bluuebunny/crossref_metadata_2025 huggingface dataset:
Cu- or Ag-containing Bi-Sb-Te for in-line roll-to-roll patterned thin-film thermoelectrics
Authors: Tao Xudong , Zheng Qianfang , Zeng Chongyang , Potter Harry , Zhang Zheng , Ellingford Joshua , Bonilla Ruy S. , Bilotti Emiliano , Grant Patrick S. , Assender Hazel E.
Published: January 2025

The Selective Metallization Technique shows promise for roll-to-roll in-line patterning of flexible electronics using evaporated metals, but challenges arise when applied to sputtering functional materials. This study overcomes these challenges with simultaneous sputtering of Bi-Sb-Te and evaporation of metal (Ag or Cu) for thermoelectric layers when using Selective Metallization Technique. Large-scale manufacturing is demonstrated through roll-to-roll processing of a 0.8 m wide polymer web at 25 m/min, achieving high-throughput production of functional thin-film patterns with nanometer thickness. The room-temperature-deposited material system exhibits significantly enhanced thermoelectric performance and facilitates an n-type-to-p-type transition in the Cu- or Ag-containing Bi-Sb-Te-based composite film. Here, we show that while applying Selective Metallization Technique, the evaporation of metal modifies the impact of residual oil on Bi-Sb-Te, which can be effectively removed with a few seconds of plasma exposure, and the fabricated thermoelectric devices are validated in wearable applications utilizing a coiled-up wristband design.
Deeper response predicts better outcomes in high-risk-smoldering-myeloma: results of the I-PRISM phase II clinical trial
Authors: Nadeem Omar , Aranha Michelle P. , Redd Robert , Timonian Michael , Magidson Sophie , Lightbody Elizabeth D. , Alberge Jean-Baptiste , Bertamini Luca , Dutta Ankit K. , El-Khoury Habib , Bustoros Mark , Laubach Jacob P. , Bianchi Giada , O’Donnell Elizabeth , Wu Ting , Tsuji Junko , Anderson Kenneth C. , Getz Gad , Trippa Lorenzo , Richardson Paul G. , Sklavenitis-Pistofidis Romanos , Ghobrial Irene M.
Published: January 2025

Early therapeutic intervention in high-risk smoldering multiple myeloma (HR-SMM) has shown benefits, however, no studies have assessed whether biochemical progression or response depth predicts long-term outcomes. The single-arm I-PRISM phase II trial (NCT02916771) evaluated ixazomib, lenalidomide, and dexamethasone in 55 patients with HR-SMM. The primary endpoint, median progression-free survival (PFS), was not reached (NR) (95% CI: 57.7–NR, median follow-up 50 months). The secondary endpoint, biochemical PFS, was 48.6 months (95% CI: 39.9–NR) and coincided with or preceded SLiM-CRAB in eight patients. For additional secondary objectives, the overall response rate was 93% with 31% achieving complete response (CR) and 45% very good partial response (VGPR) or better. CR correlated strongly with the absence of SLiM-CRAB and biochemical progression. MRD-negativity (10-5 sensitivity) predicted a 5-year biochemical PFS of 100% versus 40% in MRD-positive patients (p = 0.051), demonstrating that deep responses significantly improve time to progression. Exploratory single-cell RNA sequencing linked tumor MHC class I expression to proteasome inhibitor response, and a lower proportion of GZMB+ T cells within clonally expanded CD8+ T cells associated with suboptimal outcomes.
TOPS-speed complex-valued convolutional accelerator for feature extraction and inference
Authors: Bai Yunping , Xu Yifu , Chen Shifan , Zhu Xiaotian , Wang Shuai , Huang Sirui , Song Yuhang , Zheng Yixuan , Liu Zhihui , Tan Sim , Morandotti Roberto , Chu Sai T. , Little Brent E. , Moss David J. , Xu Xingyuan , Xu Kun
Published: January 2025

Complex-valued neural networks process both amplitude and phase information, in contrast to conventional artificial neural networks, achieving additive capabilities in recognizing phase-sensitive data inherent in wave-related phenomena. The ever-increasing data capacity and network scale place substantial demands on underlying computing hardware. In parallel with the successes and extensive efforts made in electronics, optical neuromorphic hardware is promising to achieve ultra-high computing performances due to its inherent analog architecture and wide bandwidth. Here, we report a complex-valued optical convolution accelerator operating at over 2 Tera operations per second (TOPS). With appropriately designed phasors we demonstrate its performance in the recognition of synthetic aperture radar (SAR) images captured by the Sentinel-1 satellite, which are inherently complex-valued and more intricate than what optical neural networks have previously processed. Experimental tests with 500 images yield an 83.8% accuracy, close to in-silico results. This approach facilitates feature extraction of phase-sensitive information, and represents a pivotal advance in artificial intelligence towards real-time, high-dimensional data analysis of complex and dynamic environments.
Quantum key distribution implemented with d-level time-bin entangled photons
Authors: Yu Hao , Sciara Stefania , Chemnitz Mario , Montaut Nicola , Crockett Benjamin , Fischer Bennet , Helsten Robin , Wetzel Benjamin , Goebel Thorsten A. , Krämer Ria G. , Little Brent E. , Chu Sai T. , Nolte Stefan , Wang Zhiming , Azaña José , Munro William J. , Moss David J. , Morandotti Roberto
Published: January 2025

