bluuebunny/crossref_metadata_2025 huggingface dataset:
Dispersive vacuum as a decoherence amplifier of an Unruh–DeWitt detector
Authors: Barros Pedro H M , Costa Helder A S
Published: October 2024

Recently, interest has been growing in studies on discrete or ‘pixelated’ space-time that, through modifications in the dispersion relation, can treat the vacuum as a dispersive medium. Discrete spacetime considers that spacetime has a cellular structure on the order of the Planck length, and if this is true we should certainly have observable effects. In this paper, we investigated the effects caused by the dispersive vacuum on the decoherence process of an Unruh–DeWitt detector, our setup consists of a uniformly accelerated detector, initially in a qubit state, which interacts with a massless scalar field during a time interval finite. We use dispersion relations drawn from doubly special relativity and Hořava–Lifshitz gravity, with these modifications the vacuum becomes dispersive and has a corresponding refractive index. We calculate the probability transition rates, the probability of finding the detector in the ground state, and the quantum coherence variation. Our results indicate that the decoherence process occurs more quickly in cases with changes in the dispersion relation in the regime of high accelerations and interaction time. Additionally, the decoherence increases as the vacuum becomes more dispersive due to the increase in the order of modification in the dispersion relation, and this happens because the dispersive vacuum amplifies the effects of quantum fluctuations that are captured by the detector when interacting with the field.
NIST publishes new encryption standards
Authors: Banks Michael
Published: October 2024

A set of encryption algorithms that are designed to withstand hacking attempts by a quantum computer has been released by the US National Institute of Standards and Technology.
CERN celebrates 70 years of particle physics
Authors: Banks Michael
Published: October 2024

Officials will gather on 1 October for a formal ceremony to celebrate 70 years of the CERN particle-physics lab, which is based near Geneva.
CERN at 70: the inside story
Authors: Gillies James
Published: October 2024

With CERN turning 70 this year, the lab’s former head of communications James Gillies reveals how his team handled unprecedented global interest in the world’s most powerful collider, which ranged from fears of killer black holes to visits from celebrities.
Physics cookbook fails to gel
Authors: Povey Megan J
Published: October 2024

Megan Povey reviews Physics in the Kitchen by George Vekinis.
MicroLEDs for optical neuromorphic computing—application potential and present challenges
Authors: Kraneis R , Müller M , Higgins-Wood S , Kaelin N , Wehmann H-N , von Malm N , Werner C , Waag A
Published: October 2024

The slow non-radiative surface recombination velocity of gallium nitride (GaN) in combination with its highly efficient radiative recombination makes this material ideally suited for microLEDs with dimensions as small as 1 µm and even below, serving as the fundamental building block of micro-displays. However, due to their superior miniaturization potential and energy efficiency, GaN-based microLEDs have applications that extend well beyond display technology. Their capability to produce optical patterns with high resolution, which can be modulated at extremely high frequencies, makes them suitable for numerous other applications. We suggest exploiting these exciting properties for a new and potentially equally significant application: utilizing microLEDs in optical processing units for artificial intelligence workloads. In neuromorphic computing, relevant aspects of biological neural networks are emulated directly with either electronic circuits or photonic devices, avoiding the shortcomings of conventional digital computer technology for AI workloads, which generally require massively parallel information processing. GaN microLEDs are discussed here as a promising enabling technology for optical neuromorphic processing units. We see great potential to substantially decrease power consumption through massively parallel in-memory processing combined with efficient photon production and detection. A theoretical analysis of scalability and energy efficiency is provided. A macroscopic bench-top optical microLED demonstrator is presented, which experimentally proves the feasibility of our approach. Future potential and challenges associated with miniaturizing and scaling microLED-based optical processing units are discussed. Finally, we summarize the open research questions that require attention before fully functional and miniaturized optical neuromorphic processing units based on GaN microLEDs can be realized.
Improvement of optical noise in optical-injection-locked quantum dot lasers epitaxially grown on silicon by reducing external carrier noise
Authors: Qu Luochen , Chu Qi , Wang Wenlu , Jin Zhiyong , Ding Shihao , Wang Cheng , Xu Xiaochuan , Wang Jiawei , Duan Jianan
Published: October 2024

This study theoretically investigates the impact of external carrier noise from pumping sources on the optical noise of epitaxial quantum dot (QD) lasers on silicon. The findings indicate that the spectral linewidth and relative intensity noise (RIN) of silicon-based QD lasers using a quiet pump are significantly reduced. At 5.5 times the threshold current, the spectral linewidth decreases from 337.2 kHz to 213.2 kHz, and the RIN decreases from −141.3 dB Hz−1 to −168.8 dB Hz−1. This reduction is attributed to the lower external carrier noise level of the quiet pump, which also suppresses the spectral linewidth rebroadening effect at a high bias current. Moreover, when external optical injection locking is applied, the spectral linewidth further decreases to 24 kHz at an injection ratio of −70 dB and to 1.8 mHz at 0 dB. The RIN also slightly decreases to −172.4 dB Hz−1 with an injection ratio of 10. These results demonstrate that using a quiet pump is an effective and manageable strategy for significantly reducing both the spectral linewidth and RIN of QD lasers, thereby facilitating their application in next-generation photonic integrated circuits, continuous-variable quantum key distribution, quantum computing and ultra-precise quantum sensing.
Diffusion of adzuki bean (Vigna angularis) oligomeric polyphenols from seed coats to cotyledons during boiling
Authors: Aoyama Yutaka , Masuda Kaoru , Mitsui Satoko , Yokoi Takuya
Published: October 2024

