bluuebunny/crossref_metadata_2025 huggingface dataset:
The endophytic fungus Serendipita indica affects auxin distribution in Arabidopsis thaliana roots through alteration of auxin transport and conjugation to promote plant growth
Authors: González Ortega‐Villaizán Adrián , King Eoghan , Patel Manish K. , Pérez‐Alonso Marta‐Marina , Scholz Sandra S. , Sakakibara Hitoshi , Kiba Takatoshi , Kojima Mikiko , Takebayashi Yumiko , Ramos Patricio , Morales‐Quintana Luis , Breitenbach Sarah , Smolko Ana , Salopek‐Sondi Branka , Bauer Nataša , Ludwig‐Müller Jutta , Krapp Anne , Oelmüller Ralf , Vicente‐Carbajosa Jesús , Pollmann Stephan
Published: June 2024

Plants share their habitats with a multitude of different microbes. This close vicinity promoted the evolution of interorganismic interactions between plants and many different microorganisms that provide mutual growth benefits both to the plant and the microbial partner. The symbiosis of Arabidopsis thaliana with the beneficial root colonizing endophyte Serendipita indica represents a well‐studied system. Colonization of Arabidopsis roots with S. indica promotes plant growth and stress tolerance of the host plant. However, until now, the molecular mechanism by which S. indica reprograms plant growth remains largely unknown. This study used comprehensive transcriptomics, metabolomics, reverse genetics, and life cell imaging to reveal the intricacies of auxin‐related processes that affect root growth in the symbiosis between A. thaliana and S. indica. Our experiments revealed the sustained stimulation of auxin signalling in fungus infected Arabidopsis roots and disclosed the essential role of tightly controlled auxin conjugation in the plant–fungus interaction. It particularly highlighted the importance of two GRETCHEN HAGEN 3 (GH3) genes, GH3.5 and GH3.17, for the fungus infection‐triggered stimulation of biomass production, thus broadening our knowledge about the function of GH3s in plants. Furthermore, we provide evidence for the transcriptional alteration of the PIN2 auxin transporter gene in roots of Arabidopsis seedlings infected with S. indica and demonstrate that this transcriptional adjustment affects auxin signalling in roots, which results in increased plant growth.
Comprehensive identification, characterization and expression analysis of genes underpinning heat acclimatization in Triticum durum and Aegilops tauschii
Authors: Kumari Dipti , Jain Alok , Mukhopadhyay Kunal
Published: June 2024

Wheat (Triticum aestivum L.) is an important cereal crop cultivated and consumed worldwide. Global warming‐induced escalation of temperature during the seedling and grain‐filling phase adversely affects productivity. To survive under elevated temperatures, most crop plants develop natural mechanisms at molecular level by activating heat shock proteins. However, other heat stress‐related proteins like heat acclimatization (HA) proteins are documented in hexaploid wheat but have not been explored in detail in its diploid and tetraploid progenitors, which might help to overcome elevated temperature regimes for short periods. Our study aims to explore the potential HA genes in progenitors Triticum durum and Aegilops tauschii that perform well at higher temperatures. Seven genes were identified and phylogenetically classified into three families: K homology (KH), Chloroplast protein‐enhancing stress tolerance (CEST), and heat‐stress‐associated 32 kDa (HSA32). Protein‐protein interaction network revealed partner proteins that aid mRNA translation, protein refolding, and reactive species detoxification. Syntenic analysis displayed highly conserved relationships. RT‐qPCR‐based expression profiling revealed HA genes to exhibit diverse and dynamic patterns under high‐temperature regimes, suggesting their critical role in providing tolerance to heat stress. The present study furnishes genetic landscape of HA genes that might help in developing climate‐resilient wheat with higher acclimatization potential.
Influence of larval and adult diets on the maturation of male and female reproductive organs of the avian vampire fly, Philornis downsi (Diptera: Muscidae)
Authors: Lahuatte Paola Fernanda , Pérez‐Staples Diana , Causton Charlotte E. , Díaz‐Fleischer Francisco
Published: June 2024

The invasive avian vampire fly, Philornis downsi, Dodge and Aitken (Diptera: Muscidae) is a threat to the long‐term conservation of Darwin's finches and other landbirds in the Galapagos Islands. Adult flies feed on fermented fruit, but their larvae are obligate parasites that feed on, and often cause the mortality of, the developing nestlings. Various techniques for the control of this parasite are currently under study, but the inability to rear flies in captivity has slowed progress. To help understand the reproductive behaviour of P. downsi, in this study, we measured the reproductive organs of male and female flies to determine the age flies mature physiologically, as well as the influence of the larval and adult diets on this process. Both females and males reared from larvae that had developed in the wild on live birds reached physiological maturity at 6 days; in the males, this was associated with increased pigmentation of the testes and the presence of free sperm, and in the females, mature eggs. Females reared in the laboratory on an artificial diet produced mature eggs at 6 days. However, the ovaries of laboratory‐reared females were statistically smaller than those of wild females, suggesting that egg production was affected by larval diet. Physiological maturity was delayed in laboratory‐reared males, taking twice as long. The testes of these males had more unpigmented areas and deformities indicating that the artificial larval diet was insufficient. Enrichment of the adult diet could help compensate for this. The addition of methoprene (M) to the diet was found to have a positive effect on the sexual development of the flies. In females, a diet of sugar + yeast hydrolysate (YH) in a 3:1 ratio combined with M favoured the development of larger ovaries and the production of mature eggs at an earlier age (3 days). In the case of males, a diet with YH increased testis size and M accelerated the growth of testis length even when males were fed only with sugar and without YH. Additional studies are recommended for improving the diets for mass‐rearing this highly harmful fly.
Potholes, 311 reports, and a theory of heterogeneous resident demand for city services
Authors: Cook Scott J. , Zuhlke Samantha , Saywitz Robin
Published: June 2024

