bluuebunny/crossref_metadata_2025 huggingface dataset:
Deciphering the tumour immune microenvironment of hepatocellular carcinoma
Authors: Liu Sha , Jia Man , Dai Rongyang
Published: September 2023

Current treatments for hepatocellular carcinoma (HCC) are less effective and prone to recurrence after surgery, so it's needed to seek new ideas for its therapy. Tumour immune microenvironment (TME) is crucial for the pathogenesis, development and metastasis of HCC. Interactions between immune cells and tumour cells significantly impact responses to immunotherapies and patient prognosis. In recent years, immunotherapies for HCC have shown promising potential, but the response rate is still unsatisfactory. Understanding their cross‐talks is helpful for selecting potential therapeutic targets, predicting immunotherapy responses, determining immunotherapy efficacy, identifying prognostic markers and selecting individualized treatment options. In this paper, we reviewed the research advances on the roles of immune cells and multi‐omic research associated with HCC pathogenesis and therapy, and future perspectives on TME.
Effects of tempo ofself‐selectedmusic on isokinetic strength performance and psychological outcomes
Authors: Svoboda Stephanie M. , Kostrna Jason
Published: September 2023

Substantial research has supported using musical stimuli as an ergogenic aid before and during various forms of exercise. Researchers have demonstrated that music shifts attention from associative to dissociative, decreases perceived effort and discomfort, and increases arousal and pleasantness in longer‐duration, low‐to‐moderate‐intensity exercises. Strength training is shorter in duration and higher in intensity than aerobic or muscular endurance training. Limited research has examined the effects of music on strength performance and psychological outcomes. Therefore, the purpose of this study was to investigate the effects of the tempo of self‐selected music on isokinetic knee extension and flexion performance, effort, discomfort, attention, arousal, and pleasantness in resistance‐trained young adults. Thirty resistance‐trained college‐aged adults completed three exercise testing sessions. In a randomized, counterbalanced order, a repeated measures design was used to expose the participants to three conditions (fast music, slow music, and no music). The Biodex isokinetic dynamometer and standardized psychological Likert‐style scales were used to measure concentric maximum effort knee extension and flexion torque at 60°/s and psychological variables, respectively. This study found that music improves knee extension torque but not knee flexion in resistance‐trained young adults. In addition, music or the tempo of music did not influence any psychological outcomes during isokinetic strength testing. Therefore, listening to music is not detrimental to performance or psychological outcomes, but this study provides minimal support for music's use as an ergogenic aid during strengthening exercise.
“Marriage fraud” or social constraint? Reasons for understanding tongzhi and tongqi in mixed‐orientation marriages in China
Authors: Song Changhui , Ding Runze , Xie Hui
Published: September 2023

This qualitative study was conducted in the context of ongoing debates on “marriage fraud” to explore the underlying social structural and individual reasons for entering mixed‐orientation marriages affecting men who have sex with men (tongzhi in Chinese) and non‐complicit women (tongqi) who married tongzhi in China. Using a phenomenological approach, sixty‐eight (34 tongzhi and 34 tongqi, unpaired) semi‐structured interviews were conducted through in‐person interviews or WeChat audio interviews between 2018 and 2019 in China. Guided by thematic analysis, three themes explaining the shared pressure from the societal, family, and individual levels that drove individuals' decisions about whom they partnered with, and when and how they entered marriage among tongzhi and tongqi: marriage normativity, filial piety, and conformity with conventional marriage. The findings showed that marital decisions for tongzhi and tongqi were constrained by the similar social power of marriage normativity, filial piety, and heteronormativity in China. Some marriages fell within the scope of marriage fraud, but most of them fell within the scope of performing conventional marriages. This phenomenon was beyond simple explanations of marriage fraud. Future studies need to investigate multi‐level constraints concerning family relations for sexual minorities in China on a large scale.
Reputation and prosocial lies in development
Authors: Guo Cynthia Xinran , Rochat Philippe
Published: September 2023

Children start to engage in self‐serving deception from approximately 2½ years of age. This emerging self‐centered propensity toward the deliberate covering of truth is predicted by the child's degree of executive function and level of theory of mind. In contrast, existing studies on the emergence of other‐oriented lies point to a significant developmental lag—children begin to produce prosocial lies not prior to 3–4 years of age. What may account for such a lag? In this article, we review the recent literature and conclude that the existing cognitive account does not fully explain the developmental lag between self‐ and other‐serving deception. As an alternative, we propose that reputational concerns may drive the ontogeny of prosocial lies and account for their later emergence.
Banal gastronationalism and anti‐EU populism
Authors: Pospěch Pavel
Published: September 2023

The common market of the EU imposes standards on food products and minimum requirements for their quality. Products that do not meet these requirements have to be renamed. This article analyses the media coverage of a prominent political controversy surrounding four food products, produced in the Czech Republic: Inland Rum, Fruit Marmalade, Spread Butter and Almond Brandy. The renaming of these products has triggered a wave of nationalist sentiments and anti‐EU backlash. To explain these developments, the article follows the strong programme in cultural sociology, and it introduces the concept ‘banal gastronationalism’. It argues that the anti‐EU backlash is culturally rooted in two deeply rooted binary distinctions: the split between the centre (of the EU) and the periphery and the tension between the inner and the external. Together, these distinctions co‐create an imagined community of consumers and readers, which gets mobilised through a perceived threat to its food products.
Influence of a single oral dose of trazodone on intradermal histamine reactivity in clinically healthy dogs
Authors: Lewis Sarah Taylor , Kennis Robert Allen , Clark‐Price Stuart Charles , White Amelia Grant
Published: September 2023

Background

Drug interactions are significant considerations for intradermal testing (IDT). Trazodone (TRZ) is an anxiolytic and selective histaminergic (H1) antagonist with no interaction in human prick tests; however, interaction in canine IDT is unknown.

