bluuebunny/crossref_metadata_2025 huggingface dataset:
On the longevity and inherent hermeticity of silicon-ICs: evaluation of bare-die and PDMS-coated ICs after accelerated aging and implantation studies
Authors: Nanbakhsh Kambiz , Shah Idil Ahmad , Lamont Callum , Dücső Csaba , Akgun Ömer Can , Horváth Domonkos , Tóth Kinga , Meszéna Domokos , Ulbert István , Mazza Federico , Constandinou Timothy G. , Serdijn Wouter , Vanhoestenberghe Anne , Donaldson Nick , Giagka Vasiliki
Published: January 2025

Silicon integrated circuits (ICs) are central to the next-generation miniature active neural implants, whether packaged in soft polymers for flexible bioelectronics or implanted as bare die for neural probes. These emerging applications bring the IC closer to the corrosive body environment, raising reliability concerns, particularly for chronic use. Here, we evaluate the inherent hermeticity of bare die ICs, and examine the potential of polydimethylsiloxane (PDMS), a moisture-permeable elastomer, as a standalone encapsulation material. For this aim, the electrical and material performance of ICs sourced from two foundries was evaluated through one-year accelerated in vitro and in vivo studies. ICs featured custom-designed test structures and were partially PDMS coated, creating two regions on each chip, uncoated “bare die” and “PDMS-coated”. During the accelerated in vitro study, ICs were electrically biased and periodically monitored. Results revealed stable electrical performance, indicating the unaffected operation of ICs even when directly exposed to physiological fluids. Despite this, material analysis revealed IC degradation in the bare regions. PDMS-coated regions, however, revealed limited degradation, making PDMS a suitable IC encapsulant for years-long implantation. Based on the new insights, guidelines are proposed that may enhance the longevity of implantable ICs, broadening their applications in the biomedical field.
Comparative 3D ultrastructure of Plasmodium falciparum gametocytes
Authors: Evers Felix , Roverts Rona , Boshoven Cas , Kea-te Lindert Mariska , Verhoef Julie M. J. , Sommerdijk Nico , Sinden Robert E. , Akiva Anat , Kooij Taco W. A.
Published: January 2025

Despite the enormous significance of malaria parasites for global health, some basic features of their ultrastructure remain obscure. Here, we apply high-resolution volumetric electron microscopy to examine and compare the ultrastructure of the transmissible male and female sexual blood stages of Plasmodium falciparum as well as the more intensively studied asexual blood stages revisiting previously described phenomena in 3D. In doing so, we challenge the widely accepted notion of a single mitochondrion by demonstrating the presence of multiple mitochondria in gametocytes. We also provide evidence for a gametocyte-specific cytostome, or cell mouth. Furthermore, we generate the first 3D reconstructions of the parasite’s endoplasmic reticulum (ER) and Golgi apparatus as well as gametocyte-induced extraparasitic structures in the infected red blood cell. Assessing interconnectivity between organelles, we find frequent structural appositions between the nucleus, mitochondria, and apicoplast. We provide evidence that the ER is a promiscuous interactor with numerous organelles and the trilaminar pellicle of the gametocyte. Public availability of these volumetric electron microscopy resources will facilitate reinterrogation by others with different research questions and expertise. Taken together, we reconstruct the 3D ultrastructure of P. falciparum gametocytes at nanometre scale and shed light on the unique organellar biology of these deadly parasites.
Overlapping qubits from non-isometric maps and de Sitter tensor networks
Authors: Cao ChunJun , Chemissany Wissam , Jahn Alexander , Zimborás Zoltán
Published: January 2025

The emergence of a local effective theory from a more fundamental theory of quantum gravity with seemingly fewer degrees of freedom is a major puzzle of theoretical physics. A recent approach to this problem is to consider general features of the Hilbert space maps relating these theories. In this work, we construct approximately local observables, or overlapping qubits, from such non-isometric maps. We show that local processes in effective theories can be spoofed with a quantum system with fewer degrees of freedom, with deviations from actual locality identifiable as features of quantum gravity. For a concrete example, we construct two tensor network models of de Sitter space-time, demonstrating how exponential expansion and local physics can be spoofed for a long period before breaking down. Our results highlight the connection between overlapping qubits, Hilbert space dimension verification, degree-of-freedom counting in black holes, holography, and approximate locality in quantum gravity.
Long non-coding RNAs direct the SWI/SNF complex to cell type-specific enhancers
Authors: Oo James A. , Warwick Timothy , Pálfi Katalin , Lam Frederike , McNicoll Francois , Prieto-Garcia Cristian , Günther Stefan , Cao Can , Zhou Yinuo , Gavrilov Alexey A. , Razin Sergey V. , Cabrera-Orefice Alfredo , Wittig Ilka , Pullamsetti Soni Savai , Kurian Leo , Gilsbach Ralf , Schulz Marcel H. , Dikic Ivan , Müller-McNicoll Michaela , Brandes Ralf P. , Leisegang Matthias S.
Published: January 2025

