bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wildfire Smoke Demonstrates Significant and Predictable Black Carbon Light Absorption Enhancements
Authors: Lee James E. , Gorkowski Kyle , Meyer Aaron G. , Benedict Katherine B. , Aiken Allison C. , Dubey Manvendra K. 
Published: July 2022

AbstractBlack carbon (BC) is estimated to have the second largest anthropogenic radiative forcing in earth‐systems models (ESMs), but there is significant uncertainty in its impact due to complex mixing with organics. Laboratory‐generated particles show that co‐mixed non‐absorbing material enhances absorption by BC by a factor of 2–3.5 as predicted by optical models. However, weak or no enhancements are often reported for field studies. The cause of lower‐than‐expected absorption is not well understood and implies a lower radiative impact of BC compared to how many ESMs currently treat aerosols. By analyzing BC aerosol particle‐by‐particle we reconcile observed and expected absorption for ambient smoke plumes varying in geographic origin, fuel types, burn conditions, atmospheric age and transport. Although particle‐by‐particle tracking is computationally prohibitive for sophisticated ESMs we show that realistic BC absorption is reliably estimated by bulk properties of the plume providing a suitable parameterization to constrain black carbon radiative forcing.
Thermophysical and Compositional Properties of Paleobedforms on Mars
Authors: Weintraub Aaron Robert , Edwards Christopher Scott , Chojnacki Matthew , Edgar Lauren A. , Fenton Lori K. , Piqueux Sylvain , Gullikson Amber L. 
Published: July 2022

AbstractBedforms on Earth and Mars are often preserved in the rock record in the form of sedimentary rock with distinct cross‐bedding. On rare occasions, the full‐surface geometry of a bedform can be preserved through burial and lithification. These features, known as paleobedforms, are found in a variety of geographic locations on Mars. Evidence in the morphology of paleobedforms, such as the retention of impact craters and steep erosional scarps, suggests that these features are well‐lithified and capable of withstanding prolonged weathering and erosion. Here, we present results from thermophysical and compositional analyses on a subset of the best preserved paleobedform candidate fields on Mars. Thermophysical modeling elucidates the changes these bedforms underwent from their unconsolidated, particulate nature to their currently observed properties. Certain paleobedforms have elevated thermal inertias (e.g., ∼300–500 J·m−2·s−1/2·K−1) when compared with modern bedforms (∼250 J·m−2·s−1/2·K−1), and modeling indicates that they have cement volumes of 0.8%–1.5% even as high as 30%. However, most paleobedform candidates have unexpectedly low thermal inertia when compared with modern dunes. Additionally, compositional analyses reveal a range of spectral characteristics within paleobedforms (e.g., primary and secondary alteration products). These features add to the already existing class of Martian surfaces in which thermal inertia does not seem to correspond to erodibility, cohesion, or mechanical strength. Studying paleobedforms with both raised and nonraised thermal inertia has provided new insights into lithification on Mars and constrained the environmental conditions leading to the formation of these enigmatic features.
Single-cell multiomics analysis reveals regulatory programs in clear cell renal cell carcinoma
Authors: Long Zhilin , Sun Chengfang , Tang Min , Wang Yin , Ma Jiayan , Yu Jichuan , Wei Jingchao , Ma Jianzhu , Wang Bohan , Xie Qi , Wen Jiaming 
Published: July 2022

AbstractThe clear cell renal cell carcinoma (ccRCC) microenvironment consists of many different cell types and structural components that play critical roles in cancer progression and drug resistance, but the cellular architecture and underlying gene regulatory features of ccRCC have not been fully characterized. Here, we applied single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) to generate transcriptional and epigenomic landscapes of ccRCC. We identified tumor cell-specific regulatory programs mediated by four key transcription factors (TFs) (HOXC5, VENTX, ISL1, and OTP), and these TFs have prognostic significance in The Cancer Genome Atlas (TCGA) database. Targeting these TFs via short hairpin RNAs (shRNAs) or small molecule inhibitors decreased tumor cell proliferation. We next performed an integrative analysis of chromatin accessibility and gene expression for CD8+ T cells and macrophages to reveal the different regulatory elements in their subgroups. Furthermore, we delineated the intercellular communications mediated by ligand–receptor interactions within the tumor microenvironment. Taken together, our multiomics approach further clarifies the cellular heterogeneity of ccRCC and identifies potential therapeutic targets.
Multifocal organoids reveal clonal associations between synchronous intestinal tumors with pervasive heterogeneous drug responses
Authors: Jeong Nahyun , Kim Soon-Chan , Park Ji Won , Park Seul Gi , Nam Ki-Hoan , Lee Ja Oh , Shin Young-Kyoung , Bae Jeong Mo , Jeong Seung-Yong , Kim Min Jung , Ku Ja-Lok 
Published: July 2022

