bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial single cell analysis of tumor microenvironment remodeling pattern in primary central nervous system lymphoma
Authors: Xia Yuan , Sun Tao , Li Guosheng , Li Mingying , Wang Dongmei , Su Xiuhua , Ye Jingjing , Ji Chunyan 
Published: April 2023

AbstractTo determine the overall tumor microenvironment (TME), characteristics, and transition mechanisms in primary central nervous system lymphoma (PCNSL), we performed spatial transcriptomics and matched the corresponding single-cell sequencing data of PCNSL patients. We found that tumor cells may achieve a “TME remodeling pattern” through an “immune pressure-sensing model”, in which they could choose to reshape the TME into a barrier environment or a cold environment according to the immune pressure. A key FKBP5+ tumor subgroup was found to be responsible for pushing tumors into the barrier environment, which provides a possible way to evaluate the stage of PCNSL. The specific mechanism of the TME remodeling pattern and the key molecules of the immune pressure-sensing model were identified through the spatial communication analysis. Finally, we discovered the spatial and temporal distributions and variation characteristics of immune checkpoint molecules and CAR-T target molecules in immunotherapy. These data clarified the TME remodeling pattern of PCNSL, provided a reference for its immunotherapy, and provided suggestions for the TME remodeling mechanism of other cancers.
Genetic loci of beta-aminoisobutyric acid are associated with aging-related mild cognitive impairment
Authors: Granot-Hershkovitz Einat , Spitzer Brian , Yang Yunju , Tarraf Wassim , Yu Bing , Boerwinkle Eric , Fornage Myriam , Mosley Thomas H. , DeCarli Charles , Kristal Bruce S. , González Hector M. , Sofer Tamar 
Published: April 2023

AbstractWe studied the genetic associations of a previously developed Metabolomic Risk Score (MRS) for Mild Cognitive Impairment (MCI) and beta-aminoisobutyric acid metabolite (BAIBA)—the metabolite highlighted by results from a genome-wide association study (GWAS) of the MCI-MRS, and assessed their association with MCI in datasets of diverse race/ethnicities. We first performed a GWAS for the MCI-MRS and BAIBA, in Hispanic/Latino adults (n = 3890) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We identified ten independent genome-wide significant (pvalue <5 × 10−8) variants associated with MCI-MRS or BAIBA. Variants associated with the MCI-MRS are located in the Alanine-Glyoxylate Aminotransferase 2 (AGXT2gene), which is known to be associated with BAIBA metabolism. Variants associated with BAIBA are located in theAGXT2gene and in theSLC6A13gene. Next, we tested the variants’ association with MCI in independent datasets ofn = 3178 HCHS/SOL older individuals,n = 3775 European Americans, andn = 1032 African Americans from the Atherosclerosis Risk In Communities (ARIC) study. Variants were considered associated with MCI if theirpvalue <0.05 in the meta-analysis of the three datasets and their direction of association was consistent with expectation. Rs16899972 and rs37369 from theAGXT2region were associated with MCI. Mediation analysis supported the mediation effect of BAIBA between the two genetic variants and MCI (pvalue = 0.004 for causal mediated effect). In summary, genetic variants in theAGXT2region are associated with MCI in Hispanic/Latino, African, and European American populations in the USA, and their effect is likely mediated by changes in BAIBA levels.
Artificial intelligence approach for the analysis of placebo-controlled clinical trials in major depressive disorders accounting for individual propensity to respond to placebo
Authors: Gomeni Roberto , Bressolle-Gomeni Françoise , Fava Maurizio 
Published: April 2023