High-dimensional photon states (qudits) are pivotal to enhance the information capacity, noise robustness, and data rates of quantum communications. Time-bin entangled qudits are promising candidates for implementing high-dimensional quantum communications over optical fiber networks with processing rates approaching those of classical telecommunications. However, their use is hindered by phase instability, timing inaccuracy, and low scalability of interferometric schemes needed for time-bin processing. As well, increasing the number of time bins per photon state typically requires decreasing the repetition rate of the system, affecting in turn the effective qudit rates. Here, we demonstrate a fiber-pigtailed, integrated photonic platform enabling the generation and processing of picosecond-spaced time-bin entangled qudits in the telecommunication C band via an on-chip interferometry system. We experimentally demonstrate the Bennett-Brassard-Mermin 1992 quantum key distribution protocol with time-bin entangled qudits and extend it over a 60 km-long optical fiber link, by showing dimensionality scaling without sacrificing the repetition rate. Our approach enables the manipulation of time-bin entangled qudits at processing speeds typical of standard telecommunications (10 s of GHz) with high quantum information capacity per single frequency channel, representing an important step towards an efficient implementation of high-data rate quantum communications in standard, multi-user optical fiber networks.
Intratumor heterogeneity of EGFR expression mediates targeted therapy resistance and formation of drug tolerant microenvironment
Authors: Alsaed Bassel , Lin Linh , Son Jieun , Li Jiaqi , Smolander Johannes , Lopez Timothy , Eser Pinar Ö. , Ogino Atsuko , Ambrogio Chiara , Eum Yoonji , Thai Tran , Wang Haiyun , Sutinen Eva , Mutanen Hilma , Duàn Hanna , Bobik Nina , Borenius Kristian , Feng William W. , Nabet Behnam , Mustjoki Satu , Laaksonen Sanna , Eschle Benjamin K. , Poitras Michael J. , Barbie David , Ilonen Ilkka , Gokhale Prafulla , Jänne Pasi A. , Haikala Heidi M.
Published: January 2025

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are commonly used to treat non-small cell lung cancers with EGFR mutations, but drug resistance often emerges. Intratumor heterogeneity is a known cause of targeted therapy resistance and is considered a major factor in treatment failure. This study identifies clones of EGFR-mutant non-small cell lung tumors expressing low levels of both wild-type and mutant EGFR protein. These EGFR-low cells are intrinsically more tolerant to EGFR inhibitors, more invasive, and exhibit an epithelial-to-mesenchymal-like phenotype compared to their EGFR-high counterparts. The EGFR-low cells secrete Transforming growth factor beta (TGFβ) family cytokines, leading to increased recruitment of cancer-associated fibroblasts and immune suppression, thus contributing to the drug-tolerant tumor microenvironment. Notably, pharmacological induction of EGFR using epigenetic inhibitors sensitizes the resistant cells to EGFR inhibition. These findings suggest that intrinsic drug resistance can be prevented or reversed using combination therapies.
Functional large-conductance calcium and voltage-gated potassium channels in extracellular vesicles act as gatekeepers of structural and functional integrity
Authors: Sanghvi Shridhar , Sridharan Divya , Evans Parker , Dougherty Julie , Szteyn Kalina , Gabrilovich Denis , Dyta Mayukha , Weist Jessica , Pierre Sandrine V. , Gururaja Rao Shubha , Halm Dan R. , Chen Tingting , Athanasopoulos Panagiotis S. , Dolga Amalia M. , Yu Lianbo , Khan Mahmood , Singh Harpreet
Published: January 2025

Extracellular vesicles (EVs) are associated with intercellular communications, immune responses, viral pathogenicity, cardiovascular diseases, neurological disorders, and cancer progression. EVs deliver proteins, metabolites, and nucleic acids into recipient cells to effectively alter their physiological and biological response. During their transportation from the donor to the recipient cell EVs face differential ionic concentrations, which can be detrimental to their integrity and impact their cargo content. EVs are known to possess ion channels and transporters in their membrane but neither the function nor the role of these channels in EVs is known. In this study, we discover a functional calcium-activated large-conductance potassium channel (BKCa) in the membrane of EVs. Furthermore, we establish that BKCa is essential for the structural and functional integrity of EVs. Together, these findings establish the critical role of ion channels such as BKCa in functioning as gatekeepers and maintaining EV-mediated signaling.
An aperiodic chiral tiling by topological molecular self-assembly
Authors: Voigt Jan , Baljozović Miloš , Martin Kévin , Wäckerlin Christian , Avarvari Narcis , Ernst Karl-Heinz
Published: January 2025

Studying the self-assembly of chiral molecules in two dimensions offers insights into the fundamentals of crystallization. Using scanning tunneling microscopy, we examine an uncommon aggregation of polyaromatic chiral molecules on a silver surface. Dense packing is achieved through a chiral triangular tiling of triads, with N and N ± 1 molecules at the edges. The triangles feature a random distribution of mirror-isomers, with a significant excess of one isomer. Chirality at the domain boundaries causes a lateral shift, producing three distinct topological defects where six triangles converge. These defects partially contribute to the formation of supramolecular spirals. The observation of different equal-density arrangements suggests that entropy maximization must play a crucial role. Despite the potential for regular patterns, all observed tiling is aperiodic. Differences from previously reported aperiodic molecular assemblies, such as Penrose tiling, are discussed. Our findings demonstrate that two-dimensional molecular self-assembly can be governed by topological constraints, leading to aperiodic tiling induced by intermolecular forces.
Exact projected entangled pair ground states with topological Euler invariant
Authors: Wahl Thorsten B. , Jankowski Wojciech J. , Bouhon Adrien , Chaudhary Gaurav , Slager Robert-Jan
Published: January 2025

