bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breast cancers with high proliferation and low ER-related signalling have poor prognosis and unique molecular features with implications for therapy
Authors: Licata Luca , Barreca Marco , Galbardi Barbara , Dugo Matteo , Viale Giulia , Győrffy Balàzs , Karn Thomas , Pusztai Lajos , Gianni Luca , Callari Maurizio , Bianchini Giampaolo 
Published: November 2023

Abstract
Background
Luminal breast cancers with high proliferation (MKShi) and low ER-related signalling (ERSlo) have a poor prognosis. We investigated treatment responses and molecular features of MKShi/ERSlo tumours to inform potential therapies.

Methods
Gene expression data from patients who received neoadjuvant chemotherapy (NAC) without (MDACC, N = 199) or with pembrolizumab (I-SPY2, N = 40), or endocrine therapy (NET) without (POETIC, N = 172) or with palbociclib (NeoPalAna, N = 32) were analyzed to assess treatment response by MKS/ERS-subgroups. TCGA was used to assess the mutational landscape and biomarkers associated with palbociclib-resistance (Cyclin-E, RBsig, IRPR) and immunotherapy-response (TMB, TILs, T-cell inflamed) by MKS/ERS-subgroups.

Results
Compared to MKShi/ERShi tumours, MKShi/ERSlo tumours had higher pathological response rates to NAC (22% vs 8%, p = 0.06) but a higher recurrence risk (4-year metastasis-free survival 70% vs 94%, p = 0.01). MKShi/ERSlo tumours frequently harboured TP53 (34%) and PIK3CA (33%) mutations, and showed high expression of Cyclin-E, RBsig and IRPR, high TMB and elevated TIL and T-cell inflamed metagene expression. MKShi/ERSlo tumours retained high proliferation after NET with or without palbociclib but had higher pathological complete response rates when pembrolizumab was added to NAC (42% vs 21%, p = 0.07).

Conclusions
MKShi/ERSlo tumours have dismal outcomes and are enriched in chemotherapy-sensitive but ET- and palbociclib-resistant tumours. Biomarker analysis and clinical data suggest a potential role for immunotherapy in this group.
A criterion for strange metallicity in the Lorenz ratio
Authors: Tulipman Evyatar , Berg Erez 
Published: November 2023

AbstractThe Wiedemann-Franz (WF) law, stating that the Lorenz ratio L = κ/(Tσ) between the thermal and electrical conductivities in a metal approaches a universal constant $${L}_{0}={\pi }^{2}{k}_{B}^{2}/(3{e}^{2})$$

L

0

=

π

2

k

B

2

/

(

3

e

2

)

at low temperatures, is often interpreted as a signature of fermionic Landau quasi-particles. In contrast, we show that various models of weakly disordered non-Fermi liquids also obey the WF law at T → 0. Instead, we propose using the leading low-temperature correction to the WF law, L(T) − L0 (proportional to the inelastic scattering rate), to distinguish different types of strange metals. As an example, we demonstrate that in a solvable model of a marginal Fermi-liquid, L(T) − L0 ∝ − T. Using the quantum Boltzmann equation (QBE) approach, we find analogous behavior in a class of marginal- and non-Fermi liquids with a weakly momentum-dependent inelastic scattering. In contrast, in a Fermi-liquid, L(T) − L0 is proportional to − T2. This holds even when the resistivity grows linearly with T, due to T − linear quasi-elastic scattering (as in the case of electron-phonon scattering at temperatures above the Debye frequency). Finally, by exploiting the QBE approach, we demonstrate that the transverse Lorenz ratio, Lxy = κxy/(Tσxy), exhibits the same behavior.
Capsaicin alleviates neuronal apoptosis and schizophrenia-like behavioral abnormalities induced by early life stress
Authors: Xu Shilin , Hao Keke , Xiong Ying , Xu Rui , Huang Huan , Wang Huiling 
Published: November 2023