Adzuki beans (Vigna angularis) are major legumes in East Asia, commonly used in traditional Japanese confections in the form of a paste. Although various types of polyphenols are present in seed coats, there are no reports on the diffusion of polyphenols to cotyledons during boiling. This study revealed that oligomeric polyphenols—such as dimeric and more proanthocyanidins—diffused more easily from seed coats to cotyledons than monomeric polyphenols—such as (+)-catechin and (−)-epicatechin—during heating. Microscopy suggested that diffusing polyphenols were bound to cotyledon proteins. Furthermore, bound polyphenols, poorly extracted by ethanol and acetone, contributed to the 1,1- diphenyl-2-picrylhydrazyl radical-scavenging activity of cooked cotyledons. Thus, smooth adzuki bean paste, made by boiling adzuki beans and removing the seed coats, contains oligomeric polyphenols that contribute to its antioxidant activity. By clarifying further physiological activities of polyphenols diffused through cotyledons, adzuki bean paste can be a potential functional ingredient.
Comprehensive mutational profiling identifies new driver events in cutaneous leiomyosarcoma
Authors: van der Weyden Louise , Del Castillo Velasco-Herrera Martin , Cheema Saamin , Wong Kim , Boccacino Jacqueline M , Offord Victoria , Droop Alastair , Jones David R A , Vermes Ian , Anderson Elizabeth , Hardy Claire , de Saint Aubain Nicolas , Ferguson Peter M , Clarke Emily L , Merchant William , Mogler Carolin , Frew Derek , Harms Paul W , Monteagudo Carlos , Billings Steven D , Arends Mark J , Ferreira Ingrid , Brenn Thomas , Adams David J
Published: October 2024

Background

Cutaneous leiomyosarcoma (cLMS) is a rare soft-tissue neoplasm, showing smooth muscle differentiation, that arises from the mesenchymal cells of the dermis. To date, genetic investigation of these tumours has involved studies with small sample sizes and limited analyses that identified recurrent somatic mutations in RB1 and TP53, copy number gain of MYOCD and IGF1R, and copy number loss of PTEN.

Objectives

To better understand the molecular pathogenesis of cLMS, we comprehensively explored the mutational landscape of these rare tumours to identify candidate driver events.

Methods

In this retrospective, multi-institutional study, we performed whole-exome sequencing and RNA sequencing in 38 cases of cLMS.

Results

TP53 and RB1 were identified as significantly mutated and thus represent validated driver genes of cLMS. COSMIC mutational signatures SBS7a/b and DBS1 were recurrent; thus, ultraviolet light exposure may be an aetiological factor driving cLMS. Analysis of significantly recurrent somatic copy number alterations, which represent candidate driver events, found focal (< 10 Mb) deletions encompassing TP53 and KDM6B, and amplifications encompassing ZMYM2, MYOCD, MAP2K4 and NCOR1. A larger (24 Mb) recurrent deletion encompassing CYLD was also identified as significant. Significantly recurrent broad copy number alterations, involving at least half of a chromosome arm, included deletions of 6p/q, 10p/q, 11q, 12q, 13q and 16p/q, and amplification of 15q. Notably PTEN is located on 10q, RB1 on 13q and IGFR1 on 15q. Fusion gene analysis identified recurrent CRTC1/CRTC3::MAML2 fusions, as well as many novel fusions in individual samples.

Conclusions

Our analysis of the largest number of cases of cLMS to date highlights the importance of large cohort sizes and exploration beyond small targeted gene panels when performing molecular analyses, as it allowed a comprehensive exploration of the mutational landscape of these tumours and identification of novel candidate driver events. It also uniquely afforded the opportunity to compare the molecular phenotype of cLMS with LMS of other tissue types, such as uterine and soft-tissue LMS. Given that molecular profiling has resulted in the development of novel targeted treatment approaches for uterine and soft-tissue LMS, our study now allows the same opportunities to become available for patients with cLMS.
Does pollination by non-flying mammals contribute substantially to fruit set of Banksia (Proteaceae)? A test in four species with contrasting floral traits
Authors: Wawrzyczek Stanislaw K , Davis Robert A , Krauss Siegfried L , Hoebee Susan E , Phillips Ryan D
Published: October 2024

