bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of dietary krill oil supplementation on horse red blood cell membrane fatty acid composition and blood parameters
Authors: Nyquist Nicole Frost , Burri Lena , Jensen Rasmus Bovbjerg
Published: May 2023

Supplementation with marine‐derived n−3 long‐chain polyunsaturated fatty acids (LC PUFAs), eicosapentaenoic acid (EPA, 20:5 n−3) and docosahexaenoic acid (DHA, 22:6 n−3) is linked to beneficial health effects in both humans and horses. Krill oil (KO), which is extracted from the Antarctic krill (Euphausia superba), is well documented as a safe and biologically available dietary supplement in humans and several animal species, but there is a lack of documentation regarding its effect as a dietary ingredient for horses. The objective of this study was to test whether KO as a dietary supplement had the ability to raise horse red blood cell (RBC) membrane EPA and DHA, expressed as the n−3 index. Five nonworking Norwegian cold‐blooded trotter horse geldings (body weight [BW]: 567 ± 38 kg) were supplemented with KO (10 mL/100 kg BW) for 35 days in a longitudinal study. Blood samples were analysed for RBC membrane fatty acid (FA) profile, haematology and serum biochemistry every 7th day. KO was well accepted by all horses, and no adverse health effects were observed during the 35‐day trial period. KO supplementation affected the RBC membrane FA profile by increasing the n−3 index from Day 0 to 35 (Day 0: 0.53% vs. Day 35: 4.05% of total RBC FAs). The observed increase in the sum of EPA and DHA (p < 0.001), total n−3 FAs (p < 0.001) and the reduction of n−6 FAs (p < 0.044) resulted in a lower n–6:n−3 ratio (p < 0.001) by Day 35 of KO supplementation. In conclusion, the RBC n−3 index was increased and the general n−6:n−3 ratio was decreased in horses receiving 35‐day dietary KO supplementation.
Reasons for Leaving: Causes and Initial Triggers for Disaffiliation from Orthodox Judaism
Authors: Miles Rona , Chavarga Alla , Hirsch Estee , Eisen Pesach , Keller Yehudis
Published: May 2023

Investigating both the causes and initial triggers for disaffiliation from Orthodox Judaism is an important part of understanding the complex lived experiences of exiters. This study documents an extensive number of causes for leaving Orthodox Judaism, as well as initial triggers, a less‐often investigated, yet important component of disaffiliation. Using an online survey, over 700 open‐ended responses were collected from 303 participants who self‐identified as having grown up practicing Orthodox Judaism but had since stopped practicing. Content analysis was used to organize responses, resulting in distinct categories that fit into two themes: intellectual and social‐emotional, the former more often reported by males and the latter by females. The most commonly reported causes and initial triggers, respectively, were issues with the community and lack of belief in Torah and Orthodoxy. Our results give voice to exiters by documenting nuanced accounts of the full disaffiliation journey, beginning with the initial trigger.
An interview with Professor Barbara Comber
Authors: Comber Barbara
Published: May 2023

As part of this special issue on ‘Literacy for social justice’, and at this moment of post‐pandemic transitions in education, we invited Professor Barbara Comber to reflect on the needs for and trends in critical literacy education, both in her local context, in Australia, and internationally. In September 2022, we met with Barbara online to discuss her thoughts about what critical literacy educators need, how scholars and educators can work together to produce change, and where we can see hope in critical literacy and social justice education right now, as part of promising anti‐racist, decolonizing, and intersectional literacy frameworks and practices.
Evolutionary consequences of loss of sexual reproduction on male‐related traits in parthenogenetic lineages of the pea aphid
Authors: Defendini Hélène , Rimbault Maud , Mahéo Frédérique , Cloteau Romuald , Denis Gaëtan , Mieuzet Lucie , Outreman Yannick , Simon Jean‐Christophe , Jaquiéry Julie
Published: May 2023

Transition from sexual reproduction to parthenogenesis constitutes a major life‐history change with deep evolutionary consequences for sex‐related traits, which are expected to decay. The pea aphid Acyrthosiphon pisum shows intraspecific reproductive polymorphism, with cold‐resistant cyclically parthenogenetic (CP) lineages that alternate sexual and asexual generations and cold‐sensitive obligately parthenogenetic (OP) lineages that produce only asexual females but still males. Here, the genotyping of 219 pea aphid lineages collected in cold‐winter and mild‐winter regions revealed contrasting population structures. Samples from cold‐winter regions consisted mostly of distinct multilocus genotypes (MLGs) usually represented by a single sample (101 different MLGs for 111 samples) and were all phenotyped as CP. In contrast, fewer MLGs were found in mild‐winter regions (28 MLGs for 108 samples), all but one being OP. Since the males produced by OP lineages are unlikely to pass on their genes (sexual females being rare in mild‐winter regions), we tested the hypothesis that their traits could degenerate due to lack of selection by comparing male production and male reproductive success between OP and CP lineages. Male production was indeed reduced in OP lineages, but a less clear pattern was observed for male reproductive success: females mated with OP males laid fewer eggs (fertilized or not) but OP and CP males fertilized the same proportion of eggs. These differences may stem from the type of selective forces: male production may be counter‐selected whereas male performances may evolve under the slower process of relaxed selection. The overall effective reproductive capacity of OP males could result from recent sex loss in OP lineages or underestimated reproductive opportunities.
Parental effects in a filamentous fungus: Phenotype, fitness and mechanism
Authors: Villalba de la Peña Mariana , Summanen Pauliina A. M. , Moghadam Neda N. , Kronholm Ilkka
Published: May 2023

