bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct Stromal and Immune Features Collectively Contribute to Long-Term Survival in Pancreatic Cancer
Authors: Sadozai Hassan , Acharjee Animesh , Eppenberger-Castori Serenella , Gloor Beat , Gruber Thomas , Schenk Mirjam , Karamitopoulou Eva 
Published: February 2021

Background: The aggressive biology and treatment refractory nature of pancreatic ductal adenocarcinoma (PDAC) significantly limits long-term survival. Examining the tumor microenvironment (TME) of long-term survivors (LTS) of PDAC offers the potential of unveiling novel biological insights and therapeutic targets.Methods: We performed an integrated approach involving immunophenotyping, stromal scoring and histomorphological profiling of a cohort of 112 PDAC-cases, including 25 long-term survivors (LTSs, OS ≥ 60 months). Mutational frequencies were assessed using targeted next generation sequencing. Finally, we validated our findings in silico using an external cohort of microarray data from PDAC patients.Results: LTS cases exhibit a largely quiescent population of cancer-associated fibroblasts (CAFs). Immune profiling revealed key differences between LTS and NON-LTS cases in the intratumoral and stromal compartments. In both compartments, LTS cases exhibit a T cell inflamed profile with higher density of CD3+ T cells, CD4+ T cells, iNOS+ leukocytes and strikingly diminished numbers of CD68+ total macrophages, CD163+ (M2) macrophages and FOXP3+ Tregs. A large proportion of LTS cases exhibited tertiary lymphoid tissue (TLT) formation, which has been observed to be a positive prognostic marker in a number of tumor types. Using a Random-Forest variable selection approach, we identified the density of stromal iNOS+ cells and CD68+ cells as strong positive and negative prognostic variables, respectively. In an external cohort, computational cell-type deconvolution revealed a higher abundance of T cells, B lymphocytes and dendritic cells (DCs) in patients with long-term OS compared to short-term survivors. Thus, in silico profiling of long-term survivors in an external cohort, strongly corroborated the T cell-inflamed TME observed in our LTS group.Conclusions: Collectively, our findings highlight the prognostic importance of TME profiles in PDAC, underlining the crucial role of tumor associated macrophages (TAMs) and the potential interdependence between immunosuppressive TAMs and activated CAFs in pancreatic cancer. Additionally, our data has potential for precision medicine and patient stratification. Patients with a T cell inflamed TME might derive benefit from agonistic T cell antibodies (e.g., OX40 or CD137 agonists). Alternately, patients with activated CAFs and high infiltration of immunosuppressive TAMs are highly likely to exhibit therapeutic responses to macrophage targeted drugs (e.g., anti-CSF1R) and anti-CAF agents.
Texturing of Glass Surface using Micro-slurry Jet Machining Process
Authors: Yamaguchi Hajime , Sakata Koshi , Kasamura Keiji , Nakashima Yuta , Nakanishi Yoshitaka 
Published: February 2021

Existing methods for the microfabrication of convex structures on a glass surface require a complex and expensive masking process. In this study, a simple microfabrication method that combines the masking process using polyimide tapes and a micro-slurry jet (MSJ) process was developed. The masking process was performed using a CO₂ laser machine, and the surface of the processed glass was observed using a three-dimensional laser microscope. Although the geometric shape of the mask was not a perfect circle, convex structures with a diameter of approximately 1.0 mm and heights of more than 1.5 μm were formed on soda-lime glass surfaces. The deepest structures were observed to create convex structures with a height of 19 µm. The effects of the travel speed of the nozzle and number of repetitions of the MSJ process on the height of the convex structures on the glass surface were also investigated. It was found that the masking process combining polyimide tapes and the MSJ process could form high-convexity structures on the glass surface. The proposed method is expected to enable the fabrication of devices with various functional properties for materials that cannot be processed using existing methods.
The Effects of 0.01% Atropine on Adult Myopes’ Contrast Sensitivity
Authors: Cheng Ziyun , Mei Jianhui , Cao Suqi , Zhang Ran , Zhou Jiawei , Wang Yuwen 
Published: February 2021

