in the retinal circuitry. The presented results are validated with experimental data reported in the literature and correlated with findings in blind patients with a retinal prosthetic implant collected by our group.
MR-proADM as prognostic factor of outcome in COVID-19 patients
Authors: Sozio Emanuela , Tascini Carlo , Fabris Martina , D’Aurizio Federica , De Carlo Chiara , Graziano Elena , Bassi Flavio , Sbrana Francesco , Ripoli Andrea , Pagotto Alberto , Giacinta Alessandro , Gerussi Valentina , Visentini Daniela , De Stefanis Paola , Merelli Maria , Saeed Kordo , Curcio Francesco
Published: March 2021

Mid Regional pro-ADM (MR-proADM) is a promising novel biomarker in the evaluation of deteriorating patients and an emergent prognosis factor in patients with sepsis, septic shock and organ failure. It can be induced by bacteria, fungi or viruses. We hypothesized that the assessment of MR-proADM, with or without other inflammatory cytokines, as part of a clinical assessment of COVID-19 patients at hospital admission, may assist in identifying those likely to develop severe disease. A pragmatic retrospective analysis was performed on a complete data set from 111 patients admitted to Udine University Hospital, in northern Italy, from 25th March to 15th May 2020, affected by SARS-CoV-2 pneumonia. Clinical scoring systems (SOFA score, WHO disease severity class, SIMEU clinical phenotype), cytokines (IL-6, IL-1b, IL-8, TNF-α), and MR-proADM were measured. Demographic, clinical and outcome data were collected for analysis. At multivariate analysis, high MR-proADM levels were significantly associated with negative outcome (death or orotracheal intubation, IOT), with an odds ratio of 4.284 [1.893–11.413], together with increased neutrophil count (OR = 1.029 [1.011–1.049]) and WHO disease severity class (OR = 7.632 [5.871–19.496]). AUROC analysis showed a good discriminative performance of MR-proADM (AUROC: 0.849 [95% Cl 0.771–0.730]; p < 0.0001). The optimal value of MR-proADM to discriminate combined event of death or IOT is 0.895 nmol/l, with a sensitivity of 0.857 [95% Cl 0.728–0.987] and a specificity of 0.687 [95% Cl 0.587–0.787]. This study shows an association between MR-proADM levels and the severity of COVID-19. The assessment of MR-proADM combined with clinical scoring systems could be of great value in triaging, evaluating possible escalation of therapies, and admission avoidance or inclusion into trials. Larger prospective and controlled studies are needed to confirm these findings.
Reading without phonology: ERP evidence from skilled deaf readers of Spanish
Authors: Costello Brendan , Caffarra Sendy , Fariña Noemi , Duñabeitia Jon Andoni , Carreiras Manuel
Published: March 2021

Reading typically involves phonological mediation, especially for transparent orthographies with a regular letter to sound correspondence. In this study we ask whether phonological coding is a necessary part of the reading process by examining prelingually deaf individuals who are skilled readers of Spanish. We conducted two EEG experiments exploiting the pseudohomophone effect, in which nonwords that sound like words elicit phonological encoding during reading. The first, a semantic categorization task with masked priming, resulted in modulation of the N250 by pseudohomophone primes in hearing but not in deaf readers. The second, a lexical decision task, confirmed the pattern: hearing readers had increased errors and an attenuated N400 response for pseudohomophones compared to control pseudowords, whereas deaf readers did not treat pseudohomophones any differently from pseudowords, either behaviourally or in the ERP response. These results offer converging evidence that skilled deaf readers do not rely on phonological coding during visual word recognition. Furthermore, the finding demonstrates that reading can take place in the absence of phonological activation, and we speculate about the alternative mechanisms that allow these deaf individuals to read competently.
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

The 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

The 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

The 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

Puromycin 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

This 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

To 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

Early 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

We 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

The 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

This 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

USP7, 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

Respiratory 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

The 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

Quality 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.
Site-specific N-glycosylation analysis of animal cell culture-derived Zika virus proteins
Authors: Pralow Alexander , Nikolay Alexander , Leon Arnaud , Genzel Yvonne , Rapp Erdmann , Reichl Udo
Published: March 2021