Pollination by non-flying mammals (NFMs) is thought to be associated with cryptic, dull coloured, strongly scented flowers. In Western Australia, various Banksia species exhibit these traits, suggesting adaptation to primary pollination by NFMs, particularly the marsupial honey possum (Tarsipes rostratus). Here, we compare floral visitation rates and assess contribution to fruit set of NFMs and other pollinators in four species of Banksia with contrasting floral traits. Camera trap-based surveys revealed that honeyeater birds visited all species equally and were more frequent visitors than NFMs to the brightly coloured, unscented flowers of B. sessilis and B. splendida. By contrast, NFMs were more frequent visitors of the cryptic, strongly scented flowers of B. shuttleworthiana and B. subulata. Selective pollinator exclusion experiments showed that NFMs, birds, and insects contributed to pollination of all four species but indicated primary pollination by NFMs in B. subulata. Surprisingly, the most frequent visitors of this species were mice, not marsupials, providing the first compelling evidence of primary pollination by rodents in Australia. Notably, honey possums contributed substantially to fruit set of B. sessilis and B. splendida, despite infrequent visitation to these species. These findings challenge the assumption that in Banksia floral crypsis and strong scents are adaptations to primary pollination by honey possums. Instead, they suggest a spectrum of bird-NFM pollination systems, with rodents as key pollinators of some species.
Dysregulation of protein SUMOylation networks in Huntington’s disease R6/2 mouse striatum
Authors: Kachemov Marketta , Vaibhav Vineet , Smith Charlene , Sundararaman Niveda , Heath Marie , Pendlebury Devon F , Matlock Andrea , Lau Alice , Morozko Eva , Lim Ryan G , Reidling Jack , Steffan Joan S , Van Eyk Jennifer E , Thompson Leslie M
Published: October 2024

Huntington’s disease is a neurodegenerative disorder caused by an expanded CAG repeat mutation in the Huntingtin (HTT) gene. The mutation impacts neuronal protein homeostasis and cortical/striatal circuitry. SUMOylation is a post-translational modification with broad cellular effects including via modification of synaptic proteins.

Here, we used an optimized SUMO protein-enrichment and mass spectrometry method to identify the protein SUMOylation/SUMO interaction proteome in the context of Huntington’s disease using R6/2 transgenic and non-transgenic mice.

Significant changes in the enrichment of SUMOylated and SUMO-interacting proteins were observed, including those involved in presynaptic function, cytomatrix at the active zone, cytoskeleton organization and glutamatergic signalling. Mitochondrial and RNA-binding proteins also showed altered enrichment. Modified SUMO-associated pathways in Huntington’s disease tissue include clathrin-mediated endocytosis signalling, synaptogenesis signalling, synaptic long-term potentiation and SNARE signalling. To evaluate how modulation of SUMOylation might influence functional measures of neuronal activity in Huntington’s disease cells in vitro, we used primary neuronal cultures from R6/2 and non-transgenic mice. A receptor internalization assay for the metabotropic glutamate receptor 7 (mGLUR7), a SUMO-enriched protein in the mass spectrometry, showed decreased internalization in R6/2 neurons compared to non-transgenic neurons. SiRNA-mediated knockdown of the E3 SUMO ligase protein inhibitor of activated STAT1 (Pias1), which can SUMO modify mGLUR7, reduced this Huntington’s disease phenotype. In addition, microelectrode array analysis of primary neuronal cultures indicated early hyperactivity in Huntington’s disease cells, while later time points demonstrated deficits in several measurements of neuronal activity within cortical neurons. Huntington’s disease phenotypes were rescued at selected time points following knockdown of Pias1.

Collectively, our results provide a mouse brain SUMOome resource and show that significant alterations occur within the post-translational landscape of SUMO-protein interactions of synaptic proteins in Huntington’s disease mice, suggesting that targeting of synaptic SUMO networks may provide a proteostatic systems-based therapeutic approach for Huntington’s disease and other neurological disorders.
Gateway to the study of the amygdala and emotion
Authors: Romanski Lizabeth M
Published: October 2024

The study of the amygdala and its role in the processing of emotions has become a common focus in neuroscience. The modern expansion of research in this area is partly due to the discovery of a subcortical pathway for the transmission of emotional information and the experimental paradigm that was developed to study it. Groundbreaking experiments during the 90s utilized anatomical, neurophysiological, and behavioral lesion studies in a rodent animal model to uncover the neural circuitry of a simple emotional memory. These studies demonstrated the essential role of a specific monosynaptic pathway in emotional memory, using traditional tools and behavioral methods. The development of an animal model with a simple and appropriate classical conditioning paradigm made experimental investigations into the neural basis of emotion tenable and available to a generation of neuroscientists. These tools and a focus on the amygdala’s neural connections and their essential role in emotional memory were a driving force in the explosion of research regarding the amygdala and emotion.
Determination of Residual Dimethyl Sulfate in Cephalosporin Using HS-SPME/GC–MS
Authors: Lu Rongchun
Published: October 2024

Dimethyl sulfate (DMS) is widely used in manufacturing process but because of its genotoxicity nature, it should be monitored at trace levels (1 μg/mL). It is complicated and difficult to quantify DMS in cephalosporin with traditional method. Herein, a method for quantifying residual DMS in cephalosporin was developed, without complex sample preprocessing, no need for a large amount of solvent, employing headspace solid-phase microextraction (SPME) and gas chromatography–mass spectrometry (GC–MS). Compared with polydimethylsiloxane (PDMS)/divinylbenzene and polyacrylate fibers, PDMS was more suitable for absorbing DMS. The research showed that the PDMS fiber should be changed after 50 adsorption–desorption cycles. Linear regression analysis of the calibration curve demonstrated a robust linear relationship, with R2 of 0.999, across a concentration range of 0.25 to 4.0 μg/mL. The method underwent rigorous validation for specificity, linearity, precision and accuracy. This method was proven effective in measuring DMS in complex matrices. The limits of detection and quantification for this method is 0.05 and 0.25 μg/mL, respectively, which has room for improvement.
Primary Care Guidance for Providers Who Care for Persons With Human Immunodeficiency Virus: 2024 Update by the HIV Medicine Association of the Infectious Diseases Society of America
Authors: Horberg Michael , Thompson Melanie , Agwu Allison , Colasanti Jonathan , Haddad Marwan , Jain Mamta , McComsey Grace , Radix Asa , Rakhmanina Natella , Short William R , Singh Tulika , Tookes Hansel
Published: October 2024

