bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-352: CD4+ follicular helper-like T cells are key players in anti-tumor immunity
Authors: Ganesan Anusha Preethi 
Published: September 2020

Abstract
CD4+ T helper cells (TH) are central orchestrators of an efficient immune response. However, within the tumor microenvironment (TME), it is unknown what type of CD4+ TH cells or CD4 helper-derived signals are essential to generate robust CD8+ CTL and TRM anti-tumor immune responses, which are positively associated with patient prognosis.
To determine the nature of CD4+ T cells that provide ‘help' for generating robust anti-tumor CD8+ CTL responses, we profiled the transcriptomes of patient-matched CD4+ and CD8+ T cells present in the TME of treatment-naïve patients with lung cancer and analyzed them jointly using a novel approach, integrated weighted gene correlation network analysis.
We found that the follicular helper T cell (TFH) program in CD4+ T cells was strongly associated with proliferation and tissue-residency in CD8+ CTLs. Single-cell transcriptomic analysis demonstrated the presence of tumor-infiltrating TFH-like cells, a subset of which lacked CXCR5 expression but displayed superior functional properties such as provision of CD8+ ‘help', cytotoxicity and proliferation. Because these anti-tumor functions were not previously ascribed to TFH cells which are known to support B cell responses, we validated our findings using independent in vitro and in vivo approaches. Multi-parametric immunohistochemistry showed co-localization of TFH cells with CD8+ TRM cells within tumors, the density of which was positively correlated with that of TFH cells. Adoptive transfer or induction of TFH cells in mouse tumor models resulted in augmented CD8+ CTL responses and impairment of tumor growth, indicating an important role of TFH-like CD4+ T cells in anti-tumor immunity. Furthermore, tumor-infiltrating TFH-like cells expressed PD-1 and were enriched in tumors following checkpoint blockade, suggesting that they may respond to anti-PD-1 therapy in addition to CD8+ CTLs. Our findings provide insights into the molecular identity and functional status of CD4+ T cells within tumors that mount robust CTL responses and uncover potential targets for tumor immunotherapy.
Citation Format: Anusha Preethi Ganesan. CD4+ follicular helper-like T cells are key players in anti-tumor immunity [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-352.
Abstract LB-379: Dominant negative PD1 armored CAR-T cells induce remission in relapsed or refractory non-Hodgkin lymphoma (NHL) patients
Authors: Yuan Yan , Huang Liansheng , Su Yang , Pu Chengfei , Ding Tianling , Xiao Xibin , Jin Lina , Cao Zhiyuan , Wu Ting , Chen Tong , Ding Luying , Zhang Xiaohong , Lan Haifeng , Wu Zhao , Xiao Lei 
Published: September 2020

Abstract
The chimeric antigen receptor (CAR) T cell treatment has been demonstrated as an effective therapy to treat relapsed/refractory B cell malignancy. However, tumor microenvironment influences and affects the efficacy of CAR T treatment. For example, programmed death ligand 1/2 (PDL1/2) may inhibit the CAR T cells via interaction with up-regulated programmed cell death protein 1 (PD1) after T cells activation, suppressing the tumor-killing capability of the CAR T cells. Thus, blockade of the PD1-PDL1/2 interaction may enhance the anti-tumor efficacy of CAR T therapy.Here, we generated CAR T expressed an anti-CD19 CAR molecule and a dominant-negative PD1 molecule. Compared with conventional CART cells, these “armored” CART cells showed the enhanced capability of tumor-killing and more “memory-like” phenotypes after multiple-round tumor challenging. These results suggest dominant-negative PD1 molecules may protect CART cells from exhaustion in the tumor microenvironment.Further, we reported the findings of a clinical trial for six relapsed or refractory B-cell non-Hodgkin lymphoma (NHLs) patients treated using our armored CAR T cells. These six patients failed multiple rounds of chemotherapy and radiotherapy. In the clinical trial, the patients were infused with autologous CAR T cells range from1×106/kg to 8×106/kg. PET/CT showed significant tumor shrinkage and SUV max declines in all six patients, and the ongoing responses were monitored. The best overall response rate (ORR)was 100%. Conclusion: The results of these six patients in the clinical trial showed that our armored CAR T cells achieved the significant anti-bulky lymphoma response while causing limited and tolerated cytokine release syndrome and central nervous system toxicity. Thus, dominant-negative PD1 molecules may increase CAR T cells persistence in patients, enhancing the efficacy of CAR T cells for treating blood cancer. Finally, dominant-negative PD1 can be used as a platform technology and may be applied to other adoptive cellular immunotherapies such as TCR-T or TIL in the treatment of solid tumors. We are continuing to monitor current patients and recruit more patients for the clinical trial.
Citation Format: Yan Yuan, Liansheng Huang, Yang Su, Chengfei Pu, Tianling Ding, Xibin Xiao, Lina Jin, Zhiyuan Cao, Ting Wu, Tong Chen, Luying Ding, Xiaohong Zhang, Haifeng Lan, Zhao Wu, Lei Xiao. Dominant negative PD1 armored CAR-T cells induce remission in relapsed or refractory non-Hodgkin lymphoma (NHL) patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-379.
A new approach for improving clustering algorithms performance
Authors: Alrammahi Anfal F. N. , Aljanabi Kadhim B. S. 
Published: September 2020

