julilili42/papers huggingface dataset:
Remarkably Efficient [4+4] Dimerization of [n]-Cyclacenes
2025-04-12

Cyclacenes with the general formula C4nH2n are cyclic analogs of acenes. Acenes are well-known for their high reactivity, which increases with the number of fused benzene rings. The cyclic strain, absence of a Clar sextet, and diradical or polyradical nature are expected to render cyclacenes highly reactive under ambient conditions. Their primary decomposition pathway is anticipated to involve dimerization or polymerization. We explore the reaction pathway of the [π4s + π4s] dimerization of [n]-cyclacenes for 6 ≤ n ≤ 20 by density functional theory (DFT) using spin-unrestricted and thermally-assisted-occupation (TAO) formalisms. Computational analysis predicts a stepwise reaction mechanism that starts with the formation of a van der Waals complex and proceeds through a transition state to an intermediate with a single new C–C bond and two unsaturated valences. A subsequent second transition state results in the formation of the dimerization product. However, for smaller cyclacenes (n &lt; 10), neither the van der Waals complex nor the first transition state is involved, and the intermediate is formed without a barrier. The largest [20]-cyclacene investigated exhibits the highest barriers for these processes. However, with a barrier as low as 3.9 kcal/mol at the UB3LYP-D3(BJ)/6-31G(d) level of theory, dimerization is anticipated to occur very rapidly.
Surface Water Monitoring with Sedimentation Boxes: Assessing the Sampling Performance and Its Effect on Microplastic Concentration
2025-04-12

Currently, there are still no harmonized and thus reproducible methods for microplastics (MP) sampling. Infrequent spot sampling with, e.g., nets, pumps, or containers, does not reflect the large spatial and temporal variety of MP abundance, and there is little experience with time-integrated, passive sampling methods. However, passive samplers have been applied thoroughly to recover suspended particulate matter (SPM) from water bodies. The physical and chemical characteristics of MP are in range with those of other materials belonging to SPM, and we state that MP are an integral component of SPM. In general, passive samplers like the sedimentation box decrease the flow velocity, enhancing the sedimentation of SPM within the device. The retention rates of particles in sedimentation boxes depend on various factors such as the flow velocity, the SPM size and density, but precise information remains scarce. Therefore, we performed laboratory tests to assess the retention rates of the polymers polystyrene and polyethylene and analyzed the dependency of sedimentation on the flow velocity and particle sizes. The quantification of MP in samples collected by sedimentation boxes underestimates the concentration of smaller-sized particles due to their lower retention rate, and MP concentrations should be reported accordingly. Subsequently, we carried out a series of field experiments with sedimentation boxes and showed that MP can be retained from different water bodies with diverse characteristics. Due to their robust sampling mechanism, sedimentation boxes are promising devices for time-integrated, long-term sampling of MP.
Design and In Vivo Evaluation of an Intraocular Electrode for Ciliary Muscle Biopotential Measurement in a Non-Human Primate Model of Human Accommodation
2025-04-13

The measurement of electrical potentials in the human body is becoming increasingly important in healthcare as a valuable diagnostic parameter. In ophthalmology, while these signals are primarily used to assess retinal function, other applications, such as recording accommodation-related biopotentials from the ciliary muscle, remain poorly understood. Here, we present the development and evaluation of a novel implantable ring electrode for recording biopotentials from the ciliary muscle. Inspired by capsular tension rings, the electrode was fabricated using laser cutting, wiring, and physical vapor deposition coating. The constant impedance and weight over a simulated aging period of 391 days, demonstrated the electrode’s stability. In vivo testing in non-human primates further validated the electrode’s surgical handling and long-term stability, with no delamination or tissue ingrowth after 100 days of implantation. Recorded biopotentials from the ciliary muscle (up to 700 μV) exceeded amplitudes reported in the literature. While the results are promising, further research is needed to investigate the signal quality and origin as well as the correlation between these signals and ciliary muscle activity. Ultimately, this electrode will be used in an implanted device to record ciliary muscle biopotentials to control an artificial lens designed to restore accommodation in individuals with presbyopia.
Machine learning models for pharmacogenomic variant effect predictions – recent developments and future frontiers
2025-04-13

