bluuebunny/crossref_metadata_2025_split huggingface dataset:
The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern
Authors: Abdelnabi Rana , Foo Caroline S. , Jochmans Dirk , Vangeel Laura , De Jonghe Steven , Augustijns Patrick , Mols Raf , Weynand Birgit , Wattanakul Thanaporn , Hoglund Richard M. , Tarning Joel , Mowbray Charles E. , Sjö Peter , Escudié Fanny , Scandale Ivan , Chatelain Eric , Neyts Johan 
Published: February 2022

AbstractThere is an urgent need for potent and selective antivirals against SARS-CoV-2. Pfizer developed PF-07321332 (PF-332), a potent inhibitor of the viral main protease (Mpro, 3CLpro) that can be dosed orally and that is in clinical development. We here report that PF-332 exerts equipotent in vitro activity against the four SARS-CoV-2 variants of concerns (VoC) and that it can completely arrest replication of the alpha variant in primary human airway epithelial cells grown at the air-liquid interface. Treatment of Syrian Golden hamsters with PF-332 (250 mg/kg, twice daily) completely protected the animals against intranasal infection with the beta (B.1.351) and delta (B.1.617.2) SARS-CoV-2 variants. Moreover, treatment of SARS-CoV-2 (B.1.617.2) infected animals with PF-332 completely prevented transmission to untreated co-housed sentinels.
Cancer patient survival can be parametrized to improve trial precision and reveal time-dependent therapeutic effects
Authors: Plana Deborah , Fell Geoffrey , Alexander Brian M. , Palmer Adam C. , Sorger Peter K. 
Published: February 2022

AbstractIndividual participant data (IPD) from oncology clinical trials is invaluable for identifying factors that influence trial success and failure, improving trial design and interpretation, and comparing pre-clinical studies to clinical outcomes. However, the IPD used to generate published survival curves are not generally publicly available. We impute survival IPD from ~500 arms of Phase 3 oncology trials (representing ~220,000 events) and find that they are well fit by a two-parameter Weibull distribution. Use of Weibull functions with overall survival significantly increases the precision of small arms typical of early phase trials: analysis of a 50-patient trial arm using parametric forms is as precise as traditional, non-parametric analysis of a 90-patient arm. We also show that frequent deviations from the Cox proportional hazards assumption, particularly in trials of immune checkpoint inhibitors, arise from time-dependent therapeutic effects. Trial duration therefore has an underappreciated impact on the likelihood of success.
Gut metagenome associations with extensive digital health data in a volunteer-based Estonian microbiome cohort
Authors: Aasmets Oliver , Krigul Kertu Liis , Lüll Kreete , Metspalu Andres , Org Elin 
Published: February 2022

AbstractMicrobiome research is starting to move beyond the exploratory phase towards interventional trials and therefore well-characterized cohorts will be instrumental for generating hypotheses and providing new knowledge. As part of the Estonian Biobank, we established the Estonian Microbiome Cohort which includes stool, oral and plasma samples from 2509 participants and is supplemented with multi-omic measurements, questionnaires, and regular linkages to national electronic health records. Here we analyze stool data from deep metagenomic sequencing together with rich phenotyping, including 71 diseases, 136 medications, 21 dietary questions, 5 medical procedures, and 19 other factors. We identify numerous relationships (n = 3262) with different microbiome features. In this study, we extend the understanding of microbiome-host interactions using electronic health data and show that long-term antibiotic usage, independent from recent administration, has a significant impact on the microbiome composition, partly explaining the common associations between diseases.
Global patterns in functional rarity of marine fish
Authors: Trindade-Santos Isaac , Moyes Faye , Magurran Anne E. 
Published: February 2022

AbstractRare species, which represent a large fraction of the taxa in ecological assemblages, account for much of the biological diversity on Earth. These species make substantial contributions to ecosystem functioning, and are targets of conservation policy. Here we adopt an integrated approach, combining information on the rarity of species trait combinations, and their spatial restrictedness, to quantify the biogeography of rare fish (a taxon with almost 13,000 species) in the world’s oceans. We find concentrations of rarity, in excess of what is predicted by a null expectation, near the coasts and at higher latitudes. We also observe mismatches between these rarity hotspots and marine protected areas. This pattern is repeated for both major groupings of fish, the Actinopterygii (bony fish) and Elasmobranchii (sharks, skates and rays). These results uncover global patterns of rarity that were not apparent from earlier work, and highlight the importance of using metrics that incorporate information on functional traits in the conservation and management of global marine fishes.
Structural basis for SARS-CoV-2 Delta variant recognition of ACE2 receptor and broadly neutralizing antibodies
Authors: Wang Yifan , Liu Caixuan , Zhang Chao , Wang Yanxing , Hong Qin , Xu Shiqi , Li Zuyang , Yang Yong , Huang Zhong , Cong Yao 
Published: February 2022