PurposeAtropine at a low concentration is considered a safe and effective treatment to mitigate myopia progression. However, the potential unwanted side effects of administering atropine at a low dose on visual functions other than best corrected visual acuity has not been investigated. In this study, we investigate the short-term (12,16, and 20 h) and long-term (1, 2, and 4 weeks) effects of 0.01% atropine (i.e., 0.1 mg/ml) on contrast sensitivity (CS) in patients with myopia.MethodsThirty adults (23.33 ± 2.93 years old) with myopia between -1.00 and -6.00 diopters (D), astigmatism of -1.50 D or less, and anisometropia of 1.00 D or less, participated in this prospective, masked, placebo-controlled, randomized study. The participants were randomly assigned to receive 0.01% atropine or polyvinyl alcohol eye drops once nightly to both eyes for four weeks. CS was measured binocularly at baseline and 12, 16, 20 h, 1, 2, and 4 weeks after the first use of the eye drops.ResultsThere was no statistically significant differences of CS found between atropine and placebo-controlled groups in both short-term and long-term. There was no statistically significant interaction effect found between the time and group.ConclusionWe demonstrated no significant deleterious effect of 0.01% atropine on adult myopes’ CS.
Endothelial Regulation by Exogenous Annexin A1 in Inflammatory Response and BBB Integrity Following Traumatic Brain Injury
Authors: Liu Han , He Junchi , Wu Yue , Du Yang , Jiang Yinghua , Chen Chengzhi , Yu Zhanyang , Zhong Jianjun , Wang Zhigang , Cheng Chongjie , Sun Xiaochuan , Huang Zhijian 
Published: February 2021

Background and TargetFollowing brain trauma, blood–brain barrier (BBB) disruption and inflammatory response are critical pathological steps contributing to secondary injury, leading to high mortality and morbidity. Both pathologies are closely associated with endothelial remodeling. In the present study, we concentrated on annexin A1 (ANXA1) as a novel regulator of endothelial function after traumatic brain injury.MethodsAfter establishing controlled cortical impact (CCI) model in male mice, human recombinant ANXA1 (rANXA1) was administered intravenously, followed by assessments of BBB integrity, brain edema, inflammatory response, and neurological deficits.ResultAnimals treated with rANXA1 (1 μg/kg) at 1 h after CCI exhibited optimal BBB protection including alleviated BBB disruption and brain edema, as well as endothelial junction proteins loss. The infiltrated neutrophils and inflammatory cytokines were suppressed by rANXA1, consistent with decreased adhesive and transmigrating molecules from isolated microvessels. Moreover, rANXA1 attenuated the neurological deficits induced by CCI. We further found that the Ras homolog gene family member A (RhoA) inhibition has similar effect as rANXA1 in ameliorating brain injuries after CCI, whereas rANXA1 suppressed CCI-induced RhoA activation.ConclusionOur findings suggest that the endothelial remodeling by exogenous rANXA1 corrects BBB disruption and inflammatory response through RhoA inhibition, hence improving functional outcomes in CCI mice.
Decoding Spatial Versus Non-spatial Processing in Auditory Working Memory
Authors: Erhart Mira , Czoschke Stefan , Fischer Cora , Bledowski Christoph , Kaiser Jochen 
Published: February 2021

ObjectiveResearch on visual working memory has shown that individual stimulus features are processed in both specialized sensory regions and higher cortical areas. Much less evidence exists for auditory working memory. Here, a main distinction has been proposed between the processing of spatial and non-spatial sound features. Our aim was to examine feature-specific activation patterns in auditory working memory.MethodsWe collected fMRI data while 28 healthy adults performed an auditory delayed match-to-sample task. Stimuli were abstract sounds characterized by both spatial and non-spatial information, i.e., interaural time delay and central frequency, respectively. In separate recording blocks, subjects had to memorize either the spatial or non-spatial feature, which had to be compared with a probe sound presented after a short delay. We performed both univariate and multivariate comparisons between spatial and non-spatial task blocks.ResultsProcessing of spatial sound features elicited a higher activity in a small cluster in the superior parietal lobe than did sound pattern processing, whereas there was no significant activation difference for the opposite contrast. The multivariate analysis was applied using a whole-brain searchlight approach to identify feature-selective processing. The task-relevant auditory feature could be decoded from multiple brain regions including the auditory cortex, posterior temporal cortex, middle occipital gyrus, and extended parietal and frontal regions.ConclusionIn summary, the lack of large univariate activation differences between spatial and non-spatial processing could be attributable to the identical stimulation in both tasks. In contrast, the whole-brain multivariate analysis identified feature-specific activation patterns in widespread cortical regions. This suggests that areas beyond the auditory dorsal and ventral streams contribute to working memory processing of auditory stimulus features.
Breastfeeding Rate, Food Supplementation, Dietary Diversity Among Children Aged 6–59 Months, and Associated Factors in Papua New Guinea
Authors: Pham Bang Nguyen , Silas Vinson D. , Okely Anthony D. , Pomat William 
Published: February 2021

