bluuebunny/crossref_metadata_2025 huggingface dataset:
Lathyrol reduces the RCC invasion and incidence of EMT via affecting the expression of AR and SPHK2 in RCC mice
Authors: Song Shengyou , Tai Lunwei , Xu Yuqi , Jiang Junling , Zhou Lei , Zhao Junfeng
Published: July 2024

Objective

To investigate the effects of Lathyrol on the expression of androgen receptor (AR) and sphingosine kinase 2 (SPHK2) in renal cell carcinoma (RCC) mice and to further explore the mechanism by which Lathyrol inhibits the invasion and incidence of epithelial-mesenchymal transition (EMT).

Methods

An RCC xenograft mouse model was constructed, and the mice were randomly divided into a model group, an experiment group and a negative control group. The experiment group was intragastrically gavaged with Lathyrol solution (20 mg/kg), the model group was intragastrically gavaged with 0.9% NaCl (same volume as that used in the experiment group), and the negative control group was injected intraperitoneally with 2 mg/kg cisplatin aqueous solution. Changes in the body weight and tumor volume of the mice were recorded. Western blot (WB) was used to assess the protein expression levels of AR, p-AR, CYP17A1, PARP1, E-cadherin, N-cadherin, vimentin, α-SMA, β-catenin, and ZO-1. Protein expression levels of SPHK2, metal matrix protease 2 (MMP2), MMP9 and urokinase-type plasminogen activator (uPA) in tumor tissues were assessed by immunohistochemistry (IHC). AR expression in tumor tissues was assessed after immunofluorescence (IF) staining.

Results

After 14 days of drug administration, compared with that in the model group, the tumor volumes in the negative control and experiment groups were lower; the difference in tumor volume among the model, control and experiment groups was statistically significant (P < 0.05). The differences in body weight among the three groups were not statistically significant (P > 0.05). In the model group, the protein expression levels of AR, p-AR, CYP17A1, SPHK2, and PARP1 were relatively increased, the protein expression levels of E-cadherin and ZO-1 were relatively reduced (P < 0.05), and the protein expression levels of N-cadherin, β-catenin, vimentin, and α-SMA were relatively increased (P < 0.05). In the negative control and experiment groups, the protein expression levels of AR, p-AR, CYP17A1, SPHK2, and PARP1 were relatively decreased (P < 0.05), the protein expression levels of E-cadherin and ZO-1 were relatively increased (P < 0.05), and the protein expression levels of N-cadherin, β-catenin, vimentin and α-SMA were relatively decreased (P < 0.05).

Conclusion

Lathyrol and cisplatin inhibit the proliferation of RCC xenografts, reduce the protein expression levels of AR, CYP17A1, SPHK2, PARP1, E-cadherin, and ZO-1 in tumor tissues (P < 0.05), and promote the protein expression levels of N-cadherin, β-catenin, vimentin and α-SMA (P < 0.05). Therefore, Lathyrol reduces RCC invasion and EMT by affecting the expression of AR and SPHK2 in RCC mice.
Changes in Learning Outcomes of Students Participating in Problem-Based Learning for the First Time: A Case Study of a Financial Management Course
Authors: Lee Yung-Chuan
Published: July 2024

The aim of this study was to explore how first-time problem-based learning (PBL) participants can improve their learning outcomes. Empirical results showed that students with higher academic performance and attendance rates significantly enhanced their critical thinking and problem-solving skills through PBL compared to traditional lecture-based methods. However, PBL was less effective for students with lower academic performance or attendance rates compared to traditional lectures, highlighting the impact of student characteristics on PBL outcomes. Tutors should focus on students with lower academic or attendance rates, encouraging their active participation to improve overall learning outcomes. Results of path model analysis revealed that tutor performance significantly influences both the learning process and the development of critical thinking and problem-solving skills. Self-directed learning greatly influences critical thinking, while the functionality of tutorial groups significantly affects problem-solving skills. These findings emphasized the importance of tutor performance in enhancing the learning outcomes of students new to PBL. Therefore, educational institutions should invest in PBL teaching seminars to boost tutor performance and ultimately improve student learning outcomes.
Three old problems from the Polish school of mathematics
Authors: Montejano Luis
Published: July 2024

This note deals with three problems posed in the 1930s by two prominent members of the Polish school of mathematics. The first problem is known as the isometric Banach conjecture and deals with the simplest characterization of Hilbert spaces among Banach spaces. It was stated in 1932 by Stephan Banach in his book Théorie des opérations linéaires, 1987. The second is Problem 68 in the Scottish Book, 2015, posed by Stanislaw Ulam in 1936, and the third is the well known floating body problem stated by Stanislaw Ulam in 1935 and which is also known as Problem 19 of the Scottish Book.
Intuitionistic fuzzy pattern recognition model in assessment of the social empowerment index for Azerbaijan
Authors: Imanov G. , Aliyev A.
Published: July 2024