Advances in antiretroviral therapy (ART) have made it possible for persons with human immunodeficiency virus (HIV) to have a lifespan that approaches that of people without HIV without progressing to AIDS or transmitting HIV to sexual partners or infants. There is, therefore, increasing emphasis on maintaining health throughout the lifespan. To receive optimal medical care and achieve desired outcomes, persons with HIV must be consistently engaged in care and able to access uninterrupted treatment, including ART. Comprehensive, evidence-based HIV primary care guidance is, therefore, more important than ever. Creating a patient-centered, stigma-free care environment is essential for care engagement. Barriers to care must be decreased at the societal, health system, clinic, and individual levels. As the population ages and noncommunicable diseases arise, providing comprehensive healthcare for persons with HIV becomes increasingly complex, including management of multiple comorbidities and the associated challenges of polypharmacy while also attending to HIV-specific health concerns. Clinicians must address issues specific to preventive health, including cancer screening, providing recommended vaccinations, and promoting sexual health, including sexually transmitted infection diagnosis, treatment, and prevention. Clinicians also must address issues for specific populations, including persons of childbearing potential during preconception and pregnancy, children, adolescents, and transgender and gender-diverse individuals. This guidance from an expert panel of the HIV Medicine Association of the Infectious Diseases Society of America updates the previous 2020 HIV Primary Care Guidance.
Peak expiratory flow predicts the occurrence of postoperative pneumonia after esophagectomy for esophageal cancer
Authors: Sawai Shota , Nakatani Eiji , Sato Shinsuke , Hawke Philip , Mochizuki Takuma , Nishida Masato , Ogiso Hiroshi , Watanabe Masaya
Published: October 2024

Expiratory flow is an important factor in the achievement of airway clearance that is required to prevent postoperative pneumonia (POP). Although peak expiratory flow (PEF) has been shown to predict the occurrence of POP in lung cancer patients after lobectomy, its predictive power in relation to esophagectomy for esophageal cancer remains unknown. This study assesses PEF as a predictor of POP in patients with esophageal cancer undergoing radical esophagectomy.

We conducted a single-center, retrospective cohort study of patients who underwent radical esophagectomy with gastric tube reconstruction at our institution between January 2007 and December 2022. Preoperative pulmonary functions, including PEF, were assessed before surgery. Additionally, POP was diagnosed as a Clavien-Dindo classification of Grade II or higher. Survival and pneumonia incidence were compared using the Kaplan–Meier method. Logistic regression analysis was used to examine the relationship between these variables and POP.

The study included 513 patients, of which 441 were men. POP occurred in 86 patients (16.7%). When all patients were stratified by %PEF into two groups, the group with %PEF lower that 80% had significantly poorer prognosis and higher incidence of pneumonia. Multivariable logistic regression analysis indicated that %PEF (OR: 0.986, 95%CI: 0.974–0.999, P = 0.030), along with age, BMI, preoperative treatment, and recurrent laryngeal nerve palsy were independent protective factors against POP.

These results reveal that %PEF predicts the development of POP following esophagectomy for esophageal cancer.
Compiling a versatile toolbox for inducible gene expression in Methanosarcina mazei
Authors: Hüttermann Johanna , Schmitz Ruth
Published: October 2024

Methanosarcina mazei is a model organism, providing a platform to explore methanoarchaeal regulation mechanisms on the transcriptional and translational level. This study investigates and evaluates various molecular tools to allow inducible gene expression in M. mazei. (i) The TetR/TetO system was utilized to induce expression of a designed antisense RNA directed against sRNA154 allowing to increase transcripts of asRNA154 (500-fold), resulting in a significant decrease of sRNA154 levels (tetracycline-induced knockdown mutant). Strong reduction of sRNA154 was further confirmed in the knockdown mutant by up to 50-fold decreased transcript levels of the genes nifH, glnK1, and glnA1, the stability of which is increased by sRNA154. (ii) For translational regulation, an RNA thermometer was designed and first-ever utilized in an archaeon, inserted into the 5′-untranslated region of a reporter gene, which showed enhanced protein expression upon a temperature shift from 30°C to 40°C. (iii) The long 5′-UTR of a trimethylamine (TMA)-inducible polycistronic mRNA was evaluated and studied as a potential genetic tool for induced gene expression on the translational level. However, we discovered TMA-dependent regulation occurs most likely on the transcript level. (iv) A new selection marker (nourseothricin resistance) was established for M. mazei using the streptothricin acetyltransferase gene. Taken together, our findings provide a foundation for future exploration of genetic regulation and inducible gene expression in M. mazei and other methanoarchaea, advancing genetic studies in these organisms and enhancing their potential for biotechnology applications.
A geometric view of seismic wavefields: implications for imaging dense clusters of events
Authors: Harris David B
Published: October 2024

