bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early detection of pancreatic cancer by comprehensive serum miRNA sequencing with automated machine learning
Authors: Kawai Munenori , Fukuda Akihisa , Otomo Ryo , Obata Shunsuke , Minaga Kosuke , Asada Masanori , Umemura Atsushi , Uenoyama Yoshito , Hieda Nobuhiro , Morita Toshihiro , Minami Ryuki , Marui Saiko , Yamauchi Yuki , Nakai Yoshitaka , Takada Yutaka , Ikuta Kozo , Yoshioka Takuto , Mizukoshi Kenta , Iwane Kosuke , Yamakawa Go , Namikawa Mio , Sono Makoto , Nagao Munemasa , Maruno Takahisa , Nakanishi Yuki , Hirai Mitsuharu , Kanda Naoki , Shio Seiji , Itani Toshinao , Fujii Shigehiko , Kimura Toshiyuki , Matsumura Kazuyoshi , Ohana Masaya , Yazumi Shujiro , Kawanami Chiharu , Yamashita Yukitaka , Marusawa Hiroyuki , Watanabe Tomohiro , Ito Yoshito , Kudo Masatoshi , Seno Hiroshi 
Published: August 2024

Abstract
Background
Pancreatic cancer is often diagnosed at advanced stages, and early-stage diagnosis of pancreatic cancer is difficult because of nonspecific symptoms and lack of available biomarkers.

Methods
We performed comprehensive serum miRNA sequencing of 212 pancreatic cancer patient samples from 14 hospitals and 213 non-cancerous healthy control samples. We randomly classified the pancreatic cancer and control samples into two cohorts: a training cohort (N = 185) and a validation cohort (N = 240). We created ensemble models that combined automated machine learning with 100 highly expressed miRNAs and their combination with CA19-9 and validated the performance of the models in the independent validation cohort.

Results
The diagnostic model with the combination of the 100 highly expressed miRNAs and CA19-9 could discriminate pancreatic cancer from non-cancer healthy control with high accuracy (area under the curve (AUC), 0.99; sensitivity, 90%; specificity, 98%). We validated high diagnostic accuracy in an independent asymptomatic early-stage (stage 0-I) pancreatic cancer cohort (AUC:0.97; sensitivity, 67%; specificity, 98%).

Conclusions
We demonstrate that the 100 highly expressed miRNAs and their combination with CA19-9 could be biomarkers for the specific and early detection of pancreatic cancer.
Tuning the B-CLL microenvironment: evidence for BAG3 protein- mediated regulation of stromal fibroblasts activity
Authors: Basile Anna , Giudice Valentina , Mettivier Laura , Falco Antonia , Cammarota Anna Lisa , D’Ardia Angela , Selleri Carmine , De Marco Margot , De Maio Nicola , Turco Maria Caterina , Marzullo Liberato , Rosati Alessandra 
Published: August 2024

AbstractThe Bcl2-associated athanogene-3 (BAG3) protein, a critical regulator of cellular survival, has been identified as a potential therapeutic target in various malignancies. This study investigates the role of BAG3 within stromal fibroblasts and its interaction with B-cell chronic lymphocytic leukemia (B-CLL) cells. Previous research demonstrated that BAG3 maintains the active state of pancreatic stellate cells (PSCs) and aids pancreatic ductal adenocarcinoma (PDAC) spread via cytokine release. To explore BAG3’s role in bone marrow-derived stromal fibroblasts, BAG3 was silenced in HS-5 cells using siRNA. In co-culture experiments with PBMCs from B-CLL patients, BAG3 silencing in HS-5 cells increased apoptosis and decreased phosphorylation of BTK, AKT, and ERK in B-CLL cells, thus disrupting their pro-survival key signaling pathways. The observation of fibroblast-activated protein (FAP) positive cells in infiltrated bone marrow specimens co-expressing BAG3 further support the involvement of the protein in fibroblast-mediated tumor survival. Additionally, BAG3 appears to support B-CLL survival by modulating cytokine networks, including IL-10 and CXCL12, which are essential for leukemic cell survival and proliferation. A robust correlation between BAG3 expression and the levels of CXCL12 and IL-10 was observed in both co-cultures and patient specimens. These findings point out the need for a more in-depth comprehension of the intricate network of interactions within the tumor microenvironment and provide valuable insights for the selection of new potential therapeutic targets in the medical treatment of CLL.
Metal-polyphenol-network coated R612F nanoparticles reduce drug resistance in hepatocellular carcinoma by inhibiting stress granules
Authors: Zhou Yue , Zhang Tongjia , Wang Shujie , Jiao Zitao , Lu Kejia , Liu Xinyi , Li Hui , Jiang Wei , Zhang Xiaowei 
Published: August 2024