<p class="Abstract">Clustering represents one of the most popular and used Data Mining techniques due to its usefulness and the wide variations of the applications in real world. Defining the number of the clusters required is an application oriented context, this means that the number of clusters k is an input to the whole clustering process. The proposed approach represents a solution for estimating the optimum number of clusters. It is based on the use of iterative K-means clustering under three different criteria; centroids convergence, total distance between the objects and the cluster centroid and the number of migrated objects which can be used effectively to ensure better clustering accuracy and performance. A total of 20000 records available on the internet were used in the proposed approach to test the approach. The results obtained from the approach showed good improvement on clustering accuracy and algorithm performance over the other techniques where centroids convergence represents a major clustering criteria. C# and Microsoft Excel were the software used in the approach.</p>
Infarct Collagen Topography Regulates Fibroblast Fate via p38-Yes-Associated Protein Transcriptional Enhanced Associate Domain Signals
Authors: Bugg Darrian , Bretherton Ross , Kim Peter , Olszewski Emily , Nagle Abigail , Schumacher Austin E. , Chu Nick , Gunaje Jagadambika , DeForest Cole A. , Stevens Kelly , Kim Deok-Ho , Davis Jennifer 
Published: September 2020

Rationale:
Myocardial infarction causes spatial variation in collagen organization and phenotypic diversity in fibroblasts, which regulate the heart’s ECM (extracellular matrix). The relationship between collagen structure and fibroblast phenotype is poorly understood but could provide insights regarding the mechanistic basis for myofibroblast heterogeneity in the injured heart.

Objective:
To investigate the role of collagen organization in cardiac fibroblast fate determination.

Methods and Results:
Biomimetic topographies were nanofabricated to recapitulate differential collagen organization in the infarcted mouse heart. Here, adult cardiac fibroblasts were freshly isolated and cultured on ECM topographical mimetics for 72 hours. Aligned mimetics caused cardiac fibroblasts to elongate while randomly organized topographies induced circular morphology similar to the disparate myofibroblast morphologies measured in vivo. Alignment cues also induced myofibroblast differentiation, as >60% of fibroblasts formed αSMA (α-smooth muscle actin) stress fibers and expressed myofibroblast-specific ECM genes like Postn (periostin). By contrast, random organization caused 38% of cardiac fibroblasts to express αSMA albeit with downregulated myofibroblast-specific ECM genes. Coupling topographical cues with the profibrotic agonist, TGFβ (transforming growth factor beta), additively upregulated myofibroblast-specific ECM genes independent of topography, but only fibroblasts on flat and randomly oriented mimetics had increased percentages of fibroblasts with αSMA stress fibers. Increased tension sensation at focal adhesions induced myofibroblast differentiation on aligned mimetics. These signals were transduced by p38-YAP (yes-associated protein)-TEAD (transcriptional enhanced associate domain) interactions, in which both p38 and YAP-TEAD (yes-associated protein transcriptional enhanced associate domain) binding were required for myofibroblast differentiation. By contrast, randomly oriented mimetics did not change focal adhesion tension sensation or enrich for p38-YAP-TEAD interactions, which explains the topography-dependent diversity in fibroblast phenotypes observed here.