Pharmacogenomic variations in genes involved in drug disposition and in drug targets is a major determinant of inter-individual differences in drug response and toxicity. While the effects of common variants are well established, millions of rare variations remain functionally uncharacterized, posing a challenge for the implementation of precision medicine. Recent advances in machine learning (ML) have significantly enhanced the prediction of variant effects by considering DNA as well as protein sequences, as well as their evolutionary conservation and haplotype structures. Emerging deep learning models utilize techniques to capture evolutionary conservation and biophysical properties, and ensemble approaches that integrate multiple predictive models exhibit increased accuracy, robustness, and interpretability. This review explores the current landscape of ML-based variant effect predictors. We discuss key methodological differences and highlight their strengths and limitations for pharmacogenomic applications. We furthermore discuss emerging methodologies for the prediction of substrate-specificity and for consideration of variant epistasis. Combined, these tools improve the functional effect prediction of drug-related variants and offer a viable strategy that could in the foreseeable future translate comprehensive genomic information into pharmacogenetic recommendations.
Impact of alcohol consumption on outcomes and potential of immune biomarkers for postoperative complications in trauma patients
2025-04-14

Introduction Alcohol consumption is a significant risk factor for adverse outcomes in trauma patients. Despite this, effective predictive biomarkers for postoperative complications remain elusive. This study aims to identify potential immune system biomarkers associated with postoperative complications in trauma patients with a history of chronic alcohol consumption. Methods A prospective cohort study was conducted on trauma patients admitted to a level 1 Trauma Center. Chronic alcohol consumption and drinking habits were assessed using the Alcohol Use Disorders Identification Test (AUDIT-C) questionnaire. Specifically, 26% of patients reported no alcohol consumption, 44% reported moderate alcohol consumption, and 30% were identified as having risky alcohol consumption. Acute systemic alcohol levels at the time of injury were not measured or considered in this study, as the focus was on chronic consumption patterns. Routine blood screening data were analyzed. Results Except for CRP, blood values were comparable between patients with risky alcohol consumption and controls. However, CRP’s ability to predict complications in patients with risky alcohol consumption remained limited (ROC-AUC = 0.6288). In order to identify other predictive markers, patients were matched based on relevant covariates in further analyses. Cytokine Array screening identified CD28, B7-1, Eotaxin-3, TIMP-1, and IL-13 as potential markers to predict complications. Verification with ELISA, however, showed that potential differences could only be detected in the control group. The discrepancies observed between cytokine array and ELISA results can be best explained by methodological differences, particularly since the serum samples were pooled for initial target screening. Additionally, variations in assay sensitivity, dynamic range, and calibration protocols contribute to these discrepancies. Discussion These findings suggest that chronic alcohol consumption alters cytokine responses, posing challenges for identifying reliable immune biomarkers for postoperative complications. Future studies should explore alternative approaches for biomarker validation and consider individualized assessment strategies for trauma patients with alcohol consumption history.
Genome-wide association meta-analyses of drug-resistant epilepsy
2025-04-15

This work is part of the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 279062 (EpiPGX) and the Centers for Common Disease Genomics (CCDG) program, funded by the National Human Genome Research Institute (NHGRI) and the National Heart, Lung, and Blood Institute (NHLBI).
Cross‐Sectional Brain Age Assessments Are Limited in Predicting Future Brain Change
2025-04-15

ABSTRACT The concept of brain age (BA) describes an integrative imaging marker of brain health, often suggested to reflect aging processes. However, the degree to which cross‐sectional MRI features, including BA, reflect past, ongoing, and future brain changes across different tissue types from macro‐ to microstructure remains controversial. Here, we use multimodal imaging data of 39,325 UK Biobank participants, aged 44–82 years at baseline and 2,520 follow‐ups within 1.12–6.90 years to examine BA changes and their relationship to anatomical brain changes. We find insufficient evidence to conclude that BA reflects the rate of brain aging. However, modality‐specific differences in brain ages reflect the state of the brain, highlighting diffusion and multimodal MRI brain age as potentially useful cross‐sectional markers.
Contribution of arbuscular mycorrhiza and exoenzymes to nitrogen acquisition of sorghum under drought
2025-04-15

