bluuebunny/crossref_metadata_2025 huggingface dataset:
Vascularization of human islets by adaptable endothelium for durable and functional subcutaneous engraftment
Authors: Li Ge , Craig-Schapiro Rebecca , Redmond David , Chen Kevin , Lin Yang , Geng Fuqiang , Gao Meng , Rabbany Sina Y. , Suresh Gayathri , Pearson Bradley , Schreiner Ryan , Rafii Shahin
Published: January 2025

Tissue-specific endothelial cells (ECs) are critical for the homeostasis of pancreatic islets and most other tissues. In vitro recapitulation of islet biology and therapeutic islet transplantation both require adequate vascularization, which remains a challenge. Using human reprogrammed vascular ECs (R-VECs), human islets were functionally vascularized in vitro, demonstrating responsive, dynamic glucose-stimulated insulin secretion and Ca
2+
influx. Subcutaneous transplantation of islets with R-VECs reversed hyperglycemia in diabetic mice, with high levels of human insulin detected within recipient serum and relapses of hyperglycemia following graft removal. Examination of retrieved grafts demonstrated that engrafted human islets were mainly vascularized by the cotransplanted R-VECs, which had anastomosed with the host microcirculation. Notably, single-cell RNA-sequencing revealed that R-VECs, when cocultured with islets, acquired islet EC-specific characteristics. Together, R-VECs establish an adaptable vascular niche that supports islet homeostasis both in vitro and in vivo.
Parasitoid wasp venoms degrade
Drosophila
imaginal discs for successful parasitism
Authors: Kamiyama Takumi , Shimada-Niwa Yuko , Mori Hitoha , Tani Naoki , Takemata-Kawabata Hitomi , Fujii Mitsuki , Takasu Akira , Katayama Minami , Kuwabara Takayoshi , Seike Kazuki , Matsuda-Imai Noriko , Senda Toshiya , Katsuma Susumu , Nakamura Akira , Niwa Ryusuke
Published: January 2025

Parasitoid wasps, one of the most diverse and species-rich animal groups on Earth, produce venoms that manipulate host development and physiology to exploit resources. However, mechanisms of actions of these venoms remain poorly understood. Here, we discovered that the endoparasitoid wasp,
Asobara japonica
, induces apoptosis, autophagy, and mitotic arrest in the adult tissue precursors of its host
Drosophila
larvae. We termed this phenomenon imaginal disc degradation (IDD). A multi-omics approach facilitated identification of two venom proteins of
A. japonica
necessary for IDD, which is critical for parasitism success. Our study highlights a venom-mediated hijacking strategy of the parasitoid wasp that allows the host larvae to grow, but ultimately prevents their metamorphosis.
Massively parallel Hong-Ou-Mandel interference based on independent soliton microcombs
Authors: Huang Long , Wang Weiqiang , Wang Fangxiang , Wang Yang , Zou Changling , Tang LinHan , Little Brent E. , Zhao Wei , Han Zhengfu , Yang Jun , Wang Guochao , Chen Wei , Zhang Wenfu
Published: January 2025

Hong-Ou-Mandel (HOM) interference is the foundation of quantum optics to test the degree of indistinguishability of two incoming photons, playing a key role in quantum communication, sensing, and photonic quantum computing. Realizing high-visibility HOM interference with massively parallel optical channels is challenging due to the lack of available natural optical references for aligning independent arrayed laser pairs. Here, we demonstrate 50 parallel comb-teeth pairs of continuous-wave weak coherent photons HOM interference using two independently frequency post-aligned soliton microcombs (SMCs), achieving an average fringe visibility over 46%. The frequencies of all comb-teeth pairs are long-term aligned by developing two sets of fully frequency-stabilized SMCs with independent reference and adjusting free spectral range beyond 100 kilohertz through perturbations in soliton state. The verification experiment proves the feasibility of constructing massively quantum information channels by co-opting classical wavelength division multiplexing optical communications, which paves the way for practical large-scale quantum communication systems.
Century-long West Antarctic snow accumulation changes induced by tropical teleconnections
Authors: Man Kai , Luterbacher Jürg , Holland David M. , Yuan Naiming , Geng Lei , Wang Yetang , Liu Yonggang , Shi Guitao , Hou Yurong , Cai Wenju , Li Xichen
Published: January 2025

Ice core measurements reveal dipole-like snow accumulation trends over West Antarctica throughout the 20th century, with an increase of >2000 billion metric tons over the Antarctic Peninsula and Ellsworth Land but a decrease of ~500 billion metric tons over Marie Byrd Land. Although atmospheric teleconnections were frequently revealed, linking variability between tropics and higher latitudes on interannual and decadal timescales, centennial-scale teleconnection is absent from literature. Here, using statistical analysis and numerical experiments, we reveal that changes of tropical oceans throughout the 20th century drive the long-term Antarctic snowfall trend. A pronounced warming over the tropical Atlantic and a moderate cooling over the equatorial Pacific have driven an adjustment of moisture transport and thus snowfall pattern in West Antarctica. Our study reveals a centennial tropical-polar teleconnection, producing long-term trends with opposing changes across the regions. Remote forcing from the tropics increased the mass accumulation over Antarctica, balanced rapid iceshelf thinning in recent decades, contributing to global sea-level changes.
SnRK2 kinases sense molecular crowding and form condensates to disrupt ABI1 inhibition
Authors: Yuan Xian-Ping , Zhao Yang
Published: January 2025

