bluuebunny/crossref_metadata_2025 huggingface dataset:
A new chapter in CML treatment: the promise of asciminib
Authors: Akhtar Maimoona , Jamal Zoha , Mughal Sanila , Mahmmoud Fadelallah Eljack Mohammed
Published: February 2025

Asciminib, a groundbreaking treatment for chronic myeloid leukemia (CML), has gained FDA approval as the first STAMP inhibitor. Targeting the myristoyl pocket of the BCR-ABL1 protein, this drug offers a unique mechanism to overcome resistance to traditional tyrosine kinase inhibitors (TKIs). Clinical trials, such as the ASC4FIRST study, demonstrate asciminib’s superior efficacy compared to existing TKIs, achieving higher molecular response rates and fewer severe side effects. Its favorable safety profile, characterized by reduced vascular and pulmonary risks, supports improved patient adherence and long-term outcomes. While asciminib shows promise as a second-line or even frontline therapy, long-term data on its durability, adverse effects, and potential drug interactions are still evolving. Current research highlights its potential use in pediatric cases and in combination therapies for other leukemia types. Asciminib represents a significant advancement in CML treatment, paving the way for more targeted and tolerable cancer therapies.
A rare case of symmetric quadriplegia in a patient with japanese encephalitis: a case report
Authors: Basnet Prava , Singh Praveer Raj , Pudasaini Kshitiz Raj , Shrestha Suju , Kc Anjil
Published: February 2025

Introduction and importance:

Acute flaccid paralysis is a rare neurological complication of Japanese Encephalitis infection, which may involve one or multiple limbs. Symmetric involvement of upper and lower limbs such as in this case is rarely reported.

Presentation of case:

We present a case of a 30-year young male from terai region of Nepal who presented with fever, altered level of consciousness, and symmetrical quadriplegia. Based on these clinical findings, cerebrospinal fluid (CSF) analysis was done which came back negative. And based on results, Polymerase Chain Reaction (PCR) for herpes simplex virus (HSV) type I and II was done which came out negatively. Other neurological conditions such as Amyotrophic Lateral Sclerosis (ALS) and spinal dystrophy were ruled out because of the presence of fever and altered mental status. He was eventually diagnosed with Japanese encephalitis based on his cerebrospinal fluid analysis and positive result for JE serology/IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (MAC-ELISA) test.

Clinical discussion:

The patient presented with fever, altered mental status and symmetrical flaccid paralysis of the bilateral upper and lower limb. Symmetrical involvement of the upper and the lower limbs is unusual in most cases of Japanese Encephalitis.

Conclusion:

This case highlights the importance of awareness on the part of the clinician about the possibilities of atypical presentation in Japanese encephalitis (JE). It also emphasizes that Japanese encephalitis should be a part of the differential in patients with atypical neurological presentation in endemic areas.
Children’s Emergency Department Provider Experiences With Lethal Means Restriction Counseling and Firearm Access
Authors: Shibi Rosen Arielle , Bechtel Kirsten
Published: February 2025

Objective:

Assessing firearm access and providing lethal means restriction counseling (LMRC) is paramount for harm reduction, but evidence indicates that it is not commonly provided by Children’s Emergency Department (ED) providers. This study aimed to explore provider perspectives and determine avenues to increase discharge safety for patients with behavioral health emergencies.

Methods:

Twenty-nine Children’s ED providers completed semistructured interviews which were recorded, transcribed, iteratively coded, and organized into themes.

Results:

We identified the following 5 themes: (1) Children’s ED providers have varying experiences with firearms which could influence their clinical practices. (2) Most providers expressed knowledge of LMRC as a necessary component of safety planning for behavioral health patients. (3) The role of medical providers is commonly assumed to be only in medical clearance, with LMRC falling to social workers and psychiatrists. (4) Many Children’s ED providers seem to underestimate the gravity of risk associated with firearm access for children with behavioral health complaints. (5) Training and resources could help facilitate effective LMRC and support caregiver implementation of firearm secure storage.

Conclusions:

Despite a wide range of perspectives and barriers that prevent the consistent provision of LMRC, we saw that providers are amenable to interventions to increase comfort, consistency, and efficacy of safety planning. Understanding these perspectives can inform future initiatives for comprehensive LMRC that include firearm secure storage and address this crucial gap in care.
Optimization of physiology in organ donors in the intensive care unit - what you need to know
Authors: Swanson Elizabeth A. , Hayes Anthony J. , Malinoski Darren J.
Published: February 2025

Optimizing the physiology of organ donors is a critical component of preserving the option for organ donation and addressing the shortage of organs available for transplantation. In this article, we review common physiologic alterations seen in organ donors with a focus on brain-dead organ donors. These physiologic alterations and recommended interventions to optimize the physiology of the brain-dead organ donor are discussed by organ system, providing a framework for trauma surgeons and intensivists involved in the care of organ donors.
Bacteria in the brain: do they have a role in the pathogenesis of Alzheimer's disease?
Authors: Bhattacharya Arnav , Shepherd Claire , El-Assaad Fatima , Mather Karen A.
Published: February 2025

Purpose of review

Worldwide efforts continue to unravel the complex pathological pathways that lead to Alzheimer's disease. The gut–brain–microbiome axis, a communication pathway between the gut, brain and microorganisms, is emerging as a potential mechanism involved in Alzheimer's disease pathogenesis. While the gut microbiome's role in Alzheimer's disease has gained significant attention, the brain microbiome remains relatively unexplored. This review summarizes the latest research on the brain microbiome in Alzheimer's disease.