Background: Along the socioeconomic changes in the past decades, Papua New Guinea (PNG) has undergone significant food transition. Little is known about the influence of household and maternal socioeconomic demographic factors on dietary intake and diversity among children under 5 years of age (CU5).Objective: This study aimed to examine breastfeeding rate, food supplementation, dietary intake, and diversity among children aged 6–59 months and to identify associations with household and maternal socioeconomic demographic factors in PNG.Method: Data from 2,943 children were extracted from the Comprehensive Health and Epidemiological Surveillance System database, operated by the PNG Institute of Medical Research and used to estimate breastfeeding rate, food supplementation, and dietary intake of CU5 in a typical week. Dietary diversity score (DDS) was used as a proxy indicator to measure nutrient adequacy. Associations of DDS with household and maternal socioeconomic and demographic factors were examined using multivariate logistic regression analysis.Result: The breastfeeding rate among children aged 6–8 months was 85% (70% in urban and 90% in rural sectors), and 50% of children of this age group were fed with supplementary foods. Twenty percent of children aged 6–23 months were currently breastfed and received solid, semisolid, and soft foods three times or more per day. Forty-eight percent of children aged 6–59 months had a total DDS below the average level (23 scores). Place of residence, mother's education, and household wealth were associated with dietary diversity among studied children. Children in urban areas are 10% more likely to have a lower level of total DDS than those in rural areas (OR: 1.11 [0.79–1.56]; p-value: 0.5). Children whose mothers had a primary education level were 1.6-fold more likely to have a lower level of total DDS than children whose mothers had vocational training or college education (OR: 1.63 [0.68–3.92]; p-value: 0.28). Children from the poorest households were 1.2-fold more likely to have a lower DDS than those from the richest households (OR: 1.22 [0.79–1.87]; p-value: 0.37).Discussion: A range of factors has been identified, contributing to the eating behaviors among CU5 in PNG, in which mother's education and household wealth are among the most important determinants of childhood dietary diversity as they have a direct effect on accessibility to and affordability of a variety of foods at the household level.Conclusion: Evidence-based integrated and comprehensive approaches are needed to improve women education and household wealth, contributing to the improvement of food diversity among young children in PNG.
Capsule Size Alters the Timing of Metabolic Alkalosis Following Sodium Bicarbonate Supplementation
Authors: Middlebrook India , Peacock Joe , Tinnion Daniel J. , Leach Nicholas K. , Hilton Nathan P. , Saunders Bryan , Sparks S. Andy , Mc Naughton Lars R. 
Published: February 2021

