bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digestive cancers: mechanisms, therapeutics and management
Authors: Zhan Tianzuo , Betge Johannes , Schulte Nadine , Dreikhausen Lena , Hirth Michael , Li Moying , Weidner Philip , Leipertz Antonia , Teufel Andreas , Ebert Matthias P. 
Published: January 2025

Abstract
Cancers of the digestive system are major contributors to global cancer-associated morbidity and mortality, accounting for 35% of annual cases of cancer deaths. The etiologies, molecular features, and therapeutic management of these cancer entities are highly heterogeneous and complex. Over the last decade, genomic and functional studies have provided unprecedented insights into the biology of digestive cancers, identifying genetic drivers of tumor progression and key interaction points of tumor cells with the immune system. This knowledge is continuously translated into novel treatment concepts and targets, which are dynamically reshaping the therapeutic landscape of these tumors. In this review, we provide a concise overview of the etiology and molecular pathology of the six most common cancers of the digestive system, including esophageal, gastric, biliary tract, pancreatic, hepatocellular, and colorectal cancers. We comprehensively describe the current stage-dependent pharmacological management of these malignancies, including chemo-, targeted, and immunotherapy. For each cancer entity, we provide an overview of recent therapeutic advancements and research progress. Finally, we describe how novel insights into tumor heterogeneity and immune evasion deepen our understanding of therapy resistance and provide an outlook on innovative therapeutic strategies that will shape the future management of digestive cancers, including CAR-T cell therapy, novel antibody-drug conjugates and targeted therapies.
Helicobacter pylori CagA promotes gastric cancer immune escape by upregulating SQLE
Authors: Liu Sifan , Zhang Nan , Ji Xu , Yang Shuyue , Zhao Zheng , Li Peng 
Published: January 2025

Abstract

Helicobacter pylori (H. pylori) infection is a well-established risk factor for gastric cancer, primarily due to its virulence factor, cytotoxin-associated gene A (CagA). Although PD-L1/PD-1-mediated immune evasion is critical in cancer development, the impact of CagA on PD-L1 regulation remains unclear. This study revealed that H. pylori CagA upregulated squalene epoxidase (SQLE) expression, a key enzyme in the cholesterol biosynthesis pathway. Elevated SQLE activity increased cellular palmitoyl-CoA levels, enhancing PD-L1 palmitoylation while decreasing its ubiquitination. This ultimately increases PD-L1 stability, suppressing T cell activity and facilitating immune evasion in gastric cancer. In summary, our findings highlight the crucial role of the CagA-SQLE-PD-L1 axis in gastric cancer progression, suggesting potential therapeutic strategies for targeting CagA-positive gastric cancer.
Involvement of p38 MAPK and MAPKAPK2 in promoting cell death and the inflammatory response to ischemic stress associated with necrotic glioblastoma
Authors: Kim Soo Yeon , Tang Miaolu , Chih Stephen Y. , Sallavanti Jessica , Gao Yan , Qiu Zhiqiang , Wang Hong-Gang , Li Wei 
Published: January 2025

Abstract
The association of necrosis in tumors with poor prognosis implies a potential tumor-promoting role. However, the mechanisms underlying cell death in this context and how damaged tissue contributes to tumor progression remain unclear. Here, we identified p38 mitogen-activated protein kinases (p38 MAPK, a.k.a. p38) as a key player in promoting cell death and the inflammatory response to ischemic stress associated with necrotic tumors. We found that glioblastoma (GBM) cells expressing patient-derived Kirsten rat sarcoma (KRAS) or phosphoinositide-3-kinase (PI3K) active mutants showed enhanced cell death under ischemia-mimetic conditions in vitro and were more likely to develop into necrotic tumors in vivo. Cell death in both settings depended on p38, which is also required for tumor progression driven by KRAS or PI3K. Under ischemia-mimetic conditions, GBM cells undergo reactive oxygen species (ROS)-dependent cell death. Gene expression in these cells recapitulated multiple features observed in peri-necrotic tumors from patient GBM. Further studies showed the involvement of a positive feedback loop between the p38-MAPK-activated protein kinase 2 (MAPKAPK2, a.k.a. MK2) signaling axis and the unfolded protein response signaling components activating transcription factor 4 (ATF4) and inositol-requiring enzyme 1 (IRE1α) in driving ischemic tumor cell death. This signaling cascade was further potentiated by RAS or PI3K activation under ischemic conditions, contributing to the inflammatory gene expression response. Therefore, our study suggests that p38 could be targeted to relieve the inflammatory response in necrotic tumors and inhibit GBM progression.
Potential plant extinctions with the loss of the Pleistocene mammoth steppe
Authors: Courtin Jérémy , Stoof-Leichsenring Kathleen R. , Lisovski Simeon , Liu Ying , Alsos Inger Greve , Biskaborn Boris K. , Diekmann Bernhard , Melles Martin , Wagner Bernd , Pestryakova Luidmila , Russell James , Huang Yongsong , Herzschuh Ulrike 
Published: January 2025

