bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Method to Identify the Maximum Time Interval between Individual Events in Compound Rainstorm and Heatwave Events
Authors: Zhang Junlin , Xu Wei , Qiao Yu , Liao Xinli , Meng Chenna , Han Qinmei
Published: June 2024

Growing evidence indicates that extreme heat and rain may occur in succession within short time periods and cause greater impacts than individual events separated in time and space. Therefore, many studies have examined the impacts of compound hazard events on the social-ecological system at various scales. The definition of compound events is fundamental for such research. However, there are no existing studies that support the determination of time interval between individual events of a compound rainstorm and heatwave (CRH) event, which consists of two or more potentially qualifying component heatwave and rainstorm events. To address the deficiency in defining what individual events can constitute a CRH event, this study proposed a novel method to determine the maximum time interval for CRH events through the change in CRH event frequency with increasing time interval between individual events, using southern China as a case study. The results show that the threshold identified by the proposed method is reasonable. For more than 90% of the meteorological stations, the frequency of CRH events has reached a maximum when the time interval is less than or equal to the threshold. This study can aid in time interval selection, which is an important step for subsequent study of CRH events.
Perioperative Management of Hemophilia Patients
Authors: Lowell Aliena E. , Calgi Michael P. , Caruso Joseph J. , Man Louise M. , McNeil John S.
Published: June 2024

Purpose of Review

Hemophilia is a rare, typically inherited, condition where a specific clotting factor is reduced or even near absent. Patients with hemophilia who present for an invasive procedure, whether elective or urgent, are at increased risk of bleeding intraoperatively and postoperatively.

Recent Findings

Ten years ago, most patients with hemophilia with moderate or severe disease were treated with standard half-life factor replacement therapy, either prophylactic or on-demand. Now, patients may present on extended half-life factor therapy, or on a non-factor hemostatic therapy, or as a recipient of gene therapy. Further complicating the challenge of caring for these patients is that most of these new modalities will typically require supplementation with traditional factor therapy when surgery is required.

An in-depth understanding of all the potential treatment options for hemophilia is essential when anesthesiologists care for a patient with hemophilia. And there are several perioperative arenas (neuraxial procedures, point-of-care coagulation tests such as ROTEM or TEG, and cardiopulmonary bypass) where hemophilia creates unique considerations.
Spatial-temporal memory enhanced multi-level attention network for origin-destination demand prediction
Authors: Lu Jiawei , Pan Lin , Ren Qianqian
Published: June 2024

Origin-destination demand prediction is a critical task in the field of intelligent transportation systems. However, accurately modeling the complex spatial-temporal dependencies presents significant challenges, which arises from various factors, including spatial, temporal, and external influences such as geographical features, weather conditions, and traffic incidents. Moreover, capturing multi-scale dependencies of local and global spatial dependencies, as well as short and long-term temporal dependencies, further complicates the task. To address these challenges, a novel framework called the Spatial-Temporal Memory Enhanced Multi-Level Attention Network (ST-MEN) is proposed. The framework consists of several key components. Firstly, an external attention mechanism is incorporated to efficiently process external factors into the prediction process. Secondly, a dynamic spatial feature extraction module is designed that effectively captures the spatial dependencies among nodes. By incorporating two skip-connections, this module preserves the original node information while aggregating information from other nodes. Finally, a temporal feature extraction module is proposed that captures both continuous and discrete temporal dependencies using a hierarchical memory network. In addition, multi-scale features cascade fusion is incorporated to enhance the performance of the proposed model. To evaluate the effectiveness of the proposed model, extensively experiments are conducted on two real-world datasets. The experimental results demonstrate that the ST-MEN model achieves excellent prediction accuracy, where the maximum improvement can reach to 19.1%.
Conformalized prescriptive machine learning for uncertainty-aware automated decision making: the case of goodwill requests
Authors: Haas Stefan , Hüllermeier Eyke
Published: June 2024

Due to the inherent presence of uncertainty in machine learning (ML) systems, the usage of ML is until now out of scope for many critical (financial) business processes. One such process is goodwill assessment at car manufacturers, where a large part of goodwill cases is still assessed manually by human experts. To increase the degree of automation while still providing an overall reliable assessment service, we propose a selective uncertainty-aware automated decision making approach based on uncertainty quantification through conformal prediction. In our approach, goodwill requests are still shifted to human experts in case the risk of a wrong assessment is too high. Nevertheless, ML can be introduced into the process with reduced and controllable risk. We hereby determine the risk of wrong ML assessments through two hierarchical conformal predictors that make use of the prediction set and interval size as the main criteria for quantifying uncertainty. We also utilize conformal prediction’s property to output empty prediction sets if no prediction is significant enough and abstain from an automatic decision in that case. Instead of providing mathematical guarantees for limited risk, we focus on the risk vs. degree of automation trade-off and how a business decision maker can select in an a posteriori fashion a trade-off that best suits the business problem at hand from a set of pareto optimal solutions. We also show empirically on a goodwill data set of a BMW National Sales Company that by only selecting certain requests for automated decision making we can significantly increase the accuracy of automatically processed requests. For instance, from 92 to 98% for labor and from 90 to 98% for parts contributions respectively, while still maintaining a degree of automation of approximately 70%.
Bayesian hierarchical network autocorrelation models for estimating direct and indirect effects of peer hospitals on outcomes of hospitalized patients
Authors: Chen Guanqing , O’Malley A. James
Published: June 2024