Hypothesis/Objectives

Trazodone will not adversely affect intradermal histamine reactions in dogs.

Animals

Fourteen nonanxious, nonatopic, healthy client‐owned dogs were enrolled in this randomised, blinded, cross‐over study.

Materials and Methods

Dogs were randomised to receive low‐dose TRZ (4 mg/kg) (Teva Pharmaceuticals), high‐dose TRZ (8 mg/kg) or no TRZ per os two hours before intravenous sedation with dexmedetomidine (5 mcg/kg) (Dexdomitor; Zoetis). Intradermal testing was performed with five quadrupling dilutions of histamine (1:100,000 to 1:25,600,000 w/v; Greer) and 0.9% saline (Hospira), observing a minimum two weeks washout period between treatments. Two observers, who were blinded to treatment and the identity of the injections, evaluated each test using previously established subjective and objective methods.

Results

The mean wheal diameter of histamine 1:1,600,000 w/v was significantly smaller with low‐dose TRZ (4 mg/kg) compared to the control group (p = 0.048; repeated measures ANOVA with post hoc Tukey's test). For all other histamine dilutions and saline, mean wheal diameter was not significantly different among groups. There were no significant differences in the subjective scores of all histamine dilutions and saline (p > 0.05; Friedman test).

Conclusion and Clinical Relevance

A single oral dose of TRZ does not adversely affect intradermal histamine reactions in dogs.
Poor success rates with double pelvic osteotomy for craniodorsal luxation of total hip prosthesis in 11 dogs
Authors: Thibault Alexandre , Haudiquet Philippe H.
Published: September 2023

Objective

To report the outcome of double pelvic osteotomy (DPO) for craniodorsal luxation of total hip replacement (THR).

Study design

Retrospective case series.

Animals

Eleven client‐owned animals.

Methods

Dogs with craniodorsal luxation of THR and high angle of lateral opening (ALO) were considered candidates for DPO. The ALO and the version angle (VA) were measured on pre‐ and post‐DPO radiographs. Pre‐ and post‐DPO ALO and VA were compared using a Wilcoxon signed‐rank test. Clinical and radiographic outcomes were assessed at 2 and 6 months post‐DPO.

Results

Eleven DPOs were performed on 11 dogs after THR luxation. The ALO was reduced from a median of 66.2° (range 37.3–73.1°) to 55.9° (range 13.2–60.0°) (p ≤ .001), and VA increased from a median of 25.6° (range 6.8–51.9°) to 35.3° (range 15.1–51.7°) (p ≤ .03). Craniodorsal luxation recurred in five dogs and was managed with closed reduction (one dog), capsulorrhaphy (one dog), or repositioning of the acetabular cup (three dogs). The median clinical follow‐up duration was 19.7 months (range 3.4–73.0). In the long term, seven dogs required explantation (five aseptic loosenings, two infections) (median 8.2 months, range 2.6–50.6).

Conclusion

Reluxation was frequent after DPO, 5/11 dogs requiring additional procedures, including three cup revisions. The long‐term outcome was considered to be poor due to frequent explantation.

Clinical significance

Double pelvic osteotomy may be considered to avoid cup replacement when managing craniodorsal THR luxations in dogs but is not recommended due to high complication rates.
Real-Time Hand Gesture Recognition Using YOLO and (Darknet-19) Convolution Neural Networks
Authors: Mohamed Raad Ahmed , Hussein Karim Q
Published: September 2023

There are at least three hundred and fifty million people in the world that cannot hear or speak. These are what are called deaf and dumb. Often this segment of society is partially isolated from the rest of society due to the difficulty of dealing, communicating and understanding between this segment and the rest of the healthy society. As a result of this problem, a number of solutions have been proposed that attempt to bridge this gap between this segment and the rest of society. The main reason for this is to simplify the understanding of sign language. The basic idea is building program to recognize the hand movement of the interlocutor and convert it from images to symbols or letters found in the dictionary of the deaf and dumb. This process itself follows mainly the applications of artificial intelligence, where it is important to distinguish, identify, and extract the palm of the hand from the regular images received by the camera device, and then convert this image of the movement of the paws or hands into understandable symbols. In this paper, the method of image processing and artificial intelligence, represented by the use of artificial neural networks after synthesizing the problem under research was used. Scanning the image to determine the areas of the right and left palm. Non-traditional methods that use artificial intelligence like Convolutional Neural Networks are used to fulfill this part. YOLO V-2 specifically was used in the current research with excellent results. Part Two: Building a pictorial dictionary of the letters used in teaching the deaf and dumb, after generating the image database for the dictionary, neural network Dark NET-19 were used to identify (classification) the images of characters extracted from the first part of the program. The results obtained from the research show that the use of neural networks, especially convolution neural networks, is very suitable in terms of accuracy, speed of performance, and generality in processing the previously unused input data. Many of the limitations associated with using such a program without specifying specific shapes (general shape) and templates, hand shape, hand speed, hand color and other physical expressions and without using any other physical aids were overcome through the optimal use of artificial convolution neural networks.
Mass-Heat Coupling in Film Cooling Experiments—The Influence of Temperature and Turbulence on the Dufour Effect
Authors: Wiese Connor J. , Rutledge James L.
Published: September 2023