Introduction: Sodium bicarbonate (NaHCO3) is a well-established nutritional ergogenic aid that is typically ingested as a beverage or consumed in gelatine capsules. While capsules may delay the release of NaHCO3 and reduce gastrointestinal (GI) side effects compared with a beverage, it is currently unclear whether the capsule size may influence acid–base responses and GI symptoms following supplementation.Aim: This study aims to determine the effects of NaHCO3 supplementation, administered in capsules of different sizes, on acid–base responses, GI symptoms, and palatability.Methods: Ten healthy male subjects (mean ± SD: age 20 ± 2 years; height 1.80 ± 0.09 m; weight 78.0 ± 11.9 kg) underwent three testing sessions whereby 0.3 g NaHCO3/kg of body mass was consumed in either small (size 3), medium (size 0), or large (size 000) capsules. Capillary blood samples were procured pre-ingestion and every 10 min post-ingestion for 180 min. Blood samples were analyzed using a radiometer (Radiometer ABL800, Denmark) to determine blood bicarbonate concentration ([HCO3-]) and potential hydrogen (pH). GI symptoms were measured using a questionnaire at the same timepoints, whereas palatability was recorded pre-consumption.Results: Capsule size had a significant effect on lag time (the time [HCO3-] changed, Tlag) and the timing of peak blood [HCO3-] (Tmax). Bicarbonate Tlag was significantly higher in the large-sized (28 ± 4 min) compared with the small-sized (13 ± 2 min) capsules (P = 0.009). Similarly, Tmax was significantly lower in the small capsule (94 ± 24 min) compared with both the medium-sized (141 ± 27 min; P &lt; 0.001) and the large-sized (121 ± 29 min; P &lt; 0.001) capsules. The GI symptom scores were similar for small-sized (3 ± 3 AU), medium-sized (5 ± 3 AU), and large-sized (3 ± 3 AU) capsules, with no significant difference between symptom scores (F = 1.3, P = 0.310). Similarly, capsule size had no effect on palatability (F = 0.8, P = 0.409), with similar scores between different capsule sizes.Conclusion: Small capsule sizes led to quicker Tlag and Tmax of blood [HCO3-] concentration compared to medium and large capsules, suggesting that individuals could supplement NaHCO3 in smaller capsules if they aim to increase extracellular buffering capacity more quickly.
Multiple Myeloma Cells Alter Adipogenesis, Increase Senescence-Related and Inflammatory Gene Transcript Expression, and Alter Metabolism in Preadipocytes
Authors: Fairfield Heather , Costa Samantha , Falank Carolyne , Farrell Mariah , Murphy Connor S. , D’Amico Anastasia , Driscoll Heather , Reagan Michaela R. 
Published: February 2021

Within the bone marrow microenvironment, mesenchymal stromal cells (MSCs) are an essential precursor to bone marrow adipocytes and osteoblasts. The balance between this progenitor pool and mature cells (adipocytes and osteoblasts) is often skewed by disease and aging. In multiple myeloma (MM), a cancer of the plasma cell that predominantly grows within the bone marrow, as well as other cancers, MSCs, preadipocytes, and adipocytes have been shown to directly support tumor cell survival and proliferation. Increasing evidence supports the idea that MM-associated MSCs are distinct from healthy MSCs, and their gene expression profiles may be predictive of myeloma patient outcomes. Here we directly investigate how MM cells affect the differentiation capacity and gene expression profiles of preadipocytes and bone marrow MSCs. Our studies reveal that MM.1S cells cause a marked decrease in lipid accumulation in differentiating 3T3-L1 cells. Also, MM.1S cells or MM.1S-conditioned media altered gene expression profiles of both 3T3-L1 and mouse bone marrow MSCs. 3T3-L1 cells exposed to MM.1S cells before adipogenic differentiation displayed gene expression changes leading to significantly altered pathways involved in steroid biosynthesis, the cell cycle, and metabolism (oxidative phosphorylation and glycolysis) after adipogenesis. MM.1S cells induced a marked increase in 3T3-L1 expression of MM-supportive genes including Il-6 and Cxcl12 (SDF1), which was confirmed in mouse MSCs by qRT-PCR, suggesting a forward-feedback mechanism. In vitro experiments revealed that indirect MM exposure prior to differentiation drives a senescent-like phenotype in differentiating MSCs, and this trend was confirmed in MM-associated MSCs compared to MSCs from normal donors. In direct co-culture, human mesenchymal stem cells (hMSCs) exposed to MM.1S, RPMI-8226, and OPM-2 prior to and during differentiation, exhibited different levels of lipid accumulation as well as secreted cytokines. Combined, our results suggest that MM cells can inhibit adipogenic differentiation while stimulating expression of the senescence associated secretory phenotype (SASP) and other pro-myeloma molecules. This study provides insight into a novel way in which MM cells manipulate their microenvironment by altering the expression of supportive cytokines and skewing the cellular diversity of the marrow.
Multiregional-Based Magnetic Resonance Imaging Radiomics Combined With Clinical Data Improves Efficacy in Predicting Lymph Node Metastasis of Rectal Cancer
Authors: Liu Xiangchun , Yang Qi , Zhang Chunyu , Sun Jianqing , He Kan , Xie Yunming , Zhang Yiying , Fu Yu , Zhang Huimao 
Published: February 2021