AbstractEarly life stress (ELS) is associated with the later development of schizophrenia. In the rodent model, the maternal separation (MS) stress may induce neuronal apoptosis and schizophrenia-like behavior. Although the TRPV1 agonist capsaicin (CAP) has been reported to reduce apoptosis in the central nervous system, its effect in MS models is unclear. Twenty-four hours of MS of Wistar rat pups on postnatal day (PND9) was used as an ELS. Male rats in the adult stage were the subjects of the study. CAP (1 mg/kg/day) intraperitoneal injection pretreatment was undertaken before behavioral tests for 1 week and continued during the tests. Behavioral tests included open field, novel object recognition, Barnes maze test, and pre-pulse inhibition (PPI) test. MS rats showed behavioral deficits and cognitive impairments mimicking symptoms of schizophrenia compared with controls. MS decreased the expression of TRPV1 in the frontal association cortex (FrA) and in the hippocampal CA1, CA3, and dentate gyrus (DG) regions compared with the control group resulting in the increase of pro-apoptotic proteins (BAX, Caspase3, Cleaved-Caspase3) and the decrease of anti-apoptotic proteins (Bcl-2). The number of NeuN++TUNEL+ cells increased in the MS group in the FrA, CA1, CA3, and DG compared with the control group. Neuronal and behavioral impairments of MS were reversed by treatment with CAP. Exposure to ELS may lead to increased neuronal apoptosis and impaired cognitive function with decreased TRPV1 expression in the prefrontal cortex and hippocampus in adulthood. Sustained low-dose administration of CAP improved neuronal apoptosis and cognitive function. Our results provide evidence for future clinical trials of chili peppers or CAP as dietary supplements for the reversal treatment of schizophrenia.
The application value of high-frequency ultrasound in the feasibility assessment of endoscopic retrograde appendicitis therapy in children with appendicitis
Authors: Guo Xiaoya , Yang Hengli , Zhao Ping , Li Jinghua , Zeng Lingchao , Wang Chunhui , Yang Yilin , Yang Ruijing 
Published: November 2023

AbstractAcute appendicitis is one of the common acute abdominal diseases in pediatrics. However, the implementation of radiological examination guided endoscopic retrograde appendicitis therapy (ERAT) in adults is limited in children. Our previous research explored the non-invasive guidance of high-frequency ultrasound (HFUS) for ERAT and achieved good therapeutic effects. This study mainly focuses on exploring the application value of HFUS in the feasibility assessment of ERAT in children with appendicitis. 163 children with appendicitis received ERAT guided by HFUS were analyzed retrospectively. According to the parameters evaluated by HFUS before and during ERAT, the results indicated that the distance between the appendix orifice and the ileocecal valve significantly affected the time required for the guidewire to enter the appendix cavity (P < 0.05). The diameter and the texture of the fecalith, the thickness of the intestinal wall of the appendiceal orifice all had significant effects on the successful removal of the fecalith (P < 0.05). The success rate, treatment time and final flushing effect of the guidewire to reach the blind end of the appendix were significantly affected by the tortuosity of the appendix and whether there was adhesion with surrounding tissues (P < 0.05). HFUS can accurately assess the feasibility of ERAT in children with appendicitis.
Optimized backpropagation neural network for risk prediction in corporate financial management
Authors: Gu Lingzi 
Published: November 2023

AbstractCorporate financial management is responsible for constructing, optimizing, and modifying finance-related structures for an unremitting function. The finance optimization model incorporates risk prediction and fund balancing for distinguishable corporate operations. This risk prediction is handled using sophisticated computing models with artificial intelligence and machine learning for self-training and external learning. Therefore, this article introduces a Backpropagation-aided Neural Network for designing an Optimal Risk Prediction (ORP-BNN) to pre-validate existing and new financial imbalances. The risk prediction model is designed to cope with corporate standards and minimum riskless financial management. This is designed as a linear snowfall model wherein the BNN decides the significance between fund allocation and restraining. The snowfall model significantly relies on allocation or restraining, which is achieved by assigning significant weights depending on the previous financial decision outcome. The weight factor is determined using gradient loss functions associated with the computing model. The training process is pursued using different structural modifications used for successful financial management in the past. In particular, the risk thwarted financial planning using a snowfall-like computing model, and its data inputs are used for training optimization. Therefore, the proposed model's successful risk mitigation stands high under prompt decisions.
Mechanisms and heterogeneity in the construction of network infrastructure to help rural households bridge the “digital divide”
Authors: Meng Xiangtai , Wang Xinting , Nisar Ubair , Sun Shiying , Ding Xin 
Published: November 2023