We report on a class of gapped projected entangled pair states (PEPS) with non-trivial Euler topology motivated by recent progress in band geometry. In the non-interacting limit, these systems have optimal conditions relating to saturation of quantum geometrical bounds, allowing for parent Hamiltonians whose lowest bands are completely flat and which have the PEPS as unique ground states. Protected by crystalline symmetries, these states evade restrictions on capturing tenfold-way topological features with gapped PEPS. These PEPS thus form the first tensor network representative of a non-interacting, gapped two-dimensional topological phase, similar to the Kitaev chain in one dimension. Using unitary circuits, we then formulate interacting variants of these PEPS and corresponding gapped parent Hamiltonians. We reveal characteristic entanglement features shared between the free-fermionic and interacting states with Euler topology. Our results hence provide a rich platform of PEPS models that have, unexpectedly, a finite topological invariant, forming the basis for new spin liquids, quantum Hall physics, and quantum information pursuits.
Telomere-to-telomere DNA replication timing profiling using single-molecule sequencing with Nanotiming
Authors: Theulot Bertrand , Tourancheau Alan , Simonin Chavignier Emma , Jean Etienne , Arbona Jean-Michel , Audit Benjamin , Hyrien Olivier , Lacroix Laurent , Le Tallec Benoît
Published: January 2025

Current temporal studies of DNA replication are either low-resolution or require complex cell synchronisation and/or sorting procedures. Here we introduce Nanotiming, a single-molecule, nanopore sequencing-based method producing high-resolution, telomere-to-telomere replication timing (RT) profiles of eukaryotic genomes by interrogating changes in intracellular dTTP concentration during S phase through competition with its analogue bromodeoxyuridine triphosphate (BrdUTP) for incorporation into replicating DNA. This solely demands the labelling of asynchronously growing cells with an innocuous dose of BrdU during one doubling time followed by BrdU quantification along nanopore reads. We demonstrate in S. cerevisiae model eukaryote that Nanotiming reproduces RT profiles generated by reference methods both in wild-type and mutant cells inactivated for known RT determinants. Nanotiming is simple, accurate, inexpensive, amenable to large-scale analyses, and has the unique ability to access RT of individual telomeres, revealing that Rif1 iconic telomere regulator selectively delays replication of telomeres associated with specific subtelomeric elements.
Deciphering metabolic differentiation during Bacillus subtilis sporulation
Authors: Tibocha-Bonilla Juan D. , Lyda Jelani , Riley Eammon , Pogliano Kit , Zengler Karsten
Published: January 2025

The bacterium Bacillus subtilis undergoes asymmetric cell division during sporulation, producing a mother cell and a smaller forespore connected by the SpoIIQ-SpoIIIA (or Q-A) channel. The two cells differentiate metabolically, and the forespore becomes dependent on the mother cell for essential building blocks. Here, we investigate the metabolic interactions between mother cell and forespore using genome-scale metabolic and expression models as well as experiments. Our results indicate that nucleotides are synthesized in the mother cell and transported in the form of nucleoside di- or tri-phosphates to the forespore via the Q-A channel. However, if the Q-A channel is inactivated later in sporulation, then glycolytic enzymes can form an ATP and NADH shuttle, providing the forespore with energy and reducing power. Our integrated in silico and in vivo approach sheds light into the intricate metabolic interactions underlying cell differentiation in B. subtilis, and provides a foundation for future studies of metabolic differentiation.
Surface molecular engineering to enable processing of sulfide solid electrolytes in humid ambient air
Authors: Liu Mengchen , Hong Jessica J. , Sebti Elias , Zhou Ke , Wang Shen , Feng Shijie , Pennebaker Tyler , Hui Zeyu , Miao Qiushi , Lu Ershuang , Harpak Nimrod , Yu Sicen , Zhou Jianbin , Oh Jeong Woo , Song Min-Sang , Luo Jian , Clément Raphaële J. , Liu Ping
Published: January 2025

Sulfide solid-state electrolytes (SSEs) are promising candidates to realize all solid-state batteries (ASSBs) due to their superior ionic conductivity and excellent ductility. However, their hypersensitivity to moisture requires processing environments that are not compatible with today’s lithium-ion battery manufacturing infrastructure. Herein, we present a reversible surface modification strategy that enables the processability of sulfide SSEs (e. g., Li6PS5Cl) under humid ambient air. We demonstrate that a long chain alkyl thiol, 1-undecanethiol, is chemically compatible with the electrolyte with negligible impact on its ion conductivity. Importantly, the thiol modification extends the amount of time that the sulfide SSE can be exposed to air with 33% relative humidity (33% RH) with limited degradation of its structure while retaining a conductivity of above 1 mS cm-1 for up to 2 days, a more than 100-fold improvement in protection time over competing approaches. Experimental and computational results reveal that the thiol group anchors to the SSE surface, while the hydrophobic hydrocarbon tail provides protection by repelling water. The modified Li6PS5Cl SSE maintains its function after exposure to ambient humidity when implemented in a Li0.5In | |LiNi0.8Co0.1Mn0.1O2 ASSB. The proposed protection strategy based on surface molecular interactions represents a major step forward towards cost-competitive and energy-efficient sulfide SSE manufacturing for ASSB applications.
G-quadruplex stabilization provokes DNA breaks in human PKD1, revealing a second hit mechanism for ADPKD
Authors: Parsons Agata M. , Byrne Seth , Kooistra Jesse , Dewey John , Zebolsky Aaron L. , Alvarado Gloria , Bouma Gerrit J. , Vanden Heuvel Gregory B. , Larson Erik D.
Published: January 2025

