bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a stable antibody production system utilizing an Hspa5 promoter in CHO cells
Authors: Tanemura Hiroki , Masuda Kenji , Okumura Takeshi , Takagi Eri , Kajihara Daisuke , Kakihara Hirofumi , Nonaka Koichi , Ushioda Ryo
Published: May 2022

Chinese hamster ovary (CHO) cells are widely used for manufacturing antibody drugs. We attempted to clone a novel high-expression promoter for producing monoclonal antibodies (mAbs) based on transcriptome analysis to enhance the transcriptional abundance of mAb genes. The efficacy of conventional promoters such as CMV and hEF1α decrease in the latter phase of fed-batch cell culture. To overcome this, we screened genes whose expression was maintained or increased throughout the culture period. Since CHO cells have diverse genetic expression depending on the selected clone and culture medium, transcriptome analysis was performed on multiple clones and culture media anticipated to be used in mAb manufacturing. We thus acquired the Hspa5 promoter as a novel high-expression promoter, which uniquely enables mAb productivity per cell to improve late in the culture period. Productivity also improved for various IgG subclasses under Hspa5 promoter control, indicating this promoter’s potential universal value for mAb production. Finally, it was suggested that mAb production with this promoter is correlated with the transcription levels of endoplasmic reticulum stress-related genes. Therefore, mAb production utilizing the Hspa5 promoter might be a new method for maintaining protein homeostasis and achieving stable expression of introduced mAb genes during fed-batch culture.
Phenomenology and content of the inhaled N, N-dimethyltryptamine (N, N-DMT) experience
Authors: Lawrence David Wyndham , Carhart-Harris Robin , Griffiths Roland , Timmermann Christopher
Published: May 2022

Understanding the phenomenology and content of the inhaledN,N, dimethyltryptamine (N,N-DMT) experience is critical to facilitate and support ongoing research and therapeutic models targeting mental health conditions and central nervous system pathology. A qualitative analysis was conducted of allN,N-DMT experiences posted to the r/DMT Reddit community over a 10-year period from 2009 to 2018. A total of 3778 experiences from 3305 posts were included in this study. A median dose ofN,N-DMT of 40.0 mg [interquartile range (IQR), 27.5 to 50.0] and a median experience duration of 10 min (IQR, 5.0 to 15.0) were identified. The most common somatic effects were somaesthesias (n = 1415, 37.5%) and an auditory ringing (n = 583, 15.4%). Visualizations predominantly consisted of fractals, shapes, patterns (n = 1231, 32.6%) and vivid colours (n = 953, 25.2%). Entity encounters were reported in 45.5% (n = 1719) of the experiences and involved predominantly a feminine phenotype (n = 416, 24.2%); deities (n = 293, 17.0%); aliens (n = 281, 16.3%); creature-based entities (n = 158, 9.2%, including reptilian and insectoid beings); mythological beings (n = 144, 8.4%, including machine elves); and jesters (n = 112, 6.5%). Entity interactions were predominantly positive (n = 600, 34.9% of encounters) involving benevolent, comforting, protecting, or outwardly caring interactions. A companion-type, pedagogical, or guide-type interaction was identified 32.4% of encounters (n = 557). Common typology, architecture, and structural features of the “DMT world” included descriptions of alternate or higher dimensions (n = 952, 25.2%); rooms [n = 582, 15.4%, including the “waiting room” (n = 105, 2.8%)], and a tunnel (n = 390, 10.3%). Features of mystical and ego-dissolution experiences were common. Additional rewarding aspects were identified, including a sense of familiarity and the acceptance/removal of the fear of death. Challenging and difficult responses were less frequent but also documented. Statements of profundity were identified in 232 experiences (6.1%), including pronouncing the experience or an aspect of the experience as the most “beautiful” or feeling the most “beautiful” of their life (n = 47, 1.2%). This study identified common phenomenological themes and content of naturalistic inhaledN,N-DMT experiences. Major thematic domains included (1) physical and somatic experiences; (2) visualizations and imagery; (3) entity encounters including entity phenotype, descriptors, attributes, disposition, and characteristics of the interaction; (4) typology, architectural features, structural characteristics, and scenery of the “DMT world”; (5) alerations in consciousness (including mystical experiences, out-of-body experiences, and ego-dissolution); (6) emotional responses (including positive, rewarding, difficult, and challenging); and (7) statements of profundity.
Dominant predictors of early post-transplant outcomes based on the Korean Organ Transplantation Registry (KOTRY)
Authors: Jeong Jong Cheol , Koo Tai Yeon , Ro Han , Lee Dong Ryeol , Lee Dong Won , Oh Jieun , Kim Jayoun , Chae Dong-Wan , Kim Young Hoon , Huh Kyu Ha , Park Jae Berm , Kim Yeong Hoon , Han Seungyeup , Choi Soo Jin Na , Lee Sik , Min Sang-Il , Ha Jongwon , Kim Myoung Soo , Ahn Curie , Yang Jaeseok ,   The KOTRY Study Group, Ahn Curie , Kim Myoung Soo , Yang Jaeseok , Kong Jin Min , Kwon Oh Jung , Kim Deok Gie , Jung Cheol Woong , Kim Yeong Hoon , Kim Joong Kyung , Kim Chan-Duck , Min Ji Won , Park Sung Kwang , Park Yeon Ho , Park Jae Berm , Park Jung Hwan , Park Jong-Won , Ban Tae Hyun , Song Sang Heon , Song Seung Hwan , Shin Ho Sik , Yang Chul Woo , Yoon Hye Eun , Lee Kang Wook , Lee Dong Ryeol , Lee Dong Won , Lee Sam Yeol , Lee Sang-Ho , Lee Su Hyung , Lee Yu Ho , Lee Jung Pyo , Lee Jeong-Hoon , Jeon Jin Seok , Jun Heungman , Jeong Kyunghwan , Chung Ku Yong , Cho Hong Rae , Ki Ju Man , Chae Dong-Wan , Choi Soo Jin Na , Shin Sung , Han Seungyeup , Huh Kyu Ha
Published: May 2022

