bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enabling target-aware molecule generation to follow multi objectives with Pareto MCTS
Authors: Yang Yaodong , Chen Guangyong , Li Jinpeng , Li Junyou , Zhang Odin , Zhang Xujun , Li Lanqing , Hao Jianye , Wang Ercheng , Heng Pheng-Ann 
Published: September 2024

AbstractTarget-aware drug discovery has greatly accelerated the drug discovery process to design small-molecule ligands with high binding affinity to disease-related protein targets. Conditioned on targeted proteins, previous works utilize various kinds of deep generative models and have shown great potential in generating molecules with strong protein-ligand binding interactions. However, beyond binding affinity, effective drug molecules must manifest other essential properties such as high drug-likeness, which are not explicitly addressed by current target-aware generative methods. In this article, aiming to bridge the gap of multi-objective target-aware molecule generation in the field of deep learning-based drug discovery, we propose ParetoDrug, a Pareto Monte Carlo Tree Search (MCTS) generation algorithm. ParetoDrug searches molecules on the Pareto Front in chemical space using MCTS to enable synchronous optimization of multiple properties. Specifically, ParetoDrug utilizes pretrained atom-by-atom autoregressive generative models for the exploration guidance to desired molecules during MCTS searching. Besides, when selecting the next atom symbol, a scheme named ParetoPUCT is proposed to balance exploration and exploitation. Benchmark experiments and case studies demonstrate that ParetoDrug is highly effective in traversing the large and complex chemical space to discover novel compounds with satisfactory binding affinities and drug-like properties for various multi-objective target-aware drug discovery tasks.
Unforeseen advantage of looser focusing in vacuum laser acceleration
Authors: De Andres Aitor , Bhadoria Shikha , Marmolejo Javier Tello , Muschet Alexander , Fischer Peter , Reza Barzegar Hamid , Blackburn Thomas , Gonoskov Arkady , Hanstorp Dag , Marklund Mattias , Veisz Laszlo 
Published: September 2024

AbstractAcceleration of electrons in vacuum directly by intense laser fields holds great promise for the generation of high-charge, ultrashort, relativistic electron bunches. While the energy gain is expected to be higher with tighter focusing, this does not account for the reduced acceleration range, which is limited by diffraction. Here, we present the results of an experimental investigation that exposed nanotips to relativistic few-cycle laser pulses. We demonstrate the vacuum laser acceleration of electron beams with 100s pC charge and 15 MeV energy. Two different focusing geometries, with normalized vector potential a0 of 9.8 and 3.8, produced comparable overall charge and electron spectra, despite a factor of almost ten difference in peak intensity. Our results are in good agreement with 3D particle-in-cell simulations, which indicate the importance of dephasing.
Robust future projections of global spatial distribution of major tropical cyclones and sea level pressure gradients
Authors: Murakami Hiroyuki , Cooke William F. , Mizuta Ryo , Endo Hirokazu , Yoshida Kohei , Wang Shuai , Hsu Pang-Chi 
Published: September 2024

AbstractDespite the profound societal impacts of intense tropical cyclones (TCs), prediction of future changes in their regional occurrence remains challenging owing to climate model limitations and to the infrequent occurrence of such TCs. Here we reveal projected changes in the frequency of major TC occurrence (i.e., maximum sustained wind speed: ≥ 50 m s−1) on the regional scale. Two independent high-resolution climate models projected similar changes in major TC occurrence. Their spatial patterns highlight an increase in the Central Pacific and a reduction in occurrence in the Southern Hemisphere—likely attributable to anthropogenic climate change. Furthermore, this study suggests that major TCs can modify large-scale sea-level pressure fields, potentially leading to the abrupt onset of strong wind speeds even when the storm centers are thousands of kilometers away. This study highlights the amplified risk of storm-related hazards, specifically in the Central Pacific, even when major TCs are far from the populated regions.
Large area kidney imaging for pre-transplant evaluation using real-time robotic optical coherence tomography
Authors: Ma Xihan , Moradi Mousa , Ma Xiaoyu , Tang Qinggong , Levi Moshe , Chen Yu , Zhang Haichong K. 
Published: September 2024