The “secondhit” pathway is responsible for biallelic inactivation of many tumor suppressors, where a pathogenic germline allele is joined by somatic mutation of the remaining functional allele. The mechanisms are unresolved, but the human PKD1 tumor suppressor is a good experimental model for identifying the molecular determinants. Inactivation of PKD1 results in autosomal dominant polycystic kidney disease, a very common disorder characterized by the accumulation of fluid-filled cysts and end-stage renal disease. Since human PKD1 follows second hit and mouse Pkd1 heterozygotes do not, we reasoned that there is likely a molecular difference that explains the elevated mutagenesis of the human gene. Here we demonstrate that guanine quadruplex DNA structures are abundant throughout human, but not mouse, PKD1 where they activate the DNA damage response. Our results suggest that guanine quadruplex DNAs provoke DNA breaks in PKD1, providing a potential mechanism for cystogenesis in autosomal dominant polycystic kidney disease specifically and for the inactivation of guanine quadruplex-rich tumor suppressors generally.
Structures of Saccharolobus solfataricus initiation complexes with leaderless mRNAs highlight archaeal features and eukaryotic proximity
Authors: Bourgeois Gabrielle , Coureux Pierre-Damien , Lazennec-Schurdevin Christine , Madru Clément , Gaillard Thomas , Duchateau Magalie , Chamot-Rooke Julia , Bourcier Sophie , Mechulam Yves , Schmitt Emmanuelle
Published: January 2025

The archaeal ribosome is of the eukaryotic type. TACK and Asgard superphyla, the closest relatives of eukaryotes, have ribosomes containing eukaryotic ribosomal proteins not found in other archaea, eS25, eS26 and eS30. Here, we investigate the case of Saccharolobus solfataricus, a TACK crenarchaeon, using mainly leaderless mRNAs. We characterize the small ribosomal subunit of S. solfataricus bound to SD-leadered or leaderless mRNAs. Cryo-EM structures show eS25, eS26 and eS30 bound to the small subunit. We identify two ribosomal proteins, aS33 and aS34, and an additional domain of eS6. Leaderless mRNAs are bound to the small subunit with contribution of their 5’-triphosphate group. Archaeal eS26 binds to the mRNA exit channel wrapped around the 3’ end of rRNA, as in eukaryotes. Its position is not compatible with an SD:antiSD duplex. Our results suggest a positive role of eS26 in leaderless mRNAs translation and possible evolutionary routes from archaeal to eukaryotic translation.
The hybrid lipoplex induces cytoskeletal rearrangement via autophagy/RhoA signaling pathway for enhanced anticancer gene therapy
Authors: Hu Xueyi , Wang Yichun , Wang Ruohan , Pu Yiyao , Jin Rongrong , Nie Yu , Shuai Xintao
Published: January 2025

Delivering plasmid DNA (pDNA) to solid tumors remains a significant challenge due to the requirement for multiple transport steps and the need to promote delivery efficiency. Herein, we present a virus-mimicking hybrid lipoplex, composed of an arginine-rich cationic lipid, hyaluronic acid derivatives coated gold nanoparticles, and pDNA. This system induces cytoskeletal rearrangements through “outside-in” mechanical and “inside-out” biochemical signaling, overcoming intra- and intercellular barriers to enhance pDNA delivery. By modulating autophagy, RhoA signaling, and cytoskeletal dynamics, we achieve a 20-fold increase in gene expression with high tissue specificity in solid tumors. Furthermore, the system is applied to co-deliver a p53 plasmid and an MDM2 inhibitor, demonstrating significant synergistic antitumor effects in hepatocellular and lung carcinomas.
Effect of titanium and vanadium nano-carbide size on hydrogen embrittlement of ferritic steels
Authors: Boot Tim , Kömmelt Pascal , Brouwer Hans J. C. , Böttger Amarante , Popovich Vera
Published: January 2025

The effect of TiC and VC nano-precipitate size on the hydrogen embrittlement of ferritic steels was studied in this work. Steels containing two size distributions (10 nm or less and 10 - 100 nm) of TiC and VC carbides are subjected to tensile tests in-situ in an electrochemical hydrogen charging environment. Hydrogen is found to be trapped in interstitial matrix sites on the precipitate/matrix interface with activation energies of 14 - 20 kJ/mol and inside misfit dislocation cores with energies of 27 - 37 kJ/mol. All steels are embrittled by 15 to 20%, except the TiC steel with semi-coherent carbides up to 100 nm, which is embrittled by 37%. This is caused by accelerated intergranular fracture as a result of hydrogen trapped in dislocation pile-ups around grain boundary precipitates. The steel with coherent VC nano-carbides retained the highest strength and ductility during in-situ testing. This is therefore the optimal carbide configuration for use in hydrogen environments.
Plasma proteomic signatures of social isolation and loneliness associated with morbidity and mortality
Authors: Shen Chun , Zhang Ruohan , Yu Jintai , Sahakian Barbara J. , Cheng Wei , Feng Jianfeng
Published: January 2025

