bluuebunny/crossref_metadata_2025_split huggingface dataset:
ZIC2 induces pro-tumor macrophage polarization in nasopharyngeal carcinoma by activating the JUNB/MCSF axis
Authors: Liu Qian , Yang Ting , Zhang Yu , Hu Ze-Dong , Liu Yan-Min , Luo Yi-Ling , Liu Shang-Xin , Zhang Hua , Zhong Qian 
Published: July 2023

AbstractNasopharyngeal carcinoma (NPC) is a common malignant epithelial tumor of the head and neck that often exhibits local recurrence and distant metastasis. The molecular mechanisms are understudied, and effective therapeutic targets are still lacking. In our study, we found that the transcription factor ZIC2 was highly expressed in NPC. Although ZIC family members play important roles in neural development and carcinogenesis, the specific mechanism and clinical significance of ZIC2 in the tumorigenesis and immune regulation of NPC remain elusive. Here, we first reported that high expression of ZIC2 triggered the secretion of MCSF in NPC cells, induced M2 polarization of tumor-associated macrophages (TAMs), and affected the secretion of TAM-related cytokines. Mechanistically, ChIP-seq and RNA-seq analyses identified JUNB as a downstream target of ZIC2. Furthermore, ZIC2 was significantly enriched in the promoter site of JUNB and activated JUNB promoter activity, as shown by ChIP-qPCR and luciferase assays. In addition, JUNB and MCSF participated in ZIC2-induced M2 TAMs polarization. Thus, blocking JUNB and MCSF could reverse ZIC2-mediated M2 TAMs polarization. Moreover, Kaplan-Meier survival analyses indicated that high expression of ZIC2, JUNB, and CD163 was positively associated with a poor prognosis in NPC. Overexpression of ZIC2 induced tumor growth in vivo, with the increase of JUNB, MCSF secretion, and CD163. In summary, our study implies that ZIC2 induces M2 TAM polarization, at least in part through regulation of JUNB/MCSF and that ZIC2, JUNB, and CD163 can be utilized as prognostic markers for NPC and as therapeutic targets for cancer immunotherapy.
Elastin stabilization prevents impaired biomechanics in human pulmonary arteries and pulmonary hypertension in rats with left heart disease
Authors: Kucherenko Mariya M. , Sang Pengchao , Yao Juquan , Gransar Tara , Dhital Saphala , Grune Jana , Simmons Szandor , Michalick Laura , Wulsten Dag , Thiele Mario , Shomroni Orr , Hennig Felix , Yeter Ruhi , Solowjowa Natalia , Salinas Gabriela , Duda Georg N. , Falk Volkmar , Vyavahare Naren R. , Kuebler Wolfgang M. , Knosalla Christoph 
Published: July 2023