The coordination of chromatin remodeling is essential for DNA accessibility and gene expression control. The highly conserved and ubiquitously expressed SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex plays a central role in cell type- and context-dependent gene expression. Despite the absence of a defined DNA recognition motif, SWI/SNF binds lineage specific enhancers genome-wide where it actively maintains open chromatin state. It does so while retaining the ability to respond dynamically to cellular signals. However, the mechanisms that guide SWI/SNF to specific genomic targets have remained elusive. Here we demonstrate that trans-acting long non-coding RNAs (lncRNAs) direct the SWI/SNF complex to cell type-specific enhancers. SWI/SNF preferentially binds lncRNAs and these predominantly bind DNA targets in trans. Together they localize to enhancers, many of which are cell type-specific. Knockdown of SWI/SNF- and enhancer-bound lncRNAs causes the genome-wide redistribution of SWI/SNF away from enhancers and a concomitant differential expression of spatially connected target genes. These lncRNA-SWI/SNF-enhancer networks support an enhancer hub model of SWI/SNF genomic targeting. Our findings reveal that lncRNAs competitively recruit SWI/SNF, providing a specific and dynamic layer of control over chromatin accessibility, and reinforcing their role in mediating enhancer activity and gene expression.
Optical single-shot readout of spin qubits in silicon
Authors: Gritsch Andreas , Ulanowski Alexander , Pforr Jakob , Reiserer Andreas
Published: January 2025

Small registers of spin qubits in silicon can exhibit hour-long coherence times and exceeded error-correction thresholds. However, their connection to larger quantum processors is an outstanding challenge. To this end, spin qubits with optical interfaces offer key advantages: they can minimize the heat load and give access to modular quantum computing architectures that eliminate cross-talk and offer a large connectivity. Here, we implement such an efficient spin-photon interface based on erbium dopants in a nanophotonic resonator. We demonstrate optical single-shot readout of a spin in silicon whose coherence exceeds the Purcell-enhanced optical lifetime, paving the way for entangling remote spins via photon interference. As erbium dopants can emit coherent photons in the minimal-loss band of optical fibers, and tens of such qubits can be spectrally multiplexed in each resonator, the demonstrated hardware platform offers unique promise for distributed quantum information processing based on scalable, integrated silicon devices.
Dissipative Landau-Zener tunneling in the crossover regime from weak to strong environment coupling
Authors: Dai X. , Trappen R. , Chen H. , Melanson D. , Yurtalan M. A. , Tennant D. M. , Martinez A. J. , Tang Y. , Mozgunov E. , Gibson J. , Grover J. A. , Disseler S. M. , Basham J. I. , Novikov S. , Das R. , Melville A. J. , Niedzielski B. M. , Hirjibehedin C. F. , Serniak K. , Weber S. J. , Yoder J. L. , Oliver W. D. , Zick K. M. , Lidar D. A. , Lupascu A.
Published: January 2025

Landau-Zener tunneling, which describes the transition in a two-level system during a sweep through an anti-crossing, is a model applicable to a wide range of physical phenomena. Realistic quantum systems are affected by dissipation due to coupling to their environments. An important aspect of understanding such open quantum systems is the relative energy scales of the system itself and the system-environment coupling, which distinguishes the weak- and strong-coupling regimes. Using a tunable superconducting flux qubit, we observe the crossover from weak to strong coupling to the environment in Landau-Zener tunneling. Our results confirm previous theoretical studies of dissipative Landau-Zener tunneling in the weak and strong coupling limits. We devise a spin bath model that effectively captures the crossover regime. This work is relevant for understanding the role of dissipation in quantum annealing, where the system is expected to go through a cascade of Landau-Zener transitions before reaching the target state.
Characterizing cell-type spatial relationships across length scales in spatially resolved omics data
Authors: dos Santos Peixoto Rafael , Miller Brendan F. , Brusko Maigan A. , Aihara Gohta , Atta Lyla , Anant Manjari , Atkinson Mark A. , Brusko Todd M. , Wasserfall Clive H. , Fan Jean
Published: January 2025

Spatially resolved omics (SRO) technologies enable the identification of cell types while preserving their organization within tissues. Application of such technologies offers the opportunity to delineate cell-type spatial relationships, particularly across different length scales, and enhance our understanding of tissue organization and function. To quantify such multi-scale cell-type spatial relationships, we present CRAWDAD, Cell-type Relationship Analysis Workflow Done Across Distances, as an open-source R package. To demonstrate the utility of such multi-scale characterization, recapitulate expected cell-type spatial relationships, and evaluate against other cell-type spatial analyses, we apply CRAWDAD to various simulated and real SRO datasets of diverse tissues assayed by diverse SRO technologies. We further demonstrate how such multi-scale characterization enabled by CRAWDAD can be used to compare cell-type spatial relationships across multiple samples. Finally, we apply CRAWDAD to SRO datasets of the human spleen to identify consistent as well as patient and sample-specific cell-type spatial relationships. In general, we anticipate such multi-scale analysis of SRO data enabled by CRAWDAD will provide useful quantitative metrics to facilitate the identification, characterization, and comparison of cell-type spatial relationships across axes of interest.
Restoring small water bodies to improve lake and river water quality in China
Authors: Shen Wangzheng , Zhang Liang , Ury Emily A. , Li Sisi , Xia Biqing , Basu Nandita B.
Published: January 2025