The use of foreign gases in laboratory film cooling experiments is attractive since variable density ratios can be achieved with coolant-to-freestream temperature ratios near unity, often reducing the cost and difficulty of the experimental campaign. In adiabatic effectiveness experiments employing pressure sensitive paint along with the mass transfer analogy to heat transfer, isothermal surfaces are often an experimental requirement. Furthermore, low-temperature laboratory experiments using thermal techniques often employ relatively close matches between the coolant and freestream temperatures. Using foreign gases, however, introduces off-diagonal couplings of heat and mass transport, which can produce unexpected results in film cooling experiments. In particular, the Dufour effect—also called the diffusion-thermo effect—which is the transfer of thermal energy by mass transfer processes, can manifest in surface temperatures that break the traditional bounds of thermal adiabatic effectiveness experiments: outside the upper and lower bounds of the coolant and freestream temperature. Beyond the expected confusion for the researcher, this effect can also be detrimental to those that assume that matching the coolant and freestream temperatures are the necessary and sufficient conditions to ensure isothermal surface conditions in traditional pressure sensitive paint experiments. In this work, the influence of cooling gas selection, experimental temperature, and experimental freestream turbulence conditions are explored on a simulated leading edge with compound injection from a cylindrical cooling hole. Air, argon, carbon dioxide, helium, and nitrogen coolants were analyzed due to their use in prior film cooling studies. The Dufour effect was found to be significant when using helium as the coolant, though temperature separation was also observed in argon and carbon dioxide cases. Additionally, elevated experiment temperatures generally increased temperature separation. Finally, high freestream turbulence intensity was found to reduce, but not eliminate, the Dufour effect in helium experiments.
Propulsion Aerodynamics for a Novel High-Speed Exhaust System
Authors: Tsentis Spyros , Goulos Ioannis , Prince Simon , Pachidis Vassilios , Zmijanovic Vladeta
Published: September 2023

A key requirement to achieve sustainable high-speed flight and efficiency improvements in space access lies in the advanced performance of future propulsive architectures. Such concepts often feature high-speed nozzles, similar to rocket engines, but employ different configurations tailored to their mission. Additionally, they exhibit complex interaction phenomena between high-speed and separated flow regions at the base, which are not yet well understood. This paper presents a numerical investigation on the aerodynamic performance of a representative, novel exhaust system, which employs a high-speed nozzle and a complex-shaped cavity region at the base. Reynolds-Averaged Navier–Stokes computations are performed for a number of nozzle pressure ratios (NPRs) and freestream Mach numbers in the range of 2.7 < NPR < 24 and 0.7 < M∞ < 1.2, respectively. The corresponding Reynolds number lies within the range of 1.06 × 106 < Red < 1.28 × 106 based on the maximum diameter of the configuration. The impact of the cavity is revealed by direct comparison to an identical noncavity configuration. Results show a consistent trend of increasing base drag with increasing NPR for both configurations, owing to the jet entrainment effect. Cavity is found to have no impact on the incipient separation location of the nozzle flow. At conditions of M∞ = 1.2 and high NPRs, the cavity has a significant effect on the aerodynamic performance, transitioning nozzle operation to underexpanded conditions. This results in approximately 12% higher drag coefficient compared to the noncavity case and shifts the minimum NPR required for positive gross propulsive force to higher values.
Pollutant Emissions Reporting and Performance Considerations for Ammonia-Blended Fuels in Gas Turbines
Authors: Douglas Christopher M. , Martz Thomas D. , Steele Robert C. , Noble David R. , Emerson Benjamin L. , Lieuwen Timothy C.
Published: September 2023

To limit climate change and promote energy security, there is widespread interest toward transitioning existing fossil fueled combustion systems to sustainable, alternative fuels such as hydrogen (H2) and ammonia (NH3) without negatively impacting air quality. However, quantifying the emission rate of air pollutants such as nitrogen oxides (NOx) is a nuanced process when comparing pollutant emissions across different fuels, as discussed in our paper GT2022-80971 presented last year. That study indicated that the standardized approach for measuring combustion emissions in terms of dry, oxygen-referenced volumetric concentrations (i.e., dry ppmv at the reference O2 concentration (ppmvdr)) inflates reported pollutant emissions by up to 40% for hydrogen combustion relative to natural gas. In this paper, we extend our prior analysis of these so-called “indirect effects” on emissions values to ammonia (NH3) and cracked ammonia (i.e., molecular hydrogen and nitrogen, 3H2 per N2) fuel blends. The results reveal that ppmvdr-based pollutant reporting approaches have a less prominent influence on emissions interpretations for molecular ammonia–methane blends than for hydrogen–methane blends. Nonetheless, we still find that ppmvdr reporting induces up to a 10% relative increase in apparent emissions when comparing 100% NH3 and 100% methane (CH4) fuels at an equal mass-per-work emission rate. Cracking the ammonia is shown to increase this relative bias up to 21% in comparison to a methane system. Further analysis shows how drying, dilution, thermodynamic, and performance effects each influence the relationship between ppmvdr and mass-per-work emissions across the spectrum of fuels and fuel blends. Following discussion of these findings, we conclude that quantifying combustion emissions using ppmvdr is generally inappropriate for emissions comparisons and advise the combustion community to shift toward robust mass-per-energy metrics when quantifying pollutant emissions.
Buckling-induced transmission switching in phononic waveguides
Authors: Kanj Ali , Vakakis Alexander F. , Tawfick Sameh
Published: September 2023