Abstract
During the Pleistocene-Holocene transition, the dominant mammoth steppe ecosystem across northern Eurasia vanished, in parallel with megafauna extinctions. However, plant extinction patterns are rarely detected due to lack of identifiable fossil records. Here, we introduce a method for detection of plant taxa loss at regional (extirpation) to potentially global scale (extinction) and their causes, as determined from ancient plant DNA metabarcoding in sediment cores (sedaDNA) from lakes in Siberia and Alaska over the past 28,000 years. Overall, potential plant extinctions track changes in temperature, in vegetation, and in megafauna extinctions at the Pleistocene-Holocene transition. Estimated potential plant extinction rates were 1.7–5.9 extinctions per million species years (E/MSY), above background extinction rates but below modern estimates. Major potential plant extinction events were detected around 17,000 and 9000 years ago which lag maximum vegetation turnover. Our results indicate that herbaceous taxa and taxa contributing less to beta diversity are more vulnerable to extinction. While the robustness of the estimates will increase as DNA reference libraries and ancient sedaDNA data expand, the available data support that plants are more resilient to environmental changes than mammals.
Principled neuromorphic reservoir computing
Authors: Kleyko Denis , Kymn Christopher J. , Thomas Anthony , Olshausen Bruno A. , Sommer Friedrich T. , Frady E. Paxon 
Published: January 2025

Abstract
Reservoir computing advances the intriguing idea that a nonlinear recurrent neural circuit—the reservoir—can encode spatio-temporal input signals to enable efficient ways to perform tasks like classification or regression. However, recently the idea of a monolithic reservoir network that simultaneously buffers input signals and expands them into nonlinear features has been challenged. A representation scheme in which memory buffer and expansion into higher-order polynomial features can be configured separately has been shown to significantly outperform traditional reservoir computing in prediction of multivariate time-series. Here we propose a configurable neuromorphic representation scheme that provides competitive performance on prediction, but with significantly better scaling properties than directly materializing higher-order features as in prior work. Our approach combines the use of randomized representations from traditional reservoir computing with mathematical principles for approximating polynomial kernels via such representations. While the memory buffer can be realized with standard reservoir networks, computing higher-order features requires networks of ‘Sigma-Pi’ neurons, i.e., neurons that enable both summation as well as multiplication of inputs. Finally, we provide an implementation of the memory buffer and Sigma-Pi networks on Loihi 2, an existing neuromorphic hardware platform.
Inhalable biohybrid microrobots: a non-invasive approach for lung treatment
Authors: Li Zhengxing , Guo Zhongyuan , Zhang Fangyu , Sun Lei , Luan Hao , Fang Zheng , Dedrick Jeramy L. , Zhang Yichen , Tang Christine , Zhu Audrey , Yu Yiyan , Ding Shichao , Wang Dan , Chang An-Yi , Yin Lu , Russell Lynn M. , Gao Weiwei , Fang Ronnie H. , Zhang Liangfang , Wang Joseph 
Published: January 2025