AbstractStress granules (SGs) are considered to be the nonmembrane discrete assemblies present in the cytoplasm to cope with various environmental stress. SGs can promote the progression and drug resistance of hepatocellular carcinoma (HCC). Therefore, it is important to explore the mechanism of SG formation to reduce drug resistance in HCC. In this study, we demonstrate that p110α is required for SGs assembly. Mechanistically, the Arg-Gly (RG) motif of p110α is required for SG competence and regulates the recruitment of SG components. The methylation of p110α mediated by protein arginine methyltransferase 1 (PRMT1) interferes with the recruitment of p110α to SG components, thereby inhibiting the promotion of p110α to SGs. On this basis, we generated metal-polyphenol-network-coated R612F nanoparticles (MPN-R612F), which can efficiently enter HCC cells and maintain the hypermethylation state of p110α, thereby inhibiting the assembly of SGs and ultimately reducing the resistance of HCC cells to sorafenib. The combination of MPN-R612F nanoparticles and sorafenib can kill HCC cells more effectively and play a stronger anti-tumor effect. This study provides a new perspective for targeting SGs in the treatment of HCC.
Inhibition of TOPORS ubiquitin ligase augments the efficacy of DNA hypomethylating agents through DNMT1 stabilization
Authors: Kaito Satoshi , Aoyama Kazumasa , Oshima Motohiko , Tsuchiya Akiho , Miyota Makiko , Yamashita Masayuki , Koide Shuhei , Nakajima-Takagi Yaeko , Kozuka-Hata Hiroko , Oyama Masaaki , Yogo Takao , Yabushita Tomohiro , Ito Ryoji , Ueno Masaya , Hirao Atsushi , Tohyama Kaoru , Li Chao , Kawabata Kimihito Cojin , Yamaguchi Kiyoshi , Furukawa Yoichi , Kosako Hidetaka , Yoshimi Akihide , Goyama Susumu , Nannya Yasuhito , Ogawa Seishi , Agger Karl , Helin Kristian , Yamazaki Satoshi , Koseki Haruhiko , Doki Noriko , Harada Yuka , Harada Hironori , Nishiyama Atsuya , Nakanishi Makoto , Iwama Atsushi 
Published: August 2024

AbstractDNA hypomethylating agents (HMAs) are used for the treatment of myeloid malignancies, although their therapeutic effects have been unsatisfactory. Here we show that CRISPR-Cas9 screening reveals that knockout of topoisomerase 1-binding arginine/serine-rich protein (TOPORS), which encodes a ubiquitin/SUMO E3 ligase, augments the efficacy of HMAs on myeloid leukemic cells with little effect on normal hematopoiesis, suggesting that TOPORS is involved in resistance to HMAs. HMAs are incorporated into the DNA and trap DNA methyltransferase-1 (DNMT1) to form DNA-DNMT1 crosslinks, which undergo SUMOylation, followed by proteasomal degradation. Persistent crosslinking is cytotoxic. The TOPORS RING finger domain, which mediates ubiquitination, is responsible for HMA resistance. In TOPORS knockout cells, DNMT1 is stabilized by HMA treatment due to inefficient ubiquitination, resulting in the accumulation of unresolved SUMOylated DNMT1. This indicates that TOPORS ubiquitinates SUMOylated DNMT1, thereby promoting the resolution of DNA-DNMT1 crosslinks. Consistently, the ubiquitination inhibitor, TAK-243, and the SUMOylation inhibitor, TAK-981, show synergistic effects with HMAs through DNMT1 stabilization. Our study provides a novel HMA-based therapeutic strategy that interferes with the resolution of DNA-DNMT1 crosslinks.
hnRNP R promotes O-GlcNAcylation of eIF4G and facilitates axonal protein synthesis
Authors: Zare Abdolhossein , Salehi Saeede , Bader Jakob , Schneider Cornelius , Fischer Utz , Veh Alexander , Arampatzi Panagiota , Mann Matthias , Briese Michael , Sendtner Michael 
Published: August 2024