Here, we present for the first time, a site-specific N-glycosylation analysis of proteins from a Brazilian Zika virus (ZIKV) strain. The virus was propagated with high yield in an embryo-derived stem cell line (EB66, Valneva SE), and concentrated by g-force step-gradient centrifugation. Subsequently, the sample was proteolytically digested with different enzymes, measured via a LC–MS/MS-based workflow, and analyzed in a semi-automated way using the in-house developed glyXtoolMS software. The viral non-structural protein 1 (NS1) was glycosylated exclusively with high-mannose structures on both potential N-glycosylation sites. In case of the viral envelope (E) protein, no specific N-glycans could be identified with this method. Nevertheless, N-glycosylation could be proved by enzymatic de-N-glycosylation with PNGase F, resulting in a strong MS-signal of the former glycopeptide with deamidated asparagine at the potential N-glycosylation site N444. This confirmed that this site of the ZIKV E protein is highly N-glycosylated but with very high micro-heterogeneity. Our study clearly demonstrates the progress made towards site-specific N-glycosylation analysis of viral proteins, i.e. for Brazilian ZIKV. It allows to better characterize viral isolates, and to monitor glycosylation of major antigens. The method established can be applied for detailed studies regarding the impact of protein glycosylation on antigenicity and human pathogenicity of many viruses including influenza virus, HIV and corona virus.
Gene expression for secondary metabolite biosynthesis in hop (Humulus lupulus L.) leaf lupulin glands exposed to heat and low-water stress
Authors: Eriksen Renée L. , Padgitt-Cobb Lillian K. , Townsend M. Shaun , Henning John A.
Published: March 2021

Hops are valued for their secondary metabolites, including bitter acids, flavonoids, oils, and polyphenols, that impart flavor in beer. Previous studies have shown that hop yield and bitter acid content decline with increased temperatures and low-water stress. We looked at physiological traits and differential gene expression in leaf, stem, and root tissue from hop (Humulus lupulus) cv. USDA Cascade in plants exposed to high temperature stress, low-water stress, and a compound treatment of both high temperature and low-water stress for six weeks. The stress conditions imposed in these experiments caused substantial changes to the transcriptome, with significant reductions in the expression of numerous genes involved in secondary metabolite biosynthesis. Of the genes involved in bitter acid production, the critical gene valerophenone synthase (VPS) experienced significant reductions in expression levels across stress treatments, suggesting stress-induced lability in this gene and/or its regulatory elements may be at least partially responsible for previously reported declines in bitter acid content. We also identified a number of transcripts with homology to genes shown to affect abiotic stress tolerance in other plants that may be useful as markers for breeding improved abiotic stress tolerance in hop. Lastly, we provide the first transcriptome from hop root tissue.
An association between body image dissatisfaction and digit ratio among Chinese children and adolescents
Authors: Yuan Yongting , Hu Jingyao , Sun Lili , Zhang Yifei , Wang Bangxuan , Yao Rongying , Han Hui , Fu Lianguo
Published: March 2021

Body image dissatisfaction (BID) is a negative evaluation of personal physical characteristics, including dissatisfaction with body shape, gender, sexual organs, appearance and so forth, and it plays an important role in growth and development. The second-to-fourth digit ratio (2D:4D) is recognized as a putative indicator of intra-uterine testosterone to estrogen ratio exposure, and it has been observed that higher levels of fetal testosterone exposure are associated with a lower 2D:4D. The present paper contributes to a better understanding of the biological underpinnings of BID by analyzing BID and the digit ratio (2D:4D). We found that the 2D:4D was positively related to appearance dissatisfaction in boys with first spermatorrhea, which means that low prenatal androgen exposure may increase boys’ dissatisfaction with their appearance. In girls with breast development being lower than Tanner stage II, their 2D:4D was negatively related to their body shape dissatisfaction, which means that high prenatal androgen exposure may increase girls’ dissatisfaction with their body shape. These results suggest that the prenatal androgen exposure level might play an important role in the body image dissatisfaction of the offspring.
Factors associated with physician decision making on withholding cardiopulmonary resuscitation in prehospital medicine
Authors: Zajic Paul , Zoidl Philipp , Deininger Marlene , Heschl Stefan , Fellinger Tobias , Posch Martin , Metnitz Philipp , Prause Gerhard
Published: March 2021