Recent findings

In the past 4 years, four out of five studies have found bacteria, such as Streptococcus pneumoniae, in postmortem samples of both control and Alzheimer's disease brains, supporting the idea that the brain is not a sterile environment. Two studies report the overabundance of several bacterial phyla, including Proteobacteria and Actinomycetes, in postmortem Alzheimer's disease brains versus controls. One study reported the presence of Borrelia burgdorferi in a subset of Alzheimer's disease cases compared to controls.

Limitations and challenges persist in studying the brain microbiome, including the lack of standardized assays and data analysis methods, small sample sizes, and inconsistent use of controls for environmental microbial contamination during sample processing. Well designed studies that employ reproducible and rigorous methods are required to elucidate whether microbes are involved in the pathogenesis of Alzheimer's disease.
Atmospheric sounding using Earth-based occultations
Authors: Encrenaz Therese , Sicardy Bruno , Roques Françoise , Coustenis Athena
Published: February 2025

The observation of Earth-based stellar occultations by solar system planets and satellites has been used for decades to retrieve information on the physical properties of their atmospheres. From the variations of the stellar flux during ingress and egress and, in some favourable cases, from the central flash, one can infer the vertical density, pressure and temperature profiles around the half-light level (typically in the range of a few μbars), as well as zonal wind regimes and the presence of hazes. Earth-based occultations have been successfully applied to all planets and satellites surrounded by an atmosphere, and have delivered unique and significant information that are often complementary to the results obtained by planetary space missions. The great improvement of the stellar catalogues provided by the Gaia astrometric space mission has drastically enlarged the capabilities of the stellar occultation method, which appears especially promising for probing the tenuous atmospheres of distant objects of the solar system.

This article is part of the theme issue ‘Major advances in planetary sciences thanks to stellar occultations’.
Infection caused by a cryptic fungal species, Blastomyces gilchristii, in a tiger
Authors: Rajeev Sreekumari , Reed Porsha , Llanes Alejandro , Jones Rebekah , Cushing Andrew , Craig Linden E. , Johnson Brian
Published: February 2025

Blastomycosis is a serious fungal disease affecting humans and animals. It is typically caused by the thermally dimorphic fungus, Blastomyces dermatitidis. In this report, we describe an infection caused by the cryptic fungal species, Blastomyces gilchristii, in a tiger (Panthera tigris).
Spatial self-organization of confined bacterial suspensions
Authors: Hokmabad Babak Vajdi , Martinez-Calvo Alejandro , Gonzalez La Corte Sebastian , Datta Sujit S
Published: February 2025

Lab studies of bacteria usually focus on cells in spatially-extended, nutrient-replete settings, such as in liquid cultures and on agar surfaces. By contrast, many biological and environmental settings---ranging from mucus in the body to ocean sediments and the soil beneath our feet---feature multicellular bacterial populations that are confined to tight spots where essential metabolic substrates (e.g., oxygen) are scarce. What influence does such confinement have on a bacterial population? Here, we address this question by studying suspensions of motile Escherichia coli confined to quasi two-dimensional (2D) droplets. We find that when the droplet size and cell concentration are both large enough, the initially-uniform suspension spatially self-organizes into a concentrated, immotile inner "core" that coexists with a more dilute, highly-motile surrounding "shell". By simultaneously measuring cell concentration, oxygen concentration, and motility-generated fluid flow, we show that this behavior arises from the interplay between oxygen transport through the droplet from its boundary, uptake by the cells, and corresponding changes in their motility in response to oxygen variations. Furthermore, we use theory and simulations to develop quantitative principles describing this interplay---establishing a biophysical framework that unifies all our experimental observations. Our work thereby sheds new light on the rich collective behaviors that emerge for bacterial populations, and other forms of chemically-reactive living and active matter, in confined environments, and provides a way to predict and control these behaviors more broadly.
Gut microbial-derived short chain fatty acids enhance kidney proximal tubule cell secretory function
Authors: Giordano Laura , Ahmed Sabbir , van der made Thom K , masereeuw Rosalinde , Mihaila Silvia Maria
Published: February 2025

The organic anion transporter-1 (OAT1), located at the basal side of kidney proximal tubule cells, is actively involved in metabolic waste excretion. During chronic kidney disease (CKD), the progressive decline in renal function, results in the accumulation of endogenous metabolites in the bloodstream, exacerbating comorbidities. CKD also leads to gut dysbiosis, resulting in an increased production of uremic metabolites and a reduced production of nephroprotective short chain fatty acid (SCFAs), mainly acetate, propionate and butyrate, thereby contributing to disease progression. Here, we studied the potential of SCFAs to enhance kidney function by modulating OAT1 activity, thereby facilitating uremic toxins secretion. Our findings demonstrate that propionate and butyrate significantly boost OAT1 activity by upregulating SLC22A6/ OAT1 gene and protein expression, with butyrate enhancing the secretion of the uremic toxin indoxyl sulfate to the luminal compartment in our kidney-on-chip (KoC) system. Interestingly, SCFAs function independently of G-protein coupled receptor (GPCR) activation, inhibiting gene expression of class II histone deacetylases (HDACs). Transcriptome analysis suggests that such inhibition modulates cyclic AMP signaling pathway, activating CREB1 and PI3K gene expression, both implicated in cell metabolism and resilience against stress, enhancing cellular fitness. These findings highlight the therapeutic potential of SCFAs in enhancing proximal tubule secretory activity, emphasizing their value as nutritional interventions in CKD management.
OpenCafeMol: A GPU-accelerated coarse-grained biomolecular dynamics simulator with OpenMM library
Authors: Murata Yutaka , Niina Toru , Takada Shoji
Published: February 2025