AbstractTreatment effect in clinical trials for major depressive disorders (RCT) can be viewed as the resultant of treatment specific and non-specific effects. Baseline individual propensity to respond non-specifically to any treatment or intervention can be considered as a major non-specific confounding effect. The greater is the baseline propensity, the lower will be the chance to detect any treatment-specific effect. The statistical methodologies currently applied for analyzing RCTs doesn’t account for potential unbalance in the allocation of subjects to treatment arms due to heterogenous distributions of propensity. Hence, the groups to be compared may be imbalanced, and thus incomparable. Propensity weighting methodology was used to reduce baseline imbalances between arms. A randomized, double-blind, placebo controlled, three arms, parallel group, 8-week, fixed-dose study to evaluate efficacy of paroxetine CR 12.5 and 25 mg/day is presented as a cases study. An artificial intelligence model was developed to predict placebo response at week 8 in subjects assigned to placebo arm using changes from screening to baseline of individual Hamilton Depression Rating Scale items. This model was used to predict the probability to respond to placebo in each subject. The inverse of the probability was used as weight in the mixed-effects model applied to assess treatment effect. The analysis with and without propensity weight indicated that the weighted analysis provided an estimate of treatment effect and effect-size about twice larger than the non-weighted analysis. Propensity weighting provides an unbiased strategy to account for heterogeneous and uncontrolled placebo effect making patients’ data comparable across treatment arms.
Facilitating dental disease screening program in prisoners using an intraoral camera in teledentistry
Authors: Santipipat Charnchai , Kaewkamnerdpong Issarapong , Limpuangthip Nareudee 
Published: April 2023

Abstract
Objectives
To facilitate dental disease screening program in prisoners by testing the diagnostic accuracy of teledentistry examination in comparison to direct oral examination by a dentist.

Materials and methods
This crossover study comprised three phases. Phase I, prisoner health volunteers (PHVs) enrolled teledentistry training for an intraoral camera (IOC) use. Phase II, the PHV used IOC for examining dental diseases of prisoners who reported dental-related problems, and captured symptomatic areas. The PHV and dentist independently determined tentative dental treatment need, comprising dental fillings, scaling, extraction, and surgical removal of impacted tooth. Phase III, another dentist performed direct oral examination of the prisoners who reported problems in phase II and determined dental treatment needs. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated, using direct oral examination by dentist as a true positive.

Results
Diagnostic accuracy was determined in 152 prisoners with 215 teeth. Sensitivity, specificity, PPV, and NPV of teledentistry and direct examination between two dentists were above 80%. The lowest sensitivity and specificity of teledentistry examination by the PHV were scaling and surgical removal.

Conclusions
IOC use in teledentistry facilitates dentists in dental diseases screening for prisoners with acceptable diagnostic accuracy in identifying possible treatment needs. However, the imaging obtained from teledentistry is not adequate to accurately identify all dental treatment needs.
Integrated circulating tumour DNA and cytokine analysis for therapy monitoring of ALK-rearranged lung adenocarcinoma
Authors: Angeles Arlou Kristina , Janke Florian , Daum Ann-Kathrin , Reck Martin , Schneider Marc A. , Thomas Michael , Christopoulos Petros , Sültmann Holger 
Published: April 2023

Abstract
Background
Detection of circulating tumour DNA (ctDNA) in biological fluids is a minimally invasive alternative to tissue biopsy for therapy monitoring. Cytokines are released in the tumour microenvironment to influence inflammation and tumorigenic mechanisms. Here, we investigated the potential biomarker utility of circulating cytokines vis-à-vis ctDNA in ALK-rearranged+ lung adenocarcinoma (ALK + NSCLC) and explored the optimal combination of molecular parameters that could indicate disease progression.

Methods
Longitudinal serum samples (n = 296) were collected from ALK + NSCLC patients (n = 38) under tyrosine kinase inhibitor (TKI) therapy and assayed to quantify eight cytokines: IFN-γ, IL-1β, IL-6, IL-8, IL-10, IL-12p70, MCP1 and TNF-α. Generalised linear mixed-effect modelling was performed to test the performance of different combinations of cytokines and previously determined ctDNA parameters in identifying progressive disease.

Results
Serum IL-6, IL-8 and IL-10 were elevated at progressive disease, with IL-8 having the most significant impact as a biomarker. Integrating changes in IL-8 with ctDNA parameters maximised the performance of the classifiers in identifying disease progression, but this did not significantly outperform the model based on ctDNA alone.

Conclusions
Serum cytokine levels are potential disease progression markers in ALK + NSCLC. Further validation in a larger and prospective cohort is necessary to determine whether the addition of cytokine evaluation could improve current tumour monitoring modalities in the clinical setting.
Anticipating changes in the HER2 status of breast tumours with disease progression—towards better treatment decisions in the new era of HER2-low breast cancers
Authors: Bergeron Anthony , Bertaut Aurélie , Beltjens Françoise , Charon-Barra Céline , Amet Alix , Jankowski Clémentine , Desmoulins Isabelle , Ladoire Sylvain , Arnould Laurent 
Published: April 2023

Abstract
Background
HER2 expression is often negative or low in primary breast cancers (BCs) but its changes with disease progression remain poorly known. We aimed to estimate them between primary and recurrent tumours, and identify predictive factors.