In this work, an intuitionistic fuzzy pattern recognition model is developed to evaluate the social empowerment index (SEI) for Azerbaijan. The global social and economic indices are usually computed with classical methods, in which the data uncertainty and fuzziness are not taken into account. The main advantageous points of the current research are to take into account the fuzziness of input data and incurring fuzziness along the computation process which also are the main reasons for the application of fuzzy logic extension-based tools. The presented work integrates the following operations: normalization of negative and positive affecting indicators, fuzzification of normalized data, intuitionistic fuzzy preference relation-based weight computation, checking the consistency of intuitionistic fuzzy preference relation matrices, intuitionistic fuzzy aggregation of indicators and sub-indices, and intuitionistic fuzzy pattern recognition based on similarity measures. The set-up algorithm in the proposed paper makes it a comprehensive approach in the computation of socio-economic indices, compared to the existing multiple criteria decision-making methods. The obtained results exhibit SEI level in Azerbaijan, and the proposed approach can be applied in the analysis and estimation of other socio-economic phenomena.
Intra-migrant workplace conflict: impediment to improving migrants’ workforce integration
Authors: Chatrath Puja , Hack-Polay Dieu
Published: July 2024

This study examines the tensions between newcomer migrants and established immigrants in the workforce in the United Kingdom. Semi-structured interviews were conducted with 23 participants in a food-manufacturing company to investigate how solidarity and conflict among groups of migrants impact their ability to integrate into the workplace. The research found that heightened levels of conflict occur between new and long-term immigrants. This engenders segregation as well as discrimination within the immigrant groups, which then hampers their career growth opportunities. The results have important consequences for diversity and inclusion in the workforce. The study shows that diversity needs a greater and wider focus than the current emphasis on the local population vs. immigrant paradigm. More attention should be devoted to tackling tensions between groups of immigrants.
A comprehensive dataset for dynamic analysis of ocean front
Authors: Yang Yuting , Gao Ying , Sun Xin , Ju Yakun , Zhang Cong , Lam Kin-Man
Published: July 2024

This paper proposes an ocean front database and a method for its construction tailored for studying the dynamic evolution of ocean fronts. Ocean fronts play a crucial role in the interactions between the ocean and atmosphere, affecting the transfer of heat and matter in the ocean. In recent years, research on ocean fronts has emerged as a significant and rapidly evolving area within oceanography. With the development of ocean remote sensing technology, the amount of available ocean remote sensing data has been increasing. However, the potential of this expanding volume of ocean front data remains largely untapped. The lag in data processing technology has hindered research progress in understanding ocean fronts despite the growing amount of data available. To bridge this gap, this paper proposes an ocean front dynamic evolution database along with a method for its construction to further promote research into the variations and interactions of ocean fronts. This is especially relevant for studies utilizing deep learning to explore the dynamic evolution of ocean fronts. Specifically, the proposed database is designed to capture the variation processes of ocean front enhancement and attenuation, as well as the interactions during ocean front splitting and merging. The proposed database construction method allows for the segmentation and extraction of specific ocean fronts of interest from ocean front images. The proposed method is beneficial for analyzing the dynamic evolution between multiple ocean fronts on the same timeline.
Acute myeloid leukemia first presentation with central nervous system (CNS) involvement: a case report
Authors: Shateri Amiri Bahareh , Aliabadi Fatemeh , Ghalamkari Marziyeh , Omidali Mehrnia , Babaheidarian Pegah , Ayoubpour Mohamadreza , Hejrati Alireza , Bubur Jan Bozorgi Negar , Rekabi Vahab
Published: July 2024

Background

Acute myeloid leukemia (AML) typically presents with bone marrow myeloblast replacement, which can interfere with normal hematopoiesis. In rare cases, extramedullary involvement of myeloblasts can occur and affect various organs. When AML affects the central nervous system at the time of diagnosis, it is considered to be an unusual occurrence, with less than 5% of incidence.

Case presentation

A 19-year-old girl presented with progressively worsening frontal tension headache and blurred vision over a month. She also experienced sudden onset right eye strabismus and diplopia 25 days prior to her visit. Additionally, her complete blood count revealed pancytopenia.

Following a thorough evaluation, including cytology and flow cytometry, of cerebrospinal fluid and bone marrow biopsy, she was diagnosed as AML with meningeal involvement.

Conclusion

Physicians should consider underlying malignancy in patients with meningeal symptoms, cranial nerve involvement, and/or resistance to conventional therapies.
A Machine Learning‐Based Approach to Quantify ENSO Sources of Predictability
Authors: Colfescu Ioana , Christensen Hannah , Gagne David John
Published: July 2024

A machine learning method is used to identify sources of long‐term ENSO predictability in the ocean (sea surface temperature (SST) and heat content) and the atmosphere (near‐surface zonal wind (U10)). Tropical SST represents the primary source of predictability skill. While U10 does not increase the skill when associated with SST, our analysis suggests U10 alone has apredictive skill comparable to that of SST between 11 and 21 months in advance, from late fall up to late spring. The long‐lead signal originates from coupled wind‐SST interactions across the Indian Ocean (IO) and propagates across the Pacific via an atmospheric bridge mechanism. A linear correlation analysis supports this mechanism, suggesting a precursor link between anomalies in SST in the western and wind in the eastern IO. Our results have important implications for ENSO predictions beyond 1 year ahead and identify the key role of U10 over the IO.
Molecular Composition Evolution of Dissolved Organic Matter With Water Depth in Prydz Bay of East Antarctic: Carbon Export Implications
Authors: Jiang Bin , Zhao Jun , Li Dong , Zhan Liyang , Gao Zhongyong , Sun Heng , Zhou Yuping , Pan Jianming , Sun Yongge
Published: July 2024

