bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased mortality and increased side effects in COVID-19 patients treated with IL-6 receptor antagonists: systematic review and meta-analysis
Authors: Malgie Jishnu , Schoones Jan W. , Zeegers Maurice P. , Pijls Bart G. 
Published: November 2021

AbstractThere is controversy whether IL-6 (receptor) antagonists are beneficial in treating COVID-19 patients. We therefore update our systematic review to answer the following research questions: (1) Do patients hospitalized for COVID-19 treated with IL-6 (receptor) antagonists have lower mortality compared to standard of care? (2) Do patients hospitalized for COVID-19 treated with IL-6 (receptor) antagonists have more side effects compared to standard of care? The following databases were search up to December 1st 2020: PubMed, PMC PubMed Central, MEDLINE, WHO COVID-19 Database, Embase, Web-of-Science, COCHRANE LIBRARY, Emcare and Academic Search Premier. In order to pool the risk ratio (RR) and risk difference of individual studies we used random effects meta-analysis. The search strategy retrieved 2975 unique titles of which 71 studies (9 RCTs and 62 observational) studies comprising 29,495 patients were included. Mortality (RR 0.75) and mechanical ventilation (RR 0.78) were lower and the risk of neutropenia (RR 7.3), impaired liver function (RR 1.67) and secondary infections (RR 1.26) were higher for patients treated with IL-6 (receptor) antagonists compared to patients not treated with treated with IL-6 (receptor) antagonists. Our results showed that IL-6 (receptor) antagonists are effective in reducing mortality in COVID-19 patients, while the risk of side effects was higher. The baseline risk of mortality was an important effect modifier: IL-6 (receptor) antagonists were effective when the baseline mortality risk was high (e.g. ICU setting), while they could be harmful when the baseline mortality risk was low.
A unique amphiphilic triblock copolymer, nontoxic to human blood and potential supramolecular drug delivery system for dexamethasone
Authors: Mushtaq Irrum , Akhter Zareen , Farooq Muhammad , Jabeen Farukh , Rehman Ashfaq Ur , Rehman Sadia , Ayub Sidra , Mirza Bushra , Siddiq Muhammad , Zaman Farasat 
Published: November 2021

AbstractThe drug delivery system (DDS) often causes toxicity, triggering undesired cellular injuries. Thus, developing supramolecules used as DDS with tunable self-assembly and nontoxic behavior is highly desired. To address this, we aimed to develop a tunable amphiphilic ABA-type triblock copolymer that is nontoxic to human blood cells but also capable of self-assembling, binding and releasing the clinically used drug dexamethasone. We synthesized an ABA-type amphiphilic triblock copolymer (P2L) by incorporating tetra(aniline) TANI as a hydrophobic and redox active segment along with monomethoxy end-capped polyethylene glycol (mPEG2k; Mw = 2000 g mol−1) as biocompatible, flexible and hydrophilic part. Cell cytotoxicity was measured in whole human blood in vitro and lung cancer cells. Polymer-drug interactions were investigated by UV–Vis spectroscopy and computational analysis. Our synthesized copolymer P2L exhibited tuned self-assembly behavior with and without external stimuli and showed no toxicity in human blood samples. Computational analysis showed that P2L can encapsulate the clinically used drug dexamethasone and that drug uptake or release can also be triggered under oxidation or low pH conditions. In conclusion, copolymer P2L is nontoxic to human blood cells with the potential to carry and release anticancer/anti-inflammatory drug dexamethasone. These findings may open up further investigations into implantable drug delivery systems/devices with precise drug administration and controlled release at specific locations.
Hierarchical climate-driven dynamics of the active channel length in temporary streams
Authors: Botter Gianluca , Vingiani Filippo , Senatore Alfonso , Jensen Carrie , Weiler Markus , McGuire Kevin , Mendicino Giuseppe , Durighetto Nicola 
Published: November 2021

