bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in Drought Characteristics and Heatwave Propagation Over Groundwater Basins in Australia
Authors: Ndehedehe Christopher E. , Adeyeri Oluwafemi E.
Published: September 2024

The commitment to reduce emissions in global climate change science meetings shows collective responsibility to mitigate the risk of climatic extremes in the Anthropocene. However, growing anthropogenic footprint and climate change will exacerbate the impacts of extreme events on freshwater systems, necessitating the need to enhance contemporary understanding of future changes in drought characteristics (e.g., severity, duration, etc.) and climatic extremes in groundwater basins to assess their implications for water supplies and allocation. Using bias-corrected ensemble mean of nine Coupled Model Intercomparison Project Phase 6 (CMIP6) models, drought characteristics are assessed for two future socio-economic scenarios (SSP 370 and 585). Two drought indicators (standardised precipitation index and standardised runoff index) were combined with Heatwave total length (HWTL) to measure changes in drought characteristics and heatwave propagation, respectively, over four groundwater basins (South West Western Australia-SWWA; Murray Darling Basin-MDB; Cambrian Limestone Aquifer-CLA; and South Australia-SA) in Australia. Our findings indicate that as Australian summers become considerably warmer, particularly toward the late twenty-first century, the relationship between rainfall and runoff extremes, which exhibited strong connections historically (e.g., in CLA; r = 0.87), will vary in the future. This relationship is expected to increase in SA, showing stronger correlations (r = 0.67 and 0.82 for SSP 370 and SSP 585, respectively) but decrease in SWWA (r = 0.43 and 0.20, for SSP 370 and SSP 585, respectively). In the MDB, heatwaves are projected to propagate more rapidly into hydrological drought during summer and autumn under the SSP 585 scenario. Even though drought-affected areas are expected to decline in between decades across Australia, the duration and intensity in some locations show no signs of reduction. Increasing drought duration and intensity could limit freshwater availability, and such impact can potentially be exacerbated by the observed shifts and considerable changes in the propagation time of meteorological drought and HTWL to hydrological drought in some basins.
Fulvic and Salicylic Acids Improve Morpho-Physio-Biochemical Attributes, Yield and Fruit Quality of Two Mango Cultivars Exposed to Dual Salinity and Heat Stress Conditions
Authors: Samad Asmaa G. A. Abdel , Shaaban Ahmed
Published: October 2024

Purpose

The present research’s main objective was to explore the potential stimulative effect of fulvic acid (FA) as a soil conditioner and salicylic acid (SA) as foliar spraying on morpho-physio-biochemical attributes, fruit yield, and quality of ‘Sediek’ and ‘Ewais’ mango cultivars (cvs.) grown under saline calcareous soil and heat stress conditions

Methods

Eight treatments, namely, 200 (FA200) and 400 (FA400) g FA tree−1 as a soil addition, 200 (SA200) or 400 (SA400) mg SA L−1 as foliar spraying, and their bilateral combinations (e.g., FA200 + SA200, FA200 + SA400, FA400 + SA200, and FA400 + SA400) compared to untreated control on morpho-physio-biochemical attributes, yield, and fruit quality of ‘Sediek’ and ‘Ewais’ mango cvs. grown under saline calcareous soil and heat stress conditions were assessed. These treatments were carried out using a split-plot arrangement in a randomized complete block design replicated three times during the 2022 and 2023 seasons.

Results

Cultivar Sediek had higher SPAD value, leaf proline and phenolic content, leaf area, fruit weight, yield and vitamin C than Ewais which had higher tree water status and shoot length. Saline calcareous and heat-stressed mango trees without FA or/and SA treatment had a significant decline in their water status, photosynthetic traits, biochemical responses that adversely affected growth and yield and fruit quality. However, soil FA addition and foliar SA spraying alone or in combination at any application level attenuated the negative effects of saline calcareous and heat-stress conditions via enhancing the morpho-physio-biochemical attributes, positively reflecting in tree growth, yield, and fruit quality. FA treatment alone improved tree water status (membrane stability index; MSI and relative water content; RWC), photosynthetic traits (SPAD value and maximum photochemical efficiency; Fv/Fm), leaf area, fruit weight, fruit yield, and fruit vitamin C (fruit vit.C), while SA treatment alone enhanced leaf proline and phenolic content, shoot length, and fruit total soluble solids (fruit TSS) compared to the non-FA or SA-treated control. Moreover, co-application of FA400 and SA400 effectively alleviated the harmful impacts of dual stress of heat and salinity on mango trees by improving MSI, RWC, SPAD value, Fv/Fm, proline and phenolic content, fruit weight, fruit yield, fruit TSS, fruit vit.C by 19.7, 26.1, 46.7, 18.7, 101.7, 390.7, 42.7, 6.8, 22.6, 69.6% (averages of the two seasons), respectively, compared to the non-FA or SA-treated trees.