When an hypothesized peer effect (also termed social influence or contagion) is believed to act between units (e.g., hospitals) above the level at which data is observed (e.g., patients), a network autocorrelation model may be embedded within a hierarchical data structure thereby formulating the peer effect as a dependency between latent variables. In such a situation, a patient’s own hospital can be thought of as a mediator between the effects of peer hospitals and their outcome. However, as in mediation analyses, there may be interest in allowing the effects of peer units to directly impact patients of other units. To accommodate these possibilities, we develop two hierarchical network autocorrelation models that allow for direct and indirect peer effects between hospitals when modeling individual outcomes of the patients cared for at the hospitals. A Bayesian approach is used for model estimation while a simulation study assesses the performance of the models and sensitivity of results to different prior distributions. We construct a United States New England region patient-sharing hospital network and apply newly developed Bayesian hierarchical models to study the diffusion of robotic surgery and hospital peer effects in patient outcomes using a cohort of United States Medicare beneficiaries in 2016 and 2017. The comparative fit of models to the data is assessed using Deviance information criteria tailored to hierarchical models that include peer effects as latent variables.
Monitoring and tracking changes in sensitivity to zoxamide fungicide in Plasmopara viticola in Italy
Authors: Nanni Irene M. , Oggiano Ivano , Laricchia Maria , Cempini Martina , Collina Marina
Published: June 2024

Plasmopara viticola is controlled by fungicides with different modes of action, which include zoxamide. Zoxamide was developed in 1998 by Dow AgroSciences LIC (Indianapolis, IN) and has been commercialized since 2001 by Rohm and Haas Company. This fungicide is highly effective against oomycetes, used for foliar application in vine crops, potato, and other vegetables to control oomycete-induced diseases. Zoxamide acts by causing mitotic arrest by binding to β-tubulin, inhibiting tubulin polymerization and cell division of the pathogen. In the past three decades, the management of fungicide resistance has emerged as a significant concern for both growers and regulatory authorities; this is primarily due to the substantial increase in resistance, in terms of occurrence and spread, towards most fungicide groups. The monitoring of the effectiveness of fungicides is the only way to accurately identify as soon as possible the onset of resistance. In this study, we were interested in tracking the changes in the sensitivity of zoxamide to P. viticola populations collected during a 6-year monitoring (2017–2022) in two Italian locations: the autonomous province of Trento and the autonomous region of Friuli-Venezia Giulia. Bioassays on leaf discs were carried out, and EC50 and MIC values were elaborated. From our results, zoxamide showed for a long period of time high sensitivity, but over the last years we observed a change, as in 2022 most of the samples tested in these two regions showed MIC > 100 mg L−1.
The Combination Between Super Absorbent Polymers (SAPs) and Biofertilizers Could be an Ecofriendly Approach for Soil Chemical Properties Improving and Sustainable Wheat (Triticum Sativum) Production in Sandy Loam Soil
Authors: Negim Osama I. A. , Moharam Moustafa H. A. , Elsayed Elsayed F. , Thabit Fatma N.
Published: June 2024

Sustainable agriculture aims to provide food needs while improving soil health and protecting it from degradation and contamination from excessive chemical fertilizer use. Sandy-textured soils have low fertility and water-holding capacity. This study assessed the integrated impact of super absorbent polymers (SAPs) and biofertilizer application on the soil chemical characteristics and wheat growth parameters in sandy loam soil. Two super absorbent polymers (SAPs) included Barbary plant G3 (P1) and Aqua Gool polymer (P2), and four microbial inoculations (Trichoderma harzianum (T), Actinomycetes (Streptomyces rochei and Streptomyces atrovirens) (AC1 and AC2), and Bacillus subtilis (B)) as biofertilizers were used in our pot experiment. The SAPs were applied to soil at a level of 0.2% (w/w), while biofertilizers were applied in the form of microbial cell suspensions (50 ml per pot) in addition to treating wheat seed with these suspensions during cultivation. Wheat plants were irrigated every 8 days to field capacity level. Amending soil with super absorbent polymers and microbes either individually or in combination significantly reduced pH and EC, increased organic matter level, and the availability of macro- and micronutrients in soil. Wheat growth metrics, including shoot length, tiller number, biomass accumulation, leaf area, and grain yield, exhibited considerable enhancements relative to the plants of the control treatment. The interaction between P1 polymer and Streptomyces atrovirens (AC2) showed the highest performance in improving the almost studied parameters. The application of SAPs with microbial biofertilizers offers a promising eco-friendly method for enhancing soil health and wheat yield.
Do NGOs recognise the climate-biodiversity nexus? Insights from 107 climate NGOs in Germany
Authors: Oelschläger Lucie Maj , Kim Rakhyun E.
Published: June 2024