Climate change, population growth, and agricultural intensification are increasing nitrogen (N) inputs, while driving the loss of inland water bodies that filter excess N. However, the interplay between N inputs and water body dynamics, and its implications for water quality remain poorly understood. Analyzing data from 1995 to 2015 across China, here, we find a 71% reduction in the area of small (<104.5 m2) water bodies (SWB), primarily in high-N-input agricultural regions. Preferential loss of SWBs, the most efficient nutrient filters, places 42% of China at high water quality risk due to increasing N inputs and declining SWB density. Currently, N removal by water bodies is 986 kilotonnes year−1, but restoring 2.3 million hectares of SWB could increase removal by 21%, compared to just 5% for equivalent restoration of large water bodies. Targeted SWB restoration is crucial for improving water quality and mitigating N pollution in China.
A review of displacement cascade simulations using molecular dynamics emphasizing interatomic potentials for TPBAR components
Authors: Roy Ankit , Nandipati Giridhar , Casella Andrew M. , Senor David J. , Devanathan Ram , Soulami Ayoub
Published: January 2025

This review explores molecular dynamics simulations for studying radiation damage in Tritium Producing Burnable Absorber Rod (TPBAR) materials, emphasizing the role of interatomic potentials in displacement cascades. Recent machine learning potentials (MLPs), trained on quantum data, enhance prediction accuracy over traditional models like EAM. We highlight temperature, PKA energy, and composition effects on damage evolution in TPBAR components, recommending suitable potentials and discussing advancements for materials in extreme radiation environments.
Tropical cyclone risk for global ecosystems in a changing climate
Authors: Kropf Chahan M. , Vaterlaus Lisa , Bresch David N. , Pellissier Loïc
Published: January 2025

Coastal ecosystems provide a range of services including erosion prevention, clean water provision and carbon sequestration. With climate change, the rapid change in frequency and intensity of tropical cyclones may alter the composition of the ecosystems themselves potentially degrading the services they provide. Here we classify global ecoregions into dependent, resilient and vulnerable and show that a combined 9.4% of the surface of all terrestrial ecosystems is susceptible to transformation due to cyclone pattern changes between 1980–2017 and 2015–2050 under climate scenario SSP5-8.5 using the STORM model. Even for the most resilient ecosystems already experiencing winds >60 m s−1 regularly, the average interval between two storms is projected to decrease from 19 to 12 years which is potentially close to their recovery time. Our study advocates for a shift in the consideration of the tropical cyclone impact from immediate damage to effects on long-term natural recovery cycles.
Ferrimagnetic Heusler tunnel junctions with fast spin-transfer torque switching enabled by low magnetization
Authors: Garg Chirag , Filippou Panagiotis Ch. , Ikhtiar  , Ferrante Yari , Yang See-Hun , Hughes Brian , Rettner Charles T. , Phung Timothy , Faleev Sergey , Topuria Teya , Samant Mahesh G. , Jeong Jaewoo , Parkin Stuart S. P.
Published: January 2025

Magnetic random-access memory that uses magnetic tunnel junction memory cells is a high-performance, non-volatile memory technology that goes beyond traditional charge-based memories. Today, its speed is limited by the high magnetization of the memory storage layer. Here we prepare magnetic tunnel junction memory devices with a low magnetization ferrimagnetic Heusler alloy Mn3Ge as the memory storage layer on technologically relevant amorphous substrates using a combination of a nitride seed layer and a chemical templating layer. We switch the magnetic state of the storage layer with nanosecond long write pulses at a reliable write error rate of 10−7 and detect a tunnelling magnetoresistance of 87% at ambient temperature. These results provide a strategy towards lower write switching currents using ferrimagnetic Heusler materials and, therefore, to the scaling of high-performance magnetic random-access memories beyond those nodes possible with ferromagnetic memory layers.
Single immunization with genetically attenuated Pf∆mei2 (GA2) parasites by mosquito bite in controlled human malaria infection: a placebo-controlled randomized trial
Authors: Roozen Geert V. T. , van Schuijlenburg Roos , Hensen Annefleur D. O. , Koopman Jan Pieter R. , Lamers Olivia A. C. , Geurten Fiona J. A. , Sijtsma Jeroen C. , Baalbergen Els , Janse Jacqueline J. , Chevalley-Maurel Séverine , Naar Chanel M. , Bezemer Sascha , Kroeze Hans , van de Stadt Huybert J. F. , de Visser Bram , Meij Pauline , Tihaya Mara S. , Colstrup Emil , Iliopoulou Eva , de Bes-Roeleveld Helena M. , Wessels Els , van der Stoep M. Y. Eileen C. , Janse Chris J. , Murugan Rajagopal , Franke-Fayard Blandine M. D. , Roestenberg Meta
Published: January 2025

Malaria vaccines consisting of metabolically active Plasmodium falciparum (Pf) sporozoites can offer improved protection compared with currently deployed subunit vaccines. In a previous study, we demonstrated the superior protective efficacy of a three-dose regimen of late-arresting genetically attenuated parasites administered by mosquito bite (GA2-MB) compared with early-arresting counterparts (GA1-MB) against a homologous controlled human malaria infection. Encouraged by these results, we explored the potency of a single GA2-MB immunization in a placebo-controlled randomized trial. Primary outcomes were safety and tolerability, time-to-parasitemia and protective efficacy. Humoral and cellular immunological results were considered secondary outcomes. Here we report the safe administration of GA2-MB with no breakthrough malaria and sterile protection in nine of ten participants at 6 weeks after a single immunization with 50 GA2-infected mosquitoes, compared with none of five mock-immunized participants, against a homologous controlled human malaria infection. Immunization increased circulating Pf-specific polyfunctional effector memory CD4+ T cells coexpressing tumor necrosis factor and interleukin-2. This unprecedented 90% protective efficacy after a single low-dose immunization holds great promise for the potency of GA2 immunization. Future studies should demonstrate whether GA2 is similarly efficacious in pre-exposed populations and whether the favorable safety profile reported here holds up in larger groups. ClinicalTrials.gov registration: NCT05468606.
Optimizing solar performance of CFTSe-based solar cells using MoSe2 as an innovative buffer layers
Authors: Moustafa Mohamed , Abu Waar Ziad , Yasin Shadi
Published: January 2025