Conclusion

It is recommended to add 400 g FA tree−1 to soil integrated with 400 mg SA L−1 foliar spraying four times at 30-day intervals for improving water status and photosynthetic traits, proline and phenolic accumulation, thereby growth, yield, and fruit quality of mango trees exposed to dual stress of heat and salinity under arid conditions.
Dissecting the Single-Cell Diversity and Heterogeneity Underlying Cervical Precancerous Lesions and Cancer Tissues
Authors: Han Yanling , Shi Lu , Jiang Nan , Huang Jiamin , Jia Xiuzhi , Zhu Bo
Published: October 2024

The underlying cellular diversity and heterogeneity from cervix precancerous lesions to cervical squamous cell carcinoma (CSCC) is investigated. Four single-cell datasets including normal tissues, normal adjacent tissues, precancerous lesions, and cervical tumors were integrated to perform disease stage analysis. Single-cell compositional data analysis (scCODA) was utilized to reveal the compositional changes of each cell type. Differentially expressed genes (DEGs) among cell types were annotated using BioCarta. An assay for transposase-accessible chromatin sequencing (ATAC-seq) analysis was performed to correlate epigenetic alterations with gene expression profiles. Lastly, a logistic regression model was used to assess the similarity between the original and new cohort data (HRA001742). After global annotation, seven distinct cell types were categorized. Eight consensus-upregulated DEGs were identified in B cells among different disease statuses, which could be utilized to predict the overall survival of CSCC patients. Inferred copy number variation (CNV) analysis of epithelial cells guided disease progression classification. Trajectory and ATAC-seq integration analysis identified 95 key transcription factors (TF) and one immunohistochemistry (IHC) testified key-node TF (YY1) involved in epithelial cells from CSCC initiation to progression. The consistency of epithelial cell subpopulation markers was revealed with single-cell sequencing, bulk sequencing, and RT-qPCR detection. KRT8 and KRT15, markers of Epi6, showed progressively higher expression with disease progression as revealed by IHC detection. The logistic regression model testified the robustness of the resemblance of clusters among the various datasets utilized in this study. Valuable insights into CSCC cellular diversity and heterogeneity provide a foundation for future targeted therapy.
Ukraine, Wagner, and Russia's Convict-Soldiers
Authors: Pattison James
Published: October 2024

One of the most pronounced features of the war in Ukraine has been the heavy reliance of the Russian forces on convict-soldiers, most notably by the private military and security company (PMSC) the Wagner Group. In this essay, I explore the ethical problems with using convict-soldiers and assess how using them compares to other military arrangements, such as conscription or an all-volunteer force. Overall, I argue that the central issue with using prisoners to fight wars is their perceived expendability. To do this, I present three arguments. First, although many prisoners have been under major duress, using convict-soldiers may be somewhat preferable to using conscripts in this regard. Second, convict-soldiers are more likely to be subject to human rights abuses than other types of soldiers and this should be seen as the main problem with their use. Third, convict-soldiers’ liability to lethal force for fighting in an unjust war does not render it permissible to treat them as expendable.
Introduction: Ethics and the War against Ukraine
Authors: Braun Christian Nikolaus
Published: October 2024

Now in its third year, the Russian war of aggression against Ukraine remains at the very top of the international security agenda. This conflict has largely refocused the West's attention away from the counterterrorism and counterinsurgency campaigns that followed the terrorist attacks of September 11, 2001. In February 2022, German chancellor Olaf Scholz went so far as to declare that the invasion signaled a zeitenwende, or “dawn of a new era.”1 Russia's aggression and the threat of having to fight a peer or near-peer competitor raises difficult questions, many of which are ethical in nature. The essays gathered in this roundtable seek to provide answers to some of those questions. They are the result of a workshop I organized for the King's College London Centre for Military Ethics in October 2023. One of my ambitions for this workshop was to put leading academics working on the ethics of war into discussion with military practitioners, making sure to include Ukrainian voices. I was very fortunate to succeed in these objectives, and I am convinced that the published essays have benefited enormously from our conversations.
Multi‐Elemental Statistical Features of Early Paleogene Sediments From the Mid‐Latitude Eastern Indian Ocean
Authors: Kuwahara Yusuke , Yasukawa Kazutaka , Tanaka Erika , Nakamura Kentaro , Ikehara Minoru , Kato Yasuhiro
Published: September 2024

The early Paleogene, including the Paleocene and Eocene, is characterized by Warmhouse and Hothouse climate states with superimposed transient warming events known as hyperthermals. While these paleoenvironmental changes are well‐documented in the Pacific and Atlantic Oceans, records of such changes in the Indian Ocean are limited. Here, we present a new data set of bulk chemical composition and stable isotopic ratios from the late Paleocene to middle Eocene sediments on the Exmouth Plateau in the mid‐latitude eastern Indian Ocean. The bulk δ13C and δ18O suggest a warming period called the Early Eocene Climatic Optimum (EECO) and cooling toward the middle Eocene in a long‐term perspective. In the short‐term, we identified at least six hyperthermals (Paleocene–Eocene Thermal Maximum, H2, I1, J, ETM3, and L) in the studied sections. By applying independent component (IC) analyses (ICA) to the bulk chemical composition data, we identified six ICs corresponding to sediment source materials and post‐depositional processes. The ICA result infers an increase in detrital materials or a decrease in carbonate rain flux, and an increased population of higher‐order consumers in the oceanic ecosystem during both long‐term (EECO) and short‐term (hyperthermal) warmings around the Exmouth Plateau. Furthermore, ICs representing diagenetic processes and post‐depositional remobilization of elements showed excursions across the hyperthermal horizons, indicating that changes in the redox state of pore or bottom water are associated with hyperthermals. This study provides critical insights into the paleoceanography of the Indian Ocean, highlighting the response of marine environments to both long‐term and short‐term climatic events during the early Paleogene.
Paleomagnetic Constraints on the Rapid Plate Shift of North China Block During the Jurassic From ∼155 Ma Dykes and Sills
Authors: Wang Pengfei , Yi Zhiyu , Meert Joseph G. , Liu Yu‐Shu , Yang Silin , Wang Fei , Li Zaijun , Huang Baochun
Published: September 2024