Biodiversity loss and climate change are deeply intertwined and constitute a complex and interdependent crisis. These interlinked sustainability issues need to be addressed through an integrated approach. However, governments have been slow to integrate the need to protect both climate and biodiversity into environmental governance. NGOs, as non-profit organisations promoting public good, are seen as having the potential to recognise and advocate for this much-needed holistic protection of climate and biodiversity. But to what extent and in what ways do NGOs recognise this climate-biodiversity nexus? This article addresses these questions through an analysis of 107 German climate NGOs, examining their 190 annual reports from two time periods, 2016/2017 and 2021/2022. We found that, while German climate NGOs have made significant progress in recognising the climate-biodiversity nexus, they lack recognition of the role of biodiversity in stabilising the climate and the unintended negative consequences of climate policies and measures for biodiversity, highlighting that NGOs are still far from being holistic environmental stewards. Climate NGOs need to integrate the interplay between climate and biodiversity objectives into their organisational activities and align their mandates to promote synergies and minimise trade-offs between climate and biodiversity actions. We suggest that one way forward is to increase collaboration between NGOs. NGOs could then complement each other’s expertise and be better placed to jointly contribute to finding integrated solutions for climate and biodiversity protection and mainstreaming biodiversity into climate policy.
Application of the Bagged Trees Technique on Retrieving the Nighttime Ionospheric Peak Density From OI‐135.6 nm Airglow
Authors: Lin Chi‐Yen , Liu Jann‐Yenq , Chien‐Hung Lin Charles , Rajesh P. K. , Duann Yi , Wen Yun‐Cheng
Published: June 2024

The NASA global‐scale observations of the limb and disk (GOLD) mission is a measurement opportunity to scan the far ultraviolet airglow at ∼134–162 nm over the American Hemisphere since October 2018. The FORMOSAT‐7/COSMIC‐2 (F7/C2) satellite mission has provided thousands of daily radio occultation soundings in the low‐ and mid‐latitude regions since July 2019. The nighttime OI–135.6 nm emission is mainly through radiative recombination, and the radiance is used to derive the peak electron density. Comparison with corresponding F7/C2 observations demonstrates good correlation in low‐latitudes, while is overestimated near mid‐latitudes in winter, induced by the photoelectrons emanating from magnetically conjugate Hemisphere. The machine learning technique Bagged Trees is implemented to develop an intensity to peak density model training from GOLD and F7/C2 observations. The validation demonstrates that Bagged Trees peak‐density has less influence from conjugate photoelectrons and indicates the power of machine learning techniques for geophysics data processing.
Sources of Southern Hemisphere Marine Aerosols: Insights From Carbonaceous Fraction Concentration and Stable Carbon Isotope Analysis
Authors: Gu Weihua , Xie Zhouqing , Jiang Bei , Yue Fange , Yu Xiawei , Chen Afeng
Published: June 2024

Marine carbonaceous aerosols, originating from marine and continental sources, are significant global aerosol components. The understanding of marine carbonaceous aerosols is currently limited, especially in the Southern Hemisphere. Furthermore, there is an ongoing debate regarding the contributions of marine fresh and ancient carbon to marine aerosols. To address these gaps, we conducted an extensive investigation utilizing a long‐term data set of aerosol samples collected during six Antarctic cruises (28°N–78°S) from 2013 to 2020. Our analysis revealed an average organic carbon (OC) concentration of 1.29 ± 1.15 μg/m3 and an element carbon (EC) concentration of 0.13 ± 0.18 μg/m3 in the samples. These concentrations varied within a range spanning from background marine samples to those impacted by substantial continental transport. Fossil fuel combustion remained the primary source of continental influence in the marine environment, as evidenced by the OC/EC ratio. The δ13CTC value for all samples range from −22.3‰ to −28.4‰, with a mean value of −26.3 ‰. Using a three‐endmember isotopic source model, we find that continental carbonaceous aerosols make substantial contributions in the Eastern Indian Ocean (81 ± 4%), while their prevalence is lower in the Southern Ocean (SO) (44 ± 20%). In contrast to mid‐latitudes, primary marine aerosol of the SO exhibits a significantly higher contribution from the fresh carbon pool (52 ± 19%). Furthermore, our study suggests that SO sea ice may play a potential role in driving emissions from the fresh carbon pool. These findings contribute to a comprehensive understanding of the effects of carbonaceous aerosols on climate change and the ocean‐atmosphere carbon cycle.
Assessing the Impact of Climate Change on Atmospheric Rivers: A Modeling Perspective
Authors: Ordaz Osorio C. , Booth J. F. , LeGrande A. N. , Naud C. M.
Published: June 2024

Atmospheric rivers (ARs) play a crucial role in the poleward transport of water vapor, and the AR‐associated precipitation is a critical component of global water supplies, making it critical that we understand how ARs may change in the future. To approach this issue, integrations of the NASA Goddard Institute for Space Studies global climate model ModelE version 2.1 (GISSE2.1) are employed. Multiple configurations of the model simulating different climates are analyzed: (a) the last‐glacial maximum; (b) present day; (c) the end of the 21st century. The thermodynamic and dynamic components of changes to AR frequency are analyzed using a decomposition method. This method utilizes differences in distinct AR seasonal climatology frequencies derived from various vertically integrated water vapor transport (IVT) thresholds to resolve AR frequency into its components. Global mean state changes in poleward AR frequency for different climates are dominated by precipitable water vapor (PWV) changes. A set of idealized cold and warm climates in which present day sea surface temperatures are uniformly changed are considered for a targeted analysis of the south Pacific Ocean basin. For this analysis, frequency and distribution of AR events in the model runs are analyzed by comparing them to changes in the jet stream as well as the Eulerian storm tracks and low‐level baroclinicity. Latitudinal shifts in the ARs in the south Pacific Ocean basin using our integrations are not as tightly coupled to these two storm‐related climatological metrics in the midlatitudes but fare better on the poleward side of the storm tracks.
Aerosol and Dimethyl Sulfide Sensitivity to Sulfate Chemistry Schemes
Authors: Bhatti Yusuf A. , Revell Laura E. , McDonald Adrian J. , Archibald Alex T. , Schuddeboom Alex J. , Williams Jonny , Hardacre Catherine , Mulcahy Jane , Lin Dongqi
Published: June 2024