Understanding the needs of residents is vital in public administration and management, as this helps officials when making choices on policies and service distribution. Increasingly, cities rely on 311 systems to elicit information from residents on emergent needs in particular policy areas (e.g., road quality, pest control). For residents, 311 systems provide a low‐cost means of voicing concerns, whereas for public officials and researchers, they provide low‐cost data on specific, discrete needs. We argue that residents systematically differ in their engagement with 311 systems, with lower‐income, minority communities less likely to participate and, therefore, less likely to receive city services. We test this argument using census‐tract data from the city of Houston and find that 311 reports are significantly less frequent in areas with lower average socioeconomic status, more Black residents, and more Hispanic residents. Furthermore, we find that these same areas are more likely to have potholes. Taken together, our results indicate that despite greater need (more potholes), fewer services are demanded (less 311 reports) in areas with lower socioeconomic status and a higher percentage of minority residents. This suggests that public officials need to carefully consider heterogeneity in 311 participation to ensure these systems do not inadvertently exacerbate inequities in public services.
Aversive contexts enhance defensive responses to conditioned threat
Authors: Stegmann Yannik , Paulus Judith , Wieser Matthias J. , Gamer Matthias
Published: June 2024

The ability to flexibly transition between defensive states is crucial for adaptive responding in life‐threatening situations. Potentially threatening situations typically induce a sustained feeling of apprehension in association with hypervigilance, while acute threat is usually characterized by an intense and transient response to cope with the imminent danger. While potential and acute threat states have traditionally been viewed as mutually exclusive, this distinction is being challenged by a growing body of evidence suggesting a more complex interplay during simultaneous activation of these states. However, the interaction between potential and acute threat on a psychophysiological level remains elusive. To fill this gap, 94 healthy individuals participated in one of two contextual fear‐conditioning paradigms. In both paradigms, a differential fear‐learning phase was conducted, followed by a test phase in which the conditioned stimuli were presented in front of either conditioned or inherently aversive contextual images compared to neutral contexts. To capture defensive responses, we recorded subjective (threat and expectancy ratings) and physiological (electrodermal and cardiovascular) activity to the conditioned stimuli as a function of contextual threat. Besides indices of successful fear conditioning, our results revealed stronger threat and unconditioned stimulus expectancy ratings, cardiac deceleration, and skin conductance responses for threat and safety cues presented in inherently aversive compared to neutral contexts. Conditioned contexts had less impact on physiological responses to threat and safety cues than inherently aversive contexts. These findings provide new insights into the additive nature of defensive responses to fear cues and situations of contextual threat.
Glycerol supplementation in farmed fish species: A review from zootechnical performance to metabolic utilisation
Authors: Coelho Margarida , Palma Mariana , Tavares Ludgero C. , Panserat Stéphane , Viegas Ivan , Magnoni Leonardo J.
Published: June 2024

Glycerol, an abundant by‐product of biodiesel production, has gained attention due to its price and availability for potential commercial applications, and thus utilisation as an animal feed ingredient. This article comprehensively reviews glycerol utilisation in fish and its potential as a dietary ingredient for aquaculture. While dietary inclusion of glycerol may offer cost‐effective energy and metabolic intermediates, studies report inconsistent results regarding its effects on nutrient digestibility, zootechnical performance, and product quality. Recent studies however have demonstrated that dietary glycerol supplementation in fish induces metabolic shifts, such as alterations to gluconeogenesis and/or lipogenesis, modifying energy utilisation. Additionally, glycerol has been proposed to reduce protein catabolism, minimising nitrogen excretion and its environmental impact, but its influence on protein retention remains uncertain. Nevertheless, it is important to carefully consider the balance between feed palatability and these potential metabolic alterations when incorporating glycerol in aquafeeds. This review highlights the need for more studies to expand our understanding of glycerol metabolism in fish, since it does not seem to be metabolised by carnivorous species as much as omnivorous. Future research should explore the effects of glycerol supplementation on fish with different feeding habits and in developmental stages, as well as diverse environmental salinities and temperatures. Insight into the impact of impurities and the optimisation of glycerol inclusion in aquafeeds are recommended to support sustainable aquaculture practices and the utilisation of glycerol as a valuable resource.
LCEVES: A locally constrained evolutionary algorithm for vehicle evacuation scheduling under urban waterlogging risk
Authors: Rao Luowen , Tan Xicheng , Zhong Yanfei , Chen Chunhui , Hussain Zeenat Khadim , Ma Ailong , Wang Huamin , Yin Shengpeng , Liu Fangyu , Mei Zhiyuan
Published: June 2024