AbstractLooking across a landscape, river networks appear deceptively static. However, flowing streams expand and contract following ever-changing hydrological conditions of the surrounding environment. Despite the ecological and biogeochemical value of rivers with discontinuous flow, deciphering the temporary nature of streams and quantifying their extent remains challenging. Using a unique observational dataset spanning diverse geomorphoclimatic settings, we demonstrate the existence of a general hierarchical structuring of river network dynamics. Specifically, temporary stream activation follows a fixed and repeatable sequence, in which the least persistent sections activate only when the most persistent ones are already flowing. This hierarchical phenomenon not only facilitates monitoring activities, but enables the development of a general mathematical framework that elucidates how climate drives temporal variations in the active stream length. As the climate gets drier, the average fraction of the flowing network decreases while its relative variability increases. Our study provides a novel conceptual basis for characterizing temporary streams and quantifying their ecological and biogeochemical impacts.
Prognostic value of neutrophil-to-lymphocyte ratio in COVID-19 compared with Influenza and respiratory syncytial virus infection
Authors: Prozan Lior , Shusterman Eden , Ablin Jacob , Mitelpunkt Alexis , Weiss-Meilik Ahuva , Adler Amos , Choshen Guy , Kehat Orli 
Published: November 2021

AbstractA high neutrophil to lymphocyte ratio (NLR) is considered an unfavorable prognostic factor in various diseases, including COVID-19. The prognostic value of NLR in other respiratory viral infections, such as Influenza, has not hitherto been extensively studied. We aimed to compare the prognostic value of NLR in COVID-19, Influenza and Respiratory Syncytial Virus infection (RSV). A retrospective cohort of COVID-19, Influenza and RSV patients admitted to the Tel Aviv Medical Center from January 2010 to October 2020 was analyzed. Laboratory, demographic, and clinical parameters were collected. Two way analyses of variance (ANOVA) was used to compare the association between NLR values and poor outcomes among the three groups. ROC curve analyses for each virus was applied to test the discrimination ability of NLR. 722 COVID-19, 2213 influenza and 482 RSV patients were included. Above the age of 50, NLR at admission was significantly lower among COVID-19 patients (P < 0.001). NLR was associated with poor clinical outcome only in the COVID-19 group. ROC curve analysis was performed; the area under curve of poor outcomes for COVID-19 was 0.68, compared with 0.57 and 0.58 for Influenza and RSV respectively. In the COVID-19 group, multivariate logistic regression identified a high NLR (defined as a value above 6.82) to be a prognostic factor for poor clinical outcome, after adjusting for age, sex and Charlson comorbidity score (odds ratio of 2.9, P < 0.001). NLR at admission is lower and has more prognostic value in COVID-19 patients, when compared to Influenza and RSV.
Large voltage-induced coercivity change in Pt/Co/CoO/amorphous TiOx structure and heavy metal insertion effect
Authors: Nozaki Tomohiro , Tamaru Shingo , Konoto Makoto , Nozaki Takayuki , Kubota Hitoshi , Fukushima Akio , Yuasa Shinji 
Published: November 2021

AbstractThere is urgent need for spintronics materials exhibiting a large voltage modulation effect to fulfill the great demand for high-speed, low-power-consumption information processing systems. Fcc-Co (111)-based systems are a promising option for research on the voltage effect, on account of their large perpendicular magnetic anisotropy (PMA) and high degree of freedom in structure. Aiming to observe a large voltage effect in a fcc-Co (111)-based system at room temperature, we investigated the voltage-induced coercivity (Hc) change of perpendicularly magnetized Pt/heavy metal/Co/CoO/amorphous TiOx structures. The thin CoO layer in the structure was the result of the surface oxidation of Co. We observed a large voltage-induced Hc change of 20.2 mT by applying 2 V (0.32 V/nm) to a sample without heavy metal insertion, and an Hc change of 15.4 mT by applying 1.8 V (0.29 V/nm) to an Ir-inserted sample. The relative thick Co thickness, Co surface oxidation, and large dielectric constant of TiOx layer could be related to the large voltage-induced Hc change. Furthermore, we demonstrated the separate adjustment of Hc and a voltage-induced Hc change by utilizing both upper and lower interfaces of Co.
Indirect impact of Covid-19 on hospital care pathways in Italy
Authors: Spadea Teresa , Di Girolamo Chiara , Landriscina Tania , Leoni Olivia , Forni Silvia , Colais Paola , Fanizza Caterina , Allotta Alessandra , Onorati Roberta , Gnavi Roberto ,   the Mimico-19 working group, Spadea Teresa , Gnavi Roberto , Landriscina Tania , Onorati Roberta , Migliardi Alessandro , Costa Giuseppe , Leoni Olivia , Ercolanoni Michele , Di Girolamo Chiara , Berti Elena , Caranci Nicola , Moro Maria Luisa , Forni Silvia , Di Fabrizio Valeria , D’Arienzo Sara , Gemmi Fabrizio , Colais Paola , Pinnarelli Luigi , D’Ovidio Mariangela , Balducci Maria , Davoli Marina , Fanizza Caterina , Petrarolo Vito , Piepoli Giulia , Bisceglia Lucia , Allotta Alessandra , Cernigliaro Achille , Scondotto Salvatore 
Published: November 2021

