bluuebunny/crossref_metadata_2025_split huggingface dataset:
Equilibrium selection via current sheet relaxation and guide field amplification
Authors: Yoon Young Dae , Wendel Deirdre E. , Yun Gunsu S. 
Published: January 2023

AbstractAlthough there is a continuous spectrum of current sheet equilibria, how a particular equilibrium is selected by a given system remains a mystery. Yet, only a limited number of equilibrium solutions are used for analyses of magnetized plasma phenomena. Here we present the exact process of equilibrium selection, by analyzing the relaxation process of a disequilibrated current sheet under a finite guide field. It is shown via phase-space analyses and particle-in-cell simulations that the current sheet relaxes in such a way that the guide field is locally amplified, yielding a mixed equilibrium from the spectrum. Comparisons to spacecraft observations and solar wind current sheet statistics demonstrate that such mixed equilibria are ubiquitous and exist as underlying local structures in various physical environments.
Choice selective inhibition drives stability and competition in decision circuits
Authors: Roach James P. , Churchland Anne K. , Engel Tatiana A. 
Published: January 2023

AbstractDuring perceptual decision-making, the firing rates of cortical neurons reflect upcoming choices. Recent work showed that excitatory and inhibitory neurons are equally selective for choice. However, the functional consequences of inhibitory choice selectivity in decision-making circuits are unknown. We developed a circuit model of decision-making which accounts for the specificity of inputs to and outputs from inhibitory neurons. We found that selective inhibition expands the space of circuits supporting decision-making, allowing for weaker or stronger recurrent excitation when connected in a competitive or feedback motif. The specificity of inhibitory outputs sets the trade-off between speed and accuracy of decisions by either stabilizing or destabilizing the saddle-point dynamics underlying decisions in the circuit. Recurrent neural networks trained to make decisions display the same dependence on inhibitory specificity and the strength of recurrent excitation. Our results reveal two concurrent roles for selective inhibition in decision-making circuits: stabilizing strongly connected excitatory populations and maximizing competition between oppositely selective populations.
SARS-CoV-2 viral entry and replication is impaired in Cystic Fibrosis airways due to ACE2 downregulation
Authors: Bezzerri Valentino , Gentili Valentina , Api Martina , Finotti Alessia , Papi Chiara , Tamanini Anna , Boni Christian , Baldisseri Elena , Olioso Debora , Duca Martina , Tedesco Erika , Leo Sara , Borgatti Monica , Volpi Sonia , Pinton Paolo , Cabrini Giulio , Gambari Roberto , Blasi Francesco , Lippi Giuseppe , Rimessi Alessandro , Rizzo Roberta , Cipolli Marco 
Published: January 2023

AbstractAs an inherited disorder characterized by severe pulmonary disease, cystic fibrosis could be considered a comorbidity for coronavirus disease 2019. Instead, current clinical evidence seems to be heading in the opposite direction. To clarify whether host factors expressed by the Cystic Fibrosis epithelia may influence coronavirus disease 2019 progression, here we describe the expression of SARS-CoV-2 receptors in primary airway epithelial cells. We show that angiotensin converting enzyme 2 (ACE2) expression and localization are regulated by Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channel. Consistently, our results indicate that dysfunctional CFTR channels alter susceptibility to SARS-CoV-2 infection, resulting in reduced viral entry and replication in Cystic Fibrosis cells. Depending on the pattern of ACE2 expression, the SARS-CoV-2 spike (S) protein induced high levels of Interleukin 6 in healthy donor-derived primary airway epithelial cells, but a very weak response in primary Cystic Fibrosis cells. Collectively, these data support that Cystic Fibrosis condition may be at least partially protecting from SARS-CoV-2 infection.
Role of air-sea heat flux on the transformation of Atlantic Water encircling the Nordic Seas
Authors: Huang Jie , Pickart Robert S. , Chen Zhuomin , Huang Rui Xin 
Published: January 2023