This study seeks to identify factors that are associated with decisions of prehospital physicians to start (continue, if ongoing) or withhold (terminate, if ongoing) CPR in patients with OHCA. We conducted a retrospective study using anonymised data from a prehospital physician response system. Data on patients attended for cardiac arrest between January 1st, 2010 and December 31st, 2018 except babies at birth were included. Logistic regression analysis with start of CPR by physicians as the dependent variable and possible associated factors as independent variables adjusted for anonymised physician identifiers was conducted. 1525 patient data sets were analysed. Obvious signs of death were present in 278 cases; in the remaining 1247, resuscitation was attempted in 920 (74%) and were withheld in 327 (26%). Factors significantly associated with higher likelihood of CPR by physicians (OR 95% CI) were resuscitation efforts by EMS before physician arrival (60.45, 19.89–184.29), first monitored heart rhythm (3.07, 1.21–7.79 for PEA; 29.25, 1.93–442. 51 for VF / pVT compared to asystole); advanced patient age (modelled using cubic splines), physician response time (0.92, 0.87–0.97 per minute) and malignancy (0.22, 0.05–0.92) were significantly associated with lower odds of CPR. We thus conclude that prehospital physicians make decisions to start or withhold resuscitation routinely and base those mostly on situational information and immediately available patient information known to impact outcomes.
Telomeres and replicative cellular aging of the human placenta and chorioamniotic membranes
Authors: Lai Tsung-Po , Simpson Mark , Patel Krunal , Verhulst Simon , Noh Jungsik , Roche Natalie , Heller Debra , Guirguis George , Shay Jerry W. , Herbig Utz , Aviv Abraham
Published: March 2021

Recent hypotheses propose that the human placenta and chorioamniotic membranes (CAMs) experience telomere length (TL)-mediated senescence. These hypotheses are based on mean TL (mTL) measurements, but replicative senescence is triggered by short and dysfunctional telomeres, not mTL. We measured short telomeres by a vanguard method, the Telomere shortest length assay, and telomere-dysfunction-induced DNA damage foci (TIF) in placentas and CAMs between 18-week gestation and at full-term. Both the placenta and CAMs showed a buildup of short telomeres and TIFs, but not shortening of mTL from 18-weeks to full-term. In the placenta, TIFs correlated with short telomeres but not mTL. CAMs of preterm birth pregnancies with intra-amniotic infection showed shorter mTL and increased proportions of short telomeres. We conclude that the placenta and probably the CAMs undergo TL-mediated replicative aging. Further research is warranted whether TL-mediated replicative aging plays a role in all preterm births.
COVID-19 engages clinical markers for the management of cancer and cancer-relevant regulators of cell proliferation, death, migration, and immune response
Authors: Souchelnytskyi Serhiy , Nera Andriy , Souchelnytskyi Nazariy
Published: March 2021

Clinical reports show that the management of cancer patients infected with SARS-CoV-2 requires modifications. Understanding of cancer-relevant mechanisms engaged by the virus is essential for the evidence-based management of cancer. The network of SARS-CoV-2 regulatory mechanisms was used to study potential engagement of oncogenes, tumor suppressors, other regulators of tumorigenesis and clinical markers used in the management of cancer patients. Our network analysis confirms links between COVID-19 and tumorigenesis that were predicted in epidemiological reports. The COVID-19 network shows the involvement of tumorigenesis regulators and clinical markers. Regulators of cell proliferation, death, migration, and the immune system were retrieved. Examples are pathways initiated by EGF, VEGF, TGFβ and FGF. The SARS-CoV-2 network engages markers for diagnosis, prognosis and selection of treatment. Intersection with cancer diagnostic signatures supports a potential impact of the virus on tumorigenesis. Clinical observations show the diversity of symptoms correlating with biological processes and types of cells engaged by the virus, e.g. epithelial, endothelial, smooth muscle, glial and immune system cells. Our results describe an extensive engagement of cancer-relevant mechanisms and clinical markers by COVID-19. Engagement by the virus of clinical markers provides a rationale for clinical decisions based on these markers.
Polyunsaturated ω-3 fatty acids inhibit ACE2-controlled SARS-CoV-2 binding and cellular entry
Authors: Goc Anna , Niedzwiecki Aleksandra , Rath Matthias
Published: March 2021