AbstractThe SARS-CoV-2 Delta variant is currently the dominant circulating strain in the world. Uncovering the structural basis of the enhanced transmission and altered immune sensitivity of Delta is particularly important. Here we present cryo-EM structures revealing two conformational states of Delta spike and S/ACE2 complex in four states. Our cryo-EM analysis suggests that RBD destabilizations lead to population shift towards the more RBD-up and S1 destabilized fusion-prone state, beneficial for engagement with ACE2 and shedding of S1. Noteworthy, we find the Delta T478K substitution plays a vital role in stabilizing and reshaping the RBM loop473-490, enhancing interaction with ACE2. Collectively, increased propensity for more RBD-up states and the affinity-enhancing T478K substitution together contribute to increased ACE2 binding, providing structural basis of rapid spread of Delta. Moreover, we identify a previously generated MAb 8D3 as a cross-variant broadly neutralizing antibody and reveal that 8D3 binding induces a large K478 side-chain orientation change, suggesting 8D3 may use an “induced-fit” mechanism to tolerate Delta T478K mutation. We also find that all five RBD-targeting MAbs tested remain effective on Delta, suggesting that Delta well preserves the neutralizing antigenic landscape in RBD. Our findings shed new lights on the pathogenicity and antibody neutralization of Delta.
Incidence of COVID-19 infection in hospital workers from March 1, 2020 to May 31, 2021 routinely tested, before and after vaccination with BNT162B2
Authors: Larese Filon Francesca , Rui Francesca , Ronchese Federico , De Michieli Paola , Negro Corrado 
Published: February 2022

AbstractTo evaluate the incidence of COVID-19 infection in health care workers from the start of the COVID-19 pandemic in NE Italy, vaccination with BNT162b2. This was a retrospective cohort study. Healthcare workers were routinely tested for SARS-CoV-2 infection using real-time polymerase chain reaction tests in nasopharyngeal swabs. Logistic regression was used to calculate the incidence rate ratios (IRRs) of the factors associated with COVID-19. A total of 4251 workers were followed up, and the prevalence of COVID-19 was 13.6%. In March 2021 the incidence of infection was 4.88 and 103.55 cases for 100,000 person-days in vaccinated and non-vaccinated workers, respectively, with an adjusted IRRs of 0.05 (95% CI 0.02–0.08). Our study evaluated the monthly incidence in health care workers in Trieste hospitals before and after vaccination, finding an estimated vaccine effectiveness of 95% in health care workers routinely tested.
Ion transport and current rectification in a charged conical nanopore filled with viscoelastic fluids
Authors: Trivedi Mohit , Nirmalkar Neelkanth 
Published: February 2022

AbstractThe ionic current rectification (ICR) is a non-linear current-voltage response upon switching the polarity of the potential across nanopore which is similar to the I–V response in the semiconductor diode. The ICR phenomenon finds several potential applications in micro/nano-fluidics (e.g., Bio-sensors and Lab-on-Chip applications). From a biological application viewpoint, most biological fluids (e.g., blood, saliva, mucus, etc.) exhibit non-Newtonian visco-elastic behavior; their rheological properties differ from Newtonian fluids. Therefore, the resultant flow-field should show an additional dependence on the rheological material properties of viscoelastic fluids such as fluid relaxation time $$(\lambda )$$

(
λ
)

and fluid extensibility $$(\varepsilon )$$

(
ε
)

. Despite numerous potential applications, the comprehensive investigation of the viscoelastic behavior of the fluid on ionic concentration profile and ICR phenomena has not been attempted. ICR phenomena occur when the length scale and Debye layer thickness approaches to the same order. Therefore, this work extensively investigates the effect of visco-elasticity on the flow and ionic mass transfer along with the ICR phenomena in a single conical nanopore. The Poisson–Nernst–Planck (P–N–P) model coupled with momentum equations have been solved for a wide range of conditions such as, Deborah number, $$1\le De \le 100$$

