bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medication adherence and cognitive performance in schizophrenia-spectrum and bipolar disorder: results from the PsyCourse Study
Authors: Senner Fanny , Hiendl Lena , Bengesser Susanne , Adorjan Kristina , Anghelescu Ion-George , Baune Bernhardt T. , Budde Monika , Dannlowski Udo , Dietrich Detlef E. , Falkai Peter , Fallgatter Andreas J. , Hasan Alkomiet , Heilbronner Maria , Jäger Markus , Juckel Georg , Kalman Janos L. , Konrad Carsten , Kohshour Mojtaba Oraki , Papiol Sergi , Reich-Erkelenz Daniela , Reimer Jens , Schaupp Sabrina K. , Schmauß Max , Senner Simon , Spitzer Carsten , Vogl Thomas , Zimmermann Jörg , Heilbronner Urs , Schulte Eva C. , Schulze Thomas G. , Reininghaus Eva Z. , Kirchner Sophie-Kathrin , Dalkner Nina 
Published: March 2023

AbstractExisting guidelines recommend psychopharmacological treatment for the management of schizophrenia and bipolar disorder as part of holistic treatment concepts. About half of the patients do not take their medication regularly, although treatment adherence can prevent exacerbations and re-hospitalizations. To date, the relationship between medication adherence and cognitive performance is understudied. Therefore, this study investigated the relationship between medication adherence and cognitive performance by analyzing the data of 862 participants with schizophrenia-spectrum and bipolar disorders (mean [SD] age, 41.9 [12.48] years; 44.8% female) from a multicenter study (PsyCourse Study). Z-scores for three cognitive domains were calculated, global functioning was measured with the Global Assessment of Functioning Scale, and adherence was assessed by a self-rating questionnaire. We evaluated four multiple linear regression models and built three clusters with hierarchical cluster analyses. Higher adherence behavior (p < 0.001) was associated with better global functioning but showed no impact on the cognitive domains learning and memory, executive function, and psychomotor speed. The hierarchical cluster analysis resulted in three clusters with different cognitive performances, but patients in all clusters showed similar adherence behavior. The study identified cognitive subgroups independent of diagnoses, but no differences were found in the adherence behavior of the patients in these new clusters. In summary, medication adherence was associated with global but not cognitive functioning in patients with schizophrenia-spectrum and bipolar disorders. In both diagnostic groups, cognitive function might be influenced by various factors but not medication adherence.
Pathological regression of primary tumour and metastatic lymph nodes following chemotherapy in resectable OG cancer: pooled analysis of two trials
Authors: Athauda Avani , Nankivell Matthew , Langer Rupert , Pritchard Susan , Langley Ruth E. , von Loga Katharina , Starling Naureen , Chau Ian , Cunningham David , Grabsch Heike I. 
Published: March 2023

AbstractBackgroundNo definitive largescale data exist evaluating the role of pathologically defined regression changes within the primary tumour and lymph nodes (LN) of resected oesophagogastric (OG) adenocarcinoma following neoadjuvant chemotherapy and the impact on survival.MethodsData and samples from two large prospective randomised trials (UK MRC OE05 and ST03) were pooled. Stained slides were available for central pathology review from 1619 patients. Mandard tumour regression grade (TRG) and regression of tumour within LNs (LNR: scored as present/absent) were assessed and correlated with overall survival (OS) using a Cox regression model. An exploratory analysis to define subgroups with distinct prognoses was conducted using a classification and regression tree (CART) analysis.ResultsNeither trial demonstrated a relationship between TRG score and the presence or absence of LNR. In univariable analysis, lower TRG, lower ypN stage, lower ypT stage, presence of LNR, presence of well/moderate tumour differentiation, and absence of tumour at resection margin were all associated with better OS. However, the multivariable analysis demonstrated that only ypN, ypT, grade of differentiation and resection margin (R0) were independent indicators of prognosis. Exploratory CART analysis identified six subgroups with 3-year OS ranging from 83% to 22%; with ypN stage being the most important single prognostic variable.ConclusionsPathological LN stage within the resection specimen was the single most important determiner of survival. Our results suggest that the assessment of regression changes within the primary tumour or LNs may not be necessary to define the prognosis further.
SIM2s directed Parkin-mediated mitophagy promotes mammary epithelial cell differentiation
Authors: Sanchez Lilia , Epps Jessica , Wall Steven , McQueen Cole , Pearson Scott J. , Scribner Kelly , Wellberg Elizabeth A. , Giles Erin D. , Rijnkels Monique , Porter Weston W. 
Published: March 2023