This study analyzes the molecular composition of dissolved organic matter (DOM) in Prydz Bay by Fourier Transform Ion Cyclotron Resonance mass spectrometry to probe the carbon sequestration capacity in the continental shelf system. Concentrations of particulate organic carbon (POC), particulate nitrogen and dissolved organic carbon (DOC) with water depth show that POC could be mainly decomposed into DOC and/or microbially degraded. Highly labile DOC is further degraded and remineralized by microorganisms within the upper 200 m, as evidenced by a downward enrichment of 13CPOC and increases in the average molecular weight, oxygen atom number (O) and double bond equivalents of DOM molecules, indicating that biodegradation is the main driver for particulate organic matter and DOM evolution with water depth. Semi‐quantitative calculation demonstrates that ∼83% of POC was transformed to DOC as well as dissolved inorganic carbon (DIC), and ∼30% of DOC further to DIC via microbial degradation within the upper 200 m in summer, resulting in a relatively low total organic carbon content in sediments of Prydz Bay. The newly transformed DIC and residue DOC can be preserved in the deep layer due to the formation of well stratified and stable water body in summer of Prydz Bay, ultimately entering the regional circulation system instead of being released back into the atmosphere. This could be one of the most important processes determining the atmosphere CO2 uptake in the continental shelf system of Southern Ocean.
Climate Change Can Intensify the Effects of Local Interventions: A Morphological Modeling Study of a Highly Engineered Estuary
Authors: Siemes Rutger W. A. , Duong Trang Minh , Borsje Bas W. , Hulscher Suzanne J. M. H.
Published: July 2024

Estuaries worldwide are susceptible and adapting to climate change (CC) impacts from both the river and coastal boundaries. Furthermore, engineering efforts are undertaken to improve flood safety, to claim land for human use or for port operations, which change estuary morphology. This paper aims to gain an understanding of the combined effects of CC and human interventions on the estuarine‐wide morphological response by analyzing the sediment infilling of highly engineered estuaries. A schematized process‐based morphodynamic model is used (Delft3D‐FM, in 2DH), resembling a highly engineered estuary in the Rhine‐Meuse Delta, The Netherlands. Three types of changes were implemented, both in isolation and in combination: (a) local interventions (changing channel depth or wetland area), (b) upstream human interventions (changing fluvial sediment supply) and (c) extreme CC scenarios (with projections for the future forcings and bathymetry). Results show that a CC scenario can elicit both positive and negative changes in the estuary's sediment budget. The direction and magnitude of the change depend on the local intervention and can align with the effect of the local intervention, intensifying its impact. The combined effects can even reverse the sign of the sediment budget. This stresses the need of analyzing CC impacts in combination with human interventions. Additionally, a relationship was identified which quantifies how a change in peak flow velocity due to both local interventions and sea‐level rise affects the annual sediment budget. These findings can help determine how local interventions affect morphodynamics of engineered estuaries in present and future climates.
A High‐Performance Coupled Human And Natural Systems (CHANS) Model for Flood Risk Assessment and Reduction
Authors: Qin Haoyang , Liang Qiuhua , Chen Huili , De Silva Varuna
Published: July 2024

In recent years, flood risk in urban areas has been rapidly increasing due to unsustainable urban development, changes of hydrological processes and frequent occurrence of extreme weather events. Flood risk assessment should realistically take into account the complex interactions between human and natural systems to better inform risk management and improve resilience. In this study, we propose a novel Coupled Human And Natural Systems (CHANS) modeling framework to capture the intricate interactive human behaviors and flooding process at a high spatial resolution. The new CHANS modeling framework integrates a high‐performance hydrodynamic model with an agent‐based model to simulate the complex responses of individual households to the evolving flood conditions, leveraging the computing power of graphics processing units (GPUs) to achieve real‐time simulation. The framework is applied to reproduce the 2015 Desmond flood in the 2,500 km2 Eden Catchment in England, demonstrating its ability to predict interactive flood‐human dynamics and assess flood impact at the household‐level. The study also further explores the effectiveness of different flood risk management strategies, including the provision of early warning and distribution of sandbags, in mitigating flood impact. The new CHANS model potentially provides a useful tool for understanding short‐term human behaviors and their impact on flood risk during a flood event, which is important for the development of effective disaster risk management plans.
Original Insights Into Rock Slope Damage Processes Until Collapse From Passive Seismic Monitoring
Authors: Bottelin P. , Baillet L.
Published: July 2024

We performed a passive seismic monitoring of the La Praz ∼14,000 m3 unstable slope (French Alps) spanning over 10 years. During the last 6 months prior to collapse, we detected a clear 24% decrease in the slope's fundamental resonance frequency, f0, caused by a reduction in overall rock mass stiffness. The combined study of f0 and slope deformation suggested the alternating importance of sudden brittle failure processes versus more ductile phases with possible sliding. Seismic monitoring revealed slope damage that remained ambiguous or undetected with ground surface deformation monitoring, and highlighted critical periods with intense damage. Only some of these critical damage periods could be related to clear external forcing factors such as intense rainfall episodes. These new insights into rock slope's structural condition at depth represent an asset for future monitoring systems. Surface deformation and passive seismic stiffness tracking combined could reveal active slopes with ongoing damage processes.
Cyclone‐Like Features Within the Stratospheric Polar‐Night Vortex
Authors: Davies Huw C. , Sprenger Michael
Published: July 2024