The global rising level of climate change has caused significant disruptions in city traffic patterns due to intense heavy rains causing urban waterlogging disasters worldwide. These disasters have also resulted in massive economic losses and casualties. In consideration of these issues, the current challenge for urban disaster emergency response is to determine strategies to arrange for emergency vehicle scheduling as soon as urban waterlogging expands in a way that minimizes casualties and financial losses. This article proposes the Locally Constraint Evolutionary algorithm for Vehicle Evacuation Scheduling (LCEVES), which includes the following features to address the vehicle emergency evacuation problems in urban waterlogging zones specifically for regulated vehicles (e.g., buses, vehicles transporting hazardous materials, etc.). Firstly, a general technical route for vehicle emergency evacuation under urban waterlogging risk, secondly an optional routes search mechanism for vehicle evacuation in the waterlogging area and thirdly a locally constraint evolutionary algorithm for vehicle evacuation in the waterlogging area. The experiments show that LCEVES improves vehicle evacuation efficiency and reduces the risk of affected vehicles, providing an effective means for vehicle evacuation in the waterlogging zone. This research provides an effective method for solving vehicle evacuation scheduling challenges during urban waterlogging and also has significance for vehicle scheduling in other types of disasters.
The finger weeder cultivator for intra‐row mechanical weed control: Effects of uprooting force on selected weed species
Authors: Asaf Evyatar , Shulner Itai , Bakshian Hila , Kapiluto Omer , Eizenberg Hanan , Lati Ran Nisim
Published: June 2024

Mechanical weed control tools are commonly used in the production of many vegetable and field crops. This study aimed to determine the impact of weed species and growth stage on the finger weeder performances and to reveal the relation between root morphology, uprooting force and control efficacy. A one‐month field experiment with two model species, Triticum aestivum L. (grass) and Sinapis alba L. (broadleaf), showed that finger weeder control efficacy was affected by species and growth stage: Finger‐weeder application during the first two growth stages (cotyledon and second leaf) was more effective for S. alba than for T. aestivum (p < 0.0001), but at fourth‐leaf stage values for control efficacy were not significantly different (p = 0.134). In an experiment conducted in pots it was found that, at all three growth stages, the uprooting force required for S. alba was significantly lower than that for T. aestivum (p < 0.0001), indicating a lower anchoring force of the former. Determination of root‐morphology parameters revealed significantly higher root parameters, like length, in T. aestivum than in S. alba at the early developmental stages. Correlation of the control efficacy and uprooting force revealed a 2.5‐N threshold value for effective weed control. Additionally, net‐house and field experiments showed significant differences in the uprooting forces required for 10 different Mediterranean grasses versus broadleaves weed species at all developmental stages. To translate these findings into applicative recommendations, future research should characterize the relationship between the operational factors of this tool and the required uprooting force.
Trends in inpatient burden from pressure injuries in the United States: Cross‐sectional study National Inpatient Sample 2009–2019
Authors: Choragudi Siri , Andrade Luis F. , Maskan Bermudez Narges , Burke Olivia , Sa Brianna Christina , Kirsner Robert S.
Published: June 2024

Pressure injuries are a significant comorbidity and lead to increased overall healthcare costs. Several European and global studies have assessed the burden of pressure injuries; however, no comprehensive analysis has been completed in the United States. In this study, we investigated the trends in the burden of pressure injuries among hospitalised adults in the United States from 2009 to 2019, stratified by sociodemographic subgroups. The length of admission, total cost of hospitalisation, and sociodemographic data was extracted from the National Inpatient Sample provided by the Healthcare Cost and Utilisation Project, Agency for Healthcare Research and Quality. Overall, the annual prevalence of pressure injuries and annual mean hospitalisation cost increased ($69,499.29 to $102,939.14), while annual mean length of stay decreased (11.14–9.90 days). Among all races, minority groups had higher average cost and length of hospitalisation. Our findings suggest that while the length of hospitalisation is decreasing, hospital costs and prevalence are rising. In addition, differing trends among racial groups exist with decreasing prevalence in White patients. Further studies and targeted interventions are needed to address these differences, as well as discrepancies in racial groups.
p∞$p^{\infty }$‐Selmer ranks of CM abelian varieties
Authors: Bell Jamie
Published: June 2024

For an elliptic curve with complex multiplication over a number field, the ‐Selmer rank is even for all . Česnavičius proved this using the fact that admits a ‐isogeny whenever splits in the complex multiplication field, and invoking known cases of the ‐parity conjecture. We give a direct proof, and generalise the result to abelian varieties.
Spatial acoustic properties recovery with deep learning
Authors: Liu Ruixian , Gerstoft Peter
Published: June 2024

The physics-informed neural network (PINN) can recover partial differential equation (PDE) coefficients that remain constant throughout the spatial domain directly from measurements. We propose a spatially dependent physics-informed neural network (SD-PINN), which enables recovering coefficients in spatially dependent PDEs using one neural network, eliminating the requirement for domain-specific physical expertise. The network is trained by minimizing a combination of loss functions involving data-fitting and physical constraints, in which the requirement for satisfying the assumed governing PDE is encoded. For the recovery of spatially two-dimensional (2D) PDEs, we store the PDE coefficients at all locations in the 2D region of interest into a matrix and incorporate a low-rank assumption for this matrix to recover the coefficients at locations without measurements. We apply the SD-PINN to recovering spatially dependent coefficients of the wave equation to reveal the spatial distribution of acoustic properties in the inhomogeneous medium.
Attentional Foci and Coping Strategies During Matches of Young Fencers in a Training Center: A Naturalistic Video-Assisted Study
Authors: Maurin Mathéo , Bracco Maëlle , Le Pape Steven , Lienhart Noémie , Bossard Cyril , Doron Julie , Martinent Guillaume
Published: June 2024