AbstractThe functionally differentiated mammary gland adapts to extreme levels of stress from increased demand for energy by activating specific protective mechanisms to support neonatal health. Here, we identify the breast tumor suppressor gene, single-minded 2 s (SIM2s) as a novel regulator of mitophagy, a key component of this stress response. Using tissue-specific mouse models, we found that loss ofSim2reduced lactation performance, whereas gain (overexpression) ofSim2senhanced and extended lactation performance and survival of mammary epithelial cells (MECs). Using an in vitro model of MEC differentiation, we observed SIM2s is required for Parkin-mediated mitophagy, which we have previously shown as necessary for functional differentiation. Mechanistically, SIM2s localizes to mitochondria to directly mediate Parkin mitochondrial loading. Together, our data suggest that SIM2s regulates the rapid recycling of mitochondria via mitophagy, enhancing the function and survival of differentiated MECs.
Fatostatin induces ferroptosis through inhibition of the AKT/mTORC1/GPX4 signaling pathway in glioblastoma
Authors: Cai Jiayang , Ye Zhang , Hu Yuanyuan , Ye Liguo , Gao Lun , Wang Yixuan , sun Qian , Tong Shiao , Zhang Shenqi , Wu Liquan , Yang Ji’an , Chen Qianxue 
Published: March 2023

AbstractGlioblastoma multiforme (GBM) is the most common and fatal primary malignant central nervous system tumor in adults. Although there are multiple treatments, the median survival of GBM patients is unsatisfactory, which has prompted us to continuously investigate new therapeutic strategies, including new drugs and drug delivery approaches. Ferroptosis, a kind of regulated cell death (RCD), has been shown to be dysregulated in various tumors, including GBM. Fatostatin, a specific inhibitor of sterol regulatory element binding proteins (SREBPs), is involved in lipid and cholesterol synthesis and has antitumor effects in a variety of tumors. However, the effect of fatostatin has not been explored in the field of ferroptosis or GBM. In our study, through transcriptome sequencing, in vivo experiments, and in vitro experiments, we found that fatostatin induces ferroptosis by inhibiting the AKT/mTORC1/GPX4 signaling pathway in glioblastoma. In addition, fatostatin inhibits cell proliferation and the EMT process through the AKT/mTORC1 signaling pathway. We also designed a p28-functionalized PLGA nanoparticle loaded with fatostatin, which could better cross the blood-brain barrier (BBB) and be targeted to GBM. Our research identified the unprecedented effects of fatostatin in GBM and presented a novel drug-targeted delivery vehicle capable of penetrating the BBB in GBM.
Mutations in the B30.2 and the central helical scaffold domains of pyrin differentially affect inflammasome activation
Authors: Chirita Daria , Bronnec Pauline , Magnotti Flora , Dalmon Sarah , Martin Amandine , Popoff Michel , Gerfaud-Valentin Mathieu , Sève Pascal , Belot Alexandre , Contis Anne , Duquesne Agnes , Nocturne Gaetane , Lemelle Irene , Georgin-Lavialle Sophie , Boursier Guilaine , Touitou Isabelle , Jamilloux Yvan , Henry Thomas 
Published: March 2023