Distinctive synoptic‐scale (∼1,500 km) flow features are identified within the core of the stratospheric polar‐night vortex at stratopause altitudes (∼50 km). Typically they comprise a train or a complex pattern of transient vortices, each characterized by enhanced values of potential vorticity (PV) and relative vorticity but with a weaker thermal signal. In the MERRA‐2 (and two other) reanalysis fields these cyclone‐like features persist for several days, occur episodically, and form essentially within the core of the polar‐night vortex itself. Their origin is plausibly linked to a form of barotropic instability associated with a radiatively‐induced annular ring of enhanced PV. Moreover, their ubiquity and dynamics carries possible implications for: ‐ the structure of the larger‐scale polar vortex and its preconditioning ahead of a Sudden Stratospheric Warming event; the distribution of trace‐constituents within the core; and the features representation in extended range/seasonal prediction and climate models.
Not So Fast: A New Catalog of Meteor Persistent Trains
Authors: Cordonnier L. E. , Obenberger K. S. , Holmes J. M. , Taylor G. B. , Vida D.
Published: July 2024

This paper presents the results of a nearly 2‐year long campaign to detect and analyze meteor persistent trains (PTs)—self‐emitting phenomena which can linger up to an hour after their parent meteor. The modern understanding of PTs has been primarily developed from the Leonid storms at the turn of the century; our goal was to assess the validity of these conclusions using a diverse sample of meteors with a wide range of velocities and magnitudes. To this end, year‐round observations were recorded by the Widefield Persistent Train camera, 2nd edition (WiPT2) and were passed through a pipeline to filter out airplanes and flag potential meteors. These were classified by visual inspection based on the presence and duration of trains. Observed meteors were cross‐referenced with the Global Meteor Network (GMN) database, which independently detects and calculates meteor parameters, enabling statistical analysis of PT‐leaving meteors. There were 4,726 meteors codetected by the GMN, with 636 of these leaving trains. Among these were a large population of slow, dim meteors that left PTs; these slower meteors had a greater train production rate relative to their faster counterparts. Unlike prior research, we did not find a clear magnitude cutoff or a strong association with fast meteor showers. Additionally, we note several interesting trends not previously reported, which include PT eligibility being primarily determined by a meteor's terminal height and an apparent dynamical origin dependence that likely reflects physical meteoroid properties.
Rearrangements involving 11q23.3/KMT2A in adult AML: mutational landscape and prognostic implications – a HARMONY study
Authors: Hernández-Sánchez Alberto , González Teresa , Sobas Marta , Sträng Eric , Castellani Gastone , Abáigar María , Valk Peter J. M. , Villaverde Ramiro Ángela , Benner Axel , Metzeler Klaus H. , Azibeiro Raúl , Tettero Jesse M. , Martínez-López Joaquín , Pratcorona Marta , Martínez Elicegui Javier , Mills Ken I. , Thiede Christian , Sanz Guillermo , Döhner Konstanze , Heuser Michael , Haferlach Torsten , Turki Amin T. , Reinhardt Dirk , Schulze-Rath Renate , Barbus Martje , Hernández-Rivas Jesús María , Huntly Brian , Ossenkoppele Gert , Döhner Hartmut , Bullinger Lars
Published: July 2024

Balanced rearrangements involving the KMT2A gene (KMT2Ar) are recurrent genetic abnormalities in acute myeloid leukemia (AML), but there is lack of consensus regarding the prognostic impact of different fusion partners. Moreover, prognostic implications of gene mutations co-occurring with KMT2Ar are not established. From the HARMONY AML database 205 KMT2Ar adult patients were selected, 185 of whom had mutational information by a panel-based next-generation sequencing analysis. Overall survival (OS) was similar across the different translocations, including t(9;11)(p21.3;q23.3)/KMT2A::MLLT3 (p = 0.756). However, independent prognostic factors for OS in intensively treated patients were age >60 years (HR 2.1, p = 0.001), secondary AML (HR 2.2, p = 0.043), DNMT3A-mut (HR 2.1, p = 0.047) and KRAS-mut (HR 2.0, p = 0.005). In the subset of patients with de novo AML < 60 years, KRAS and TP53 were the prognostically most relevant mutated genes, as patients with a mutation of any of those two genes had a lower complete remission rate (50% vs 86%, p < 0.001) and inferior OS (median 7 vs 30 months, p < 0.001). Allogeneic hematopoietic stem cell transplantation in first complete remission was able to improve OS (p = 0.003). Our study highlights the importance of the mutational patterns in adult KMT2Ar AML and provides new insights into more accurate prognostic stratification of these patients.
Neuroimaging and natural language processing-based classification of suicidal thoughts in major depressive disorder
Authors: Lee Dong Yun , Byeon Gihwan , Kim Narae , Son Sang Joon , Park Rae Woong , Park Bumhee
Published: July 2024

Suicide is a growing public health problem around the world. The most important risk factor for suicide is underlying psychiatric illness, especially depression. Detailed classification of suicide in patients with depression can greatly enhance personalized suicide control efforts. This study used unstructured psychiatric charts and brain magnetic resonance imaging (MRI) records from a psychiatric outpatient clinic to develop a machine learning-based suicidal thought classification model. The study included 152 patients with new depressive episodes for development and 58 patients from a geographically different hospital for validation. We developed an eXtreme Gradient Boosting (XGBoost)-based classification models according to the combined types of data: independent components-map weightings from brain T1-weighted MRI and topic probabilities from clinical notes. Specifically, we used 5 psychiatric symptom topics and 5 brain networks for models. Anxiety and somatic symptoms topics were significantly more common in the suicidal group, and there were group differences in the default mode and cortical midline networks. The clinical symptoms plus structural brain patterns model had the highest area under the receiver operating characteristic curve (0.794) versus the clinical notes only and brain MRI only models (0.748 and 0.738, respectively). The results were consistent across performance metrics and external validation. Our findings suggest that focusing on personalized neuroimaging and natural language processing variables improves evaluation of suicidal thoughts.
Urinary metabolomics signature of animal and plant protein intake and its association with 24-h blood pressure: the African-PREDICT study
Authors: Strauss-Kruger Michél , Pieters Marlien , van Zyl Tertia , Kruger Ruan , Jacobs Adriaan , Jansen van Vuren Esmé , Louw Roan , Mels Carina
Published: July 2024