AbstractEarlier in 2020, seven Italian regions, which cover 62% of the Italian population, set up the Mimico-19 network to monitor the side effects of the restrictive measures against Covid-19 on volumes and quality of care. To this aim, we retrospectively analysed hospital discharges data, computing twelve indicators of volume and performance in three clinical areas: cardiology, oncology, and orthopaedics. Weekly indicators for the period January–July 2020 were compared with the corresponding average for 2018–2019; comparisons were performed within 3 sub-periods: pre-lockdown, lockdown, and post-lockdown. The weekly trend of hospitalisations for ST-segment elevation myocardial infarction (STEMI) showed a 40% reduction, but the proportion of STEMI patients with a primary PTCA did not significantly change from previous years. Malignant neoplasms surgery volumes differed substantially by site, with a limited reduction for lung cancer (< 20%) and greater declines (30–40%) for breast and prostate cancers. The percentage of timely surgery for femoral neck in the elderly remained constantly higher than the previous 2 years whereas hip and knee replacements fell dramatically. Hospitalisations have generally decreased, but the capacity of a timely and effective response in time-dependent pathways of care was not jeopardized throughout the period. General trends did not show important differences across regions, regardless of the different burden of Covid-19. Preventive and primary care services should adopt a pro-active approach, moving towards the identification of at-risk conditions that were neglected during the pandemic and timely addressing patients to the secondary care system.
Self-powered bifunctional sensor based on tribotronic planar graphene transistors
Authors: Meng Yanfang , Gao Guoyun , Zhu Jiaxue 
Published: November 2021

AbstractWith the development of material science, micro-nano-fabrication and microelectronics, the higher level requirements are posed on the electronic skins (E-skin). The lower energy consumption and multiple functions are the imperative requirements to spurred scientists and mechanists to make joint efforts to meet. To achieve lower energy consumption, a promising energy-harvesting style of triboelectric nanogenerators (TENG) is incorporated into the field effect transistors (FETs) to play the important role for sensor. For bifunctional sensor, to harness the difficult for reflecting the magnitude of frequency, we resorted to synaptic transistors to achieve more intelligentization. Furthermore, with regards to the configuration of FET, we continued previous work: using the electrolyte gate dielectrics of FET—ion gel as the electrification layer to achieve high efficient, compact and extensively adoption for mechanosensation. The working principle of the GFET was based on the coupling effects of the FET and the TENG. This newly emerged self-powered sensor would offer a new platform for lower power consumption sensor for human–machine interface and intelligent robot.
Short high fat diet triggers reversible and region specific effects in DCX+ hippocampal immature neurons of adolescent male mice
Authors: Chiazza Fausto , Bondi Heather , Masante Irene , Ugazio Federico , Bortolotto Valeria , Canonico Pier Luigi , Grilli Mariagrazia 
Published: November 2021

AbstractAdolescence represents a crucial period for maturation of brain structures involved in cognition. Early in life unhealthy dietary patterns are associated with inferior cognitive outcomes at later ages; conversely, healthy diet is associated with better cognitive results. In this study we analyzed the effects of a short period of hypercaloric diet on newborn hippocampal doublecortin+ (DCX) immature neurons in adolescent mice. Male mice received high fat diet (HFD) or control low fat diet (LFD) from the 5th week of age for 1 or 2 weeks, or 1 week HFD followed by 1 week LFD. After diet supply, mice were either perfused for immunohistochemical (IHC) analysis or their hippocampi were dissected for biochemical assays. Detailed morphometric analysis was performed in DCX+ cells that displayed features of immature neurons. We report that 1 week-HFD was sufficient to dramatically reduce dendritic tree complexity of DCX+ cells. This effect occurred specifically in dorsal and not ventral hippocampus and correlated with reduced BDNF expression levels in dorsal hippocampus. Both structural and biochemical changes were reversed by a return to LFD. Altogether these studies increase our current knowledge on potential consequences of hypercaloric diet on brain and in particular on dorsal hippocampal neuroplasticity.
Optimizing and evaluating PCR-based pooled screening during COVID-19 pandemics
Authors: Yu Jiali , Huang Yiduo , Shen Zuo-Jun 
Published: November 2021