A large‐scale apparent polar wander occurred during the Jurassic interval, which is interpreted as true polar wander (TPW). As the motion is nearly orthogonal to the TPW axis, the North China Block (NCB) experienced the largest latitudinal and environmental changes and provides unique constraints on Jurassic TPW. However, due to the lack and uneven quality of paleomagnetic data, TPW records in North China are controversial. Here, we report a new paleomagnetic pole (80.8°N, 13.0°E, A95 = 7.4°) from the late Jurassic sills and dykes that intrude the Nandaling and Xiahuayuan formations in the NCB. The new pole places the NCB at 36.8° ± 7.4°N at 155 ± 3.4 Ma, using Beijing as the reference site. Combined with the reliable Jurassic poles, our study reveals a large, steady southward shift of 37.3° ± 7.2° for the NCB during the Middle and Late Jurassic, and reflects a component of TPW. The position of ∼155 Ma pole also supports significant TPW prior to ∼160 Ma and agrees with proposals attributing the diachronous 165–155 Ma aridification across the Eastern Asian blocks.
Temperature‐Driven Dengue Transmission in a Changing Climate: Patterns, Trends, and Future Projections
Authors: Feng Fengliu , Ma Yuxia , Qin Pengpeng , Zhao Yuhan , Liu Zongrui , Wang Wanci , Cheng Bowen
Published: September 2024

Dengue is a rapidly spreading mosquito‐borne infectious disease that is sensitive to climate factors and poses a major public health concern worldwide. We analyzed dengue incidence trends and the relationship between annual mean minimum temperatures (AMMTs) and dengue incidence rates from 1990 to 2019 in 122 countries using the Global Burden of Disease and TerraClimate data sets. We also projected global dengue incidence rates under different carbon emission scenarios using temperature data from the Coupled Model Intercomparison Project Phase 6 (CMIP6) data set. Our results reveal a significant increase in global dengue cases from 1990 to 2019 and a positive correlation between temperature and dengue incidence. The association between AMMT and dengue incidence strengthened at temperatures exceeding 21°C. Central and eastern sub‐Saharan Africa, as well as Oceania, were identified as the regions most sensitive to dengue; males and individuals aged 15–19 or 70–84 years were the most susceptible to dengue under rising temperatures. Our projections suggest that global dengue incidence will substantially increase by 2050 and 2100. By 2100, regions including Africa, the Arabian Peninsula, the southern United States, southern China, and island countries in the Pacific and Indian Oceans are projected to become year‐round dengue‐endemic under a high‐emission climate scenario. Our findings underscore the importance of implementing effective measures to mitigate the impact of climate change on dengue transmission. Identifying high‐risk areas and susceptible populations, along with understanding the projected expansion of dengue‐endemic regions, will provide valuable guidance for targeted interventions to address this growing global health challenge in the face of changing climatic conditions.
The Evolution of the Hunga Hydration in a Moistening Stratosphere
Authors: Millán L. , Read W. G. , Santee M. L. , Lambert A. , Manney G. L. , Neu J. L. , Pitts M. C. , Werner F. , Livesey N. J. , Schwartz M. J.
Published: September 2024

The 2022 Hunga eruption caused unprecedented stratospheric hydration. Aura Microwave Limb Sounder (MLS) measurements show that the stratospheric water vapor mass remains essentially unchanged as of early 2024 and that the Hunga hydration occurred atop a robust (possibly accelerating) moistening trend in the stratosphere. Enhanced by the excess Hunga water vapor, dehydration via polar stratospheric cloud sedimentation in the 2023 Antarctic vortex exceeded climatological values by 50%. Simple projections based on modeled exponential decay illustrate that the timing of the return to humidity levels that would have been expected absent the Hunga hydration depends on the ongoing stratospheric water vapor trend. With the Hunga hydration compounding an underlying moistening trend, the stratosphere could remain anomalously humid for an extended period.
EMPPIC: A PIC Code for Nuclear Electromagnetic Pulse
Authors: Yao Jiansheng , Zhao Yingkui , Wang Min , Xia Yin , Ye Difa
Published: October 2024

The nuclear electromagnetic pulse (NEMP) is a pulsed electromagnetic wave generated by the prompt gamma emitted from a nuclear explosion. In the 1970s, Longley and Longmire proposed a simulation method for the NEMP, which has been widely used in the NEMP simulation such as the widely used code CHAP. Constrained by the computational capabilities of the time, the CHAP program relied on numerous assumptions, which have been scrutinized in recent years. In addition to the CHAP method, in 2016, Friedman et al. proposed the idea of constructing a NEMP program based on the Particle‐in‐Cell (PIC) method. The PIC method not only accurately simulates the dynamics of electrons but also self‐consistently simulates the influence of pulsed electromagnetic fields on electrons, and requires fewer assumptions. Unfortunately, due to the excessively computational consuming of the PIC method, Friedman et al. couldn't simulate the full‐scale NEMP spanning tens of kilometers. In this paper, we present the first full‐scale simulation program for the NEMP based on the PIC‐fluid coupling method. By utilizing the moving window method, double‐grid methods and linked list storage techniques, we significantly reduce the computational consuming. Additionally, a mixed scattering collision method is used to efficiently simulate elastic collisions between Compton electrons and atmospheric molecules. Detailed discussions of the relevant simulation results are also provided.
Renal fibroblasts are involved in fibrogenic changes in kidney fibrosis associated with dysfunctional telomeres
Authors: Saraswati Sarita , Martínez Paula , Serrano Rosa , Mejías Diego , Graña-Castro Osvaldo , Álvarez Díaz Ruth , Blasco Maria A.
Published: October 2024