Conclusions:
Spatial variations in collagen organization regulate cardiac fibroblast phenotype through mechanical activation of p38-YAP-TEAD signaling, which likely contribute to myofibroblast heterogeneity in the infarcted myocardium.
Long-term consistency despite cross-seasonal changes in personality traits of common waxbills
Authors: Guerra Soraia , Gomes Ana Cristina R. , Cardoso Gonçalo C. 
Published: September 2020

Abstract
Tests of long-term consistency in personality differences are not abundant. We studied personality in common waxbills (Estrilda astrild) from one Autumn to the next, and also from Autumn to a subsequent Spring, using a behavioural assay for their proactive-reactive personality axis (mirror test) and for tonic immobility. From one Autumn to the next, individual differences were consistent and the population median behaviours did not change, indicating long-term stability of personality differences. From Autumn to Spring, behavioural differences remained consistent, despite the population shifting to more proactive behaviour and individual differences being accentuated in the proactive-reactive personality axis. This increase in personality differences was not found between the two previous Autumns, suggesting a seasonal rather than longitudinal change, and a possible role for personality differences during the Spring breeding season. We conclude that waxbill personality differences are stable in the long term, despite changes in behaviour between Autumn and Spring.
The Economic World of the populus Romanus
Authors: Russell Amy 
Published: September 2020

Abstract
Rome’s transformation from city-state to territorial empire involved a massive increase in wealth; it also both created and responded to fundamental political changes, in a moment often positioned as the creation myth of republicanism. James Tan has modelled the Republican economy as a three-way relationship between aristocrats, the state, and the people. Aristocrats competed with the state for access to the riches of conquest; simultaneously the state’s dependence on citizen taxation declined. This article examines the relationship between state and people as both practical and ideological. The People were sovereign, yet it was the People who increasingly lost their status as economic and political stakeholders even as their empire grew. The complex relationship between the people and the populus (‘the People’ as an institution) had economic as well as political elements, and is central to how we should apply notions of economic sovereignty to Republican Rome.
Acceptability and Adherence to Peanut-Based Energy-Dense Nutritional Supplement Among Adult Malnourished Pulmonary Tuberculosis Patients in Ballabgarh Block of Haryana, India
Authors: Kumar Rakesh , Krishnan Anand , Singh Manjula , Singh Urvashi B. , Singh Archna , Guleria Randeep 
Published: September 2020

Background: Undernutrition is a leading risk factor for tuberculosis and is associated with adverse treatment outcomes. Energy-dense nutritional supplement (EDNS) may be helpful in managing undernutrition in tuberculosis patients. Methods: A longitudinal study was conducted among 102 newly diagnosed pulmonary tuberculosis patients in the Ballabgarh tuberculosis unit in Haryana, India, between September 2018 and February 2019. Participants were provided daily supplementation with 2 sachets of peanut-based EDNS providing 1000 kcal along with the tuberculosis chemotherapy for 2 months. Acceptability was assessed after one month of supplementation. Reported side effects were assessed every 15 days for 2 months and adherence, in terms of proportion of supplement consumed, was assessed on weekly basis for 2 months. Weight was measured at baseline and after 1 month and 2 months. Results: Mean age of participants was 33 years (standard deviation: 13.8) and 75.5% of the participants were male. Almost 100% of the participants found the taste, smell, consistency, and color of the EDNS acceptable. Three participants rejected it after one month of consuming EDNS and another 7 rejected after 2 months of consuming EDNS. After consuming EDNS for 2 months, 13.9% of the participants complained of nausea, 11.9% complained of vomiting, 10.9% complained of diarrhea, and 9.9% complained of pain in the abdomen and abdominal fullness or bloating anytime during the period of supplementation. The adherence to EDNS among the participants was reported as 92.6%. Conclusion: A peanut-based EDNS was highly acceptable and safe, and the adherence to it was high among patients with pulmonary tuberculosis.
Factors associated with quality of life in cutaneous lupus erythematosus using the Revised Wilson and Cleary Model
Authors: Ogunsanya Motolani E , Cho Sung Kyung , Hudson Andrew , Chong Benjamin F 
Published: September 2020