On-chip phononic circuits tailor the transmission of elastic waves and couple to electronics and photonics to enable new signal manipulation capabilities. Phononic circuits rely on waveguides that transmit elastic waves within desired frequency passbands, which are typically designed based on the Bloch modes of the constitutive unit cell of the waveguide, assuming periodicity. Acoustic microelectromechanical system waveguides composed of coupled drumhead resonators offer megahertz operation frequencies for applications in acoustic switching. Here, we construct a reduced-order model (ROM) to demonstrate the mechanism of transmission switching in coupled drumhead-resonator waveguides. The ROM considers the mechanics of buckling under the effect of temperature variation. Each unit cell has two degrees of freedom: translation to capture the symmetric bending modes and angular motion to capture the asymmetric bending modes of the membranes. We show that thermoelastic buckling induces a phase transition triggered by temperature variation, causing the localization of the first-passband modes, similar to Anderson localization caused by disorders. The proposed ROM is essential to understanding these phenomena since Bloch mode analysis fails for weakly disordered (<5%) finite waveguides due to the disorder amplification caused by the thermoelastic buckling. The illustrated transmission control can be extended to two-dimensional circuits in the future.
Codependencies of mTORC1 signaling and endolysosomal actin structures
Authors: Priya Amulya , Antoine-Bally Sandra , Macé Anne-Sophie , Monteiro Pedro , Sabatet Valentin , Remy David , Dingli Florent , Loew Damarys , Demetriades Constantinos , Gautreau Alexis M. , Chavrier Philippe
Published: September 2023

The mechanistic target of rapamycin complex 1 (mTORC1) is part of the amino acid sensing machinery that becomes activated on the endolysosomal surface in response to nutrient cues. Branched actin generated by WASH and Arp2/3 complexes defines endolysosomal microdomains. Here, we find mTORC1 components in close proximity to endolysosomal actin microdomains. We investigated for interactors of the mTORC1 lysosomal tether, RAGC, by proteomics and identified multiple actin filament capping proteins and their modulators. Perturbation of RAGC function affected the size of endolysosomal actin, consistent with a regulation of actin filament capping by RAGC. Reciprocally, the pharmacological inhibition of actin polymerization or alteration of endolysosomal actin obtained upon silencing of WASH or Arp2/3 complexes impaired mTORC1 activity. Mechanistically, we show that actin is required for proper association of RAGC and mTOR with endolysosomes. This study reveals an unprecedented interplay between actin and mTORC1 signaling on the endolysosomal system.
Distribution modeling quantifies collective T
H
cell decision circuits in chronic inflammation
Authors: Burt Philipp , Thurley Kevin
Published: September 2023

Immune responses are tightly regulated by a diverse set of interacting immune cell populations. Alongside decision-making processes such as differentiation into specific effector cell types, immune cells initiate proliferation at the beginning of an inflammation, forming two layers of complexity. Here, we developed a general mathematical framework for the data-driven analysis of collective immune cell dynamics. We identified qualitative and quantitative properties of generic network motifs, and we specified differentiation dynamics by analysis of kinetic transcriptome data. Furthermore, we derived a specific, data-driven mathematical model for T helper 1 versus T follicular helper cell-fate decision dynamics in acute and chronic lymphocytic choriomeningitis virus infections in mice. The model recapitulates important dynamical properties without model fitting and solely by using measured response-time distributions. Model simulations predict different windows of opportunity for perturbation in acute and chronic infection scenarios, with potential implications for optimization of targeted immunotherapy.
Earth beyond six of nine planetary boundaries
Authors: Richardson Katherine , Steffen Will , Lucht Wolfgang , Bendtsen Jørgen , Cornell Sarah E. , Donges Jonathan F. , Drüke Markus , Fetzer Ingo , Bala Govindasamy , von Bloh Werner , Feulner Georg , Fiedler Stephanie , Gerten Dieter , Gleeson Tom , Hofmann Matthias , Huiskamp Willem , Kummu Matti , Mohan Chinchu , Nogués-Bravo David , Petri Stefan , Porkka Miina , Rahmstorf Stefan , Schaphoff Sibyll , Thonicke Kirsten , Tobian Arne , Virkki Vili , Wang-Erlandsson Lan , Weber Lisa , Rockström Johan
Published: September 2023

This planetary boundaries framework update finds that six of the nine boundaries are transgressed, suggesting that Earth is now well outside of the safe operating space for humanity. Ocean acidification is close to being breached, while aerosol loading regionally exceeds the boundary. Stratospheric ozone levels have slightly recovered. The transgression level has increased for all boundaries earlier identified as overstepped. As primary production drives Earth system biosphere functions, human appropriation of net primary production is proposed as a control variable for functional biosphere integrity. This boundary is also transgressed. Earth system modeling of different levels of the transgression of the climate and land system change boundaries illustrates that these anthropogenic impacts on Earth system must be considered in a systemic context.
Past extent of lunar permanently shadowed areas
Authors: Schörghofer Norbert , Rufu Raluca
Published: September 2023