1
≤
D
e
≤
100

, Debye length parameter, $$1\le \kappa R_t \le 50$$

1
≤
κ

R
t

≤
50

, fluid extensibility parameter, $$0.05\le \varepsilon \le 0.25$$

0.05
≤
ε
≤
0.25

, applied electric potential, $$-40\le V \le 40$$

-
40
≤
V
≤
40

, and surface charge density $$\sigma = -10$$

σ
=
-
10

and $$-50$$

-
50

. Limited results for Newtonian fluid ($$De = 0$$

D
e
=
0

, and $$\varepsilon = 0$$

ε
=
0

) have also been shown in order to demonstrate the effectiveness of non-Newtonian fluid behaviour over the Newtonian fluid behaviour. Four distinct novel characteristics of electro-osmotic flow (EOF) in a conical nanopore have been investigated here, namely (1) detailed structure of flow field and velocity distribution in viscoelastic fluids (2) influence of Deborah number and fluid extensibility parameter on ionic current rectification (ICR) (3) volumetric flow rate calculation as a function of Deborah number and fluid extensibility parameter (4) effect of viscoelastic parameters on concentration distribution of ions in the nanopore. At high applied voltage, both the extensibility parameter and Deborah number facilitate the ICR phenomena. In addition, the ICR phenomena are observed to be more pronounced at low values of $$\kappa R_t$$

κ

R
t

than the high values of $$\kappa R_t$$

κ

R
t

. This effect is due to the overlapping of the electric double layer at low values of $$\kappa R_t$$

κ

R
t

.
Closing the yellow gap with Eu- and Tb-doped GaN: one luminescent host resulting in three colours
Authors: Braun Cordula , Mereacre Liuda , Chen Zheng , Slabon Adam 
Published: February 2022

AbstractGallium nitride (GaN) is a key material when it comes to light-emitting diodes (LEDs) and has pushed the LED revolution in lighting and displays. The concept of down-conversion of a GaN-based blue LED offers the possibility to provide efficient generation of monochromatic, high-color purity light resulting in a highly efficient warm-white all-nitride phosphor-converted light emitting diode (pc-LED). Although the down conversion of blue light from InGaN LEDs has become a dominant technique for producing white light, there are still some technical challenges, e.g. the immiscibility of GaN and InN and the lattice mismatch between the substrate and InGaN, that have to be overcome. Here we demonstrate the doping of bulk GaN with europium, terbium and the combination of both resulting in intriguing luminescence properties, pushing the role of GaN:Eu,Tb as a chief component in future light emitting diodes. This colour tuning proves that one luminescence host can provide three colours (red, green and orange) and that even the so called “yellow gap” could be closed with a III-nitride. By using one material for all colours, it will be possible to overcome the technical challenges in building up LED devices, which will open up new capabilities for modern highly efficient phosphors.
Relationship between the dynamics of non-alcoholic fatty liver disease and incident diabetes mellitus
Authors: Han Ji Eun , Shin Han-Bit , Ahn Young Hwan , Cho Hyo Jung , Cheong Jae Youn , Park Bumhee , Kim Soon Sun 
Published: February 2022

AbstractThe aim of the current study was to evaluate the association between changes in non-alcoholic fatty liver disease (NAFLD) over time and risk of incident diabetes mellitus (DM). In total, 3047 subjects without underlying DM were followed up for 14 years from the Anseong-Ansan cohort. NAFLD status was determined biennially using the hepatic steatosis index (HSI), and subjects were clustered into seven groups according to changes in HSI, body mass index (BMI), and homeostatic model assessment of insulin resistance (HOMA-IR): none, persistent, transient, transient resolved, resolved, incident, and recurrent NAFLD (Groups 1–7, respectively). Predictive abilities were compared between the dynamics of HSI and single time points. Regarding the changes in HSI, the risk of incident DM was highest in Group 2 (hazard ratio [HR] 2.710; P < 0.001), followed by Groups 7 (HR 2.062; P < 0.001) and 3 (HR 1.559; P = 0.027). The predictive ability for DM was powerful in order of HOMA-IR, HSI and BMI. The dynamics of NAFLD were less predictive of incident DM than single time-point NAFLD. In conclusion, NAFLD is more useful than BMI in predicting incident DM. However, NAFLD status at single time points can better predict incident DM than dynamic changes in HSI.
Convalescent plasma in the treatment of moderate to severe COVID-19 pneumonia: a randomized controlled trial (PROTECT-Patient Trial)
Authors: van den Berg Karin , Glatt Tanya Nadia , Vermeulen Marion , Little Francesca , Swanevelder Ronel , Barrett Claire , Court Richard , Bremer Marise , Nyoni Cynthia , Swarts Avril , Mmenu Cordelia , Crede Thomas , Kritzinger Gerdien , Naude Jonathan , Szymanski Patryk , Cowley James , Moyo-Gwete Thandeka , Moore Penny L. , Black John , Singh Jaimendra , Bhiman Jinal N. , Baijnath Prinita , Mody Priyesh , Malherbe Jacques , Potgieter Samantha , van Vuuren Cloete , Maasdorp Shaun , Wilkinson Robert J. , Louw Vernon J. , Wasserman Sean 
Published: February 2022