Tubulointerstitial fibrosis associated with chronic kidney disease (CKD) represents a global health care problem. We previously reported that short and dysfunctional telomeres lead to interstitial renal fibrosis; however, the cell-of-origin of kidney fibrosis associated with telomere dysfunction is currently unknown. We induced telomere dysfunction by deleting the Trf1 gene encoding a telomere-binding factor specifically in renal fibroblasts in both short-term and long-term life-long experiments in mice to identify the role of fibroblasts in renal fibrosis. Short-term Trf1 deletion in renal fibroblasts was not sufficient to trigger kidney fibrosis but was sufficient to induce inflammatory responses, ECM deposition, cell cycle arrest, fibrogenesis, and vascular rarefaction. However, long-term persistent deletion of Trf1 in fibroblasts resulted in kidney fibrosis accompanied by an elevated urinary albumin-to-creatinine ratio (uACR) and a decrease in mouse survival. These cellular responses lead to the macrophage-to-myofibroblast transition (MMT), endothelial-to-mesenchymal transition (EndMT), and partial epithelial-to-mesenchymal transition (EMT), ultimately causing kidney fibrosis at the humane endpoint (HEP) when the deletion of Trf1 in fibroblasts is maintained throughout the lifespan of mice. Our findings contribute to a better understanding of the role of dysfunctional telomeres in the onset of the profibrotic alterations that lead to kidney fibrosis.
Taming hemoglobin chemistry—a new hemoglobin-based oxygen carrier engineered with both decreased rates of nitric oxide scavenging and lipid oxidation
Authors: Cooper Chris E. , Simons Michelle , Dyson Alex , Leiva Eriksson Nélida , Silkstone Gary G. A. , Syrett Natalie , Allen-Baume Victoria , Bülow Leif , Ronda Luca , Mozzarelli Andrea , Singer Mervyn , Reeder Brandon J.
Published: October 2024

The clinical utility of hemoglobin-based oxygen carriers (HBOC) is limited by adverse heme oxidative chemistry. A variety of tyrosine residues were inserted on the surface of the γ subunit of recombinant fetal hemoglobin to create novel electron transport pathways. This enhanced the ability of the physiological antioxidant ascorbate to reduce ferryl heme and decrease lipid peroxidation. The γL96Y mutation presented the best profile of oxidative protection unaccompanied by loss of protein stability and function. N-terminal deletions were constructed to facilitate the production of recombinant hemoglobin by fermentation and phenylalanine insertions in the heme pocket to decrease the rate of NO dioxygenation. The resultant mutant (αV1del. αL29F, γG1del. γV67F, γL96Y) significantly decreased NO scavenging and lipid peroxidation in vitro. Unlike native hemoglobin or a recombinant control (αV1del, γG1del), this mutation showed no increase in blood pressure immediately following infusion in a rat model of reperfusion injury, suggesting that it was also able to prevent NO scavenging in vivo. Infusion of the mutant also resulted in no meaningful adverse physiological effects apart from diuresis, and no increase in oxidative stress, as measured by urinary isoprostane levels. Following PEGylation via the Euro-PEG-Hb method to increase vascular retention, this novel protein construct was compared with saline in a severe rat reperfusion injury model (45% blood volume removal for 90 minutes followed by reinfusion to twice the volume of shed blood). Blood pressure and survival were followed for 4 h post-reperfusion. While there was no difference in blood pressure, the PEGylated Hb mutant significantly increased survival.
Artificial intelligent-driven decision-making for automating root fracture detection in periapical radiographs
Authors: Abdelazim Riem , Fouad Eman M.
Published: October 2024

Background

The detection and early diagnosis of root fractures can be challenging; this difficulty applies particularly to newly qualified dentists. Aside from clinical examination, diagnosis often requires radiographic assessment. Nonetheless, human fallibility can introduce errors due to a lack of experience.

Aim

The proposed system aimed to assist in detecting root fractures through the integration of artificial intelligence techniques into the diagnosis process as a step for automating dental diagnosis and decision-making processes.

Materials and method

A total of 400 radiographic images of fractured and unfractured teeth were obtained for the present research. Data handling techniques were implemented to balance the distribution of the samples. The AI-based system used the voting technique for five different pretrained models namely, VGG16, VGG19, ResNet50. DenseNet121, and DenseNet169 to perform the analysis. The parameters used for the analysis of the models are loss and accuracy curves.

Results

VGG16 exhibited notable success with low training and validation losses (0.09% and 0.18%, respectively), high specificity, sensitivity, and positive predictive value (PPV). VGG19 showed potential overfitting concerns, while ResNet50 displayed progress in minimizing loss but exhibited bias toward unfractured cases. DenseNet121 effectively addressed overfitting and noise issues, achieving balanced metrics and impressive PPVs for both fractured and unfractured cases (0.933 and 0.898 respectively). With increased depth, DenseNet169 demonstrated enhanced generalization capability.

Conclusion

The proposed AI- based system demonstrated high precision and sensitivity for detecting root fractures in endodontically treated teeth by utilizing the voting method.
Prognostic role of pre-diagnostic circulating inflammatory biomarkers in breast cancer survival: evidence from the EPIC cohort study
Authors: Castro-Espin Carlota , Cairat Manon , Navionis Anne-Sophie , Dahm Christina C. , Antoniussen Christian S. , Tjønneland Anne , Mellemkjær Lene , Mancini Francesca Romana , Hajji-Louati Mariem , Severi Gianluca , Le Cornet Charlotte , Kaaks Rudolf , Schulze Matthias B. , Masala Giovanna , Agnoli Claudia , Sacerdote Carlotta , Crous-Bou Marta , Sánchez Maria-Jose , Amiano Pilar , Chirlaque María-Dolores , Guevara Marcela , Smith-Byrne Karl , Heath Alicia K. , Christakoudi Sofia , Gunter Marc J. , Rinaldi Sabina , Agudo Antonio , Dossus Laure
Published: September 2024

Background

Inflammation influences tumour progression and cancer prognosis, but its role preceding breast cancer (BC) and its prognostic implications remain inconclusive.