ObjectiveTo develop and validate a multiregional-based magnetic resonance imaging (MRI) radiomics model and combine it with clinical data for individual preoperative prediction of lymph node (LN) metastasis in rectal cancer patients.Methods186 rectal adenocarcinoma patients from our retrospective study cohort were randomly selected as the training (n = 123) and testing cohorts (n = 63). Spearman’s rank correlation coefficient and the least absolute shrinkage and selection operator were used for feature selection and dimensionality reduction. Five support vector machine (SVM) classification models were built using selected clinical and semantic variables, single-regional radiomics features, multiregional radiomics features, and combinations, for predicting LN metastasis in rectal cancer. The performance of the five SVM models was evaluated via the area under the receiver operator characteristic curve (AUC), accuracy, sensitivity, and specificity in the testing cohort. Differences in the AUCs among the five models were compared using DeLong’s test.ResultsThe clinical, single-regional radiomics and multiregional radiomics models showed moderate predictive performance and diagnostic accuracy in predicting LN metastasis with an AUC of 0.725, 0.702, and 0.736, respectively. A model with improved performance was created by combining clinical data with single-regional radiomics features (AUC = 0.827, (95% CI, 0.711–0.911), P = 0.016). Incorporating clinical data with multiregional radiomics features also improved the performance (AUC = 0.832 (95% CI, 0.717–0.915), P = 0.015).ConclusionMultiregional-based MRI radiomics combined with clinical data can improve efficacy in predicting LN metastasis and could be a useful tool to guide surgical decision-making in patients with rectal cancer.
Chemotherapy Plus Radiotherapy Versus Chemotherapy Alone for Patients With Peripheral T-Cell Lymphoma, Not Otherwise Specified
Authors: Chen Zegeng , Huang He , Li Xiaoqian , Fang Xiaojie , Wang Zhao , Hong Huangming , Zhang Zhihui , Cai Qingqing , Li Zhiming , Chen Meiting , Yao Yuyi , Pan Fei , Chen Limin , Lin Tongyu 
Published: February 2021

PurposePeripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a clinically and biologically heterogeneous disease with poor prognosis. As the role of radiation therapy (RT) is still unclear, we carried out this study to evaluate the potential efficacy of RT in PTCL-NOS.MethodsPatients diagnosed with PTCL-NOS between 2000 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching was used to balance the characteristics between patients who received radiotherapy and those who did not receive radiotherapy. In addition, we validated the findings in an external validation cohort retrospectively recruited from two high-capacity cancer center in China between 2006 and 2016. Kaplan-Meier curves and Cox regression models were used for survival analysis.ResultsOf the 2,768 patients with chemotherapy records in the SEER cohort, 27.6% of 844 patients with early-stage disease and 6.8% of 1,924 patients with advanced-stage disease received RT. The application of RT was significantly associated with an improvement in overall survival (5-year OS rate 58.5 versus 35.1%, P &lt;0.001) and disease-specific survival (5-year DSS rate 66.3 versus 44.0%, P &lt;0.001) in the early-stage subgroup, while no apparent survival benefit of adding RT was identified in patients with advanced-stage disease (5-year OS rate 28.7 versus 24.4%, P = 0.089; 5-year DSS rate 32.9 versus 31.3%, P = 0.223). After adjustment, a matched cohort of 1,044 patients (348 in the RT combined with CT group and 696 in the CT alone group) was created. And RT was still significantly associated with a survival benefit in the early-stage subset, but not in the advanced-stage disease group. In the validation cohort with more comprehensive data, RT also significantly improved the survival of early-stage PTCL-NOS patients.ConclusionAdding RT was associated with significant improvement in survival in early-stage PTCL-NOS, but the survival benefit of RT was not obvious in advanced-stage disease. The incorporation of RT for treatment in early-stage PTCL-NOS should be highly considered. Further prospective studies with more comprehensive data are needed to evaluate the effectiveness and toxicity of RT in PTCL-NOS.