AbstractPopulation screening played a substantial role in safely reopening the economy and avoiding new outbreaks of COVID-19. PCR-based pooled screening makes it possible to test the population with limited resources by pooling multiple individual samples. Our study compared different population-wide screening methods as transmission-mitigating interventions, including pooled PCR, individual PCR, and antigen screening. Incorporating testing-isolation process and individual-level viral load trajectories into an epidemic model, we further studied the impacts of testing-isolation on test sensitivities. Results show that the testing-isolation process could maintain a stable test sensitivity during the outbreak by removing most infected individuals, especially during the epidemic decline. Moreover, we compared the efficiency, accuracy, and cost of different screening methods during the pandemic. Our results show that PCR-based pooled screening is cost-effective in reversing the pandemic at low prevalence. When the prevalence is high, PCR-based pooled screening may not stop the outbreak. In contrast, antigen screening with sufficient frequency could reverse the epidemic, despite the high cost and the large numbers of false positives in the screening process.
Anticancer properties of dried-pericarp water extracts of Camellia japonica L. fermented with Aspergillus oryzae through regulation of IGFBP-2/mTOR pathway
Authors: Cho Eugene , Kim Jin , Jeong Da Hye , Kim Hyoun Woo 
Published: November 2021

AbstractThis study aimed to investigate the anticancer activity of dried-pericarp water extract offermented C. japonicus(CJ). The dried-pericarp water extracts of CJ were fermented usingAspergillus oryzaeandSaccharomyces cerevisiaeat 30 °C and 35 °C. The anticancer activities of both water extracts fermented at 30 °C and 35 °C usingA. oryzaeagainst FaDu cells were remarkably changed compared with unfermented dried-pericarp water extract of CJ, which has no anticancer activity. Cleaved-PARP, caspase 3, and apoptotic cells stained with annexin V/PI were significantly increased by treatment withA. oryzaeextracts fermented at 30 °C. The insulin-like growth factor-binding protein 2 (IGFBP-2) protein level and mTOR phosphorylation byA. oryzaefermented extracts (AOFE) were dramatically reduced, and the expression levels of IGFBP-2 and phosphorylated mTOR were significantly increased depending on the glucose concentrations in FaDu cells. These results suggested that the cell viabilities in AOFE were restored as the glucose concentrations increased. Furthermore, it was confirmed LC/MS/MS that the content of gallic acid was increased by fermentation ofAspergillus oryzae(5.596 ± 0.1746 μg/mg) compared to the unfermented extract (1.620 ± 0.0432 μg/mg). Based on these results, the anticancer effect of AOFE was achieved through inhibition of the IGFBP-2/mTOR signaling pathway. These results suggest that AOFE may be a potential treatment for head and neck cancer.
A molecular structure-informed viscoelastic constitutive model for natural rubber materials
Authors: Jung Jiwon , Park Chanwook , Ryu Myung Shin , Yun Gun Jin 
Published: October 2021

Abstract
This paper presents a molecular structure-informed viscoelastic constitutive equation that adopts the Doi–Edward’s tube model with coarse-grained molecular dynamics simulation and primitive path analysis. Since this model contains polymer physics-related parameters directly obtained from molecular simulations, it can reflect molecular information in predictions of the viscoelastic behavior of elastomers, unlike other empirical models. The proposed incremental formulations and constitutive stiffness matrix were implemented into implicit finite element analysis codes as a user-supplied material model and viscoelastic properties (storage, loss modulus, and

tan
δ

) were calculated from the constitutive equation. While obtaining polymer dynamics parameter of the molecular system, a relationship between self-diffusivity coefficient (

D

c

) and the polymerization degree of the polymer was confirmed. Furthermore, a series of parametric studies showed that increase of the primitive path length (L) and decrease of

D

c

have led to the strengthening of moduli and decrease of

tan
δ

peak. Moreover, under the same condition, the shift of

tan
δ

peak to low-frequency domain was observed, which implies a decline in free volume in the molecular system and an increase in the glass transition temperature.
Development of an integrated structural biology platform specialized for sub-100 kDa protein complexes to support biologics discovery and rational engineering
Authors: Iozzo Yuri , Svidritskiy Egor , Qiu Yu , Xu Albert , Park Anna , Wendt Maria , Zhou Yanfeng 
Published: October 2021

Abstract

Background
Developing a biologic medicine requires successful decision making during selection and optimization in addition to the pool of candidates at early research stages. Knowing structural information and binding patterns between drug target and discovery candidates greatly increases the probability of success.