Dimethyl sulfide (DMS) is the largest source of natural sulfur in the atmosphere and undergoes oxidation reactions resulting in gas‐to‐particle conversion to form sulfate aerosol. Climate models typically use independent chemical schemes to simulate these processes, however, the sensitivity of sulfate aerosol to the schemes used by CMIP6 models has not been evaluated. Current climate models offer oversimplified DMS oxidation pathways, adding to the ambiguity surrounding the global sulfur burden. Here, we implemented seven DMS and sulfate chemistry schemes, six of which are from CMIP6 models, in an atmosphere‐only Earth system model. A large spread in aerosol optical depth (AOD) is simulated (0.077), almost twice the magnitude of the pre‐industrial to present‐day increase in AOD. Differences are largely driven by the inclusion of the nighttime DMS oxidation reaction with NO3, and in the number of aqueous phase sulfate reactions. Our analysis identifies the importance of DMS‐sulfate chemistry for simulating aerosols. We suggest that optimizing DMS/sulfur chemistry schemes is crucial for the accurate simulation of sulfate aerosols.
Deep‐Learning‐Based Phase Picking for Volcano‐Tectonic and Long‐Period Earthquakes
Authors: Zhong Yiyuan , Tan Yen Joe
Published: June 2024

The application of deep‐learning‐based seismic phase pickers has surged in recent years. However, the efficacy of these models when applied to monitoring volcano seismicity has yet to be fully evaluated. Here, we first compile a data set of seismic waveforms from various volcanoes globally. We then show that the performances of two widely used deep‐learning pickers deteriorate systematically as the earthquakes' frequency content decreases. Therefore, the performances are especially poor for long‐period earthquakes often associated with fluid/magma movement. Subsequently, we train new models which perform significantly better, including when tested on two data sets where no training data were used: volcanic earthquakes along the Cascadia subduction zone and tectonic low‐frequency earthquakes along the Nankai Trough. Our model/workflow can be applied to improve monitoring of volcano seismicity globally while our compiled data set can be used to benchmark future methods for characterizing volcano seismicity, especially long‐period earthquakes which are difficult to monitor.
Asymmetry in Uranus' High Energy Proton Radiation Belt
Authors: Acevski M. , Masters A. , Zomerdijk‐Russell S.
Published: June 2024

Uranus is one of the least explored planets in our solar system, it exhibits a unique magnetic field structure which was observed by NASA's Voyager 2 mission nearly 50 years ago. Notably, Uranus displays extreme magnetic field asymmetry, a feature exclusive to the icy giants. We use the Boris algorithm to investigate how high energy protons behave within this unusual magnetic field, which is motivated by Voyager 2's observation of lower‐than‐expected high energy proton radiation belt intensities at Uranus. When considering full drift motions of high energy protons around Uranus, the azimuthal drift velocity can vary by as much as 15% around the planet. This results in areas around Uranus where particles will be more depleted (faster drift) and other regions where there is a surplus of particles (slower drift). This could provide a partial explanation for the “weak” proton radiation belts observed by Voyager 2.
Permafrost Cloud Feedback May Amplify Climate Change
Authors: de Vrese Philipp , Stacke Tobias , Gayler Veronika , Brovkin Victor
Published: June 2024

Rising temperatures entail important changes in the soil hydrologic processes of the northern permafrost zone. Using the ICON‐Earth System Model, we show that a large‐scale thaw of essentially impervious frozen soil layers may cause a positive feedback by which permafrost degradation amplifies the causative warming. The thawing of the ground increases its hydraulic connectivity and raises drainage rates which facilitates a drying of the landscapes. This limits evapotranspiration and the formation of low‐altitude clouds during the snow‐free season. A decrease in summertime cloudiness, in turn, increases the shortwave radiation reaching the surface, hence, temperatures and advances the permafrost degradation. Our simulations further suggest that the consequences of a permafrost cloud feedback may not be limited to the regional scale. For a near‐complete loss of the high‐latitude permafrost, they show significant temperature impacts on all continents and northern‐hemisphere ocean basins that raise the global mean temperature by 0.25 K.
Relationship Between Circulation Types and Extreme Precipitation Over Scandinavia Is Stable Under Climate Change
Authors: Hansen F. , Belušić D. , Wyser K.
Published: June 2024

The atmospheric large‐scale environment determines the occurrence of local extreme precipitation, and it is unclear how climate change affects this relationship. Here we investigate the present‐day relationship between large‐scale circulation types (CTs) and daily precipitation extremes over Scandinavia and its future change. A 50‐member EC‐Earth3 large ensemble is used to assess future changes against internal variability. We show that CTs are related to extreme precipitation over the entire domain. The intensity of extreme daily precipitation increases in all seasons in the future climate, generally following the strength of warming in the six different future scenarios considered. However, no significant future change is found in the relationship between extreme precipitation and the CTs in any season or scenario. The results have important implications for applications that rely on the stability of this relationship, such as statistical and event‐based dynamical downscaling of future weather and climate predictions and long‐term climate projections.
Big data and deep learning for RNA biology
Authors: Hwang Hyeonseo , Jeon Hyeonseong , Yeo Nagyeong , Baek Daehyun
Published: June 2024