Methods

We studied pre-diagnostic plasma inflammatory biomarkers in 1538 women with BC from the EPIC study. Cox proportional hazards models assessed their relationship with all-cause and BC-specific mortality, adjusting for tumour characteristics and lifestyle factors.

Results

Over a 7-year follow-up after diagnosis, 229 women died, 163 from BC. Elevated IL-6 levels were associated with increased all-cause mortality risk (HR1-SD 1.25, 95% CI 1.07–1.47). Among postmenopausal, IL-6 was associated with higher all-cause (HR1-SD 1.41, 95% CI 1.18–1.69) and BC-specific mortality (HR1-SD 1.31, 95% CI 1.03–1.66), (PHeterogeneity (pre/postmenopausal) < 0.05 for both), while IL-10 and TNFα were associated with all-cause mortality only (HR1-SD 1.19, 95% CI 1.02–1.40 and HR1-SD 1.28, 95% CI 1.06–1.56). Among ER+PR+, IL-10 was associated with all-cause and BC-specific mortality (HR1-SD 1.35, 95% CI 1.10–1.65 and HR1-SD 1.42 95% CI 1.08–1.86), while TNF-α was associated with all-cause mortality in HER2- (HR1-SD 1.31, 95% CI 1.07–1.61). An inflammatory score predicted higher all-cause mortality, especially in postmenopausal women (HR1-SD 1.30, 95% CI 1.07–1.58).

Conclusions

Higher pre-diagnosis IL-6 levels suggest poorer long-term survival among BC survivors. In postmenopausal survivors, elevated IL-6, IL-10, and TNFα and inflammatory scores seem to predict all-cause mortality.
Novel FABP4+C1q+ macrophages enhance antitumor immunity and associated with response to neoadjuvant pembrolizumab and chemotherapy in NSCLC via AMPK/JAK/STAT axis
Authors: Zhang Dong , Wang Min , Liu Gen , Li Xin , Yu Wenwen , Hui Zhenzhen , Ren Xiubao , Sun Qian
Published: October 2024

Immune checkpoint inhibitors (ICIs) immunotherapy facilitates new approaches to achieve precision cancer treatment. A growing number of patients with non-small cell lung cancer (NSCLC) have benefited from treatment with neoadjuvant ICIs combined with chemotherapy. However, the mechanisms and associations between the therapeutic efficacy of neoadjuvant pembrolizumab and chemotherapy (NAPC) and macrophage subsets are still unclear. We performed single-cell RNA sequencing (scRNA-seq) and identified a novel FABP4+C1q+ macrophage subtype, which exhibited stronger proinflammatory cytokine production and phagocytic ability. This subtype was found to be more abundant in tumor tissues and lymph nodes of major pathological response (MPR) patients compared to non-MPR patients, and was associated with a good efficacy of NAPC. Multiplex fluorescent immunohistochemical (mIHC) staining was subsequently used to verify our findings. Further mechanistic studies indicated that FABP4 and C1q regulate the expression of proinflammatory cytokines synergistically. In addition, FABP4 and C1q promote fatty acid synthesis, enhance anti-apoptosis ability and phagocytic ability of macrophage via the interaction of AMPK/JAK/STAT axis. This study provides novel insights into the underlying mechanisms and predictive biomarkers of NAPC. Our findings contribute to improving the prognosis of patients with NSCLC by potentially guiding more precise patient selection and treatment strategies.

Novelty & Impact Statements

We identified a group of macrophages (FABP4+C1q+ macrophages) related to the therapeutic efficacy of neoadjuvant chemoimmunotherapy. FABP4+C1q+ macrophages highly expressed proinflammatory cytokines-related genes and had a strong cytokine production and phagocytic ability. We believe that our study provides a novel insight into the synergistic mechanism of neoadjuvant ICI combined with chemotherapy and may lead to improved clinical outcomes in patients with NSCLC in the future.
STAT6/LINC01637 axis regulates tumor growth via autophagy and pharmacological targeting STAT6 as a novel strategy for uveal melanoma
Authors: Liu Bo , Yao Xueting , Huang Qinying , Fan Yichao , Yu Bo , Wang Jing , Wu Wencan , Dai Jinhui
Published: October 2024

Compelling evidence has revealed a novel function of the STAT pathway in the pathophysiology of uveal melanoma (UM); however, its regulatory mechanisms remain unclear. Here, we analyzed the clinical prognostic value of STAT family genes in UM patients using bioinformatics approaches and found that high STAT6 expression is associated with poor prognosis. Furthermore, cellular experiments and a nude mouse model demonstrated that STAT6 promotes UM progression through the autophagy pathway both in vivo and in vitro. Next, RIP-PCR revealed that STAT6 protein binds to LINC01637 mRNA, which in turn regulates STAT6 expression to promote UM growth. Finally, molecular docking indicated that STAT6 is a target of Zoledronic Acid, which can delay UM tumorigenicity by inhibiting STAT6 expression. Taken together, our results indicate that the STAT6/LINC01637 axis promotes UM progression via autophagy and may serve as a potential therapeutic target for UM.
Structural basis for the rescue of hyperexcitable cells by the amyotrophic lateral sclerosis drug Riluzole
Authors: Hollingworth David , Thomas Frances , Page Dana A. , Fouda Mohamed A. , De Castro Raquel Lopez-Rios , Sula Altin , Mykhaylyk Vitaliy B. , Kelly Geoff , Ulmschneider Martin B. , Ruben Peter C. , Wallace B. A.
Published: September 2024