There has been an increasing demand for longer-timescale molecular dynamics (MD) simulations of larger biomolecular systems. To meet these demands, using the C++ API of OpenMM, we developed a fast and flexible MD software, OpenCafeMol, for residue-resolution protein and lipid models that shows high performance on graphics processing unit (GPU) machines. We validated OpenCafeMol for folding small proteins, lipid membrane dynamics, and membrane protein structures. Benchmark tests of the computation times showed that OpenCafeMol with one GPU for proteins and lipid membranes can be approximately 100 and 240 times faster than the corresponding simulations on a typical CPU machine (eight cores), respectively. We also illustrated the application of OpenCafeMol to vesicle fusion dynamics. The source code for OpenCafeMol is fully available.
Lonely plants in arid land are functionally hyperdiverse
Authors: Liancourt Pierre , Martin Raphael , Le Bagousse-Pinguet Yoann , Maestre Fernando T. , Berdugo Miguel , Delgado-Baquerizo Manuel , Eldridge David J. , Saiz Hugo , Soliveres Santiago , Valencia Enrique , GROSS Nicolas
Published: February 2025

In Gross et al.1 we produced the largest ever standardized dryland plant trait database including 133,769 trait measurements from 301 perennial plant species surveyed across 326 plots and six continents. Our findings indicate that arid and hyper-arid drylands act as a global reservoir of plant phenotypic diversity, challenging the common assumption that harsh environmental conditions reduce plant trait diversity. Tordoni et al.2 speculate that the larger phenotypic diversity in harsh environments found in our study is overestimated and misinterpreted. The re-analyses presented here further confirm that the patterns we originally reported are robust, and thus that the concerns from Tordoni et al. are not well-founded and do not apply to our study. We stand for the main conclusions of our study and maintain that lonely plants in arid land are functionally hyperdiverse.
Capturing R-loops at base-pair resolution unveils clustered R-loops regulate gene expression in a number-dependent manner
Authors: Li Yaoyi , Sheng Yingliang , Di Chao , Yao Hongjie
Published: February 2025

R-loops are prevalent triplex nucleic strands found across various organisms, involved in numerous biological processes. However, the physiological and pathological functions of R-loops remain largely unknown due to a lack of effective and high-resolution detection methods. Here, using nuclease P1, T5 exonuclease, and lambda exonuclease mediated digestion of ssRNA, ssDNA, and dsDNA while preserving RNA:DNA hybrid, we report a method named R-loop identification assisted by nuclease and high-throughput sequencing (RIAN-seq) for genome-wide mapping of R-loops at base-pair resolution. RIAN-seq represents ultra-accuracy in position and size of R-loops and identifies an order of magnitude more R-loops than current methods. Notably, we find the majority of R-loops ranging from 60 bp to 130 bp and reveal previously unresolvable patterns of R-loops aggerated in clusters across the genome. Clustered R-loops at gene promoters recruit zinc finger transcription factors (VEZF1 and SP5) to promote transcription. The number of R-loops within a cluster positively correlates with the diversity of bound transcription factors. Furthermore, clustered R-loops are less susceptible to transcription perturbation as the number of R-loops within clusters increases. Overall, we demonstrate the ability to identify R-loops at unprecedented resolution and facilitate investigating the mechanisms of clustered R-loops in gene regulation in diverse biological processes.
Habitat complexity reduces feeding strength of freshwater predators
Authors: Aranbarri Mireia , Flores Lorea , de Guzman Ioar , Larranaga Aitor , Elosegi Arturo , Rall Bjorn C. , Reiss Julia
Published: February 2025