Data for Asian kidney transplants are very limited. We investigated the relative importance of prognostic markers in Asian kidney transplants by using Korean Organ Transplantation Registry (KOTRY) cohort. Prediction models were developed by data-driven variable selection approach. The relative importance of the selected predictors was measured by dominance analysis. A total of 4854 kidney transplant donor-recipient pairs were analyzed. Overall patient survival rates were 99.8%, 98.8%, and 91.8% at 1, 3, and 5 years, respectively. Death-censored graft survival rates were 98.4%, 97.0%, and 95.8% at 1, 3, and 5 years. Biopsy-proven acute rejection free survival rates were 90.1%, 87.4%, and 87.03% at 1, 3, and 5 years. The top 3 dominant predictors for recipient mortality within 1 year were recipient cardiovascular disease history, deceased donor, and recipient age. The dominant predictors for death-censored graft loss within 1 year were acute rejection, deceased donor, and desensitization. The dominant predictors to acute rejection within 1 year were donor age, HLA mismatched numbers, and desensitization. We presented clinical characteristics of patients enrolled in KOTRY during the last 5 years and investigated dominant predictors for early post-transplant outcomes, which would be useful for clinical decision-making based on quantitative measures.
Saccharomyces cerevisiae does not undergo a quorum sensing-dependent switch of budding pattern
Authors: Winters Michela , Aru Violetta , Howell Kate , Arneborg Nils
Published: May 2022

Saccharomyces cerevisiae can alter its morphology to a filamentous form associated with unipolar budding in response to environmental stressors. Induction of filamentous growth is suggested under nitrogen deficiency in response to alcoholic signalling molecules through quorum sensing. To investigate this further, we analysed the budding pattern of S. cerevisiae cells over time under low nitrogen conditions while concurrently measuring cell density and extracellular metabolite concentration. We found that the proportion of cells displaying unipolar budding increased between local cell densities of 4.8 × 106 and 5.3 × 107 cells/ml. This increase in unipolar budding was not reproduced with cells growing at the critical cell density and in conditioned media. Growth under high nitrogen conditions also resulted in increased unipolar budding between local cell densities of 5.2 × 106 and 8.2 × 107 cells/ml, but with differences in metabolite concentration compared to low nitrogen conditions. Neither cell density, metabolite concentration, nor nitrogen deficiency were therefore sufficient to increase unipolar budding. Therefore, by using the budding pattern as an early indicator of filamentous growth, our results suggest that quorum sensing may not control the switch of budding behaviour in S. cerevisiae. Only a high concentration of the putative signalling molecule, 2-phenylethanol, resulted in an increase in unipolar budding. However, this concentration was not physiologically relevant, suggesting toxicity rather than a known quorum sensing mechanism.
Sulforaphane suppresses the activity of sterol regulatory element-binding proteins (SREBPs) by promoting SREBP precursor degradation
Authors: Miyata Shingo , Kodaka Manami , Kikuchi Akito , Matsunaga Yuki , Shoji Kenta , Kuan Yen-Chou , Iwase Masamori , Takeda Keita , Katsuta Ryo , Ishigami Ken , Matsumoto Yu , Suzuki Tsukasa , Yamamoto Yuji , Sato Ryuichiro , Inoue Jun
Published: May 2022

Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate various genes involved in cholesterol and fatty acid synthesis. In this study, we describe that naturally occurring isothiocyanate sulforaphane (SFaN) impairs fatty acid synthase promoter activity and reduces SREBP target gene (e.g., fatty acid synthase and acetyl-CoA carboxylase 1) expression in human hepatoma Huh-7 cells. SFaN reduced SREBP proteins by promoting the degradation of the SREBP precursor. Amino acids 595–784 of SREBP-1a were essential for SFaN-mediated SREBP-1a degradation. We also found that such SREBP-1 degradation occurs independently of the SREBP cleavage-activating protein and the Keap1-Nrf2 pathway. This study identifies SFaN as an SREBP inhibitor and provides evidence that SFaN could have major potential as a pharmaceutical preparation against hepatic steatosis and obesity.
An efficient geometric approach to quantum-inspired classifications
Authors: Leporini Roberto , Pastorello Davide
Published: May 2022

Optimal measurements for the discrimination of quantum states are useful tools for classification problems. In order to exploit the potential of quantum computers, feature vectors have to be encoded into quantum states represented by density operators. However, quantum-inspired classifiers based on nearest mean and on Helstrom state discrimination are implemented on classical computers. We show a geometric approach that improves the efficiency of quantum-inspired classification in terms of space and time acting on quantum encoding and allows one to compare classifiers correctly in the presence of multiple preparations of the same quantum state as input. We also introduce the nearest mean classification based on Bures distance, Hellinger distance and Jensen–Shannon distance comparing the performance with respect to well-known classifiers applied to benchmark datasets.
COVID-19 pandemic influence on self-reported health status and well-being in a society
Authors: Moniuszko-Malinowska Anna , Czupryna Piotr , Dubatówka Marlena , Łapińska Magda , Kazberuk Małgorzata , Szum-Jakubowska Aleksandra , Sołomacha Sebastian , Sowa Paweł , Kiszkiel Łukasz , Szczerbiński Łukasz , Bukłaha Anna , Laskowski Piotr Paweł , Kamiński Karol Adam
Published: May 2022