The purpose of this study was twofold: (a) identify attentional foci (AF) and coping strategies used by young fencers during matches and (b) explore the links between these variables using a grounded-theory approach. Using a naturalistic qualitative video-assisted approach, analyses revealed the emergence of five categories of AF (movements and techniques, strategies and tactics, situation evaluation, states, and extraneous attention) and six categories of coping strategies (mastery coping, internal regulation, goal-withdrawal strategies, behavioral regulation, no regulation, and automatic regulation). The grounded theory highlighted that pleasant emotional experiences tended to be related to mastery coping, which in turn favored the orientation of the attention toward AF that appeared to be most effective in winning points (i.e., opponent, distance, plan). Conversely, unpleasant emotional experiences were consistently associated with goal-withdrawal strategies (or no regulation), which generally led to a lack of AF and lower performance. Intervention suggestions are made in relation to the results of the proposed grounded theory.
Nuclear factor κB overactivation in the intervertebral disc leads to macrophage recruitment and severe disc degeneration
Authors: Burt Kevin G. , Kim Min Kyu M. , Viola Dan C. , Abraham Adam C. , Chahine Nadeen O.
Published: June 2024

Persistent inflammation has been associated with severe disc degeneration (DD). This study investigated the effect of prolonged nuclear factor κB (NF-κB) activation in DD. Using an inducible mouse model, we genetically targeted cells expressing aggrecan, a primary component of the disc extra cellular matrix, for activation of the canonical NF-κB pathway. Prolonged NF-κB activation led to severe structural degeneration accompanied by increases in gene expression of inflammatory molecules (
Il1b
,
Cox2
,
Il6
, and
Nos2
), chemokines (
Mcp1
and
Mif
), and catabolic enzymes (
Mmp3
,
Mmp9
, and
Adamts4
). Increased recruitment of proinflammatory (F4/80
+
,CD38
+
) and inflammatory resolving (F4/80
+
,CD206
+
) macrophages was observed within caudal discs. We found that the secretome of inflamed caudal disc cells increased macrophage migration and inflammatory activation. Lumbar discs did not exhibit phenotypic changes, suggestive of regional spinal differences in response to inflammatory genetic overactivation. Results suggest prolonged NF-κB activation can induce severe DD through increases in inflammatory cytokines, chemotactic proteins, catabolic enzymes, and the recruitment and activation of macrophage cell populations.
Gene regulatory network topology governs resistance and treatment escape in glioma stem-like cells
Authors: Park James H. , Hothi Parvinder , de Lomana Adrian Lopez Garcia , Pan Min , Calder Rachel , Turkarslan Serdar , Wu Wei-Ju , Lee Hwahyung , Patel Anoop P. , Cobbs Charles , Huang Sui , Baliga Nitin S.
Published: June 2024

Poor prognosis and drug resistance in glioblastoma (GBM) can result from cellular heterogeneity and treatment-induced shifts in phenotypic states of tumor cells, including dedifferentiation into glioma stem-like cells (GSCs). This rare tumorigenic cell subpopulation resists temozolomide, undergoes proneural-to-mesenchymal transition (PMT) to evade therapy, and drives recurrence. Through inference of transcriptional regulatory networks (TRNs) of patient-derived GSCs (PD-GSCs) at single-cell resolution, we demonstrate how the topology of transcription factor interaction networks drives distinct trajectories of cell-state transitions in PD-GSCs resistant or susceptible to cytotoxic drug treatment. By experimentally testing predictions based on TRN simulations, we show that drug treatment drives surviving PD-GSCs along a trajectory of intermediate states, exposing vulnerability to potentiated killing by siRNA or a second drug targeting treatment-induced transcriptional programs governing nongenetic cell plasticity. Our findings demonstrate an approach to uncover TRN topology and use it to rationally predict combinatorial treatments that disrupt acquired resistance in GBM.
B1-B2 transition in shock-compressed MgO
Authors: Wicks June K. , Singh Saransh , Millot Marius , Fratanduono Dayne E. , Coppari Federica , Gorman Martin G. , Ye Zixuan , Rygg J. Ryan , Hari Anirudh , Eggert Jon H. , Duffy Thomas S. , Smith Raymond F.
Published: June 2024

Magnesium oxide (MgO) is a major component of the Earth’s mantle and is expected to play a similar role in the mantles of large rocky exoplanets. At extreme pressures, MgO transitions from the NaCl
B
1 crystal structure to a CsCl
B
2 structure, which may have implications for exoplanetary deep mantle dynamics. In this study, we constrain the phase diagram of MgO with laser-compression along the shock Hugoniot, with simultaneous measurements of crystal structure, density, pressure, and temperature. We identify the
B
1 to
B
2 phase transition between 397 and 425 gigapascal (around 9700 kelvin), in agreement with recent theory that accounts for phonon anharmonicity. From 425 to 493 gigapascal, we observe a mixed-phase region of B1 and B2 coexistence. The transformation follows the Watanabe-Tokonami-Morimoto mechanism. Our data are consistent with
B
2-liquid coexistence above 500 gigapascal and complete melting at 634 gigapascal. This study bridges the gap between previous theoretical and experimental studies, providing insights into the timescale of this phase transition.
Consistent time allocation fraction to vegetation green-up versus senescence across northern ecosystems despite recent climate change
Authors: Meng Fandong , Felton Andrew J. , Mao Jiafu , Cong Nan , Smith William K. , Körner Christian , Hu Zhongmin , Hong Songbai , Knott Jonathan , Yan Yanzi , Guo Bixi , Deng Ying , Leisz Stephen , Dorji Tsechoe , Wang Shiping , Chen Anping
Published: June 2024