In this study, we explore the photovoltaic performance of an innovative high efficiency heterostructure utilizing the quaternary semiconductor Cu2FeSnSe4 (CFTSe). This material features a kesterite symmetrical structure and is distinguished by its non-toxic nature and abundant presence in the earth’s crust. Utilizing the SCAPS simulator, we explore various electrical specifications such as short circuit current (Jsc), open circuit voltage (Voc), the fill factor (FF), and power conversion efficiency (PCE) were explored at a large range of thicknesses, and the acceptor carrier concentration doping (NA). Our results demonstrate that optimized parameters yield a remarkable PCE of 26.47%, accompanied by a Voc of 1.194 V, Jsc of 35.37 mA/cm2, and FF of 62.65% at a CFTSe absorber thickness of 0.5 μm. Furthermore, the performance of the photovoltaic cell is assessed for the defect levels in the CFTSe absorber and MoSe2 buffer layers. Results indicate that deep defect levels above 1 × 1017 cm− 3 lead to a decrease in Jsc. The study also investigates the effect of operating temperature on cell performance within the 300–500 K range. A notable decline in Voc is observed, likely due to an increase in saturation current, suggesting an interaction between temperature and cell behavior. In this work, we propose a practical CFTSe-based structure that replaces conventional buffer layers, such as CdS, with MoSe2 TMDC as a promising alternative buffer layer, paving the way for more sustainable solar technology.
Chitosan nanoencapsulation of Turbinaria triquetra metabolites in the management of podocyturia in nephrotoxic rats
Authors: Abdel-Aal Abdullah , F. Abdel-Aziz A. , El-khayat Zakaria , Mohamed Nadia , Rostom Merit , Tolba Emad , Galal El-Din Shams El-Din Nihal , Mettwally Walaa S. A. , Hamdy Abdelhamid Aly
Published: January 2025

Cisplatin is a chemotherapeutic drug, which exhibits undesirable side effects. Chitosan nanoparticles are promising for drug delivery. The aim of this study was to determine the effect of the brown alga Turbinaria triquetra ethyl acetate fraction and polysaccharides, either loaded on chitosan nanoparticles or free, against podocyturia and cisplatin nephrotoxicity in rats. Sixty-six male rats were distributed into 11 equal groups: untreated control, chitosan (CSNPs), ethyl acetate fraction (EAE), polysaccharide (PS), EAE loaded on chitosan nanoparticles (EAE-CSNPs), PS loaded on chitosan nanoparticles (PS-CSNPs), Cisplatin or cis-diamminedichloroplatinum(II) (CDDP), CDDP + EAE, CDDP + PS, CDDP + EAE-CSNPs, and CDDP + PS-CSNPs. Serum urea, creatinine, creatinine clearance, renal malondialdehyde, nitric oxide, paraoxonase 1, renal nephrin, and podocin, and their renal mRNA gene expressions, as well as urinary nephrin and podocin were determined. The results indicated that the ethyl acetate fraction and polysaccharides, either free or loaded, efficiently attenuated podocyturia and cisplatin nephrotoxicity compared to the Cis group. However, the improvement was higher in the nephrotoxic groups treated with EAE-CSNPs and PS-CSNPs. The current study revealed that chitosan nanoencapsulation showed ameliorative effects against podocyturia and cisplatin nephrotoxicity in rats compared to free extracts, offering a new therapeutic strategy for attenuating podocyturia and CDDP-induced nephrotoxicity.
Discovery of potent anti-toxoplasmosis drugs from secondary metabolites in Citrus limon (lemon) leaves, supported in-silico study
Authors: Mohammed Magdy Mostafa Desoky , Mohammed Hala Sh. , El Wafa Salwa A. Abu , Ahmed Doaa A. , Heikal Elham A. , Elgohary Islam , Barakat Ashraf M.
Published: January 2025

Toxoplasmosis induced by Toxoplasma gondii is a well-known health threat, that prompts fatal encephalitis increased with immunocompromised patients, in addition, it can cause chorioretinitis, microcephaly, stillbirth in the fetus and even led to death. Standard therapy uses sulfadiazine and pyrimethamine drugs revealed beneficial results during the acute stage, however, it has severe side effects. UPLC-ESI-MS/MS used to explore C. limon MeOH ext. constituents, which revealed a list of 41 metabolites of different classes encompasses; unsaturated fatty acid, tricarboxylic acids, phenolic aldehyde, phenolic acids, phenolic glycosides, coumarins, sesquiterpene lactone, limonoid, steroid and flavonoids. C. limon MeOH ext. and the isolates reduced significantly the number of T. gondii tachyzoites. Consequently, histopathological examination, proved significant reduction in the number of mononuclear inflammatory cells in the kidney and liver sections, besides, lowering the number of shrunken and degenerative neurons in the brain sections of infected mice. Molecular docking study was performed targeted certain receptors, which are important for the life cycle fundamentals for the parasite mobility including invasion and egress, and further molecular dynamics simulation was conducted to get insights into the structural changes of the formed complexes, along with a pharmacophoric mapping approach, that confirmed the need for a free hydroxyl group and/or a phenolic substituted one, in order to form HB, Hyd/Aro and ML interactions, through which, cell cycle disruption via iron chelation, could be achieved. In addition, the ADMIT properties of all identified metabolites were predicted.
Multiplication rate variation of malaria parasites from hospital cases and community infections
Authors: Stewart Lindsay B. , Escolar Elena Lantero , Philpott James , Claessens Antoine , Amambua-Ngwa Alfred , Conway David J.
Published: January 2025