To assess the frequency of persisting symptoms after SARS-CoV-2 infection and assessment of the effects of COVID-19 pandemic on selected parameters of self-reported health status and well-being half a year after the disease. The study population consisted of 3 groups: post-COVID-19 group I—172 patients; group II—172 patients with chronic disease, who have not suffered from COVID-19; group III—81 patients from a population study cohort—Bialystok PLUS. A standardized interview questionnaire was used to collect data in the three groups using the CATI (computer assisted telephone interviewing) technique. Interviews were conducted between October 2020 and January 2021, thus during the second wave of the pandemic in Poland. The subjective state of health in comparison with the state of health before the COVID-19 pandemic deteriorated in COVID-19 convalescents. Patients, who suffered from symptomatic COVID-19 were more prone to nervousness, anxiousness, tension than patients with oligosymptomatic course of the disease. Moreover, anxiety, fear and irritability were more frequent in Group I and II in comparison to Group III, whereas Group I and II did not differ significantly. The decrease in physical activity observed in COVID-19 patients mirrored the changes in general population. The most frequent persistent symptoms after COVID-19 are: general malaise, cough, smell and taste disorder, dyspnea. COVID-19 convalescents who experienced symptomatic disease are more prone to development of nervousness, anxiousness, tension and anxiety than patients with oligosymptomatic course of the disease. Females and younger patients who suffered from COVID-19 are more prone to development of mental distress than healthy population. No significant differences between COVID-19 convalescents and healthy population was observed as far as the attitude towards physical activity is concerned.
An analytical four-layer horizontal electric current dipole model for analysing underwater electric potential in shallow seawater
Authors: Woloszyn Miroslaw , Buszman Krystian , Rutkowski Tomasz , Tarnawski Jaroslaw , Rodrigo Saura Francisco Javier
Published: May 2022

The paper presents a new analytical four-layer (air–water–bottom–non-conductive layer) horizontal electric dipole model which allows an accurate approximation of ship's Underwater Electric Potential (UEP) from a sufficient depth in shallow coastal marine waters. The numerical methods, usually Finite Element Method (FEM) or Boundary Elements Method (BEM), are typically used to estimate the electric field and the distribution of static electric components of UEP around the ship. These methods enable analyses with high accuracy but, compared to other point-electrode methods and the proposed analytical model, they are relatively complex and need high computational time. The developed analytical model proposed in this paper allows real-time calculations without significant loss of accuracy of the UEP estimations. In the model, the problem of boundary values at the borders of individual layers is solved using the reflection/image method and applying the idea of continuity of electric potential at a given boundary between two adjacent layers. Its accuracy is verified based on the synthetic data provided by specialised software packages making use of FEM and BEM numerical methods. A dimensionless quantitative analysis of the relationships between basic parameters of the proposed four-layer analytical model and their impact on the accuracy of representation of individual electric field strength components is also delivered. The relationships between water and bottom conductivity and between water depth and bottom thickness are investigated and described. The obtained results show that the developed model allows detailed and reliable analysis of the electric field, especially in shallow coastal waters.
Assessment of antimicrobial, cytotoxicity, and antiviral impact of a green zinc oxide/activated carbon nanocomposite
Authors: Hassan Hassan S. , Abol-Fotouh Deyaa , Salama Eslam , Elkady Marwa F.
Published: May 2022

This work deals with the synthesis of zinc oxide nanoparticles/activated carbon (ZnO NPs/AC) nanocomposites with different weight ratios (3:1, 1:1, and 1:3), where the antimicrobial, antiviral, and cytotoxicity impact of the formulated nanocomposites were evaluated versus the crude ZnO and AC samples. The formula (3:1; designated Z3C1) exhibited the utmost bactericidal effect against Gram positive group, unicellular and filamentous fungi. Regarding Gram negative group, the sample (Z3C1) was remarkably effective against Klebsiella pneumonia, unlike the case of Escherichia coli. Moreover, the whole samples showed negligible cytotoxicity against the human WI38 cell line, where the most brutality (4%) was exerted by 1000 µg/mL of the formula (Z1C3). Whilst, the formula (Z3C1) exerted the apical inhibition impact against Herpes simplex (HSV1) virus. Consequently, the synthesized (Z3C1) nanocomposite was sorted out to be fully characterized via different physicochemical techniques including FTIR, XRD, SEM, TEM, Zeta potential, TGA, and BET. XRD indicated a predominance of the crystalline pattern of ZnO NPs over the amorphous AC, while the FTIR chart confirmed an immense combination between the ZnO NPs and AC. SEM, TEM, and size distribution images illustrated that the fabricated ZnO NPs/AC was in the nanoscale size swung from 30 to 70 nm. The distinctive surface area of composite material, recording 66.27 m2/g, clearly disclosed its bioactivity toward different bacterial, fungal, and virus species.
In silico design and analyses of a multi-epitope vaccine against Crimean-Congo hemorrhagic fever virus through reverse vaccinology and immunoinformatics approaches
Authors: Omoniyi Akinyemi Ademola , Adebisi Samuel Sunday , Musa Sunday Abraham , Nzalak James Oliver , Bauchi Zainab Mahmood , Bako Kerkebe William , Olatomide Oluwasegun Davis , Zachariah Richard , Nyengaard Jens Randel
Published: May 2022