The strain SARS-CoV-2, newly emerged in late 2019, has been identified as the cause of COVID-19 and the pandemic declared by WHO in early 2020. Although lipids have been shown to possess antiviral efficacy, little is currently known about lipid compounds with anti-SARS-CoV-2 binding and entry properties. To address this issue, we screened, overall, 17 polyunsaturated fatty acids, monounsaturated fatty acids and saturated fatty acids, as wells as lipid-soluble vitamins. In performing target-based ligand screening utilizing the RBD-SARS-CoV-2 sequence, we observed that polyunsaturated fatty acids most effectively interfere with binding to hACE2, the receptor for SARS-CoV-2. Using a spike protein pseudo-virus, we also found that linolenic acid and eicosapentaenoic acid significantly block the entry of SARS-CoV-2. In addition, eicosapentaenoic acid showed higher efficacy than linolenic acid in reducing activity of TMPRSS2 and cathepsin L proteases, but neither of the fatty acids affected their expression at the protein level. Also, neither reduction of hACE2 activity nor binding to the hACE2 receptor upon treatment with these two fatty acids was observed. Although further in vivo experiments are warranted to validate the current findings, our study provides a new insight into the role of lipids as antiviral compounds against the SARS-CoV-2 strain.
Synthesis of Ni(ii)–Mn(ii) complexes using a new mononuclear Ni(ii) complex of an unsymmetrical N2O3 donor ligand: structures, magnetic properties and catalytic oxidase activity
Authors: Maity Souvik , Mahapatra Prithwish , Ghosh Tanmoy Kumar , Gomila Rosa M. , Frontera Antonio , Ghosh Ashutosh
Published: March 2021

Three new NiII–MnII complexes have been synthesized by employing a new Ni(ii) complex of an unsymmetrical N2O3 donor ligand; one of which containing azide co-anions readily oxidizes 3,5-DTBC to 3,5-DTBQ.
Designing bioinspired green nanosilicas using statistical and machine learning approaches
Authors: Dewulf Luc , Chiacchia Mauro , Yeardley Aaron S. , Milton Robert A. , Brown Solomon F. , Patwardhan Siddharth V.
Published: March 2021

This is a first comparison of the sequential design of experiments strategy and global sensitivity analysis for nanomaterials, thus enabling sustainable product and process design in future.
Moving-bed biofilm reactor combined with three-dimensional electrochemical pretreatment (MBBR–3DE) for 2,4-D herbicide treatment: application for real wastewater, improvement of biodegradability
Authors: Dargahi Abdollah , Shokoohi Reza , Asgari Ghorban , Ansari Amin , Nematollahi Davood , Samarghandi Mohammad Reza
Published: March 2021

Application for real wastewater, kinetics modelling, effect of operating parameters on removal of 2,4-D using MBBR–3DE processes, improvement of biodegradability and Identification of herbicide-degrading microorganisms.
Side-chain-extended conjugation: a strategy for improving the photocatalytic hydrogen production performance of a linear conjugated polymer
Authors: Wang Wen-Rui , Li Jia , Li Qian , Xu Zi-Wen , Liu Li-Na , Chen Xue-Qiang , Xiao Wen-Jing , Yao Jianhua , Zhang Fang , Li Wei-Shi
Published: March 2021

As compared to P0, P2 showed a 160-fold performance improvement, much larger than 3.6-fold for P1.
“Sweet tooth”-oriented SN38 prodrug delivery nanoplatform for targeted gastric cancer therapy
Authors: Ding Ning , Xu Shengjun , Zheng Sheng , Ye Qianwei , Xu Li , Ling Sunbin , Xie Shanshan , Chen Wenwen , Zhang Zizhen , Xue Meng , Lin Zhenghua , Xu Xiao , Wang Liangjing
Published: March 2021

Motivated by the overexpression of GLUT1 in gastric cancer, a targeted SN38 prodrug delivery nanoplatform was constructed and exhibited potent antitumor efficiency, which brought a new insight to the design of nanomedicine against cancer.
Biosynthesis of chiral cyclic and heterocyclic alcohols via CO/C–H/C–O asymmetric reactions
Authors: Qin Lei , Wu Lunjie , Nie Yao , Xu Yan
Published: March 2021