The significance of multiplication rate variation in malaria parasites needs to be determined, particularly for Plasmodium falciparum, the species that causes most virulent infections. To investigate this, parasites from cases presenting to hospital in The Gambia and from local community infections were culture-established and then tested under exponential growth conditions in a standardised six-day multiplication rate assay. The multiplication rate distribution was lower than seen previously in clinical isolates from another area in West Africa where infection is more highly endemic. Multiplication rates were higher in cultured isolates derived from hospital cases (N = 23, mean = 2.9-fold per 48 h) than in those from community infections (N = 11, mean = 1.8-fold)(Mann-Whitney P < 0.001). There was a positive correlation between levels of parasitaemia in peripheral blood of sampled individuals and multiplication rates of the isolates in culture (Spearman’s rho = 0.45, P = 0.017). There was no significant difference between isolates containing single parasite genotypes or multiple genotypes at the time of assay, suggesting that parasites do not modify their multiplication rates in response to the presence of different genotypes. It will be important to uncover the mechanisms of this intrinsic multiplication rate variation, and to also investigate the epidemiological distribution and potential associations with infection phenotypes in other populations.
Exploring the structure and properties of $$\alpha$$-sheet based bilayer borophenes
Authors: Rakshit Subrata , Gonzalez Szwacki Nevill
Published: January 2025

Recent experimental realizations of bilayer boron materials motivated us to study the structure and properties of $$\alpha$$-sheet-based bilayer borophenes with interlayer covalent bonds. As shown here, at least three stacking variations are possible: AA, AB, and $$\hbox {AB}'$$. The on-top AA-stacking has been obtained experimentally supported on a metallic substrate. The AB-stacking is the most stable among neutral freestanding structures, whereas the AA and $$\hbox {AB}'$$ stacking sequences are very close in energy, both for neutral and negatively charged cases. The studied bilayer borophenes exhibit extraordinarily high electric conductivity with values as high as $${\sim } 10^7\mathrm {~S}/\textrm{m}$$ for the experimentally observed AA-stacking. The highly stable AB-stacking bilayer, reported here for the first time, exhibits an anisotropic conductivity with an average value of $$6.0 \times 10^6~\mathrm {~S}/\textrm{m}$$. Contrary to the AA-stacking bilayer that retains the 6-fold fold rotational symmetry of the $$\alpha$$-sheet, the AB-stacking structure has 2-fold symmetry, which leads to the anisotropic transport properties.
Exploring the causal impact of body mass index on metabolic biomarkers and cholelithiasis risk: a Mendelian randomization analysis
Authors: Zhao Feng , Yang Yanjiang , Yang Wenwen
Published: January 2025

Obesity is a well-established risk factor for various diseases, but the mechanisms through which it influences disease development remain unclear. Using Mendelian randomization (MR) analysis, we examined the causal relationship between BMI, 249 metabolic traits, and cholelithiasis. BMI data were obtained from four sources, and cholelithiasis data were from two distinct datasets. We analyzed the direct effect of BMI on cholelithiasis and identified key metabolic mediators. BMI was found to be positively associated with the risk of cholelithiasis across all datasets analyzed. A total of 176 metabolites were identified to be significantly associated with BMI, including amino acids, cholesterol esters, free cholesterol, triglycerides, and phospholipids. Among these, 49 metabolites were identified as mediators in the BMI-cholelithiasis relationship. Specifically, fatty acid levels, cholesteryl esters, phospholipids, triglycerides, and free cholesterol were key mediators in this relationship, with mediation proportions ranging from − 2.38–7.14%. This study provides robust evidence that BMI significantly impacts metabolic biomarkers, which in turn affect the risk of cholelithiasis. These findings highlight the importance of managing BMI to mitigate metabolic dysfunction and reduce the risk of gallstone formation. Future research should explore the specific metabolic pathways involved to identify potential therapeutic targets.
Serum inflammation-related proteins in a acute compartment syndrome rat model
Authors: Wang Tao , Cao Jingcheng , Hou Zhiyong , Zhang Qi
Published: January 2025