Introduction For low-fertile and degraded soils of sub-Saharan Africa, nitrogen (N) is often the most growth-limiting factor restricting crop yields. The often-suggested exploitation of advantageous rhizosphere traits such as enzyme secretion and/or the symbiosis with arbuscular mycorrhizal fungi (AMF) remains to be validated as a potential strategy to overcome N limitation, especially when N deficiency co-occurs with further abiotic stresses such as water scarcity. Methods Three sorghum genotypes were cultivated in soil mesocosms with a root-exclusion compartment, where only AMF could scavenge for nutrients under drought and optimal conditions. Plant carbon (C) investment into the rhizosphere and N uptake were tracked by 15 N application coupled with 13 CO 2 labeling Results Under drought, uptake of mineral 15 N by AMF from the root-exclusion compartment increased 4–12 times compared to well-watered conditions. In addition, water stress enhanced below-ground allocation of recently assimilated C into microbial biomass. Drought reduced the enzymatic potential (Vmax) of chitinase while increasing leucine aminopeptidase (LAP) activity. This suggests that N acquisition via protein mineralization in soil was relatively enhanced compared to that of chitin following moisture limitation. LAP substrate affinity (Km) was reduced by drought compared to that of chitinase with genotype-specific shifts in the rhizosphere enzyme systems observed. Conclusion Our findings suggest that below-ground C allocation activated AMF symbiosis and its associated microbiome. This not only led to a shift in enzyme-driven exploitation of distinct organic N sources but also induced a strong increase in AMF-based mineral N acquisition from the mycosphere. This trait plasticity in response to drought may be harnessed to stabilize food production from low-fertile soil under the increasingly negative impacts of droughts due to climate change.
Dual Nickel/Titanium Catalyzed Cross‐Electrophile Coupling of Thioesters with Benzylic Alcohols
2025-04-15

Abstract This work focuses on the development of a new method for ketone synthesis via cross electrophile coupling (XEC) starting from widely available and low‐cost reagents. We demonstrate the XEC of benzylic alcohols and thioesters under reductive conditions and in the presence of trimethylsilyl chloride (TMSCl) using a dual catalytic system consisting of an air‐stable nickel pre‐catalyst and titanocene dichloride. The reaction shows a strong dependence on substituents of both substrates. It was found that an electron‐withdrawing group on the thiol moiety of thioester is necessary to reduce by‐product formation. In contrast, electron‐donating substituents are required on the benzylic alcohol for a successful XEC. Mechanistic investigations indicate that TMSCl is presumably necessary for the in situ activation of alcohol via benzyl chloride formation. This electrophile more readily forms the benzyl radical that was captured in radical trapping experiments. Additionally, the involvement of an organomanganese or a silylether species was excluded.
Genomic analysis of carbapenemase-encoding plasmids and antibiotic resistance in carbapenem-resistant Klebsiella pneumoniae isolates from Vietnam, 2021
2025-04-15