Neuronal hyperexcitability is a key element of many neurodegenerative disorders including the motor neuron disease Amyotrophic Lateral Sclerosis (ALS), where it occurs associated with elevated late sodium current (INaL). INaL results from incomplete inactivation of voltage-gated sodium channels (VGSCs) after their opening and shapes physiological membrane excitability. However, dysfunctional increases can cause hyperexcitability-associated diseases. Here we reveal the atypical binding mechanism which explains how the neuroprotective ALS-treatment drug riluzole stabilises VGSCs in their inactivated state to cause the suppression of INaL that leads to reversed cellular overexcitability. Riluzole accumulates in the membrane and enters VGSCs through openings to their membrane-accessible fenestrations. Riluzole binds within these fenestrations to stabilise the inactivated channel state, allowing for the selective allosteric inhibition of INaL without the physical block of Na+ conduction associated with traditional channel pore binding VGSC drugs. We further demonstrate that riluzole can reproduce these effects on a disease variant of the non-neuronal VGSC isoform Nav1.4, where pathologically increased INaL is caused directly by mutation. Overall, we identify a model for VGSC inhibition that produces effects consistent with the inhibitory action of riluzole observed in models of ALS. Our findings will aid future drug design and supports research directed towards riluzole repurposing.
Caspase-1-dependent spatiality in triple-negative breast cancer and response to immunotherapy
Authors: Zheng Weiyue , Marini Wanda , Murakami Kiichi , Sotov Valentin , Butler Marcus , Gorrini Chiara , Ohashi Pamela S. , Reedijk Michael
Published: October 2024

Tumor immune microenvironment (TIME) spatial organization predicts outcome and therapy response in triple-negative breast cancer (TNBC). An immunosuppressive TIME containing elevated tumor-associated macrophages (TAM) and scarce CD8+ T cells is associated with poor outcome, but the regulatory mechanisms are poorly understood. Here we show that ETS1-driven caspase-1 expression, required for IL1β processing and TAM recruitment, is negatively regulated by estrogen receptors alpha (ERα) and a defining feature of TNBC. Elevated tumoral caspase-1 is associated with a distinct TIME characterized by increased pro-tumoral TAMs and CD8+ T cell exclusion from tumor nests. Mouse models prove the functional importance of ERα, ETS1, caspase-1 and IL1β in TIME conformation. Caspase-1 inhibition induces an immunoreactive TIME and reverses resistance to immune checkpoint blockade, identifying a therapeutically targetable mechanism that governs TNBC spatial organization.
Temporal asymmetries in inferring unobserved past and future events
Authors: Xu Xinming , Zhu Ziyan , Zheng Xueyao , Manning Jeremy R.
Published: October 2024

Unlike temporally symmetric inferences about simple sequences, inferences about our own lives are asymmetric: we are better able to infer the past than the future, since we remember our past but not our future. Here we explore whether there are asymmetries in inferences about the unobserved pasts and futures of other people’s lives. In two experiments (analyses of the replication experiment were pre-registered), our participants view segments of two character-driven television dramas and write out what they think happens just before or after each just-watched segment. Participants are better at inferring unseen past (versus future) events. This asymmetry is driven by participants’ reliance on characters’ conversational references in the narrative, which tend to favor the past. This tendency is also replicated in a large-scale analysis of conversational references in natural conversations. Our work reveals a temporal asymmetry in how observations of other people’s behaviors can inform inferences about the past and future.
Cellular location shapes quaternary structure of enzymes
Authors: Abrusán György , Zelezniak Aleksej
Published: October 2024

The main forces driving protein complex evolution are currently not well understood, especially in homomers, where quaternary structure might frequently evolve neutrally. Here we examine the factors determining oligomerisation by analysing the evolution of enzymes in circumstances where homomers rarely evolve. We show that 1) In extracellular environments, most enzymes with known structure are monomers, while in the cytoplasm homomers, indicating that the evolution of oligomers is cellular environment dependent; 2) The evolution of quaternary structure within protein orthogroups is more consistent with the predictions of constructive neutral evolution than an adaptive process: quaternary structure is gained easier than it is lost, and most extracellular monomers evolved from proteins that were monomers also in their ancestral state, without the loss of interfaces. Our results indicate that oligomerisation is context-dependent, and even when adaptive, in many cases it is probably not driven by the intrinsic properties of enzymes, like their biochemical function, but rather the properties of the environment where the enzyme is active. These factors might be macromolecular crowding and excluded volume effects facilitating the evolution of interfaces, and the maintenance of cellular homeostasis through shaping cytoplasm fluidity, protein degradation, or diffusion rates.
Reduced subthalamic and subthalamic-cortical coherences associated with the therapeutic carryover effect of coordinated reset deep brain stimulation
Authors: Zheng Lvpiao , Luo Ziling , Mohanty Biswaranjan , Amoozegar Sana , Johnson Luke A. , Vitek Jerrold L. , Wang Jing
Published: September 2024