Extended growing season lengths under climatic warming suggest increased time for plant growth. However, research has focused on climatic impacts to the timing or duration of distinct phenological events. Comparatively little is known about impacts to the relative time allocation to distinct phenological events, for example, the proportion of time dedicated to leaf growth versus senescence. We use multiple satellite and ground-based observations to show that, despite recent climate change during 2001 to 2020, the ratio of time allocated to vegetation green-up over senescence has remained stable [1.27 (± 0.92)] across more than 83% of northern ecosystems. This stability is independent of changes in growing season lengths and is caused by widespread positive relationships among vegetation phenological events; longer vegetation green-up results in longer vegetation senescence. These empirical observations were also partly reproduced by 13 dynamic global vegetation models. Our work demonstrates an intrinsic biotic control to vegetation phenology that could explain the timing of vegetation senescence under climate change.
Mechanism of human PINK1 activation at the TOM complex in a reconstituted system
Authors: Raimi Olawale G. , Ojha Hina , Ehses Kenneth , Dederer Verena , Lange Sven M. , Rivera Cristian Polo , Deegan Tom D. , Chen Yinchen , Wightman Melanie , Toth Rachel , Labib Karim P. M. , Mathea Sebastian , Ranson Neil , Fernández-Busnadiego Rubén , Muqit Miratul M. K.
Published: June 2024

Loss-of-function mutations in PTEN-induced kinase 1 (PINK1) are a frequent cause of early-onset Parkinson’s disease (PD). Stabilization of PINK1 at the translocase of outer membrane (TOM) complex of damaged mitochondria is critical for its activation. The mechanism of how PINK1 is activated in the TOM complex is unclear. Here, we report that co-expression of human PINK1 and all seven TOM subunits in
Saccharomyces cerevisiae
is sufficient for PINK1 activation. We use this reconstitution system to systematically assess the role of each TOM subunit toward PINK1 activation. We unambiguously demonstrate that the TOM20 and TOM70 receptor subunits are required for optimal PINK1 activation and map their sites of interaction with PINK1 using AlphaFold structural modeling and mutagenesis. We also demonstrate an essential role of the pore-containing subunit TOM40 and its structurally associated subunits TOM7 and TOM22 for PINK1 activation. These findings will aid in the development of small-molecule activators of PINK1 as a therapeutic strategy for PD.
Human γδ T cells in diverse tissues exhibit site-specific maturation dynamics across the life span
Authors: Gray Joshua I. , Caron Daniel P. , Wells Steven B. , Guyer Rebecca , Szabo Peter , Rainbow Daniel , Ergen Can , Rybkina Ksenia , Bradley Marissa C. , Matsumoto Rei , Pethe Kalpana , Kubota Masaru , Teichmann Sarah , Jones Joanne , Yosef Nir , Atkinson Mark , Brusko Maigan , Brusko Todd M. , Connors Thomas J. , Sims Peter A. , Farber Donna L.
Published: June 2024

During ontogeny, γδ T cells emerge from the thymus and directly seed peripheral tissues for in situ immunity. However, their functional role in humans has largely been defined from blood. Here, we analyzed the phenotype, transcriptome, function, and repertoire of human γδ T cells in blood and mucosal and lymphoid tissues from 176 donors across the life span, revealing distinct profiles in children compared with adults. In early life, clonally diverse Vδ1 subsets predominate across blood and tissues, comprising naïve and differentiated effector and tissue repair functions, whereas cytolytic Vδ2 subsets populate blood, spleen, and lungs. With age, Vδ1 and Vδ2 subsets exhibit clonal expansions and elevated cytolytic signatures, which are disseminated across sites. In adults, Vδ2 cells predominate in blood, whereas Vδ1 cells are enriched across tissues and express residency profiles. Thus, antigenic exposures over childhood drive the functional evolution and tissue compartmentalization of γδ T cells, leading to age-dependent roles in immunity.
Hide-&-Go-PhiP-Seq: Finding an elusive predictive MS biomarker
Authors: Wallace Annabel , O’Connor Kevin C.
Published: June 2024

Whole-proteome autoantibody profiling reveals an immunological signature that predates the clinical onset of multiple sclerosis.
Improved complete genome sequence of
Bdellovibrio bacteriovorus
109J, a widely studied laboratory strain of predatory bacteria
Authors: Hoshiko Yuki , Okuno Miki , Yamamoto Takeshi , Maeda Toshinari , Ogura Yoshitoshi
Published: June 2024

The complete genome sequence of
Bdellovibrio bacteriovorus
109J, a well-studied laboratory strain of predatory bacteria, first determined in 2014. Here we report an improved complete genome sequence of
B. bacteriovorus
109J, incorporating 16 assembly and 87 nucleotide corrections. This revised genome will be helpful to studies on the predatory bacteria.
Discrimination of tectonic provinces using zircon U-Pb ages from bedrock and detrital samples in the northern Andes
Authors: Sandoval Jose Ricardo , Pérez-Consuegra Nicolás , Mora Andrés , Horton Brian K. , Parra Mauricio , Beltrán Alejandro , Gómez Ricardo Andrés , Ibanez Mauricio , Valencia Víctor
Published: June 2024