Crimean Congo Hemorrhagic Fever virus (CCHFV) is a deadly human pathogen that causes an emerging zoonotic disease with a broad geographic spread, especially in Africa, Asia, and Europe, and the second most common viral hemorrhagic fever and widely transmitted tick-borne viral disease. Following infection, the patients are presented with a variety of clinical manifestations and a fatality rate of 40%. Despite the high fatality rate, there are unmet clinical interventions, as no antiviral drugs or vaccines for CCHF have been approved. Immunoinformatics pipeline and reverse vaccinology were used in this study to design a multi-epitope vaccine that may elicit a protective humoral and cellular immune response against Crimean-Congo hemorrhagic fever virus infection. Three essential virulent and antigenic proteins (S, M, and L) were used to predict seven CTL and 18 HTL epitopes that were non-allergenic, antigenic, IFN-γ inducing, and non-toxic. The epitopes were connected using linkers and 50S ribosomal protein L7/L12 was used as an adjuvant and raised a multi-epitope vaccine (MEV) that is 567 amino acids long. Molecular docking and simulation of the predicted 3D structure of the MEV with the toll-like (TLR2, TLR3, and TLR4) receptors and major histocompatibility complex (MCH-I and MCH-II) indicate high interactions and stability of the complexes, MM-GBSA free binding energy calculation revealed a favourable protein–protein complex. Maximum MEV expression was achieved with a CAI value of 0.98 through in silico cloning in theDrosophila melanogasterhost. According to the immune simulation, IgG1, T-helper cells, T-cytotoxic cells, INF-γ, and IL-2 were predicted to be significantly elevated. These robust computational analyses demonstrated that the proposed MEV is effective in preventing CCHFV infections. However, it is still necessary to conduct both in vitro and in vivo experiments to validate the potential of the vaccine.
Unveiling microbiome profiles in human inner body fluids and tumor tissues with pancreatic or biliary tract cancer
Authors: Okuda Shujiro , Hirose Yuki , Takihara Hayato , Okuda Akiko , Ling Yiwei , Tajima Yosuke , Shimada Yoshifumi , Ichikawa Hiroshi , Takizawa Kazuyasu , Sakata Jun , Wakai Toshifumi
Published: May 2022

With the discovery of bacterial symbiosis in the tissues of various cancers, the study of the tumor microbiome is attracting a great deal of attention. Anatomically, since the gastrointestinal tract, liver, and pancreas form a continuous ductal structure, the microbiomes in the digestive juices of these organs may influence each other. Here, we report a series of microbiome data in tumor-associated tissues such as tumor, non-tumor, and lymph nodes, and body fluids such as saliva, gastric juice, pancreatic juice, bile, and feces of patients with pancreatic or biliary tract cancers. The results show that the microbiome of tumor-associated tissues has a very similar bacterial composition, but that in body fluids has different bacterial composition which varies by location, where some bacteria localize to specific body fluids. Surprisingly, Akkermansia was only detected in the bile of patients with biliary tract cancer and its presence was significantly associated with the performance of external biliary drainage (P = 0.041). Furthermore, we found that tumor-associated tissues and body fluids in deep inner body are mostly inhabited by unidentified and uncharacterized bacteria, suggesting that such bacteria may be potential targets for precision therapy in the future.
Odor blocking of stress hormone responses
Authors: Lee Eun Jeong , Saraiva Luis R. , Hanchate Naresh K. , Ye Xiaolan , Asher Gregory , Ho Jonathan , Buck Linda B.
Published: May 2022

Scents have been employed for millennia to allay stress, but whether or how they might do so is largely unknown. Fear and stress induce increases in blood stress hormones controlled by hypothalamic corticotropin releasing hormone neurons (CRHNs). Here, we report that two common odorants block mouse stress hormone responses to three potent stressors: physical restraint, predator odor, and male–male social confrontation. One odorant inhibits restraint and predator odor activation of excitatory neurons upstream of CRHNs in the bed nucleus of the stria terminalis (BNSTa). In addition, both activate inhibitory neurons upstream of CRHNs in the hypothalamic ventromedial nucleus (VMH) and silencing of VMH inhibitory neurons hinders odor blocking of stress. Together, these findings indicate that odor blocking can occur via two mechanisms: (1) Inhibition of excitatory neurons that transmit stress signals to CRHNs and (2) activation of inhibitory neurons that act directly or indirectly to inhibit stressor activation of CRHNs.
Influence of Si wall thickness of CsI(Tl) micro-square-frustums on the performance of the structured CsI(Tl) scintillation screen in X-ray imaging
Authors: Sun Zhixiang , Gu Mu , Liu Xiaolin , Liu Bo , Zhang Juannan , Huang Shiming , Ni Chen
Published: May 2022

To improve the detection efficiency of the structured scintillation screen with CsI(Tl) micro-square-frustums based on oxidized Si micropore array template in the case of a period as small as microns, the influence of Si wall thickness of the CsI(Tl) micro-square-frustums on the performance of the structured screen in X-ray imaging was investigated. The results show that when CsI(Tl) at the bottom of the screen is structured, the detective quantum efficiency (DQE) improves at almost all spatial frequency as the top thickness of the Si wall tSi decreases. However, when CsI (Tl) at the bottom of the screen is not structured, the DQE becomes better at low-frequency and worse at high-frequency as tSi decreases. The results can provide guidance for optimizing tSi according to the comprehensive requirements of detection efficiency and spatial resolution in X-ray imaging.
Rapid measurement of thoracolumbar kyphosis with the integrated inclinometer of a smartphone: a validity and reliability study
Authors: Huang Tianji , Zhao Zenghui , Wang Lin , Zhang Chao , Zhao Runhan , Xiong Chuang , Zhong Weiyang , Luo Xiaoji
Published: May 2022