Objectives The purpose of this study was to characterize the impact of cutaneous lupus erythematosus (CLE) in adults and identify the clinical and non-clinical factors associated with quality of life (QoL), using the Revised Wilson and Cleary Model. Methods 101 patients diagnosed with CLE were included in this cross-sectional study. QoL was measured with the Cutaneous Lupus Erythematosus Quality of Life (CLEQoL) scale and disease activity and damage with the Cutaneous Lupus Activity and Severity Index (CLASI). Patient demographics, clinical, and disease characteristics were also collected. Descriptive statistics were calculated, and multiple regression was employed to determine significant (p < 0.05) predictors of overall QoL. Data were analyzed using SPSS v24. Results The overall regression QoL model was significantly different from zero, (F = 24.96; df = 14, 76; p = <0.001). Disease activity (β = 0.13), pain (β = 0.13), fatigue (β = 0.24), body image (β = 0.62), and side effects (β = –0.13) were significant predictors of overall QoL while controlling for other predictor variables. Patients who experienced higher levels of disease activity, fatigue severity, pain levels, and greater degree of body dissatisfaction had significantly poorer QoL. Fewer side effects experienced from CLE medications were significantly associated with higher QoL. Conclusions Study findings support the considerable burden associated with CLE. Several modifiable variables such as pain, fatigue, body image, and disease activity were associated with QoL. Therefore, interventions that incorporate these variables may reduce negative impacts on QoL life and improve health outcomes in CLE patients. Furthermore, given the chronic and recurring nature of the condition, strategies focused on improving QoL are needed for this vulnerable population.
The Influence of the Food and Drug Administration Pregnancy and Lactation Labeling Rule on Drug Information Resources
Authors: Harris John Brock , Holmes Amy P. , Eiland Lea S. 
Published: September 2020

Background Drug information resources are commonly used by health-care providers answering pregnancy-related medication questions. In 2015, the United States Food and Drug Administration approved a new pregnancy and lactation medication labeling content and format, removing the pregnancy category, and using a narrative. Despite labeling requirements changing, it is unknown if drug information resources updated monographs to reflect these changes. Objective The primary objective was to evaluate if commonly used drug information resources provide pregnancy information listed similar to the requirements of the Pregnancy and Lactation Labeling Rule (PLLR). Secondary analyses included evaluating the references and inclusion of the pregnancy category rating. Methods Pregnancy recommendations for 23 medications were evaluated in 9 drug information resources (Clinical Pharmacology, Drugs in Pregnancy and Lactation, Epocrates®, First Databank, LexiComp® Online, LexiComp® Online Pregnancy & Lactation, In-Depth, Medi-Span®, Micromedex®, and Multum®). The number of references per drug monograph and most recent reference publication year was obtained. Results LexiComp® Online Pregnancy & Lactation, In-Depth mimics the new PLLR structure and consistently had the highest number of and most recent references when the medication was included. Drugs in Pregnancy and Lactation was the next most similar in content with the PLLR and second in most references per monograph; however, the most recent reference was the textbook publication year. Conclusion and Relevance LexiComp® Online Pregnancy & Lactation, In-Depth and Drugs in Pregnancy and Lactation provided pregnancy information in a format most similar to the PLLR. However, several drug information resources contained pregnancy categories ratings that were to be removed from medication labeling per the PLLR.
Bisphosphonate Versus Bisphosphonate and Calcitonin for the Treatment of Moderate to Severe Hypercalcemia of Malignancy
Authors: Khan Attiya A. , Gurnani Payal K. , Peksa Gary D. , Whittier William L. , DeMott Joshua M. 
Published: September 2020