Plants sense and respond to hyperosmotic stress via quick activation of sucrose nonfermenting 1–related protein kinase 2 (SnRK2). Under unstressed conditions, the protein phosphatase type 2C (PP2C) in clade A interact with and inhibit SnRK2s in subgroup III, which are released from the PP2C inhibition via pyrabactin resistance 1–like (PYL) abscisic acid receptors. However, how SnRK2s are released under osmotic stress is unclear. Here, we outline how subgroup I SnRK2s sense molecular crowding to interrupt PP2C-mediated inhibition in plants. Severe hyperosmotic stress triggers condensate formation to activate the subgroup I SnRK2s, which requires their intrinsically disordered region. PP2Cs interact with and inhibit subgroup I SnRK2s, and this interaction is disrupted by phase separation of SnRK2s. The subgroup I SnRK2s are critical for severe osmotic stress responses. Our findings elucidate a mechanism for how macromolecular crowding is sensed in plants and demonstrate that physical separation of signaling molecules can segregate negative regulators to initiate signaling.
Ketogenesis supports hepatic polyunsaturated fatty acid homeostasis via fatty acid elongation
Authors: Queathem Eric D. , Moazzami Zahra , Stagg David B. , Nelson Alisa B. , Fulghum Kyle , Hayir Abdirahman , Seay Alisha , Gillingham Jacob R. , d’Avignon D. André , Han Xianlin , Ruan Hai-Bin , Crawford Peter A. , Puchalska Patrycja
Published: January 2025

Ketogenesis is a dynamic metabolic conduit supporting hepatic fat oxidation particularly when carbohydrates are in short supply. Ketone bodies may be recycled into anabolic substrates, but a physiological role for this process has not been identified. Here, we use mass spectrometry–based
13
C-isotope tracing and shotgun lipidomics to establish a link between hepatic ketogenesis and lipid anabolism. Unexpectedly, mouse liver and primary hepatocytes consumed ketone bodies to support fatty acid biosynthesis via both de novo lipogenesis (DNL) and polyunsaturated fatty acid (PUFA) elongation. While an acetoacetate intermediate was not absolutely required for ketone bodies to source DNL, PUFA elongation required activation of acetoacetate by cytosolic acetoacetyl–coenzyme A synthetase (AACS). Moreover, AACS deficiency diminished free and esterified PUFAs in hepatocytes, while ketogenic insufficiency depleted PUFAs and increased liver triacylglycerols. These findings suggest that hepatic ketogenesis influences PUFA metabolism, representing a molecular mechanism through which ketone bodies could influence systemic physiology and chronic diseases.
A look beyond topography: Transient phenomena of
Escherichia coli
cell division captured with high-speed in-line force mapping
Authors: Ganser Christian , Nishiguchi Shigetaka , Chan Feng-Yueh , Uchihashi Takayuki
Published: January 2025

Life on the nanoscale has been made accessible in recent decades by the development of fast and noninvasive techniques. High-speed atomic force microscopy (HS-AFM) is one such technique that shed light on single protein dynamics. Extending HS-AFM to effortlessly incorporate mechanical property mapping while maintaining fast imaging speed allows a look deeper than topography and reveal details of nanoscale mechanisms that govern life. Here, we present high-speed in-line force mapping (HS-iFM) to record mechanical properties and topography maps with high spatiotemporal resolution. Using HS-iFM, a comprehensive study of the nanoscale mechanical properties of living
Escherichia coli
revealed localized stiffening and details during cell division, formation and diffusion of pores in the membrane, and the impact of depressurization of a cell. The frame time was as low as 15 seconds with a spatial resolution of 5.5 nanometers per pixel in topography and 22 nanometers per pixel in force maps, allowing the capture of transient phenomena on bacterial surfaces in striking detail.
Flexible electronic brush: Real-time multimodal sensing powered by reservoir computing through whisker dynamics
Authors: Nakamura Haruki , Honda Satoko , Matsumura Guren , Wakabayashi Seiji , Uehara Koh , Nakajima Kohei , Takei Kuniharu
Published: January 2025

Multimodal sensing using soft body dynamics plays a crucial role in controlling soft robotic motions. An intriguing application of such soft robot control is to mimic whiskers and digitize soft body motion through whisker dynamics. The challenge herein is to simultaneously monitor the directions, speed, force, and slip information of the whisker motion. The existing whisker-like sensors cannot detect slip information effectively. To address this challenge, this study develops a multitasking electronic brush (e-brush) composed of bundle of whiskers powered by reservoir computing (RC). Four pressure sensors are integrated into the brush to monitor its motion, speed, force, slip, and target surface. These sensors can provide long-term, low-pressure detection as low as 50 pascals, allowing for the precise monitoring of brush movements. A RC algorithm is developed to extract multiple brush motion parameters, including the slip. As a proof of concept for multitasking e-brush, the motion trajectory of handwriting is successfully detected.
Synthesis of naphthalene derivatives via nitrogen-to-carbon transmutation of isoquinolines
Authors: Zhu Tongtong , Cui Xuhui , Ma Wenjun , Qi Xiujuan , Wei Hao
Published: January 2025