AbstractThere is a need for effective therapy for COVID-19 pneumonia. Convalescent plasma has antiviral activity and early observational studies suggested benefit in reducing COVID-19 severity. We investigated the safety and efficacy of convalescent plasma in hospitalized patients with COVID-19 in a population with a high HIV prevalence and where few therapeutic options were available. We performed a double-blinded, multicenter, randomized controlled trial in one private and three public sector hospitals in South Africa. Adult participants with COVID-19 pneumonia requiring non-invasive oxygen were randomized 1:1 to receive a single transfusion of 200 mL of either convalescent plasma or 0.9% saline solution. The primary outcome measure was hospital discharge and/or improvement of ≥ 2 points on the World Health Organisation Blueprint Ordinal Scale for Clinical Improvement by day 28 of enrolment. The trial was stopped early for futility by the Data and Safety Monitoring Board. 103 participants, including 21 HIV positive individuals, were randomized at the time of premature trial termination: 52 in the convalescent plasma and 51 in the placebo group. The primary outcome occurred in 31 participants in the convalescent plasma group and and 32 participants in the placebo group (relative risk 1.03 (95% CI 0.77 to 1.38). Two grade 1 transfusion-related adverse events occurred. Participants who improved clinically received convalescent plasma with a higher median anti-SARS-CoV-2 neutralizing antibody titre compared with those who did not (298 versus 205 AU/mL). Our study contributes additional evidence for recommendations against the use of convalescent plasma for COVID-19 pneumonia. Safety and feasibility in this population supports future investigation for other indications.
Sodium salt-assisted low temperature activation of bentonite for the adsorptive removal of methylene blue
Authors: Shattar Siti Fairos Ab , Foo Keng Yuen 
Published: February 2022

AbstractThe sodium salt-assisted low temperature activation of bentonite (BB) was attempted. The unique features of the raw bentonite and BB were characterized with respect to the morphological, functional, and textural analysis. The adsorptive behaviour was evaluated by adopting methylene blue (MB) as the model pollutant via batch adsorption experiment. The experimental data were fitted to the non-linear isotherm equations (Freundlich, Langmuir, and Temkin), while the adsorption modelling was interpreted by the pseudo-first order, pseudo-second order and Elovich models. The adsorptive mechanism was ascertained according to intraparticle-diffusion and boyd models. The intercalation of sodium salt into the bentonite surface give rise to the specific surface area and total pore volume from 120.34 to 426.91, m2/g and 0.155 to 0.225 cm3/g, respectively, indicating a large proportion of the newly formed surfaces may be connected to new pore walls, associated with the silanol (≡SiOH), and aluminol (≡AlOH), and hydroxyl (–OH) groups for the possible entrapment MB onto the adsorbent. The equilibrium data was satisfactory described by the Langmuir isotherm and pseudo-second order model, with a monolayer adsorption capacity for MB of 318.38 mg/g, while the thermodynamic study verified spontaneous, feasible, and endothermic of the adsorption process.
Deep learning detection of nanoparticles and multiple object tracking of their dynamic evolution during in situ ETEM studies
Authors: Faraz Khuram , Grenier Thomas , Ducottet Christophe , Epicier Thierry 
Published: February 2022