Imaging dense clusters of seismicity is crucial to many problems in seismology: to delineate complex systems of faults, provide constraints on the causes of volcanic and cryogenic swarms, and to shed light on possible means to prevent damaging induced seismicity in mining, geothermal, and oil and gas extraction activities. Current imaging methods rely upon high-resolution relative location techniques, commonly requiring arrival-time picks for seismic phases. This paper examines an alternative approach, based upon concepts drawn from differential geometry, that images directly from waveform data. It relies upon the common assumption of spatial continuity of seismic wavefield observations, which implies that a differentiable map exists between the source region to be imaged and waveform observations considered as elements of a vector space. The map creates an image of event clusters on a Riemannian manifold embedded in that vector space. The image can be visualized by projecting the observations into a tangent space of the manifold and is a distorted rendering of cluster geometry. However, the distortion can be predicted and removed if a model for wavefield propagation is available.

This visualization approach is applicable to clusters of uniform events with highly similar waveforms, such as are commonly acquired with correlation detectors or other pattern matching techniques. To assess its performance, it is applied to the closely related reciprocal problem of imaging the (known) geometry of an array from observations by the array of several regional events. Differences between the original problem and its reciprocal analogue are noted and controlled for in the analysis. Chief among the differences is the necessity for aligning the waveforms in the original problem, which, to maintain consistency with the original problem, is solved in the reciprocal problem by a generalization of the VanDecar–Crosson algorithm. The VanDecar–Crosson algorithm exhibits a bias, shown through an analysis of the situation when the observed wavefields are adequately modelled as plane waves. In that circumstance, the bias can be predicted and removed.

In a test using a portion of a large-N array, this imaging approach is shown to successfully reconstruct the array geometry. The method is applicable directly to infinitesimal array apertures, but is extended to a larger aperture by partitioning the image into local, effectively infinitesimal overlapping subsets. These are inverted, then assembled into a global picture of the array geometry using constraints provided by the overlapped regions. Although demonstrated in a reciprocal array context, the method appears viable for imaging clusters of events with highly similar source mechanisms and time histories.
Delivering large genes using adeno-associated virus and the CRE-lox DNA recombination system
Authors: Datta Poppy , Rhee Kun-Do , Staudt Rylee J , Thompson Jacob M , Hsu Ying , Hassan Salma , Drack Arlene V , Seo Seongjin
Published: October 2024

Adeno-associated virus (AAV) is a safe and efficient gene delivery vehicle for gene therapies. However, its relatively small packaging capacity limits its use as a gene transfer vector. Here, we describe a strategy to deliver large genes that exceed the AAV’s packaging capacity using up to four AAV vectors and the CRE-lox DNA recombination system. We devised novel lox sites by combining non-compatible and reaction equilibrium-modifying lox site variants. These lox sites facilitate sequence-specific and near-unidirectional recombination of AAV vector genomes, enabling efficient reconstitution of up to 16 kb of therapeutic genes in a pre-determined configuration. Using this strategy, we have developed AAV gene therapy vectors to deliver IFT140, PCDH15, CEP290, and CDH23 and demonstrate efficient production of full-length proteins in cultured mammalian cells and mouse retinas. Notably, AAV-IFT140 gene therapy vectors ameliorated retinal degeneration and preserved visual functions in an IFT140-associated retinitis pigmentosa mouse model. The CRE-lox approach described here provides a simple, flexible, and effective platform for generating AAV gene therapy vectors beyond AAV’s packaging capacity.
The amino acid permease SlAAP6 contributes to tomato growth and salt tolerance by mediating branched-chain amino acid transport
Authors: Qiang Qi , Zhang Zhonghui , Li Xianggui , Li Chun , Mao Mengdi , Ding Xiangyu , Zhang Jianing , Li Shixuan , Lai Zesen , Yang Jie , Cao Peng , Ye Weizhen , Wang Shouchuang , Yang Jun
Published: October 2024

Branched-chain amino acids (BCAAs) are essential amino acids in tomato (Solanum lycopersicum) required for protein synthesis, which also modulate growth and abiotic stress responses. To date, little is known about their uptake and transport in tomato especially under abiotic stress. Here, the tomato amino acid permease 6 (SlAAP6) gene was identified as an amino acid transporter that restored mutant yeast cell growth on media with a variety of amino acids, including BCAAs. Overexpression of SlAAP6 (SlAAP6-OE) in tomato raised the BCAA content and elevated the fresh weight, while SlAAP6 knockouts (slaap6) showed reduced levels of neutral and basic amino acids in seedling tissues and lower total free amino acid distribution to shoots. In comparison to wild type and slaap6 mutants, SlAAP6-OE alleviated root limited growth by elevated BCAA transport and upregulated the expression of root-growth-related genes by increasing BCAAs in vivo. As SlAAP6 serves as a positive regulator for BCAA abundance, SlAAP6-OE lines showed greater salinity tolerance, while slaap6 mutants exhibited increased salt sensitivity. The salt tolerance of SlAAP6-OE plants was further enhanced by the application of exogenous BCAAs. In addition, BCAA supplementation reduced the accumulation of H2O2 in root under salt stress conditions. Based on these findings, SlAAP6-mediated uptake and transport of BCAAs facilitated growth and salt tolerance in tomato. By characterizing this key amino acid transporter, this study provides a novel approach to simultaneously enhance tomato nutritional quality, growth and development, and stress resistance through genetic improvement.
Glycerophosphodiester phosphodiesterase 1 mediates G3P accumulation for Eureka lemon resistance to citrus yellow vein clearing virus
Authors: Liao Ping , Dan Xue , Ge Wen , Zhang Qi , Zhao Jinfa , Zhou Changyong , Zhou Yan
Published: October 2024