Heteroarene skeletal editing is gaining popularity in synthetic chemistry. Transmuting single atoms generates molecules that have distinctly varied properties, thereby fostering potent molecular exchanges that can be extensively used to synthesize functional molecules. Herein, we present a convenient protocol for nitrogen-carbon single-atom transmutations in isoquinolines, which is inspired by the Wittig reaction and enables easy access to substituted naphthalene derivatives. The reaction uses an inexpensive and commercially available phosphonium ylide as the carbon source to furnish a wide range of substituted naphthalenes. The key to the success of this transformation is the formation of a triene intermediate through ring opening, which undergoes 6π-electrocyclization and elimination processes to afford the naphthalene product. Furthermore, this strategy enables the facile synthesis of
13
C-labeled naphthalenes using
13
CH
3
PPh
3
I as a commercial
13
C source and facilitates modifying the directing group for C─H functionalization.
Anti-icing properties of polar bear fur
Authors: Carolan Julian , Jakubec Martin , Xavier Neubi F. , Motala Adam Pestana , Bifulco Ersilia , Aars Jon , Andersen Magnus , Schmidt Anne Lisbeth , Cabré Marc Brunet , Singh Vikaramjeet , Colavita Paula E. , Selfors Espen Werdal , Sacchi Marco , O’Reilly Shane , Halskau Øyvind , Tiwari Manish K. , Hobbs Richard G. , Holst Bodil
Published: January 2025

The polar bear (
Ursus maritimus
) is the only Arctic land mammal that dives into water to hunt. Despite thermal insulation provided by blubber and fur layers and low Arctic temperatures, their fur is typically observed to be free of ice. This study investigates the anti-icing properties of polar bear fur. Here, we show that polar bear fur exhibits low ice adhesion strengths comparable to fluorocarbon-coated fibers, with the low ice adhesion a consequence of the fur sebum (hair grease). Lipid analyses reveal the presence of cholesterol, diacylglycerols, anteisomethyl-branched fatty acids, and the unexpected absence of squalene. Quantum chemical calculations predict low ice adsorption energies for identified lipids and high adsorption for squalene, suggesting that sebum composition is responsible for the observed anti-icing properties. Our work enhances understanding of polar bears and their interactions with their environment and builds on Inuit knowledge of natural anti-icing materials.
A phytoplasma effector suppresses insect melanization immune response to promote pathogen persistent transmission
Authors: Zhang Xiao-Feng , Li Zhanpeng , Qiu Jiaxin , Zhang Ruonan , Jiang Zhoumian , Wang Tengfei , Chen Hongyan , Wei Taiyun
Published: January 2025

Insect melanization triggered by the conversion of prophenoloxidase to active phenoloxidase via serine proteases (SPs) is an important immediate immune response. However, how phytoplasmas evade this immune response to promote their propagation in insect vectors remains unknown. Here, we demonstrate that infection of leafhopper vectors with rice orange leaf phytoplasma (ROLP) activates the mild melanization response in hemolymph. ROLP-encoded effector protein SRP1 is highly expressed in leafhopper hemolymph, where it competitively binds to SP2, thereby inhibiting SP2-mediated cleavage of prophenoloxidase into active phenoloxidase. Consequently, microinjection of SRP1 effectively suppresses the melanization response and enhances ROLP propagation. The histidine residue at position 23 of SRP1 is essential for SRP1-SP2 interaction, and the mutation of this position abolishes its ability to inhibit such SP2-meidated cleavage, ultimately promoting melanization response and inhibiting ROLP propagation. Our findings provide insights into how phytoplasmas antagonize insect melanization response to facilitate their persistent transmission.
Hamiltonian learning for 300 trapped ion qubits with long-range couplings
Authors: Guo Shi-An , Wu Yu-Kai , Ye Jing , Zhang Lin , Wang Ye , Lian Wen-Qian , Yao Rui , Xu Yu-Lin , Zhang Chi , Xu Yu-Zi , Qi Bin-Xiang , Hou Pan-Yu , He Li , Zhou Zi-Chao , Duan Lu-Ming
Published: January 2025

Quantum simulators with hundreds of qubits and engineerable Hamiltonians have the potential to explore quantum many-body models that are intractable for classical computers. However, learning the simulated Hamiltonian, a prerequisite for any quantitative applications of a quantum simulator, remains an outstanding challenge due to the fast increasing time cost with the qubit number and the lack of high-fidelity universal gate operations in the noisy intermediate-scale quantum era. Here, we demonstrate the Hamiltonian learning of a two-dimensional ion trap quantum simulator with 300 qubits. We use global manipulations and single-qubit–resolved state detection to efficiently learn the all-to-all–coupled Ising model Hamiltonian, with the required quantum resources scaling at most linearly with the qubit number. We further demonstrate a physically guided learning scheme with the quantum sample complexity independent of system sizes by carefully fitting the anharmonic trap potential. Our work paves the way for wide applications of large-scale ion trap quantum simulators.
Safety-assured high-speed navigation for MAVs
Authors: Ren Yunfan , Zhu Fangcheng , Lu Guozheng , Cai Yixi , Yin Longji , Kong Fanze , Lin Jiarong , Chen Nan , Zhang Fu
Published: January 2025

Micro air vehicles (MAVs) capable of high-speed autonomous navigation in unknown environments have the potential to improve applications like search and rescue and disaster relief, where timely and safe navigation is critical. However, achieving autonomous, safe, and high-speed MAV navigation faces systematic challenges, necessitating reduced vehicle weight and size for high-speed maneuvering, strong sensing capability for detecting obstacles at a distance, and advanced planning and control algorithms maximizing flight speed while ensuring obstacle avoidance. Here, we present the safety-assured high-speed aerial robot (SUPER), a compact MAV with a 280-millimeter wheelbase and a thrust-to-weight ratio greater than 5.0, enabling agile flight in cluttered environments. SUPER uses a lightweight three-dimensional light detection and ranging (LIDAR) sensor for accurate, long-range obstacle detection. To ensure high-speed flight while maintaining safety, we introduced an efficient planning framework that directly plans trajectories using LIDAR point clouds. In each replanning cycle, two trajectories were generated: one in known free spaces to ensure safety and another in both known and unknown spaces to maximize speed. Compared with baseline methods, this framework reduced failure rates by 35.9 times while flying faster and with half the planning time. In real-world tests, SUPER achieved autonomous flights at speeds exceeding 20 meters per second, successfully avoiding thin obstacles and navigating narrow spaces. SUPER represents a milestone in autonomous MAV systems, bridging the gap from laboratory research to real-world applications.
A hyperelastic torque-reversal mechanism for soft joints with compression-responsive transient bistability
Authors: Choi Woo-Young , Kim Woongbae , Choi Jae-Ryeong , Yu Sung Yol , Moon Seunguk , Park Yong-Jai , Cho Kyu-Jin
Published: January 2025