The contrasting relationships of plant and animal protein intake with blood pressure (BP) may be partially attributed to the differential non-protein (e.g., saturated fat and fibre) and amino acid (AA) compositions. This study determined whether animal and plant protein intake were related to differential metabolomic profiles associated with BP. This study included 1008 adults from the African-PREDICT study (aged 20–30 years). Protein intake was determined using 24-h dietary recalls. Twenty-four-hour ambulatory BP was measured. Amino acids and acylcarnitines were analysed in spot urine samples using liquid chromatography-tandem mass spectrometry-based metabolomics. Participants with a low plant, high animal protein intake had higher SBP (by 3 mmHg, p = 0.011) than those with high plant, low animal protein intake (low-risk group). We found that the relationships of plant and animal protein intake with 24-h SBP were partially mediated by BMI and saturated fat intake, which were independently associated with SBP. Protein intake was therefore not related to SBP in multiple regression analysis after adjusting for confounders. In the low-risk group, methionine (Std. β = −0.217; p = 0.034), glutamic acid (Std. β = −0.220; p = 0.031), glycine (Std. β = −0.234; p = 0.025), and proline (Std. β = −0.266; p = 0.010) were inversely related to SBP, and beta-alanine (Std. β = −0.277; p = 0.020) to DBP. Ultimately a diet high in animal and low in plant protein intake may contribute to higher BP by means of increased BMI and saturated fat intake. Conversely, higher levels of urinary AAs observed in adults consuming a plant rich diet may contribute to lower BP.
Association between the C-reactive protein-triglyceride glucose index and erectile dysfunction in US males: results from NHANES 2001–2004
Authors: Mei Yangyang , Li Yangmeina , Zhang Bo , Xu Renfang , Feng Xingliang
Published: July 2024

The C-reactive protein-triglyceride glucose index (CTI) is emerging as a novel indicator for comprehensively assessing the severity of both inflammation and insulin resistance. However, the association between CTI and erectile dysfunction (ED) remains largely unexplored. Participant data for this study were sourced from NHANES 2001–2004, with exclusion criteria applied to those lacking information on clinical variables. The CTI was defined as 0.412*Ln (CRP) + ln [T.G. (mg/dL) × FPG (mg/dL)/2]. Weighted univariable and multivariable logistic regression models were utilized to examine the correlation between the CTI and ED, assessing the CTI as both a continuous and categorical variable (quartile). Moreover, subgroup analyses were conducted to pinpoint sensitive populations, and interaction analysis was performed to validate the findings. A total of 1502 participants were included in the final analysis, encompassing 302 with ED and 1200 without ED. After adjusting for potential confounders, the CTI was positively associated with ED incidence (OR = 1.56, 95% CI: 1.27–1.90, P = 0.002). The fourth quartile of the CTI significantly increased the incidence of ED (OR = 2.69, 95% CI: 1.07–6.74, P = 0.04), and the lowest quartile of CTI was used as the reference. The dose-response curve revealed a positive linear relationship between the CTI and the incidence of ED. Subgroup analysis confirmed the consistent positive relationship between the CTI and ED. The interaction test indicated no significant impact on this association. Finally, a sensitivity analysis was performed to verify the significant positive correlation between the CTI and severe ED (OR = 1.44, 95% CI: 1.19–1.76, P = 0.004). Our national data indicate that a greater CTI is positively linked to an increased risk of ED in US men, suggesting its potential for use in clinical practice for ED prevention or early intervention. Additional large-scale prospective studies are warranted to substantiate the causative relationship between CTI and ED.
Enhancing extracellular vesicle cargo loading and functional delivery by engineering protein-lipid interactions
Authors: Peruzzi Justin A. , Gunnels Taylor F. , Edelstein Hailey I. , Lu Peilong , Baker David , Leonard Joshua N. , Kamat Neha P.
Published: July 2024

Naturally generated lipid nanoparticles termed extracellular vesicles (EVs) hold significant promise as engineerable therapeutic delivery vehicles. However, active loading of protein cargo into EVs in a manner that is useful for delivery remains a challenge. Here, we demonstrate that by rationally designing proteins to traffic to the plasma membrane and associate with lipid rafts, we can enhance loading of protein cargo into EVs for a set of structurally diverse transmembrane and peripheral membrane proteins. We then demonstrate the capacity of select lipid tags to mediate increased EV loading and functional delivery of an engineered transcription factor to modulate gene expression in target cells. We envision that this technology could be leveraged to develop new EV-based therapeutics that deliver a wide array of macromolecular cargo.
Shallow-level defect passivation by 6H perovskite polytype for highly efficient and stable perovskite solar cells
Authors: Kim Hobeom , Yoo So-Min , Ding Bin , Kanda Hiroyuki , Shibayama Naoyuki , Syzgantseva Maria A. , Tirani Farzaneh Fadaei , Schouwink Pascal , Yun Hyung Joong , Son Byoungchul , Ding Yong , Kim Beom-Soo , Kim Young Yun , Park Junmo , Syzgantseva Olga A. , Jeon Nam Joong , Dyson Paul J. , Nazeeruddin Mohammad K.
Published: July 2024