The objective of this study was to evaluate the accuracy, reliability, and time requirements of two methods for measuring thoracolumbar kyphosis: a conventional method using a picture archiving and communication system (PACS) and this new method using the integrated inclinometer of a smartphone. The thoracolumbar kyphotic angles of one hundred consecutive patients were measured by a PACS and this novel smartphone method. The measured angles were analysed by multiple statistical methods, and the two measurement tools were compared in terms of accuracy, reliability, and time requirements. The mean result of thoracolumbar kyphosis measured by the PACS was 21.43 ± 12.96°, and the mean value measured by the smartphone was 21.03 ± 13.01°. A Bland–Altman plot for these two methods showed a mean difference of 0.4°, with the limits of agreement being -2.4° and 3.2°. One-way ANOVA showed no significant difference (F = 0.080, P = 0.999) among measurements by different observers and different methods. The intraclass correlation coefficients (ICCs) of the mean values of four repeated measurements of thoracolumbar kyphosis between these two methods were 0.997 (0.995–0.998), revealing that the two methods were highly correlated. The ICC results showed that the concordance between these two methods was very good for all measurements of thoracolumbar kyphosis, and the inter- and intra-observer reliability of the novel smartphone method were very good. The PACS method (36.95 ± 0.98 s) took significantly longer than the smartphone method (17.68 ± 0.97 s) when compared by an independent-samples t test (P = 0.000). This new method using the integrated inclinometer of a smartphone has satisfactory validity and reliability compared to the PACS method. Additionally, the new method took significantly less time than the PACS method. Measuring with a smartphone is more convenient than using a PACS, which is always rooted in a full-sized computer. In summary, this new method using the integrated inclinometer of a smartphone is rapid, convenient, accurate and reliable when measuring thoracolumbar kyphosis in osteoporotic vertebral compression fracture (OVCF) patients.
Clinical measures, radiomics, and genomics offer synergistic value in AI-based prediction of overall survival in patients with glioblastoma
Authors: Fathi Kazerooni Anahita , Saxena Sanjay , Toorens Erik , Tu Danni , Bashyam Vishnu , Akbari Hamed , Mamourian Elizabeth , Sako Chiharu , Koumenis Costas , Verginadis Ioannis , Verma Ragini , Shinohara Russell T. , Desai Arati S. , Lustig Robert A. , Brem Steven , Mohan Suyash , Bagley Stephen J. , Ganguly Tapan , O’Rourke Donald M. , Bakas Spyridon , Nasrallah MacLean P. , Davatzikos Christos
Published: May 2022

Multi-omic data, i.e., clinical measures, radiomic, and genetic data, capture multi-faceted tumor characteristics, contributing to a comprehensive patient risk assessment. Here, we investigate the additive value and independent reproducibility of integrated diagnostics in prediction of overall survival (OS) in isocitrate dehydrogenase (IDH)-wildtype GBM patients, by combining conventional and deep learning methods. Conventional radiomics and deep learning features were extracted from pre-operative multi-parametric MRI of 516 GBM patients. Support vector machine (SVM) classifiers were trained on the radiomic features in the discovery cohort (n = 404) to categorize patient groups of high-risk (OS < 6 months) vs all, and low-risk (OS ≥ 18 months) vs all. The trained radiomic model was independently tested in the replication cohort (n = 112) and a patient-wise survival prediction index was produced. Multivariate Cox-PH models were generated for the replication cohort, first based on clinical measures solely, and then by layering on radiomics and molecular information. Evaluation of the high-risk and low-risk classifiers in the discovery/replication cohorts revealed area under the ROC curves (AUCs) of 0.78 (95% CI 0.70–0.85)/0.75 (95% CI 0.64–0.79) and 0.75 (95% CI 0.65–0.84)/0.63 (95% CI 0.52–0.71), respectively. Cox-PH modeling showed a concordance index of 0.65 (95% CI 0.6–0.7) for clinical data improving to 0.75 (95% CI 0.72–0.79) for the combination of all omics. This study signifies the value of integrated diagnostics for improved prediction of OS in GBM.
The normal and fibrotic mouse lung classified by spatial proteomic analysis
Authors: Ciccimarra Roberta , Bolognesi Maddalena M. , Zoboli Matteo , Cattoretti Giorgio , Stellari Franco F. , Ravanetti Francesca
Published: May 2022

Single cell classification is elucidating homeostasis and pathology in tissues and whole organs. We applied in situ spatial proteomics by multiplex antibody staining to routinely processed mouse lung, healthy and during a fibrosis model. With a limited validated antibody panel (24) we classify the normal constituents (alveolar type I and II, bronchial epithelia, endothelial, muscular, stromal and hematopoietic cells) and by quantitative measurements, we show the progress of lung fibrosis over a 4 weeks course, the changing landscape and the cell-specific quantitative variation of a multidrug transporter. An early decline in AT2 alveolar cells and a progressive increase in stromal cells seems at the core of the fibrotic process.
No association between intravenous fluid volume and endothelial glycocalyx shedding in patients undergoing resuscitation for sepsis in the emergency department
Authors: Macdonald Stephen , Bosio Erika , Shapiro Nathan I. , Balmer Lois , Burrows Sally , Hibbs Moira , Jowitt Thomas , Smart Lisa , Arendts Glenn , Fatovich Daniel
Published: May 2022

Endothelial glycocalyx (EG) shedding is associated with septic shock and described following intravenous (IV) fluid administration. To investigate the possible impact of IV fluids on the pathobiology of septic shock we investigated associations between biomarkers of EG shedding and endothelial cell activation, and relationships with IV fluid volume. Serum samples were obtained on admission (T0) and at 24 h (T24) in patients undergoing haemodynamic resuscitation for suspected septic shock in the emergency department. Biomarkers of EG shedding—Syndecan-1 (Syn-1), Syndecan-4 (Syn-4), Hyaluronan, endothelial activation—Endothelin-1 (ET-1), Angiopoeitin-2 (Ang-2), Vascular Endothelial Growth Factor Receptor-1(VEGF-1) and leucocyte activation/inflammation—Resistin, Neutrophil Gelatinase Associated Lipocalin (NGAL) and a marker of cardiac stretch—Pro-Atrial Natriuretic Peptide (Pro-ANP) were compared to the total IV fluid volume administered using Tobit regression. Data on 86 patients (52 male) with a mean age of 60 (SD 18) years were included. The mean fluid volume administered to T24 was 4038 ml (SD 2507 ml). No significant association between fluid volume and Pro-ANP or any of the biomarkers were observed. Syn-1 and Syn-4 were significantly correlated with each other (Spearman Rho 0.43, p < 0.001) but not with Hyaluronan. Syn-1 and Syn-4 both correlated with VEGFR-1 (Rho 0.56 and 0.57 respectively, p < 0.001) whereas Hyaluronan correlated with ET-1 (Rho 0.43, p < 0.001) and Ang-2 (Rho 0.43, p < 0.001). There was no correlation between Pro-ANP and any of the EG biomarkers. Distinct patterns of association between biomarkers of EG shedding and endothelial cell activation were observed among patients undergoing resuscitation for sepsis. No relationship between IV fluid volume and Pro-ANP or any of the other biomarkers was observed.
Effect of rock loading rate based on crack extension and propagation
Authors: Yang Mengze , Huang Houxu , Yang Yu
Published: May 2022

