bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calcium-binding protein S100P is a new target gene of MACC1, drives colorectal cancer metastasis and serves as a prognostic biomarker
Authors: Schmid Felicitas , Dahlmann Mathias , Röhrich Hanna , Kobelt Dennis , Hoffmann Jens , Burock Susen , Walther Wolfgang , Stein Ulrike 
Published: May 2022

Abstract
Background
The metastasis inducing gene MACC1 is a prognostic and predictive biomarker for metastasis in several cancers. Its mechanism of inducing metastasis includes the transcriptional control of other cancer-related target genes. Here, we investigate the interplay with the metastasis driver S100P in CRC progression.

Methods
MACC1-dependent S100P expression was analysed by qRT-PCR. The binding of MACC1 to the S100P promoter was determined by ChIP. Alterations in cell proliferation and motility were determined by functional in vitro assays. In vivo metastasis after intrasplenic transplantation was assessed by bioluminescence imaging and evaluation of tumour growth and liver metastasis. The prognostic value of S100P was determined in CRC patients by ROC-based Kaplan–Meier analyses.

Results
Expression of S100P and MACC1 correlated positively in CRC cells and colorectal tumours. MACC1 was found binding to the S100P promoter and induces its expression. The overexpression of S100P increased proliferation, migration and invasion in vitro and significantly induced liver metastasis in vivo. S100P expression was significantly elevated in metachronously metastasising CRC and was associated with shorter metastasis-free survival.

Conclusions
We identified S100P as a transcriptional target gene of MACC1. Expression of S100P increases the metastatic potential of CRC cells in vitro and in vivo, and serves as a prognostic biomarker for metastasis-free survival of CRC patients, emphasising novel therapeutic interventions targeting S100P.
Regulatory T cells induce a suppressive immune milieu and promote lymph node metastasis in intrahepatic cholangiocarcinoma
Authors: Konishi Daisuke , Umeda Yuzo , Yoshida Kazuhiro , Shigeyasu Kunitoshi , Yano Shuya , Toji Tomohiro , Takeda Sho , Yoshida Ryuichi , Yasui Kazuya , Fuji Tomokazu , Matsumoto Kazuyuki , Kishimoto Hiroyuki , Michiue Hiroyuki , Teraishi Fuminori , Kato Hironari , Tazawa Hiroshi , Yanai Hiroyuki , Yagi Takahito , Goel Ajay , Fujiwara Toshiyoshi 
Published: May 2022

Abstract
Background
Emerging evidence indicates that immunogenicity plays an important role in intrahepatic cholangiocarcinoma (ICC). Herein, we systematically evaluated the clinical relevance of immunogenicity in ICC.

Methods
Highly immunogenic ICCs identified in the public dataset and the Cancer Immunome Atlas (TCIA) were assessed to determine the prognostic impact of immunogenicity in ICC and key components after curative resection. We also investigated the clinical relevance of the immune milieu in ICC.

Results
Using the Gene Expression Omnibus dataset 89749 and TCIA, we identified CD8+/forkhead box P3 (FoxP3)+ tumour-infiltrating lymphocytes (TILs), T-cell immunoglobulin and mucin domain 3 (TIM-3) and human leukocyte antigen-A (HLA-A) in highly immunogenic ICCs. Immunohistochemical analysis of the in-house cohort showed that intratumoral FoxP3+ TILs correlated with CD8+ TILs (P = 0.045, Fisher’s exact test) and that high FoxP3+/CD8+ ratio (FCR) was an important marker for poor survival (P < 0.001, log-rank test). Furthermore, the FCR was higher in tumour-free lymph nodes in ICCs with lymph node metastases than in those without lymph node metastases (P = 0.003, Mann–Whitney U test).

Conclusions
FCR should be considered an important biomarker that represents the immune environment of ICC based on its potentially important role in tumour progression, especially lymph node metastasis.
Dedifferentiation-mediated stem cell niche maintenance in early-stage ductal carcinoma in situ progression: insights from a multiscale modeling study
Authors: Butner Joseph D. , Dogra Prashant , Chung Caroline , Ruiz-Ramírez Javier , Nizzero Sara , Plodinec Marija , Li Xiaoxian , Pan Ping-Ying , Chen Shu-hsia , Cristini Vittorio , Ozpolat Bulent , Calin George A. , Wang Zhihui 
Published: May 2022

