bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Reflection on How Carcinoma-Associated Fibroblasts Were Recognized as Active Participants of Epithelial Tumorigenesis
Authors: Cukierman Edna 
Published: September 2021

Abstract
Today's view of cancer as a systemic disease was facilitated by studies accentuating the local as well as the systemic role that non-tumorigenic cells, such as carcinoma-associated fibroblasts, play in cancer onset, development, and progression. The study highlighted in this Cancer Research Landmark was instrumental for supporting the idea that cancer is a full-body disease that depends on reciprocal interactions between cancer cells and the tumor microenvironment. Fibroblasts are mesenchymal cells of the connective tissue and are responsible for maintaining tissue homeostasis. Importantly, contractile myofibroblastic activation and immunoregulatory fibroblastic nemosis (the process of mesenchymal cell activation, followed by death, associated with release of proinflammatory molecules) constitute two functional aspects of fibroblasts that are essential for organogenesis as well as for modulating wound healing. Yet, in epithelial cancers, fibroblastic cell functions are chronically misregulated. The study by Olumi and colleagues published in Cancer Research in 1999 exemplifies how normal fibroblasts play a tumor-suppressive role and how modulating fibroblastic activity provides carcinoma-associated fibroblasts with tumor-promoting functions, similar to the needed “second hit” in a tumor suppressor gene. The emphasis on tumor/fibroblast interactions has provided a new framework for thinking about tumorigenesis as well as new targets for therapeutic intervention.
See related article by Olumi and colleagues, Cancer Res 1999;59:5002–11
Lung Cancer as a Subsequent Malignant Neoplasm in Survivors of Childhood Cancer
Authors: Ghosh Taumoha , Chen Yan , Dietz Andrew C. , Armstrong Gregory T. , Howell Rebecca M. , Smith Susan A. , Mulrooney Daniel A. , Turcotte Lucie M. , Yuan Yan , Yasui Yutaka , Neglia Joseph P. 
Published: September 2021

Abstract

Background:
Lung cancer, the most common cause of cancer-related death in adults, has not been well studied as a subsequent malignant neoplasm (SMN) in childhood cancer survivors. We assessed prevalence, risk factors, and outcomes for lung SMN in the Childhood Cancer Survivor Study (CCSS) cohort.

Methods:
Among 25,654 5-year survivors diagnosed with childhood cancer (&lt;21 years), lung cancer was self-reported and confirmed by pathology record review. Standardized incidence ratios (SIR) and cumulative incidences were calculated, comparing survivors to the general population, and hazard ratios (HR) were estimated using Cox regression for diagnosis and treatment exposures.

Results:
Forty-two survivors developed a lung SMN [SIR, 4.0; 95% confidence interval (CI), 2.9–5.4] with a cumulative incidence of 0.16% at 30 years from diagnosis (95% CI, 0.09%–0.23%). In a treatment model, chest radiation doses of 10–30 Gy (HR, 3.4; 95% CI, 1.05–11.0), &gt;30–40 Gy (HR, 4.6; 95% CI, 1.5–14.3), and &gt;40 Gy (HR, 9.1; 95% CI, 3.1–27.0) were associated with lung SMN, with a monotone dose trend (Ptrend &lt; 0.001). Survivors of Hodgkin lymphoma (SIR, 9.3; 95% CI, 6.2–13.4) and bone cancer (SIR, 4.4; 95% CI, 1.8–9.1) were at greatest risk for lung SMN.

Conclusions:
Survivors of childhood cancer are at increased risk for lung cancer compared with the general population. Greatest risk was observed among survivors who received chest radiotherapy or with primary diagnoses of Hodgkin lymphoma or bone cancer.