Abstract
Amidst the rising prevalence of respiratory diseases, the importance of effective lung treatment modalities is more critical than ever. However, current drug delivery systems face significant limitations that impede their efficacy and therapeutic outcome. Biohybrid microrobots have shown considerable promise for active in vivo drug delivery, especially for pulmonary applications via intratracheal routes. However, the invasive nature of intratracheal administration poses barriers to its clinical translation. Herein, we report on an efficient non-invasive inhalation-based method of delivering microrobots to the lungs. A nebulizer is employed to encapsulate picoeukaryote algae microrobots within small aerosol particles, enabling them to reach the lower respiratory tract. Post nebulization, the microrobots retain their motility (~55 μm s-1) to help achieve a homogeneous lung distribution and long-term retention exceeding five days in the lungs. Therapeutic efficacy is demonstrated in a mouse model of acute methicillin-resistant Staphylococcus aureus pneumonia using this pulmonary inhalation approach to deliver microrobots functionalized with platelet membrane-coated polymeric nanoparticles loaded with vancomycin. These promising findings underscore the benefits of inhalable biohybrid microrobots in a setting that does not require anesthesia, highlighting the substantial translational potential of this delivery system for routine clinical applications.
Nonlinear exposure-response associations of daytime, nighttime, and day-night compound heatwaves with mortality amid climate change
Authors: Liu Jiangdong , Kim Ho , Hashizume Masahiro , Lee Whanhee , Honda Yasushi , Kim Satbyul Estella , He Cheng , Kan Haidong , Chen Renjie 
Published: January 2025

Abstract
Heatwaves are commonly simplified as binary variables in epidemiological studies, limiting the understanding of heatwave-mortality associations. Here we conduct a multi-country study across 28 East Asian cities that employed the Cumulative Excess Heatwave Index (CEHWI), which represents excess heat accumulation during heatwaves, to explore the potentially nonlinear associations of daytime-only, nighttime-only, and day-night compound heatwaves with mortality from 1981 to 2010. Populations exhibited high adaptability to daytime-only and nighttime-only heatwaves, with non-accidental mortality risks increasing only at higher CEHWI levels (75th–90th percentiles). In contrast, compound heatwaves posed a super-linear increase in mortality risks after the 25th percentile of CEHWI. Associations of heatwaves with cardiovascular mortality mirrored those with non-accidental mortality but were more pronounced at higher CEHWI levels, while significant associations with respiratory mortality emerged at low-to-moderate CEHWI levels. These results highlight the necessity of considering the nonlinear health responses to heatwaves of different types in disease burden assessments and heatwave-health warning systems amid climate change.
Nanocarrier imaging at single-cell resolution across entire mouse bodies with deep learning
Authors: Luo Jie , Molbay Muge , Chen Ying , Horvath Izabela , Kadletz Karoline , Kick Benjamin , Zhao Shan , Al-Maskari Rami , Singh Inderjeet , Ali Mayar , Bhatia Harsharan Singh , Minde David-Paul , Negwer Moritz , Hoeher Luciano , Calandra Gian Marco , Groschup Bernhard , Su Jinpeng , Kimna Ceren , Rong Zhouyi , Galensowske Nikolas , Todorov Mihail Ivilinov , Jeridi Denise , Ohn Tzu-Lun , Roth Stefan , Simats Alba , Singh Vikramjeet , Khalin Igor , Pan Chenchen , Arús Bernardo A. , Bruns Oliver T. , Zeidler Reinhard , Liesz Arthur , Protzer Ulrike , Plesnila Nikolaus , Ussar Siegfried , Hellal Farida , Paetzold Johannes , Elsner Markus , Dietz Hendrik , Erturk Ali 
Published: January 2025

Abstract
Efficient and accurate nanocarrier development for targeted drug delivery is hindered by a lack of methods to analyze its cell-level biodistribution across whole organisms. Here we present Single Cell Precision Nanocarrier Identification (SCP-Nano), an integrated experimental and deep learning pipeline to comprehensively quantify the targeting of nanocarriers throughout the whole mouse body at single-cell resolution. SCP-Nano reveals the tissue distribution patterns of lipid nanoparticles (LNPs) after different injection routes at doses as low as 0.0005 mg kg−1—far below the detection limits of conventional whole body imaging techniques. We demonstrate that intramuscularly injected LNPs carrying SARS-CoV-2 spike mRNA reach heart tissue, leading to proteome changes, suggesting immune activation and blood vessel damage. SCP-Nano generalizes to various types of nanocarriers, including liposomes, polyplexes, DNA origami and adeno-associated viruses (AAVs), revealing that an AAV2 variant transduces adipocytes throughout the body. SCP-Nano enables comprehensive three-dimensional mapping of nanocarrier distribution throughout mouse bodies with high sensitivity and should accelerate the development of precise and safe nanocarrier-based therapeutics.
Algae extract-based nanoemulsions for photoprotection against UVB radiation: an electrical impedance spectroscopy study
Authors: Hernández Aura Rocío , Sepulveda Lady , Hata Yoshie , Castellanos Leonardo , Björklund Sebastian , Ruzgas Tautgirdas , Aragón Marcela 
Published: January 2025