The physical structure of an environment potentially influences feeding interactions among organisms by providing refuges for prey. We examined how habitat complexity affects the functional feeding response of an ambush predator (damselfly larvae Ischnura elegans) and a pursuit predator (backswimmer Notonecta glauca) feeding on the isopod Asellus aquaticus. We run experiments in aquatic microcosms with an increasing number of structural elements (0, 2, or 3 rings of plastic plants in different spatial configurations), resulting in five habitat complexity levels. Across these levels, predators were presented with different prey densities to determine their functional response. The experimental design and statistical analysis allowed us to test for effects of structure presence, amount, and complexity level on functional response in one pass, without confounding predictors. The feeding for both predators across all complexity levels was best described by a Type II functional response model and habitat drove feeding strength. Regarding the latter, the predators showed different responses to the complexity treatments. The overall feeding rate of I. elegans was mainly driven by the absence vs. presence of structure. Yet, in the case of N. glauca feeding rate was strongly dependent on habitat complexity with the predator showing unique maximum feeding rates (i.e. the inverse of the handling time) for each complexity level and a decreasing attack rate with increasing amount of habitat. Overall, prey consumption was less than half for both predators when complex structures were present, compared to the no habitat structure environment. Our findings demonstrate that habitat complexity dampens feeding rates and therefore plays a key role in the stability of freshwater ecosystems.
High genomic stability ofwMelWolbachiaafter introgression into three geographically distinctAedes aegyptipopulations
Authors: Dainty Kimberley R , Hawkey Jane , Supriyati Endah , Judd Louise M , Uribe Alexander , Velez Ivan D. , Anh Dang D. , Arguni Eggi , Tantowijoyo Warsito , O'Neill Scott , Holt Kat , Simmons Cameron P , Flores Heather A
Published: February 2025

The introgression ofwMelWolbachiaintoAedes aegyptipopulations is being used for the biocontrol of arboviruses such as dengue and chikungunya in 14 countries to date. AwMel infection inAe. aegyptiboth reduces the transmission of viruses by the mosquito and causes a reproductive manipulation that aidswMel introgression into naive populations. However, a critical concern is whetherwMel could evolve over time, potentially diminishing these desired phenotypes. Here, we investigated the stability of thewMel genome inAe. aegyptireleased for biocontrol in Colombia, Indonesia, and Vietnam. We sequenced thewMel genome at the start of releases and up to six years afterwMel introgression into each population. Our study identifies very few genomic changes, suggesting thewMel genome is not rapidly evolving despite its release into three geographically different field sites and subsequent exposure to novel environments. These results align with previouswMel sequencing studies from Australia and provide strong evidence for the long-term genomic stability ofwMel, reinforcing its potential as a reliable biocontrol tool againstAe. aegypti-transmitted arboviruses.
Detection of Danger-Associated Molecular Patterns in Kidney Preservation Fluid as Predictors of Delayed Graft Function after Transplantation
Authors: Hoyos-Domingo Andrea , Ruiz-Lopez Fatima , Garcia-Bueno Belen , de la Torre-Alamo Maria Magdalena , Mateo Sandra V , Vidal-Correoso Daniel , Guzman Martinez-Valls Pablo Luis , Lopez-Abad Alicia , Garcia-Rivas Francisco , Lopez-Cubillana Pedro , Baroja-Mazo Alberto
Published: February 2025

Background: Kidney transplantation is the preferred treatment for end-stage renal disease, but delayed graft function remains a significant complication. Cold ischemia during organ preservation can lead to the release of danger-associated molecular patterns (DAMPs), which may influence graft outcomes. This study aimed to quantify DAMPs in kidney preservation fluid and assess their correlation with delayed graft function (DGF). Methods: Preservation fluid samples from 88 deceased kidney donors were analyzed for various DAMPs, including mitochondrial DNA (mitDNA), cytochrome c, nucleosomes, hyaluronan, and inflammasome-related molecules (IL-18 and IL-1β). The influence of donor type (DBD vs. DCD) and cold ischemia time (CIT) on DAMP concentrations was evaluated. Additionally, the correlation between DAMP levels and DGF was assessed. Results: Multiple DAMPs were detected in preservation fluid, including mitDNA, cytochrome c, nucleosomes, and hyaluronan. The type of donation (DBD vs. DCD) had minimal impact on DAMP concentrations, except for HSP70, which was significantly higher in DCD donors. CIT positively correlated with hyaluronan and nucleosome levels. Cytochrome c emerged as a potential biomarker for DGF, showing a significant increase in patients with early dysfunction and correlating with post-transplant creatinine levels. Conclusions: Quantifying DAMPs in kidney preservation fluid is feasible and may provide valuable insights into graft quality and early post-transplant outcomes. Cytochrome c, in particular, shows promise as a biomarker for predicting delayed graft dysfunction. These findings highlight the importance of minimizing cold ischemia time and suggest that DAMP analysis could improve graft assessment prior to transplantation.
De Novo Design of Peptide Masks Enables Rapid Generation of Conditionally-Active Miniprotein Binders
Authors: Montaner Cristina , Lucchi Roberta , Escobar-Rosales Montserrat , Exposit Marc , Diaz-Perlas Cristina , Baker David , Oller-Salvia Benjami
Published: February 2025

The widespread expression of many therapeutic targets in both diseased and healthy tissues presents a significant challenge for protein therapeutics, often resulting in dose-limiting side effects. To focus the action of biotherapeutics at the disease site, they can be reversibly inactivated by tethering an affinity mask through a linker cleavable by a disease-specific cue. However, current methods to generate affinity masks require extensive screening of masking sequence libraries. Here, we report a workflow to design the first de novo peptide masks for the reversible inactivation of miniprotein binders and we show its application on an EGFR antagonist miniprotein. By extending the C-terminus of the miniprotein to cover the binding interface, a masking sequence is generated that decreases binding to EGFR over 1000 times. Binding of the parental miniprotein can be fully rescued by cleavage of the linker between the binder and the mask with tumor-specific proteases. Additionally, by site-specifically conjugating the peptide mask through a chemical linker, we show we can render the protein responsive to alternative stimuli such as light. Our approach opens the doors to dramatically accelerating the development of affinity-based masks for other proteins with therapeutic potential to render them conditionally active to any stimulus.
Network based statistics shows that rem sleep behavior disorder and visual hallucinations increase functional connectivity in early dementia with Lewy bodies
Authors: Carini Laura , Sommariva Sara , Famà Francesco , Giorgetti Laura , Mattioli Pietro , Orso Beatrice , Mancini Raffaele , Pardini Matteo , Piana Michele , Arnaldi Dario
Published: February 2025