Methods
We compared the HER2 status, and clinical and pathological characteristics by its evolution category (stable or changed), between all primary BCs and matched recurrences registered in our database in 2000–2020 (n = 512).

Results
HER2-low tumours were the most prevalent at diagnosis (44.9%), followed by HER2-negative tumours (39.3%). HER2 status significantly changed in 37.3% of recurrences, mainly of HER2-negative and HER2-low tumours. HER2-negative tumours which relapsed as HER2-low significantly more frequently expressed oestrogen receptors (ER) and recurred later than stably HER2-negative tumours. Changed HER2 status in distant metastases correlated with lower proliferation rates and higher ER expression in primary tumours, and among metastases of hormone receptor-positive (HR+) tumours—with weak progesterone receptor (PR) expression in primary tumours.

Conclusions
HER2 status changes with BC progression, with enrichment of HER2-low tumours in advanced stages. The ER+/PR− status, low proliferation index and time to late recurrence correlated with these changes. These findings highlight the need of retesting recurrences, especially of HR + primary tumours, to identify candidates for new anti-HER2 therapies.
Perturbation of the host cell Ca2+ homeostasis and ER-mitochondria contact sites by the SARS-CoV-2 structural proteins E and M
Authors: Poggio Elena , Vallese Francesca , Hartel Andreas J. W. , Morgenstern Travis J. , Kanner Scott A. , Rauh Oliver , Giamogante Flavia , Barazzuol Lucia , Shepard Kenneth L. , Colecraft Henry M. , Clarke Oliver Biggs , Brini Marisa , Calì Tito 
Published: April 2023

AbstractCoronavirus disease (COVID-19) is a contagious respiratory disease caused by the SARS-CoV-2 virus. The clinical phenotypes are variable, ranging from spontaneous recovery to serious illness and death. On March 2020, a global COVID-19 pandemic was declared by the World Health Organization (WHO). As of February 2023, almost 670 million cases and 6,8 million deaths have been confirmed worldwide. Coronaviruses, including SARS-CoV-2, contain a single-stranded RNA genome enclosed in a viral capsid consisting of four structural proteins: the nucleocapsid (N) protein, in the ribonucleoprotein core, the spike (S) protein, the envelope (E) protein, and the membrane (M) protein, embedded in the surface envelope. In particular, the E protein is a poorly characterized viroporin with high identity amongst all the β-coronaviruses (SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-OC43) and a low mutation rate. Here, we focused our attention on the study of SARS-CoV-2 E and M proteins, and we found a general perturbation of the host cell calcium (Ca2+) homeostasis and a selective rearrangement of the interorganelle contact sites. In vitro and in vivo biochemical analyses revealed that the binding of specific nanobodies to soluble regions of SARS-CoV-2 E protein reversed the observed phenotypes, suggesting that the E protein might be an important therapeutic candidate not only for vaccine development, but also for the clinical management of COVID designing drug regimens that, so far, are very limited.
Oligomeric states of ASC specks regulate inflammatory responses by inflammasome in the extracellular space
Authors: Yu Tae-Geun , Cha Jeong Seok , Kim Gijeong , Sohn Yoo-Kyoung , Yoo Youngki , Kim Uijin , Song Ji-Joon , Cho Hyun-Soo , Kim Hak-Sung 
Published: April 2023

AbstractInflammasomes are multi-protein complexes and play a crucial role in host defense against pathogens. Downstream inflammatory responses through inflammasomes are known to be related to the oligomerization degree of ASC specks, but the detailed mechanism still remains unexplored. Here, we demonstrate that oligomerization degrees of ASC specks regulate the caspase-1 activation in the extracellular space. A protein binder specific for a pyrin domain (PYD) of ASC (ASCPYD) was developed, and structural analysis revealed that the protein binder effectively inhibits the interaction between PYDs, disassembling ASC specks into low oligomeric states. ASC specks with a low oligomerization degree were shown to enhance the activation of caspase-1 by recruiting and processing more premature caspase-1 through interactions between CARD of caspase-1 (caspase-1CARD) and CARD of ASC (ASCCARD). These findings can provide insight into controlling the inflammasome-mediated inflammatory process as well as the development of inflammasome-targeting drugs.
Zero-field quantum beats and spin decoherence mechanisms in CsPbBr3 perovskite nanocrystals
Authors: Cai Rui , Wadgaonkar Indrajit , Lim Jia Wei Melvin , Dal Forno Stefano , Giovanni David , Feng Minjun , Ye Senyun , Battiato Marco , Sum Tze Chien 
Published: April 2023