AbstractIn situ transmission electron microscopy (TEM) studies of dynamic events produce large quantities of data especially under the form of images. In the important case of heterogeneous catalysis, environmental TEM (ETEM) under gas and temperature allows to follow a large population of supported nanoparticles (NPs) evolving under reactive conditions. Interpreting properly large image sequences gives precious information on the catalytic properties of the active phase by identifying causes for its deactivation. To perform a quantitative, objective and robust treatment, we propose an automatic procedure to track nanoparticles observed in Scanning ETEM (STEM in ETEM). Our approach involves deep learning and computer vision developments in multiple object tracking. At first, a registration step corrects the image displacements and misalignment inherent to the in situ acquisition. Then, a deep learning approach detects the nanoparticles on all frames of video sequences. Finally, an iterative tracking algorithm reconstructs their trajectories. This treatment allows to deduce quantitative and statistical features about their evolution or motion, such as a Brownian behavior and merging or crossing events. We treat the case of in situ calcination of palladium (oxide) / delta-alumina, where the present approach allows a discussion of operating processes such as Ostwald ripening or NP aggregative coalescence.
Pseudo contrastive labeling for predicting IVF embryo developmental potential
Authors: Erlich I. , Ben-Meir A. , Har-Vardi I. , Grifo J. , Wang F. , Mccaffrey C. , McCulloh D. , Or Y. , Wolf L. 
Published: February 2022

AbstractIn vitro fertilization is typically associated with high failure rates per transfer,
leading to an acute need for the identification of embryos with high developmental potential. Current methods are tailored to specific times after fertilization, often require expert inspection, and have low predictive power. Automatic methods are challenged by ambiguous labels, clinical heterogeneity, and the inability to utilize multiple developmental points. In this work, we propose a novel method that trains a classifier conditioned on the time since fertilization. This classifier is then integrated over time and its output is used to assign soft labels to pairs of samples. The classifier obtained by training on these soft labels presents a significant improvement in accuracy, even as early as 30 h post-fertilization. By integrating the classification scores, the predictive power is further improved. Our results are superior to previously reported methods, including the commercial KIDScore-D3 system, and a group of eight senior professionals, in classifying multiple groups of favorable embryos into groups defined as less favorable based on implantation outcomes, expert decisions based on developmental trajectories, and/or genetic tests.
A chemically-defined plastic scaffold for the xeno-free production of human pluripotent stem cells
Authors: Shimizu Eiko , Iguchi Hiroki , Le Minh Nguyen Tuyet , Nakamura Yuta , Kobayashi Daigo , Arai Yuhei , Takakura Kenta , Benno Seiko , Yoshida Noriko , Tsukahara Masayoshi , Haneda Satoshi , Hasegawa Kouichi 
Published: February 2022

AbstractClinical use of human pluripotent stem cells (hPSCs) is hampered by the technical limitations of their expansion. Here, we developed a chemically synthetic culture substrate for human pluripotent stem cell attachment and maintenance. The substrate comprises a hydrophobic polyvinyl butyral-based polymer (PVB) and a short peptide that enables easy and uniform coating of various types of cell culture ware. The coated ware exhibited thermotolerance, underwater stability and could be stored at room temperature. The substrate supported hPSC expansion in combination with most commercial culture media with an efficiency similar to that of commercial substrates. It supported not only the long-term expansion of examined iPS and ES cell lines with normal karyotypes during their undifferentiated state but also directed differentiation of three germ layers. This substrate resolves major concerns associated with currently used recombinant protein substrates and could be applied in large-scale automated manufacturing; it is suitable for affordable and stable production of clinical-grade hPSCs and hPSC-derived products.
The oculomotor signature of expected surprise
Authors: Drążyk Dominika , Missal Marcus 
Published: February 2022

AbstractExpected surprise, defined as the anticipation of uncertainty associated with the occurrence of a future event, plays a major role in gaze shifting and spatial attention. In the present study, we analyzed its impact on oculomotor behavior. We hypothesized that the occurrence of anticipatory saccades could decrease with increasing expected surprise and that its influence on visually-guided responses could be different given the presence of sensory information and perhaps competitive attentional effects. This hypothesis was tested in humans using a saccadic reaction time task in which a cue indicated the future stimulus position. In the ‘no expected surprise’ condition, the visual target could appear only at one previously cued location. In other conditions, more likely future positions were cued with increasing expected surprise. Anticipation was more frequent and pupil size was larger in the ‘no expected surprise’ condition compared with all other conditions, probably due to increased arousal. The latency of visually-guided saccades increased linearly with the logarithm of surprise (following Hick’s law) but their maximum velocity repeated the arousal-related pattern. Therefore, expected surprise affects anticipatory and visually-guided responses differently. Moreover, these observations suggest a causal chain linking surprise, attention and saccades that could be disrupted in attentional or impulse control disorders.