AbstractThe warm-to-cold densification of Atlantic Water (AW) around the perimeter of the Nordic Seas is a critical component of the Atlantic Meridional Overturning Circulation (AMOC). However, it remains unclear how ongoing changes in air-sea heat flux impact this transformation. Here we use observational data, and a one-dimensional mixing model following the flow, to investigate the role of air-sea heat flux on the cooling of AW. We focus on the Norwegian Atlantic Slope Current (NwASC) and Front Current (NwAFC), where the primary transformation of AW occurs. We find that air-sea heat flux accounts almost entirely for the net cooling of AW along the NwAFC, while oceanic lateral heat transfer appears to dominate the temperature change along the NwASC. Such differing impacts of air-sea interaction, which explain the contrasting long-term changes in the net cooling along two AW branches since the 1990s, need to be considered when understanding the AMOC variability.
Predictors of success in establishing orthotopic patient-derived xenograft models of triple negative breast cancer
Authors: Echeverria Gloria V. , Cai Shirong , Tu Yizheng , Shao Jiansu , Powell Emily , Redwood Abena B. , Jiang Yan , McCoy Aaron , Rinkenbaugh Amanda L. , Lau Rosanna , Trevarton Alexander J. , Fu Chunxiao , Gould Rebekah , Ravenberg Elizabeth E. , Huo Lei , Candelaria Rosalind , Santiago Lumarie , Adrada Beatriz E. , Lane Deanna L. , Rauch Gaiane M. , Yang Wei T. , White Jason B. , Chang Jeffrey T. , Moulder Stacy L. , Symmans W. Fraser , Hilsenbeck Susan G. , Piwnica-Worms Helen 
Published: January 2023

AbstractPatient-derived xenograft (PDX) models of breast cancer are an effective discovery platform and tool for preclinical pharmacologic testing and biomarker identification. We established orthotopic PDX models of triple negative breast cancer (TNBC) from the primary breast tumors of patients prior to and following neoadjuvant chemotherapy (NACT) while they were enrolled in the ARTEMIS trial (NCT02276443). Serial biopsies were obtained from patients prior to treatment (pre-NACT), from poorly responsive disease after four cycles of Adriamycin and cyclophosphamide (AC, mid-NACT), and in cases of AC-resistance, after a 3-month course of different experimental therapies and/or additional chemotherapy (post-NACT). Our study cohort includes a total of 269 fine needle aspirates (FNAs) from 217 women, generating a total of 62 PDX models (overall success-rate = 23%). Success of PDX engraftment was generally higher from those cancers that proved to be treatment-resistant, whether poorly responsive to AC as determined by ultrasound measurements mid-NACT (p = 0.063), RCB II/III status after NACT (p = 0.046), or metastatic relapse within 2 years of surgery (p = 0.008). TNBC molecular subtype determined from gene expression microarrays of pre-NACT tumors revealed no significant association with PDX engraftment rate (p = 0.877). Finally, we developed a statistical model predictive of PDX engraftment using percent Ki67 positive cells in the patient’s diagnostic biopsy, positive lymph node status at diagnosis, and low volumetric reduction of the patient’s tumor following AC treatment. This novel bank of 62 PDX models of TNBC provides a valuable resource for biomarker discovery and preclinical therapeutic trials aimed at improving neoadjuvant response rates for patients with TNBC.
Predicting lattice thermal conductivity via machine learning: a mini review
Authors: Luo Yufeng , Li Mengke , Yuan Hongmei , Liu Huijun , Fang Ying 
Published: January 2023

AbstractOver the past few decades, molecular dynamics simulations and first-principles calculations have become two major approaches to predict the lattice thermal conductivity (κL), which are however limited by insufficient accuracy and high computational cost, respectively. To overcome such inherent disadvantages, machine learning (ML) has been successfully used to accurately predictκLin a high-throughput style. In this review, we give some introductions of recent ML works on the direct and indirect prediction ofκL, where the derivations and applications of data-driven models are discussed in details. A brief summary of current works and future perspectives are given in the end.
InvitroSPI and a large database of proteasome-generated spliced and non-spliced peptides
Authors: Roetschke Hanna P. , Rodriguez-Hernandez Guillermo , Cormican John A. , Yang Xiaoping , Lynham Steven , Mishto Michele , Liepe Juliane 
Published: January 2023