The northern Andes of southern Colombia contain a rich geologic history recorded by Proterozoic to Cenozoic metamorphic, igneous, and sedimentary rocks. The region plays a pivotal role in understanding the evolution of topography in northwestern South America and the development of large river systems, such as the Amazon, Orinoco, and Magdalena rivers. However, understanding of the basement framework has been hindered by challenging access, security concerns, tropical climate, and outcrop scarcity. Further, an insufficient geochronologic characterization of Andean basement complicates provenance interpretations of adjacent basins and restricts understanding of the paleogeographic evolution of southern Colombia. To address these issues, this paper presents a zircon U-Pb geochronological dataset derived for 24 bedrock samples and 19 modern river samples. The zircon U-Pb results reveal that the Eastern Cordillera of southern Colombia is underlain by basement rocks that originated in various tectonic events since ca. 1.5 Ga, including the accretion of discrete terranes. The oldest rocks, found in the Garzon Massif, are high-grade metamorphic rocks with contrasting Proterozoic protolith crystallization ages. Whereas the SW part of the massif formed during the Putumayo Orogeny (ca. 1.2–0.9 Ga), we report orthogneisses for the NE segment with protoliths formed at ca. 1.5 Ga, representing the NW continuation of the Rio Negro Jurena province of the Amazonian Craton. In contrast, crystalline rocks of the Central Cordillera primarily consist of Permian–Triassic (ca. 270–250 Ma) and Jurassic–Cretaceous (ca. 180–130 Ma) igneous rocks formed in a magmatic arc. In southernmost Colombia, the Putumayo Mountains mainly consist of Jurassic–Cretaceous (180–130 Ma) plutonic and volcanic rocks. Furthermore, we analyzed the heavy mineral abundances in modern river sands in southern Colombia (spanning 1°N–5°N) and found that key minerals such as garnet and epidote can be utilized to trace high-grade metamorphic and igneous lithologies, respectively, in the river catchments. The differentiation of basement ages for separate tectonic provinces, combined with heavy mineral abundances in modern sands, can serve as unique fingerprints in provenance analyses to trace the topographic and exhumational evolution of different Andean regions through time.
Utility and acceptability of remote 6-lead electrocardiographic monitoring in children with inherited cardiac conditions
Authors: Lawley Claire Margaret , Luczak-Wozniak Katarzyna , Chung Sheng-Chia , Field Ella , Barnes Annabelle , Starling Luke , Cervi Elena , Kaski Juan Pablo
Published: June 2024

Objective

This pilot study sought to investigate the utility and acceptability of the KardiaMobile 6-lead ECG (KM6LECG) as a tool for remote monitoring in children with inherited cardiac conditions.

Design

A single-centre prospective cohort study. Children underwent standard clinical evaluation including a 12-lead ECG and a KM6LECG in the clinic. Participants recorded KM6LECGs monthly at home for 3 months. Families completed a questionnaire on their experience.

Setting

Great Ormond Street Hospital Centre for Inherited Cardiovascular Diseases.

Participants

64 children: 22 with hypertrophic cardiomyopathy (HCM); 22 with long QT syndrome and 20 unaffected siblings (controls).

Main outcome measures

Comparison of data extracted from the clinic 12-lead ECG and supervised KM6LECG, and the supervised and unsupervised KM6LECG recording.

Results

Of 64 children (35% female, mean age 12 years), 58 had a baseline 12-lead ECG and appropriate baseline KM6LECG. In children with HCM, abnormalities in ventricular depolarisation/repolarisation in the limb leads of the 12-lead ECG were reliably reproduced. From the whole cohort, there was a strong positive correlation between the corrected QT interval from the 12-lead ECG and baseline KM6LECG (intraclass correlation coefficient=0.839) and baseline KM6LECG with an unsupervised KM6LECG (intraclass correlation coefficient=0.736). Suspected ‘lead’ misplacement impacted 18% of unsupervised recordings. Overall, the acceptability of the KM6LECG to families was good.

Conclusions

The KM6LECG provides an accurate tool for assessing some ECG abnormalities associated with paediatric inherited cardiovascular disease and may provide a useful at-home adjunct to face-to-face clinical care of children requiring ECG assessment.
How do we define therapy-resistant constipation in children aged 4–18 years old? A systematic review with meta-narrative synthesis
Authors: Sinopoulou Vassiliki , Gordon Morris , Rajindrajith Shaman , Hathagoda Watshala , Rane Aditi Bhupendra , Sedghi Anita , Tabbers Merit , Di Lorenzo Carlo , Saps Miguel , Benninga Marc A
Published: June 2024

Background

Therapy-resistant constipation often is a frustrating clinical entity recognised by the persistence of infrequent and painful bowel movements faecal incontinence and abdominal pain despite intensive treatment. It is important to clearly define therapy-resistant constipation before children are subjected to invasive diagnostic and therapeutic procedures.

Aim

To conduct a systematic review determining how paediatric interventional studies define therapy-resistant constipation.

Method

We searched CENTRAL, MEDLINE, Embase, WHO ICTR and ClinicalTrials.gov. Studies that included patients with therapy-resistant constipation were identified. Data were extracted on criteria used for defining therapy-resistant constipation and reported using a meta-narrative approach highlighting areas of convergence and divergence in the findings.