We aim to explore variations of serum inflammation-related proteins in an acute compartment syndrome (ACS) rat model. We collected serum from 25 healthy Sprague-Dawley rats (control group, CG) and 50 rats with tibial fractures, including 25 rats with ACS (ACS group, AG), and 25 rats without ACS (fracture group, FG). Ten samples per group were randomly chosen for proximity extension assay analysis of 92 inflammation-related proteins, and all samples were verified by enzyme-linked immunosorbent assays. Receiver-operating characteristic curve analysis was used to identify the diagnostic ability and cut-off values. Our findings showed that the levels of Il6 and Prdx5 in the FG and Il6, Prdx5, Dctn2, and Plin1 in the AG, were significantly higher than those in the CG. Notably, compared with the FG, high expression of Prdx5, Dctn2, and Plin1 was observed in the AG. Additionally, we identified 58.8764, 14.023, and 31.8730 pg/ml as the cut-off values of Prdx5, Dctn2, and Plin1 to predict ACS in rats. Similarly, the cut-off values of Il6, Prdx5, Dctn2, and Plin1 to predict ACS in healthy rats were 10.6783, 766.5879, 12.5627, and 14.3623 pg/ml, respectively. Furthermore, the combination of these proteins had the highest diagnostic accuracy. We identified Prdx5, Dctn2, and Plin1 as potential biomarkers of ACS compared with fracture in rats and revealed that combination of Il6, Prdx5, Dctn2, and Plin1 had the highest diagnostic accuracy to predict ACS compared with the healthy condition. Furthermore, the cut-off values for these biomarkers were determined, providing a new method to rapidly assess the risk of ACS and manage early targeted interventions.
The optimal neoadjuvant treatment strategy for HR+/HER2 + breast cancer: a network meta-analysis
Authors: Liu Shiwei , Yu Miao , Mou Exian , Wang Meihua , Liu Shuanghua , Xia Li , Li Hui , Tang Hao , Feng Yajing , Yu Xin , Mi Kun , Wang Hao
Published: January 2025

The efficacy of neoadjuvant therapy varies significantly with hormone receptor (HR) status for patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer (BC). Despite extensive research on HER2 + BC, the optimal neoadjuvant strategy for HR+/HER2 + BC remains inconclusive. This study aimed to identify the optimal neoadjuvant regimen for HR+/HER2 + BC treatment. We conducted a systematic search for trials comparing neoadjuvant regimens for HR+/HER2 + BC and a network meta-analysis. Odds ratios for pathological complete response (pCR) and hazard ratios for event-free survival (EFS) were calculated. Treatment regimens were ranked using the surface under the cumulative ranking curve. 20 trials with 2809 patients were included. In pCR analysis, three neoadjuvant regimens sequentially ranked at the top, namely those comprising T-DM1, pertuzumab with trastuzumab, and tyrosine kinase inhibitor with trastuzumab, demonstrating significantly higher pCR rates than monotherapies. In EFS analysis, pertuzumab with trastuzumab ranked the first while T-DM1 containing regimen ranked the last. Anthracycline-free regimens showed a marginally higher pCR rate than anthracycline-containing regimens, while carboplatin-containing regimens demonstrated a numerically higher pCR rate than carboplatin-free regimens. Significant heterogeneity was observed in endocrine therapy analysis, which may be caused by different strategies for incorporating endocrine therapy. In conclusion, trastuzumab plus pertuzumab stands out as the optimal neoadjuvant HER2-targeting regimen for HR+/HER2 + BC Furthermore, anthracycline-free carboplatin-containing chemotherapy emerges as a promising combination treatment. Further investigation is required to clarify the role of endocrine therapy in HR+/HER2 + BC to guide its clinical application.
Cows that are less active in the chute have more optimal grazing distribution
Authors: Creamer Maggie , Horback Kristina
Published: January 2025

Individual grazing patterns among cattle can contribute to sustainability of land use, however, little is known about the consistency of these grazing patterns. To address this knowledge gap, fifty Angus x Hereford cows were observed in repeated assays: A management assay (handling procedure, narrow chute, hydraulic squeeze), a social-feed trade-off assay (SFTA; choice between social mates and feed item), and novel approach assay (choice between social mates and feed item with novel pattern). The same cattle were tracked with GPS collars over two grazing seasons (June-August 2021 and 2022) and average grazing-related metrics (e.g., elevation used, distance traveled) were calculated within each season. Cows with a more passive response in the chute were found at higher elevation (p = 0.017), further from water (p = 0.043), and closer to supplement sites (p = 0.029). Cows that had higher latency to supplement in the SFTA traveled shorter distances on rangeland (p = 0.035). Thus, there was some evidence that cows with a more passive response to isolation and management had more optimal grazing patterns (grazed underutilized areas of the range at higher elevations and further from water sources). Selecting cattle with more optimal foraging patterns based on observable behaviors during handling and isolation could improve the sustainability of rangeland grazing.
Differential diagnosis of iron deficiency anemia from aplastic anemia using machine learning and explainable Artificial Intelligence utilizing blood attributes
Authors: Darshan B. S. Dhruva , Sampathila Niranjana , Bairy G. Muralidhar , Prabhu Srikanth , Belurkar Sushma , Chadaga Krishnaraj , Nandish S.
Published: January 2025

As per world health organization, Anemia is a most prevalent blood disorder all over the world. Reduced number of Red Blood Cells or decrease in the number of healthy red blood cells is considered as Anemia. This condition also leads to the decrease in the oxygen carrying capacity of the blood. The main goal of this research is to develop a dependable method for diagnosing Aplastic Anemia and Iron Deficiency Anemia by examining the blood test attributes. As of today, there are no studies which use Interpretable Artificial Intelligence to perform the above differential diagnosis. The dataset used in this study is collected from Kasturba Medical College, Manipal. The dataset consisted of various blood test attributes such as Red Blood cell count, Hemoglobin level, Mean Corpuscular Volume, etc. One of the trending topics in Machine Learning is Explainable Artificial Intelligence. They are known to demystify the machine learning outputs to all its stakeholders. Hence, Five XAI tools including SHAP, LIME, Eli5, Qlattice and Anchor are used to understand the model’s predictions. The importance characteristics according to XAI models are PLT, PCT, MCV, PDW, HGB, ABS LYMP, WBC, MCH, and MCHC. are employed to train and test the data. The goal of using data analytic techniques is to give medical professionals a useful tool that improves decision-making, enhances resource management, and eventually raises the standard of patient care. By considering the unique qualities of each patient, medical professionals who must rely on AI-assisted diagnosis and treatment suggestions, XAI offers arguments to strengthen their faith in the model outcomes.
Adaptive hip exoskeleton control using heart rate feedback reduces oxygen cost during ecological locomotion
Authors: Manzoori Ali Reza , Malatesta Davide , Mortier Alexandre , Garcia Johan , Ijspeert Auke , Bouri Mohamed
Published: January 2025