AbstractMotoneurons critically depend on precise spatial and temporal control of translation for axon growth and the establishment and maintenance of neuromuscular connections. While defects in local translation have been implicated in the pathogenesis of motoneuron disorders, little is known about the mechanisms regulating axonal protein synthesis. Here, we report that motoneurons derived from Hnrnpr knockout mice show reduced axon growth accompanied by lowered synthesis of cytoskeletal and synaptic components in axons. Mutant mice display denervated neuromuscular junctions and impaired motor behavior. In axons, hnRNP R is a component of translation initiation complexes and, through interaction with O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt), modulates O-GlcNAcylation of eIF4G. Restoring axonal O-GlcNAc levels rescued local protein synthesis and axon growth defects of hnRNP R knockout motoneurons. Together, these findings demonstrate a function of hnRNP R in controlling the local production of key factors required for axon growth and formation of neuromuscular innervations.
Developmental signals control chromosome segregation fidelity during pluripotency and neurogenesis by modulating replicative stress
Authors: de Jaime-Soguero Anchel , Hattemer Janina , Bufe Anja , Haas Alexander , van den Berg Jeroen , van Batenburg Vincent , Das Biswajit , di Marco Barbara , Androulaki Stefania , Böhly Nicolas , Landry Jonathan J. M. , Schoell Brigitte , Rosa Viviane S. , Villacorta Laura , Baskan Yagmur , Trapp Marleen , Benes Vladimir , Chabes Andrei , Shahbazi Marta , Jauch Anna , Engel Ulrike , Patrizi Annarita , Sotillo Rocio , van Oudenaarden Alexander , Bageritz Josephine , Alfonso Julieta , Bastians Holger , Acebrón Sergio P. 
Published: August 2024

AbstractHuman development relies on the correct replication, maintenance and segregation of our genetic blueprints. How these processes are monitored across embryonic lineages, and why genomic mosaicism varies during development remain unknown. Using pluripotent stem cells, we identify that several patterning signals—including WNT, BMP, and FGF—converge into the modulation of DNA replication stress and damage during S-phase, which in turn controls chromosome segregation fidelity in mitosis. We show that the WNT and BMP signals protect from excessive origin firing, DNA damage and chromosome missegregation derived from stalled forks in pluripotency. Cell signalling control of chromosome segregation declines during lineage specification into the three germ layers, but re-emerges in neural progenitors. In particular, we find that the neurogenic factor FGF2 induces DNA replication stress-mediated chromosome missegregation during the onset of neurogenesis, which could provide a rationale for the elevated chromosomal mosaicism of the developing brain. Our results highlight roles for morphogens and cellular identity in genome maintenance that contribute to somatic mosaicism during mammalian development.
Photoredox phase engineering of transition metal dichalcogenides
Authors: Lim Juhwan , Lee Jung-In , Wang Ye , Gauriot Nicolas , Sebastian Ebin , Chhowalla Manish , Schnedermann Christoph , Rao Akshay 
Published: August 2024

AbstractCrystallographic phase engineering plays an important part in the precise control of the physical and electronic properties of materials. In two-dimensional transition metal dichalcogenides (2D TMDs), phase engineering using chemical lithiation with the organometallization agent n-butyllithium (n-BuLi), to convert the semiconducting 2H (trigonal) to the metallic 1T (octahedral) phase, has been widely explored for applications in areas such as transistors, catalysis and batteries1–15. Although this chemical phase engineering can be performed at ambient temperatures and pressures, the underlying mechanisms are poorly understood, and the use of n-BuLi raises notable safety concerns. Here we optically visualize the archetypical phase transition from the 2H to the 1T phase in mono- and bilayer 2D TMDs and discover that this reaction can be accelerated by up to six orders of magnitude using low-power illumination at 455 nm. We identify that the above-gap illumination improves the rate-limiting charge-transfer kinetics through a photoredox process. We use this method to achieve rapid and high-quality phase engineering of TMDs and demonstrate that this methodology can be harnessed to inscribe arbitrary phase patterns with diffraction-limited edge resolution into few-layer TMDs. Finally, we replace pyrophoric n-BuLi with safer polycyclic aromatic organolithiation agents and show that their performance exceeds that of n-BuLi as a phase transition agent. Our work opens opportunities for exploring the in situ characterization of electrochemical processes and paves the way for sustainably scaling up materials and devices by photoredox phase engineering.
Activity of nested neural circuits drives different courtship songs in Drosophila
Authors: Shiozaki Hiroshi M. , Wang Kaiyu , Lillvis Joshua L. , Xu Min , Dickson Barry J. , Stern David L. 
Published: August 2024