Snap-through, a rapid transition of a system from an equilibrium state to a nonadjacent equilibrium state, is a valuable design element of soft devices for converting a monolithic stimulus into systematic responses with impulsive motions. A common way to benefit from snap-through is to embody it within structures and materials, such as bistable structures. Torque-reversal mechanisms discovered in nature, which harness snap-through instability via muscular forces, may have comparative advantages. However, the current intricacy of artificial torque-reversal mechanisms, which require sophisticated kinematics/kinetics, constrains design possibilities for soft joints and devices. Here, we harnessed hyperelasticity to implement a torque-reversal mechanism in a soft joint, generating repetitive cilia-like beating motions through an embedded tendon. The developed hyperelastic torque-reversal mechanism (HeTRM) exhibits transient bistability under a specific compressive displacement/force threshold, with snap-through occurring at the point where the transience ends. To validate the effectiveness of this design principle, we explored the functionalities of HeTRM in energy storage and release, dual modes for impulsive and continuous motion, mechanical fuse, and rapid three-dimensional motions, through proof-of-concept soft machines. We expect that this design principle provides insight into incorporating snap-through behavior in soft machines and may aid in understanding the relationship between torque-reversal mechanisms and bistability.
Diversity and dynamics of multiple symbionts contribute to early development of broadcast spawning reef-building coral
Dipsastraea veroni
Authors: Guo Minglan , Jiang Lei , Zhou Guowei , Lian Jiansheng , Yu Xiaolei , Huang Hui
Published: January 2025

Sexual reproduction and recruitment enhance the genetic diversity and evolution of reef-building corals for population recovery and coral reef conservation under climate change. However, new recruits are vulnerable to physical changes and the mechanisms of symbiosis establishment remain poorly understood. Here,
Dipsastraea veroni
, a broadcast spawning hermaphrodite reef-building coral, was subjected to settlement and juvenile growth in flow-through
in situ
seawater at 27.93 ± 0.96°C. Symbiosis of Symbiodiniaceae, bacteria, and/or archaea by horizontal acquisition and/or hypothetical vertical transmission through the mucus with symbionts from the parent appears to be a heritable process of selection and adaptation in
D. veroni
at the egg, larva, juvenile (5 days post settlement, d p.s. and 32 d p.s.) stages. Symbiodiniaceae was dominated by the genera
Cladocopium
,
Durusdinium
,
Symbiodinium,
with increasing relative abundance of
Durusdinium
at 5 d p.s. and
Symbiodinium
at 32 d p.s. Mixed acquisition of the dominant phyla Pseudomonadota, Bacteroidota, Cyanobacteriota, Bacillota, Planctomycetota, and Actinomycetota in egg, larva, and/or juvenile showed a winnowing and regulated bacterial diversity and dynamics, resulting in stage-abundant orders Pseudomonadales and Bacillales in egg and Rhodobacterales, Rhodospirillales, Cyanobacteria, and Cyanobacteriales in larva and/or juvenile. The photoautotrophic Chloroflexales, Cyanobacteriales, and Chlorobiales were abundant in adults. The stable archaeal community contained predominant Crenarchaeota, Halobacterota, Nanoarchaeia Thermoplasmatota, and eight rare phyla, with increased relative abundance of the genera
Bathyarchaeota
,
Candidatus_Nitrosopumilus
,
Candidatus_Nitrocosmicus
,
Nitrosarchaeum
,
Candidatus_Nitrosotenuis
,
Candidatus_Nitrosopelagicus
,
Cenarchaeum
,
Haladaptatus
,
Halogranum
,
Halolamina,
and
Woesearchaeales
and
GW2011-AR15
in juveniles. All results revealed flexible symbiotic mechanisms in
D. veroni
during early ontogeny for coral survival and evolution.

IMPORTANCE

Flexible symbioses of Symbiodiniaceae, bacteria, and archaea appear to be a heritable process of selection and adaptation in
Dipsastraea veroni
in the field, benefiting early coral development and facilitating coral population recovery and reef conversation.
Two NADPH-dependent 2-ketogluconate reductases involved in 2-ketogluconate assimilation in
Gluconobacter
sp. strain CHM43
Authors: Nakashima Sakura , Matsutani Minenosuke , Kataoka Naoya , Adachi Osao , Yamashita Riku , Matsushita Kazunobu , Tippayasak Uraiwan , Theeragool Gunjana , Yakushi Toshiharu
Published: January 2025