Glycerophosphodiester phosphodiesterase 1 (GDPD1) plays an important function in the abiotic stress responses and participates in the accumulation of sn-glycerol-3-phosphate (G3P) in plants, which is key to plant systemic acquired resistance (SAR). However, the role of GDPD1 in plant responses to biotic stress remains poorly understood. This study characterized the antivirus function of the GDPD1 gene (designated as ClGDPD1) from Eureka lemon. ClGDPD1 is located in the membrane and endoplasmic reticulum, where it interacts with the citrus yellow vein clearing virus (CYVCV) coat protein (CP). Compared to individually expressed ClGDPD1 or coexpressed ClGDPD1 + CP140-326, transiently coexpressed ClGDPD1 + CP or ClGDPD1 + CP1-139 significantly upregulated the key substance contents and genes expression involved in glycerophospholipid metabolism. Over-expression of ClGDPD1 significantly facilitated the accumulation of G3P, upregulated the expression of SAR-related genes, and increased the resistance of transgenic Eureka lemon to CYVCV infection. Furthermore, exogenous glycerol treatment and over-expression of ClGPDH increased the G3P content and reduced CYVCV titers in plants or hairy roots. These results indicated that the enhanced resistance of ClGDPD1 transgenic Eureka lemon to CYVCV may be due to facilitating G3P accumulation through the interaction of ClGDPD1 with CP. Our findings provide novel insights into the role of ClGDPD1 as an important regulatory center in mediating the citrus defense response to viral infections.
On long-time asymptotic behavior and Painlevé asymptotic to the matrix Hirota equation
Authors: Zhang Xiao-Fan , Tian Shou-Fu
Published: October 2024

The nonlinear descent method is extended to study the long-time asymptotic behavior of the matrix Hirota equation with $4\times 4$ Lax pair in Schwartz space. The implementation of spectral analysis successfully transforms the Cauchy problem of the matrix Hirota equation into the corresponding high-order Riemann–Hilbert (RH) with $4\times 4$ jump matrix, and further analyses the established oscillation RH problem to study the asymptotic behavior of the solution in the space-time plane. Interestingly, the space-time plane $\{(x,t)|-\infty <x<+\infty , t>0\}$ can be divided into three different asymptotic regions based on the phase function and $\xi =x/t$. The first one is the oscillatory region $\xi <\frac{\alpha ^{2}}{3\beta }$, whose leading-term can be approximated applying the Weber equation with an error of $\mathcal{O}(t^{-1}\log t)$. The second region is the Painlevé region $\xi \approx \frac{\alpha ^{2}}{3\beta }$, whose leading-term can be approximated by the coupled Painlevé II equation, which is related to a $4\times 4$ matrix RH problem with an error of $\mathcal{O}(t^{-\frac{2}{3}})$. The last region is the fast decay region $\xi>\frac{\alpha ^{2}}{3\beta }$, which solution is rapidly decreasing as $t\rightarrow \infty $. Our results provide a detailed proof for the asymptotic analysis for the solution of the matrix Hirota equation on the complete space-time plane.
“Kingsway leads the way to modern living”: British Profit-seeking and Modernism in Ghana and Nigeria 1920–1970
Authors: Harrison Ewan , Jackson Iain , Appeaning Addo Irene , Muraina Oluwaseun
Published: October 2024

This article examines the operative uses of modernist design by the Kingsway Stores, an elite department store chain active across West Africa. Kingsway responded to independence by instrumentalizing a particularly modernist domesticity through a series of didactic marketing efforts and the construction of boldly modernist new stores. While it was responding to African demands, this instrumentalization of modernist design was planned and executed as a business survival strategy: modernism is here revealed as complexly imbricated with colonial and neocolonial profit-seeking.
Bank Capital Regulation in a Zero Interest Environment
Authors: Döttling Robin
Published: October 2024

How does the zero lower bound on deposit rates (ZLB) affect how banks respond to capital regulation? I study this question in a model in which households value the liquidity services of deposits yet do not accept negative deposit rates. When deposit rates are constrained by the ZLB, tight capital requirements disproportionately hurt franchise values and are therefore less effective in curbing excessive risk taking. The model delivers a novel rationale for “interest-dependent” capital regulation that is optimally laxer when the ZLB binds and tighter when the ZLB is slack but may bind in the future.
Sharpening complexity results in quantified probability logic
Authors: Speranski Stanislav O
Published: October 2024