The exponential growth of big data in RNA biology (RB) has led to the development of deep learning (DL) models that have driven crucial discoveries. As constantly evidenced by DL studies in other fields, the successful implementation of DL in RB depends heavily on the effective utilization of large-scale datasets from public databases. In achieving this goal, data encoding methods, learning algorithms, and techniques that align well with biological domain knowledge have played pivotal roles. In this review, we provide guiding principles for applying these DL concepts to various problems in RB by demonstrating successful examples and associated methodologies. We also discuss the remaining challenges in developing DL models for RB and suggest strategies to overcome these challenges. Overall, this review aims to illuminate the compelling potential of DL for RB and ways to apply this powerful technology to investigate the intriguing biology of RNA more effectively.
Optimal design of synthetic circular RNAs
Authors: Choi Seo-Won , Nam Jin-Wu
Published: June 2024

Circular RNAs are an unusual class of single-stranded RNAs whose ends are covalently linked via back-splicing. Due to their versatility, the need to express circular RNAs in vivo and in vitro has increased. Efforts have been made to efficiently and precisely synthesize circular RNAs. However, a review on the optimization of the processes of circular RNA design, synthesis, and delivery is lacking. Our review highlights the multifaceted aspects considered when producing optimal circular RNAs and summarizes the available options for each step of exogenous circular RNA design and synthesis, including circularization strategies. Additionally, this review describes several potential applications of circular RNAs.
Linking haploinsufficiency of the autism- and schizophrenia-associated gene Cyfip1 with striatal-limbic-cortical network dysfunction and cognitive inflexibility
Authors: Haddon Josephine E. , Titherage Daniel , Heckenast Julia R. , Carter Jennifer , Owen Michael J. , Hall Jeremy , Wilkinson Lawrence S. , Jones Matthew W.
Published: June 2024

Impaired behavioural flexibility is a core feature of neuropsychiatric disorders and is associated with underlying dysfunction of fronto-striatal circuitry. Reduced dosage of Cyfip1 is a risk factor for neuropsychiatric disorder, as evidenced by its involvement in the 15q11.2 (BP1–BP2) copy number variant: deletion carriers are haploinsufficient for CYFIP1 and exhibit a two- to four-fold increased risk of schizophrenia, autism and/or intellectual disability. Here, we model the contributions of Cyfip1 to behavioural flexibility and related fronto-striatal neural network function using a recently developed haploinsufficient, heterozygous knockout rat line. Using multi-site local field potential (LFP) recordings during resting state, we show that Cyfip1 heterozygous rats (Cyfip1+/−) harbor disrupted network activity spanning medial prefrontal cortex, hippocampal CA1 and ventral striatum. In particular, Cyfip1+/− rats showed reduced influence of nucleus accumbens and increased dominance of prefrontal and hippocampal inputs, compared to wildtype controls. Adult Cyfip1+/− rats were able to learn a single cue-response association, yet unable to learn a conditional discrimination task that engages fronto-striatal interactions during flexible pairing of different levers and cue combinations. Together, these results implicate Cyfip1 in development or maintenance of cortico-limbic-striatal network integrity, further supporting the hypothesis that alterations in this circuitry contribute to behavioural inflexibility observed in neuropsychiatric diseases including schizophrenia and autism.
Anti-T-lymphocyte globulin (ATLG) compared to post-transplant cyclophosphamide as GvHD prophylaxis in ALL patients undergoing allogeneic stem cell transplantation
Authors: Steiner Normann , Massoud Radwan , Klyuchnikov Evgeny , Gagelmann Nico , Richter Johanna , Niederwieser Christian , Rathje Kristin , Urbanowicz Tatjana , Kunte Ameya , Engelmann Janik , Ihne Christina , Lastovytska Iryna , Lindhauer Cecilia , Marquard Franziska , Reichard Mirjam , Ryzhkova Alla , Sabauri Rusudan , Schäfersküpper Mathias , Seyedi Niloufar , Kalogeropoulos Georgios , Heidenreich Silke , Rudolph Ina , Zeck Gaby , Janson Dietlinde , Wolschke Christine , Ayuk Francis , Kröger Nicolaus
Published: June 2024

We retrospectively analyzed high-risk ALL patients in CR1 receiving total body irradiation based conditioning regimen with ATLG (n = 74) or PTCy (n = 73) for GVHD prophylaxis. The 3-year OS and LFS were similar in both groups: 65 and 60% in the ATLG group and 64 and 67% in the PTCy group (p = 0.9 and 0.5, respectively). CIR and NRM rate at three years was 12 and 21% after PTCy and 19 and 20% after ATLG (p = 0.4 and p = 0.9, respectively). Acute GvHD grades II-IV and grades III/IV at 100 days was 46 and 19% after PTCy and 33 and 10% after ATLG (p = 0.08 and p = 0.9, respectively). Chronic GvHD of all grade at two years was higher after PTCy: 55% versus 26% (p < 0.001). Based on the propensity score matching (PSM) analysis, aGvHD grades II-IV was trending higher in the PTCy group compared to the ATLG group (p = 0.07). In contrast to the PSM analysis, on multivariate analysis the receipt of PTCy compared with ATLG was associated with a reduced CIR (p = 0.026). Our retrospective single-center analysis shows a lower incidence of acute and chronic GvHD while displaying similar LFS and OS after ATLG compared to PTCy in TBI based allogeneic stem cell transplantation for high-risk ALL.
Carbon nanotubes functionalized with α-aminoisobutyric acid-containing peptide increase gene delivery efficiency in plant mitochondria
Authors: Law Simon Sau Yin , Kuzumoto Mako , Fujita Seiya , Fujigaya Tsuyohiko , Numata Keiji
Published: June 2024