Results

A total of 1553 abstracts were screened in duplicate, and 47 studies were included in the review. There were at least seven definitions used in the paediatric literature to define medically resistant constipation. The term intractable was used in 24 articles and 21 used the term refractory to describe therapy-resistant constipation. Out of them, only 14 articles have attempted to provide an explicit definition including a predefined time and prior therapy. There were 10 studies without a clear definition for therapy-resistant constipation. The duration before being diagnosed as therapy-resistant constipation varied from 1 months to 2 years among studies. Seven studies employed the Rome criteria (Rome III or Rome IV) to characterising constipation while five adopted the Rome III and European and North American paediatric societies definition of paediatric gastroenterology, hepatology and nutrition guideline of management of constipation in children.

Conclusion

The current literature has no explicit definition for therapy-resistant constipation in children. There is a need for a detailed consensus definition to ensure consistency of future research and to avoid unnecessary and maybe even harmful, invasive diagnostic and therapeutic interventions.
Assessing venous invasion in stage II colon cancer: optimal elastin stains and survival analysis
Authors: Lee Soo Hyun , Yilmaz Omer , Padmanabha Nandan , Deshpande Vikram , Yilmaz Osman
Published: June 2024

Aims

Venous invasion (VI) in colorectal carcinoma influences treatment strategies, especially in early stages. Despite elastin staining effectiveness in detecting VI, guidelines for its routine application, including the optimal number of slides for staining, are limited.

Methods

Elastin staining was performed for VI assessment in patients with colorectal adenocarcinoma. Patients were categorised into two groups: single elastin stain group (SEG, n=248) and multiple elastin stain group (MEG, n=204).

Results

The average number of elastin-stained blocks was 2±1.7, increasing to 3.3±1.9 in MEG. VI detection was significantly higher in patients in MEG (50.5%) compared with SEG (37.0%) (p=0.004). VI detection rate was higher in MEG (63.7%) than in SEG (46.0%) among patients with stage III–IV disease (p=0.011), but did not significantly differ among patients with stage I–II disease. Staining two blocks improved VI detection without additional gains from more stains. Compared with elastin performed on a single block, VI detected by elastin stain on two or more blocks did not significantly impact progression-free or disease-free survival with stage II patients.

Conclusions

Employing two elastin stains on separate blocks significantly enhances VI detection in colorectal carcinoma without additional benefits from more extensive staining. This study suggests that while increasing sensitivity for VI detection, staining beyond two blocks may not benefit prognostication and could be counterproductive, warranting further research. We emphasise the need for strategic use of the elastin stain and cautious interpretation of the increased detection sensitivity of multiple elastin stains.
Long-term survival follow-up for tebentafusp in previously treated metastatic uveal melanoma
Authors: Sacco Joseph J , Carvajal Richard D , Butler Marcus O , Shoushtari Alexander N , Hassel Jessica C , Ikeguchi Alexandra , Hernandez-Aya Leonel , Nathan Paul , Hamid Omid , Piulats Josep M , Rioth Matthew , Johnson Douglas B , Luke Jason J , Espinosa Enrique , Leyvraz Serge , Collins Laura , Holland Chris , Sato Takami
Published: June 2024

Background

Tebentafusp, a bispecific (gp100×CD3) ImmTAC, significantly improved overall survival (OS) outcomes for HLA-A*02:01+ adult patients with untreated metastatic uveal melanoma (mUM) and showed promising survival in previously treated mUM with 1-year OS of 62% in the primary analysis of study IMCgp100-102. Here we report long-term outcomes from this phase 1/2 study in pretreated mUM.

Patients and methods

Patients with previously treated mUM received tebentafusp weekly intravenous at 20 µg dose 1, 30 µg dose 2 and either 54, 64, 68, or 73 µg (phase 1) or 68 µg (phase 2) dose 3+. The primary objective was overall response rate. Secondary objectives included OS and safety. OS was estimated by Kaplan-Meier methods. Association between OS and baseline covariates, on-treatment Response Evaluation Criteria in Solid Tumors (RECIST) response, baseline tumor biopsy and circulating-tumor DNA (ctDNA) changes were assessed.

Results

146 patients were treated with tebentafusp: 19 in phase 1 and 127 in phase 2. With a median follow-up duration of 48.5 months, the median OS was 17.4 months (95% CI, 13.1 to 22.8), and the 1-year, 2-year, 3-year and 4-year OS rates were 62%, 40%, 23% and 14%, respectively. Improved survival was associated with lower ctDNA baseline levels and greater ctDNA reductions by week 9 on-treatment, with 100% 1-year, 73% 2-year and 45% 3-year OS rates for patients with ctDNA clearance. Baseline gp100 expression was not associated with survival, despite more RECIST responses among patients with higher expression. No new safety signals were reported with long-term dosing.

Conclusions

This study represents the longest follow-up of a Tcell receptor bispecific to date and confirms the durable survival benefits achieved with tebentafusp in previously treated mUM with good tolerability long-term. A role for ctDNA reduction as an early indicator of clinical benefit was again suggested for patients treated with tebentafusp.
Extending the clinical spectrum of X-linked Tonne-Kalscheuer syndrome (TOKAS): new insights from the fetal perspective
Authors: Cuinat Silvestre , Quélin Chloé , Effray Claire , Dubourg Christèle , Le Bouar Gwenaelle , Cabaret-Dufour Anne-Sophie , Loget Philippe , Proisy Maia , Sauvestre Fanny , Sarreau Mélie , Martin-Berenguer Sophie , Beneteau Claire , Naudion Sophie , Michaud Vincent , Arveiler Benoit , Trimouille Aurélien , Macé Pierre , Sigaudy Sabine , Glazunova Olga , Torrents Julia , Raymond Laure , Saint-Frison Marie-Hélène , Attié-Bitach Tania , Lefebvre Mathilde , Capri Yline , Bourgon Nicolas , Thauvin-Robinet Christel , Tran Mau-Them Frédéric , Bruel Ange-Line , Vitobello Antonio , Denommé-Pichon Anne-Sophie , Faivre Laurence , Brehin Anne-Claire , Goldenberg Alice , Patrier-Sallebert Sophie , Perani Alexandre , Dauriat Benjamin , Bourthoumieu Sylvie , Yardin Catherine , Marquet Valentine , Barnique Marion , Fiorenza-Gasq Maryse , Marey Isabelle , Tournadre Danielle , Doumit Raïa , Nugues Frédérique , Barakat Tahsin Stefan , Bustos Francisco , Jaillard Sylvie , Launay Erika , Pasquier Laurent , Odent Sylvie
Published: June 2024