AbstractOptical coherence tomography (OCT) can be used to image microstructures of human kidneys. However, current OCT probes exhibit inadequate field-of-view, leading to potentially biased kidney assessment. Here we present a robotic OCT system where the probe is integrated to a robot manipulator, enabling wider area (covers an area of 106.39 mm by 37.70 mm) spatially-resolved imaging. Our system comprehensively scans the kidney surface at the optimal altitude with preoperative path planning and OCT image-based feedback control scheme. It further parameterizes and visualizes microstructures of large area. We verified the system positioning accuracy on a phantom as 0.0762 ± 0.0727 mm and showed the clinical feasibility by scanning ex vivo kidneys. The parameterization reveals vasculatures beneath the kidney surface. Quantification on the proximal convoluted tubule of a human kidney yields clinical-relevant information. The system promises to assess kidney viability for transplantation after collecting a vast amount of whole-organ parameterization and patient outcomes data.
Upwind moisture supply increases risk to water security
Authors: Posada-Marín José , Salazar Juan , Rulli Maria Cristina , Wang-Erlandsson Lan , Jaramillo Fernando 
Published: September 2024

AbstractTransboundary assessments of water security typically adopt an ‘upstream’ perspective, focusing on hazards and vulnerabilities occurring within a given hydrological basin. However, as the moisture that provides precipitation in the hydrological basin probably originates ‘upwind’, hazards and vulnerabilities potentially altering the moisture supply can be overlooked. Here we perform a global assessment of risk to water security in 379 hydrological basins accounting for upwind vulnerabilities and hazards from limited governance and environmental performance. We compare this upwind assessment with the more conventional approach focusing upstream. We find that accounting for upwind moisture supply increases the assessed risk to water security. The upwind perspective results in 32,900 km3 yr−1 of water requirements (that is, the specific water needs of vegetation for their development) under very high risk, compared with 20,500 km3 yr−1 under the upstream perspective. This study pinpoints the need to account for upwind moisture dependencies in global water-related risk assessments.
Stalled ribosome rescue factors exert different roles depending on types of antibiotics in Escherichia coli
Authors: Mikami Mayu , Shimizu Hidehiko , Iwama Norika , Yajima Mihono , Kuwasako Kanako , Ogura Yoshitoshi , Himeno Hyouta , Kurita Daisuke , Nameki Nobukazu 
Published: September 2024

AbstractEscherichia coli possesses three stalled-ribosome rescue factors, tmRNA·SmpB (primary factor), ArfA (alternative factor to tmRNA·SmpB), and ArfB. Here, we examined the susceptibility of rescue factor-deficient strains from E. coli SE15 to various ribosome-targeting antibiotics. Aminoglycosides specifically decreased the growth of the ΔssrA (tmRNA gene) strain, in which the levels of reactive oxygen species were elevated. The decrease in growth of ΔssrA could not be complemented by plasmid-borne expression of arfA, arfB, or ssrAAA to DD mutant gene possessing a proteolysis-resistant tag sequence. These results highlight the significance of tmRNA·SmpB-mediated proteolysis during growth under aminoglycoside stress. In contrast, tetracyclines or amphenicols decreased the growth of the ΔarfA strain despite the presence of tmRNA·SmpB. Quantitative RT-PCR revealed that tetracyclines and amphenicols, but not aminoglycosides, considerably induced mRNA expression of arfA. These findings indicate that tmRNA·SmpB, and ArfA exert differing functions during stalled-ribosome rescue depending on the type of ribosome-targeting antibiotic.
Quantitative microbiology with widefield microscopy: navigating optical artefacts for accurate interpretations
Authors: Hardo Georgeos , Li Ruizhe , Bakshi Somenath 
Published: September 2024

AbstractTime-resolved live-cell imaging using widefield microscopy is instrumental in quantitative microbiology research. It allows researchers to track and measure the size, shape, and content of individual microbial cells over time. However, the small size of microbial cells poses a significant challenge in interpreting image data, as their dimensions approache that of the microscope’s depth of field, and they begin to experience significant diffraction effects. As a result, 2D widefield images of microbial cells contain projected 3D information, blurred by the 3D point spread function. In this study, we employed simulations and targeted experiments to investigate the impact of diffraction and projection on our ability to quantify the size and content of microbial cells from 2D microscopic images. This study points to some new and often unconsidered artefacts resulting from the interplay of projection and diffraction effects, within the context of quantitative microbiology. These artefacts introduce substantial errors and biases in size, fluorescence quantification, and even single-molecule counting, making the elimination of these errors a complex task. Awareness of these artefacts is crucial for designing strategies to accurately interpret micrographs of microbes. To address this, we present new experimental designs and machine learning-based analysis methods that account for these effects, resulting in accurate quantification of microbiological processes.
Spin and orbital magnetism by light in rutile altermagnets
Authors: Adamantopoulos Theodoros , Merte Maximilian , Freimuth Frank , Go Dongwook , Zhang Lishu , Ležaić Marjana , Feng Wanxiang , Yao Yugui , Sinova Jairo , Šmejkal Libor , Blügel Stefan , Mokrousov Yuriy 
Published: September 2024