Functionalized carbon nanotubes have shown tremendous promise in the field of plant biotechnology for genetic engineering and cargo delivery; recent findings have shown that they can be delivered within specific organelles, such as mitochondria and chloroplasts, in intact plants. 2-Aminoisobutyric acid is an unnatural amino acid that promotes helical conformation and has been demonstrated to increase membrane permeability. Rational substitution of this amino acid into a mitochondrial targeting peptide induced a helical conformation that, when functionalized onto polymer-coated carbon nanotubes, conferred increased membrane permeability compared with that of the native peptide. The secondary structure was maintained on the surface and, when used to deliver pDNA, led to an increase in gene expression, suggesting that this method may be used to enhance the delivery efficiency of existing functional peptides.
Two distinct archaeal type IV pili structures formed by proteins with identical sequence
Authors: Liu Junfeng , Eastep Gunnar N. , Cvirkaite-Krupovic Virginija , Rich-New Shane T. , Kreutzberger Mark A. B. , Egelman Edward H. , Krupovic Mart , Wang Fengbin
Published: June 2024

Type IV pili (T4P) represent one of the most common varieties of surface appendages in archaea. These filaments, assembled from small pilin proteins, can be many microns long and serve diverse functions, including adhesion, biofilm formation, motility, and intercellular communication. Here, we determine atomic structures of two distinct adhesive T4P from Saccharolobus islandicus via cryo-electron microscopy (cryo-EM). Unexpectedly, both pili were assembled from the same pilin polypeptide but under different growth conditions. One filament, denoted mono-pilus, conforms to canonical archaeal T4P structures where all subunits are equivalent, whereas in the other filament, the tri-pilus, the same polypeptide exists in three different conformations. The three conformations in the tri-pilus are very different from the single conformation found in the mono-pilus, and involve different orientations of the outer immunoglobulin-like domains, mediated by a very flexible linker. Remarkably, the outer domains rotate nearly 180° between the mono- and tri-pilus conformations. Both forms of pili require the same ATPase and TadC-like membrane pore for assembly, indicating that the same secretion system can produce structurally very different filaments. Our results show that the structures of archaeal T4P appear to be less constrained and rigid than those of the homologous archaeal flagellar filaments that serve as helical propellers.
Single-cell and spatially resolved interactomics of tooth-associated keratinocytes in periodontitis
Authors: Easter Quinn T. , Fernandes Matuck Bruno , Beldorati Stark Germán , Worth Catherine L. , Predeus Alexander V. , Fremin Brayon , Huynh Khoa , Ranganathan Vaishnavi , Ren Zhi , Pereira Diana , Rupp Brittany T. , Weaver Theresa , Miller Kathryn , Perez Paola , Hasuike Akira , Chen Zhaoxu , Bush Mandy , Qu Xufeng , Lee Janice , Randell Scott H. , Wallet Shannon M. , Sequeira Inês , Koo Hyun , Tyc Katarzyna M. , Liu Jinze , Ko Kang I. , Teichmann Sarah A. , Byrd Kevin M.
Published: June 2024

Periodontitis affects billions of people worldwide. To address relationships of periodontal niche cell types and microbes in periodontitis, we generated an integrated single-cell RNA sequencing (scRNAseq) atlas of human periodontium (34-sample, 105918-cell), including sulcular and junctional keratinocytes (SK/JKs). SK/JKs displayed altered differentiation states and were enriched for effector cytokines in periodontitis. Single-cell metagenomics revealed 37 bacterial species with cell-specific tropism. Fluorescence in situ hybridization detected intracellular 16 S and mRNA signals of multiple species and correlated with SK/JK proinflammatory phenotypes in situ. Cell-cell communication analysis predicted keratinocyte-specific innate and adaptive immune interactions. Highly multiplexed immunofluorescence (33-antibody) revealed peri-epithelial immune foci, with innate cells often spatially constrained around JKs. Spatial phenotyping revealed immunosuppressed JK-microniches and SK-localized tertiary lymphoid structures in periodontitis. Here, we demonstrate impacts on and predicted interactomics of SK and JK cells in health and periodontitis, which requires further investigation to support precision periodontal interventions in states of chronic inflammation.
A blueprint for precise and fault-tolerant analog neural networks
Authors: Demirkiran Cansu , Nair Lakshmi , Bunandar Darius , Joshi Ajay
Published: June 2024