Dementia with Lewy Bodies (DLB) is a heterogeneous disease characterized by four core clinical features, namely visual hallucinations, REM sleep behaviour disorder (RBD), cognitive fluctuations and parkinsonism. In this paper, we perform for the first time a comprehensive study on the relationship between all these features and functional connectivity derived from high-density electroencephalographic data. To quantify functional connectivity, we used two different connectivity metrics, each one averaged on individual theta and alpha frequency bands. The latter were defined by determining the individual theta-to-alpha transition frequency through a previously validated package called transfreq. The study was performed using a cohort comprising 33 subjects affected by early stage DLB (mean age 82 +/- 6 years, males/females: 23/10) and 21 healthy controls (mean age 71 +/- 9 years, males/female: 10/11) . After showing that overall DLB determines a shift toward lower frequencies of posterior dominant rhythm and theta-alpha transition, we used Network Based Statistic (NBS) to explore differential connectivity networks between subgroups of DLB patients with different core features. We consistently found that the presence of both visual hallucinations and RBD is associated with increased connectivity in early DLB patients mostly in the left hemisphere, while cognitive fluctuations and parkinsonism appear to have a non-significant impact on functional connectivity metrics. These findings may represent an initial compensatory mechanism in response to underlying neurodegeneration.
The overlooked impact of background diet and adherence in nutrition trials
Authors: Ottaviani Javier I , Schroeter Hagen , Bier Dennis M , Erdman John W , Sesso Howard D , Manson JoAnn E , Kuhnle Gunter Georg Christian
Published: February 2025

Importance Randomized controlled trials in nutrition (RCTN) face unique challenges such as the influence of participants' background diets and varying adherence to the intervention, factors that are difficult to quantify and can mask true intervention effects. However, the exact impact of these factors remains unclear. Objective To quantify the impact of background diet and adherence, estimated using validated nutritional biomarkers of flavanol intake, on the outcomes of a large-scale RCTN. Design, Setting, and Participants This study was nested within the COcoa Supplement and Multivitamin Outcomes Study (COSMOS;NCT02422745), a randomized, double-blind, placebo-controlled, 2x2 factorial trial conducted among 21,442 older adults in the United States. Analyses focused on participants (n=6,532) in the placebo and cocoa-extract intervention arms who had available biospecimens and outcome data. Exposures Daily supplementation with a cocoa flavanol (CF). Main Outcomes and Measures We used validated flavanol biomarkers in urine to assess background dietary flavanol intake and adherence to the cocoa extract intervention. Outcomes included total cardiovascular disease (CVD) events, CVD mortality, all-cause mortality, and major CVD events. Hazard ratios (HRs) with 95% CIs were estimated using intention-to-treat, per-protocol, and biomarker-based analyses. Results Of the 6,532 participants, 20% in both the placebo and intervention arms had a background flavanol intake similar to that provided by the intervention; only 5% had no background flavanol intake. In the intervention group, 33% of participants were not adherent based on expected biomarker levels, that was larger than the15% estimated based on self-reported pill-taking. Accounting for biomarker-estimated background diet and adherence resulted in a significant impact on effect sizes. For total CVD events, the HR (95% CI) of 0.79 (0.59-1.05) in the per-protocol analysis (PP), was reduced to 0.65 (0.47-0.89) in the biomarker-based analysis. Similar changes were observed for CVD mortality (from 0.51 (0.23; 1.14) to 0.44 (0.20; 0.97)), all-cause mortality (0.69 (0.45; 1.05) to 0.54 (0.37; 0.80)) and major CVD events (from 0.62 (0.43; 0.91) to 0.48 (0.31; 0.74)). Overall, biomarker-based analyses consistently produced stronger effect estimates than ITT and PP analyses that do not consider the impact of background diet or assess adherence using self-reported methods. Conclusions and Relevance These results highlight the importance of considering diet and adherence in RCTN using nutritional biomarker-based analyses. This may help to improve consistency and reliability of outcomes of RTC testing nutritional interventions.
RIPK3-dependent sequential recruitment of MLKL and RIPK1 drives PANoptotic cell death and chemokine production
Authors: YANG YU , WANG YUE , WANG YANG , WU ERPENG , CHEN HAO , SUN LIMING , ZHANG CHI , CAO SHUHUI , LI JINGWEN , QIANG HUIPING , ZHANG LINCHENG , LOU YUQING , ZHOU SHENAO , ZHOU YAN , ZHONG RUNBO , ZHONG HUA
Published: February 2025