We shall be concerned with two natural expansions of the quantifier-free ‘polynomial’ probability logic of Fagin et al. (A logic for reasoning about probabilities, Inform Comput, 1990; 87:78–128). One of these, denoted by ${\textsf{QPL}}^{\textrm{e}}$, is obtained by adding quantifiers over arbitrary events, and the other, denoted by $\underline{{\textsf{QPL}}}^{\textrm{e}}$, uses quantifiers over propositional formulas—or equivalently, over events expressible by such formulas. The earlier proofs of the complexity lower bound results for ${\textsf{QPL}}^{\textrm{e}}$ and $\underline{{\textsf{QPL}}}^{\textrm{e}}$ relied heavily on multiplication, and therefore on the polynomiality of the basic parts. We shall obtain the same lower bounds for natural fragments of ${\textsf{QPL}}^{\textrm{e}}$ and $\underline{{\textsf{QPL}}}^{\textrm{e}}$ in which only linear combinations of a very special form are allowed. Also, it will be studied what happens if we add quantifiers over reals.
Comparing the efficacy and safety of first-line treatments for chronic lymphocytic leukemia: a network meta-analysis
Authors: Wen Tingyu , Sun Guangyi , Jiang Wenxin , Steiner Kat , Bridge Suzannah , Liu Peng
Published: October 2024

Background

The chronic lymphocytic leukemia treatment strategies have transitioned from chemotherapy and chemoimmunotherapy to chemotherapy-free regimens. Frequentist network meta-analysis allows for direct and indirect comparisons between different treatments.

Methods

Randomized controlled trials assessing first-line treatments were included. Outcomes were progression-free survival (PFS), overall survival, undetectable minimal residual disease, objective response rate, and adverse events. Studies with comparable characteristics also underwent subgroup analysis, stratifying by age, comorbidities, IGHV status, and cytogenetic abnormalities.

Results

A total of 30 eligible trials involved 12 818 patients, and 30 treatments were included. Acalabrutinib demonstrated a PFS advantage over ibrutinib and obinutuzumab-venetoclax in patients aged older than 65 years or with unmutated IGHV. In younger patients with comorbidities, acalabrutinib-obinutuzumab had superior PFS compared with ibrutinib-obinutuzumab, ibrutinib-venetoclax, and obinutuzumab-venetoclax. For older patients with comorbidities, acalabrutinib and acalabrutinib-obinutuzumab outperformed obinutuzumab-venetoclax without statistically difference between them. Minimal residual disease–guided ibrutinib-venetoclax surpassed obinutuzumab-venetoclax in patients without comorbidities. Ibrutinib-obinutuzumab exhibited extended PFS benefits compared with obinutuzumab-venetoclax in patients with mutated IGHV or with del(17p) and/or TP53 mutations. Ibrutinib-venetoclax and ibrutinib-obinutuzumab had lower neutropenia rates than obinutuzumab-venetoclax. Ibrutinib-venetoclax had fewer infections than acalabrutinib and acalabrutinib-obinutuzumab. Acalabrutinib-obinutuzumab caused less diarrhea than ibrutinib-venetoclax but more headaches than ibrutinib-obinutuzumab and obinutuzumab-venetoclax. Obinutuzumab-venetoclax had lower hypertension rates than ibrutinib-obinutuzumab. Ibrutinib-venetoclax had fewer arthralgia than acalabrutinib-obinutuzumab. For any grade secondary primary neoplasms, ibrutinib-venetoclax and obinutuzumab-venetoclax was less than acalabrutinib-obinutuzumab.

Conclusion

Tailored chemotherapy-free regimens can be selected based on age, comorbidities, IGHV status, and cytogenetic abnormalities to optimize treatment outcomes while considering different adverse events spectra.
Risk factors for second primary breast cancer by laterality, age, and race and ethnicity
Authors: John Esther M , Koo Jocelyn , Ingles Sue A , Keegan Theresa H , Gomez Scarlett L , Haiman Christopher A , Kurian Allison W , Kwan Marilyn L , Neuhausen Susan L , Shariff-Marco Salma , Thomsen Catherine , Wu Anna H , Cheng Iona
Published: October 2024

Background

Epidemiological studies of risk factors for second primary breast cancer (SBC) have been conducted primarily in non-Hispanic White (NHW) women.

Methods

A racially and ethnically diverse population-based pooled cohort of 9639 women with first primary stage I-III invasive breast cancer (FBC) was linked with the California Cancer Registry; 618 contralateral SBC (CSBC) and 278 ipsilateral SBC (ISBC), diagnosed more than 6 months after FBC, were identified. Using Fine and Gray models accounting for competing risks, we assessed associations of CSBC and ISBC risk with FBC clinical characteristics and epidemiological factors.

Results

In younger women (FBC at age <50 years), higher CSBC risk was associated with ER/PR-negative FBC (hazard ratio [HR] = 1.68), breast cancer family history (HR = 2.20), and nulliparity (HR = 1.37). In older women (FBC at age ≥50 years), higher risk was associated with breast cancer family history (HR = 1.32), premenopausal status (HR = 1.49), overweight (HR = 1.39), and higher alcohol consumption (HR = 1.34). For ISBC, higher risk was associated with married status (HR = 1.94) in younger women, and overweight (HR = 1.60) among older women. For CSBC, HR estimates were generally similar across racial and ethnic groups. Even after adjustment for these risk factors, compared with NHW women, risk remained elevated for CSBC in younger African American, Asian American, and Hispanic women, and for ISBC in older African American and Hispanic women with ER/PR-positive FBC.