AbstractNoncanonical epitopes presented by Human Leucocyte Antigen class I (HLA-I) complexes to CD8+ T cells attracted the spotlight in the research of novel immunotherapies against cancer, infection and autoimmunity. Proteasomes, which are the main producers of HLA-I-bound antigenic peptides, can catalyze both peptide hydrolysis and peptide splicing. The prediction of proteasome-generated spliced peptides is an objective that still requires a reliable (and large) database of non-spliced and spliced peptides produced by these proteases. Here, we present an extended database of proteasome-generated spliced and non-spliced peptides, which was obtained by analyzing in vitro digestions of 80 unique synthetic polypeptide substrates, measured by different mass spectrometers. Peptides were identified through invitroSPI method, which was validated through in silico and in vitro strategies. The peptide product database contains 16,631 unique peptide products (5,493 non-spliced, 6,453 cis-spliced and 4,685 trans-spliced peptide products), and a substrate sequence variety that is a valuable source for predictors of proteasome-catalyzed peptide hydrolysis and splicing. Potential artefacts and skewed results due to different identification and analysis strategies are discussed.
Solid-phase synthesis and pathological evaluation of pyroglutamate amyloid-β3-42 peptide
Authors: Cho Illhwan , Lee HeeYang , Lee Donghee , Park In Wook , Yoon Soljee , Kim Hye Yun , Kim YoungSoo 
Published: January 2023

AbstractPyroglutamate amyloid-β3-42 (AβpE3-42) is an N-terminally truncated and pyroglutamate-modified Aβ peptide retaining highly hydrophobic, amyloidogenic, and neurotoxic properties. In Alzheimer’s disease (AD) patients, AβpE3-42 peptides accumulate into oligomers and induce cellular toxicity and synaptic dysfunction. AβpE3-42 aggregates further seed the formation of amyloid plaques, which are the pathological hallmarks of AD. Given that AβpE3-42 peptides play critical roles in the development of neurodegeneration, a reliable and reproducible synthetic access to these peptides may support pathological and medicinal studies of AD. Here, we synthesized AβpE3-42 peptides through the microwave-assisted solid-phase peptide synthesis (SPPS). Utilizing thioflavin T fluorescence assay and dot blotting analysis with anti-amyloid oligomer antibody, the amyloidogenic activity of synthesized AβpE3-42 peptides was confirmed. We further observed the cytotoxicity of AβpE3-42 aggregates in cell viability test. To examine the cognitive deficits induced by synthetic AβpE3-42 peptides, AβpE3-42 oligomers were intracerebroventricularly injected into imprinting control region mice and Y-maze and Morris water maze tests were performed. We found that AβpE3-42 aggregates altered the expression level of postsynaptic density protein 95 in cortical lysates. Collectively, we produced AβpE3-42 peptides in the microwave-assisted SPPS and evaluated the amyloidogenic and pathological function of the synthesized peptides.
Activity networks determine project performance
Authors: Vazquez Alexei , Pozzana Iacopo , Kalogridis Georgios , Ellinas Christos 
Published: January 2023

AbstractProjects are characterised by activity networks with a critical path, a sequence of activities from start to end, that must be finished on time to complete the project on time. Watching over the critical path is the project manager’s strategy to ensure timely project completion. This intense focus on a single path contrasts the broader complex structure of the activity network, and is due to our poor understanding on how that structure influences this critical path. Here, we use a generative model and detailed data from 77 real world projects (+ $10 bn total budget) to demonstrate how this network structure forces us to look beyond the critical path. We introduce a duplication-split model of project schedules that yields (i) identical power-law in- and-out degree distributions and (ii) a vanishing fraction of critical path activities with schedule size. These predictions are corroborated in real projects. We demonstrate that the incidence of delayed activities in real projects is consistent with the expectation from percolation theory in complex networks. We conclude that delay propagation in project schedules is a network property and it is not confined to the critical path.
Development and validation of a prognostic nomogram for Takotsubo syndrome patients in the intensive care units: a retrospective cohort study
Authors: Chen Jun , Wang Yimin , Shou Xinyang , Liu Qiang , Mei Ziwei 
Published: January 2023