Coordinated reset deep brain stimulation (CR DBS), a promising treatment for Parkinson’s disease (PD), is hypothesized to desynchronize neuronal populations. However, little in vivo data probes this hypothesis. In a parkinsonian nonhuman primate, we found that subthalamic CR DBS suppressed subthalamic and cortical-subthalamic coherences in the beta band, correlating with motor improvements. Our results support the desynchronizing mechanism of CR DBS and propose potential biomarkers for closed-loop CR DBS.
Empirical modelling of 2205 DSS flow curves using strain-compensated Arrhenius rate-type constitutive model
Authors: Gonya Elvis M. , Siyasiya Charles W. , Makhatha Mamookho E.
Published: September 2024

This work predicts, hot flow curves of 2205 DSS using strain-compensated Arrhenius rate-type constitutive model. Twenty-five (25) × Ø10 diameter × 15 mm height cylindrical samples were hot compressed at a temperature between 850 and 1050 °C at an interval of 50 °C and strain rates between 0.001 and 5 s−1, using Gleeble 1500D. After the tests, corrected flow curves were plotted followed by computation of deformations constants at various deformation conditions using steady state stress. The values of the constants were (α = 0.009708, Q = 445 kJ/mol and n = 3.7) and seemed comparable to the previous studies of DSS. Steady state predictive model was then constructed using the calculated constants and showed a reasonably good accuracy with low value of MARE = 7.78%. Furthermore, calculated strain compensated Arrhenius rate type model was used to predict flow curves at various deformation. The model had a good estimation of flow curves of flow curves at 900–1050 °C across all strain rates as reflected by MARE = 5.47%. A notable discrepancy between predicted and experimental flow stress was observed at 850 °C and across all the strain rates. A model refinement using generalised reduced gradient improved the accuracy of the model by 34.7% despite deformation conditions at 850 °C and low strain rates (0.01/ 0.1) s−1 showing minimum improvement. Further modification of Z-parameter by compensating for the strain rate improved the accuracy of the model at 850 °C/0.01 s−1/0.1 s−1. Lastly, a comparison of the current model with the other non-linear model showed that the latter was more accurate in estimation of flow curves since it relied on characteristics flow stress points controlled by underlying active deformation mechanisms.
Optimal parameter identification of solid oxide fuel cell using modified fire Hawk algorithm
Authors: Khajuria Rahul , Bukya Mahipal , Lamba Ravita , Kumar Rajesh
Published: September 2024

An accurate and efficient approach is required to identify the unknown parameters of solid oxide fuel cell (SOFC) mathematical model for a robust design of any energy system considering SOFC. This research study proposes a modified fire hawk algorithm (MFHA) to determine the values of SOFC model parameters. The performance evaluation of MFHA is tested on two case studies. Firstly, the performance of MFHA is tested on commercially available cylindrical cell developed by Siemens at four temperatures. Results reveal that the least value of sum of squared error (SSE) is 1.04E−05, 2.30E−05, 1.03E−05, and 1.60E−05 at 1073 K, 1173 K, 1213 K, and 1273 K respectively. Results obtained using MFHA have been compared with original fire hawk algorithm (FHA) and other well established and recent algorithms. Secondly, MFHA is implemented for estimating unknown parameters of a 5 kW dynamic tabular stack of 96 cells at various pressures and temperatures. The obtained value of SSE at different temperatures of 873 K, 923 K, 973 K, 1023 K and 1073 K is 1.18E−03, 6.12E−03, 2.21E−02, 5.18E−02, and 6.00E−02, respectively whereas, SSE at different pressures of 1 atm, 2 atm, 3 atm, 4 atm, and 5 atm is 6.05E−02, 6.11E−02, 5.53E−02, 5.11E−02, and 6.64E−02 respectively.
Lack of optimistic bias during social evaluation learning reflects reduced positive self-beliefs in depression and social anxiety, but via distinct mechanisms
Authors: Hoffmann Janina A. , Hobbs Catherine , Moutoussis Michael , Button Katherine S.
Published: September 2024

Processing social feedback optimistically may maintain positive self-beliefs and stable social relationships. Conversely, a lack of this optimistic bias in depression and social anxiety may perpetuate negative self-beliefs and maintain symptoms. Research investigating this mechanism is scarce, however, and the mechanisms by which depressed and socially anxious individuals respond to social evaluation may also differ. Using a range of computational approaches in two large datasets (mega-analysis of previous studies, n = 450; pre-registered replication study, n = 807), we investigated how depression (PHQ-9) and social anxiety (BFNE) symptoms related to social evaluation learning in a computerized task. Optimistic bias (better learning of positive relative to negative evaluations) was found to be negatively associated with depression and social anxiety. Structural equation models suggested this reflected a heightened sensitivity to negative social feedback in social anxiety, whereas in depression it co-existed with a blunted response to positive social feedback. Computational belief-based learning models further suggested that reduced optimism was driven by less positive trait-like self-beliefs in both depression and social anxiety, with some evidence for a general blunting in belief updating in depression. Recognizing such transdiagnostic similarities and differences in social evaluation learning across disorders may inform approaches to personalizing treatment.
Experimental study on the parameters affecting the performance of spiral tube pump
Authors: Meseret Million , Wami Dawit , Nallamothu Ramesh Babu
Published: September 2024