In nature, organisms have to cope with constantly changing environments. In certain conditions, it may be advantageous for the parents to pass on information about the environment, or resources to their offspring. Such transfers are known as parental effects, and they are well documented in plants and animals, but not in other eukaryotes, such as fungi. Many fungi disperse through spores, and fungal spores can potentially carry information or resources to the next generation. Understanding parental effects and their evolutionary consequences in fungi is of vital importance as they perform crucial ecosystem functions. In this study, we investigated whether parental effects are present in the filamentous fungus Neurospora crassa, how long do they last, whether the effects are adaptive, and what is their mechanism. We performed a fully factorial match/mismatch experiment for a good and a poor quality environment, in which we measured the initial growth of strains that experienced either a matched or mismatched environment in their previous generation. We found a strong silver‐spoon effect in initial mycelium growth, which lasted for one generation, and increased fitness during competition experiments. By using deletion mutants that lacked key genes in epigenetic processes, we show that epigenetic mechanisms are not involved in this effect. Instead, we show that spore glycogen content, glucose availability and a radical transcription shift in spores are the main mechanisms behind this parental effect.
Learning new words via feedback—Association between feedback‐locked ERPs and recall performance—An exploratory study
Authors: Albrecht Christine , van de Vijver Ruben , Bellebaum Christian
Published: May 2023

Feedback learning is thought to involve the dopamine system and its projection sites in the basal ganglia and anterior cingulate cortex (ACC), regions associated with procedural learning. Under certain conditions, such as when feedback is delayed, feedback‐locked activation is pronounced in the medial temporal lobe (MTL), which is associated with declarative learning. In event‐related potential research, the feedback‐related negativity (FRN) has been linked to immediate feedback processing, while the N170, possibly reflecting MTL activity, has been related to delayed feedback processing. In the current study, we performed an exploratory investigation on the relation between N170 and FRN amplitude and memory performance in a test for declarative memory (free recall), also exploring the role of feedback delay. To this end, we adapted a paradigm in which participants learned associations between non‐objects and non‐words with either immediate or delayed feedback, and added a subsequent free recall test. We indeed found that N170, but not FRN amplitudes, depended on later free recall performance, with smaller amplitudes for later remembered non‐words. In an additional analysis with memory performance as dependent variable, the N170, but not the FRN amplitude predicted free recall, modulated by feedback timing and valence. This finding shows that the N170 reflects an important process during feedback processing, possibly related to expectations and their violation, but is distinct from the process reflected by the FRN.
The perils of embedded experiments
Authors: Drèze Jean
Published: May 2023

Abstract

There is growing interest in experiments conducted by researchers and policymakers as a team. The attraction of these ‘embedded experiments’ is that they seem to facilitate speedy translation of research into policy. This approach, however, can trivialise public policy and compromise the independence of the researchers. It is also a fountain of ethical dilemmas including consent issues, conflicts of interest and compensation norms. The perils of embedded experiments, and possible safeguards, are discussed with the help of a case study.
Deterministic Optimization Approach for High-Performance Externally Fired Biomass-Fueled Micro-Gas Turbines
Authors: Bollas Konstantinos D. , Efstathiadis Theofilos G. , Kalfas Anestis I.
Published: May 2023

This work focuses on a dual-objective optimization of a 100 kWe externally fired micro-gas turbine utilizing the producer gas from a biomass gasifier. Although externally fired micro-gas turbines are convenient for resolving operability issues in biomass combined heat and power applications, these configurations are still lacking in efficiency compared to the commercial natural-gas fired microturbines. The main cause is the material temperature limitations in the recuperator and the current uneconomical use of high-temperature resistance materials. Toward the achievement of higher efficiency by keeping system economic viability, an optimization process is followed based on the Normal Constraint Method, which generates evenly distributed solutions of a Pareto front. The selected method can determine high-performance solutions, being unidentified by one-dimensional approaches, providing information about the distribution of critical cycle parameters, across the complete objective space by the evaluation of a relatively small set of Pareto points. These critical parameters are the pressure ratio, the recuperator temperature difference, and maximum temperature. The exergetic efficiency and the relative recuperator cost are the optimization objectives. The deterministic Nelder–Mead algorithm is used for the acquisition of Pareto solutions, along with a penalty-based method to perform the constrained optimization. The implemented optimization method can identify superior solutions compared to one-dimensional approaches, as the latter result in higher recuperator costs around 41–112% at the same exergetic efficiency, revealing that high-performance is not only restricted by the recuperator but also by the compressor operating range.
Effects of High Rotational Speed on Leakage and Windage Heating of Staggered Labyrinth Seals With Smooth and Honeycomb Lands
Authors: Liu Hao , Li Guoqing , Li Ang , Zhang Shen , Li Hui , Lu Xingen
Published: May 2023