Incomplete oxidation of glucose by
Gluconobacter
sp. strain CHM43 produces gluconic acid and then 2- or 5-ketogluconic acid. Although 2-keto-D-gluconate (2KG) is a valuable compound, it is sometimes consumed by
Gluconobacter
itself via an unknown metabolic pathway. We anticipated that 2KG reductase (2KGR) would be a key enzyme in 2KG metabolism.
GLF_0478
and
GLF_1777
were identified in the genome of strain CHM43, which encode proteins with 70% and 48% amino acid sequence identity, respectively, to the 2KGR of
Gluconobacter oxydans
strain 621H. Constructed mutant derivatives of strain CHM43 lacking
GLF_0478
,
GLF_1777
, or both were examined for their 2KG consumption ability. Strains ∆
GLF_0478
and ∆
GLF_1777
consumed 2KG like the parental strain. However, the double-deletion (∆∆) strain did not consume 2KG at all, although it produced 2KG like the parental strain. Strains ∆
GLF_0478
and ∆
GLF_1777
each showed decreased 2KGR activity compared with the parental strain, and strain ΔΔ lost 2KGR activity. These results suggest that reduction of 2KG catalyzed by GLF_0478 and GLF_1777 is the committed step in 2KG metabolism in
Gluconobacter
sp. strain CHM43. The two 2KGRs showed high activity at neutral pH and lower
K
M
values for NADPH than NADH. Results of induction experiments suggest that GLF_0478 is constitutively expressed at a low level but induced by 2KG, and GLF_1777 is also inducible by 2KG but repressed in the absence of an inducer. Our study that characterizes the key genes for 2KG consumption in
Gluconobacter
gives insights for improvement of biological 2KG production systems.

IMPORTANCE

2-Keto-D-gluconate (2KG), a product of incomplete oxidation of glucose by acetic acid bacteria including
Gluconobacter
spp., is used for various purposes, including in the food industry.
Gluconobacter
also consumes 2KG via an unclear metabolic pathway. It is reported that
Pseudomonas
spp. and
Cupriavidus necator
phosphorylate 2KG in the first step of 2KG metabolism, but some enteric bacteria including
Escherichia coli
reduce 2KG. This study evaluated the 2KG consumption ability of a mutant derivative of a strain of
Gluconobacter
that lacks two putative 2KGR-encoding genes. The mutant strain did not consume 2KG at all; the two 2KGRs were each found to catalyze 2KG reduction. It is concluded that reduction of 2KG is the committed step in 2KG metabolism in
Gluconobacter
. The results presented here give insights that might facilitate improvement of 2KG production systems that use
Gluconobacter
.
Pathogen genomic surveillance and the AI revolution
Authors: Lytras Spyros , Lamb Kieran D. , Ito Jumpei , Grove Joe , Yuan Ke , Sato Kei , Hughes Joseph , Robertson David L.
Published: January 2025

The unprecedented sequencing efforts during the COVID-19 pandemic paved the way for genomic surveillance to become a powerful tool for monitoring the evolution of circulating viruses. Herein, we discuss how a state-of-the-art artificial intelligence approach called protein language models (pLMs) can be used for effectively analyzing pathogen genomic data. We highlight examples of pLMs applied to predicting viral properties and evolution and lay out a framework for integrating pLMs into genomic surveillance pipelines.
Exploration of the genetic landscape of bacterial dsDNA viruses reveals an ANI gap amid extensive mosaicism
Authors: Ndovie Wanangwa , Havránek Jan , Leconte Jade , Koszucki Janusz , Chindelevitch Leonid , Adriaenssens Evelien M. , Mostowy Rafal J.
Published: January 2025

Average nucleotide identity (ANI) is a widely used metric to estimate genetic relatedness, especially in microbial species delineation. While ANI calculation has been well optimized for bacteria and closely related viral genomes, accurate estimation of ANI below 80%, particularly in large reference data sets, has been challenging due to a lack of accurate and scalable methods. To bridge this gap, we introduce MANIAC, an efficient computational pipeline optimized for estimating ANI and alignment fraction (AF) in viral genomes with divergence around ANI of 70%. Using a rigorous simulation framework, we demonstrate MANIAC’s accuracy and scalability compared to existing approaches, even to data sets of hundreds of thousands of viral genomes. Applying MANIAC to a curated data set of complete bacterial dsDNA viruses revealed a multimodal ANI distribution, with a distinct gap around 80%, akin to the bacterial ANI gap (~90%) but shifted, likely due to viral-specific evolutionary processes such as recombination dynamics and mosaicism. We then evaluated ANI and AF as predictors of genus-level taxonomy using a logistic regression model. We found that this model has strong predictive power (PR-AUC = 0.981), but that it works much better for virulent (PR-AUC = 0.997) than temperate (PR-AUC = 0.847) bacterial viruses. This highlights the complexity of taxonomic classification in temperate phages, known for their extensive mosaicism, and cautions against over-reliance on ANI in such cases. MANIAC can be accessed at
https://github.com/bioinf-mcb/MANIAC
.

IMPORTANCE

We introduce a novel computational pipeline called MANIAC, designed to accurately assess average nucleotide identity (ANI) and alignment fraction (AF) between diverse viral genomes, scalable to data sets of over 100k genomes. Using computer simulations and real data analyses, we show that MANIAC could accurately estimate genetic relatedness between pairs of viral genomes of around 60%–70% ANI. We applied MANIAC to investigate the question of ANI discontinuity in bacterial dsDNA viruses, finding evidence for an ANI gap, akin to the one seen in bacteria but around ANI of 80%. We then assessed the ability of ANI and AF to predict taxonomic genus boundaries, finding its strong predictive power in virulent, but not in temperate phages. Our results suggest that bacterial dsDNA viruses may exhibit an ANI threshold (on average around 80%) above which recombination helps maintain population cohesiveness, as previously argued in bacteria.
TccP4: a novel effector identified in the
Escherichia albertii
strain 1551-2 required for attaching and effacing lesion formation on infected Nck-null cells
Authors: Fernandes Iranildo do A. , Ooka Tadasuke , de Lira Daiany R. P. , Martins Fernando H. , Orsi Henrique , Jones Nina , Elias Waldir P. , Hayashi Tetsuya , Gomes Tânia A. T. , Hernandes Rodrigo T.
Published: January 2025