As the Moon migrated away from Earth, it experienced a major spin axis reorientation. Permanently shadowed regions (PSRs), which are thought to have trapped ices and are a main focus of lunar exploration, appeared and grew after this (Cassini state) transition and are often younger than their host craters. Here, we calculate the lunar spin axis orientation and the extent of PSRs based on recent advances for the time evolution of the Earth-Moon distance. The solar declination reached twice its current value 2.1 billion years (Ga) ago, when the PSR area was about half as large. The PSR area becomes negligible beyond 3.4 Ga ago. The site of an artificial impact in Cabeus Crater, where various volatiles have been detected, became continuously shadowed only about 0.9 Ga ago, and hence, cold-trapping has continued into this relatively recent time period. Overall estimates for the amount of cold-trapped ices have to be revised downward.
PARP14 is a PARP with both ADP-ribosyl transferase and hydrolase activities
Authors: Đukić Nina , Strømland Øyvind , Elsborg Jonas Damgaard , Munnur Deeksha , Zhu Kang , Schuller Marion , Chatrin Chatrin , Kar Pulak , Duma Lena , Suyari Osamu , Rack Johannes Gregor Matthias , Baretić Domagoj , Crudgington Dorian Richard Kenneth , Groslambert Joséphine , Fowler Gerissa , Wijngaarden Sven , Prokhorova Evgeniia , Rehwinkel Jan , Schüler Herwig , Filippov Dmitri V. , Sanyal Sumana , Ahel Dragana , Nielsen Michael L , Smith Rebecca , Ahel Ivan
Published: September 2023

PARP14 is a mono–ADP-ribosyl transferase involved in the control of immunity, transcription, and DNA replication stress management. However, little is known about the ADP-ribosylation activity of PARP14, including its substrate specificity or how PARP14-dependent ADP-ribosylation is reversed. We show that PARP14 is a dual-function enzyme with both ADP-ribosyl transferase and hydrolase activity acting on both protein and nucleic acid substrates. In particular, we show that the PARP14 macrodomain 1 is an active ADP-ribosyl hydrolase. We also demonstrate hydrolytic activity for the first macrodomain of PARP9. We reveal that expression of a PARP14 mutant with the inactivated macrodomain 1 results in a marked increase in mono(ADP-ribosyl)ation of proteins in human cells, including PARP14 itself and antiviral PARP13, and displays specific cellular phenotypes. Moreover, we demonstrate that the closely related hydrolytically active macrodomain of SARS2 Nsp3, Mac1, efficiently reverses PARP14 ADP-ribosylation in vitro and in cells, supporting the evolution of viral macrodomains to counteract PARP14-mediated antiviral response.
Chimeric hemagglutinin split vaccines elicit broadly cross-reactive antibodies and protection against group 2 influenza viruses in mice
Authors: Puente-Massaguer Eduard , Vasilev Kirill , Beyer Annika , Loganathan Madhumathi , Francis Benjamin , Scherm Michael J. , Arunkumar Guha Asthagiri , González-Domínguez Irene , Zhu Xueyong , Wilson Ian A. , Coughlan Lynda , Sun Weina , Palese Peter , Krammer Florian
Published: September 2023

Seasonal influenza virus vaccines are effective when they are well matched to circulating strains. Because of antigenic drift/change in the immunodominant hemagglutinin (HA) head domain, annual vaccine reformulations are necessary to maintain a match with circulating strains. In addition, seasonal vaccines provide little to no protection against newly emerging pandemic strains. Sequential vaccination with chimeric HA (cHA) constructs has been proven to direct the immune response toward the immunosubdominant but more conserved HA stalk domain. In this study, we show that immunization with group 2 cHA split vaccines in combination with the CpG 1018 adjuvant elicits broadly cross-reactive antibodies against all group 2 HAs, as well as systemic and local antigen-specific T cell responses. Antibodies elicited after sequential vaccination are directed to conserved regions of the HA such as the stalk and the trimer interface and also to the N2 neuraminidase (NA). Immunized mice were fully protected from challenge with a broad panel of influenza A viruses.
A microtubule stabilizer ameliorates protein pathogenesis and neurodegeneration in mouse models of repetitive traumatic brain injury
Authors: Zhao Xinyi , Zeng Wen , Xu Hong , Sun Zihan , Hu Yingxin , Peng Beibei , McBride Jennifer D. , Duan Jiangtao , Deng Juan , Zhang Bin , Kim Soo-Jung , Zoll Bryan , Saito Takashi , Sasaguri Hiroki , Saido Takaomi C. , Ballatore Carlo , Yao Haishan , Wang Zhaoyin , Trojanowski John Q. , Brunden Kurt R. , Lee Virginia M.-Y. , He Zhuohao
Published: September 2023