When subjected to constant static load, after a period of damage accumulation and crack development, the rock will fail under a load lower than its compressive strength. The transform of loading rate may have a certain influence on the mechanical properties of rock. In order to investigate the effect of loading rate on mechanical properties of red sandstone, the propagation form of internal cracks in the subcritical propagation stage in rock under static loading is defined as tensile. Based on Maxwell model, the expression of effective tensile stress for crack extension in rock is deduced, which explains the phenomenon of rock tensile failure. Based on the uniaxial compression test of red sandstone under different loading rates, and the surface deformation field of specimens is analysed with the method of digital image correlation, and the corresponding relationship between the loading rate effect and the change of mechanical properties as well as the energy accumulation and release characteristics is analysed, the phenomenon of rock tensile failure is further verified. This research can be effectively applied to geotechnical engineering disaster warning.
Prognosis of patients with acute respiratory failure due to the SARS-CoV-2 501Y.V2 variant: a multicenter retrospective matched cohort study
Authors: Puech Bérénice , Legrand Antoine , Simon Olivier , Combe Chloé , Jaffar-Bandjee Marie-Christine , Caron Margot , Vidal Charles , Mavingui Patrick , Blonde Renaud , Boue Yvonnick , Berguigua Hamza , Allyn Jérôme , Bruneau Léa , Ferdynus Cyril , Allou Nicolas
Published: May 2022

The aim of this study was to compare the prognosis of patients with acute respiratory failure (ARF) due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant 501Y.V2 to that of patients with ARF due to the original strain. This retrospective matched cohort study included all consecutive patients who were hospitalized for ARF due to SARS-CoV-2 in Reunion Island University Hospital between March 2020 and March 2021. Twenty-eight in hospital mortality was evaluated before and after matching. A total of 218 patients with ARF due to SARS-CoV-2 were enrolled in the study. Of these, 83 (38.1%) were infected with the 501Y.V2 variant. During intensive care unit stay, 104 (47.7%) patients received invasive mechanical ventilation and 20 (9.2%) patients were supported by venovenous extracorporeal membrane oxygenation. Patients infected with the 501Y.V2 variant were younger (58 [51–68] vs. 67 [56–74] years old, P = 0.003), had less hypertension (54.2% vs 68.1%, P = 0.04), and had less chronic kidney disease (13.3% vs. 31.9%, P = 0.002) than patients infected with the original strain. After controlling for confounding variables (62 matched patients in each group), 28-day mortality was higher in the group of patients infected with the 501Y.V2 variant (30.6%) than in the group of patients infected with the original strain (19.4%, P = 0.04). In Reunion Island, where SARS-CoV-2 incidence remained low until February 2021 and the health care system was never saturated, mortality was higher in patients with ARF infected with the 501Y.V2 variant than in patients infected with the original strain.
Identification of gene signatures for COAD using feature selection and Bayesian network approaches
Authors: Wang Yangyang , Gao Xiaoguang , Ru Xinxin , Sun Pengzhan , Wang Jihan
Published: May 2022

The combination of TCGA and GTEx databases will provide more comprehensive information for characterizing the human genome in health and disease, especially for underlying the cancer genetic alterations. Here we analyzed the gene expression profile of COAD in both tumor samples from TCGA and normal colon tissues from GTEx. Using the SNR-PPFS feature selection algorithms, we discovered a 38 gene signatures that performed well in distinguishing COAD tumors from normal samples. Bayesian network of the 38 genes revealed that DEGs with similar expression patterns or functions interacted more closely. We identified 14 up-DEGs that were significantly correlated with tumor stages. Cox regression analysis demonstrated that tumor stage, STMN4 and FAM135B dysregulation were independent prognostic factors for COAD survival outcomes. Overall, this study indicates that using feature selection approaches to select key gene signatures from high-dimensional datasets can be an effective way for studying cancer genomic characteristics.
In vivo multi spectral colonoscopy in mice
Authors: Hohmann Martin , Ganzleben Ingo , Grünberg Alexander , Gonzales-Menezes Jean , Klämpfl Florian , Lengenfelder Benjamin , Liebing Eva , Heichler Christina , Neufert Clemens , Becker Christoph , Neurath Markus F. , Waldner Maximilian J. , Schmidt Michael
Published: May 2022