The biology underlying the connection between social relationships and health is largely unknown. Here, leveraging data from 42,062 participants across 2,920 plasma proteins in the UK Biobank, we characterized the proteomic signatures of social isolation and loneliness through proteome-wide association study and protein co-expression network analysis. Proteins linked to these constructs were implicated in inflammation, antiviral responses and complement systems. More than half of these proteins were prospectively linked to cardiovascular disease, type 2 diabetes, stroke and mortality during a 14 year follow-up. Moreover, Mendelian randomization (MR) analysis suggested causal relationships from loneliness to five proteins, with two proteins (ADM and ASGR1) further supported by colocalization. These MR-identified proteins (GFRA1, ADM, FABP4, TNFRSF10A and ASGR1) exhibited broad associations with other blood biomarkers, as well as volumes in brain regions involved in interoception and emotional and social processes. Finally, the MR-identified proteins partly mediated the relationship between loneliness and cardiovascular diseases, stroke and mortality. The exploration of the peripheral physiology through which social relationships influence morbidity and mortality is timely and has potential implications for public health.
A magneto-thermoelectric with a high figure of merit in topological insulator Bi88Sb12
Authors: Pan Yu , He Bin , Feng Xiaolong , Li Fan , Chen Dong , Burkhardt Ulrich , Felser Claudia
Published: January 2025

High thermoelectric performance is generally achieved by synergistically optimizing two or even three of the contradictorily coupled thermoelectric parameters. Here we demonstrate magneto-thermoelectric correlation as a strategy to achieve simultaneous gain in an enhanced Seebeck coefficient and reduced thermal conductivity in topological materials. We report a large magneto-Seebeck effect and high magneto-thermoelectric figure of merit of 1.7 ± 0.2 at 180 K and 0.7 T in a single-crystalline Bi88Sb12 topological insulator. This result fills a gap of a high performance below 300 K and is promising for low-temperature thermoelectric applications. The large magneto-Seebeck response is attributed to the ultrahigh mobility and the Dirac band dispersion. The application of a low magnetic field to achieve a high thermoelectric performance can be extended to topological materials with similar features that are rapidly emerging because it synergistically optimizes the thermoelectric parameters.
Phenotypic evolution of SARS-CoV-2 spike during the COVID-19 pandemic
Authors: Furnon Wilhelm , Cowton Vanessa M. , De Lorenzo Giuditta , Orton Richard , Herder Vanessa , Cantoni Diego , Ilia Georgios , Mendonca Diogo Correa , Kerr Karen , Allan Jay , Upfold Nicole , Meehan Gavin R. , Bakshi Siddharth , Das Udeet Ranjan , Molina Arias Sergi , McElwee Marion , Little Sarah , Logan Nicola , Kwok Kirsty , Smollett Katherine , Willett Brian J. , Da Silva Filipe Ana , Robertson David L. , Grove Joe , Patel Arvind H. , Palmarini Massimo
Published: January 2025

SARS-CoV-2 variants are mainly defined by mutations in their spike. It is therefore critical to understand how the evolutionary trajectories of spike affect virus phenotypes. So far, it has been challenging to comprehensively compare the many spikes that emerged during the pandemic in a single experimental platform. Here we generated a panel of recombinant viruses carrying different spike proteins from 27 variants circulating between 2020 and 2024 in the same genomic background. We then assessed several of their phenotypic traits both in vitro and in vivo. We found distinct phenotypic trajectories of spike among and between variants circulating before and after the emergence of Omicron variants. Spike of post-Omicron variants maintained enhanced tropism for the nasal epithelium and large airways but displayed, over time, several phenotypic traits typical of the pre-Omicron variants. Hence, spike with phenotypic features of both pre- and post-Omicron variants may continue to emerge in the future.
Proteomic changes upon treatment with semaglutide in individuals with obesity
Authors: Maretty Lasse , Gill Dipender , Simonsen Lotte , Soh Keng , Zagkos Loukas , Galanakis Michael , Sibbesen Jonas , Iglesias Miquel Triana , Secher Anna , Valkenborg Dirk , Purnell Jonathan Q. , Knudsen Lotte Bjerre , Tahrani Abd A. , Geybels Milan
Published: January 2025

Obesity and type 2 diabetes are prevalent chronic diseases effectively managed by semaglutide. Here we studied the effects of semaglutide on the circulating proteome using baseline and end-of-treatment serum samples from two phase 3 trials in participants with overweight or obesity, with or without diabetes: STEP 1 (n = 1,311) and STEP 2 (n = 645). We identified evidence supporting broad effects of semaglutide, implicating processes related to body weight regulation, glycemic control, lipid metabolism and inflammatory pathways. Several proteins were regulated with semaglutide, after accounting for changes in body weight and HbA1c at end of trial, suggesting effects of semaglutide on the proteome beyond weight loss and glucose lowering. A comparison of semaglutide with real-world proteomic profiles revealed potential benefits on disease-specific proteomic signatures including the downregulation of specific proteins associated with cardiovascular disease risk, supporting its reported effects of lowering cardiovascular disease risk and potential drug repurposing opportunities. This study showcases the potential of proteomics data gathered from randomized trials for providing insights into disease mechanisms and drug repurposing opportunities. These data also highlight the unmet need for, and importance of, examining proteomic changes in response to weight loss pharmacotherapy in future trials.
ApisTox: a new benchmark dataset for the classification of small molecules toxicity on honey bees
Authors: Adamczyk Jakub , Poziemski Jakub , Siedlecki Pawel
Published: January 2025