AbstractMultifocal colorectal cancer (CRC) comprises both clonally independent primary tumors caused by inherited predisposition and clonally related tumors mainly due to intraluminal spreading along an intact basement membrane. The distinction between these multifocal CRCs is essential because therapeutic strategies vary according to the clonal association of multiple tumor masses. Here, we report one unique case of synchronous intestinal cancer (SIC) with tumors occurring along the entire bowel tract, including the small intestine. We established six patient-derived organoids (PDOs), and patient-derived cell lines (PDCs) from each site of the SIC, which were subjected to extensive genomic, transcriptomic, and epigenomic sequencing. We also estimated the drug responses of each multifocal SIC to 25 clinically relevant therapeutic compounds to validate how the clinically actionable alternations between SICs were associated with drug sensitivity. Our data demonstrated distinct clonal associations across different organs, which were consistently supported by multi-omics analysis, as well as the accordant responses to various therapeutic compounds. Our results indicated the imminent drawback of a single tumor-based diagnosis of multifocal CRC and suggested the necessity of an in-depth molecular analysis of all tumor regions to avoid unexpected resistance to the currently available targeted therapies.
High sensitivity and broad linearity range pressure sensor based on hierarchical in-situ filling porous structure
Authors: Xu Jin , Li Huayang , Yin Yiming , Li Xin , Cao Jinwei , Feng Hanfang , Bao Wandi , Tan Hao , Xiao Fanyuan , Zhu Guang 
Published: July 2022

AbstractFlexible piezoresistive pressure sensor with high sensitivity over a broad linearity range have been attracting tremendous attention for its applications in health monitoring, artificial intelligence, and human-machine interfaces. Herein, we report a hierarchical in-situ filling porous piezoresistive sensor (HPPS) by direct ink writing (DIW) printing and curing of carbon nanofibers (CNFs)/polydimethylsiloxane (PDMS) emulsion. Hierarchical geometry significantly increases the contact area, distributes stress to multilayered lattice and internal porous structure, resulting in a broad sensing range. Moreover, unlike conventional hollow porous structure, the CNFs networks in-situ filling porous structure generates more contact sites and conductive pathways during compression, thereby achieving high sensitivity and linearity over entire sensing range. Therefore, the optimized HPPS achieves high sensitivity (4.7 kPa−1) and linearity (coefficient of determination, R2 = 0.998) over a broad range (0.03–1000 kPa), together with remarkable response time and repeatability. Furthermore, the applications in diverse pressure scenarios and healthcare monitoring are demonstrated.
LRRK2 kinase activity regulates GCase level and enzymatic activity differently depending on cell type in Parkinson’s disease
Authors: Kedariti Maria , Frattini Emanuele , Baden Pascale , Cogo Susanna , Civiero Laura , Ziviani Elena , Zilio Gianluca , Bertoli Federico , Aureli Massimo , Kaganovich Alice , Cookson Mark R. , Stefanis Leonidas , Surface Matthew , Deleidi Michela , Di Fonzo Alessio , Alcalay Roy N. , Rideout Hardy , Greggio Elisa , Plotegher Nicoletta 
Published: July 2022