AbstractWhile the understanding of altermagnetism is still at a very early stage, it is expected to play a role in various fields of condensed matter research, for example spintronics, caloritronics and superconductivity. In the field of optical magnetism, it is still unclear to which extent altermagnets as a class can exhibit a distinct behavior. Here we choose RuO2, a prototype metallic altermagnet with a giant spin splitting, and CoF2, an experimentally known insulating altermagnet, to study the light-induced magnetism in rutile altermagnets from first-principles. We demonstrate that in the non-relativisic limit the allowed sublattice-resolved orbital response exhibits symmetries, imposed by altermagnetism, which lead to a drastic canting of light-induced moments. On the other hand, we find that inclusion of spin-orbit interaction enhances the overall effect drastically, introduces a significant anisotropy with respect to the light polarization and strongly suppresses the canting of induced moments. Remarkably, we observe that the moments induced by linearly-polarized laser pulses in light altermagnets can even exceed in magnitude those predicted for heavy ferromagnets exposed to circularly polarized light. By resorting to microscopic tools we interpret our results in terms of the altermagnetic spin splittings and of their reciprocal space distribution. Based on our findings, we speculate that optical excitations may provide a unique tool to switch and probe the magnetic state of rutile altermagnets.
REV-ERBα agonist SR10067 attenuates Th2 cytokine-mediated barrier dysfunction in human bronchial epithelial cells
Authors: Duraisamy Santhosh Kumar , Sundar Isaac Kirubakaran 
Published: September 2024

Abstract
Allergens and Th2 cytokines affect the homeostatic environment in the airways, leading to increased mucus production by goblet cells associated with altered adherens junctional complex (AJC) and tight junction (TJ) proteins responsible for maintaining epithelial barrier function. Circadian clock-dependent regulatory mechanisms such as inflammation and epithelial barrier function are gaining more attention due to their therapeutic potential against allergic inflammatory lung diseases. Currently, there are no studies to support whether REV-ERBα activation can attenuate Th2 cytokine-induced epithelial barrier dysfunction in human bronchial epithelial cells. We hypothesized that Th2 cytokine-induced epithelial barrier dysfunction may be protected by activating REV-ERBα. Treatment with Th2 cytokines or HDM significantly reduced the cell impedance, as confirmed by transepithelial electrical resistance (TEER). However, pre-treatment with SR10067 attenuated Th2 cytokine-induced barrier dysfunction, such as decreased permeability, improved TEER, localization of AJC and TJ proteins, and mRNA and protein levels of selected epithelial barrier and circadian clock targets. Overall, we showed for the first time that REV-ERBα activation regulates altered epithelial barrier function that may have direct implications for the treatment of asthma and other allergic diseases.
Eighteen new fast radio bursts in the High Time Resolution Universe survey
Authors: Trudu M. , Possenti A. , Pilia M. , Bailes M. , Keane E. F. , Kramer M. , Balakrishnan V. , Bhandari S. , Bhat N. D. R. , Burgay M. , Cameron A. , Champion D. J. , Jameson A. , Johnston S. , Keith M. J. , Levin L. , Ng C. , Sengar R. , Tiburzi C. 
Published: September 2024