AbstractMotor systems implement diverse motor programs to pattern behavioral sequences, yet how different motor actions are controlled on a moment-by-moment basis remains unclear. Here, we investigated the neural circuit mechanisms underlying the control of distinct courtship songs in Drosophila. Courting males rapidly alternate between two types of song: pulse and sine. By recording calcium signals in the ventral nerve cord in singing flies, we found that one neural population is active during both songs, whereas an expanded neural population, which includes neurons from the first population, is active during pulse song. Brain recordings showed that this nested activation pattern is present in two descending pathways required for singing. Connectomic analysis reveals that these two descending pathways provide structured input to ventral nerve cord neurons in a manner consistent with their activation patterns. These results suggest that nested premotor circuit activity, directed by distinct descending signals, enables rapid switching between motor actions.
Deformation-based morphometry applied to FDG PET data reveals hippocampal atrophy in Alzheimer’s disease
Authors: Frings Lars , Blazhenets Ganna , Brumberg Joachim , Rau Alexander , Urbach Horst , Meyer Philipp T. 
Published: August 2024

AbstractCerebral atrophy is a key finding in patients with dementia and usually determined on MRI. We tested whether cerebral atrophy can be imaged with FDG PET by applying deformation-based morphometry (DBM). We retrospectively identified 26 patients with a biomarker-supported clinical diagnosis of Alzheimer’s disease (AD) who had received FDG PET on a fully-digital PET/CT system and structural MRI and compared them to 13 healthy elderly controls (HEC). We performed DBM with FDG PET data (FDG-DBM). As a reference standard for determining atrophy we used voxel-based morphometry of MRI data (MRI-VBM). For conventional analysis of hypometabolism, scaled FDG PET scans (reference: brain parenchyma) were compared between groups. Receiver operating characteristic (ROC) analyses were performed. ROI read-outs were tested for associations with cognitive test performance. FDG-DBM showed abnormalities in AD mainly in the bilateral hippocampi. Similarly, MRI-VBM showed hippocampal atrophy. By contrast, conventional FDG PET analysis revealed reduced bilateral temporo-parietal FDG uptake (all p < 0.05, FWE-corrected). FDG-DBM measures of the hippocampus significantly separated AD from HEC with an AUC of 0.81; MRI-VBM achieved an AUC of 0.87; the difference between the two ROC curves was not significant (p = 0.40). Whereas FDG uptake of the hippocampus did not separate AD from HEC, FDG uptake of the Landau Meta-ROI achieved an AUC of 0.88. Verbal memory was significantly associated with FDG-DBM measures of the hippocampus (p = 0.009), but not of the Landau Meta-ROI (p > 0.1). The opposite held true for conventional FDG uptake (p > 0.1 and p = 0.001, respectively). Hippocampal atrophy in AD can be detected by applying DBM to clinical, fully-digital FDG PET. It correlates with cognitive performance and might constitute a biomarker of neurodegeneration that is complementary to conventional FDG PET analysis of regional hypometabolism.
Environmental impact assessment based on particulate matter, and chlorophyll content of urban trees
Authors: Abriha-Molnár Vanda Éva , Szabó Szilárd , Magura Tibor , Tóthmérész Béla , Abriha Dávid , Sipos Bianka , Simon Edina 
Published: August 2024

AbstractThe amount of dust deposited on tree leaves is a cost-effective indicator of air quality. Our aim was to explore the leaf surface deposition, and chlorophyll content of leaves along a road section that started at an intersection, and ended in a less disturbed suburban area in Debrecen, Hungary. We also assessed the impact of meteorological conditions on the amount of deposited dust. Leaf samples were collected in July, and September 2022 from Celtis occidentalis, a frequent species in green urban areas of Debrecen. We found a significant negative correlation between dust deposition, and the distance from the intersection in July. In September, dust deposition decreased considerably compared to July, due to rainfall before the second sampling. Surprisingly, we found a positive correlation between dust deposition and chlorophyll content in July. Our findings suggest that dust deposition on leaves serves as a reliable indicator of traffic intensity, because the excess dust caused by the proximity of vehicle traffic can be detected on the leaf surface. Although, rainfall can disrupt the patterns in dust deposition that have developed over an extended period through wash-off and resuspension. Hence, it is advisable to consider these effects while selecting the sampling time and evaluating the results.
Onscreen Chemistry
Authors: O’Donoghue John 
Published: August 2024