AbstractLeucine-rich repeat kinase 2 (LRRK2) is a kinase involved in different cellular functions, including autophagy, endolysosomal pathways, and immune function. Mutations in LRRK2 cause autosomal-dominant forms of Parkinson’s disease (PD). Heterozygous mutations in GBA1, the gene encoding the lysosomal enzyme glucocerebrosidase (GCase), are the most common genetic risk factors for PD. Moreover, GCase function is altered in idiopathic PD and in other genetic forms of the disease. Recent work suggests that LRRK2 kinase activity can regulate GCase function. However, both a positive and a negative correlation have been described. To gain insights into the impact of LRRK2 on GCase, we performed a comprehensive analysis of GCase levels and activity in complementary LRRK2 models, including (i) LRRK2 G2019S knock in (GSKI) mice, (ii) peripheral blood mononuclear cell (PBMCs), plasma, and fibroblasts from PD patients carrying LRRK2 G2019S mutation, (iii) patient iPSCs-derived neurons; (iv) endogenous and overexpressed cell models. In some of these models we found a positive correlation between the activities of LRRK2 and GCase, which was further confirmed in cell lines with genetic and pharmacological manipulation of LRRK2 kinase activity. GCase protein level is reduced in GSKI brain tissues and in G2019S iPSCs-derived neurons, but increased in fibroblasts and PBMCs from patients, suggesting cell-type-specific effects. Overall, our study indicates that LRRK2 kinase activity affects both the levels and the catalytic activity of GCase in a cell-type-specific manner, with important implications in the context of therapeutic application of LRRK2 inhibitors in GBA1-linked and idiopathic PD.
Archaic chaperone–usher pili self-secrete into superelastic zigzag springs
Authors: Pakharukova Natalia , Malmi Henri , Tuittila Minna , Dahlberg Tobias , Ghosal Debnath , Chang Yi-Wei , Myint Si Lhyam , Paavilainen Sari , Knight Stefan David , Lamminmäki Urpo , Uhlin Bernt Eric , Andersson Magnus , Jensen Grant , Zavialov Anton V. 
Published: July 2022

AbstractAdhesive pili assembled through the chaperone–usher pathway are hair-like appendages that mediate host tissue colonization and biofilm formation of Gram-negative bacteria1–3. Archaic chaperone–usher pathway pili, the most diverse and widespread chaperone–usher pathway adhesins, are promising vaccine and drug targets owing to their prevalence in the most troublesome multidrug-resistant pathogens1,4,5. However, their architecture and assembly–secretion process remain unknown. Here, we present the cryo-electron microscopy structure of the prototypical archaic Csu pilus that mediates biofilm formation of Acinetobacter baumannii—a notorious multidrug-resistant nosocomial pathogen. In contrast to the thick helical tubes of the classical type 1 and P pili, archaic pili assemble into an ultrathin zigzag architecture secured by an elegant clinch mechanism. The molecular clinch provides the pilus with high mechanical stability as well as superelasticity, a property observed for the first time, to our knowledge, in biomolecules, while enabling a more economical and faster pilus production. Furthermore, we demonstrate that clinch formation at the cell surface drives pilus secretion through the outer membrane. These findings suggest that clinch-formation inhibitors might represent a new strategy to fight multidrug-resistant bacterial infections.
Conditioned media of pancreatic cancer cells and pancreatic stellate cells induce myeloid-derived suppressor cells differentiation and lymphocytes suppression
Authors: Chong Yuen Ping , Peter Evelyn Priya , Lee Feon Jia Ming , Chan Chu Mun , Chai Shereen , Ling Lorni Poh Chou , Tan Eng Lai , Ng Sook Han , Masamune Atsushi , Ghafar Siti Aisyah Abd , Ismail Norsharina , Ho Ket Li 
Published: July 2022

AbstractAs pancreatic cancer cells (PCCs) and pancreatic stellate cells (PSCs) are the two major cell types that comprise the immunosuppressive tumor microenvironment of pancreatic cancer, we aimed to investigate the role of conditioned medium derived from PCCs and PSCs co-culture on the viability of lymphocytes. The conditioned medium (CM) collected from PCCs and/or PSCs was used to treat peripheral blood mononuclear cells (PBMCs) to determine CM ability in reducing lymphocytes population. A proteomic analysis has been done on the CM to investigate the differentially expressed protein (DEP) expressed by two PCC lines established from different stages of tumor. Subsequently, we investigated if the reduction of lymphocytes was directly caused by CM or indirectly via CM-induced MDSCs. This was achieved by isolating lymphocyte subtypes and treating them with CM and CM-induced MDSCs. Both PCCs and PSCs were important in suppressing lymphocytes, and the PCCs derived from a metastatic tumor appeared to have a stronger suppressive effect than the PCCs derived from a primary tumor. According to the proteomic profiles of CM, 416 secreted proteins were detected, and 13 DEPs were identified between PANC10.05 and SW1990. However, CM was found unable to reduce lymphocytes viability through a direct pathway. In contrast, CM that contains proteins secreted by PCC and/or PSC appear immunogenic as they increase the viability of lymphocytes subtypes. Lymphocyte subtype treated with CM-induced MDSCs showed reduced viability in T helper 1 (Th1), T helper 2 (Th2), and T regulatory (Treg) cells, but not in CD8+ T cells, and B cells. As a conclusion, the interplay between PCCs and PSCs is important as their co-culture displays a different trend in lymphocytes suppression, hence, their co-culture should be included in future studies to better mimic the tumor microenvironment.
A systematic review of healthcare provider-targeted mobile applications for non-communicable diseases in low- and middle-income countries
Authors: Geldsetzer Pascal , Flores Sergio , Wang Grace , Flores Blanca , Rogers Abu Bakarr , Bunker Aditi , Chang Andrew Y. , Tisdale Rebecca 
Published: July 2022