Context. Current observational evidence reveals that fast radio bursts (FRBs) exhibit bandwidths ranging from a few dozen MHz to several GHz. Traditional FRB searches primarily employ matched filter methods on time series collapsed across the entire observational bandwidth. However, with modern ultrawideband receivers featuring gigahertz-scale observational bandwidths, this approach may overlook a significant number of events.
Aims. We investigate the efficacy of sub-banded searches for FRBs, whereby we look for bursts within limited portions of the bandwidth. The aim of these searches is to enhance the significance of FRB detections by mitigating the impact of noise outside the targeted frequency range, thereby improving signal-to-noise ratios.
Methods. We conducted a series of Monte Carlo simulations for the 400-MHz bandwidth Parkes 21-cm multi-beam (PMB) receiver system and the Parkes Ultra-Wideband Low (UWL) receiver, simulating bursts down to frequency widths of about 100 MHz. Additionally, we performed a complete reprocessing of the high-latitude segment of the High Time Resolution Universe South survey (HTRU-S) of the Parkes-Murriyang telescope using sub-banded search techniques.
Results. Simulations reveal that a sub-banded search can enhance the burst search efficiency by 67−42+133% for the PMB system and 1433−126+143% for the UWL receiver. Furthermore, the reprocessing of HTRU led to the confident detection of 18 new bursts, nearly tripling the count of FRBs found in this survey.
Conclusions. These results underscore the importance of employing sub-banded search methodologies to effectively address the often modest spectral occupancy of these signals.
Processus d’innovation des agriculteurs dans les palmeraies du sud du Bénin : quelles perspectives pour l’intensification agroécologique ?
Authors: Koussihouèdé Hermione , Yemadje Rolland H. , Aholoukpè Hervé N.S. , Clermont-Dauphin Cathy , Rafflegeau Sylvain 
Published: September 2024

L’agroforesterie constitue une forme d’intensification agroécologique. Les agriculteurs du sud du Bénin innovent ainsi dans leurs palmeraies pour faire face aux pressions foncière et alimentaire, corollaires de l’accroissement démographique. Afin d’accompagner les actions collectives en faveur de la durabilité, cette étude vise à identifier les freins et les leviers au développement des innovations en cours dans les palmeraies du sud du Bénin en s’appuyant sur les connaissances disponibles sur le système sociotechnique, la gestion agronomique et les performances atteintes. Sur le plan méthodologique, ces connaissances sont issues de travaux de recherches qui mobilisent le diagnostic agronomique régional et sociotechnique. Dans les systèmes traditionnels où des palmiers « tout venant » sont plantés par les propriétaires terriens pour produire du vin de palme, les métayers augmentent le nombre de cycles de cultures annuelles associées en intégrant les fertilisations minérale et organique à leurs pratiques. Dans les systèmes villageois, les élaeiculteurs introduisent différentes cultures annuelles entre les palmiers immatures pour satisfaire différents objectifs selon les types d’exploitation. Les freins au développement de ces innovations sont liés aux incompatibilités entre les visions et stratégies innovantes des différents acteurs. Dans les systèmes traditionnels, cette divergence de vision génère des conflits fonciers entre les métayers et les propriétaires terriens qui observent un ralentissement de la croissance des palmiers et rompent les accords fonciers en pensant que les pratiques des métayers épuisent leurs sols. Dans les systèmes villageois, l’accompagnement technique des acteurs de la recherche-développement est axé sur des itinéraires normatifs de culture du palmier à huile, alors que les élaeiculteurs ont aussi besoin de raisonner la fertilisation des cultures associées. Plusieurs perspectives d’intensification agroécologique sont ensuite discutées pour soutenir la transition agroécologique de la filière béninoise du palmier à huile.
Prognostic Impact of Surgical Margin Status on Overall Survival of Patients with Early Breast Cancer: A Retrospective Analysis from the Department for Women’s Medicine at Charité – University Hospital Berlin
Authors: Beck Maximilian Heinz , Weiler Karoline Barbara Stephanie , Trelinska-Finger Anna , Blohmer Jens-Uwe 
Published: September 2024