AbstractPulmonary hypertension worsens outcome in left heart disease. Stiffening of the pulmonary artery may drive this pathology by increasing right ventricular dysfunction and lung vascular remodeling. Here we show increased stiffness of pulmonary arteries from patients with left heart disease that correlates with impaired pulmonary hemodynamics. Extracellular matrix remodeling in the pulmonary arterial wall, manifested by dysregulated genes implicated in elastin degradation, precedes the onset of pulmonary hypertension. The resulting degradation of elastic fibers is paralleled by an accumulation of fibrillar collagens. Pentagalloyl glucose preserves arterial elastic fibers from elastolysis, reduces inflammation and collagen accumulation, improves pulmonary artery biomechanics, and normalizes right ventricular and pulmonary hemodynamics in a rat model of pulmonary hypertension due to left heart disease. Thus, targeting extracellular matrix remodeling may present a therapeutic approach for pulmonary hypertension due to left heart disease.
Obesity-associated changes in molecular biology of primary breast cancer
Authors: Nguyen Ha-Linh , Geukens Tatjana , Maetens Marion , Aparicio Samuel , Bassez Ayse , Borg Ake , Brock Jane , Broeks Annegien , Caldas Carlos , Cardoso Fatima , De Schepper Maxim , Delorenzi Mauro , Drukker Caroline A. , Glas Annuska M. , Green Andrew R. , Isnaldi Edoardo , Eyfjörð Jórunn , Khout Hazem , Knappskog Stian , Krishnamurthy Savitri , Lakhani Sunil R. , Langerod Anita , Martens John W. M. , McCart Reed Amy E. , Murphy Leigh , Naulaerts Stefan , Nik-Zainal Serena , Nevelsteen Ines , Neven Patrick , Piccart Martine , Poncet Coralie , Punie Kevin , Purdie Colin , Rakha Emad A. , Richardson Andrea , Rutgers Emiel , Vincent-Salomon Anne , Simpson Peter T. , Schmidt Marjanka K. , Sotiriou Christos , Span Paul N. , Tan Kiat Tee Benita , Thompson Alastair , Tommasi Stefania , Van Baelen Karen , Van de Vijver Marc , Van Laere Steven , van’t Veer Laura , Viale Giuseppe , Viari Alain , Vos Hanne , Witteveen Anke T. , Wildiers Hans , Floris Giuseppe , Garg Abhishek D. , Smeets Ann , Lambrechts Diether , Biganzoli Elia , Richard François , Desmedt Christine 
Published: July 2023

AbstractObesity is associated with an increased risk of developing breast cancer (BC) and worse prognosis in BC patients, yet its impact on BC biology remains understudied in humans. This study investigates how the biology of untreated primary BC differs according to patients’ body mass index (BMI) using data from >2,000 patients. We identify several genomic alterations that are differentially prevalent in overweight or obese patients compared to lean patients. We report evidence supporting an ageing accelerating effect of obesity at the genetic level. We show that BMI-associated differences in bulk transcriptomic profile are subtle, while single cell profiling allows detection of more pronounced changes in different cell compartments. These analyses further reveal an elevated and unresolved inflammation of the BC tumor microenvironment associated with obesity, with distinct characteristics contingent on the estrogen receptor status. Collectively, our analyses imply that obesity is associated with an inflammaging-like phenotype. We conclude that patient adiposity may play a significant role in the heterogeneity of BC and should be considered for BC treatment tailoring.
Vertically grown ultrathin Bi2SiO5 as high-κ single-crystalline gate dielectric
Authors: Chen Jiabiao , Liu Zhaochao , Dong Xinyue , Gao Zhansheng , Lin Yuxuan , He Yuyu , Duan Yingnan , Cheng Tonghuai , Zhou Zhengyang , Fu Huixia , Luo Feng , Wu Jinxiong 
Published: July 2023

AbstractSingle-crystalline high-κ dielectric materials are desired for the development of future two-dimensional (2D) electronic devices. However, curent 2D gate insulators still face challenges, such as insufficient dielectric constant and difficult to obtain free-standing and transferrable ultrathin films. Here, we demonstrate that ultrathin Bi2SiO5 crystals grown by chemical vapor deposition (CVD) can serve as excellent gate dielectric layers for 2D semiconductors, showing a high dielectric constant (>30) and large band gap (~3.8 eV). Unlike other 2D insulators synthesized via in-plane CVD on substrates, vertically grown Bi2SiO5 can be easily transferred onto other substrates by polymer-free mechanical pressing, which greatly facilitates its ideal van der Waals integration with few-layer MoS2 as high-κ dielectrics and screening layers. The Bi2SiO5 gated MoS2 field-effect transistors exhibit an ignorable hysteresis (~3 mV) and low drain induced barrier lowering (~5 mV/V). Our work suggests vertically grown Bi2SiO5 nanoflakes as promising candidates to improve the performance of 2D electronic devices.
Synthesis of propenone-linked covalent organic frameworks via Claisen-Schmidt reaction for photocatalytic removal of uranium
Authors: Niu Cheng-Peng , Zhang Cheng-Rong , Liu Xin , Liang Ru-Ping , Qiu Jian-Ding 
Published: July 2023