Being an important component of aero-engines, the labyrinth seal has always been the focus of research for leakage characteristics. Rotation is usually neglected or taken for minimal effect on seal leakage in previous studies. However, the effect of high rotational speed is inevitable to understand the leakage characteristics of labyrinth seal accurately. Meanwhile, due to high rotational speed, viscous heat is generated massively to result in the rapid temperature rise of leakage flow. Also, the influence of rotational speed on windage heating inside the seal clearance has not been indicated completely. Therefore, the leakage and windage heating of staggered labyrinth seals with smooth and honeycomb lands were experimentally and numerically studied. The large-scale and multifunctional sealing test rig were employed to carry out the experiments with rotational speed 12,000 rpm and pressure ratio range 1.1–2.2. The simulation data obtained by three-dimensional computational fluid dynamics methodology show great agreement with experimental results. Notably, the leakage coefficient is not monotonically decreasing with increased rotational speed, but exists a maximum peak at RPM = 8000. The variation of axial kinetic energy in seal clearance entrances provides a clear explanation of the phenomenon. Rotational speed plays an important role in windage heating, and honeycomb cell size is of secondary importance. Based on simulation data, the calculating formula of windage heating is fitted and shows great performance. This study can provide theory and data support for the follow-up structural optimum design of the labyrinth seal.
Peeling of Finite-Length Plates From an Elastomeric Foundation: A 1D Cylindrical Bending Solution
Authors: Plaut Raymond H. , Dillard David A.
Published: May 2023

Quasi-static peeling of a finite-length, flexible, horizontal, one-dimensional (1D) plate (strip, thin film) from a horizontal, thin, elastomeric layer (foundation) is considered. The displaced end of the plate is subjected to an upward deflection or to a rotation. The top of the interlayer is perfectly bonded to the plate, and its lower surface is bonded to a rigid, flat substrate. A transversality (debonding) condition is derived for peeling, based on the common fracture mechanics approach. Whereas debonding from a Winkler foundation can be expressed in terms of the displacement (or equivalently the foundation stress2) at the bond termination, the sixth-order formulation required for elastomeric foundations involves a more complex debonding criterion. Transversality relationships are used to describe this limit state (here the onset of debonding) in terms of co-state variables, herein the deflection and slope at the peel front. In the analysis, bending is assumed to be paramount, linear Kirchhoff–Love (classical) plate theory is used to model the deformation, and therefore displacements are assumed to be small. The foundation is linearly elastic and incompressible. The effects of the work of adhesion, the length of the plate, and the initial nonbonded length of the plate are investigated. The results are compared to those for a Winkler foundation. By replacing the shear modulus of the interlayer by viscosity, and displacements by their time derivatives, the results are expected to apply to viscous liquid interlayers as well.
Design and Manufacture of Power Skiving Cutter From Target Circular Spline Geometry
Authors: Cheng Yun-Hao , Chen Yi-Cheng
Published: May 2023

In this study, a novel design scheme for a power skiving cutter and its grinding wheel profile is proposed based on the geometry of a target circular spline (CS) workpiece. First, a generalized mathematical model of a target CS profile is expressed using a B-spline curve. Subsequently, the nominal cutting edge of the skiving cutter for generating an error-free CS is derived based on power skiving kinematics. In addition, the axial profile of the grinding wheel for generating the derived nominal cutting edge is resolved based on lengthwise-reciprocating grinding kinematics. The proposed design process for the skiving cutter and its grinding wheel is illustrated using numerical examples. The profile accuracy of the CS yielded by the designed nominal cutting edge is computed to validate the proposed design processes. Moreover, errors of the skived CS profile resulting from various resharpening depths by grinding back the stepped rake face of the skiving cutter are investigated. Finally, to effectively extend the tool life of the skiving cutter, a compensation rolling angle is introduced into the CS skiving process.
Design, Analysis, and Experiment of the Origami Robot Based on Spherical-Linkage Parallel Mechanism
Authors: Guan Yuntao , Zhuang Zheming , Zhang Ze , Dai Jian S.
Published: May 2023

Origami robot is a hotspot for research in the field of soft robot. However, there are still some major limitations to their application. This study proposed an origami robot based on spherical-linkage parallel mechanism (SLPM) for realizing some functions that cannot be accomplished by conventional robots. This study designed the manufacturing and assembling processes for the SLPM section according to the needs of practical applications, to explore the influence of flexible hinge on the resistance of SLPM section to lateral and torsional forces, the finite element simulation of SLPM section was performed, and the physical model of SLPM section was made to conduct a series of experiment. Also, an origami robot based on SLPM was also made, and the motion form of the robot was explored by adams. At last, through establishing a mathematical model, the relationship for conversion between the two control modes of the robot was deduced. Based on this, an experiment on the bending angle of the robot was carried out, and the simulation results were compared. This paper will promote the research of origami robot in structure design, motion control, etc.
Investigation on Flow Characteristics and Its Effect on Heat Transfer Enhancement in a Wide Channel With Staggered Diamond-S Pin Fins
Authors: Duan Jingtian , Zhang Ke , Xu Jin , Lei Jiang , Wu Junmei
Published: May 2023