AbstractWe present a multiscale agent-based model of ductal carcinoma in situ (DCIS) to study how key phenotypic and signaling pathways are involved in the early stages of disease progression. The model includes a phenotypic hierarchy, and key endocrine and paracrine signaling pathways, and simulates cancer ductal growth in a 3D lattice-free domain. In particular, by considering stochastic cell dedifferentiation plasticity, the model allows for study of how dedifferentiation to a more stem-like phenotype plays key roles in the maintenance of cancer stem cell populations and disease progression. Through extensive parameter perturbation studies, we have quantified and ranked how DCIS is sensitive to perturbations in several key mechanisms that are instrumental to early disease development. Our studies reveal that long-term maintenance of multipotent stem-like cell niches within the tumor are dependent on cell dedifferentiation plasticity, and that disease progression will become arrested due to dilution of the multipotent stem-like population in the absence of dedifferentiation. We have identified dedifferentiation rates necessary to maintain biologically relevant multipotent cell populations, and also explored quantitative relationships between dedifferentiation rates and disease progression rates, which may potentially help to optimize the efficacy of emerging anti-cancer stem cell therapeutics.
Antibiotic pretreatment attenuates liver ischemia–reperfusion injury by Farnesoid X receptor activation
Authors: Liu Hanyi , Wang Jinglin , Ding Yitao , Shi Xiaolei , Ren Haozhen 
Published: May 2022

AbstractProphylactic antibiotics (Abx) are used before liver surgery, and the influence of antibiotic pretreatment on hepatic ischemia–reperfusion injury (IRI) remains unclear. Hence, we explored the impact of Abx pretreatment on hepatic IRI in the present work. The gut microbiota has an essential role in hepatic bile acid (BA) metabolism, and we assumed that depletion of the gut microbiota could affect the composition of hepatic BAs and affect liver IRI. The IRI model demonstrated that Abx pretreatment attenuated liver IRI by alleviating cell apoptosis, reducing the inflammatory response, and decreasing the recruitment of CCR2+ monocytes. Mechanistically, Abx pretreatment reshaped the gut microbiota, especially decreasing the relative abundance of Firmicutes and increasing the relative abundance of Clostridium, which were related to the transformation of BAs and were consistent with the altered bile acid species (unconjugated BAs, especially UDCA). These altered BAs are known FXR agonists and lead to the activation of the farnesoid X receptor (FXR), which can directly bind to the FXR response element (FXRE) harbored in the TLR4 promoter and further suppress downstream mitogen-activated protein kinase (MAPK) and nuclear kappa B (NF-κB) pathways. Meanwhile, the CCL2–CCR2 axis was also involved in the process of FXR activation, as we confirmed both in vivo and in vitro. Importantly, we proved the importance of FXR in mice and clinical occlusion samples, which were inversely correlated with liver injury. Taken together, our study identified that Abx pretreatment before liver resection was a beneficial event by activating FXR, which might become a potential therapeutic target in treating liver injury.
A novel spiral infinity reactor for continuous hydrothermal synthesis of nanoparticles
Authors: Pukkella Arjun Kumar , Nadimpalli Naga Ravikumar Varma , Runkana Venkataramana , Subramanian Sivakumar 
Published: May 2022

AbstractHydrothermal synthesis is an attractive route to make nanoparticles utilizing inexpensive precursors under moderate process conditions. Though it provides flexibility and robustness in controlling particle characteristics, process scale-up for continuous production is a major challenge. A novel ‘infinity-’ shaped spiral continuous flow reactor is proposed here, to exploit the large density difference between the precursor solution and supercritical water to provide rapid mixing, leading to uniform conditions for reaction kinetics and particle growth. Hydrothermal synthesis is simulated by coupling computational fluid dynamics with population balance modeling and appropriate reaction kinetics. Simulations indicate three distinct regimes of declining, recovering, and stable flow fields. These regimes are strongly dependent on the flow ratio between the precursor solution and supercritical water. The infinity reactor provides two distinct reaction environments: initial turns of the spiral which serve as a mixed flow reactor facilitating rapid mixing and uniform reaction, followed by a plug flow reactor stabilizing the particle growth. It produces particles with a relatively small mean diameter and a narrow size distribution in comparison to the conventional batch stirred tank reactor and the T-mixer.
Patterns of alcohol consumption in Brazilian adults
Authors: Plens Juliana A. , Valente Juliana Y. , Mari Jair J. , Ferrari Gerson , Sanchez Zila M. , Rezende Leandro F. M. 
Published: May 2022