AbstractThe type of reactions and the availability of monomers for the synthesis of sp2-c linked covalent organic frameworks (COFs) are considerably limited by the irreversibility of the C=C bond. Herein, inspired by the Claisen-Schmidt condensation reaction, two propenone-linked (C=C–C=O) COFs (named Py-DAB and PyN-DAB) are developed based on the base-catalyzed nucleophilic addition reaction of ketone-activated α-H with aromatic aldehydes. The introduction of propenone structure endows COFs with high crystallinity, excellent physicochemical stability, and intriguing optoelectronic properties. Benefitting from the rational design on the COFs skeleton, Py-DAB and PyN-DAB are applied to the extraction of radionuclide uranium. In particular, PyN-DAB shows excellent removal rates (>98%) in four uranium mine wastewater samples. We highlight that such a general strategy can provide a valuable avenue toward various functional porous crystalline materials.
Dynamic in vitro culture of bovine and human ovarian tissue enhances follicle progression and health
Authors: Barbato Vincenza , Genovese Vincenzo , De Gregorio Vincenza , Di Nardo Maddalena , Travaglione Angela , De Napoli Luigi , Fragomeni Gionata , Zanetti Elisabetta M. , Adiga Satish K. , Mondrone Giuseppe , D’Hooghe Thomas , Zheng Wengijng , Longobardi Salvatore , Catapano Gerardo , Gualtieri Roberto , Talevi Riccardo 
Published: July 2023

AbstractIn vitro ovarian cortical tissue culture, followed by culture of isolated secondary follicles, is a promising future option for production of mature oocytes. Although efforts have been made to improve the culture outcome by changing the medium composition, so far, most studies used static culture systems. Here we describe the outcome of 7 days cultures of bovine and human ovarian cortical tissue in a dynamic system using a novel perifusion bioreactor in comparison to static culture in conventional and/or gas permeable dishes. Findings show that dynamic culture significantly improves follicle quality and viability, percentage and health of secondary follicles, overall tissue health, and steroid secretion in both species. Model predictions suggest that such amelioration can be mediated by an enhanced oxygen availability and/or by fluid-mechanical shear stresses and solid compressive strains exerted on the tissue.
Lifestyle practices that reduce seasonal PM2.5 exposure and their impact on COPD
Authors: Kim Hajeong , Huh Jin-Young , Na Geunjoo , Park Shinhee , Ra Seung Won , Kang Sung-Yoon , Kim Ho Cheol , Kim Hwan-Cheol , Lee Sei Won 
Published: July 2023

AbstractParticulate matter (PM) is a major air pollutant that has led to global health concerns and can cause and exacerbate chronic obstructive pulmonary disease (COPD). We asked patients with COPD to complete a detailed questionnaire about their lifestyle practices to reduce PM2.5 exposure and analyzed the relationship between ambient PM2.5 concentrations and lifestyle practices. We prospectively enrolled 104 COPD patients from four hospitals in different areas of Korea. They completed detailed questionnaires twice (at enrollment and the end of the study) and Internet of Things-based sensors were installed in their homes to continuously measure PM2.5 for 1 year. The relationship between PM2.5 concentrations, lifestyle practices, and COPD exacerbations were analyzed in each season. The PM2.5 concentration was higher outdoors than indoors in all seasons except summer, and the difference was largest in winter. The six lifestyle practices that significantly lowered the annual indoor PM2.5 concentration compared with the outdoors. The higher the economic status and educational level of patients, the lower the indoor PM2.5 concentration. Some lifestyle practices were associated with reduced small airway resistance, presented as R5–R20 determined by impulse oscillometry, and scores of the St. George’s Respiratory Questionnaire. Some lifestyle practices are associated with reduced indoor PM2.5 concentrations and can even affect clinical outcomes, including small airway resistance and quality of life of COPD patients.
Comparing clinical outcomes of ARB and ACEi in patients hospitalized for acute COVID-19
Authors: Hamada Seiji , Suzuki Tomoharu , Tokuda Yasuharu , Taniguchi Kiyosu , Shibuya Kenji 
Published: July 2023