Escherichia albertii
is a pathogen that causes sporadic cases and outbreaks of diarrhea. The main virulence feature of this bacterium is the attaching and effacing (AE) lesion formation on infected intestinal epithelial cells, which is characterized by the formation of pedestal-like structures that are rich in F-actin. The Brazilian
E. albertii
1551-2 strain can recruit F-actin using both the Nck-dependent and the Nck-independent pathways, the latter of which uses an adaptor protein named Tir-cytoskeleton coupling protein (TccP/EspF
U
). Genome analyses of the 1551-2 strain unveiled the existence of a gene encoding a putative novel TccP subtype in addition to a gene encoding for the TccP3 subtype. Amino-acid sequence comparison with known TccP subtypes (TccP/EspF
U
, TccP2, and TccP3) confirmed that the protein represents a novel TccP subtype—named here TccP4. Lack of TccP4 led to an approximately 96% reduction in the ability of the
tccP3
deletion mutant of strain 1551-2 to induce the F-actin-rich pedestals formation in the infected Nck-null mouse embryonic fibroblasts (MEF) cells. The
tccP4
gene was distributed widely in
E. albertii
, including the strains first separated from other
E. albertii
strains, suggesting that this gene was acquired at a very early stage during the diversification of
E. albertii
. The highly variable genetic organization of the
tccP4
-containing regions and the presence of various mobile genetic elements in this region may explain the lack of
tccP4
in
E. albertii
strains belonging to various lineages.

IMPORTANCE

E. albertii
, one of the new members of the genus
Escherichia,
is a diarrheagenic pathogen. The main characteristic of its pathogenicity is the formation of attaching and effacing (AE) lesions on the surface of infected epithelial cells. Here we identified a novel subtype of the TccP type 3 secretion system (T3SS) effector family (termed TccP4), which is required for the recruitment of F-actin during the AE lesion formation in infected host cells by the
E. albertii
1551-2 strain. We also revealed that TccP4 is unique to
E. albertii
and widely distributed in this species, suggesting that the
tccP4
gene was acquired at a very early stage during the diversification process of
E. albertii
. These findings expand our understanding of the function and diversity of this important T3SS effector family.
Estimation of the Contribution of Size-Fractionated Phytoplankton in the Kara Sea to Primary Production and Chlorophyll a during Different Seasons
Authors: Demidov A. B. , Belevich T. A. , Eremeeva E. V. , Tiurina A. S. , Vorobieva O. V. , Artemiev V. A. , Pronina J. O. , Flint M. V.
Published: January 2025

Based on data obtained during seven Kara Sea expeditions (2017–2023), seasonal variation in the contribution of phytoplankton size groups to the total values of primary production (PP) and chlorophyll a (chl a) are examined for the first time. Micro- and nanophytoplankton (MPh + NPh) (>3 µm) dominated in the community composition during the entire ice-free period (June–October). Its predominance was especially noticeable during the spring bloom immediately after first-year sea-ice retreat (up to 97% for PP and up to 93% for chl a). The role of picophytoplankton (PPh) (<3 µm) increased in summer (July, August) (up to 50% for PP and up to 44% for chl a) and decreased by the end of the growing season (September, October). Seasonal variation in the size composition of phytoplankton during the growing season was determined mainly by variability in water temperature and incoming solar radiation. The contribution of PPh to the total chl a increased (up to 51%) at depths of the deep chlorophyll maximum in July and August. The assimilation activity of PPh was higher than that of MPh + NPh in July–September, with an increase in its contribution to the total PP and chl a. For the first time, annual PP of Kara Sea phytoplankton size groups was assessed: 8 ТgС (65%) for MPh + NPh and 5 ТgС (35%) for PPh.
Infective endocarditis presenting as bilateral ocular choroidal ischaemia and acute visual loss
Authors: Peixoto Ricardo , Zopounidou Eleni , Khoo Jeffrey , Anwar Bhatti Samira
Published: January 2025

We present a challenging case of infective endocarditis (IE) diagnosed after visual loss from bilateral ocular choroidal infarction in the absence of retinal vasculitis, typical retinal embolic phenomenon, clinical cardiac features or obvious medical history.

Our case illustrates the difficulties in diagnosing IE and a high index of clinical suspicion is needed.
Persistent low concentrations of antiepileptics in a critically ill paediatric patient: an example of multiple potential drug interactions
Authors: Posada Lone Bak , Olesen Anne Estrup , Sørensen Tine Høg , Azuz Samuel
Published: January 2025

A middle childhood boy with epilepsy exhibited persistent low concentrations of valproic acid, lamotrigine and topiramate for over 1 month, primarily due to pharmacokinetic interactions involving fosphenytoin, meropenem and phenobarbital. Awareness of these clinically significant interactions is crucial for ensuring effective seizure control. However, further research is needed to establish optimal evidence-based treatment strategies in complex paediatric cases.
Postpartum pyogenic sacroiliitis masquerading as sciatic neuropathy
Authors: Pathrot Devendra , Nachappa A A , Mannual Sunil , M Srinath K
Published: January 2025