Multi- and hyperspectral endoscopy are possibilities to improve the endoscopic detection of neoplastic lesions in the colon and rectum during colonoscopy. However, most studies in this context are performed on histological samples/biopsies or ex vivo. This leads to the question if previous results can be transferred to an in vivo setting. Therefore, the current study evaluated the usefulness of multispectral endoscopy in identifying neoplastic lesions in the colon. The data set consists of 25 mice with colonic neoplastic lesions and the data analysis is performed by machine learning. Another question addressed was whether adding additional spatial features based on Gauss–Laguerre polynomials leads to an improved detection rate. As a result, detection of neoplastic lesions was achieved with an MCC of 0.47. Therefore, the classification accuracy of multispectral colonoscopy is comparable with hyperspectral colonoscopy in the same spectral range when additional spatial features are used. Moreover, this paper strongly supports the current path towards the application of multi/hyperspectral endoscopy in clinical settings and shows that the challenges from transferring results from ex vivo to in vivo endoscopy can be solved.
Comprehensive analysis of 65 patients with Castleman disease in a single center in China
Authors: Wang Xi-Qian , Zhong Nian-Nian , Sun Qi , Yan Si-Chen , Xu Guang-Cai , Wang Yong-Gong , Peng Li-Wei , Liu Bing , Bu Lin-Lin
Published: May 2022

This study aimed to investigate the epidemiologic, clinical, pathological characteristics, and treatment of patients with Castleman disease (CD) in a single center in China. We retrospectively analyzed the data of 65 Chinese CD patients, divided into unicentric CD (UCD) and multicentric CD (MCD) groups, and also microscopic subtypes as hypervascular (HV), plasmacytic (PC) and Mixed. Based on whether HHV-8 infection existed, MCD was subdivided into HHV-8-associated MCD and idiopathic Castleman disease (iMCD). Detailed epidemiologic, clinicopathological, and treatment data were analyzed and discussed. Of total 65 patients (UCD 33, MCD 32), HV (81.8%) accounted for the most of UCD and total. More females in UCD (60.6%) and more males in MCD (65.6%) were observed. CD occurred in all age groups, most commonly in 40–49 years. The mean age of onset of total was 38.5 years with PC higher than HV (45.5 vs. 35.1 years, P = 0.0413). The median diagnosis delay of MCD was longer than that of UCD (3.00 vs. 1.25 months, P = 0.0436). Abdomen (39.4%) and neck (30.3%) were the most-seen locations of lymphadenopathy in UCD, with neck (65.6%) being predominant in MCD. Mean major diameter of specimens of UCD was greater than MCD (6.4 vs. 3.1 cm, P < 0.0001). These results provided the featured and detailed profile of Castleman disease in Henan province in China with a considerable number of cases, which presented distinct evidence with other studies.
Kinetics and stoichiometry of gallic acid and methyl gallate in scavenging DPPH radical as affected by the reaction solvent
Authors: Shojaee Marzieh Sadat , Moeenfard Marzieh , Farhoosh Reza
Published: May 2022

The activity and capacity of gallic acid (GA) and methyl gallate (MG) in scavenging DPPH· were determined in different solvents. Based on the bimolecular rate constants k2, both antioxidants showed highest activities in EtOH, followed by in MeOH, t-BuOH, MeCN, 2-PrOH, acetone, THF, ethyl acetate, and 1,4-dioxane. GA indicated better activities (k2 value, M−1 s−1) than MG in the alcoholic solvents (51–1939 vs. 25–1530) and in MeCN (203 vs. 187) whereas MG was of higher activities in the polar aprotic solvents (1.7–41 vs. 1.6–13). The highest stoichiometries for GA vs. MG were in 2-PrOH (6.67 vs. 5.37), followed by EtOH (5.84 vs. 4.57), MeOH (5.34 vs. 3.8) ~ acetone (5.02 vs. 4.44), MeCN (3.68 vs. 3.05) ~ t-BuOH (3.14 vs. 2.99), THF (2.34 vs. 2.2), ethyl acetate (1.2 vs. 0.93), and 1,4-dioxane (0.34 vs. 0.35).
Antibody response and seroprevalence in healthcare workers after the BNT162b2 vaccination in a University Hospital at Tokyo
Authors: Igawa Gene , Ai Tomohiko , Yamamoto Takamasa , Ito Kanami , Nojiri Shuko , Saito Kaori , Wakita Mitsuru , Fukuda Hiroshi , Hori Satoshi , Misawa Shigeki , Miida Takashi , Seyama Kuniaki , Takahashi Kazuhisa , Tabe Yoko , Naito Toshio
Published: May 2022

In 2020, we reported a low seroprevalence of N-specific antibodies in 4147 health care workers (HCWs) at a frontline hospital in Tokyo, Japan. In Japan, a vaccine campaign was launched in early 2021. We re-evaluated seroprevalences of N- and S-specific antibodies in 2202 HCWs who took two doses of the BNT162b2 vaccine. In 2021, N-specific seroprevalence remains as low as 1.59%. The seroprevalences were comparable among all HCWs regardless of exposure levels. Almost all of the HCWs elicited S-specific antibodies after vaccination. However, the HCWs who had COVID-19 elicited higher S-specific antibody titers than those who did not have COVID-19. In the HCWs without a history of COVID-19, 1.1% (23 out of 2185) were seropositive with N-specific antibodies, indicating the existence of asymptomatic infections. Also, S-specific antibody titers were higher in females and younger HCWs, and in those who had severe side effects. However, S-specific antibody titers were lower depending on the number of days after the second dose of vaccination specifically in elderly individuals. In conclusion, this study indicates N-specific seroprevalence remains low in HCWs at a frontline hospital in Tokyo. The mRNA vaccine elicited S-specific antibody in HCWs, however, the titers decreased as the days proceeded.
Acinetobacter baumannii response to cefiderocol challenge in human urine
Authors: Nishimura Brent , Escalante Jenny , Tuttobene Marisel R. , Subils Tomás , Mezcord Vyanka , Pimentel Camila , Georgeos Nardin , Pasteran Fernando , Rodriguez Cecilia , Sieira Rodrigo , Actis Luis A. , Tolmasky Marcelo E. , Bonomo Robert A. , Ramirez María Soledad
Published: May 2022