AbstractContinued receipt of Renin–Angiotensin–Aldosterone inhibitors in patients with COVID-19 has shown potential in producing better clinical outcomes. However, superiority between ACEi (angiotensin-converting enzyme inhibitors) and ARB (angiotensin II receptor blockers) regarding clinical outcomes in this setting remains unknown. We retrospectively collected data on patients hospitalized for acute COVID-19 using the nationwide administrative database (Diagnosis and Procedure Combinations, DPC). The DPC data covered around 25% of all acute care hospitals in Japan. Patient outcomes, with focus on inpatient mortality, were compared between patients previously prescribed ACEi and those prescribed ARB. Comparisons based on crude, multivariate and propensity-score adjusted analysis were conducted. We examined a total of 7613 patients (ARB group, 6903; ACEi group 710). The ARB group showed lower crude in-hospital mortality, compared to the ACEi group (5% vs 8%; odds ratio, 0.65; 95% CI 0.48–0.87), however not in the multivariate-adjusted model (odds ratio, 0.95; 95% CI 0.69–1.3) or propensity-score adjusted models (odds ratio, 0.86; 95% CI 0.63–1.2). ARB shows potential in reducing hospital stay duration over ACEi in patients admitted for COVID-19, but does not significantly reduce in-hospital mortality. Further prospective studies are needed to draw a definitive conclusion, but continuation of either of these medications is warranted to improve clinical outcomes.
Effect of bubble size on ultrasound backscatter from bubble clouds in the context of gas kick detection in boreholes
Authors: Indimath Shivanandan , Fiorentini Stefano , Bøklepp Bjarne Rosvoll , Avdal Jørgen , Johansen Tonni Franke , Måsøy Svein-Erik 
Published: July 2023

AbstractEarly detection of gas influx in boreholes while drilling is of significant interest to drilling operators. Several studies suggest a good correlation between ultrasound backscatter/attenuation and gas volume fraction (GVF) in drilling muds, and thereby propose methods for quantification of GVF in boreholes. However, the aforementioned studies neglect the influence of bubble size, which can vary significantly over time. This paper proposes a model to combine existing theories for ultrasound backscatter from bubbles depending on their size, viz. Rayleigh scattering for smaller bubbles, and specular reflection for larger bubbles. The proposed model is demonstrated using simulations and experiments, where the ultrasound backscatter is evaluated from bubble clouds of varying bubbles sizes. It is shown that the size and number of bubbles strongly influence ultrasound backscatter intensity, and it is correlated to GVF only when the bubble size distribution is known. The information on bubble size is difficult to obtain in field conditions causing this correlation to break down. Consequently, it is difficult to reliably apply methods based on ultrasound backscatter, and by extension its attenuation, for the quantification of GVF during influx events in a borehole. These methods can however be applied as highly sensitive detectors of gas bubbles for GVF $$\ge$$
≥
1 vol$$\%$$
%
.
Identification and validation of fusidic acid and flufenamic acid as inhibitors of SARS-CoV-2 replication using DrugSolver CavitomiX
Authors: Hetmann M. , Langner C. , Durmaz V. , Cespugli M. , Köchl K. , Krassnigg A. , Blaschitz K. , Groiss S. , Loibner M. , Ruau D. , Zatloukal K. , Gruber K. , Steinkellner G. , Gruber C. C. 
Published: July 2023