Lights. Camera. Reaction!
How do real world discoveries affect what we see on screen? What impact does the world of film have on how we view chemistry? Are chemists the villains or the heroes?
From Transylvania and Chernobyl to generic geniuses and meth makers, explore the fascinating world of the big and small screen through a chemist’s eye as cinema and television are passed under the microscope. From the earliest silent films through to modern, multi-episode television, discover the real-life chemistry that inspired your favourite shows.
Learn how depictions of chemists have changed through the years. Are chemists always pictured as relentless in their quest, are the dangers and risks accurately represented and did the image of chemistry teachers change after the portrayal of a teacher turned illicit drug supplier?
Uncover the facts and fiction around these questions and many more with Onscreen Chemistry.
Vigilant Attention During Cognitive and Language Processing in Aphasia
Authors: Hibshman Dannielle , Riley Ellyn A. 
Published: August 2024

Purpose:
Persons with aphasia (PWA) experience differences in attention after stroke, potentially impacting cognitive/language performance. This secondary analysis investigated physiologically measured vigilant attention during linguistic and nonlinguistic processing in PWA and control participants.

Method:
To evaluate performance and attention in a language task, seven PWA read sentences aloud (linguistic task) and were compared to a previous data set of 10 controls and 10 PWA. To evaluate performance and attention in a language-independent task, 11 controls and nine PWA completed the Bivalent Shape Task (nonlinguistic task). Continuous electroencephalogram (EEG) data were collected during each session. A previously validated EEG algorithm classified vigilant-attention state for each experiment trial into high, moderate, distracted, or no attention. Dependent measures were task accuracy and amount of time spent in each attention state (measured by the number of trials).

Results:
PWA produced significantly more errors than controls on the linguistic task, but groups performed similarly on the nonlinguistic task. During the linguistic task, controls spent significantly more time than PWA in a moderate-attention state, but no statistically significant differences were found between groups for other attention states. For the nonlinguistic task, amount of time controls and PWA spent in each attention state was more evenly distributed. When directly comparing attention patterns between linguistic and nonlinguistic tasks, PWA showed significantly more time in a high-attention state during the linguistic task as compared to the nonlinguistic task; however, controls showed no significant differences between linguistic and nonlinguistic tasks.

Conclusions:
This study provides new evidence that PWA experience a heightened state of vigilant attention when language processing demands are higher (during a linguistic task) than when language demands are lower (during a nonlinguistic task). Collectively, results of this study suggest that when processing language, PWA may allocate more attentional resources than when completing other kinds of cognitive tasks.
Eye-Tracking Methodology to Detect Differences in Attention to Faces Between Developmental Language Disorder and Autism
Authors: Vacas Julia , Antolí Adoración , Sánchez-Raya Araceli , Pérez-Dueñas Carolina , Cuadrado Fátima 
Published: August 2024

Purpose:
Developmental language disorder (DLD) and autism sometimes appear as overlapping conditions in behavioral tests. There is much literature on the visual scanning pattern (VSP) of faces in autistic children, but this is scarce regarding those with DLD. The purpose of this study was to compare the VSP of faces in young children with DLD, those with autism, and typically developing peers, assessing the effect of three variables.

Method:

Two eye-tracking experiments were designed to assess the effect of the emotion and the poser's gender (Experiment 1) and the poser's age (Experiment 2) on the VSP of participants (Experiment 1:
N
= 59, age range: 32–74 months; Experiment 2:
N
= 58, age range: 32–74 months). We operationalized the VSP in terms of attentional orientation, visual preference, and depth of processing of each sort of face. We developed two paired preference tasks in which pairs of images of faces showing different emotions were displayed simultaneously to compete for children's attention.

Results:
Data analysis revealed two VSP markers common to both disorders: (a) superficial processing of faces and (b) late orientation to angry and child faces. Moreover, one specific marker for each condition was also found: typical preference for child faces in children with DLD versus diminished preference for them in autistic children.

Conclusions:
Considering the similarities found between children with DLD and those with autism, difficulties of children with DLD in attention to faces have been systematically underestimated. Thus, more effort must be made to identify and respond to the needs of this population. Clinical practice may benefit from the potential of eye-tracking methodology and the analysis of the VSP to assess attention to faces in both conditions. This would also contribute to the improvement of early differential diagnosis in the long run.