AbstractCoherent optical manipulation of exciton states provides a fascinating approach for quantum gating and ultrafast switching. However, their coherence time for incumbent semiconductors is highly susceptible to thermal decoherence and inhomogeneous broadening effects. Here, we uncover zero-field exciton quantum beating and anomalous temperature dependence of the exciton spin lifetimes in CsPbBr3 perovskite nanocrystals (NCs) ensembles. The quantum beating between two exciton fine-structure splitting (FSS) levels enables coherent ultrafast optical control of the excitonic degree of freedom. From the anomalous temperature dependence, we identify and fully parametrize all the regimes of exciton spin depolarization, finding that approaching room temperature, it is dominated by a motional narrowing process governed by the exciton multilevel coherence. Importantly, our results present an unambiguous full physical picture of the complex interplay of the underlying spin decoherence mechanisms. These intrinsic exciton FSS states in perovskite NCs present fresh opportunities for spin-based photonic quantum technologies.
Single-cell metabolic fingerprints discover a cluster of circulating tumor cells with distinct metastatic potential
Authors: Zhang Wenjun , Xu Feifei , Yao Jiang , Mao Changfei , Zhu Mingchen , Qian Moting , Hu Jun , Zhong Huilin , Zhou Junsheng , Shi Xiaoyu , Chen Yun 
Published: April 2023

AbstractCirculating tumor cells (CTCs) are recognized as direct seeds of metastasis. However, CTC count may not be the “best” indicator of metastatic risk because their heterogeneity is generally neglected. In this study, we develop a molecular typing system to predict colorectal cancer metastasis potential based on the metabolic fingerprints of single CTCs. After identification of the metabolites potentially related to metastasis using mass spectrometry-based untargeted metabolomics, setup of a home-built single-cell quantitative mass spectrometric platform for target metabolite analysis in individual CTCs and use of a machine learning method composed of non-negative matrix factorization and logistic regression, CTCs are divided into two subgroups, C1 and C2, based on a 4-metabolite fingerprint. Both in vitro and in vivo experiments demonstrate that CTC count in C2 subgroup is closely associated with metastasis incidence. This is an interesting report on the presence of a specific population of CTCs with distinct metastatic potential at the single-cell metabolite level.
Electrosynthesis of chlorine from seawater-like solution through single-atom catalysts
Authors: Liu Yangyang , Li Can , Tan Chunhui , Pei Zengxia , Yang Tao , Zhang Shuzhen , Huang Qianwei , Wang Yihan , Zhou Zheng , Liao Xiaozhou , Dong Juncai , Tan Hao , Yan Wensheng , Yin Huajie , Liu Zhao-Qing , Huang Jun , Zhao Shenlong 
Published: April 2023

AbstractThe chlor-alkali process plays an essential and irreplaceable role in the modern chemical industry due to the wide-ranging applications of chlorine gas. However, the large overpotential and low selectivity of current chlorine evolution reaction (CER) electrocatalysts result in significant energy consumption during chlorine production. Herein, we report a highly active oxygen-coordinated ruthenium single-atom catalyst for the electrosynthesis of chlorine in seawater-like solutions. As a result, the as-prepared single-atom catalyst with Ru-O4moiety (Ru-O4SAM) exhibits an overpotential of only ~30 mV to achieve a current density of 10 mA cm−2in an acidic medium (pH = 1) containing 1 M NaCl. Impressively, the flow cell equipped with Ru-O4SAM electrode displays excellent stability and Cl2selectivity over 1000 h continuous electrocatalysis at a high current density of 1000 mA cm−2. Operando characterizations and computational analysis reveal that compared with the benchmark RuO2electrode, chloride ions preferentially adsorb directly onto the surface of Ru atoms on Ru-O4SAM, thereby leading to a reduction in Gibbs free-energy barrier and an improvement in Cl2selectivity during CER. This finding not only offers fundamental insights into the mechanisms of electrocatalysis but also provides a promising avenue for the electrochemical synthesis of chlorine from seawater electrocatalysis.
Preparing high-concentration individualized carbon nanotubes for industrial separation of multiple single-chirality species
Authors: Yang Dehua , Li Linhai , Li Xiao , Xi Wei , Zhang Yuejuan , Liu Yumin , Wei Xiaojun , Zhou Weiya , Wei Fei , Xie Sishen , Liu Huaping 
Published: April 2023