Flow statistic in the mid-plane of a rectangular channel with diamond-s pin fins was obtained by means of particle imaging velocimetry at Re = 10,000. Large-scale and small-scale fluctuations were separated using proper orthogonal decomposition. The flow characteristics were compared to the Nusselt number distribution on the endwall acquired by thermochromic liquid crystal to reveal the flow mechanism driving heat transfer enhancement. Results indicate that local vorticity plays an important role in strengthening Nu on both sides of leading point (Zone 1). Downstream of the two sharp edges on both sides (Zone 2), small size disturbances from shear layer eddies drive local heat transfer. The flow characteristics and heat transfer distribution downstream of the first row (Zone 3) present alternated feature along Y direction due to the interaction between shear layers of neighboring pin fins. Lateral velocity fluctuation induced by large vortex shedding drives the heat transfer augmentation in Zone 3 where there is violent large vortex shedding. Meanwhile, small size disturbances of the shear layer drive local heat transfer enhancement in Zone 3 downstream of pin fins where large vortex shedding is suppressed. For the second and third rows, there is no difference in the flow characteristics downstream of neighboring pin fins. Small-size fluctuations distributed uniformly downstream of large vortex shedding (Zone 4) resulting in a uniformly distributed Nu.
On the bifurcation behavior of a folded notebook page
Authors: Zhang Chenguang
Published: May 2023

We study how a bound notebook page can be folded once so that the page is visible when the notebook is closed and becomes a bookmark. An additional practical requirement is that the folded page stays within the same side of the bind, so that it does not get creased further when one closes the notebook. This simple problem displays a remarkably rich bifurcation behavior, which can be analyzed using undergraduate calculus. The main finding is that the optimal way of folding the page depends on the page's aspect ratio and changes abruptly when the latter exceeds the critical value of 1.207 11. This behavior also resembles a first-order phase transition in thermodynamics despite its geometric origin.
Finding and improving bounds of real functions by thermodynamic arguments
Authors: Vallejo Andrés
Published: May 2023

The possibility of stating the second law of thermodynamics in terms of the increasing behaviour of a physical property establishes a connection between that branch of physics and the theory of algebraic inequalities. We use this connection to show how some well-known inequalities, such as the standard bounds for the logarithmic function or generalizations of Bernoulli's inequality, can be derived by thermodynamic methods. Additionally, we show that by comparing the global entropy production in processes implemented with decreasing levels of irreversibility but subject to the same change of state of one particular system, we can find progressively better bounds for the real function that represents the entropy variation of the system. As an application, some new families of bounds for the function log (1+x) are obtained by this method.
A low-cost confocal microscope for the undergraduate lab
Authors: Reguilon A. , Bethard W. , Brekke E.
Published: May 2023

We demonstrate a simple and cost-efficient scanning confocal microscope setup for use in advanced instructional physics laboratories. The setup is constructed from readily available commercial products, and the implementation of a 3D-printed flexure stage allows for further cost reduction and pedagogical opportunity. Experiments exploring the thickness of a microscope slide and the surface of solid objects with height variation are presented as foundational components of undergraduate laboratory projects and demonstrate the capabilities of a confocal microscope. This system allows observation of key components of a confocal microscope, including depth perception and data acquisition via transverse scanning, making it an excellent pedagogical resource.
Development of active noise control simulation with virtual controller based on computational aeroacoustics
Authors: Kim Dongwook , Saravanan Vignesh , Kim Hyunkee , Yuk Taeseok , Lee Soogab
Published: May 2023

Noise reduction and control research are actively conducted as increasing noise problems compel the stringent noise requirement. Active noise control (ANC) is constructively used in various applications to reduce low-frequency noise. In previous studies, ANC systems were designed based on experiments, requiring extensive effort for effective implementation. In this paper, a real-time ANC simulation in a computational aeroacoustics framework based on the virtual-controller method is presented. The aims are to investigate sound field changes following ANC system operation and gain more insight into ANC system design through a computational approach. Using a virtual-controller ANC simulation, the approximate shape of the acoustic path filter and changes in the sound field when ANC is either “on” or “off” at the target domain can be obtained, enabling practical and detailed analyses. Then, the computational results of the duct and open space cases are predicted and compared with the experimental results to validate the prediction capability of the proposed method. In addition, the ANC system design parameters and their effects on sound fields with unintended phenomena can be predicted. Through case studies, the ability to design, optimize, and predict the performance of the ANC system using the computational method is also demonstrated.
Longitudinal Analysis of Patterns and Correlates of Physical Activity and Sedentary Behavior in Women From Preconception to Postpartum: The Singapore Preconception Study of Long-Term Maternal and Child Outcomes Cohort
Authors: Chu Anne H.Y. , Padmapriya Natarajan , Tan Shuen Lin , Goh Claire Marie J.L. , Chong Yap-Seng , Shek Lynette P. , Tan Kok Hian , Gluckman Peter D. , Yap Fabian K.P. , Lee Yung Seng , Loy See Ling , Chan Jerry K.Y. , Godfrey Keith M. , Eriksson Johan G. , Chan Shiao-Yng , Bernard Jonathan Y. , Müller-Riemenschneider Falk
Published: May 2023