ABSTRACT Carbapenem resistance in gram-negative rods is increasing in low- and middle-income countries. We conducted a single-center study to identify carbapenemase-encoding plasmids in carbapenem-resistant Klebsiella pneumoniae isolates causing human infections in Vietnam. The secondary objective was to investigate the prevalence of multidrug-resistant (MDR) and hypervirulent K. pneumoniae in this setting. Our genomic analysis study characterized 105 of 245 clinical K. pneumoniae isolates at the 108 Military Hospital in Hanoi, Vietnam, collected from intensive care unit and regular wards between 1 January 2021 and 31 December 2021. All isolates were characterized using long- and short-read sequencing, followed by hybrid assembly. Comprehensive genomic analysis was performed to identify carbapenemase-encoding plasmids, complemented by extended antibiotic susceptibility testing for commonly used and novel antibiotics. We observed a high prevalence of NDM-4-related carbapenem resistance (30.5%, 32/105) mostly carried by a specific 83-kb IncFII plasmid co-carrying the bla TEM-1 (46.9%, 15/32). The genomic content of the bla NDM-4 -harboring plasmids is highly variable. While bla OXA-181 and bla OXA-48 were predominantly located on an IncX3 and an IncL plasmid, respectively, the majority of plasmids harboring bla KPC-2 were not related to any named Inc-type. All isolates exhibited the MDR phenotype; however, the majority remained susceptible to the siderophore-cephalosporin cefiderocol (79%, 83/105). All isolates were susceptible to aztreonam/avibactam. In addition, we identified a hypervirulent, carbapenem-resistant K. pneumoniae ST23 strain, confirmed through both in vitro and in vivo experiments. Our study provides insights into plasmids harboring the carbapenemases New Delhi metallo-β-lactamase, oxacillinase-48 like, and K. pneumoniae carbapenemase-2 circulating in Vietnam. IMPORTANCE Carbapenem resistance in Klebsiella pneumoniae is a major public health threat, especially in low- and middle-income countries. This study examined resistant strains from a hospital in Vietnam to understand how they spread and which antibiotics might still work. We found that a significant number of these bacteria carried resistance genes on different types of plasmids. Despite their resistance to many antibiotics, most strains remained susceptible to newer substances like cefiderocol and aztreonam/avibactam. Alarmingly, we also identified a hypervirulent strain that is carbapenem resistant, potentially posing an even greater risk to patients. This research provides insight into the epidemiology of the carbapenemase gene-harboring plasmids in a Vietnamese hospital. Understanding these resistance patterns can help guide antibiotic use and policy decisions to combat the growing threat of multidrug-resistant infections in Vietnam.
Neural signatures of model-based and model-free reinforcement learning across prefrontal cortex and striatum
2025-04-15

Abstract Animals integrate knowledge about how the state of the environment evolves to choose actions that maximise reward. Such goal-directed behaviour - or model-based (MB) reinforcement learning (RL) - can flexibly adapt choice to changes, being thus distinct from simpler habitual - or model-free (MF) RL - strategies. Previous inactivation and neuroimaging work implicates prefrontal cortex (PFC) and the caudate striatal region in MB-RL; however, details are scarce about its implementation at the single-neuron level. Here, we recorded from two PFC regions – the dorsal anterior cingulate cortex (ACC) and dorsolateral PFC (DLPFC), and two striatal regions, caudate and putamen – while two rhesus macaques performed a sequential decision-making (two-step) task in which MB-RL involves knowledge about the statistics of reward and state transitions. All four regions, but particularly the ACC, encoded the rewards received and tracked the probabilistic state transitions that occurred. However, ACC (and to a lesser extent caudate) encoded the key variables of the task - namely the interaction between reward, transition and choice – which underlies MB decision-making. ACC and caudate neurons also encoded MB-derived estimates of choice values. Moreover, caudate value estimates of the choice options flipped when a rare transition occurred, demonstrating value update based on structural knowledge of the task. The striatal regions were unique (relative to PFC) in encoding the current and previous rewards with opposing polarities, reminiscent of dopaminergic neurons, and indicative of a MF prediction error. Our findings provide a deeper understanding of selective and temporally dissociable neural mechanisms underlying goal-directed behaviour.
Highly Ordered Single Domain Peri-Tetracene Monolayers on Ag(110)
2025-04-15

The on-surface reaction of 1,1'-bitetracene (Bi4A) to <i>peri</i>-tetracene (tetrabenzo[bc,ef,kl,no]coronene) (4-PA) on Cu(110) and Ag(110) is studied by photoemission, scanning tunneling microscopy (STM) and low energy electron diffraction (LEED). Density functional theory (DFT) computations suggest that the Ag(110) substrate is well suited for the formation of large-area 4-PA monolayers with a preferential adsorption alignment of 4-PA molecules along the [11̅0] direction. The experiments confirm the formation of 4-PA and presence of large highly ordered 4-PA domains. Two distinct phases emerge, growing seamlessly over large areas and even spanning step edges. Evidence for charge transfer from the substrate to the molecule was found, resulting in a filling of the lowest unoccupied molecular orbital (LUMO) of 4-PA.
Salamandamide Lipodipeptides Are Biosynthetic Intermediate Shunt Products of the Nonamodular Nonribosomal Peptide Assembly Lines of the Viscosin Family
2025-04-15