The global decline in bee populations poses significant risks to agriculture, biodiversity, and environmental stability. To bridge the gap in existing data, we introduce ApisTox, a comprehensive dataset focusing on the toxicity of pesticides to honey bees (Apis mellifera). This dataset combines and leverages data from existing sources such as ECOTOX and PPDB, providing an extensive, consistent, and curated collection that surpasses the previous datasets. ApisTox incorporates a wide array of data, including toxicity levels for chemicals, details such as time of their publication in literature, and identifiers linking them to external chemical databases. This dataset may serve as an important tool for environmental and agricultural research, but also can support the development of policies and practices aimed at minimizing harm to bee populations. Finally, ApisTox offers a unique resource for benchmarking molecular property prediction methods on agrochemical compounds, facilitating advancements in both environmental science and chemoinformatics. This makes it a valuable tool for both academic research and practical applications in bee conservation.
Effectiveness of tacrolimus therapy in refractory ulcerative colitis compared to infliximab with propensity score matching
Authors: Yoshihara Takeo , Amano Takahiro , Shinzaki Shinichiro , Tsujii Yuri , Asakura Akiko , Tashiro Taku , Tani Mizuki , Otake-Kasamoto Yuriko , Yamada Takuya , Sakakibara Yuko , Osugi Naoto , Ishii Shuji , Egawa Satoshi , Araki Manabu , Arimoto Yuki , Nakahara Masanori , Murayama Yoko , Kobayashi Ichizo , Kinoshita Kazuo , Ogawa Hiroyuki , Hiyama Satoshi , Shibukawa Narihiro , Komori Masato , Okuda Yorihide , Kizu Takashi , Kitamura Tetsuhisa , Kato Minoru , Tsujii Yoshiki , Inoue Takahiro , Iijima Hideki , Hayashi Yoshito , Takehara Tetsuo
Published: January 2025

There is insufficient evidence comparing the outcomes of tacrolimus-based remission induction therapy with infliximab in refractory ulcerative colitis (UC) and evidence regarding optimal strategies after tacrolimus-based remission induction therapy. We conducted a multi-institutional retrospective study of patients with UC treated with tacrolimus or infliximab between January 2010 and March 2019. The proportion of clinical remission at week 8 and cumulative colectomy-free rate were examined using propensity score matching analysis. The predictors for colectomy after tacrolimus induction were also investigated. Ninety patients in the tacrolimus group and 151 in the infliximab group were enrolled. The proportion of patients in clinical remission at week 8 was 65.2% in the matched tacrolimus group and 37.3% in the matched infliximab group (P = 0.0016), and the long-term colectomy-free rate was lower in the matched tacrolimus group than in the matched infliximab group (P = 0.0003). After clinical remission with tacrolimus, a serum albumin level of ≤ 3.5 g/dL at week 8 was extracted as a factor predicting colectomy (area under the curve: 0.94). Tacrolimus showed a higher remission induction effect for UC compared to infliximab. However, a high rate of colectomy after transition to maintenance treatment was found to be a concern for tacrolimus therapy.
Annual migrations, vertical habitat use and fidelity of Atlantic bluefin tuna tracked from waters off the United Kingdom
Authors: Horton Thomas W. , Binney Francis C. T. , Birch Samantha , Block Barbara A. , Exeter Owen M. , Garzon Francesco , Plaster Alex , Righton David , van der Kooij Jeroen , Witt Matthew J. , Hawkes Lucy A.
Published: January 2025

Understanding the spatial ecology of commercially exploited species is vital for their conservation. Atlantic bluefin tuna (Thunnus thynnus, ABT) are increasingly observed in northeast Atlantic waters, yet knowledge of these individuals’ spatial ecology remains limited. We investigate the horizontal and vertical habitat use of ABT (158 to 241 cm curved fork length; CFL) tracked from waters off the United Kingdom (UK) using pop-up satellite archival tags (n = 63). Analyses reveal distinctive movements from the UK to the Bay of Biscay (BoB) and Central North Atlantic between September and December, and size-specific habitat preferences in May and July—all ABT < 175 cm CFL inhabiting the BoB and 73% of ABT ≥ 175 the Mediterranean Sea. All ABT tracked for more than 300 days (n = 25) returned to waters off the UK the following year, where most stayed (n = 22; 88%) and three continuing north with deployments ending off northwest Ireland. ABT mostly occupied waters between 0 and 20 m (daytime 49 ± 6% of time; nighttime 71 ± 6%). Vertical habitat use was coupled with illumination, mean depth occupied, maximum depth reached, and vertical movement rate increased during the daytime and when moons were brightest. These data provide valuable insights into the spatial ecology of ABT reoccupying northerly foraging areas following decades of absence.
Mechanistic modelling of allergen-induced airways disease in early life
Authors: Pybus Hannah J. , Dangarh Prakrati , Ng Man Yin Melanie , Lloyd Clare M. , Saglani Sejal , Tanaka Reiko J.
Published: January 2025