Objective: Longitudinal changes in physical activity (PA) and sedentary behavior patterns from preconception to postpartum are not fully characterized. We examined changes and baseline sociodemographic/clinical correlates of PA and sedentary behavior in women from preconception to postpartum. Methods: The Singapore Preconception Study of Long-Term Maternal and Child Outcomes cohort recruited 1032 women planning pregnancy. Participants completed questionnaires at preconception, 34 to 36 weeks gestation, and 12 months postpartum. Repeated-measures linear regression models were used to analyze changes in walking, moderate to vigorous PA (MVPA), screen time, and total sedentary time, and to identify sociodemographic/clinical correlates associated with these changes. Results: Of the 373 women who delivered singleton live births, 281 provided questionnaires for all time points. Walking time increased from preconception to late pregnancy but decreased postpartum (adjusted means [95% CI]: 454 [333–575], 542 [433–651], and 434 [320–547] min/wk, respectively). Vigorous-intensity PA and MVPA decreased from preconception to late pregnancy but increased postpartum (vigorous-intensity PA: 44 [11–76], 1 [−3–5], and 11 [4–19] min/wk, MVPA: 273 [174–372], 165 [95–234], and 226 [126–325] min/wk, respectively). Screen time and total sedentary time remained consistent from preconception to pregnancy but decreased postpartum (screen: 238 [199–277], 244 [211–277], and 162 [136–189] min/d, total: 552 [506–598], 555 [514–596], and 454 [410–498] min/d, respectively). Individual characteristics of ethnicity, body mass index, employment, parity, and self-rated general health significantly influenced women’s activity patterns. Conclusion: During late pregnancy, walking time increased, while MVPA declined significantly, and partially returned to preconception levels postpartum. Sedentary time remained stable during pregnancy but decreased postpartum. The identified set of sociodemographic/clinical correlates underscores need for targeted strategies.
A rationally designed ICAM1 antibody drug conjugate eradicates late-stage and refractory triple-negative breast tumors in vivo
Authors: Guo Peng , Huang Jing , Zhu Bing , Huang Andrew C. , Jiang Lingxiao , Fang Jianmin , Moses Marsha A.
Published: May 2023

Triple-negative breast cancer (TNBC) remains the most lethal form of breast cancer, and effective targeted therapeutics are in urgent need to improve the poor prognosis of TNBC patients. Here, we report the development of a rationally designed antibody drug conjugate (ADC) for the treatment of late-stage and refractory TNBC. We determined that intercellular adhesion molecule-1 (ICAM1), a cell surface receptor overexpressed in TNBC, efficiently facilitates receptor-mediated antibody internalization. We next constructed a panel of four ICAM1 ADCs using different chemical linkers and warheads and compared their in vitro and in vivo efficacies against multiple human TNBC cell lines and a series of standard, late-stage, and refractory TNBC in vivo models. An ICAM1 antibody conjugated with monomethyl auristatin E (MMAE) via a protease-cleavable valine-citrulline linker was identified as the optimal ADC formulation owing to its outstanding efficacy and safety, representing an effective ADC candidate for TNBC therapy.
The impact of defense counsel at bail hearings
Authors: Anwar Shamena , Bushway Shawn , Engberg John
Published: May 2023

Roughly half of U.S. counties do not provide defense counsel at bail hearings, and few studies have documented the potential impacts of legal representation at this stage. This paper presents the results from a field experiment in Allegheny County, Pennsylvania, that provided a public defender at a defendant’s initial bail hearing. The presence of a public defender decreased the use of monetary bail and pretrial detention without increasing failure to appear rates at the preliminary hearing. The intervention did, however, result in a short-term increase in rearrests on theft charges, although a theft incident would have to be at least 8.5 times as costly as a day in detention for jurisdictions to find this tradeoff undesirable.
Hypoxia-inducible factor orchestrates adenosine metabolism to promote liver cancer development
Authors: Cheu Jacinth Wing-Sum , Chiu David Kung-Chun , Kwan Kenneth Kin-Leung , Yang Chunxue , Yuen Vincent Wai-Hin , Goh Chi Ching , Chui Noreen Nog-Qin , Shen Wei , Law Cheuk-Ting , Li Qidong , Zhang Misty Shuo , Bao Macus Hao-Ran , Wong Bowie Po-Yee , Chan Cerise Yuen-Ki , Liu Cindy Xinqi , Sit Grace Fu-Wan , Ooi Zher Yee , Deng Haijing , Tse Aki Pui-Wah , Ng Irene Oi-Lin , Wong Carmen Chak-Lui
Published: May 2023

Hypoxia-induced adenosine creates an immunosuppressive tumor microenvironment (TME) and dampens the efficacy of immune checkpoint inhibitors (ICIs). We found that hypoxia-inducible factor 1 (HIF-1) orchestrates adenosine efflux through two steps in hepatocellular carcinoma (HCC). First, HIF-1 activates transcriptional repressor MXI1, which inhibits adenosine kinase (ADK), resulting in the failure of adenosine phosphorylation to adenosine monophosphate. This leads to adenosine accumulation in hypoxic cancer cells. Second, HIF-1 transcriptionally activates equilibrative nucleoside transporter 4, pumping adenosine into the interstitial space of HCC, elevating extracellular adenosine levels. Multiple in vitro assays demonstrated the immunosuppressive role of adenosine on T cells and myeloid cells. Knockout of ADK in vivo skewed intratumoral immune cells to protumorigenic and promoted tumor progression. Therapeutically, combination treatment of adenosine receptor antagonists and anti–PD-1 prolonged survival of HCC-bearing mice. We illustrated the dual role of hypoxia in establishing an adenosine-mediated immunosuppressive TME and offered a potential therapeutic approach that synergizes with ICIs in HCC.
Evolution of the crustal phosphorus reservoir
Authors: Walton Craig R. , Hao Jihua , Huang Fang , Jenner Frances E. , Williams Helen , Zerkle Aubrey L. , Lipp Alex , Hazen Robert M. , Peters Shanan E. , Shorttle Oliver
Published: May 2023