Chemical investigation of a salamander-mucus-associated <i>Pseudomonas tolaasii</i> strain led to the isolation and chemical characterization of salamandamide A, a new lipo-dipeptide, along with known lipopeptides of the pseudodesmin and tolaasin class. Genome mining revealed that no specific gene cluster codes for the biosynthesis of salamandamide A. Stereochemical analyses and mutagenesis experiments linked the biosynthesis of the lipo-dipeptide salamandamide A to the NRPS gene cluster of the lipo-nonapeptide pseudodesmin. Further chemical investigations showed that this finding appears to be a broader concept and that all nonamodular NRPS gene clusters of the viscosin family were capable to produce, beside the expected lipo-nonapeptide, the corresponding lipo-dipeptide as a shunt product which also led to the discovery of salamandamide B from <i>Pseudomonas lactis</i> SS101.
Functional 31P Magnetic Resonance Spectroscopy at 9.4 T
2025-04-15

ABSTRACT Functional 31 P MRS might give valuable information on the energy metabolism of the brain during stimulation. However, the tiny expected spectral changes are difficult to detect due to low SNR and large voxel sizes. Higher field strengths and sensitive multielement arrays could help to investigate the energy metabolism during brain activation. Here, we acquired functional 31 P MRS data during visual stimulation at 9.4 T using a 27‐element receive array and an optimized 3D‐CSI protocol. First, T 1 values at that field strength were measured, confirming a decrease in T 1 times for increasing fields. Then, a 4.5 min visual stimulus with varying color scheme and frequency was presented to healthy subjects during CSI acquisition for 45 min. Stimulus and rest signals were formed by averaging over five epochs, resulting in spectra with high spectral quality and SNR. Stimulus and rest spectra were almost identical, except for a very small but significant difference in the chemical shift of inorganic phosphate, which might indicate a slight increase in pH during stimulation. It was then investigated whether postprocessing algorithms might be able to detect more subtle changes. Spectral denoising using a principal component approach resulted in improved SNR with high spectral integrity but suppressed the chemical shift difference. Spatial deconvolution improved the spatial resolution but did not yield changes in the outcome. Those results indicate that only very subtle changes in the 31 P spectrum due to visual stimulation can be expected, which are difficult to detect even when taking advantage of the high SNR and spectral dispersion at 9.4 T.
Introducing “Validated entheses-Based reconstruction of activity 2.0” (VERA 2.0): Semi-automated 3D analysis of bone surface changes
2025-04-16

In archaeological sciences, the macroscopic morphology of distinct dry bone structures, such as tubercles, ridges, epicondyles, and fossae, is routinely used to infer habitual activity patterns in past human populations, extinct hominins, and other animals. This study introduces “Validated Entheses-based Reconstruction of Activity 2.0” (VERA 2.0), a new method for precisely quantifying 3D surface irregularities on enthesis-bearing bone structures. Building on VERA 1.0, first introduced by the same author in 2016 and later named in a 2021 literature review, VERA 2.0 enhances the previous approach by incorporating a semi-automated image segmentation technique that reduces manual input while maintaining accuracy. The method involves selecting a predefined broad bone surface region, after which an algorithm automatically detects subtle surface irregularities (see example video in the step-by-step protocol at dx.doi.org/10.17504/protocols.io.5jyl82z8dl2w/v3 ). Validation analyses confirm VERA 2.0’s precision and reliability for activity reconstruction through intra- and inter-observer repeatability tests, experimental research comparing activity and control laboratory specimens, and analyses of historical human skeletons with extensively detailed long-term occupational data. Moreover, while this anthropological 3D measuring protocol paper cannot and does not aim to analyze the anatomical and histological nature of bone surface irregularities, preliminary anatomical dissection and virtual analysis of a cadaveric thumb enthesis suggest a possible association with attaching muscles and ligaments. Future anatomical and histological research aiming to explore soft-hard tissue interactions could clarify how these identified surface changes exactly relate to the attaching tissues. Overall, VERA 2.0 provides a robust, efficient quantitative tool for inferring activity patterns from skeletal remains, with applications across paleontological, paleoanthropological, and bioarchaeological contexts.