Asthma affects approximately 300 million individuals worldwide and the onset predominantly arises in childhood. Children are exposed to multiple environmental irritants, such as viruses and allergens, that are common triggers for asthma onset, whilst their immune systems are developing in early life. Understanding the impact of allergen exposures on the developing immune system and resulting alterations in lung function in early life will help prevent the onset and progression of allergic asthma in children. In this study, we developed an in silico model describing the pulmonary immune response to a common allergen, house dust mite, to investigate its downstream impact on the pathophysiology of asthma, including airway eosinophilic inflammation, remodelling, and lung function. We hypothesised that altered epithelial function following allergen exposure determines the onset of airway remodelling and abnormal lung function, which are irreversible with current asthma therapies. We calibrated the in silico model using age appropriate in vivo data from neonatal and adult mice. We validated the in silico model using in vivo data from mice on the effects of current treatment strategies. The in silico model recapitulates experimental observations and provides an interpretable in silico tool to assess airway pathology and the underlying immune responses upon allergen exposure. The in silico model simulations predict the extent of bronchial epithelial barrier damage observed when allergen sensitisation occurs and demonstrate that epithelial barrier damage and impaired immune maturation are critical determinants of reduced lung function and asthma development. The in silico model demonstrates that both epithelial barrier repair and immune maturation are potential targets for therapeutic intervention to achieve successful asthma prevention.
Ironing out differences in attenuation and blooming artifact in acute stroke thrombi
Authors: Velasco Gonzalez Aglae , Görlich Dennis , Buerke Boris , Sauerland Cristina , Meier Norbert , Fobker Manfred , McCarthy Ray , Jeibmann Astrid , Heindel Walter , Faldum Andreas , Kugel Harald
Published: January 2025

This study aims to improve our understanding of acute ischemic stroke clot imaging by integrating CT attenuation information with MRI susceptibility signal of thrombi. For this proof-of-principle experimental study, fifty-seven clot analogs were produced using ovine venous blood with a broad histological spectrum. Each clot analog was analyzed to determine its RBC content and chemical composition, including water, Fe III, sodium, pH, and pO2. Non-contrast CT and a susceptibility-weighted MRI sequence were used for imaging. The study found that RBC content correlated more accurately than iron content with clot attenuation on CT. There was a strong correlation between Fe III content and RBC percentage in clots. Specifically, changes in RBC content accounted for 64% of the variance in Fe III content (R2 = 0.640; p < .0001). Thrombi with blooming artifacts (BA) displayed higher attenuation on non-contrast CT than those without (73.4 vs. 40 HU, p < .0001) and had the highest RBC and iron contents. The cut-off value of 1242 µg/g of iron predicted blooming artifacts with high sensitivity and specificity. The pH level strongly affected the appearance of blooming artifacts, particularly for negative clots with high RBC content. These findings provide significant insights into the imaging behavior of acute ischemic stroke clots across both imaging modalities and could potentially improve the diagnosis and treatment of acute stroke patients. Furthermore, these results open the possibility for future research aimed at developing pH-modulated therapeutic strategies based on the acid-base state of thrombi.
AI-based visualization of loose connective tissue as a dissectable layer in gastrointestinal surgery
Authors: Kumazu Yuta , Kobayashi Nao , Senya Seigo , Negishi Yuya , Kinoshita Kazuya , Fukui Yudai , Mita Kazuhito , Osaragi Tomohiko , Misumi Toshihiro , Shinohara Hisashi
Published: January 2025

We aimed to develop an AI model that recognizes and displays loose connective tissue as a dissectable layer in real-time during gastrointestinal surgery and to evaluate its performance, including feasibility for clinical application. Training data were created under the supervision of gastrointestinal surgeons. Test images and videos were randomly sampled and model performance was evaluated visually by 10 external gastrointestinal surgeons. The mean Dice coefficient of the 50 images was 0.46. The AI model could detect at least 75% of the loose connective tissue in 91.8% of the images (459/500 responses). False positives were found for 52.6% of the images, but most were not judged significant enough to affect surgical judgment. When comparing the surgeon’s annotation with the AI prediction image, 5 surgeons judged the AI image was closer to their own recognition. When viewing the AI video and raw video side-by-side, surgeons judged that in 99% of the AI videos, visualization was improved and stress levels were acceptable when viewing the AI prediction display. The AI model developed demonstrated performance at a level approaching that of a gastrointestinal surgeon. Such visualization of a safe dissectable layer may help to reduce intraoperative recognition errors and surgical complications.
Healthcare workers safety: a cohort study using healthcare utilisation databases on vaccination and vaccine timeliness impact against SARS-CoV-2 infection
Authors: Skrami Edlira , Faragalli Andrea , Iommi Marica , Morbidoni Marco , Mancini Cristina , Guidi Antonella , Cardone Annalisa , Pompili Marco , Serafini Pietro , Appignanesi Remo , Ferrante Luigi , Carle Flavia
Published: January 2025

Healthcare Workers (HCWs) are at ongoing risk of SARS-CoV-2 infection, potentially contributing to its transmission. This study assessed full vaccination and vaccination timeliness impact on SARS-CoV-2 infections among HCWs in Italy’s Marche Region, using Healthcare Utilization Databases. We evaluated vaccination coverage and its associated factors. The cohort comprised 21,118 HCWs aged 18–70 from the region’s five Local Health Authorities (LHA), enrolled between February 2020 - May 2021. Factors associated with full vaccination were assessed using multiple logistic regression. The impact of vaccination status, time to vaccination, occupational role, age, gender, and health status on infection risk was analysed with a multiple Cox regression model, adjusting for vaccination coverage velocity, swabbing probability, and monthly intensive care unit admissions rate in each LHA. Of the cohort, 81.2% were fully vaccinated. Factors associated with full vaccination included age, role, LHA, prior infection, and health status. Vaccination reduced infection risk by 77% (95% CI: 70–82). Infection risk was higher among healthcare assistants, nurses/physiotherapists/technicians compared to physicians, among male HCWs, and it decreased as vaccination timeliness increased. Vaccination timeliness is crucial for reducing SARS-CoV-2 infection risk among HCWs, regardless of their characteristics. This underscores the importance of efficiently organizing vaccination administration across different territories and for all HCW categories.
Perennial disaster patterns in Central Europe since 2000 and implications for hospital preparedness planning – a cross-sectional analysis
Authors: von der Forst Maik , Dietrich Maximilian , Schmitt Felix C. F. , Popp Erik , Ries Markus
Published: January 2025