The release of phosphorus (P) from crustal rocks during weathering plays a key role in determining the size of Earth’s biosphere, yet the concentration of P in crustal rocks over time remains controversial. Here, we combine spatial, temporal, and chemical measurements of preserved rocks to reconstruct the lithological and chemical evolution of Earth’s continental crust. We identify a threefold increase in average crustal P concentrations across the Neoproterozoic-Phanerozoic boundary (600 to 400 million years), showing that preferential biomass burial on shelves acted to progressively concentrate P within continental crust. Rapid compositional change was made possible by massive removal of ancient P-poor rock and deposition of young P-rich sediment during an episode of enhanced global erosion. Subsequent weathering of newly P-rich crust led to increased riverine P fluxes to the ocean. Our results suggest that global erosion coupled to sedimentary P-enrichment forged a markedly nutrient-rich crust at the dawn of the Phanerozoic.
Deformation and failure of the CrCoNi medium-entropy alloy subjected to extreme shock loading
Authors: Zhao Shiteng , Yin Sheng , Liang Xiao , Cao Fuhua , Yu Qin , Zhang Ruopeng , Dai Lanhong , Ruestes Carlos J. , Ritchie Robert O. , Minor Andrew M.
Published: May 2023

The extraordinary work hardening ability and fracture toughness of the face-centered cubic (fcc) high-entropy alloys render them ideal candidates for many structural applications. Here, the deformation and failure mechanisms of an equiatomic CrCoNi medium-entropyalloy (MEA) were investigated by powerful laser-driven shock experiments. Multiscale characterization demonstrates that profuse planar defects including stacking faults, nanotwins, and hexagonal nanolamella were generated during shock compression, forming a three-dimensional network. During shock release, the MEA fractured by strong tensile deformation and numerous voids was observed in the vicinity of the fracture plane. High defect populations, nanorecrystallization, and amorphization were found adjacent to these areas of localized deformation. Molecular dynamics simulations corroborate the experimental results and suggest that deformation-induced defects formed before void nucleation govern the geometry of void growth and delay their coalescence. Our results indicate that the CrCoNi-based alloys are impact resistant, damage tolerant, and potentially suitable in applications under extreme conditions.
Real-time Fourier-domain optical vector oscilloscope
Authors: Li Lun , Zhang Chi , Cai Yuchong , Zhang Hongguang , Li Yaoshuai , Li Xiang , Xiao Xi , Wong Kenneth Kin-Yip , Zhang Xinliang
Published: May 2023

To meet the constant demands of high-capacity telecommunications infrastructure, data rates beyond 1 terabit per second per wavelength channel and optical multiplexing are widely applied. However, these features pose challenges for existing data acquisition and optical performance monitoring techniques because of bandwidth limitation and signal synchronization. We designed an approach that would address these limitations by optically converting the frequency limit to an unlimited time axis and combining this with a chirped coherent detection to innovatively obtain the full-field spectrum. With this approach, we demonstrated a real-time Fourier-domain optical vector oscilloscope, with a 3.4-terahertz bandwidth and a 280-femtosecond temporal resolution over a 520-picosecond record length. In addition to on-off keying and binary phase-shift keying signals (128 gigabits per second), quadrature phase-shift keying wavelength division–multiplexed signals (4 × 160 gigabits per second) are simultaneously observed. Moreover, we successfully demonstrate some high-precision measurements, which indicate them as a promising scientific and industrial tool in high-speed optical communication and ultrafast optical measurement.
Microstructure optimization of bioderived polyester nanofilms for antibiotic desalination via nanofiltration
Authors: Bai Yunxiang , Liu Beibei , Li Jiachen , Li Minghui , Yao Zheng , Dong Liangliang , Rao Dewei , Zhang Peng , Cao Xingzhong , Villalobos Luis Francisco , Zhang Chunfang , An Quan-Fu , Elimelech Menachem
Published: May 2023

The successful implementation of thin-film composite membranes (TFCM) for challenging solute-solute separations in the pharmaceutical industry requires a fine control over the microstructure (size, distribution, and connectivity of the free-volume elements) and thickness of the selective layer. For example, desalinating antibiotic streams requires highly interconnected free-volume elements of the right size to block antibiotics but allow the passage of salt ions and water. Here, we introduce stevioside, a plant-derived contorted glycoside, as a promising aqueous phase monomer for optimizing the microstructure of TFCM made via interfacial polymerization. The low diffusion rate and moderate reactivity of stevioside, together with its nonplanar and distorted conformation, produced thin selective layers with an ideal microporosity for antibiotic desalination. For example, an optimized 18-nm membrane exhibited an unprecedented combination of high water permeance (81.2 liter m
−2
hour
−1
bar
−1
), antibiotic desalination efficiency (NaCl/tetracycline separation factor of 11.4), antifouling performance, and chlorine resistance.
Unearthing the Rosetta Stone of public antibody responses
Authors: Masi Gianvito
Published: May 2023