AbstractMobile health (mHealth) interventions hold promise for addressing the epidemic of noncommunicable diseases (NCDs) in low- and middle-income countries (LMICs) by assisting healthcare providers managing these disorders in low-resource settings. We aimed to systematically identify and assess provider-facing mHealth applications used to screen for, diagnose, or monitor NCDs in LMICs. In this systematic review, we searched the indexing databases of PubMed, Web of Science, and Cochrane Central for studies published between January 2007 and October 2019. We included studies of technologies that were: (i) mobile phone- or tablet-based, (ii) able to screen for, diagnose, or monitor an NCD of public health importance in LMICs, and (iii) targeting health professionals as users. We extracted disease type, intervention purpose, target population, study population, sample size, study methodology, technology stage, country of development, operating system, and cost. Our initial search retrieved 13,262 studies, 315 of which met inclusion criteria and were analyzed. Cardiology was the most common clinical domain of the technologies evaluated, with 89 publications. mHealth innovations were predominantly developed using Apple’s iOS operating system. Cost data were provided in only 50 studies, but most technologies for which this information was available cost less than 20 USD. Only 24 innovations targeted the ten NCDs responsible for the greatest number of disability-adjusted life years lost globally. Most publications evaluated products created in high-income countries. Reported mHealth technologies are well-developed, but their implementation in LMICs faces operating system incompatibility and a relative neglect of NCDs causing the greatest disease burden.
Effectiveness of automated alerting system compared to usual care for the management of sepsis
Authors: Zhang Zhongheng , Chen Lin , Xu Ping , Wang Qing , Zhang Jianjun , Chen Kun , Clements Casey M. , Celi Leo Anthony , Herasevich Vitaly , Hong Yucai 
Published: July 2022

AbstractThere is a large body of evidence showing that delayed initiation of sepsis bundle is associated with adverse clinical outcomes in patients with sepsis. However, it is controversial whether electronic automated alerts can help improve clinical outcomes of sepsis. Electronic databases are searched from inception to December 2021 for comparative effectiveness studies comparing automated alerts versus usual care for the management of sepsis. A total of 36 studies are eligible for analysis, including 6 randomized controlled trials and 30 non-randomized studies. There is significant heterogeneity in these studies concerning the study setting, design, and alerting methods. The Bayesian meta-analysis by using pooled effects of non-randomized studies as priors shows a beneficial effect of the alerting system (relative risk [RR]: 0.71; 95% credible interval: 0.62 to 0.81) in reducing mortality. The automated alerting system shows less beneficial effects in the intensive care unit (RR: 0.90; 95% CI: 0.73–1.11) than that in the emergency department (RR: 0.68; 95% CI: 0.51–0.90) and ward (RR: 0.71; 95% CI: 0.61–0.82). Furthermore, machine learning-based prediction methods can reduce mortality by a larger magnitude (RR: 0.56; 95% CI: 0.39–0.80) than rule-based methods (RR: 0.73; 95% CI: 0.63–0.85). The study shows a statistically significant beneficial effect of using the automated alerting system in the management of sepsis. Interestingly, machine learning monitoring systems coupled with better early interventions show promise, especially for patients outside of the intensive care unit.
Development of copper-catalyzed deaminative esterification using high-throughput experimentation
Authors: Shen Yuning , Mahjour Babak , Cernak Tim 
Published: July 2022