The power conversion efficiency of perovskite solar cells continues to increase. However, defects in perovskite materials are detrimental to their carrier dynamics and structural stability, ultimately limiting the photovoltaic characteristics and stability of perovskite solar cells. Herein, we report that 6H polytype perovskite effectively engineers defects at the interface with cubic polytype FAPbI3, which facilitates radiative recombination and improves the stability of the polycrystalline film. We particularly show the detrimental effects of shallow-level defect that originates from the formation of the most dominant iodide vacancy (VI+) in FAPbI3. Furthermore, additional surface passivation on top of the hetero-polytypic perovskite film results in an ultra-long carrier lifetime exceeding 18 μs, affords power conversion efficiencies of 24.13% for perovskite solar cells, 21.92% (certified power conversion efficiency: 21.44%) for a module, and long-term stability. The hetero-polytypic perovskite configuration may be considered as close to the ideal polycrystalline structure in terms of charge carrier dynamics and stability.
Radially distributed charging time constants at an electrode-solution interface
Authors: Niu Ben , Xie Ruo-Chen , Ren Bin , Long Yi-Tao , Wang Wei
Published: July 2024

An electrochemically homogeneous electrode-solution interface should be understood as spatially invariant in both terms of intrinsic reactivity for the electrode side and electrical resistance mainly for the solution side. The latter remains presumably assumed in almost all cases. However, by using optical microscopy to spatially resolve the classic redox electrochemistry occurring at the whole surface of a gold macroelectrode, we discover that the electron transfer occurs always significantly sooner (by milliseconds), rather than faster in essence, at the radial coordinates closer to the electrode periphery than the very center. So is the charging process when there is no electron transfer. Based on optical measurements of the interfacial impedance, this spatially unsynchronized electron transfer is attributed to a radially non-uniform distribution of solution resistance. We accordingly manage to eliminate the heterogeneity by engineering the solution resistance distribution. The revealed spatially-dependent charging time ‘constant’ (to be questioned) would help paint our overall fundamental picture of electrode kinetics.
Designed wrinkles for optical encryption and flexible integrated circuit carrier board
Authors: Zhong Shilong , Zhu Zhaoxiang , Huo Qizheng , Long Yubo , Gong Li , Ma Zetong , Yu Dingshan , Zhang Yi , Liang Weien , Liu Wei , Wang Cheng , Yuan Zhongke , Yang Yuzhao , Lu Shaolin , Chen Yujie , Zheng Zhikun , Chen Xudong
Published: July 2024

Patterns on polymers usually have different mechanical properties as those of the substrates, causing deformation or distortion and even detachment of the patterns from the polymer substrates. Herein, we present a wrinkling strategy, which utilizes photolithography to define the area of stress distribution by light-induced physical crosslinking of polymers and controls diffusion of residual solvent to redistribute the stress and then offers the same material for patterns as substrate by thermal polymerization, providing uniform wrinkles without worrying about force relaxation. The strategy allows the recording and hiding of up to eight switchable images in one place that can be read by the naked eye without crosstalk, applying the wrinkled polymer for optical anti-counterfeiting. The wrinkled polyimide film was also utilized to act as a substrate for the creation of fine copper circuit by a full-additive process. It generates flexible integrated circuit (IC) carrier board with copper wire density of 400% higher than that of the state-of-the-art in industry while fulfilling the standards for industrialization.
Evaluation and mitigation of the limitations of large language models in clinical decision-making
Authors: Hager Paul , Jungmann Friederike , Holland Robbie , Bhagat Kunal , Hubrecht Inga , Knauer Manuel , Vielhauer Jakob , Makowski Marcus , Braren Rickmer , Kaissis Georgios , Rueckert Daniel
Published: July 2024

Clinical decision-making is one of the most impactful parts of a physician’s responsibilities and stands to benefit greatly from artificial intelligence solutions and large language models (LLMs) in particular. However, while LLMs have achieved excellent performance on medical licensing exams, these tests fail to assess many skills necessary for deployment in a realistic clinical decision-making environment, including gathering information, adhering to guidelines, and integrating into clinical workflows. Here we have created a curated dataset based on the Medical Information Mart for Intensive Care database spanning 2,400 real patient cases and four common abdominal pathologies as well as a framework to simulate a realistic clinical setting. We show that current state-of-the-art LLMs do not accurately diagnose patients across all pathologies (performing significantly worse than physicians), follow neither diagnostic nor treatment guidelines, and cannot interpret laboratory results, thus posing a serious risk to the health of patients. Furthermore, we move beyond diagnostic accuracy and demonstrate that they cannot be easily integrated into existing workflows because they often fail to follow instructions and are sensitive to both the quantity and order of information. Overall, our analysis reveals that LLMs are currently not ready for autonomous clinical decision-making while providing a dataset and framework to guide future studies.
Extension of efficacy range for targeted malaria-elimination interventions due to spillover effects
Authors: Benjamin-Chung Jade , Li Haodong , Nguyen Anna , Barratt Heitmann Gabriella , Bennett Adam , Ntuku Henry , Prach Lisa M. , Tambo Munyaradzi , Wu Lindsey , Drakeley Chris , Gosling Roly , Mumbengegwi Davis , Kleinschmidt Immo , Smith Jennifer L. , Hubbard Alan , van der Laan Mark , Hsiang Michelle S.
Published: July 2024