AbstractAddressing the digital divide that plagues rural areas has become an important issue in narrowing the urban–rural gap and achieving common prosperity. This article examines the impact of network infrastructure on rural households’ ability to cross the digital divide by using the "broadband rural" strategy as a proxy variable for network infrastructure and combining data from the China Family Panel Studies (CFPS) with a score propensity matched difference-in-differences model (PSM-DID). The results show that network infrastructure can help farmers cross the access and use divide, but does not contribute significantly to crossing the ability divide in the current period. A triple difference model (DDD) was introduced to test the effect of network technology training on the contribution of network infrastructure to the ability gap, and the ability gap needs to be based on the use gap, so there is a delay in the response of the ability gap to policy. Further analysis reveals that network infrastructure mainly facilitates non-farm occupational groups to cross the capability divide, and facilitates middle-aged and young people to cross the digital divide, and does not have significant effects on groups involved in agricultural work and older people. In view of this, the network infrastructure should be continuously promoted, public service training on digital skills should be organized, electronic products and information services should be created exclusively for the elderly group and the group involved in agricultural production, and the ability of farmers to apply the network to their production life should be strengthened.
Increasing densities of Pacific crown-of-thorns starfish (Acanthaster cf. solaris) at Lizard Island, northern Great Barrier Reef, resolved using a novel survey method
Authors: Chandler Josie F. , Burn Deborah , Caballes Ciemon F. , Doll Peter C. , Kwong Sarah L. T. , Lang Bethan J. , Pacey Kai I. , Pratchett Morgan S. 
Published: November 2023

AbstractRecurrent population irruptions of Pacific crown-of-thorns starfish (CoTS,Acanthastercf.solaris) are among the foremost causes of coral mortality on Australia’s Great Barrier Reef (GBR). Early intervention during the initiation of new population irruptions represents the best opportunity to effectively manage this threat. However, current survey methods are not sufficiently sensitive to detect changes in CoTS densities during the early onset of population irruptions. Using scooter-assisted large area diver-based (SALAD) surveys, this study revealed increasing densities of CoTS at Lizard Island from 2019 to 2022. Inferred densities of adult CoTS (which account for distinct sets of observed feeding scars where starfish were not detected) increased from 4.90 ha−1(± 0.85 SE) in 2019 to 17.71 ha−1(± 2.3 SE) in 2022. A wide range of size classes were recorded suggesting that recruitment over several years is contributing to increasing densities. Importantly, the sustained density increases reported here denote that renewed CoTS population irruptions may soon become fully established at Lizard Island and more broadly in the northern GBR, especially without early intervention through effective population management.
Disease specific urinary biomarkers in the central nervous system
Authors: Duggins-Warf Micah , Ghalali Aram , Sesen Julie , Martinez Tyra , Fehnel Katie P. , Pineda Steven , Zurakowski David , Smith Edward R. 
Published: November 2023

AbstractUrinary biomarkers can diagnose and monitor pathophysiologic conditions in the central nervous system (CNS). However, focus is often on single diseases, with limited data on discriminatory capability of this approach in a general setting. Here, we demonstrate that different classes of CNS disease exhibit distinct biomarker patterns, evidence of disease-specific “fingerprinting.” Urine from 218 patients with pathology-confirmed tumors or cerebrovascular disease, controls (n = 33) were collected. ELISA and/or bead-based multiplexing quantified levels of 21 putative urinary biomarkers. Analysis identified biomarkers capable of distinguishing each disease from controls and other diseases. Mann–Whitney U tests identified biomarkers with differential expression between disease types and controls (P ≤ 0.001). Subsequent receiver-operating characteristic (ROC) analyses revealed distinguishing biomarkers with high sensitivity and specificity. Areas under the curve (AUCs) ranged 0.8563–1.000 (P values ≤ 0.0003), sensitivities ranged 80.00–100.00%, and specificities ranged 80.95–100.00%. These data demonstrate proof-of-principle evidence that disease-specific urinary biomarker signatures exist. In contrast to non-specific responses to ischemia or injury, these results suggest that urinary biomarkers accurately reflect unique biological processes distinct to different diseases. This work can be used to generate disease-specific panels for enhancing diagnosis, assisting less-invasive follow-up and herald utility by revealing putative disease-specific therapeutic targets.
High-level production of nervonic acid in the oleaginous yeast Yarrowia lipolytica by systematic metabolic engineering
Authors: Su Hang , Shi Penghui , Shen Zhaoshuang , Meng Huimin , Meng Ziyue , Han Xingfeng , Chen Yanna , Fan Weiming , Fa Yun , Yang Chunyu , Li Fuli , Wang Shi’an 
Published: November 2023