PANoptosis, an immunogenic programmed cell death (PCD) modality, integrates features of pyroptosis, apoptosis, and necroptosis through assembly of the PANoptosome complex. Despite its conceptualization as a distinct PCD form, PANoptosis remains controversial due to insufficient characterization of its morphological hallmarks and molecular regulation. This study aimed to investigate the molecular mechanisms underlying the assembly of PANoptosomes in the PANoptotic pathway. We identified a novel receptor-interacting protein kinase 3 (RIPK3)-initiated PANoptotic pathway that functions without pattern recognition receptors (PRRs) and the ASC (apoptosis-associated speck-like protein containing a CARD) inflammasome. Using multimodal imaging and biochemical approaches, we identify unique morphological signatures distinguishing PANoptotic cells from canonical pyroptotic, apoptotic, or necroptotic counterparts. Mechanistically, RIPK3 forms round homopolymeric scaffolds, distinct from necroptotic amyloid-like fibers, to sequentially recruit MLKL and RIPK1, forming a dynamic RIPK3-MLKL-RIPK1-FADD-caspase-8 complex (RIPK3-PANoptosome). This platform coordinates concurrent activation of pyroptotic, apoptotic, and necroptotic effectors. Cross-regulatory interactions between these pathways establish a homeostatic system where perturbations bias death modality into a certain cell death type, altering the death process and outcomes. Functionally, PANoptotic cells orchestrate chemokine secretion through parallel kinase-dependent (RIPK3-MLKL) and kinase-independent (RIPK1-IKK-NF-κB) mechanisms, driving macrophage recruitment. Our findings resolve the molecular logic of PANoptosome assembly, redefine PANoptosis as a tunable PCD paradigm, and establish its role in immunomodulation, providing a framework for targeting inflammatory cell death in disease.
A prospective trial comparing programmable targeted long-read sequencing and short-read genome sequencing for genetic diagnosis of cerebellar ataxia
Authors: Rafehi Haloom , Fearnley Liam G. , Read Justin , Snell Penny , Davies Kayli C. , Scott Liam , Gillies Greta , Thompson Genevieve C. , Field Tess A. , Eldo Aleena , Bodek Simon , Butler Ernest , Chen Luke , Drago John , Goel Himanshu , Hackett Anna , Halmagyi G. Michael , Hannaford Andrew , Kotschet Katya , Kumar Kishore R. , Kumble Smitha , Lee-Archer Matthew , Malhotra Abhishek , Paine Mark , Poon Michael , Pope Kate , Reardon Katrina , Ring Steven , Ronan Anne , Silsby Matthew , Smyth Renee , Stutterd Chloe , Wallis Mathew , Waterston John , Wellings Thomas , West Kirsty , Wools Christine , Wu Kathy H.C. , Szmulewicz David J. , Delatycki Martin B. , Bahlo Melanie , Lockhart Paul J.
Published: February 2025

The cerebellar ataxias (CAs) are a heterogeneous group of disorders characterized by progressive incoordination. Seventeen repeat expansion (RE) loci have been identified as the primary genetic cause and account for >80% of genetic diagnoses. Despite this, diagnostic testing is limited and inefficient, often utilizing single gene assays. This study evaluates the effectiveness of long- and short-read sequencing as diagnostic tools for CA. We recruited 110 individuals (48 females, 62 males) with a clinical diagnosis of CA. Short-read genome sequencing (SR-GS) was performed to identify pathogenic RE and also non-RE variants in 356 genes associated with CA. Independently, long-read sequencing with adaptive sampling (LR-AS) was performed to identify pathogenic RE. SR-GS provided a genetic diagnosis for 38% of the cohort (40/110) including seven non-RE pathogenic variants. RE causes disease in 33 individuals, with the most common condition being SCA27B (n= 24). In comparison, LR-AS identified pathogenic RE in 29 individuals. RE identification for the two methods was concordant apart from four SCA27B cases not detected by LR-AS due to low read depth. For both technologies manual review of the RE alignment enhances diagnostic outcomes. Orthogonal testing for SCA27B revealed a 15% and 0% false positive rate for SR-GS and LR-AS, respectively. In conclusion, both technologies are powerful screening tools for CA. SR-GS is a mature technology currently used by diagnostic providers, requiring only minor changes in bioinformatic workflows to enable CA diagnostics. LR-AS offers considerable advantages in the context of RE detection and characterization but requires optimization before clinical implementation.
Field-orientation-dependent magnetic phases in
GdRu2Si2
probed with muon-spin spectroscopy
Authors: Huddart B. M. , Hernández-Melián A. , Wood G. D. A. , Mayoh D. A. , Gomilšek M. , Guguchia Z. , Wang C. , Hicken T. J. , Blundell S. J. , Balakrishnan G. , Lancaster T.
Published: February 2025

Centrosymmetric GdRu2Si2 exhibits a variety of multi-Q magnetic states as a function of temperature and applied magnetic field, including a square skyrmion-lattice phase. The material's behavior is strongly dependent on the direction of the applied field, with different phase diagrams resulting for fields applied parallel or perpendicular to the crystallographic c axis. Here, we present the results of muon-spin relaxation (μ+SR) measurements on single crystals of GdRu2Si2. Our analysis is based on the computation of muon stopping sites and consideration of quantum zero-point motion effects of muons, allowing direct comparison with the underlying spin textures in the material. The muon site is confirmed experimentally, using angle-dependent measurements of the muon Knight shift. Using transverse-field μ+SR with fields applied along either the [001] or [100] crystallographic directions, we distinguish between the magnetic phases in this system via their distinct muon response, providing additional evidence for the skyrmion and meron-lattice phases, while also suggesting the existence of RKKY-driven muon hyperfine coupling. Zero-field μ+SR provides clear evidence for a transition between two distinct magnetically ordered phases at 39 K.