AbstractPatients with Takotsubo syndrome (TTS) admitted to the intensive care unit (ICU) always confront a higher risk of in-hospital death than those hospitalized in the cardiology unit. The prognosis of the latter was analyzed by a large number of studies. However, there was no utility model to predict the risk of in-hospital death for patients with TTS in the ICU. This study aimed to establish a model predicting in-hospital death in patients with TTS admitted to ICU. We retrospectively included ICU patients with TTS from the MIMIC-IV database. The outcome of the nomogram was in-hospital death. Least Absolute Shrinkage Selection Operator (LASSO) analysis selected predictors preliminarily. The model was developed by multivariable logistic regression analysis. Calibration, decision curve analysis (DCA), and receiver operating characteristic (ROC) measured the performance of the nomogram on the accuracy, clinical utility, and discrimination, respectively. Eventually, 368 ICU patients with TTS were enrolled in this research. The in-hospital mortality was 13.04%. LASSO regression and multivariate logistic regression analysis verified risk factors significantly associated with in-hospital mortality. They were potassium, prothrombin time (PT), age, myocardial infarction, white cell count (WBC), hematocrit, anion gap, and sequential organ failure assessment (SOFA) score. This nomogram excellently discriminated against patients with a risk of in-hospital death. The area under curve (AUC) was 0.779 (95%CI: 0.732–0.826) in training set and 0.775 (95%CI: 0.711–0.839) in test set. The calibration plot and DCA showed good clinical benefits for this nomogram. We developed a nomogram that predicts the probability of in-hospital death for ICU patients with TTS. This nomogram was able to discriminate patients with a high risk of in-hospital death and performed clinical utility.
Partial wavelet coherence as a robust method for assessment of neurovascular coupling in neonates with hypoxic ischemic encephalopathy
Authors: Hermans Tim , Carkeek Katherine , Dereymaeker Anneleen , Jansen Katrien , Naulaers Gunnar , Van Huffel Sabine , De Vos Maarten 
Published: January 2023

AbstractIn neonates with hypoxic ischemic encephalopathy, the computation of wavelet coherence between electroencephalogram (EEG) power and regional cerebral oxygen saturation (rSO2) is a promising method for the assessment of neurovascular coupling (NVC), which in turn is a promising marker for brain injury. However, instabilities in arterial oxygen saturation (SpO2) limit the robustness of previously proposed methods. Therefore, we propose the use of partial wavelet coherence, which can eliminate the influence of SpO2. Furthermore, we study the added value of the novel NVC biomarkers for identification of brain injury compared to traditional EEG and NIRS biomarkers. 18 neonates with HIE were monitored for 72 h and classified into three groups based on short-term MRI outcome. Partial wavelet coherence was used to quantify the coupling between C3–C4 EEG bandpower (2–16 Hz) and rSO2, eliminating confounding effects of SpO2. NVC was defined as the amount of significant coherence in a frequency range of 0.25–1 mHz. Partial wavelet coherence successfully removed confounding influences of SpO2 when studying the coupling between EEG and rSO2. Decreased NVC was related to worse MRI outcome. Furthermore, the combination of NVC and EEG spectral edge frequency (SEF) improved the identification of neonates with mild vs moderate and severe MRI outcome compared to using EEG SEF alone. Partial wavelet coherence is an effective method for removing confounding effects of SpO2, improving the robustness of automated assessment of NVC in long-term EEG-NIRS recordings. The obtained NVC biomarkers are more sensitive to MRI outcome than traditional rSO2 biomarkers and provide complementary information to EEG biomarkers.
The pre-surgical role of halo-traction in patients with cervical infection associated with refractory kyphosis: a retrospective study
Authors: Manini Daudi R. , Zhang Hong-Qi , Gao Qile , Liu Shao-Hua , YuXiang Wang , Tang Ming-Xing , An Deng , Guo Chao-Feng , YuXuan Du 
Published: January 2023