AbstractIn this work, we present DrugSolver CavitomiX, a novel computational pipeline for drug repurposing and identifying ligands and inhibitors of target enzymes. The pipeline is based on cavity point clouds representing physico-chemical properties of the cavity induced solely by the protein. To test the pipeline’s ability to identify inhibitors, we chose enzymes essential for SARS-CoV-2 replication as a test system. The active-site cavities of the viral enzymes main protease (Mpro) and papain-like protease (Plpro), as well as of the human transmembrane serine protease 2 (TMPRSS2), were selected as target cavities. Using active-site point-cloud comparisons, it was possible to identify two compounds—flufenamic acid and fusidic acid—which show strong inhibition of viral replication. The complexes from which fusidic acid and flufenamic acid were derived would not have been identified using classical sequence- and structure-based methods as they show very little structural (TM-score: 0.1 and 0.09, respectively) and very low sequence (~ 5%) identity to Mpro and TMPRSS2, respectively. Furthermore, a cavity-based off-target screening was performed using acetylcholinesterase (AChE) as an example. Using cavity comparisons, the human carboxylesterase was successfully identified, which is a described off-target for AChE inhibitors.
Single-cell chromatin accessibility profiling of acute myeloid leukemia reveals heterogeneous lineage composition upon therapy-resistance
Authors: Fan Huihui , Wang Feng , Zeng Andy , Murison Alex , Tomczak Katarzyna , Hao Dapeng , Jelloul Fatima Zahra , Wang Bofei , Barrodia Praveen , Liang Shaoheng , Chen Ken , Wang Linghua , Zhao Zhongming , Rai Kunal , Jain Abhinav K. , Dick John , Daver Naval , Futreal Andy , Abbas Hussein A. 
Published: July 2023

AbstractAcute myeloid leukemia (AML) is a heterogeneous disease characterized by high rate of therapy resistance. Since the cell of origin can impact response to therapy, it is crucial to understand the lineage composition of AML cells at time of therapy resistance. Here we leverage single-cell chromatin accessibility profiling of 22 AML bone marrow aspirates from eight patients at time of therapy resistance and following subsequent therapy to characterize their lineage landscape. Our findings reveal a complex lineage architecture of therapy-resistant AML cells that are primed for stem and progenitor lineages and spanning quiescent, activated and late stem cell/progenitor states. Remarkably, therapy-resistant AML cells are also composed of cells primed for differentiated myeloid, erythroid and even lymphoid lineages. The heterogeneous lineage composition persists following subsequent therapy, with early progenitor-driven features marking unfavorable prognosis in The Cancer Genome Atlas AML cohort. Pseudotime analysis further confirms the vast degree of heterogeneity driven by the dynamic changes in chromatin accessibility. Our findings suggest that therapy-resistant AML cells are characterized not only by stem and progenitor states, but also by a continuum of differentiated cellular lineages. The heterogeneity in lineages likely contributes to their therapy resistance by harboring different degrees of lineage-specific susceptibilities to therapy.
Upcycling rice yield trial data using a weather-driven crop growth model
Authors: Shimono Hiroyuki , Abe Akira , Kim Chyon Hae , Sato Chikashi , Iwata Hiroyoshi 
Published: July 2023

AbstractEfficient plant breeding plays a significant role in increasing crop yields and attaining food security under climate change. Screening new cultivars through yield trials in multi-environments has improved crop yields, but the accumulated data from these trials has not been effectively upcycled. We propose a simple method that quantifies cultivar-specific productivity characteristics using two regression coefficients: yield-ability (β) and yield-plasticity (α). The recorded yields of each cultivar are expressed as a unique linear regression in response to the theoretical potential yield (Yp) calculated by a weather-driven crop growth model, called as the “YpCGM method”. We apply this to 72510 independent datasets from yield trials of rice that used 237 cultivars measured at 110 locations in Japan over 38 years. The YpCGM method can upcycle accumulated yield data for use in genetic-gain analysis and genome-wide-association studies to guide future breeding programs for developing new cultivars suitable for the world’s changing climate.
Repurposing Drugs: An Empowering Approach to Drug Discovery and Development
Authors: Kumar Sahil , Roy Vandana 
Published: July 2023