Background Historically, intravenous (IV) bisphosphonates with calcitonin are the treatment of choice for hypercalcemia of malignancy. However, evidence is lacking. Objective The objective of this study was to compare the use of bisphosphonate versus bisphosphonate with calcitonin for moderate to severe hypercalcemia of malignancy. Methods This was a retrospective study evaluating patients who received bisphosphonate and/or calcitonin for treatment of moderate to severe hypercalcemia of malignancy. Patients received usual care plus either (1) bisphosphonate or (2) bisphosphonate with calcitonin. The primary outcome was change in corrected serum calcium concentrations 48 hours after treatment. Secondary outcomes included corrected calcium levels, incidence of normocalcemia and hypocalcemia, time to normocalcemia, hospital length of stay, and cost avoidance. Results The 48-hour decrease in corrected calcium was less in the bisphosphonate group than in the combination group (2.4 [1.6-3.4] vs 3.9 [3.5-5.3]; P < 0.001). However, initial calcium levels in the combination group were higher than in the bisphosphonate group, and calcium levels at 24, 48, and 72 hours were similar. Secondary outcomes did not differ. Average cost avoidance with bisphosphonate monotherapy was $11 248 per patient and $291 448 per year. Conclusions and Relevance In the treatment of moderate to severe hypercalcemia of malignancy, IV bisphosphonate in combination with calcitonin resulted in a higher difference in corrected calcium levels at 48 hours compared with bisphosphonate therapy alone. However, corrected calcium levels in the first 72 hours, time to normocalcemia, and clinical outcomes were similar. The addition of calcitonin increases cost without substantial clinical benefit, and providers may consider avoiding calcitonin.
Piezoelectric-based dither control for automobile brake squeal suppression under various braking conditions
Authors: Jung HweeKwon , Park Gyuhae , Kim Jeong Kyu 
Published: September 2020

Automobile brake squeal noise, which is nonlinear, friction-induced vibration in the frequency range 1–16 kHz, still remains a major problem for the automotive industry. This article presents analytical and experimental investigations into the application of dither control for active suppression of automobile disc brake squeal. Dither is a concept of active control that introduces high-frequency actuation into a system to suppress a much lower frequency disturbance. In this study, a specially designed brake system is built, in which a piezoelectric stack actuator in the piston of a floating caliper brake applies the dither input. In the experiments, squeal noise generated under the drag mode and various dynamic modes are considered. The results indicate that this piezoelectric-based dither control could effectively suppress the brake squeal noise by 5–10 dB and the squeal occurrence by up to 60% under various braking conditions.
JetStream Atherectomy for the Treatment of In-Stent Restenosis of the Femoropopliteal Segment: One-Year Results of the JET-ISR Study
Authors: Shammas Nicolas W. , Petruzzi Nicholas , Henao Steven , Armstrong Ehrin J. , Shimshak Thomas , Banerjee Subhash , Latif Faisal , Eaves Britton , Brothers Thomas , Golzar Jaafer , Shammas Gail A. , Jones-Miller Susan , Christensen Lori , Shammas W. John 
Published: September 2020

Purpose: To report the results of a study evaluating JetStream atherectomy for the treatment of in-stent restenosis (ISR). Materials and Methods: The JetStream XC atherectomy device, a rotational cutter with aspiration capacity, was evaluated in a prospective, multicenter study (JET-ISR) of 60 patients (mean age 70.2±10.8 years; 40 men) with femoropopliteal ISR ( ClinicalTrials.gov identifier NCT02730234). Lesion length was 19.9±13.5 cm; 33 (55%) were chronic total occlusions and 26 (45%) were TransAtlantic Inter-Society Consensus class D. No drug-bearing device was allowed, and stenting was performed only for bailout. Lesion characteristics and stent integrity were evaluated by an independent core laboratory. The primary endpoint was target lesion revascularization (TLR) at 6 months with bailout stenting considered as TLR. Secondary endpoints included TLR (without bailout stenting) and clinical patency (no restenosis or TLR) at 1 year. The Kaplan-Meier method was employed to evaluate time-to-event endpoints; estimates are given with 95% confidence interval (CI). Results: Bailout stenting was required in 6 of 60 limbs (10%). There were no stent fractures or deformities after atherectomy + adjunctive angioplasty reported by the core laboratory. Kaplan-Meier estimates of freedom from TLR at 6 months and 1 year were 79.3% (95% CI 68.9% to 89.8%) and 60.7% (95% CI 47.8% to 73.6%), respectively. When bailout stenting at the index procedure was not considered a TLR event, freedom from TLR estimates at 6 months and 1 year were 89.3% (95% CI 81.2% to 97.4%) and 66.8% (95% CI 54.3% to 74.2%), respectively. Clinical patency rates at 6 months and 1 year were 77.5% (31/40) and 51.7% (15/29), respectively. Conclusion: JetStream atherectomy using the XC device and no drug-eluting devices is feasible, with good clinical patency and 1-year freedom from TLR.