Low back pain is common in women, especially during pregnancy and puerperium. Septic sacroiliitis, a rare cause of back pain in the postpartum period can mimic other common causes of low back pain like muscle strain, urinary tract infection, pelvic inflammatory disease, endometritis and intervertebral disc prolapse. The proximity of the sacroiliac joint to the sacral nerve plexus results in septic sacroiliitis frequently presenting with symptoms mimicking intervertebral disc prolapse. Diagnosis of septic arthritis of the sacroiliac joint during the postpartum period requires a high index of suspicion. Prompt and effective management is required to avoid complications and chronic morbidity. We present a young lady presenting with low backache and left lower limb radiculopathy 3 weeks after delivery. Her case supplements a small cohort of reports in literature emphasising the identification of septic arthritis in the postpartum period, the factors leading to delay in diagnosis and the increased morbidity of this condition.
Maxillary MRSA osteomyelitis in a paediatric patient: non-surgical management
Authors: Vepakomma Deepti , Yadav Shikha
Published: January 2025

Methicillin-resistantStaphylococcus aureus(MRSA) osteomyelitis of the maxilla is a rare condition in paediatric patients, with limited evidence available for optimal treatment protocols. We present the case of a paediatric patient in the early childhood age group with post-traumatic maxillary osteomyelitis caused by MRSA. The child developed facial swelling following trauma, and imaging revealed maxillary sinus wall thickening and bone erosions. After initial treatment with analgesics, the swelling persisted, leading to surgical intervention and microbiological analysis confirming MRSA infection. The patient was treated with intravenous linezolid and amikacin for 5 days, followed by 8 weeks of oral linezolid. One year post-treatment, the child remained healthy with no recurrence. This case highlights the importance of early diagnosis, tailored antibiotic therapy and conservative surgical management to ensure positive outcomes in paediatric maxillary osteomyelitis cases. Further research is needed to establish standardised treatment protocols for facial osteomyelitis in children.
Severe left-to-right shunting from combined traumatic tricuspid valve rupture and atrial septal defect: bridge to surgical repair using veno-venous ECMO
Authors: Endo Toyokazu , Bonvillain Gabriel , Slaughter Mark S , Schumer Erin M
Published: January 2025

Our patient presented to the emergency room following a motor vehicle accident. The traumatic tricuspid valve rupture was diagnosed by transthoracic echocardiogram, and his respiratory status declined rapidly. He was placed on veno-venous extracorporeal membrane oxygenation (VV ECMO) to bridge him to surgical repair. Transoesophageal echocardiography revealed a large atrial septal defect (ASD) with the combination of both injuries leading to severe left-to-right shunting that was underappreciated in the initial management of the patient. The tricuspid valve and the ASD were repaired. In this patient, in the context of both tricuspid valve rupture and ASD, veno-arterial ECMO or percutaneous right ventricular assist devices may have also helped bridge the patient to surgical repair of his blunt cardiac injuries.
Qualitative evaluation of the Rehabilitation Exercise and psycholoGical support After COVID-19 InfectioN (REGAIN) randomised controlled trial (RCT): ‘you are not alone’
Authors: Seers Kate , Nichols Vivien P , Bruce Julie , Ennis Stuart , Heine Peter , Patel Shilpa , Sandhu Harbinder Kaur , Underwood Martin , McGregor Gordon
Published: January 2025

Background

This qualitative evaluation was embedded in the Rehabilitation Exercise and psycholoGical support After COVID-19 InfectioN (REGAIN) study, a randomised controlled trial (RCT) for those with post-COVID-19 condition (‘long COVID’) after hospital admission for COVID-19, comparing weekly home-based, live online supervised group exercise and psychological support sessions with ‘best practice usual care’ (a single session of advice).

Objective

To increase our understanding of how and why the REGAIN programme might have worked and what helped or hindered this intervention.

Design

A qualitative evaluation which utilised interviews with participants and practitioners delivering the intervention. Framework and thematic analysis were used to analyse the findings.

Setting

England and Wales, UK.

Participants

Adults discharged from National Health Service (NHS) hospitals at least 3 months previously after COVID-19, with ongoing physical and/or mental health sequelae.

Results

Twenty intervention participants, 20 control participants and five practitioners were interviewed.

The themes from the group support sessions were: (1) you are not alone; (2) sharing experiences and addressing worries; (3) gaining new perspectives; (4) hope for progression; (5) peer support and bonding; (6) integration of facilitation skills; (7) modified activity pacing and goal setting, and (8) giving participants structure. The themes from group exercise were: (1) monitoring and modification of the online exercise; (2) catering for differing abilities; (3) feeling safe and confident to exercise; (4) progression of fitness; (5) optimal timing in the recovery trajectory; (6) group effect; (7) initial apprehension about exercise group; (8) gauging exercise capabilities; (9) translating exercises into life; and (10) on-demand supplementary videos. The 1:1 consultation sessions revealed patients needed to tell their stories.

Conclusion

Being listened to and being understood by someone ‘who got it’ was very important to people with post-COVID-19 condition. The group sessions of both exercise and psychological support were valued by participants, working together, and learning from each other in the face of a new disease within a global pandemic.
Sexual and reproductive health from the perspective of patients with autoimmune rheumatic diseases in Mexico: a qualitative study
Authors: Skinner-Taylor Cassandra Michelle , Perez-Barbosa Lorena , Lujano-Negrete Abraham Yair , Arévalo-Nieto Fanny , Corral-Trujillo Maria Eugenia , Aguilar-Leal Andrea , Sandoval-Torres Génesis Guadalupe , Rodríguez-Ruiz Cecilia , Rios-Medina Melanie Gabriela , Manrique de Lara Amaranta , Galarza-Delgado Dionicio Angel , Pelaez-Ballestas Ingris
Published: January 2025

Objectives

To explore the experiences and perspectives of female patients with autoimmune rheumatic diseases (ARDs) regarding sexual and reproductive health, including contraception, family planning, and pregnancy.