AbstractFamilial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disorder. FMF is caused by mutations in the MEFV gene, encoding pyrin, an inflammasome sensor. The best characterized pathogenic mutations associated with FMF cluster in exon 10. Yet, mutations have been described along the whole MEFV coding sequence. Exon 10 encodes the B30.2 domain of the pyrin protein, but the function of this human-specific domain remains unclear. Pyrin is an inflammasome sensor detecting RhoA GTPase inhibition following exposure to bacterial toxins such as TcdA. Here, we demonstrate that the B30.2 domain is dispensable for pyrin inflammasome activation in response to this toxin. Deletion of the B30.2 domain mimics the most typical FMF-associated mutation and confers spontaneous inflammasome activation in response to pyrin dephosphorylation. Our results indicate that the B30.2 domain is a negative regulator of the pyrin inflammasome that acts independently from and downstream of pyrin dephosphorylation. In addition, we identify the central helical scaffold (CHS) domain of pyrin, which lies immediately upstream of the B30.2 domain as a second regulatory domain. Mutations affecting the CHS domain mimic pathogenic mutations in the B30.2 domain and render the pyrin inflammasome activation under the sole control of the dephosphorylation. In addition, specific mutations in the CHS domain strongly increase the cell susceptibility to steroid catabolites, recently described to activate pyrin, in both a cell line model and in monocytes from genotype-selected FMF patients. Taken together, our work reveals the existence of two distinct regulatory regions at the C-terminus of the pyrin protein, that act in a distinct manner to regulate positively or negatively inflammasome activation. Furthermore, our results indicate that different mutations in pyrin regulatory domains have different functional impacts on the pyrin inflammasome which could contribute to the diversity of pyrin-associated autoinflammatory diseases.
The effects of MYC on tumor immunity and immunotherapy
Authors: Li Jiajin , Dong Tingyu , Wu Zhen , Zhu Dacheng , Gu Hao 
Published: March 2023

AbstractThe oncogene MYC is dysregulated in a host of human cancers, and as an important point of convergence in multitudinous oncogenic signaling pathways, it plays a crucial role in tumor immune regulation in the tumor immune microenvironment (TIME). Specifically, MYC promotes the expression of immunosuppressive factors and inhibits the expression of immune activation regulators. Undoubtedly, a therapeutic strategy that targets MYC can initiate a new era of cancer treatment. In this review, we summarize the essential role of the MYC signaling pathway in tumor immunity and the development status of MYC-related therapies, including therapeutic strategies targeting MYC and combined MYC-based immunotherapy. These studies have reported extraordinary insights into the translational application of MYC in cancer treatment and are conducive to the emergence of more effective immunotherapies for cancer.
Arene C–H borylation strategy enabled by a non-classical boron cluster-based electrophile
Authors: Kim Sangmin , Treacy Joseph W. , Nelson Yessica A. , Gonzalez Jordan A. M. , Gembicky Milan , Houk K. N. , Spokoyny Alexander M. 
Published: March 2023

AbstractIntroducing a tri-coordinate boron-based functional group (e.g., boronic ester) into an unactivated C–H bond in the absence of directing groups is an ongoing challenge in synthetic chemistry. Despite previous developments in transition metal-catalyzed and -free approaches, C–H borylation of sterically hindered arenes remains a largely unsolved problem to date. Here, we report a synthetic strategy of a two-step, precious metal-free electrophilic C–H borylation of sterically hindered alkyl- and haloarenes to generate aryl boronic esters. The first step relies on electrophilic aromatic substitution (EAS) induced by cage-opening of Cs2[closo-B10H10], forming a 6-Ar-nido-B10H13product containing a B–C bond, followed by a cage deconstruction of arylated decaboranes promoted by diols. The combination of these two steps allows for the preparation of aryl boronic esters that are hardly accessible by current direct C–H borylation approaches. This reaction does not require any precious metals, highly-engineered ligands, pre-functionalized boron reagents, or inert conditions. In addition, the unique properties of a non-classical boron cluster electrophile intermediate, B10H13+, afford a regioselectivity with unique steric and electronic control without the undesirable side reactions.
Equilibrium shift, poisoning prevention, and selectivity enhancement in catalysis via dehydration of polymeric membranes
Authors: Hyeon Myeong-Hun , Park Hae-Gu , Lee Jongmyeong , Kong Chang-In , Kim Eun-Young , Kim Jong Hak , Moon Su-Young , Kim Seok Ki 
Published: March 2023