Malaria-elimination interventions aim to extinguish hotspots and prevent transmission to nearby areas. Here, we re-analyzed a cluster-randomized trial of reactive, focal interventions (chemoprevention using artemether–lumefantrine and/or indoor residual spraying with pirimiphos-methyl) delivered within 500 m of confirmed malaria index cases in Namibia to measure direct effects (among intervention recipients within 500 m) and spillover effects (among non-intervention recipients within 3 km) on incidence, prevalence and seroprevalence. There was no or weak evidence of direct effects, but the sample size of intervention recipients was small, limiting statistical power. There was the strongest evidence of spillover effects of combined chemoprevention and indoor residual spraying. Among non-recipients within 1 km of index cases, the combined intervention reduced malaria incidence by 43% (95% confidence interval, 20–59%). In analyses among non-recipients within 3 km of interventions, the combined intervention reduced infection prevalence by 79% (6–95%) and seroprevalence, which captures recent infections and has higher statistical power, by 34% (20–45%). Accounting for spillover effects increased the cost-effectiveness of the combined intervention by 42%. Targeting hotspots with combined chemoprevention and vector-control interventions can indirectly benefit non-recipients up to 3 km away.
Systematic comparison of sequencing-based spatial transcriptomic methods
Authors: You Yue , Fu Yuting , Li Lanxiang , Zhang Zhongmin , Jia Shikai , Lu Shihong , Ren Wenle , Liu Yifang , Xu Yang , Liu Xiaojing , Jiang Fuqing , Peng Guangdun , Sampath Kumar Abhishek , Ritchie Matthew E. , Liu Xiaodong , Tian Luyi
Published: July 2024

Recent developments of sequencing-based spatial transcriptomics (sST) have catalyzed important advancements by facilitating transcriptome-scale spatial gene expression measurement. Despite this progress, efforts to comprehensively benchmark different platforms are currently lacking. The extant variability across technologies and datasets poses challenges in formulating standardized evaluation metrics. In this study, we established a collection of reference tissues and regions characterized by well-defined histological architectures, and used them to generate data to compare 11 sST methods. We highlighted molecular diffusion as a variable parameter across different methods and tissues, significantly affecting the effective resolutions. Furthermore, we observed that spatial transcriptomic data demonstrate unique attributes beyond merely adding a spatial axis to single-cell data, including an enhanced ability to capture patterned rare cell states along with specific markers, albeit being influenced by multiple factors including sequencing depth and resolution. Our study assists biologists in sST platform selection, and helps foster a consensus on evaluation standards and establish a framework for future benchmarking efforts that can be used as a gold standard for the development and benchmarking of computational tools for spatial transcriptomic analysis.
Genome wide association study of seedling and adult plant leaf rust resistance in two subsets of barley genetic resources
Authors: Amouzoune Mariam , Rehman Sajid , Benkirane Rachid , Udupa Sripada , Mamidi Sujan , Kehel Zakaria , Al-Jaboobi Muamer , Amri Ahmed
Published: July 2024

Leaf rust (LR) caused by Puccinia hordei is a serious disease of barley worldwide, causing significant yield losses and reduced grain quality. Discovery and incorporation of new sources of resistance from gene bank accessions into barley breeding programs is essential for the development of leaf rust resistant varieties. To identify Quantitative Trait Loci (QTL) conferring LR resistance in the two barley subsets, the Generation Challenge Program (GCP) reference set of 142 accessions and the leaf rust subset constructed using the Focused Identification of Germplasm Strategy (FIGS) of 76 barley accessions, were genotyped to conduct a genome-wide association study (GWAS). The results revealed a total of 59 QTL in the 218 accessions phenotyped against barley leaf rust at the seedling stage using two P. hordei isolates (ISO-SAT and ISO-MRC), and at the adult plant stage in four environments in Morocco. Out of these 59 QTL, 10 QTL were associated with the seedling resistance (SR) and 49 QTL were associated with the adult plant resistance (APR). Four QTL showed stable effects in at least two environments for APR, whereas two common QTL associated with SR and APR were detected on chromosomes 2H and 7H. Furthermore, 39 QTL identified in this study were potentially novel. Interestingly, the sequences of 27 SNP markers encoded the candidate genes (CGs) with predicted protein functions in plant disease resistance. These results will provide new perspectives on the diversity of leaf rust resistance loci for fine mapping, isolation of resistance genes, and for marker-assisted selection for the LR resistance in barley breeding programs worldwide.
Metabolic remodeling and calcium handling abnormality in induced pluripotent stem cell-derived cardiomyocytes in dilated phase of hypertrophic cardiomyopathy with MYBPC3 frameshift mutation
Authors: Mori Haruka , Xu Dongzhu , Shimoda Yuzuno , Yuan Zixun , Murakata Yoshiko , Xi Binyang , Sato Kimi , Yamamoto Masayoshi , Tajiri Kazuko , Ishizu Tomoko , Ieda Masaki , Murakoshi Nobuyuki
Published: July 2024