This review covers the recent progress in various biological approaches applied to the synthesis of enantiomerically pure cyclic and heterocyclic alcohols through CO/C–H/C–O asymmetric reactions.
Two-colour photoswitching in photoresponsive inorganic thin films
Authors: Sundin Elin , Johansson Fredrik , Saavedra Becerril Valeria , Wallenstein Joachim , Gasslander August , Mårtensson Jerker , Abrahamsson Maria
Published: March 2021

Herein we present two-colour photoswitching in a photoresponsive thin film based on a Ru-sulfoxide complex immobilized onto a ZrO2 surface.
Symbiotic composite composed of MoS2and pelagic clay with enhanced disinfection efficiency
Authors: Sun Qiwei , Liu Yuhua , Liu Zhipeng , Huang Guoqing , Yuan Shisheng , Yang Guohua , Wang Kaiwen , Zhang Peiping , Li Nan
Published: March 2021

A symbiotic composite MoS2/PC was prepared and showed an enhanced disinfection efficiency toE. coli8739 under visible light.
CO2activation of bamboo residue after hydrothermal treatment and performance as an EDLC electrode
Authors: Khuong Duy Anh , Nguyen Hong Nam , Tsubota Toshiki
Published: March 2021

CO2activation was performed on hydrothermally treated bamboo for the preparation of an EDLC electrode.
Recent progress in emerging metal and covalent organic frameworks for electrochemical and functional capacitors
Authors: Pei Chengang , Choi Min Sung , Yu Xu , Xue Huaiguo , Xia Bao Yu , Park Ho Seok
Published: March 2021

The key aspects of MOFs, COFs and their derivatives are comprehensively reviewed focusing on the chemical and physical features, energy storage mechanisms and structure/property correlations of the 12 types of MOFs, COFs and their derivatives for supercapacitor application.
Active colorimetric lipid-coated polyaniline nanoparticles for redox state sensing in cancer cells
Authors: Lee Hwunjae , Kim Hyun-Ouk , Kim Hyun Soo , Kwon Ohwon , Rho Hyun-Wook , Huh Yong-Min , Hong Yoochan
Published: March 2021

The active colorimetric capability of lipid-coated polyaniline nanoparticles was confirmed via absorbance spectra when the pH was varied, and via dark field imaging and light scattering spectra in cancer cells.
Optimal allocation of soft open points in active distribution network with high penetration of renewable energy generations
Authors: Cong Pengwei , Hu Zechun , Tang Wei , Lou Chengwei , Zhang Lu
Published: March 2021

With the integration of more and more renewable energy generations (REGs), the structure of traditional distribution networks is hard to accommodate the volatile power injections of REGs. As a new power electronic device, soft open point (SOP) can be installed to control both active and reactive power flow among active distribution networks (ADNs). This paper presents a comprehensive optimization method for allocating SOPs within an ADN with high penetration of REGs. In order to find proper SOP candidate locations, a selection strategy based on two technical indices is proposed. To mitigate the risk of voltage violation caused by REG forecast errors and improve the adaptiveness of allocation results, a two‐stage robust optimization model for SOP allocation is formulated to minimize the total cost of SOP investment and network operation. The proposed model is converted into a mixed‐integer second‐order cone programming (MISCOP) problem, which is then decoupled into a master problem of planning and a subproblem of operation and solved by column and constraint generation (CCG) algorithm. Simulation results show that the proposed method can effectively find the optimal SOP allocation schemes. Comparisons with different mathematical formulation and solution methods show the advantages of the proposed method.
RETRACTED: An agile high-frequency radar used for ionospheric research
Authors: Yan Jingye , Lan Ailan , Deng Xiang , Zhang Jiaojiao , Wang Chi , Qiu Hongbin
Published: March 2021

This article is retracted at the request of the Editors-in-Chief and the Publisher, see theRetraction Notice. The paper “An agile high-frequency radar used for ionospheric research” published in the Journal of Space Weather and Space Climate (https://doi.org/10.1051/swsc/2021010) has overlapping content with papers published in Polar Science (https://doi.org/10.1016/j.polar.2020.100595) and Radio Science (https://doi-org.insu.bib.cnrs.fr/10.1029/2020RS007138).