Published by the American Physical Society
2025
Sub-MeV dark sink dark matter
Authors: Bhattiprolu Prudhvi N. , McGehee Robert , Petrosky Evan , Pierce Aaron
Published: February 2025

A dark sink uses dark-sector interactions to siphon energy from dark matter to lighter dark degrees of freedom, i.e., dark radiation. Here, we extend dark matter models containing a dark sink to sub-MeV masses. We consider a dark sink model where the dark matter is charged under a light dark photon that has kinetic mixing with the Standard Model. For sub-MeV dark matter masses, plasmon decays are the dominant mechanism for transferring energy to the dark sector. Relative to a standard freeze-in cosmology, reproducing the observed dark matter density in a dark sink structure requires an increase in the dark matter couplings to the Standard Model, and hence increased direct detection cross sections. These models provide benchmarks for current and upcoming direct detection experiments. Accounting for plasmon effects, we derive the range of possible dark matter masses and cross sections for dark sink models in the sub-MeV regime. We make the reezen code available to reproduce our benchmarks; it may be of use for other freeze-in scenarios, including those where plasmon decays to the dark matter are important.

Published by the American Physical Society
2025
Leptophilic
Z′
bosons at the FCC-ee: Discovery opportunities
Authors: Suarez Rebeca Gonzalez , Pattnaik Baibhab , Zurita José
Published: February 2025

We examine the possibility to detect new SM-neutral vector bosons (Z′) that couple exclusively to leptons in the electron-positron mode of the Future Circular Collider (FCC-ee). Focusing on the Z′ production with a radiated photon search channel, we show that the FCC-ee can significantly extend the unprobed parameter space by increasing the exclusion in the coupling by one to two orders of magnitude in the kinematically allowed mass range (from 10 to 365 GeV), with the leading sensitivity being driven by the muon channel. In doing so, it outperforms other proposed lepton collider options such as CLIC and ILC in this range of masses. Further, we discuss the possibility of improving the sensitivity of the FCC-ee to this model through the modification of the dilepton invariant mass resolution and the photon energy resolution. The impact of systematic uncertainties on the expected sensitivities is also studied.

Published by the American Physical Society
2025
Triply Efficient Shadow Tomography
Authors: King Robbie , Gosset David , Kothari Robin , Babbush Ryan
Published: February 2025

We investigate the problem of efficiently estimating expectation values of large sets of observables from copies of an unknown many-body quantum state. This task, known as shadow tomography, is crucial for quantum simulation and quantum chemistry, where the relevant observables often include k-body fermionic or k-local Pauli operators. A key goal is to achieve sample efficiency, computational efficiency, and few-copy measurements. We introduce the notion of triply efficient shadow tomography to formalize these requirements. Prior work has shown that single-copy measurements suffice for k-local Pauli operators with constant k. However, we prove that for k-body fermionic observables and the full set of

n

-qubit Pauli operators, single-copy protocols fail to achieve sample-efficient tomography. We then present new protocols based on measuring two copies of the state at a time that overcome these lower bounds, providing a triply efficient protocol.

Published by the American Physical Society
2025
The potential of AI tools in shaping digital consumers’ behavior: investigating e-commerce engagement of Chinese Generation Z
Authors: Pu Luoxi , Radics Robert , Umar Muhammad , Jeremiah Faith , Quan Zhi
Published: February 2025

Purpose

The purpose of this study is to investigate the potential adoption of AI-powered tools by Chinese Generation Z (Gen Z) consumers in e-commerce. It aims to understand how factors, such as performance expectancy, effort expectancy, social influence and facilitating conditions, affect behavioral intention and user behavior towards AI-enhanced e-commerce platforms.

Design/methodology/approach

The study employed the Unified Theory of Acceptance and Use of Technology (UTAUT) framework. A survey with 24 questions across six constructs was designed and distributed to Chinese Gen Z consumers aged 18–28. The research used convenience and quota sampling methods in four commercial complexes in a populous southwestern Chinese city, with 280 valid responses collected. The data was analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM).

Findings

It is found that performance expectancy, effort expectancy and facilitating conditions positively influence behavioral intention to use AI-powered e-commerce tools. Surprisingly, social influence shows a negative correlation with behavioral intention, suggesting that Chinese Gen Z consumers may not be swayed by others’ opinions in adopting these technologies. Facilitating conditions and behavioral intention both significantly affect user behavior. Gender differences can be observed, particularly in the impact of effort expectancy on behavioral intention.