AbstractGeneration of water as a byproduct in chemical reactions is often detrimental because it lowers the yield of the target product. Although several water removal methods, using absorbents, inorganic membranes, and additional dehydration reactions, have been proposed, there is an increasing demand for a stable and simple system that can selectively remove water over a wide range of reaction temperatures. Herein we report a thermally rearranged polybenzoxazole hollow fiber membrane with good water permselectivity and stability at reaction temperatures of up to 400 °C. Common reaction engineering challenges, such as those due to equilibrium limits, catalyst deactivation, and water-based side reactions, have been addressed using this membrane in a reactor.
Determinants of functional synaptic connectivity among amygdala-projecting prefrontal cortical neurons in male mice
Authors: Printz Yoav , Patil Pritish , Mahn Mathias , Benjamin Asaf , Litvin Anna , Levy Rivka , Bringmann Max , Yizhar Ofer 
Published: March 2023

AbstractThe medial prefrontal cortex (mPFC) mediates a variety of complex cognitive functions via its vast and diverse connections with cortical and subcortical structures. Understanding the patterns of synaptic connectivity that comprise the mPFC local network is crucial for deciphering how this circuit processes information and relays it to downstream structures. To elucidate the synaptic organization of the mPFC, we developed a high-throughput optogenetic method for mapping large-scale functional synaptic connectivity in acute brain slices. We show that in male mice, mPFC neurons that project to the basolateral amygdala (BLA) display unique spatial patterns of local-circuit synaptic connectivity, which distinguish them from the general mPFC cell population. When considering synaptic connections between pairs of mPFC neurons, the intrinsic properties of the postsynaptic cell and the anatomical positions of both cells jointly account for ~7.5% of the variation in the probability of connection. Moreover, anatomical distance and laminar position explain most of this fraction in variation. Our findings reveal the factors determining connectivity in the mPFC and delineate the architecture of synaptic connections in the BLA-projecting subnetwork.
Bacterial outer membrane vesicle based versatile nanosystem boosts the efferocytosis blockade triggered tumor-specific immunity
Authors: Zhuang Wan-Ru , Wang Yunfeng , Nie Weidong , Lei Yao , Liang Chao , He Jiaqi , Zuo Liping , Huang Li-Li , Xie Hai-Yan 
Published: March 2023

AbstractEfferocytosis inhibition is emerging as an attractive strategy for antitumor immune therapy because of the subsequent leak of abundant immunogenic contents. However, the practical efficacy is seriously impeded by the immunosuppressive tumor microenvironments. Here, we construct a versatile nanosystem that can not only inhibit the efferocytosis but also boost the following antitumor immunity. MerTK inhibitor UNC2025 is loaded into the bacterial outer membrane vesicles (OMVs), which are then modified with maleimide (mU@OMVs). The prepared mU@OMVs effectively inhibits the efferocytosis by promoting the uptake while preventing the MerTK phosphorylation of tumor associated macrophages, and then captures the released antigens through forming universal thioether bonds. The obtained in situ vaccine effectively transfers to lymph nodes by virtue of the intrinsic features of OMVs, and then provokes intense immune responses that can efficiently prevent the growth, metastasis and recurrence of tumors in mice, providing a generalizable strategy for cancer immunotherapy.
Multi-modal quantification of pathway activity with MAYA
Authors: Landais Yuna , Vallot Céline 
Published: March 2023

AbstractSignaling pathways can be activated through various cascades of genes depending on cell identity and biological context. Single-cell atlases now provide the opportunity to inspect such complexity in health and disease. Yet, existing reference tools for pathway scoring resume activity of each pathway to one unique common metric across cell types. Here, we present MAYA, a computational method that enables the automatic detection and scoring of the diverse modes of activation of biological pathways across cell populations. MAYA improves the granularity of pathway analysis by detecting subgroups of genes within reference pathways, each characteristic of a cell population and how it activates a pathway. Using multiple single-cell datasets, we demonstrate the biological relevance of identified modes of activation, the robustness of MAYA to noisy pathway lists and batch effect. MAYA can also predict cell types starting from lists of reference markers in a cluster-free manner. Finally, we show that MAYA reveals common modes of pathway activation in tumor cells across patients, opening the perspective to discover shared therapeutic vulnerabilities.
Small data machine learning in materials science
Authors: Xu Pengcheng , Ji Xiaobo , Li Minjie , Lu Wencong 
Published: March 2023