AbstractTo minimize surgical complications and staged procedures halo-traction is often used during deformity corrections. But the use of halo-traction in the treatment of refractory cervical kyphosis secondary to infections has never been reported. This study investigated the role of halo-traction in the treatment of cervical infection patients associated with refractory kyphosis. We retrospectively reviewed 48 patients with cervical infection associated with refractory kyphosis who were treated in our spine department. Patients were divided into two groups, the traction group (A) and the non-traction group (B). Group A underwent preoperative halo-traction followed by surgery, while group B underwent surgery alone. Between the two groups, we analyzed the kyphosis deformity correction, level of fusions, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), functional improvement by Neck disability index (NDI) score, and complications. Group A had a better correction of kyphosis deformity compared to group B (27.01 ± 11.54)0 versus (18.08 ± 10.04)0 (P = 0.01, Z =  − 2.44). No statistically significant differences between the two groups in terms of functional improvement, level of fusions, ESR and CRP. Group B had 3 revision surgery cases. Preoperative halo-traction followed by surgery is superior in kyphosis correction in the treatment of patients with cervical infections with refractory kyphosis.
CAR-tropic extracellular vesicles carry tumor-associated antigens and modulate CAR T cell functionality
Authors: Ukrainskaya V. M. , Musatova O. E. , Volkov D. V. , Osipova D. S. , Pershin D. S. , Moysenovich A. M. , Evtushenko E. G. , Kulakovskaya E. A. , Maksimov E. G. , Zhang H. , Rubtsov Y. P. , Maschan M. A. , Stepanov A. V. , Gabibov A. G. 
Published: January 2023

AbstractTumor-derived extracellular vesicles (EVs) are active contributors in metastasis and immunosuppression in tumor microenvironment. At least some of the EVs carry tumor surface molecules such as tumor-associated antigens (TAAs) and/or checkpoint inhibitors, and potentially could interact with T cells or CAR T cells. Upon contact with T cells, EVs could alter their phenotype and functions by triggering signaling through TCR or CAR reprogramming them to escape immune response. We hypothesize that EVs that possess TAA on the surface will probably interact with CAR T cells which can recognize and bind corresponding TAA. This interaction between EVs and CAR T cells may change the outcome of CAR T-based cancer immunotherapy since it should affect CAR T cells. Also, EVs could serve as adjuvants and antigenic components of antitumor vaccines. Herein, we isolated EVs from B cell precursor leukemia cell line (pre-B ALL) Nalm-6 and demonstrated that recognition and binding of CD19+EVs with CD19-CAR T cells strongly depends on the presence of CD19 antigen. CD19+EVs induce secretion of pro-inflammatory cytokines (IL-2 and IFN-y) and upregulated transcription of activation-related genes (IFNG, IFNGR1, FASLG, IL2) in CD19-CAR T cells. Tumor necrosis factor receptor superfamily (TNFRSF4 and TNFRSF9) and T-cell exhaustion markers (CTLA4, LAG3, TIM3 and PDCD1LG2) were also upregulated in CD19-CAR T cells after incubation with CD19+EVs. Long-term cultivation of CD19+ or PD-L1+EVs with CD19-CAR T cells led to increased terminal differentiation and functional exhaustion according to elevated expression of PD-1, TIGIT, CD57. In summary, our results suggest that chronic exposure of CD19-CAR T cells to CD19+EVs mediates activation and systemic exhaustion in antigen-specific manner, and this negative effect is accompanied by the impaired cytotoxic activity in vitro.
A strategy for evaluating potential antiviral resistance to small molecule drugs and application to SARS-CoV-2
Authors: Sargsyan Karen , Mazmanian Karine , Lim Carmay 
Published: January 2023

AbstractAlterations in viral fitness cannot be inferred from only mutagenesis studies of an isolated viral protein. To-date, no systematic analysis has been performed to identify mutations that improve virus fitness and reduce drug efficacy. We present a generic strategy to evaluate which viral mutations might diminish drug efficacy and applied it to assess how SARS-CoV-2 evolution may affect the efficacy of current approved/candidate small-molecule antivirals for Mpro, PLpro, and RdRp. For each drug target, we determined the drug-interacting virus residues from available structures and the selection pressure of the virus residues from the SARS-CoV-2 genomes. This enabled the identification of promising drug target regions and small-molecule antivirals that the virus can develop resistance. Our strategy of utilizing sequence and structural information from genomic sequence and protein structure databanks can rapidly assess the fitness of any emerging virus variants and can aid antiviral drug design for future pathogens.