AbstractThe impact of surgical margins on the prognosis of early breast cancer remains uncertain, particularly in the context of modern treatment approaches. This study aimed to investigate whether involved margins after surgery for early breast cancer affect overall survival.We conducted a retrospective analysis of 3767 patients who underwent surgery for primary breast cancer or carcinoma in situ between 2006 and 2022 at Charité – University Hospital Berlin. Survival analysis based on margin status and a subsequent multivariate Cox regression analysis were conducted.With a median follow-up of 72.2 months, clear margins were achieved in 81.4% of patients (n = 3068) after primary surgery, while 16.2% (n = 610) required re-excision. Only 2.4% of patients (n = 89) had definitively involved margins. Margin involvement was more common in hormone receptor-positive disease, lobular subtype, carcinoma in situ, or locally advanced tumors, but less frequent in patients with previous neoadjuvant chemotherapy or triple-negative breast cancer. The Kaplan–Meier survival curves showed a significant separation with worse outcomes for patients with definitive R1 resections. However, the multivariate Cox regression analysis detected no statistically significant difference in overall survival based on margin status. Breast conserving surgery (HR 0.66; 95% CI 0.54–0.81) and HER2 overexpression (HR 0.65; 95% CI 0.48–0.89) were associated with improved survival.Patients who underwent breast-conserving surgery in our study demonstrated favorable outcomes compared to patients after mastectomy. Although margin status did not significantly affect overall survival, larger multicenter studies are needed to evaluate the prognostic implications of margin involvement in breast cancer treatment in different tumor stages, tumor subtypes and local and systemic treatments.
Novel Antibody-Drug-Conjugates in Routine Clinical Practice for the Treatment of Metastatic Breast Cancer: Adherence, Efficacy and Tolerability – Real-World Data from German Breast Centers
Authors: Schäffler Henning , Jakob Dorothee , Huesmann Sophia , Pfister Kerstin , Veselinovic Kristina , Schochter Fabienne , Leinert Elena , Fink Visnja , Rack Brigitte , Englisch Alexander , Volmer Lea-Louise , Engler Tobias , Frevert Marie Louise , Juhasz-Böss Ingolf , Brucker Sara , Heublein Sabine , Janni Wolfgang , Taran Florin-Andrei , Hartkopf Andreas , Dannehl Dominik 
Published: September 2024

AbstractThe third-generation antibody-drug conjugates (ADC), trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG), recently obtained approval for metastatic breast cancer treatment across various subtypes and therapeutic contexts.This retrospective, multicentric study evaluated real-world tolerability, feasibility and efficacy in a pre-treated, real-world cohort at three major German breast cancer centers.125 patients treated with T-DXd or SG from November 2020 to June 2023 were included (T-DXd: 77 patients; SG: 48 patients). The median treatment duration was 6.0 months for T-DXd and 3.5 months for SG therapy, with a median follow-up duration of 10.4 months for T-DXd (95% CI: 8.4–11.6) and 11.8 months for SG (95% CI: 8.0–14.4). Severe neutropenia (CTC ≥ III°) occurred in 33.3% during SG therapy, with a numerical reduction observed following primary, prophylactic use of G-CSF. T-DXd-associated pneumonitis occurred in 8 out of 77 patients (10.4 %). Median progression-free survival (mPFS) was 8.6 months (95% CI: 5.8–12.4) with T-DXd (HER2+: 10.8; HER2-low: 4.7) and 4.9 months (95% CI: 2.8–6.3) with SG (TNBC 4.9; HR+/HER2−: not reached). Median overall survival (OS) was 23.8 months (95% CI: 16.1–not estimable) with T-DXd (HER2+: 27.1; HER2-low: not reached), and 12.4 months (95% CI: 8.7–not estimable) with SG therapy (TNBC: 12.4, HR+/HER2−: not reached). 95.7% of the
protocol-specified, therapeutic dose was administered for T-DXd and 89.6% for SG.Overall, this indicates good feasibility, tolerability, and effectiveness of ADC therapies in the real-world setting.
Delivery Hospitalization Cardiac and Respiratory Complications during SARS-CoV-2 Delta Variant Dominance
Authors: Wang Ruiyan M. , Friedman Alexander , Booker Whitney A. , Liu Lilly Y. , Wen Timothy 
Published: September 2024

In 2021, the severe acute respiratory syndrome coronavirus 2 Delta variant rapidly proliferated and became dominant. Some but not all research evidence supports that Delta was associated with increased maternal risk. The purpose of this study was to determine whether Delta was associated with risk for cardiac and respiratory complications in a national sample. Of an estimated 3,495,188 delivery hospitalizations in 2021, 1.8% of pre-Delta deliveries (n = 29,580; January–June) and 2.1% of Delta-period deliveries (n = 37,545; July–December) had a coronavirus disease 2019 (COVID-19) diagnosis. The Delta period was associated with increased adjusted odds of respiratory complications (adjusted odds ratio [aOR] = 1.54, 95% CI: 1.41, 1.69) and cardiac severe maternal morbidity (SMM; aOR = 1.54, 95% CI: 1.40, 1.69). Among deliveries with a COVID-19 diagnosis, the Delta period was associated with a higher incidence of respiratory complications (8.4 vs. 3.7%) and cardiac SMM (8.4 vs. 3.5%; p < 0.01 for both). These findings corroborate prior clinical studies suggesting that the Delta strain was associated with an increased maternal population-level clinical burden.
Key Points