AbstractIn this study, we aimed to describe the patterns of alcohol consumption in Brazilian adults by sociodemographic characteristics and states according to sex. Cross-sectional study including 87,555 adults from the 2019 Brazilian National Health Survey who responded to a questionnaire on alcohol consumption and were classified as non-drinkers (0 g/day), light (1–12.5 g/day), moderate (12.6–49.9 g/day), and heavy drinkers (≥ 50 g/day). Of the Brazilian adults, 73.5% were non-drinkers. Among the drinkers, 14.8% were light drinkers. 82.6% of heavy drinkers were men. White participants drank more than non-white participants, except black women who were 38% more likely to be moderate drinkers than white women (ROR 1.38, 95% CI 1.09 to 1.76). Unmarried were more likely to be drinkers. Women over 55 and men over 65 years old were less likely to be drinkers. Compared to participants with none or incomplete primary education, both men and women with higher educational attainment were more likely to be light and moderate drinkers. The largest consumption of alcohol was found in Sergipe and Mato Grosso for men, and Mato Grosso do Sul and Bahia for women. Our findings may be useful to inform policies for reducing alcohol consumption in Brazil.
Cross-sectional metabolic subgroups and 10-year follow-up of cardiometabolic multimorbidity in the UK Biobank
Authors: Mulugeta Anwar , Hyppönen Elina , Ala-Korpela Mika , Mäkinen Ville-Petteri 
Published: May 2022

AbstractWe assigned 329,908 UK Biobank participants into six subgroups based on a self-organizing map of 51 biochemical measures (blinded for clinical outcomes). The subgroup with the most favorable metabolic traits was chosen as the reference. Hazard ratios (HR) for incident disease were modeled by Cox regression. Enrichment ratios (ER) of incident multi-morbidity versus randomly expected co-occurrence were evaluated by permutation tests; ER is like HR but captures co-occurrence rather than event frequency. The subgroup with high urinary excretion without kidney stress (HR = 1.24) and the subgroup with the highest apolipoprotein B and blood pressure (HR = 1.52) were associated with ischemic heart disease (IHD). The subgroup with kidney stress, high adiposity and inflammation was associated with IHD (HR = 2.11), cancer (HR = 1.29), dementia (HR = 1.70) and mortality (HR = 2.12). The subgroup with high liver enzymes and triglycerides was at risk of diabetes (HR = 15.6). Multimorbidity was enriched in metabolically favorable subgroups (3.4 ≤ ER ≤ 4.0) despite lower disease burden overall; the relative risk of co-occurring disease was higher in the absence of obvious metabolic dysfunction. These results provide synergistic insight into metabolic health and its associations with cardiovascular disease in a large population sample.
Quantum blockchain based on asymmetric quantum encryption and a stake vote consensus algorithm
Authors: Wang Wusheng , Yu Yang , Du Lingjie 
Published: May 2022

AbstractAs emerging next-generation information technologies, blockchains have unique advantages in information transparency and transaction security. They have attracted great attentions in social and financial fields. However, the rapid development of quantum computation and the impending realization of quantum supremacy have had significant impacts on the advantages of traditional blockchain based on traditional cryptography. Here, we propose a blockchain algorithm based on asymmetric quantum encryption and a stake vote consensus algorithm. The algorithm combines a consensus algorithm based on the delegated proof of stake with node behaviour and Borda count (DPoSB) and quantum digital signature technology based on quantum state computational distinguishability with a fully flipped permutation ($${\text{QSC}}{\text{D}}_{\text{ff}}$$

QSCD
ff

) problem. DPoSB is used to generate blocks by voting, while the quantum signature applies quantum one-way functions to guarantee the security of transactions. The analysis shows that this combination offers better protection than other existing quantum-resistant blockchains. The combination can effectively resist the threat of quantum computation on blockchain technology and provide a new platform to ensure the security of blockchain.
Refractive astigmatism in phaco-canaloplasty vs phaco-non-penetrating deep sclerectomy
Authors: Byszewska Anna , Rudowicz Jacek , Lewczuk Katarzyna , Jabłońska Joanna , Rękas Marek 
Published: May 2022