AbstractThis review discussed the dilemma of small data faced by materials machine learning. First, we analyzed the limitations brought by small data. Then, the workflow of materials machine learning has been introduced. Next, the methods of dealing with small data were introduced, including data extraction from publications, materials database construction, high-throughput computations and experiments from the data source level; modeling algorithms for small data and imbalanced learning from the algorithm level; active learning and transfer learning from the machine learning strategy level. Finally, the future directions for small data machine learning in materials science were proposed.
High-performance non-Fermi-liquid metallic thermoelectric materials
Authors: Dong Zirui , Zhang Yubo , Luo Jun , Jiang Ying , Yu Zhiyang , Zhao Nan , Wu Liusuo , Ruan Yurong , Zhang Fang , Guo Kai , Zhang Jiye , Zhang Wenqing 
Published: March 2023

AbstractSearching for high-performance thermoelectric (TE) materials in the paradigm of narrow-bandgap semiconductors is hampered by a bottleneck. Here we report on the discovery of metallic compounds, TiFexCu2x−1Sb and TiFe1.33Sb, showing the thermopower exceeding many TE semiconductors and the dimensionless figure of merits zTs comparable with the state-of-the-art TE materials. A quasi-linear temperature (T) dependent electrical resistivity in 2–700 K and the logarithmic T-dependent electronic specific heat at low temperature coexist with the high thermopower, highlighting the strong intercoupling of the non-Fermi-liquid (NFL) quantum critical behavior of electrons with TE transports. Electronic structure analysis reveals a competition between the antiferromagnetic (AFM) ordering and Kondo-like spin compensation as well as a parallel two-channel Kondo effect. The T-dependent magnetic susceptibility agrees with the quantum critical scenario of strong local correlation. Our work demonstrates the correlation among high TE performance, NFL quantum criticality, and magnetic fluctuation, which opens up directions for future research.
Toward the utilisation of resources in space: knowledge gaps, open questions, and priorities
Authors: Cilliers Jan , Hadler Kathryn , Rasera Joshua 
Published: March 2023

AbstractThere are many open science questions in space resource utilisation due to the novelty and relative immaturity of the field. While many potential technologies have been proposed to produce usable resources in space, high confidence, large-scale design is limited by gaps in the knowledge of the local environmental conditions, geology, mineralogy, and regolith characteristics, as well as specific science questions intrinsic to each process. Further, the engineering constraints (e.g. energy, throughput, efficiency etc.) must be incorporated into the design. This work aims to summarise briefly recent activities in the field of space resource utilisation, as well as to identify key knowledge gaps, and to present open science questions. Finally, future exploration priorities to enable the use of space resources are highlighted.
DOPAL initiates αSynuclein-dependent impaired proteostasis and degeneration of neuronal projections in Parkinson’s disease
Authors: Masato Anna , Plotegher Nicoletta , Terrin Francesca , Sandre Michele , Faustini Gaia , Thor Andrea , Adams Stephen , Berti Giulia , Cogo Susanna , De Lazzari Federica , Fontana Camilla Maria , Martinez Paul Anthony , Strong Randy , Bandopadhyay Rina , Bisaglia Marco , Bellucci Arianna , Greggio Elisa , Dalla Valle Luisa , Boassa Daniela , Bubacco Luigi 
Published: March 2023

AbstractDopamine dyshomeostasis has been acknowledged among the determinants of nigrostriatal neuron degeneration in Parkinson’s disease (PD). Several studies in experimental models and postmortem PD patients underlined increasing levels of the dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is highly reactive towards proteins. DOPAL has been shown to covalently modify the presynaptic protein αSynuclein (αSyn), whose misfolding and aggregation represent a major trait of PD pathology, triggering αSyn oligomerization in dopaminergic neurons. Here, we demonstrated that DOPAL elicits αSyn accumulation and hampers αSyn clearance in primary neurons. DOPAL-induced αSyn buildup lessens neuronal resilience, compromises synaptic integrity, and overwhelms protein quality control pathways in neurites. The progressive decline of neuronal homeostasis further leads to dopaminergic neuron loss and motor impairment, as showed in in vivo models. Finally, we developed a specific antibody which detected increased DOPAL-modified αSyn in human striatal tissues from idiopathic PD patients, corroborating the translational relevance of αSyn-DOPAL interplay in PD neurodegeneration.