AbstractNervonic acid benefits the treatment of neurological diseases and the health of brain. In this study, we employed the oleaginous yeast Yarrowia lipolytica to overproduce nervonic acid oil by systematic metabolic engineering. First, the production of nervonic acid was dramatically improved by iterative expression of the genes ecoding β-ketoacyl-CoA synthase CgKCS, fatty acid elongase gELOVL6 and desaturase MaOLE2. Second, the biosynthesis of both nervonic acid and lipids were further enhanced by expression of glycerol-3-phosphate acyltransferases and diacylglycerol acyltransferases from Malania oleifera in endoplasmic reticulum (ER). Third, overexpression of a newly identified ER structure regulator gene YlINO2 led to a 39.3% increase in lipid production. Fourth, disruption of the AMP-activated S/T protein kinase gene SNF1 increased the ratio of nervonic acid to lignoceric acid by 61.6%. Next, pilot-scale fermentation using the strain YLNA9 exhibited a lipid titer of 96.7 g/L and a nervonic acid titer of 17.3 g/L (17.9% of total fatty acids), the highest reported titer to date. Finally, a proof-of-concept purification and separation of nervonic acid were performed and the purity of it reached 98.7%. This study suggested that oleaginous yeasts are attractive hosts for the cost-efficient production of nervonic acid and possibly other very long-chain fatty acids (VLCFAs).
Redox-responsive peptide-based complex coacervates as delivery vehicles with controlled release of proteinous drugs
Authors: Wang Jiahua , Abbas Manzar , Huang Yu , Wang Junyou , Li Yuehua 
Published: November 2023

AbstractProteinous drugs are highly promising therapeutics to treat various diseases. However, they suffer from limited circulation times and severe off-target side effects. Inspired by active membraneless organelles capable of dynamic recruitment and releasing of specific proteins, here, we present the design of coacervates as therapeutic protocells, made from small metabolites (anionic molecules) and simple arginine-rich peptides (cationic motif) through liquid-liquid phase separation. These complex coacervates demonstrate that their assembly and disassembly can be regulated by redox chemistry, which helps to control the release of the therapeutic protein. A model proteinous drugs, tissue plasminogen activator (tPA), can rapidly compartmentalize inside the complex coacervates, and the coacervates formed from peptides conjugated with arginine-glycine-aspartic acid (RGD) motif (a fibrinogen-derived peptide sequence), show selective binding to the thrombus site and thus enhance on-target efficacy of tPA. Furthermore, the burst release of tPA can be controlled by the redox-induced dissolution of the coacervates. Our proof-of-principle complex coacervate system provides insights into the sequestration and release of proteinous drugs from advanced drug delivery systems and represents a step toward the construction of synthetic therapeutic protocells for biomedical applications.
A new design approach of hardware implementation through natural language entry
Authors: Yang Kaiyuan , Liu Haotian , Zhao Yuqin , Deng Tiantai 
Published: November 2023

AbstractOpenAI's ChatGPT (GPT‐4) ushers in a superior mode of computer interaction through natural language dialogues. Notably, it generates not only engaging dialogues but also codes aligned to queries and requirements. The potential of ChatGPT in hardware implementation via natural language is implemented and a strategy for “asking the right questions” is outlined. The versatility of ChatGPT is demonstrated through three mainstream hardware designs – systolic array, ResNet and MobileNet accelerators – comparing these with hand‐coded designs. The evaluation metrics include design quality, design efforts, and limitations of code generated by ChatGPT/GPT‐4/Cursor against prevalent High‐Level Synthesis or hand‐coded HDL designs. Consequently, a novel design workflow is proposed and the constraints of using GPT, particularly in AI accelerators, are highlighted.
The multi-spacecraft high-energy solar particle event of 28 October 2021
Authors: Kouloumvakos A. , Papaioannou A. , Waterfall C. O. G. , Dalla S. , Vainio R. , Mason G. M. , Heber B. , Kühl P. , Allen R. C. , Cohen C. M. S. , Ho G. , Anastasiadis A. , Rouillard A. P. , Rodríguez-Pacheco J. , Guo J. , Li X. , Hörlöck M. , Wimmer-Schweingruber R. F. 
Published: November 2023