Abstract
Skin cancer is one of the most common types of cancer worldwide, with exposure to UVB radiation being a significant risk factor for its development. To prevent skin cancer, continuous research efforts have focused on finding suitable photoprotective ingredients from natural sources that are also environmentally friendly. This study aimed to develop oil-in-water photoprotective nanoemulsions containing marine macroalgae extract. A Box–Behnken experimental design was used to identify the most promising formulation composition, resulting in optimal physical properties. These properties, including droplet size, polydispersity index (PDI), and zeta potential, were evaluated using dynamic light scattering (DLS). To assess the photoprotection capacity of the formulations, electrical impedance spectroscopy (EIS) was employed to evaluate alterations in the electrical characteristics of excised pig skin membranes placed in Franz cells equipped with a 4-electrode set-up. The final composition of the nanoemulsion was caprylic/capric triglycerides 4%, Macrogolglycerol ricinoleate 30%, and algae extract 1%. The nanoemulsions had an average droplet size of 128.5 ± 8.6 nm, a PDI of 0.25 ± 0.06, and a zeta potential of 45.14 ± 0.02 mV. Compared to the control group, the photoprotective capacity of the oil-in-water nanoemulsions was statistically significant. Specifically, only a 15% reduction in the skin membrane electrical resistance following UVB exposure was observed when the formulation containing algae extract was used, whereas a 50% reduction was observed for the vehicle. In conclusion, this work demonstrates that the developed nanoemulsions based on natural ingredients show promising protective capacity against UVB exposure of the skin.
Impact of irrelevant speech and non-speech sounds on serial recall of verbal and spatial items in children and adults
Authors: Leist Larissa , Lachmann Thomas , Klatte Maria 
Published: January 2025

Abstract
Short-term memory for sequences of verbal items such as written words is reliably impaired by task-irrelevant background sounds, a phenomenon known as the “Irrelevant Sound Effect” (ISE). Different theoretical accounts have been proposed to explain the mechanisms underlying the ISE. Some of these assume specific interference between obligatory sound processing and phonological or serial order representations generated during task performance, whereas other posit that background sounds involuntarily divert attention away from the focal task. To explore the roles of phonological processing, serial order retention, and attention control, we analyzed the effects of environmental non-speech sounds and unfamiliar speech on serial recall of verbal items (pictures representing German nouns) and spatial items (dot locations) in children (n = 137) and adults (n = 98). In the verbal task, both age groups were equally affected by background sounds, with speech impairing recall more than environmental sounds. In the spatial task, no ISE was found in adults and fourth graders, but third graders exhibited significant performance impairment from both sounds. There was no habituation to the sound effects across the experimental trials. The findings indicate that both specific interference and attention capture may contribute to the ISE, with the impact of attention capture potentially decreasing with age.
Defect-assisted reversible phase transition in mono- and few-layer ReS2
Authors: Zograf George , Yankovich Andrew B. , Küçüköz Betül , Agrawal Abhay V. , Polyakov Alexander Yu. , Ciers Joachim , Eriksson Fredrik , Haglund Åsa , Erhart Paul , Antosiewicz Tomasz J. , Olsson Eva , Shegai Timur O. 
Published: January 2025

Abstract
2D transition metal dichalcogenide (TMD) materials have attracted interest due to their remarkable excitonic, optical, electrical, and mechanical properties, which are dependent on their crystal structure. Consequently, controlling the crystal structure of these materials is essential for fine-tuning their performance, e.g., linear and nonlinear optical, as well as charge transport properties. While various phase-switching TMD materials are available, their transitions are often irreversible. Here, we investigate the mechanism of a light-induced reversible phase transition in mono- and bilayer rhenium disulfide (ReS2). Our observations, based on transmission electron microscopy, nonlinear spectroscopy, and density functional theory, reveal a transition from the ground

$${\rm{T}}^{\prime\prime}$$

T

″

(double-distorted T) to the metastable

$${\rm{H}}^{\prime}$$

H

′

(distorted H) phase under femtosecond laser irradiation or influence of highly-energetic electrons. We show that the formation of sulfur vacancies facilitates this phenomenon. Our findings pave the way toward manipulating the crystal structure of ReS2 and possibly its heterostructures.
Integrating molecular photoswitch memory with nanoscale optoelectronics for neuromorphic computing
Authors: Alcer David , Zaiats Nelia , Jensen Thomas K. , Philip Abbey M. , Gkanias Evripidis , Ceberg Nils , Das Abhijit , Flodgren Vidar , Heinze Stanley , Borgström Magnus T. , Webb Barbara , Laursen Bo W. , Mikkelsen Anders 
Published: January 2025