The goal of this analysis is to describe seasonal disaster patterns in Central Europe in order to raise awareness and improve hospital disaster planning and resilience, particularly during peak events. Hospitals are essential pillars of a country’s critical infrastructure, vital for sustaining healthcare services and supporting public well-being—a key issue of national security. Disaster planning for hospitals is crucial to ensure their functionality under special circumstances. But the impact of climate change and seasonal variations in the utilization of hospital services are raising challenges. Therefore, the knowledge of perennial disaster patterns could help strengthen the resilience of hospitals. We conducted a cross-sectional analysis of the Emergency Events Database EM-DAT for disasters in Central Europe (Germany, France, Denmark, The Netherlands, Belgium, Luxembourg, Switzerland, Austria, Czech Republic, and Poland) between January 2000 and December 2023. Time distribution of disasters, patterns and longitudinal trends, were analyzed to discuss impact on disaster preparedness in hospitals. Out of 474 events, 83% were associated with a natural hazard and only 80 events (17%) were of technological cause. While technological disasters were spread equally over the whole year, the vast majority of disasters related to natural hazards (n = 394), i.e. storms (n = 178, 45%), floods (n = 101, 26%), and extreme temperatures (n = 93, 24%) peaked during summer and winter months. Fewer disasters were registered during autumn and especially spring seasons. More than 50% of the technological disasters were categorized in the transport accident subgroup. Technological disasters were spread equally over the whole year. Looking at the three most common disaster types, extreme temperatures, floods, and storms are clearly dominating and cause over 90% of the disasters due to natural hazards in central Europe. Overall, the number of events per year fluctuates without a clear trend, only the technological events appear to become less frequent with 70% (n = 56) of the registered disasters occurring in the first half of the study period (2000–2011). An overlap of hospital admissions due to seasonal effects and catastrophic events, mainly triggered by disasters of natural cause in vulnerable periods may lead to a partial collapse of the health care system. To close knowledge gaps, future comprehensive data collection is vital for informed decision-making. Awareness and preparedness are key: an "all-hazards" approach to manage diverse, potentially simultaneous seasonal threats is often the most versatile strategy for hospital emergency planning.
Depression among Tibetan residents in the Southeastern region of Qinghai-Tibet plateau: a cross-sectional study
Authors: Chen Yuji , Long Ga , Huang Qing , Zhang Ping , Xu Nie
Published: January 2025

Depression has emerged as a significant public health concern, with its prevalence fluctuating based on varying environmental and demographic factors. This study categorized participants based on altitude. A convenient sampling approach was used, and the hamilton depression rating scale-24 was used to assess depressed symptoms while gathering demographic information. A total of 600 Tibetan residents from the Dege area of Garze Prefecture, Sichuan, China, participated in the survey. The mean age is 56.81 years, males comprising 52.8% and females 47.2% of the sample. Of the participants, 41.2% resided permanently at elevations exceeding 3500 m. The results found that the weighted prevalence of depression in the area was 24.62%. Regardless of gender, the age group with the highest prevalence was 55–64 years old. Depression increased with age as well as gradually decreased after the age of 60. Logistic regression analysis showed that middle-aged (OR 2.86, 95% CI 1.69–4.82, P < 0.01) and elderly people (OR 2.27, 95% CI 1.30–3.98, P < 0.01), living in ultra-high altitude areas (OR 3.48, 95% CI 1.35–2.91, P < 0.01) and low BMI (OR   4.31, 95% CI 1.33–13.93) are high-risk factors for depression. This study enhances the understanding of the characteristics of depression in high-altitude regions of China, contributing to a more comprehensive view of the psychological well-being of residents in these areas. The findings underscore the need for targeted prevention and treatment strategies tailored to the specific needs of these populations.
In situ synthesis of ZnO/g-C3N4 based composites for photodegradation of methylene blue under visible light
Authors: Pourali S. , Amrollahi R. , Alamolhoda S. , Masoudpanah S. M.
Published: January 2025

In this study, in situ-synthesized ZnO/g-C3N4 based composites were used as photocatalysts for organic pollution removal. These nanocomposites were prepared through simple calcination of a mixture of melamine and ZnO nanoparticles and underwent comprehensive evaluation of their structural, morphological, optical, and photocatalytic properties, using various analytical techniques. As the g-C3N4 content increased, the band gap decreased from 3.02 to 2.94 eV. Additionally, the reduction in photoluminescence intensity confirmed the heterojunction interface between the g-C3N4 and ZnO components. The photodegradation rate of methylene blue (MB) dye exhibited an increase, rising from 0.016 (min−1) for ZnO and 0.011 (min−1) for g-C3N4 to 0.022 (min−1) for the ZnO/g-C3N4 (10 wt%) composite. Furthermore, combining ZnO (50 wt%) with g-C3N4 led to a significant enhancement in the MB dye removal efficiency, reaching 97% compared to the ZnO/g-C3N4 (10 wt%) composite. In contrast, the removal efficiencies were 90% for pristine ZnO and 73% for g-C3N4 phases.