AbstractRepurposing of amine and carboxylic acid building blocks provides an enormous opportunity to expand the accessible chemical space, because amine and acid feedstocks are typically low cost and available in high diversity. Herein, we report a copper-catalyzed deaminative esterification based on C–N activation of aryl amines via diazonium salt formation. The reaction was specifically designed to complement the popular amide coupling reaction. A chemoinformatic analysis of commercial building blocks demonstrates that by utilizing aryl amines, our method nearly doubles the available esterification chemical space compared to classic Fischer esterification with phenols. High-throughput experimentation in microliter reaction droplets was used to develop the reaction, along with classic scope studies, both of which demonstrated robust performance against hundreds of substrate pairs. Furthermore, we have demonstrated that this new esterification is suitable for late-stage diversification and for building-block repurposing to expand chemical space.
Negative polarization properties of regolith simulants
Authors: Spadaccia S. , Patty C. H. L. , Capelo H. L. , Thomas N. , Pommerol A. 
Published: July 2022

Context. Polarization phase curves of asteroids and other small airless bodies are influenced by the compositional and physical properties of their regolith. The mixing of minerals composing the regolith influences the negative polarization at small phase angles because it changes the multiple scattering properties of the medium.
Aims. This work aims to demonstrate experimentally how the mixing effect influences the polarization phase curve at small phase angles for different mineralogies relevant for asteroids, and to determine how different aggregate sizes affect the negative polarization.
Methods. We prepared a set of binary and ternary mixtures with different common minerals on asteroids and one set of the same mixture with different aggregate sizes. We measured their reflected light at 530 nm with full Stokes polarimetry at phase angles ranging from 0.8° to 30°.
Results. The mixing effect of the mixtures with both bright and dark minerals significantly changes the behavior of the phase curves in terms of minimum polarization, phase angle of the minimum, and inversion angle with respect to the mineral components that are mixed together. The changes in phase curve could explain the polarization observation of particular classes of asteroids (F and L class) and other asteroids with peculiar polarization curves or photometric properties. Furthermore, we demonstrate that the negative polarization is invariant to the presence of dust aggregates up to centimeter sizes.
Constraining masses and separations of unseen companions to five accelerating nearby stars
Authors: Mesa D. , Bonavita M. , Benatti S. , Gratton R. , Marino S. , Kervella P. , D’ Orazi V. , Desidera S. , Henning T. , Janson M. , Langlois M. , Rickman E. , Vigan A. , Zurlo A. , Baudino J.-L. , Biller B. , Boccaletti A. , Bonnefoy M. , Brandner W. , Buenzli E. , Cantalloube F. , Fantinel D. , Fontanive C. , Galicher R. , Ginski C. , Girard J. , Hagelberg J. , Kopytova T. , Lagrange A.-M. , Lazzoni C. , Le Coroller H. , Ligi R. , Llored M. , Maire A.-L. , Mouillet D. , Perrot C. , Rochat S. , Romero C. , Rouan D. , Samland M. , Schmidt T. O. B. , Sissa E. , Wildi F. 
Published: July 2022

Aims. In this work, we aim to constrain the masses and separations of potential substellar companions to five accelerating stars (HIP 1481, HIP 88399, HIP 96334, HIP 30314, and HIP 116063) using multiple data sets acquired with different techniques.
Methods. Our targets were originally observed as part of the SPHERE/SHINE survey, and radial velocity (RV) archive data were also available for four of the five objects. No companions were originally detected in any of these data sets, but the presence of significant proper motion anomalies (PMas) for all the stars strongly suggested the presence of a companion. Combining the information from the PMas with the limits derived from the RV and SPHERE data, we were able to put constraints on the characteristics of the unseen companions.
Results. Our analysis led to relatively strong constraints for both HIP 1481 and HIP 88399, narrowing down the companion masses to 2–5 MJup and 3–5 MJup and separations within 2–15 au and 3–9 au, respectively. Because of the large age uncertainties for HIP 96334, the poor observing conditions for the SPHERE epochs of HIP 30314, and the lack of RV data for HIP 116063, the results for these targets were not as well defined, but we were still able to constrain the properties of the putative companions within a reasonable confidence level.
Conclusions. For all five targets, our analysis reveals that the companions responsible for the PMa signal would be well within reach for future instruments planned for the ELT (e.g., MICADO), which would easily achieve the required contrast and angular resolution. Our results therefore represent yet another confirmation of the power of multi-technique approaches for both the discovery and characterisation of planetary systems.