Hypertrophic cardiomyopathy (HCM) is an inherited disorder characterized by left ventricular hypertrophy and diastolic dysfunction, and increases the risk of arrhythmias and heart failure. Some patients with HCM develop a dilated phase of hypertrophic cardiomyopathy (D-HCM) and have poor prognosis; however, its pathogenesis is unclear and few pathological models exist. This study established disease-specific human induced pluripotent stem cells (iPSCs) from a patient with D-HCM harboring a mutation in MYBPC3 (c.1377delC), a common causative gene of HCM, and investigated the associated pathophysiological mechanisms using disease-specific iPSC-derived cardiomyocytes (iPSC-CMs). We confirmed the expression of pluripotent markers and the ability to differentiate into three germ layers in D-HCM patient-derived iPSCs (D-HCM iPSCs). D-HCM iPSC-CMs exhibited disrupted myocardial sarcomere structures and an increased number of damaged mitochondria. Ca2+ imaging showed increased abnormal Ca2+ signaling and prolonged decay time in D-HCM iPSC-CMs. Cell metabolic analysis revealed increased basal respiration, maximal respiration, and spare-respiratory capacity in D-HCM iPSC-CMs. RNA sequencing also showed an increased expression of mitochondrial electron transport system-related genes. D-HCM iPSC-CMs showed abnormal Ca2+ handling and hypermetabolic state, similar to that previously reported for HCM patient-derived iPSC-CMs. Although further studies are required, this is expected to be a useful pathological model for D-HCM.
Unraveling the independent role of METTL3 in m6A modification and tumor progression in esophageal squamous cell carcinoma
Authors: Du Bin , Wang Pu , Wei Lingyu , Qin Kai , Pei Zhen , Zheng Jinping , Wang Jia
Published: July 2024

METTL3 and METTL14 are traditionally posited to assemble the m6A methyltransferase complex in a stoichiometric 1:1 ratio, modulating mRNA fate via m6A modifications. Nevertheless, recent investigations reveal inconsistent expression levels and prognostic significance of METTL3 and METTL14 across various tumor types, challenging their consistent functional engagement in neoplastic contexts. A pan-cancer analysis leveraging The Cancer Genome Atlas (TCGA) data has identified pronounced disparities in the expression patterns, functional roles, and correlations with tumor burden between METTL3 and METTL14, particularly in esophageal squamous cell carcinoma (ESCC). Knockdown experiments of METTL3 in EC109 cells markedly suppress cell proliferation both in vitro and in vivo, whereas METTL14 knockdown shows a comparatively muted effect on proliferation and does not significantly alter METTL3 protein levels. mRNA sequencing indicates that METTL3 singularly governs the expression of 1615 genes, with only 776 genes co-regulated with METTL14. Additionally, immunofluorescence co-localization studies suggest discrepancies in cellular localization between METTL3 and METTL14. High-performance liquid chromatography–mass spectrometry (HPLC–MS) analyses demonstrate that METTL3 uniquely associates with the Nop56p-linked pre-rRNA complex and mRNA splicing machinery, independent of METTL14. Preliminary bioinformatics and multi-omics investigations reveal that METTL3’s autonomous role in modulating tumor cell proliferation and its involvement in mRNA splicing are potentially pivotal molecular mechanisms. Our study lays both experimental and theoretical groundwork for a deeper understanding of the m6A methyltransferase complex and the development of targeted tumor therapies focusing on METTL3.
Assessment of knowledge and awareness of stroke among the Syrian population: unveiling the current landscape in Syria through the first nationally representative study
Authors: Kharaba Zelal , Alfoteih Yassen , Jirjees Feras , Albarbandi Mohammad , Hussain Zainab , Al Obaidi Hala , Mansour Sara , Ahmed Munazza , Eltayib Eyman , Barakat Muna , AlSalamat Husam A. , Alzayer Reem , El Khatib Sami , Al-Mohammad Safwan , Hallit Souheil , Malaeb Diana , Hosseini Hassan
Published: July 2024

Stroke is a global public health concern, contributing to high rates of morbidity and mortality. In Syria, the current conflict and associated challenges have had a profound impact on healthcare infrastructure, including education and awareness programs related to stroke. An essential aspect of preventing stroke is the awareness of individuals. The study aimed to investigate factors associated with knowledge and awareness of stroke among Syrian people. A cross-sectional national representative study was conducted in Syria. The questionnaire was created on Google form and disseminated as a link through online platform social media like Facebook, WhatsApp, and Twitter. The population of the study was divided using proportionate random sampling into the 14 governorates. A random sample was selected from each area. The STROBE reporting guideline for cross-sectional studies was followed. Logistic regression analysis was performed to identify the factors associated with poor knowledge of stroke. A total of 1013 Syrian adults participated in the study. With more than half of them were females (53.5%) and employed (55.6%). Significant associations were found between ability to identify at least one correct risk factor and employability status (p = 0.029), single group (p = 0.036) and smokers (p < 0.001). In addition, significant associations were found between identifying at least one correct stroke symptom and smokers (p < 0.001) and no-obese people (p = 0.048). Furthermore, younger age group (below 30 years) were significantly able to list at least one correct stroke consequence compared to the older age groups (p = 0.025). Moreover, a significantly higher number of smokers compared to non-smokers correctly identified at least one stroke consequence (p = 0.019). The study revealed that there is a relatively weak understanding of the preventable nature of stroke among Syrian population. The overall awareness is still inadequate and varies depending on lifestyle factors and employment status.