Design

Qualitative descriptive study using semi-structured interviews.

Setting

Specialised rheumatology clinic in a tertiary hospital in Monterrey, Mexico.

Participants

21 female patients aged 18–49 with a confirmed ARD diagnosis who were receiving care at the clinic. Participants were selected using convenience sampling, ensuring diversity in age, disease type and stage, socio-economic and cultural background, sexuality and disability status. All participants completed the study.

Results

Four main themes emerged from the analysis. First, participants expressed confusion and concern about the safety and effectiveness of contraceptive methods in the context of their disease and treatment. Second, many participants shared anxiety about infertility, heredity and the risks of pregnancy associated with their ARDs, leading to uncertainty in pregnancy planning. Third, there was concern about the safety of medications during pregnancy and breastfeeding, indicating a lack of guidance and information from healthcare providers. Lastly, patients often deferred decision-making about contraception and medication to their rheumatologists but recognised the importance of a multidisciplinary care approach for comprehensive sexual and reproductive health management.

Conclusions

The study revealed that women with ARDs experience significant challenges and unmet needs related to sexual and reproductive health, particularly in understanding safe contraception, pregnancy planning and medication use during pregnancy and lactation. These findings emphasise the need for rheumatologists to provide clearer guidance on these issues and collaborate closely with gynaecologists and other specialists to ensure comprehensive, patient-centred care. Enhancing communication and education strategies in rheumatology consultations could address these gaps and improve the sexual and reproductive health outcomes and decision-making processes of women with ARDs.
Barriers and facilitators to improved sedentary behaviour in coronary heart disease patients: a scoping review
Authors: Yang Yuting , Yuan Qiao , Wu Chen , Yang Lili
Published: January 2025

Introduction

The majority of patients with coronary heart disease (CHD) are at high sedentary levels, which severely affects patient prognosis and outcome. Despite the proven benefits of reducing sedentary behaviour (SB), intervention studies’ effectiveness has been limited. Thus, the factors influencing SB change in patients with CHD need to be explored. This scoping review aimed to identify barriers and facilitators to improved SB in CHD patients and map these factors to the Capability–Opportunity–Motivation-Behaviour model.

Methods

We conducted a scoping review in accordance with the Arksey and O’Malley framework. Eligibility criteria included qualitative and quantitative studies on SB in patients with CHD. Nine databases were searched (PubMed, Medline, Embase, CINAHL, Web of Science Core Collection, Scopus, CNKI, WanFang and VIP) from inception through 31 December 2023, following the scoping review methodology.

Results

A total of 24 studies, including two qualitative and 22 quantitative studies, were included, with 15 847 patients. Barriers to improved SB in CHD patients included capability (eg, physical characteristics, lack of knowledge to improve SB), opportunity (eg, lack of partnership support, lack of resources to carry out activities) and motivation (eg, maintaining the habit of SB, impaired belief in activities). Facilitators included capability (eg, exercise session, improving understanding of SB), opportunity (eg, utilisation of support, tele-rehabilitation guidance, diversification of living environments) and motivation (perceived benefit).

Conclusions

Patients with CHD have unique barriers and facilitators to improving SB. Future research should adequately reduce barriers and promote facilitators to increase the effectiveness of interventions.
Multicentre, double-blind, randomised controlled clinical trial comparing intermittent cefoxitin administration versus loading bolus followed by continuous infusion for the prevention of surgical site infection in colorectal surgery: the PROPHYLOXITIN study protocol
Authors: Saint-Genis Quentin , Birckener Julien , Gourdou Vincent , Nicolle Claire , Garnier Marc , Schwindenhammer Victor , Hannezo Cécile , Aveline Christophe , Cinotti Raphaël , Puisney Benjamin , Garot Matthias , Chevalier Stéphanie , Aubert Jean-Sébastien , Wodey Maxime , Lasocki Sigismond , Lecoeur Sylvain , Lagarrigue Charles Jean , Li Anne , Faucher Marion , Foucher Yohann , Frasca Denis , Boisson Matthieu
Published: January 2025

Introduction

Surgical site infections (SSIs) are the second leading cause of healthcare-associated infections in Europe with the highest rates being reported in colorectal surgery (ranging from 9% to 30%). Surgical antibiotic prophylaxis (SAP) is one of the most efficient measures for SSI prevention and should be started before surgical incision. Cefoxitin is an antibiotic widely used as SAP for colorectal surgery, but its continuous administration is currently the subject of debate due to its potential pharmacokinetic advantages. Therefore, the aim of the PROPHYLOXITIN study is to demonstrate that a loading dose followed by continuous infusion of cefoxitin during colorectal surgery (intervention group) decreases the rate of SSI compared to an intermittent bolus administration (control group).

Methods and analysis

The PROPHYLOXITIN study is a superiority, prospective, double-blind, randomised and multicentre study of 2000 patients undergoing colorectal surgery. The primary objective is to demonstrate the superiority of a loading dose of cefoxitin followed by continuous infusion over intermittent bolus administration in reducing the proportion of SSIs within 30 days after colorectal surgery. Subjects will be randomised 1:1 using a secure web-based random-number generator to one of two study groups. Randomised allocation of treatment will be done by minimisation and stratified according to the centre, the localisation of surgery (colon or rectum) and the type of surgical procedure (laparoscopy or laparotomy).

Ethics and dissemination

This research has been approved by an independent ethics committee and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals.

Trial registration number

EudraCT 2022-003262-20 and Clinical trialNCT05755789.