Comprehensive profiling of humoral responses to viruses reveals that germline-encoded V gene motifs govern the emergence of recurrent antibody epitopes across individuals.
High-flow oxygen therapy in moderate to severe bronchiolitis: a randomised controlled trial
Authors: Kooiman Louise , Blankespoor Fenneke , Hofman Roy , Kamps Arvid , Gorissen Monique , Vaessen-Verberne Anja , Heuts Ingrid , Bekhof Jolita
Published: May 2023

Background and objective

High-flow (HF) oxygen therapy is being used increasingly in infants with bronchiolitis, despite lack of convincing evidence of its superiority over low flow (LF). We aimed to compare the effect of HF to LF in moderate to severe bronchiolitis.

Methods

Multicentre randomised controlled trial during four winter seasons (2016–2020) including 107 children under 2 years of age admitted with moderate to severe bronchiolitis, oxygen saturation of <92% and severely impaired vital signs. Crossovers were not allowed. HF was administered at flow rates of 2 L/kg for the first 10 kg, plus 0.5 L/kg for every kg >10 kg, LF with a maximum flow rate of 3 L/min. Primary outcome was improvement of vital signs and dyspnoea severity within 24 hours assessed by a composite score. Secondary outcomes were comfort, duration of oxygen therapy, supplemental feedings, hospitalisation duration and intensive care admission for invasive ventilation.

Results

Significant improvement within 24 hours occurred in 73% of 55 patients randomised to HF and in 78% of 52 patients with LF (difference 6%, 95% CI −13% to 23%). Intention-to-treat analysis revealed no significant differences in any secondary outcome: duration of oxygen therapy, supplemental feedings, hospitalisation and need for invasive ventilation or intensive care admission, except for comfort (face, legs, activity, cry, consolability), which was one point (out of a scale of 0–10) higher in the LF group. No adverse effects occurred.

Conclusion

We found no measurable clinically relevant benefit in the use of HF compared with LF in hypoxic children with moderate to severe bronchiolitis.

Trial registration number

NCT02913040.
Two-year outcomes following a randomised platelet transfusion trial in
preterm infants
Authors: Moore Carmel Maria , D’Amore Angela , Fustolo-Gunnink Suzanne , Hudson Cara , Newton Alice , Santamaria Beatriz Lopez , Deary Alison , Hodge Renate , Hopkins Valerie , Mora Ana , Llewelyn Charlotte , Venkatesh Vidheya , Khan Rizwan , Willoughby Karen , Onland Wes , Fijnvandraat Karin , New Helen V , Clarke Paul , Lopriore Enrico , Watts Timothy , Stanworth Simon , Curley Anna
Published: May 2023

Objective

Assess mortality and neurodevelopmental outcomes at 2 years of
corrected age in children who participated in the PlaNeT-2/MATISSE
(Platelets for Neonatal Transfusion - 2/Management of Thrombocytopenia
in Special Subgroup) study, which reported that a higher platelet
transfusion threshold was associated with significantly increased
mortality or major bleeding compared to a lower one.

Design

Randomised clinical trial, enrolling from June 2011 to August 2017.
Follow-up was complete by January 2020. Caregivers were not blinded;
however, outcome assessors were blinded to treatment group.

Setting

43 level II/III/IV neonatal intensive care units (NICUs) across UK,
Netherlands and Ireland.

Patients

660 infants born at less than 34 weeks’ gestation with platelet
counts less than 50×109/L.

Interventions

Infants were randomised to undergo a platelet transfusion at
platelet count thresholds of 50×109/L (higher
threshold group) or 25×109/L (lower threshold
group).

Main outcomes measures

Our prespecified long-term follow-up outcome was a composite of
death or neurodevelopmental impairment (developmental delay, cerebral
palsy, seizure disorder, profound hearing or vision loss) at 2 years of
corrected age.

Results

Follow-up data were available for 601 of 653 (92%) eligible
participants. Of the 296 infants assigned to the higher threshold group,
147 (50%) died or survived with neurodevelopmental impairment, as
compared with 120 (39%) of 305 infants assigned to the lower threshold
group (OR 1.54, 95% CI 1.09 to 2.17, p=0.017).

Conclusions

Infants randomised to a higher platelet transfusion threshold of
50×109/L compared with
25×109/L had a higher rate of death or
significant neurodevelopmental impairment at a corrected age of 2 years.
This further supports evidence of harm caused by high prophylactic
platelet transfusion thresholds in preterm infants.

Trial registration number

NCT87736839.
Impact of the COVID-19 pandemic on young people from black and mixed ethnic groups’ mental health in West London: a qualitative study
Authors: Lenoir Romane , Wong Keri Ka-Yee
Published: May 2023

Objectives

The COVID-19 pandemic has disproportionately impacted vulnerable groups’ physical and mental health, especially young people and minority ethnic groups, yet little is known about the crux of their experiences and what support they would like. To address this gap, this qualitative study aims to uncover the effect of the COVID-19 outbreak on young people with ethnic minority backgrounds’ mental health, how this changed since the end of lockdown and what support they need to cope with these issues.