Tau pathogenesis is a hallmark of many neurodegenerative diseases, including Alzheimer’s disease (AD). Although the events leading to initial tau misfolding and subsequent tau spreading in patient brains are largely unknown, traumatic brain injury (TBI) may be a risk factor for tau-mediated neurodegeneration. Using a repetitive TBI (rTBI) paradigm, we report that rTBI induced somatic accumulation of phosphorylated and misfolded tau, as well as neurodegeneration across multiple brain areas in 7-month-old tau transgenic PS19 mice but not wild-type (WT) mice. rTBI accelerated somatic tau pathology in younger PS19 mice and WT mice only after inoculation with tau preformed fibrils and AD brain–derived pathological tau (AD-tau), respectively, suggesting that tau seeds are needed for rTBI-induced somatic tau pathology. rTBI further disrupted axonal microtubules and induced punctate tau and TAR DNA binding protein 43 (TDP-43) pathology in the optic tracts of WT mice. These changes in the optic tract were associated with a decline of visual function. Treatment with a brain-penetrant microtubule-stabilizing molecule reduced rTBI-induced tau, TDP-43 pathogenesis, and neurodegeneration in the optic tract as well as visual dysfunction. Treatment with the microtubule stabilizer also alleviated rTBI-induced tau pathology in the cortices of AD-tau–inoculated WT mice. These results indicate that rTBI facilitates abnormal microtubule organization, pathological tau formation, and neurodegeneration and suggest microtubule stabilization as a potential therapeutic avenue for TBI-induced neurodegeneration.
Domain-based mRNA vaccines encoding spike protein N-terminal and receptor binding domains confer protection against SARS-CoV-2
Authors: Stewart-Jones Guillaume B. E. , Elbashir Sayda M. , Wu Kai , Lee Diana , Renzi Isabella , Ying Baoling , Koch Matthew , Sein Caralyn E. , Choi Angela , Whitener Bradley , Garcia-Dominguez Dario , Henry Carole , Woods Angela , Ma LingZhi , Montes Berrueta Daniela , Avena Laura E. , Quinones Julian , Falcone Samantha , Hsiao Chiaowen J. , Scheaffer Suzanne M. , Thackray Larissa B. , White Phil , Diamond Michael S. , Edwards Darin K. , Carfi Andrea
Published: September 2023

With the success of messenger RNA (mRNA) vaccines against coronavirus disease 2019, strategies can now focus on improving vaccine potency, breadth, and stability. We designed and evaluated domain-based mRNA vaccines encoding the wild-type spike protein receptor binding domain (RBD) or N-terminal domain (NTD) alone or in combination. An NTD-RBD–linked candidate vaccine, mRNA-1283, showed improved antigen expression, antibody responses, and stability at refrigerated temperatures (2° to 8°C) compared with the clinically available mRNA-1273, which encodes the full-length spike protein. In BALB/c mice administered mRNA-1283 as a primary series, booster, or variant-specific booster, similar or greater immune responses from viral challenge were observed against wild-type, beta, delta, or omicron (BA.1) viruses compared with mRNA-1273–immunized mice, especially at lower vaccine dosages. K18-hACE2 mice immunized with mRNA-1283 or mRNA-1273 as a primary series demonstrated similar degrees of protection from challenge with SARS-CoV-2 Delta and Omicron variants at all vaccine dosages. These results support clinical assessment of mRNA-1283, which has now entered clinical trials (NCT05137236).
CWHM-974 is a fluphenazine derivative with improved antifungal activity against
Candida albicans
due to reduced susceptibility to multidrug transporter-mediated resistance mechanisms
Authors: Miron-Ocampo Aracely , Beattie Sarah R. , Guin Soumitra , Conway Thomas , Meyers Marvin J. , Moye-Rowley W. Scott , Krysan Damian J.
Published: September 2023

Multidrug resistance (MDR) transporters such as ATP-Binding Cassette (ABC) and Major Facilitator Superfamily proteins are important mediators of antifungal drug resistance, particularly with respect to azole class drugs. Consequently, identifying molecules that are not susceptible to this mechanism of resistance is an important goal for new antifungal drug discovery. As part of a project to optimize the antifungal activity of clinically used phenothiazines, we synthesized a fluphenazine derivative (CWHM-974) with 8-fold higher activity against
Candida
spp. compared to the fluphenazine and with activity against
Candida
spp. with reduced fluconazole susceptibility due to increased MDR transporters. Here, we show that the improved
C. albicans
activity is because fluphenazine induces its own resistance by triggering expression of
Candida
drug resistance (CDR) transporters while CWHM-974 induces expression but does not appear to be a substrate for the transporters or is insensitive to their effects through other mechanisms. We also found that fluphenazine and CWHM-974 are antagonistic with fluconazole in
C. albicans
but not in
C. glabrata
, despite inducing
CDR1
expression to high levels. Overall, CWHM-974 is one of the few examples of a molecule in which relatively small structural modifications significantly reduced susceptibility to multidrug transporter-mediated resistance.
POEMS syndrome: an unusual cause of exuberant callus formation
Authors: Malhotra Bhanu , Sood Ashwini , Malhotra Pankaj , Bhadada Sanjay
Published: September 2023

Several growth factors are expressed in distinct temporal and spatial patterns during fracture repair. Together, they lead to angiogenesis–osteogenesis coupling and hence bone healing by callus formation. Of these growth factors, vascular endothelial growth factor is of particular interest because of its ability to induce neovascularisation (angiogenesis) and osteoclast invasion in soft callus. Hyperplastic callus can be seen in metabolic bone disease, endocrine disease and in patients with traumatic brain injury, but has not been described so far in polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes (POEMS) syndrome. This report is a case of POEMS syndrome with unusual presentation in the form of exuberant callus formation at fracture sites.
Vedolizumab-induced acute interstitial nephritis with failure of steroid prophylaxis on vedolizumab rechallenge
Authors: O'Leary Cian , Wong David , Wilson Gregory
Published: September 2023