Conclusions

Our findings support genetic risk evaluation, enhanced screening, and lifestyle changes in women at higher risk of SBC. Additional risk factors must contribute to the unequal burden of SBC across racial and ethnic groups.
Implementation of a Nurse-Initiated Antibiotic Time-Out (NATO) in Childhood Cancer Patients in Central America
Authors: Licona Sergio , Chen Yichen , Aguilar Karla , Argüello Deiby , Camacho Kattia , Ceballo Gloria , Chang Alicia , Contreras Johanny , Cross Shane , Durán David , Estripeaut Dora , Gamero Mario , Hernandez Angélica , Levy Jacqueline , Luque Marco , Maradiaga Blanca , Melgar Mario , Morton Ted , Revolorio Fernanda , Devidas Meenakshi , Faughnan Lane , Pauley Jennifer L , Muniz-Talavera Hilmarie , Abraham Monnie , Wolf Joshua , Weber Lorena Segovia , Mukkada Sheena
Published: October 2024

Background

Children with cancer are at high risk for infection and frequently require antimicrobials. Antimicrobial stewardship (AMS) interventions can mitigate toxicity and development of antibiotic resistance yet the pharmacy and infectious diseases specialists who usually perform AMS are often absent in global settings. We report our experience testing a novel intervention to shift the antibiotic timeout to nurses in six pediatric oncology units in Central America.

Methods

The Nurse-initiated Antibiotic Timeout (NATO) is a scripted conversation between nurses and physicians to reevaluate antibiotic appropriateness after 48 to 72 hours of empiric use for febrile neutropenia. First, we performed a baseline assessment of AMS capacity using the WHO Practical Toolkit for AMS Programmes checklist. Based on these results, sites tailored a generic implementation plan emphasizing educational and documentation tools and iterative PDSA (Plan-Do, Study-Act) cycles to improve implementation and effectiveness outcomes.

Results

All sites collected antimicrobial use data for a minimum of two months. Four sites then piloted NATO, producing change ideas, including changes to documentation tools, antimicrobial decision categories, communication processes, and times. From August 2022 – October 2023, NATO was performed in 53.4% of febrile neutropenia episodes in the three sites reporting data. Sites had substantial NATO performance rate variation from month to month. Sites reported changes in antimicrobial therapy in 47% of episodes after a 6-month period (Figure 1).

Conclusion

The difference in performance rate of NATO underscores the importance of real-time reporting to adjust AMS implementation strategies. The change ideas developed by each site differed, however, core tools emerged, which will support AMS in other global settings. Next steps include comparing antimicrobial use pre- and post-intervention and determining a sustainability and scalability plan.

Figure 1. Incidence of change in antibiotic therapy over time.
Use of Data from a Fever Registry (FEVEREG) to Identify Quality Improvement Opportunities in a Third-Level Hospital in Panama
Authors: Levy Jacqueline , Estripeaut Dora , Chen Yichen , Devidas Meenakshi , Faughnan Lane , Licona Sergio , Muniz-Talavera Himy , Mukkada Sheena
Published: October 2024

Background

Infectious diseases in childhood cancer patients are frequent and increase the morbimortality of these patients. Hospital del Niño doctor José Renán Esquivel initiated data collection in a registry of fever and neutropenia (FEVEREG) to evaluate outcomes and management of these diseases and identify opportunities for quality improvement. The objective of this study is to describe data collected to date.

Methods

Data was collected through a data collection instrument (CRF) using Trial Master platform. It was analyzed with R Data Analytics (version 4.3.2) and descriptive statistics summarized. Only patients who were admitted due to the febrile episode or were hospitalized when fever started were included.

Results

From Sept 2021 to October 2023, we captured 138 episodes in 70 patients, with a mean age of 8 years (range 0-15) and a similar percentage of female and male patients. The most common diagnosis was acute lymphoblastic leukemia (57.14%) and the episodes occurred more during the induction phase (24%) and in patients with a relapse protocol (31.5%). The time of administration of the antibiotic varied depending on the patient location at fever onset. 44% of outpatients (46/105) received the first dose of antibiotic more than 4 hours after the onset of fever, while hospitalized patients received this dose in the first hour in 64% of cases (21/33). Time from registration of outpatients until the first dose of antibiotic was an average of 71 minutes, with 60% of the patients receiving the antibiotic during the first 60 minutes. In 45.8% of the episodes, a blood culture was taken before starting the antibiotic. The febrile neutropenia algorithm was followed on 64.5% of the days evaluated, with the main cause of deviation being treatment to the focus of infection (55%) followed by clinical decision (41%). Bacteremia occurred in 26% of episodes (20/78) and 14% of episodes had documented viral infection (11/78). The most frequently isolated bacteria in blood was Pseudomonas aeruginosa (13/33, 39.3%). Approximately 4% of the episodes (6/138) were admitted to the intensive care unit and died, half from septic shock and half from progressive disease. The average length of hospital stay was 12 days.

Conclusion

Data from FEVEREG has suggested opportunities for quality improvement in time to antibiotics and use of guideline compliant antibiotics (antimicrobial stewardship).