Abstract
Photonic solutions are potentially highly competitive for energy-efficient neuromorphic computing. However, a combination of specialized nanostructures is needed to implement all neuro-biological functionality. Here, we show that donor-acceptor Stenhouse adduct dyes integrated with III-V semiconductor nano-optoelectronics have combined excellent functionality for bio-inspired neural networks. The dye acts as synaptic weights in the optical interconnects, while the nano-optoelectronics provide neuron reception, interpretation and emission of light signals. These dyes can reversibly switch from absorbing to non-absorbing states, using specific wavelength ranges. Together, they show robust and predictable switching, low energy thermal reset and a memory dynamic range from days to sub-seconds that allows both short- and long-term memory operation at natural timescales. Furthermore, as the dyes do not need electrical connections, on-chip integration is simple. We illustrate the functionality using individual nanowire photodiodes as well as arrays. Based on the experimental performance metrics, our on-chip solution is capable of operating an anatomically validated model of the insect brain navigation complex.
Distinct anthropogenic aerosol and greenhouse gas effects on El Niño/Southern Oscillation variability
Authors: Ren Xianglin , Liu Wei 
Published: January 2025

Abstract
El Niño/Southern Oscillation variability has conspicuous impacts on ecosystems and severe weather. Here, we probe the effects of anthropogenic aerosols and greenhouse gases on El Niño/Southern Oscillation variability during the historical period using a broad set of climate models. Increased aerosols significantly amplify El Niño/Southern Oscillation variability primarily through weakening the mean advection feedback and strengthening the zonal advection and thermocline feedbacks, as linked to a weaker annual cycle of sea surface temperature in the eastern equatorial Pacific. They prevent extreme El Niño events, reduce interannual sea surface temperature skewness in the tropical Pacific, influence the likelihood of El Niño/Southern Oscillation events in April and June and allow for more El Niño transitions to Central Pacific events. While rising greenhouse gases significantly reduce El Niño/Southern Oscillation variability via a stronger sea surface temperature annual cycle and attenuated thermocline feedback. They promote extreme El Niño events, increase SST skewness, and enlarge the likelihood of El Niño/Southern Oscillation peaking in November while inhibiting Central Pacific El Niño/Southern Oscillation events.
Deep learning empowered sensor fusion boosts infant movement classification
Authors: Kulvicius Tomas , Zhang Dajie , Poustka Luise , Bölte Sven , Jahn Lennart , Flügge Sarah , Kraft Marc , Zweckstetter Markus , Nielsen-Saines Karin , Wörgötter Florentin , Marschik Peter B. 
Published: January 2025

Abstract

Background
To assess the integrity of the developing nervous system, the Prechtl general movement assessment (GMA) is recognized for its clinical value in diagnosing neurological impairments in early infancy. GMA has been increasingly augmented through machine learning approaches intending to scale-up its application, circumvent costs in the training of human assessors and further standardize classification of spontaneous motor patterns. Available deep learning tools, all of which are based on single sensor modalities, are however still considerably inferior to that of well-trained human assessors. These approaches are hardly comparable as all models are designed, trained and evaluated on proprietary/silo-data sets.

Methods
With this study we propose a sensor fusion approach for assessing fidgety movements (FMs). FMs were recorded from 51 typically developing participants. We compared three different sensor modalities (pressure, inertial, and visual sensors). Various combinations and two sensor fusion approaches (late and early fusion) for infant movement classification were tested to evaluate whether a multi-sensor system outperforms single modality assessments. Convolutional neural network (CNN) architectures were used to classify movement patterns.

Results
The performance of the three-sensor fusion (classification accuracy of 94.5%) is significantly higher than that of any single modality evaluated.

Conclusions
We show that the sensor fusion approach is a promising avenue for automated classification of infant motor patterns. The development of a robust sensor fusion system may significantly enhance AI-based early recognition of neurofunctions, ultimately facilitating automated early detection of neurodevelopmental conditions.