Acute interstitial nephritis (AIN) is a common cause of acute kidney injury and renal failure. It is typically drug induced but can also be idiopathic or secondary to chronic infective or inflammatory conditions. Recent case reports suggest vedolizumab can be a causative agent for AIN. We report the case of a young man who presented with renal failure, fevers and constitutional symptoms. He had a complex history of refractory ulcerative colitis, prior colectomy and ileo-pouch-anal anastomosis with recurrent pouchitis. He had been receiving regular vedolizumab infusions for 6 months by the time of his presentation. A renal biopsy 4 months into his follow-up demonstrated AIN. Steroid prophylaxis with vedolizumab was trialled but ultimately failed, with worsening AIN and incomplete renal function recovery. To our knowledge, this is the first case of vedolizumab-induced AIN demonstrating a failure of steroid prophylaxis to prevent recurrence of AIN following vedolizumab rechallenge.
Development of the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) guideline
Authors: Hansford Harrison J , Cashin Aidan G , Jones Matthew D , Swanson Sonja A , Islam Nazrul , Dahabreh Issa J , Dickerman Barbra A , Egger Matthias , Garcia-Albeniz Xavier , Golub Robert M , Lodi Sara , Moreno-Betancur Margarita , Pearson Sallie-Anne , Schneeweiss Sebastian , Sterne Jonathan , Sharp Melissa K , Stuart Elizabeth A , Hernan Miguel A , Lee Hopin , McAuley James H
Published: September 2023

Background

Observational studies are increasingly used to inform health decision-making when randomised trials are not feasible, ethical or timely. The target trial approach provides a framework to help minimise common biases in observational studies that aim to estimate the causal effect of interventions. Incomplete reporting of studies using the target trial framework limits the ability for clinicians, researchers, patients and other decision-makers to appraise, synthesise and interpret findings to inform clinical and public health practice and policy. This paper describes the methods that we will use to develop the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) reporting guideline.

Methods/design

The TARGET reporting guideline will be developed in five stages following recommended guidance. The first stage will identify target trial reporting practices by systematically reviewing published studies that explicitly emulated a target trial. The second stage will identify and refine items to be considered for inclusion in the TARGET guideline by consulting content experts using sequential online surveys. The third stage will prioritise and consolidate key items to be included in the TARGET guideline at an in-person consensus meeting of TARGET investigators. The fourth stage will produce and pilot-test both the TARGET guideline and explanation and elaboration document with relevant stakeholders. The fifth stage will disseminate the TARGET guideline and resources via journals, conferences and courses.

Ethics and dissemination

Ethical approval for the survey has been attained (HC220536). The TARGET guideline will be disseminated widely in partnership with stakeholders to maximise adoption and improve reporting of these studies.
SUMO-3 promotes the ubiquitin-dependent turnover of TRIM55
Authors: Hammami Nour-El-Houda , Mérindol Natacha , Plourde Mélodie B. , Maisonnet Tara , Lebel Sophie , Berthoux Lionel
Published: September 2023

Human muscle-specific RING fingers (MURFs) are members of the tripartite motif (TRIM) family of proteins characterized by their C-terminal subgroup one signature domain. MURFs play a role in sarcomere formation and microtubule dynamics. It was previously established that some TRIMs undergo post-translational modification by small ubiquitin-like modifier (SUMO). In this study, we explored the putative SUMOylation of MURF proteins as well as their interactions with SUMO. MURF proteins (TRIM54, TRIM55, and TRIM63) were not found to be SUMOylated. However, TRIM55 turnover by proteasomal and lysosomal degradation was higher upon overexpression of SUMO-3 but not of SUMO-1. Furthermore, it is predicted that TRIM55 contains two potential SUMO-interacting motifs (SIMs). We found that SIM1- and SIM2-mutated TRIM55 were more stable than the wild-type (WT) protein partly due to decreased degradation. Consistently, SIM-mutated TRIM55 was less polyubiquitinated than the WT protein, despite similar monoubiquitination levels. Using IF microscopy, we observed that SIM motifs influenced TRIM55 subcellular localization. In conclusion, our results suggest that SUMO-3 or SUMO-3-modified proteins modulate the localization, stability, and RING ubiquitin ligase activity of TRIM55.
Dam removal effect on the lower St. Regis River ice-jam floods
Authors: Huang Fengbin , Shen Hung Tao
Published: September 2023

The Hogansburg Dam in Akwesasne, NY, on the lower St. Regis River, a tributary of the St. Lawrence River, was decommissioned and removed in 2016. The dam removal restored over 893 river km of migratory fish access. However, ice jams occurred on the lower St. Regis River in winter before and after the dam removal, which caused flooding in the St. Regis Mohawk Tribe Reservation. This study reviewed the historical ice-jam conditions in the lower St. Regis River and the effect of dam removal. A two-dimensional river-ice model, DynaRICE, capable of simulating the dynamic ice transport and jamming processes, was used to evaluate pre- and post-dam-removal conditions of the Hogansburg Dam on the ice-jam flooding in the St. Regis Mohawk Tribe Reservation. The study showed that the dam removal effect decreases as the breakup discharge increases. A potential mitigation scheme for reducing ice-jam floods in the Hogansburg area using ice booms was examined and recommended.
Measuring the value and cost of BIM use—an empirical lesson learned from Taiwan’s social housing projects
Authors: Yu Wen-Der , Chang Hsien-Kuan , Wang Kun-Chi
Published: September 2023