Aims. We studied the first multi-spacecraft high-energy solar energetic particle (SEP) event of solar cycle 25, which triggered a ground level enhancement on 28 October 2021, using data from multiple observers (Parker Solar Probe, STEREO-A, Solar Orbiter, GOES, SOHO, BepiColombo, and the Mars Science Laboratory) that were widely distributed throughout the heliosphere and located at heliocentric distances ranging from 0.60 to 1.60 AU.
Methods. We present SEP observations at a broad energy range spanning from ∼10 to 600 MeV obtained from the different instruments. We performed detail modelling of the shock wave and we derived the 3D distribution and temporal evolution of the shock parameters. We further investigated the magnetic connectivity of each observer to the solar surface and examined the shock’s magnetic connection. We performed velocity dispersion analysis and time-shifting analysis to infer the SEP release time. We derived and present the peak proton flux spectra for all the above spacecraft and fluence spectra for major species recorded on board Solar Orbiter from the Suprathermal Ion Spectrograph (SIS). We performed 3D SEP propagation simulations to investigate the role of particle transport in the distribution of SEPs to distant magnetically connected observers.
Results. Observations and modelling show that a strong shock wave formed promptly in the low corona. At the SEP release time windows, we find a connection with the shock for all the observers. PSP, STEREO-A, and Solar Orbiter were connected to strong shock regions with high Mach numbers (>4), whereas the Earth and other observers were connected to lower Mach numbers. The SEP spectral properties near Earth demonstrate two power laws, with a harder (softer) spectrum in the low-energy (high-energy) range. Composition observations from SIS (and near-Earth instruments) show no serious enhancement of flare-accelerated material.
Conclusions. A possible scenario consistent with the observations and our analysis indicates that high-energy SEPs at PSP, STEREO-A, and Solar Orbiter were dominated by particle acceleration and injection by the shock, whereas high-energy SEPs that reached near-Earth space were associated with a weaker shock; it is likely that efficient transport of particles from a wide injection source contributed to the observed high-energy SEPs. Our study cannot exclude a contribution from a flare-related process; however, composition observations show no evidence of an impulsive composition of suprathermals during the event, suggestive of a non-dominant flare-related process.
Investigation of the Metabolism of Astragaloside IV in a Puromycin-Damaged Rat Model by UPLC-Q-TOF-MS/MS Analysis
Authors: Zhang Bing , Huang Shiying , Liu Zhuoting , Liu Xinhui , Jiang Zilan , Chen Jianping , Zeng Youjia 
Published: November 2023

AbstractAstragaloside IV (AS-IV) has been shown to provide renal protection in various kidney injury models. However, the metabolic profile variation of AS-IV in pathological models in vivo
is not well established. This study aims to explore the metabolic pathway of AS-IV in vivo in the classical puromycin aminonucleoside (PAN)-induced kidney injury in a rat model.
Twelve Wistar rats were randomly divided into the AS-IV (CA) and the PAN+AS-IV (PA) treatment groups. PAN was injected by a single tail intravenous (i. v.) injection at 5 mg/100 g body
weight, and AS-IV was administered intragastrically (i. g.) at 40 mg/kg for 10 days. Fecal samples of these rats were collected, and metabolites of AS-IV were detected by ultra-performance
liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) to explore the AS-IV metabolic pathway. The metabolic differences between the AS-IV and
PAN+AS-IV groups were compared. A total of 25 metabolites were detected, and deglycosylation, deoxygenation, and methyl oxidation were found to be the main metabolic pathways of AS-IV in
vivo. The abundance of most of these metabolites in the PAN+AS-IV group was lower than that in the AS-IV treatment group, and differences for seven of them were statistically
significant. Our study indicates that AS-IV metabolism is affected in the PAN-induced kidney injury rat model.
Phosphine Ligand Effects in Nickel-Catalyzed Alkene Migratory Hydroalkylation
Authors: Zhu Qing-Wei , Liu Deguang , Lu Xi , Fu Yao , Li Zhen , Wang Jia-Wang , Nie Wan 
Published: November 2023

AbstractCatalytic alkene hydroalkylation has provided to be an efficient method for synthesizing C(sp3) centers, from readily available and inexpensive alkene starting materials through alkene hydrometallation followed by cross-coupling. One of the major tasks in this field is to develop diverse ligands to achieve regioselective control. Herein, we report the investigation of nickel–triphenylphosphine-catalyzed remote hydroalkylation of alkenyl amides to access α-branched amines. Various alkenes and alkyl iodides are suitable substrates to deliver the desired products with excellent regioselectivities (>20:1 regioisomeric ratio). Density functional theory calculations reveal the reaction mechanism.