Despite their potential, exoskeletons have not reached widespread adoption in daily life, partly due to the challenge of seamlessly adapting assistance across various tasks and environments. Task-specific designs, reliance on complex sensing and extensive data-driven training often limit the practicality of the existing control strategies. To address this challenge, we introduce an adaptive control strategy for hip exoskeletons, emphasizing minimal sensing and ease of implementation. Using only insole pressure and heart rate (HR) sensing, the controller modulates assistance across various locomotor tasks. We evaluated this strategy with twelve able-bodied participants in a real-world scenario including level walking, stairs, and inclines. The controller successfully adapted assistance timing and amplitude to different activities. This resulted in effort intensity reductions (measured by oxygen uptake) of up to 12.6% compared to walking with no exoskeleton, and up to 25.5% compared to walking with the exoskeleton in zero-torque mode. Cardiodynamic response of HR, although delayed, proved sufficient for adaptation in tasks lasting longer than around 45 s, and delay-induced limitations primarily affected brief bouts of abrupt change in intensity. However, we found discernible patterns in HR shortly after the onset of such changes that can be exploited to improve responsiveness. Our findings underscore the potential of HR as a promising measure of user effort intensity, encouraging future research to explore its integration into advanced adaptive algorithms.
Preclinical evaluation of DC-CIK cells as potentially effective immunotherapy model for the treatment of glioblastoma
Authors: Lück Annika Simone , Pu Jingjing , Melhem Ahmad , Schneider Matthias , Sharma Amit , Schmidt-Wolf Ingo G. H. , Maciaczyk Jarek
Published: January 2025

Despite the favorable effects of immunotherapies in multiple types of cancers, its complete success in CNS malignancies remains challenging. Recently, a successful clinical trial of cytokine-induced killer (CIK) cell immunotherapy in patients with glioblastoma (GBM) has opened a new avenue for adoptive cellular immunotherapies in CNS malignancies. Prompt from these findings, herein, we investigated whether dendritic cells (DC) in combination with cytokine-induced killer cells (DC-CIK) could also provide an alternative and more effective way to improve the efficacy of GBM treatment. The analysis showed that DC-CIK cells exerted a significant cytotoxic effect on the glioblastoma cell lines, especially with the phenotype of stem-like cells (GSCs). In addition, the increased specific lysis of these cells subsequent to DC-CIK co-culture was confirmed with confocal fluorescence microscope. The direct interactions between tumor and effector cells were found to be highly effective in GBM organoids (GBOs). Moreover, a significant increase in apoptosis and elevated levels of IFN-γ (and not TNF-α) secretion were observed as a targeting mechanism of DC-CIK cells against GBM cell models. Overall, we provide important preliminary evidence that DC-CIK cells may have potential in the treatment of CNS malignancies, particularly glioblastoma.
Vitality insights of fish escaping from a sorting grid installed on a bottom trawl net
Authors: Petetta Andrea , Herrmann Bent , Li Veli Daniel , Canduci Giovanni , Tatone Ivan , Bonanomi Sara , De Santis Lorenzo Jacopo , Giuliani Giordano , Virgili Massimo , Carpentieri Paolo , Lucchetti Alessandro
Published: January 2025

Sorting grids to exclude the juveniles of species targeted by bottom trawl fisheries from the catch are among the most promising solutions to reduce discards. We tested a two-sections Juveniles’ Sorting Grid (JSG) in a Mediterranean fisheries restricted area. First, we provided information on the vitality of individuals escaping from the JSG bars during towing, by analysing underwater footage. Then, we evaluated the catch performance of the JSG-equipped trawl compared to a standard trawl by analysing both the full species community in the catches and the main commercial species. The probability for individuals to be alive while escaping from JSG was always higher than 65% (on average), with some species (e.g. red mullet, gurnards, 91–99% on average) showing significantly higher probability than others (e.g. European hake, crustaceans, 65–82% on average). The installation of a JSG in the trawl net did not change the overall catch composition in the codend, although significant differences were observed at the single species level. The JSG was effective at reducing undersized individuals of European hake, although a loss of legal-sized individuals was observed due to escapement. A significantly lower retention of the JSG-equipped trawl was also observed for other commercial species, such as deep-water rose shrimp and broadtail shortfin squid.
Heart-retina time analysis using electrocardiogram-coupled time-resolved dynamic optical coherence tomography
Authors: Valmaggia Philippe , Wolleb Julia , Bieder Florentin , Scholl Hendrik P. N. , Cattin Philippe C. , Maloca Peter M.
Published: January 2025