AbstractIndustrial production of single-chirality carbon nanotubes is critical for their applications in high-speed and low-power nanoelectronic devices, but both their growth and separation have been major challenges. Here, we report a method for industrial separation of single-chirality carbon nanotubes from a variety of raw materials with gel chromatography by increasing the concentration of carbon nanotube solution. The high-concentration individualized carbon nanotube solution is prepared by ultrasonic dispersion followed by centrifugation and ultrasonic redispersion. With this technique, the concentration of the as-prepared individualized carbon nanotubes is increased from about 0.19 mg/mL to approximately 1 mg/mL, and the separation yield of multiple single-chirality species is increased by approximately six times to the milligram scale in one separation run with gel chromatography. When the dispersion technique is applied to an inexpensive hybrid of graphene and carbon nanotubes with a wide diameter range of 0.8–2.0 nm, and the separation yield of single-chirality species is increased by more than an order of magnitude to the sub-milligram scale. Moreover, with present separation technique, the environmental impact and cost of producing single-chirality species are greatly reduced. We anticipate that this method promotes industrial production and practical applications of single-chirality carbon nanotubes in carbon-based integration circuits.
Recognition of an Ala-rich C-degron by the E3 ligase Pirh2
Authors: Wang Xiaolu , Li Yao , Yan Xiaojie , Yang Qing , Zhang Bing , Zhang Ying , Yuan Xinxin , Jiang Chenhao , Chen Dongxing , Liu Quanyan , Liu Tong , Mi Wenyi , Yu Ying , Dong Cheng 
Published: April 2023

AbstractThe ribosome-associated quality-control (RQC) pathway degrades aberrant nascent polypeptides arising from ribosome stalling during translation. In mammals, the E3 ligase Pirh2 mediates the degradation of aberrant nascent polypeptides by targeting the C-terminal polyalanine degrons (polyAla/C-degrons). Here, we present the crystal structure of Pirh2 bound to the polyAla/C-degron, which shows that the N-terminal domain and the RING domain of Pirh2 form a narrow groove encapsulating the alanine residues of the polyAla/C-degron. Affinity measurements in vitro and global protein stability assays in cells further demonstrate that Pirh2 recognizes a C-terminal A/S-X-A-A motif for substrate degradation. Taken together, our study provides the molecular basis underlying polyAla/C-degron recognition by Pirh2 and expands the substrate recognition spectrum of Pirh2.
Revised Minoan eruption volume as benchmark for large volcanic eruptions
Authors: Karstens Jens , Preine Jonas , Crutchley Gareth J. , Kutterolf Steffen , van der Bilt Willem G. M. , Hooft Emilie E. E. , Druitt Timothy H. , Schmid Florian , Cederstrøm Jan Magne , Hübscher Christian , Nomikou Paraskevi , Carey Steven , Kühn Michel , Elger Judith , Berndt Christian 
Published: April 2023

AbstractDespite their global societal importance, the volumes of large-scale volcanic eruptions remain poorly constrained. Here, we integrate seismic reflection and P-wave tomography datasets with computed tomography-derived sedimentological analyses to estimate the volume of the iconic Minoan eruption. Our results reveal a total dense-rock equivalent eruption volume of 34.5 ± 6.8 km³, which encompasses 21.4 ± 3.6 km³ of tephra fall deposits, 6.9 ± 2 km³ of ignimbrites, and 6.1 ± 1.2 km³ of intra-caldera deposits. 2.8 ± 1.5 km³ of the total material consists of lithics. These volume estimates are in agreement with an independent caldera collapse reconstruction (33.1 ± 1.2 km³). Our results show that the Plinian phase contributed most to the distal tephra fall, and that the pyroclastic flow volume is significantly smaller than previously assumed. This benchmark reconstruction demonstrates that complementary geophysical and sedimentological datasets are required for reliable eruption volume estimates, which are necessary for regional and global volcanic hazard assessments.