Cefiderocol (CFDC) is a novel chlorocatechol-substituted siderophore antibiotic approved to treat complicated urinary tract infections (cUTI) and hospital-acquired and ventilator-acquired pneumonia (HAP/VAP). Previous work determined that albumin-rich human fluids increase the minimum inhibitory concentration (MICs) of Acinetobacter baumannii against CFDC and reduce the expression of genes related to iron uptake systems. This latter effect may contribute to the need for higher concentrations of CFDC to inhibit growth. The presence of human urine (HU), which contains low albumin concentrations, did not modify MIC values of two carbapenem-resistant A. baumannii. Levels of resistance to CFDC were not modified by HU in strain AMA40 but were reduced in strain AB5075. Expanding the studies to other carbapenem-resistant A. baumannii isolates showed that the presence of HU resulted in unmodified or reduced MIC of CDFC values. The expression of piuA, pirA, bauA, and bfnH determined by qRT-PCR was enhanced in A. baumannii AMA40 and AB5075 by the presence of HU in the culture medium. All four tested genes code for functions related to recognition and transport of ferric-siderophore complexes. The effect of HU on expression of pbp1, pbp3, blaOXA-51-like, blaADC, and blaNDM-1, genes associated with resistance to β-lactams, as well as genes coding for efflux pumps and porins was variable, showing dependence with the strain analyzed. We conclude that the lack of significant concentrations of albumin and free iron in HU makes this fluid behave differently from others we tested. Unlike other albumin rich fluids, the presence of HU does not impact the antibacterial activity of CFDC when tested against A. baumannii.
Advances in physicochemical characterization of lead-free hybrid perovskite [NH3(CH2)3NH3]CuBr4 crystals
Authors: Lim Ae Ran , Kwac Lee Ku
Published: May 2022

To support the development of eco-friendly hybrid perovskite solar cells, structural, thermal, and physical properties of the lead-free hybrid perovskite [NH3(CH2)3NH3]CuBr4 were investigated using X-ray diffraction (XRD), differential scanning calorimetry, thermogravimetric analysis, and nuclear magnetic resonance spectroscopy. The crystal structure confirmed by XRD was monoclinic, and thermodynamic stability was observed at approximately 500 K without any phase transition. The large changes in the 1H chemical shifts of NH3 and those in C2 close to N are affected by N–H∙∙∙Br hydrogen bonds because the structural geometry of CuBr4 changed significantly. The 1H and 13C spin–lattice relaxation times (T1ρ) showed very similar molecular motions according to the Bloembergen–Purcell–Pound theory at low temperatures; however, the 1H T1ρ values representing energy transfer were about 10 times lesser than those of 13C T1ρ. Finally, the 1H and 13C T1ρ values of [NH3(CH2)3NH3]MeBr4 (Me = Cu, Zn, and Cd) were compared with those reported previously. 1H T1ρ was affected by the paramagnetic ion of the anion, while 13C T1ρ was affected by the MeBr4 structure of the anion; 13C T1ρ values in Me = Cu and Cd with the octahedral MeBr6 structure had longer values than those in Me = Zn with the tetrahedral MeBr4 structure. We believe that these detailed insights on the physical properties will play a crucial role in the development of eco-friendly hybrid perovskite solar cells.
Paleoclimate-induced stress on polar forested ecosystems prior to the Permian–Triassic mass extinction
Authors: Gulbranson Erik L. , Mellum Morgan M. , Corti Valentina , Dahlseid Aidan , Atkinson Brian A. , Ryberg Patricia E. , Cornamusini Gianluca
Published: May 2022

The end-Permian extinction (EPE) has been considered to be contemporaneous on land and in the oceans. However, re-examined floristic records and new radiometric ages from Gondwana indicate a nuanced terrestrial ecosystem response to EPE global change. Paleosol geochemistry and climate simulations indicate paleoclimate change likely caused the demise of the widespread glossopterid ecosystems in Gondwana. Here, we evaluate the climate response of plants to the EPE via dendrochronology snapshots to produce annual-resolution records of tree-ring growth for a succession of late Permian and early Middle Triassic fossil forests from Antarctica. Paleosol geochemistry indicates a shift in paleoclimate towards more humid conditions in the Early and early Middle Triassic relative to the late Permian. Paleosol morphology, however, supports inferences of a lack of forested ecosystems in the Early Triassic. The plant responses to this paleoclimate change were accompanied by enhanced stress during the latest Permian as determined by high-resolution paleoclimate analysis of wood growth intervals. These results suggest that paleoclimate change during the late Permian exerted significant stress on high-latitude forests, consistent with the hypothesis that climate change was likely the primary driver of the extinction of the glossopterid ecosystems.
Continuous phenotypic modulation explains male horn allometry in three dung beetle species
Authors: Laini Alex , Roggero Angela , Palestrini Claudia , Rolando Antonio
Published: May 2022

Many dung beetle species show male horn polyphenism, the ability of males to develop into distinct phenotypes without intermediate forms as a response to the larval growth environment. While males with long (majors) and rudimentary (minor) horn have been widely reported in literature, little is known about the existence of individuals with intermediate horn length. Here we investigate the occurrence of intermediates in natural populations of three dung beetle species (Onthophagus furcatus, Copris lunaris and C. hispanus). We analysed the body size-horn length relationship using linear, exponential, and sigmoidal models with different error structures. We inferred the number of individuals in the minor, intermediate, and major groups by combining changepoint analysis and simulation from fitted allometric models. The sigmoidal equation was a better descriptor of the body size-horn length relationship than linear or exponential equations in all the three studied species. Our results indicated that the number of intermediates equals or exceeds the number of minor and major males. This work provides evidence that, at least in the studied species, males with intermediate horn length exist in natural populations. For similar cases we therefore suggest that continuous phenotypic modulation rather than discrete polyphenism can explain variation in male horn allometry.