The eye and the heart are two closely interlinked organs, and many diseases affecting the cardiovascular system manifest in the eye. To contribute to the understanding of blood flow propagation towards the retina, we developed a method to acquire electrocardiogram (ECG) coupled time-resolved dynamic optical coherence tomography (OCT) images. This method allows for continuous synchronised monitoring of the cardiac cycle and retinal blood flow dynamics. The dynamic OCT measurements were used to calculate time-resolved blood flow profiles using fringe washout analysis. The relative fringe washout was computed to generate the flow velocity profiles within arterioles at the optic nerve head rim. We found that the blood column between the heart and the retina propagates within one cardiac cycle, denoting the arrival time as the heart-retina time (HRT). In a group of healthy subjects, the HRT was 144 ± 19 ms (mean ± SD). The HRT could provide a novel potential biomarker for cardiovascular health in direct relation to retinal perfusion.
Alendronate partially rescues the periodontal defects in OIM mouse model of osteogenesis imperfecta
Authors: Chen Po-Jung , Wang Ke , Lin Meng-Hsuan , Sharma Radhika , Kalajzic Zana , O’Brien Mara , Yadav Sumit
Published: January 2025

Osteogenesis imperfecta (OI) is a fairly common generalized connective disorder characterized by low bone mass, bone deformities and impaired bone quality that predisposes affected individuals to musculoskeletal fragility. Periodontal ligament (PDL)-alveolar bone and PDL-cementum entheses’ roles under OI conditions during physiological loading and orthodontic forces remain largely unknown. In addition, bisphosphonates (e.g., alendronate) are commonly used therapeutics for the treatment of OI. Our knowledge, in terms of the affects of alendronate treatment on the PDL entheses in OI is also far from complete. In this study, we identified craniofacial skeletal defects in an osteogenesis imperfecta (oim) murine model of OI. Relative to wild-type littermates, oim mice were found to have decreased skull length, cranial height/width/length, nose length, nasal length, and frontal length. Next, we discovered that oim mice exhibited defects in several dental structures, including short roots and decreased volumes of the alveolar bone, dentin, and cellular cementum. Further, we specifically investigated periodontal defects in the oim mice. Alveolar bone loss in oim mice was primarily associated with elevated bone resorption due to an increased osteoclast number, along with reduced bone formation related to increased sclerostin (SOST) expression. PDL fibers in oim mice were disrupted and discontinuous, while Sharpey’s fibers at the PDL-bone entheses were reduced. Mechanism-based studies showed that catabolism of the PDL was elevated in oim mice, as revealed by an increase in MMP13 and CTSK expression. Meanwhile, the quality of the collagen fibers were impaired in oim mice due to a large accumulation of uncleaved collagen I fibers. With alendronate treatment, however, we could partially rescue these phenotypes. This study, for the first time, characterized periodontal defects in oim mice, detailed craniofacial defects and demonstrated the effectiveness of alendronate in partially restoring these defects.
Point spread function estimation with computed wavefronts for deconvolution of hyperspectral imaging data
Authors: Zabic Miroslav , Reifenrath Michel , Wegner Charlie , Bethge Hans , Landes Timm , Rudorf Sophia , Heinemann Dag
Published: January 2025

Hyperspectral imaging (HSI) systems acquire images with spectral information over a wide range of wavelengths but are often affected by chromatic and other optical aberrations that degrade image quality. Deconvolution algorithms can improve the spatial resolution of HSI systems, yet retrieving the point spread function (PSF) is a crucial and challenging step. To address this challenge, we have developed a method for PSF estimation in HSI systems based on computed wavefronts. The proposed technique optimizes an image quality metric by modifying the shape of a computed wavefront using Zernike polynomials and subsequently calculating the corresponding PSFs for input into a deconvolution algorithm. This enables noise-free PSF estimation for the deconvolution of HSI data, leading to significantly improved spatial resolution and spatial co-registration of spectral channels over the entire wavelength range.
Common biomarkers of idiopathic pulmonary fibrosis and systemic sclerosis based on WGCNA and machine learning
Authors: Shan Ning , Shang Yu , He Yaowu , Wen Zhe , Ning Shangwei , Chen Hong
Published: January 2025

Interstitial lung disease (ILD) is known to be a major complication of systemic sclerosis (SSc) and a leading cause of death in SSc patients. As the most common type of ILD, the pathogenesis of idiopathic pulmonary fibrosis (IPF) has not been fully elucidated. In this study, weighted correlation network analysis (WGCNA), protein‒protein interaction, Kaplan–Meier curve, univariate Cox analysis and machine learning methods were used on datasets from the Gene Expression Omnibus database. CCL2 was identified as a common characteristic gene of IPF and SSc. The genes associated with CCL2 expression in both diseases were enriched mainly in chemokine-related pathways and lipid metabolism-related pathways according to Gene Set Enrichment Analysis. Single-cell RNA sequencing (sc-RNAseq) revealed a significant difference in CCL2 expression in alveolar epithelial type 1/2 cells, mast cells, ciliated cells, club cells, fibroblasts, M1/M2 macrophages, monocytes and plasma cells between IPF patients and healthy donors. Statistical analyses revealed that CCL2 was negatively correlated with lung function in IPF patients and decreased after mycophenolate mofetil (MMF) treatment in SSc patients. Finally, we identified CCL2 as a common biomarker from IPF and SSc, revealing the common mechanism of these two diseases and providing clues for the study of the treatment and mechanism of these two diseases.