AbstractThis study aimed to assess refractive astigmatism, in phaco-canaloplasty (PC) vs phaco-non-penetrating deep sclerectomy (PDS) in a randomized, prospective study within 24 months. Patients were randomized pre-operatively, 37 underwent PC and 38 PDS. The following data was collected: BCVA, IOP, number of antiglaucoma medications, refraction with autokeratorefractometry. The assessment of astigmatism was simple arithmetic and vector analysis (calculations included cylinder with axis in form of centroids) and included double angle plots and cumulative refractive astigmatism graphs. Pre-operative mean BCVA in PC was 0.40 ± 0.43 and was comparable to BCVA in PDS 0.30 ± 0.32logMAR (P = 0.314). In the sixth month follow-up, mean BCVA showed no difference (P = 0.708) and was 0.07 ± 0.13 and 0.05 ± 0.11, respectively. However, 2 years after the intervention mean BCVA was better in PC 0.05 ± 0.12 than in PDS 0.12 ± 0.23 and it was statistically significant (P = 0.039). Mean astigmatism in PC at baseline was 1.13 ± 0.73Dcyl, at 6 months it was 1.09 ± 0.61 and at 2 years 1.17 ± 0.51. In PDS at baseline 1.35 ± 0.91 at 6 months 1.24 ± 0.86 and at 2 years 1.24 ± 0.82. There were no differences between the groups in mean astigmatism throughout the study. Centroids (mean of a cylinder with axis) in PC were pre-operatively 0.79D@172˚ ± 1.10Dcyl, at 6 months 0.75D@166˚ ± 1.01 and at 24-months 0.64D@164˚ ± 1.11 and in PDS pre-operatively 0.28D@10˚ ± 1.63D at 6 months 0.26D@11˚ ± 1.5 and at 24-months 0.47D@20˚ ± 1.43. The direction of mean astigmatism was against the rule in all analyzed time points. The mean baseline IOP in PC was 19.4 ± 5.8 mmHg and 19.7 ± 5.4 mmHg in PDS(P = 0.639). From the 6-month IOP was lower in PC, at 24-months it was 13.8 ± 3.3 mmHg in PC and 15.1 ± 2.9 mmHg in PDS(P = 0.048). In both groups preoperatively patients used median(Me) of three antiglaucoma medications(P = 0.197), at 24-months in PC mean 0.5 ± 0.9 Me = 0.0 and 1.1 ± 1.2 Me = 1.0 in PDS(P = 0.058). Both surgeries in mid-term observation are safe and effective. They do not generate vision-threatening astigmatism and do not even change the preoperative direction of mean astigmatism. Refractive astigmatism is stable throughout the observation.
Stress-induced despair behavior develops independently of the Ahr-RORγt axis in CD4 + cells
Authors: Rivet-Noor Courtney R. , Merchak Andrea R. , Li Sihan , Beiter Rebecca M. , Lee Sangwoo , Thomas Jalon Aaron , Fernández-Castañeda Anthony , Shin Jung-Bum , Gaultier Alban 
Published: May 2022

AbstractCurrent treatments for major depressive disorder are limited to neuropharmacological approaches and are ineffective for large numbers of patients. Recently, alternative means have been explored to understand the etiology of depression. Specifically, changes in the microbiome and immune system have been observed in both clinical settings and in mouse models. As such, microbial supplements and probiotics have become a target for potential therapeutics. A current hypothesis for the mechanism of action of these supplements is via the aryl hydrocarbon receptor’s (Ahr) modulation of the T helper 17 cell (Th17) and T regulatory cell axis. As inflammatory RORγt + CD4 + Th17 T cells and their primary cytokine IL-17 have been implicated in the development of stress-induced depression, the connection between stress, the Ahr, Th17s and depression remains critical to understanding mood disorders. Here, we utilize genetic knockouts to examine the role of the microbial sensor Ahr in the development of stressinduced despair behavior. We observe an Ahr-independent increase in gut-associated Th17s in stressed mice, indicating that the Ahr is not responsible for this communication. Further, we utilized a CD4-specific RAR Related Orphan Receptor C (Rorc) knockout line to disrupt the production of Th17s. Mice lacking Rorc-produced IL-17 did not show any differences in behavior before or after stress when compared to controls. Finally, we utilize an unsupervised machine learning system to examine minute differences in behavior that could not be observed by traditional behavioral assays. Our data demonstrate that neither CD4 specific Ahr nor Rorc are necessary for the development of stress-induced anxiety- or depressive-like behaviors. These data suggest that research approaches should focus on other sources or sites of IL-17 production in stress-induced depression.
Comparative analysis of mesenchymal stem cells cultivated in serum free media
Authors: Lee Joo Youn , Kang Min Hee , Jang Ji Eun , Lee Jeong Eon , Yang Yuyeong , Choi Ji Yong , Kang Hong Seok , Lee Uiil , Choung Ji Woong , Jung Hyeryeon , Yoon Young-Chan , Jung Kyung Hee , Hong Soon–Sun , Yi Eugene C. , Park Sang Gyu 
Published: May 2022