Design

The study utilised semi-structured interviews to conduct a phenomenological analysis.

Setting

Community centre in West London, England.

Participants

Ten 15 min in-person semistructured interviews were conducted with young people aged 12–17 years old from black and mixed ethnic groups who regularly attend the community centre.

Results

Through Interpretative Phenomenological Analysis, results indicated that the participants’ mental health was negatively impacted by the COVID-19 pandemic, with feelings of loneliness being the most common experience. However, positive effects were concurrently observed including improved well-being and better coping strategies post lockdown, which is a testament to the young people’s resilience. That said, it is clear that young people from minority ethnic backgrounds lacked support during the COVID-19 pandemic and would now need psychological, practical and relational assistance to cope with these challenges.

Conclusions

While future studies would benefit from a larger ethnically diverse sample, this is a start. Study findings have the potential to inform future government policies around mental health support and access for young people from ethnic minority groups, notably prioritising support for grassroots initiatives during times of crisis.
Fungi and cancer
Authors: Saftien Aurelia , Puschhof Jens , Elinav Eran
Published: May 2023

The microbiome may impact cancer development, progression and treatment responsiveness, but its fungal components remain insufficiently studied in this context. In this review, we highlight accumulating evidence suggesting a possible involvement of commensal and pathogenic fungi in modulation of cancer-related processes. We discuss the mechanisms by which fungi can influence tumour biology, locally by activity exerted within the tumour microenvironment, or remotely through secretion of bioactive metabolites, modulation of host immunity and communications with neighbouring bacterial commensals. We examine prospects of utilising fungi-related molecular signatures in cancer diagnosis, patient stratification and assessment of treatment responsiveness, while highlighting challenges and limitations faced in performing such research. In all, we demonstrate that fungi likely constitute important members of mucosal and tumour-residing microbiomes. Exploration of fungal inter-kingdom interactions with the bacterial microbiome and the host and decoding of their causal impacts on tumour biology may enable their harnessing into cancer diagnosis and treatment.
Transcatheter aortic valve intervention in patients with cancer
Authors: Leedy Douglas , Elison David M , Farias Francisco , Cheng Richard , McCabe James M
Published: May 2023

The prevalence of concurrent cancer and severe aortic stenosis (AS) is increasing due to an ageing population. In addition to shared traditional risk factors for AS and cancer, patients with cancer may be at increased risk for AS due to off-target effects of cancer-related therapy, such as mediastinal radiation therapy (XRT), as well as shared non-traditional pathophysiological mechanisms. Compared with surgical aortic valve replacement, major adverse events are generally lower in patients with cancer undergoing transcatheter aortic valve intervention (TAVI), especially in those with history of mediastinal XRT. Similar procedural and short-to-intermediate TAVI outcomes have been observed in patients with cancer as compared with no cancer, whereas long-term outcomes are dependent on cancer survival. Considerable heterogeneity exists between cancer subtypes and stage, with worse outcomes observed in those with active and advanced-stage disease as well as specific cancer subtypes. Procedural management in patients with cancer poses unique challenges and thus requires periprocedural expertise and close collaboration with the referring oncology team. The decision to ultimately pursue TAVI involves a multidisciplinary and holistic approach in assessing the appropriateness of intervention. Further clinical trial and registry studies are needed to better appreciate outcomes in this population.
Direct medical charges of all parties in teen-involved vehicle crashes by culpability
Authors: Peek-Asa Corinne , Zhang Ling , Hamann Cara J , O'Neal Elizabeth , Yang Jingzhen
Published: May 2023

Background

Motor vehicle crashes among teen drivers often involve passengers in the teen’s vehicle and occupants of other vehicles, and the full cost burden for all individuals is largely unknown. This analysis estimated direct hospitalisation and emergency department charges for teen-involved crashes by teen culpability, comparing charges for the teen driver, passengers and occupants of other vehicles.

Methods

Probabilistic linkage was performed to link the Iowa police crash reports with Iowa emergency department and Iowa hospital inpatient data. Teen drivers aged 14–17 involved in a crash from 2016 through 2020 were included. Teen culpability was determined through the crash report and examined by teen and crash characteristics. Direct medical charges were estimated from charges through linkage to the Iowa hospital inpatient and the Iowa emergency department databases.

Results

Among the 28 062 teen drivers involved in vehicle crashes in Iowa between 2016 and 2020, 62.1% were culpable and 37.9% were not culpable. For all parties involved, the inpatient charges were $20.5 million in culpable crashes and $7.2 million in non-culpable crashes. The emergency department charges were $18.7 million in teen culpable crashes and $6.8 million in teen non-culpable crashes. Of the $20.5 million total inpatient charges in which a teen driver was culpable, charges of $9.5 million (46.3%) were for the injured teen driver and $11.0 million (53.7%) for other involved parties.

Conclusions

Culpable teen-involved crashes lead to higher proportions of injury and higher medical charges, with most of these charges covering other individuals in the crash.