Analog computing has reemerged as a promising avenue for accelerating deep neural networks (DNNs) to overcome the scalability challenges posed by traditional digital architectures. However, achieving high precision using analog technologies is challenging, as high-precision data converters are costly and impractical. In this work, we address this challenge by using the residue number system (RNS) and composing high-precision operations from multiple low-precision operations, thereby eliminating the need for high-precision data converters and information loss. Our study demonstrates that the RNS-based approach can achieve ≥99% FP32 accuracy with 6-bit integer arithmetic for DNN inference and 7-bit for DNN training. The reduced precision requirements imply that using RNS can achieve several orders of magnitude higher energy efficiency while maintaining the same throughput compared to conventional analog hardware with the same precision. We also present a fault-tolerant dataflow using redundant RNS to protect the computation against noise and errors inherent within analog hardware.
Sulfonamide-directed site-selective functionalization of unactivated C(sp3)−H enabled by photocatalytic sequential electron/proton transfer
Authors: Wang Chaodong , Chen Zhi , Sun Jie , Tong Luwei , Wang Wenjian , Song Shengjie , Li Jianjun
Published: June 2024

The generation of alkyl radical from C(sp3)−H substrates via hydrogen atom abstraction represents a desirable yet underexplored strategy in alkylation reaction since involving common concerns remain adequately unaddressed, such as the harsh reaction conditions, limited substrate scope, and the employment of noble metal- or photo-catalysts and stoichiometric oxidants. Here, we utilize the synergistic strategy of photoredox and hydrogen atom transfer (HAT) catalysis to accomplish a general and practical functionalization of unactived C(sp3)−H centers with broad reaction scope, high functional group compatibility, and operational simplicity. A combination of validation experiments and density functional theory reveals that the N-centered radicals, generated from free N − H bond in a stepwise electron/proton transfer event, are the key intermediates that enable an intramolecular 1,5-HAT or intermolecular HAT process for nucleophilic carbon-centered radicals formation to achieve heteroarylation, alkylation, amination, cyanation, azidation, trifluoromethylthiolation, halogenation and deuteration. The practical value of this protocol is further demonstrated by the gram-scale synthesis and the late-stage functionalization of natural products and drug derivatives.
Development of a natural product optimization strategy for inhibitors against MraY, a promising antibacterial target
Authors: Yamamoto Kazuki , Sato Toyotaka , Hao Aili , Asao Kenta , Kaguchi Rintaro , Kusaka Shintaro , Ruddarraju Radhakrishnam Raju , Kazamori Daichi , Seo Kiki , Takahashi Satoshi , Horiuchi Motohiro , Yokota Shin-ichi , Lee Seok-Yong , Ichikawa Satoshi
Published: June 2024

MraY (phospho-N-acetylmuramoyl-pentapeptide-transferase) inhibitory natural products are attractive molecules as candidates for a new class of antibacterial agents to combat antimicrobial-resistant bacteria. Structural optimization of these natural products is required to improve their drug-like properties for therapeutic use. However, chemical modifications of these natural products are painstaking tasks due to complex synthetic processes, which is a bottleneck in advancing natural products to the clinic. Here, we develop a strategy for a comprehensive in situ evaluation of the build-up library, which enables us to streamline the preparation of the analogue library and directly assess its biological activities. We apply this approach to a series of MraY inhibitory natural products. Through construction and evaluation of the 686-compound library, we identify promising analogues that exhibit potent and broad-spectrum antibacterial activity against highly drug-resistant strains in vitro as well as in vivo in an acute thigh infection model. Structures of the MraY-analogue complexes reveal distinct interaction patterns, suggesting that these analogues represent MraY inhibitors with unique binding modes. We further demonstrate the generality of our strategy by applying it to tubulin-binding natural products to modulate their tubulin polymerization activities.
Exploring perceived challenges, adoption, and assessment of Western values of democracy and human rights in Palestine in the 2023 War on Gaza
Authors: Jabali Oqab , Sleem Heba , Ayyoub Abed Alkarim , Saeedi Munther , Alawneh Yousef , Ishtaiyeh Muath
Published: June 2024

This study delved into the dynamics of perceived challenges, adoption, and assessment of Western values of democracy and human rights among university students in Palestine, particularly in the aftermath of the 2023 War on Gaza. A mixed-methods strategy was used in the research, with a participant pool of 384 students representing a range of demographics. By exploring the impact of geopolitical events, the results revealed a positive link between perceived challenges and the assessment of Western values. Although there is a notable gender and geographic difference in the assessment and adoption of Western values, females and those living in cities and villages are shown to have greater perceived challenges with these values. The qualitative component, including interviews with 12 students, provided valuable insights into the postwar evolution of Palestinian perspectives, highlighting a notable shift in attitudes, initially characterized by belief in the superiority of Western values, followed by a decline in faith during the war. This decline is attributed to traumatic events, biased media narratives, and the contradiction between idealized standards and harsh realities. In conclusion, the study emphasizes the need for a comprehensive understanding of the multifaceted influences on Palestinian perceptions of Western values.
The effect of body weight on the knee joint biomechanics based on subject-specific finite element-musculoskeletal approach
Authors: Adouni Malek , Aydelik Harun , Faisal Tanvir R. , Hajji Raouf
Published: June 2024