AbstractStem cells are attractive candidates for the regeneration of tissue and organ. Mesenchymal stem cells (MSCs) have been extensively investigated for their potential applications in regenerative medicine and cell therapy. For developing effective stem cell therapy, the mass production of consistent quality cells is required. The cell culture medium is the most critical aspect of the mass production of qualified stem cells. Classically, fetal bovine serum (FBS) has been used as a culture supplement for MSCs. Due to the undefined and heterologous composition of animal origin components in FBS, efforts to replace animal-derived components with non-animal-derived substances led to safe serum free media (SFM). Adipose derived mesenchymal stem cells (ADSCs) cultivated in SFM provided a more stable population doubling time (PDT) to later passage and more cells in a shorter time compared to FBS containing media. ADSCs cultivated in SFM had lower cellular senescence, lower immunogenicity, and higher genetic stability than ADSCs cultivated in FBS containing media. Differential expression analysis of mRNAs and proteins showed that the expression of genes related with apoptosis, immune response, and inflammatory response were significantly up-regulated in ADSCs cultivated in FBS containing media. ADSCs cultivated in SFM showed similar therapeutic efficacy in an acute pancreatitis mouse model to ADSCs cultivated in FBS containing media. Consideration of clinical trials, not only pre-clinical trial, suggests that cultivation of MSCs using SFM might offer more safe cell therapeutics as well as repeated administration due to low immunogenicity.
A longitudinal study of the impact of university student return to campus on the SARS-CoV-2 seroprevalence among the community members
Authors: Arnold Callum R. K. , Srinivasan Sreenidhi , Rodriguez Sophie , Rydzak Natalie , Herzog Catherine M. , Gontu Abhinay , Bharti Nita , Small Meg , Rogers Connie J. , Schade Margeaux M. , Kuchipudi Suresh V. , Kapur Vivek , Read Andrew F. , Ferrari Matthew J. 
Published: May 2022

AbstractReturning university students represent large-scale, transient demographic shifts and a potential source of transmission to adjacent communities during the COVID-19 pandemic. In this prospective longitudinal cohort study, we tested for IgG antibodies against SARS-CoV-2 in a non-random cohort of residents living in Centre County prior to the Fall 2020 term at the Pennsylvania State University and following the conclusion of the Fall 2020 term. We also report the seroprevalence in a non-random cohort of students collected at the end of the Fall 2020 term. Of 1313 community participants, 42 (3.2%) were positive for SARS-CoV-2 IgG antibodies at their first visit between 07 August and 02 October 2020. Of 684 student participants who returned to campus for fall instruction, 208 (30.4%) were positive for SARS-CoV-2 antibodies between 26 October and 21 December. 96 (7.3%) community participants returned a positive IgG antibody result by 19 February. Only contact with known SARS-CoV-2-positive individuals and attendance at small gatherings (20–50 individuals) were significant predictors of detecting IgG antibodies among returning students (aOR, 95% CI 3.1, 2.07–4.64; 1.52, 1.03–2.24; respectively). Despite high seroprevalence observed within the student population, seroprevalence in a longitudinal cohort of community residents was low and stable from before student arrival for the Fall 2020 term to after student departure. The study implies that heterogeneity in SARS-CoV-2 transmission can occur in geographically coincident populations.
Indocyanine green fluorescence image processing techniques for breast cancer macroscopic demarcation
Authors: Leiloglou Maria , Kedrzycki Martha S. , Chalau Vadzim , Chiarini Nicolas , Thiruchelvam Paul T. R. , Hadjiminas Dimitri J. , Hogben Katy R. , Rashid Faiza , Ramakrishnan Rathi , Darzi Ara W. , Leff Daniel R. , Elson Daniel S. 
Published: May 2022

AbstractRe-operation due to disease being inadvertently close to the resection margin is a major challenge in breast conserving surgery (BCS). Indocyanine green (ICG) fluorescence imaging could be used to visualize the tumor boundaries and help surgeons resect disease more efficiently. In this work, ICG fluorescence and color images were acquired with a custom-built camera system from 40 patients treated with BCS. Images were acquired from the tumor in-situ, surgical cavity post-excision, freshly excised tumor and histopathology tumour grossing. Fluorescence image intensity and texture were used as individual or combined predictors in both logistic regression (LR) and support vector machine models to predict the tumor extent. ICG fluorescence spectra in formalin-fixed histopathology grossing tumor were acquired and analyzed. Our results showed that ICG remains in the tissue after formalin fixation. Therefore, tissue imaging could be validated in freshly excised and in formalin-fixed grossing tumor. The trained LR model with combined fluorescence intensity (pixel values) and texture (slope of power spectral density curve) identified the tumor’s extent in the grossing images with pixel-level resolution and sensitivity, specificity of 0.75 ± 0.3, 0.89 ± 0.2.This model was applied on tumor in-situ and surgical cavity (post-excision) images to predict tumor presence.