This paper presents a novel approach for measuring the cost requirements and related values for building information modeling (BIM) adoption using the adaptive analytic hierarchy process approach. The proposed approach considers the importance of each BIM use item in relation to its cost, allowing for prioritization of BIM uses based on their relative value while considering prerequisite relationships and budgetary constraints. The effectiveness of the approach was demonstrated through empirical validation involving a survey of 50 construction industry professionals, and two BIM use prioritization methods (project objective- oriented and value- oriented) were recommended for decision-making under budget constraints. The lessons learned from the empirical case study include the importance of Government’s role and the industrial standards in evaluating cost-benefit and promoting for BIM adoption, the different contributions of BIM uses across project phases, and the diverse perceptions of BIM cost requirements among different participants. These lessons are invaluable for countries planning BIM implementation. This paper also demonstrates the development and empirical validation of a novel approach for BIM use adoption under limited budgets, which can assist decision-makers in selecting appropriate BIM use items and estimating their associated costs.
A pan-Canadian assessment of empirical research on post-disturbance recovery in the Canadian Forest Service
Authors: Waldron Kaysandra , Thiffault Nelson , Venier Lisa , Bognounou Fidèle , Boucher Dominique , Campbell Elizabeth , Whitman Ellen , Brehaut Lucas , Gauthier Sylvie
Published: September 2023

Information about post-disturbance regeneration success and successional dynamics is critical to predict forest ecosystem resistance and resilience to disturbances and climate change. Our objective was to identify and classify post-disturbance empirical research conducted by the Canadian Forest Service (CFS) of Natural Resources Canada and their collaborators to provide guidance on future research needs, improving our understanding of post-disturbance recovery in a Canadian context. To achieve our objective, we collected and classified peer-reviewed and non-published literature produced by the CFS between 1998 and 2020 that concerned post-disturbance ecology. We focused on research addressing natural or anthropogenic disturbances, such as wildfires, pest outbreaks, windthrows, forest management, seismic lines, and those that studied processes related to soil, vegetation, fauna, hydrology, and microbial communities. We found that forest harvesting was the disturbance most studied by CFS between 1998 and 2020, followed by fire. Despite the fact that large, forested areas are affected annually by pests, studies on recovery after pest outbreaks were scarce. Other disturbances, such as mining and seismic lines or other abiotic disturbances were rare in CFS literature. Most studies (70%) examined changes in vegetation related to forest management and fire and they were mainly focussed on post-disturbance tree regeneration success. Post-disturbance changes in understory species diversity were also well-studied. Our results provide a geographic overview of CFS research on post-disturbance recovery in Canada and enable the identification of key knowledge gaps. Notably, research focusing on recovery after natural disturbances was underrepresented in the assessed literature compared to studies centered around harvesting. Long-term research sites, chronosequences that substitute space for time, and studies focused on consecutive disturbances are especially important to maintain and establish sustainable forest management strategies in the face of climate change.
Quantum authentication method based on key-controlled maximally mixed quantum state encryption
Authors: Lim Na-Hee , Choi Ji-Woong , Kang Min-Sung , Yang Hyung-Jin , Han Sang-Wook
Published: September 2023

Quantum authentication is a fundamental first step that ensures secure quantum communication. Although various quantum authentication methods have been proposed recently, their implementation efficiency is limited. This paper proposes a key-controlled maximally mixed quantum state encryption (MMQSE) method using only a single qubit, unitary operation, minimized quantum transmissions, and a single qubit measurement, which improves implementation feasibility and operation efficiency. We applied it to representative quantum authentication applications, namely, quantum identity and message authentication. The security of our authentication schemes was verified by analyzing the relationship between the integral ratio of Uhlmann’s fidelity and probability of successful eavesdropping. Moreover, we demonstrate the higher authentication efficiency of the proposed scheme in a real quantum-channel noise environment. The upper bound of the valid noise rate was quantified using the integral ratio of Uhlmann’s fidelity in a noise environment. Finally, the optimal number of authentication sequences was estimated.
Special Memristor and Memristor-Based Compact Neuron Circuit
Authors: Altan Muhammet Alper , Orman Kamil , Babacan Yunus , Yesil Abdullah
Published: September 2023

Implementing neuron circuit using memristor can be more effective thanks to some properties of memristor such as nonlinearity. For this reason, many memristor-based neuron circuits have been found in the literature. This study presents a memristor-based floating neuron circuit that exhibits different types of spikes. In the proposed circuit, two classical memristors and one special memristor are utilized. The special memristor is designed to exhibit various pinched hysteresis loops and plays an important role in producing different spike types. The proposed special memristor can also be controlled using only one voltage source. Using memristors, we implemented a neuron circuit which can produce regular spike, bursting spike and fast spike. Also, neuron circuit has a floating structure, and so there is no restriction on using it with other circuit elements. All simulations are implemented in the SPICE simulation program with TSMC 0.18-[Formula: see text]m CMOS process parameters.