Knee osteoarthritis (OA) and obesity are major public health concerns that are closely intertwined. This intimate relationship was documented by considering obesity as the most significant preventable risk factor associated with knee OA. To date, however, the effects of obesity on the knee joint's passive-active structure and cartilage loading have been inconclusive. Hence, this study investigates the intricate relationship between obesity and knee OA, centering on the biomechanical changes in knee joint active and passive reactions during the stance phase of gait. Using a subject-specific musculoskeletal and finite element approach, muscle forces, ligament stresses, and articular cartilage contact stresses were analyzed among 60 individuals with different body mass indices (BMI) classified under healthy weight, overweight, and obese categories. Our predicted results showed that obesity significantly influenced knee joint mechanical reaction, increasing muscle activations, ligament loading, and articular cartilage contact stresses, particularly during key instances of the gait cycle—first and second peak loading instances. The study underscores the critical role of excessive body weight in exacerbating knee joint stress distribution and cartilage damage. Hence, the insights gained provide a valuable biomechanical perspective on the interaction between body weight and knee joint health, offering a clinical utility in assessing the risks associated with obesity and knee OA.
A hybrid swarm intelligence algorithm for region-based image fusion
Authors: Salgotra Rohit , Lamba Amanjot Kaur , Talwar Dhruv , Gulati Dhairya , Gandomi Amir H.
Published: June 2024

This paper proposes a novel multi-hybrid algorithm named DHPN, using the best-known properties of dwarf mongoose algorithm (DMA), honey badger algorithm (HBA), prairie dog optimizer (PDO), cuckoo search (CS), grey wolf optimizer (GWO) and naked mole rat algorithm (NMRA). It follows an iterative division for extensive exploration and incorporates major parametric enhancements for improved exploitation operation. To counter the local optima problems, a stagnation phase using CS and GWO is added. Six new inertia weight operators have been analyzed to adapt algorithmic parameters, and the best combination of these parameters has been found. An analysis of the suitability of DHPN towards population variations and higher dimensions has been performed. For performance evaluation, the CEC 2005 and CEC 2019 benchmark data sets have been used. A comparison has been performed with differential evolution with active archive (JADE), self-adaptive DE (SaDE), success history based DE (SHADE), LSHADE-SPACMA, extended GWO (GWO-E), jDE100, and others. The DHPN algorithm is also used to solve the image fusion problem for four fusion quality metrics, namely, edge-based similarity index ($$Q^{AB/F}$$QAB/F), sum of correlation difference (SCD), structural similarity index measure (SSIM), and artifact measure ($$N^{AB/F}$$NAB/F). The average$$Q^{AB/F} = 0.765508$$QAB/F=0.765508,$$SCD = 1.63185$$SCD=1.63185,$$SSIM = 0.726317$$SSIM=0.726317, and$$N^{AB/F} = 0.006617$$NAB/F=0.006617shows the best combination of results obtained by DHPN with respect to the existing algorithms such as DCH, CBF, GTF, JSR and others. Experimental and statistical Wilcoxon’s and Friedman’s tests show that the proposed DHPN algorithm performs significantly better in comparison to the other algorithms under test.
Adolescent alcohol exposure persistently alters orbitofrontal cortical encoding of Pavlovian conditional stimulus components in female rats
Authors: Pochapski Jose A. , Gómez-A Alexander , Stringfield Sierra J. , Jaggers Hannah , Boettiger Charlotte A. , Da Cunha Claudio , Robinson Donita L.
Published: June 2024

Exposure to alcohol during adolescence impacts cortical and limbic brain regions undergoing maturation. In rodent models, long-term effects on behavior and neurophysiology have been described after adolescent intermittent ethanol (AIE), especially in males. We hypothesized that AIE in female rats increases conditional approach to a reward-predictive cue and corresponding neuronal activity in the orbitofrontal cortex (OFC) and nucleus accumbens (NAc). We evaluated behavior and neuronal firing after AIE (5 g/kg intragastric) or water (CON) in adult female rats. Both AIE and CON groups expressed a ST phenotype, and AIE marginally increased sign-tracking (ST) and decreased goal-tracking (GT) metrics. NAc neurons exhibited phasic firing patterns to the conditional stimulus (CS), with no differences between groups. In contrast, neuronal firing in the OFC of AIE animals was greater at CS onset and offset than in CON animals. During reward omission, OFC responses to CS offset normalized to CON levels, but enhanced OFC firing to CS onset persisted in AIE. We suggest that the enhanced OFC neural activity observed in AIE rats to the CS could contribute to behavioral inflexibility. Ultimately, AIE persistently impacts the neurocircuitry of reward-motivated behavior in female rats.
In situ monitoring of thin alumina passive film growth by surface plasmon resonance (SPR) during an electrochemical process
Authors: Dutems J. , Crespo-Monteiro N. , Faverjon F. , Gâté V. , Turover D. , Marcellin S. , Ter-Ovanessian B. , Héau C. , Verrier I. , Normand B. , Jourlin Y.
Published: June 2024

This article presents a sensing technique to characterize the growth of an alumina passive film on an aluminum micro structured layer in situ. The technique uses surface plasmon resonance (SPR) on aluminum coated gratings with spectroscopic measurements during electrochemical polarization in 0.02M Na2SO4. The structure of the sensor was first simulated and then fabricated by photolithography. The grating was then replicated by nanoimprint (NIL) in Sol–Gel before pure aluminum layer was deposited by RF magnetron sputtering to produce the samples used in this study. Coupled plasmonic and electrochemical measurements confirmed the feasibility of in situ characterization (thickness) of alumina passive film on aluminum-based gratings in neutral aqueous media. Combining both measurements with an appropriated SPR spectrum fitting lead to alumina thickness monitoring within a few nanometers’ accuracy. The objectives and challenges of this study are to better characterize the alumina growth during electrochemical process combining in situ electrochemical process and SPR spectra in order to determine thin passive layer characteristics.