Methods
With the cryo-EM resolution revolution and rapid development of computational software, we have evaluated and integrated various tools in structural biology and the computation field and established a highly cost-effective platform which allows us to obtain fast and accurate structural information for nearly all our biologics projects with a close to 100% success rate and as fast as weeks turn-around time.

Results
Here we report four case studies selected from 38 different protein structures and share how we integrate cryo-EM structure determination, computational structure modeling, and molecular dynamics simulation. With proper decision making and strategic planning, the platform allows us to obtain quality results within days to weeks, including sub-100 kDa complexes which are usually considered a challenge due to their small size.

Conclusions
Our utilization of this differential approach and multiple software packages allows us to manage priorities and resources to achieve goals quickly and efficiently. We demonstrate how to effectively overcome particle orientation bias by altering complex composition. In several of our examples, we use glycan density to facilitate interpretation of low-resolution 3D reconstruction and epitope mapping. Protein information plays an important role in our cryo-EM projects, especially in cases where we see significant challenges in obtaining high-resolution 3D maps.
Heavy Chain Disease Reviewed on MALDI-TOF
Authors: Ewaisha Radwa , Dispenzieri Angela , Willrich Maria , Kohlhagen Mindy , Murray David 
Published: October 2021

Abstract
Heavy Chain Disease (HCD) is a group of rare B-cell proliferative disorders. Diagnosis depends on the detection of a truncated heavy chain with no associated light chain, often done by serum or urine immunofixation. This approach has been reported to have low specificity, since associated light chain bands are sometimes not visible and heavy chain bands can be mistaken for polyclonal bands. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) offers improved sensitivity in detecting monoclonal immunoglobulins. Truncation is thought to happen in the constant heavy chain (CH1) region, detected as a fragment of mass 27,000 Da on MALDI-TOF. Other mass patterns have not been reported in the literature. In this study, frozen serum samples from 8 heavy chain disease patients were analyzed by MALDI-TOF mass spectrometry. Spectra were reviewed on Mass-Fix software and visually inspected for monoclonal peaks. We detected two types of patterns for the IgG heavy chain disease. One pattern shows an IgG heavy chain with truncated mass (27,000 Da vs. 50,000 Da) and another in which the mass of the IgG heavy chain is greater than normal (65,000 Da). Follow-up work demonstrates that these are most likely dimers of truncated heavy chains. Thus, mass spectrometry-based immunofixation can provide new insights into heavy chain disease biology, mechanism, and progression, which are not identified by traditional diagnostic methods.
Weak Precipitin Ring from A Fecal Specimen with Markedly Elevated Alpha-1 Antitrypsin Level Measured by Radial Immunodiffusion
Authors: Xiao Yi , Leung Edward 
Published: October 2021

Abstract
Radial immunodiffusion (RID) is a classic methodology for antigen quantification that relies on the development of a distinct precipitin ring from precipitated antigen-antibody complex. As the precipitin ring grows, the precipitate at the inner edge of the ring constantly dissolves due to excess antigen flooding from the point of application, while new precipitate forms at the leading edge of the ring. RID plates with anti-human alpha-1-antitrypsin are prepared in our lab to measure fecal alpha-1 antitrypsin (A1AT) to aid in the diagnosis and monitoring of Protein Losing Enteropathy (PLE). The procedure has routinely produced precipitin rings with small radii and distinct edges after incubating at room temperature for 48 hours. Unexpectedly, a fecal specimen from a patient produced an extremely weak and large precipitin ring that could have been easily overlooked. Dilution studies confirmed a highly elevated A1AT level of 67 mg/g dry stool. The very weak and large precipitin ring was reproduced with a spiked specimen with similar A1AT concentration and kept expanding for several days until a distinct ring was formed eventually. Our data highlights a rare example of high-dose hook effect in RID and calls for meticulous attention and caution when reading and interpreting gel-based immunoassays with unexpected markedly elevated results to avoid additional confirmatory testing. In these cases, we recommend repeat testing with diluted specimens.