This experimental study delves into the critical parameters influencing the performance of spiral tube pumps—a centuries-old technology attributed to H.A. Wirtz in 1746. The Spiral Tube Pump system, constructed using a transparent flexible tube wound spirally on a waterwheel, harnesses the kinetic energy of a river, offering a simple, cost-effective, and emission-free irrigation solution using locally available materials. Operating on the principles of a manometer, water and air plugs are pushed into the pipe alternately by the pump. Key factors crucial to enhancing the performance of this technology are investigated, focusing on submergence ratio, rotational speed, outer diameter, and the number of turns of the spiral tube. The experimental setup involves a prototype featuring a 4-meter-long, ¾-inch diameter transparent flexible tube spirally wound on a 1.5-meter-wide water wheel, achieving a maximum output of approximately 30 L per minute discharge and a 3.3-meter head. Through a series of rigorous experimental procedures, it becomes evident that wheel speed and submergence ratio significantly impact the pump’s discharge. For 600% increase in wheel speed, up to about 500% discharge increase was observed. Also for 300% increase in submergence ratio, up to about 275% increase in discharge was observed. The number of spiral turns predominantly influences the pump’s head. For 100% increase in spiral turn, up to about 33% increment in head was observed. And the outer diameter affects both discharge and head. For 87% increase in outer diameter, up to about 80% of increase in discharge and up to about 163% increase in head was observed. These findings underscore the adaptability of the Spiral Tube Pump design to specific irrigation field conditions. For instance, in scenarios where the irrigation field is elevated relative to the river, incorporating a greater number of spiral tube turns can enhance the pump’s efficiency in transporting water to the desired location.
Assessing and correcting neighborhood socioeconomic spatial sampling biases in citizen science mosquito data collection
Authors: Padilla-Pozo Álvaro , Bartumeus Frederic , Montalvo Tomás , Sanpera-Calbet Isis , Valsecchi Andrea , Palmer John R. B.
Published: September 2024

Climatic, ecological, and socioeconomic factors are facilitating the spread of mosquito-borne diseases, heightening the importance of vector surveillance and control. Citizen science is proving to be an effective tool to track mosquito populations, but methods are needed to detect and account for small scale sampling biases in citizen science surveillance. In this article we combine two types of traditional mosquito surveillance records with data from the Mosquito Alert citizen science system to explore the ways in which the socioeconomic characteristics of urban neighborhoods result in sampling biases in citizen scientists’ mosquito reports, while also shaping the spatial distribution of mosquito populations themselves. We use Barcelona, Spain, as an example, and focus on Aedes albopictus, an invasive vector species of concern worldwide. Our results suggest citizen scientists’ sampling effort is focused more in Barcelona’s lower and middle income census tracts than in its higher income ones, whereas Ae. albopictus populations are concentrated in the city’s upper-middle income tracts. High resolution estimates of the spatial distribution of Ae. albopictus risk can be improved by controlling for citizen scientists’ sampling effort, making it possible to provide better insights for efficiently targeting control efforts. Our methodology can be replicated in other cities faced with vector mosquitoes to improve public health responses to mosquito-borne diseases, which impose massive burdens on communities worldwide.
Full-length single-cell BCR sequencing paired with RNA sequencing reveals convergent responses to pneumococcal vaccination
Authors: Morgan Duncan M. , Zhang Yiming J. , Kim Jin-Hwan , Murillo MaryAnn , Singh Suddham , Loschko Jakob , Surendran Naveen , Sekulovic Ognjen , Feng Ellie , Shi Shuting , Irvine Darrell J. , Patil Sarita U. , Kanevsky Isis , Chorro Laurent , Christopher Love J.
Published: September 2024

Single-cell RNA sequencing (scRNA-seq) can resolve transcriptional features from individual cells, but scRNA-seq techniques capable of resolving the variable regions of B cell receptors (BCRs) remain limited, especially from widely-used 3′-barcoded libraries. Here, we report a method that can recover paired, full-length variable region sequences of BCRs from 3′-barcoded scRNA-seq libraries. We first verify this method (B3E-seq) can produce accurate, full-length BCR sequences. We then apply this method to profile B cell responses elicited against the capsular polysaccharide of Streptococcus pneumoniae serotype 3 (ST3) by glycoconjugate vaccines in five infant rhesus macaques. We identify BCR features associated with specificity for the ST3 antigen which are present in multiple vaccinated monkeys, indicating a convergent response to vaccination. These results demonstrate the utility of our method to resolve key features of the B cell repertoire and profile antigen-specific responses elicited by vaccination.
Nitric oxide induces the distinct invisibility phenotype of Mycobacterium tuberculosis
Authors: Gap-Gaupool Brindha , Glenn Sarah M. , Milburn Emily , Turapov Obolbek , Crosatti Marialuisa , Hincks Jennifer , Stewart Bradley , Bacon Joanna , Kendall Sharon L. , Voskuil Martin I. , Riabova Olga , Monakhova Natalia , Green Jeffrey , Waddell Simon J. , Makarov Vadim A. , Mukamolova Galina V.
Published: September 2024

During infection Mycobacterium tuberculosis (Mtb) forms physiologically distinct subpopulations that are recalcitrant to treatment and undetectable using standard diagnostics. These difficult to culture or differentially culturable (DC) Mtb are revealed in liquid media, their revival is often stimulated by resuscitation-promoting factors (Rpf) and prevented by Rpf inhibitors. Here, we investigated the role of nitric oxide (NO) in promoting the DC phenotype. Rpf-dependent DC Mtb were detected following infection of interferon-γ-induced macrophages capable of producing NO, but not when inducible NO synthase was inactivated. After exposure of Mtb to a new donor for sustained NO release (named NOD), the majority of viable cells were Rpf-dependent and undetectable on solid media. Gene expression analyses revealed a broad transcriptional response to NOD, including down-regulation of all five rpf genes. The DC phenotype was partially reverted by over-expression of Rpfs which promoted peptidoglycan remodelling. Thus, NO plays a central role in the generation of Rpf-dependent Mtb, with implications for improving tuberculosis diagnostics and treatments.