Originality/value

This study extends the application of the UTAUT model to the rapidly evolving e-commerce sector, focusing on AI-powered tools and the unique characteristics of Chinese Gen Z consumers. By highlighting gender differences and the specific preferences of this generation, the research contributes to a more nuanced understanding of technology acceptance in e-commerce, guiding future marketing strategies and platform development.
Unlocking omnichannel capabilities to understand consumer retention: unravelling cross-channel integration and consumer empowerment
Authors: Malhotra Gunjan , Ramalingam Mahesh
Published: February 2025

Purpose

This study addresses a gap in understanding consumer retention in omnichannel retailing. It explores the impact of omnichannel capabilities on consumer retention by examining the roles of consumer empowerment, cross-channel integration, retailer uncertainty and consumer satisfaction.

Design/methodology/approach

Utilising the stimulus-organism-response theory, data from 338 Indian omnichannel consumers were analysed using SmartPLS V3 and Process Macro for SPSS. A structured questionnaire guided the investigation into the interconnected dynamics of omnichannel capabilities, consumer empowerment, cross-channel integration, retailer uncertainty and consumer satisfaction.

Findings

Findings suggest that omnichannel capabilities significantly and positively influence consumer retention, with a significant mediation impact on consumer empowerment and cross-channel integration. The results indicate that retailer uncertainty negatively moderates, whereas consumer satisfaction positively moderates the association between omnichannel capabilities and consumer retention. Moreover, the study unravels the mechanisms driving consumer retention in the omnichannel landscape.

Originality/value

This research pioneers unravelling the complexities of consumer retention in omnichannel retailing. It explores how consumer retention is enhanced through omnichannel capabilities. This study bridges a gap in existing research by examining the impact of omnichannel capabilities, consumer empowerment and cross-channel integration in omnichannel retailing. Therefore, this study provides innovative, unique and strategic adaptations in the retail industry.
High repetition rate Marx generator using inductive charging
Authors: Achour Yahia , Starzyński Jacek
Published: February 2025

Purpose

This paper aims to present a novel Marx generator architecture designed to achieve a high repetition rate while minimizing charging losses. The proposed approach demonstrates how inductive charging can enhance efficiency and robustness in pulsed power systems.

Design/methodology/approach

This study begins with a theoretical analysis of the generator’s operation, followed by validation through numerical simulations and experimental tests.

Findings

The modified Marx generator achieves significant performance improvements, including a pulse amplitude of 50 kV, a rise time of 4.5 ns and a repetition rate of 50 pps. The results validate the effectiveness of inductive charging in reducing energy losses and improving system reliability.

Originality/value

This work introduces, simulates and experimentally validates an advanced Marx generator configuration. The findings highlight the potential of inductive charging to overcome the limitations of traditional resistive designs, offering a more efficient and reliable solution for high-frequency pulsed power applications.
Coupled effects of stick-slip and thermal boundary conditions on viscous dissipation for inelastic power-law fluids
Authors: Al-Bahrani Bashaer Kadhim , Al-Muslimawi Alaa Hasan A.
Published: February 2025

Purpose

The article aims to provide an accurate and efficient numerical algorithm for viscous flows in power-law fluids under various thermal boundary and partial slip conditions.

Design/methodology/approach

We are conducting a numerical investigation using the Taylor–Galerkin/pressure correction finite element method, which builds upon the work of previous researchers. Here, attention is therefore given to the interplay of various thermal boundary and stick-slip conditions and their impact on non-isothermal inelastic fluid.

Findings

The results demonstrate the influence of the Prandtl, Brinkman and Reynolds numbers on the flow’s thermal and hydrodynamic behavior, concentrating on the impact of slip at the wall. Furthermore, we have presented the effects of these dimensionless parameters on the detailed local and average Nusselt numbers, illustrated the high accuracy we obtained for numerical convergence, and compared our results with those of previous papers, observing excellent agreement.

Practical implications

We have successfully tested the code under the presented industrial conditions. Future research directions on this topic aim for efficient and robust solvers for non-Newtonian thermal rheological models; this algorithm can be used for that purpose.

Originality/value

This algorithm has never been used for numerical analysis of such a problem previously.
Illuminating impact: a case study on Chirag’s rural solar initiatives
Authors: Malya Sapna , Pai Pratibha
Published: February 2025

Learning outcomes

This case study aims to provide an insight into the specific needs and constraints of rural communities related to energy access in India; help the students in assessing the effectiveness of the strategies in meeting the goals of the organization; help students understand the broader social responsibility of non-governmental organizations (NGOs) in contributing to United Nations Sustainable Development Goals; and empower the students to use the “theory of change methodology” to plan, execute and evaluate change implementation at the community/organizational level.

Case overview/synopsis

This case study is about a non-profit organization, Chirag Rural Development Foundation (CRDF), which provided solar lighting to empower villages in India. The NGO started its operations as a student-led initiative in 2010, and since then it was involved in various activities for rural upliftment using solar as the base. They initially provided solar equipment for home lighting which eventually grew into street lighting, school lighting and then water-lifting using solar pumps for drinking and livelihood under the integrated village development program. In 2021, Sabah Vig, the chief executive officer of CRDF, realized that the organization had grown much beyond the scope for which it was initially established. She felt the need to structure them and appropriately measure their complete sustainable impact so that CRDF could effectively track progress, optimize resource allocation and demonstrate tangible outcomes to the stakeholders.

Complexity academic level

This case study is suitable for postgraduate students.

Supplementary material

Teaching notes are available for educators only.

Subject code

CSS11: Strategy.