Introduction

Tonne-Kalscheuer syndrome (TOKAS) is a recessive X-linked multiple congenital anomaly disorder caused byRLIMvariations. Of the 41 patients reported, only 7 antenatal cases were described.

Method

After the antenatal diagnosis of TOKAS by exome analysis in a family followed for over 35 years because of multiple congenital anomalies in five male fetuses, a call for collaboration was made, resulting in a cohort of 11 previously unpublished cases.

Results

We present a TOKAS antenatal cohort, describing 11 new cases in 6 French families. We report a high frequency of diaphragmatic hernia (9 of 11), differences in sex development (10 of 11) and various visceral malformations. We report some recurrent dysmorphic features, but also pontocerebellar hypoplasia, pre-auricular skin tags and olfactory bulb abnormalities previously unreported in the literature. Although no clear genotype–phenotype correlation has yet emerged, we show that a recurrent p.(Arg611Cys) variant accounts for 66% of fetal TOKAS cases. We also report two new likely pathogenic variants inRLIM, outside of the two previously known mutational hotspots.

Conclusion

Overall, we present the first fetal cohort of TOKAS, describe the clinical features that made it a recognisable syndrome at fetopathological examination, and extend the phenotypical spectrum and the known genotype of this rare disorder.
Neurotoxicology: a clinical systems-based review
Authors: Vonberg Frederick W , Blain Peter G
Published: June 2024

Neurological disease caused by toxins is widespread but under-recognised. Despite increasing public interest and a growing number of novel potential neurotoxins, diagnosis of neurotoxic disease is often delayed or missed, resulting in poorer patient outcomes. This article discusses neurotoxic syndromes using a systems-based approach, focusing on environmental and occupational agents. We do not discuss recreational drugs, pharmaceutical agents or developmental neurotoxins in detail. We aim to provide neurologists with a working understanding of the scenarios in which a clinical presentation may be due to a neurotoxin and how to approach confirmation of the diagnosis.
Spinal cord stimulation attenuates paclitaxel-induced gait impairment and mechanical hypersensitivity via peripheral neuroprotective mechanisms in tumor-bearing rats
Authors: Bakare Ahmed Olalekan , Stephens Kimberly , Sanchez Karla R , Liu Vivian , Zheng Lei , Goel Vasudha , Guan Yun , Sivanesan Eellan
Published: June 2024

Background

Taxanes such as paclitaxel (PTX) induce dose-dependent chemotherapy-induced peripheral neuropathy (CIPN), which is associated with debilitating chronic pain and gait impairment. Increased macrophage-related proinflammatory activities have been reported to mediate the development and maintenance of neuropathic pain. While spinal cord stimulation (SCS) has been used for a number of pain conditions, the mechanisms supporting its use for CIPN remain to be elucidated. Thus, we aimed to examine whether SCS can attenuate Schwann cell-mediated and macrophage-mediated neuroinflammation in the sciatic nerve of Rowlette Nude (RNU) rats with PTX-induced gait impairment and mechanical hypersensitivity.

Methods

Adult male tumor-bearing RNU rats were used for this study examining PTX treatment and SCS. Gait and mechanical hypersensitivity were assessed weekly. Cytokines, gene expression, macrophage infiltration and polarization, nerve morphology and Schwann cells were examined in sciatic nerves using multiplex immunoassay, bulk RNA sequencing, histochemistry and immunohistochemistry techniques.

Results

SCS (50 Hz, 0.2 milliseconds, 80% motor threshold) attenuated the development of mechanical hypersensitivity (20.93±0.80 vs 12.23±2.71 grams, p<0.0096) and temporal gait impairment [swing (90.41±7.03 vs 117.27±9.71%, p<0.0076), and single stance times (94.92±3.62 vs 112.75±7.27%, p<0.0245)] induced by PTX (SCS+PTX+Tumor vs Sham SCS+PTX+Tumor). SCS also attenuated the reduction in Schwann cells, myelin thickness and increased the concentration of anti-inflammatory cytokine interleukin (IL)−10. Bulk RNA sequencing revealed differential gene expression after SCS, with 607 (59.2%) genes upregulated while 418 (40.8%) genes were downregulated. Notably, genes related to anti-inflammatory cytokines and neuronal growth were upregulated, while genes related to proinflammatory-promoting genes, increased M2γ polarization and decreased macrophage infiltration and Schwann cell loss were downregulated.

Conclusion

SCS may attenuate PTX-induced pain and temporal gait impairment, which may be partly attributed to decreases in Schwann cell loss and macrophage-mediated neuroinflammation in sciatic nerves.