AbstractDrug discovery and development is a time-consuming and costly procedure that necessitates a substantial effort. Drug repurposing has been suggested as a method for developing medicines that takes less time than developing brand new medications and will be less expensive. Also known as drug repositioning or re-profiling, this strategy has been in use from the time of serendipitous drug discoveries to the modern computer aided drug designing and use of computational chemistry. In the light of the COVID-19 pandemic too, drug repurposing emerged as a ray of hope in the dearth of available medicines. Data availability by electronic recording, libraries, and improvements in computational techniques offer a vital substrate for systemic evaluation of repurposing candidates. In the not-too-distant future, it could be possible to create a global research archive for us to access, thus accelerating the process of drug development and repurposing. This review aims to present the evolution, benefits and drawbacks including current approaches, key players and the legal and regulatory hurdles in the field of drug repurposing. The vast quantities of available data secured in multiple drug databases, assisting in drug repurposing is also discussed.
C. Difficile Infection within 6 Months before TKA Is Associated with Increased Short-Term Complications
Authors: Sax Oliver C. , Douglas Scott J. , Chen Zhongming , Bains Sandeep S. , Remily Ethan A. , Delanois Ronald E. 
Published: July 2023

AbstractA history of Clostridium difficile infection (CDI) before total knee arthroplasty (TKA) may be a marker for poor patient health and could be used to identify patients with higher risks for complications after TKA. We compared the frequency of 90-day postoperative CDI, complications, readmissions, and associated risk factors in (1) patients experiencing CDIs more than 6 months before TKA, (2) patients experiencing CDIs in the 6 months before TKA, and (3) patients without a history of CDI. We identified patients who underwent primary TKAs from 2010 to 2019 and had a history of CDI before TKA (n = 7,195) using a national, all-payer database. Patients were stratified into two groups: those with CDIs > 6 months before TKA (n = 6,027) and those experiencing CDIs ≤ 6 months before TKA (n = 1,168). These patients were compared with the remaining 1.4 million patients without a history of CDI before TKA. Chi-square and unadjusted odds ratios (ORs) with 95% confidence intervals (CI) were used to compare complication frequencies. Prior CDI during either timespan was associated with higher unadjusted odds for postoperative CDI (CDI > 6 months before TKA: OR 8.03 [95% CI 6.68–9.63]; p < 0.001; CDI ≤ 6 months before TKA: OR 59.05 [95% CI 49.66–70.21]; p < 0.001). Patients with a history of CDI before TKA were associated with higher unadjusted odds for 90-day complications and readmission compared with patients without a history of CDI before TKA. Other comorbidities and health metrics were not found to be associated with postoperative CDI (i.e., age, obesity, smoking, antibiotic use, etc.).
Conclusion CDI before TKA was associated with higher odds of postoperative CDI compared with patients without a history of CDI. CDI ≤ 6 months before TKA was associated with the highest odds for postoperative complications and readmissions. Providers should consider delaying TKA after CDI, if possible, to allow for patient recovery and eradication of infection.
2.7 Cobalt-Catalyzed Cross-Coupling Reactions
Authors: Schiltz P. , Gao M. , Gosmini C. 
Published: July 2023

AbstractTransition-metal-catalyzed cross-coupling reactions have been an essential strategy for the construction of C—C bonds, including in the syntheses of pharmaceuticals and natural products, since the pioneering work of Heck, Negishi, and Suzuki, among others. Of the widely applied catalysts based on group 8–10 metals, economical cobalt salts have been shown to be advantageous as an alternative to other commonly used expensive and/or toxic catalysts. In this review, cobalt-catalyzed cross-coupling reactions of organometallic reagents, such as organomagnesium or organozinc derivatives, to achieve the formation of C—C bonds, are summarized. Furthermore, various methods for the cobalt-catalyzed reductive cross coupling of C—X/C—O electrophiles have also been reported for selective C—C bond formation, and these are also discussed.