Impact:
This study describes the largest number of observed lung cancers in childhood cancer survivors and elucidates need for further study in this aging and growing population.
Single-Cell Analyses Reveal Mechanisms of Cancer Stem Cell Maintenance and Epithelial–Mesenchymal Transition in Recurrent Bladder Cancer
Authors: Wang Huanjun , Mei Yan , Luo Cheng , Huang Qun , Wang Zifeng , Lu Guan-Ming , Qin Lili , Sun Zhun , Huang Chao-Wen , Yang Zhi-Wen , Chen Junxing , Yin Weiguo , Qian Chao-Nan , Zeng Jianming , Chen Lingwu , Leng Qibin , Guo Yan , Jia Guangshuai 
Published: September 2021

Abstract

Purpose:
Bladder cancer treatment remains a major clinical challenge due to therapy resistance and a high recurrence rate. Profiling intratumor heterogeneity can reveal the molecular mechanism of bladder cancer recurrence.

Experimental Design:
Here, we performed single-cell RNA sequencing and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) on tumors from 13 patients with low recurrence risk, high recurrence risk, and recurrent bladder cancer.

Results:
Our study generated a comprehensive cancer-cell atlas consisting of 54,971 single cells and identified distinct cell subpopulations. We found that the cancer stem-cell subpopulation is enriched during bladder cancer recurrence with elevated expression of EZH2. We further defined a subpopulation-specific molecular mechanism whereby EZH2 maintains H3K27me3-mediated repression of the NCAM1 gene, thereby inactivating the cell invasive and stemness transcriptional program. Furthermore, taking advantage of this large single-cell dataset, we elucidated the spectrum of epithelial–mesenchymal transition (EMT) in clinical samples and revealed distinct EMT features associated with bladder cancer subtypes. We identified that TCF7 promotes EMT in corroboration with single-cell ATAC with high-throughput sequencing (scATAC-seq) analysis. Additionally, we constructed regulatory networks specific to recurrent bladder cancer.

Conclusions:
Our study and analytic approaches herein provide a rich resource for the further study of cancer stem cells and EMT in the bladder cancer research field.
Immunization with a Plasmid DNA Vaccine Encoding the N-Terminus of Insulin-like Growth Factor Binding Protein-2 in Advanced Ovarian Cancer Leads to High-level Type I Immune Responses
Authors: Cecil Denise L. , Liao John B. , Dang Yushe , Coveler Andrew L. , Kask Angela , Yang Yi , Childs Jennifer S. , Higgins Doreen M. , Disis Mary L. 
Published: September 2021

Abstract

Purpose:
Cancer vaccines targeting nonmutated proteins elicit limited type I T-cell responses and can generate regulatory and type II T cells. Class II epitopes that selectively elicit type I or type II cytokines can be identified in nonmutated cancer-associated proteins. In mice, a T-helper I (Th1) selective insulin-like growth factor binding protein-2 (IGFBP-2) N-terminus vaccine generated high levels of IFNγ secreting T cells, no regulatory T cells, and significant antitumor activity. We conducted a phase I trial of T-helper 1 selective IGFBP-2 vaccination in patients with advanced ovarian cancer.

Patients and Methods:
Twenty-five patients were enrolled. The IGFBP-2 N-terminus plasmid-based vaccine was administered monthly for 3 months. Toxicity was graded by NCI criteria and antigen-specific T cells measured by IFNγ/IL10 ELISPOT. T-cell diversity and phenotype were assessed.

Results:
The vaccine was well tolerated, with 99% of adverse events graded 1 or 2, and generated high levels of IGFBP-2 IFNγ secreting T cells in 50% of patients. Both Tbet+ CD4 (P = 0.04) and CD8 (P = 0.007) T cells were significantly increased in immunized patients. There was no increase in GATA3+ CD4 or CD8, IGFBP-2 IL10 secreting T cells, or regulatory T cells. A significant increase in T-cell clonality occurred in immunized patients (P = 0.03, pre- vs. post-vaccine) and studies showed the majority of patients developed epitope spreading within IGFBP-2 and/or to other antigens. Vaccine nonresponders were more likely to have preexistent IGFBP-2 specific immunity and demonstrated defects in CD4 T cells, upregulation of PD-1, and downregulation of genes associated with T-cell activation, after immunization.

Conclusions:
IGFBP-2 N-terminus Th1 selective vaccination safely induces type I T cells without evidence of regulatory responses.
The MAGNOLIA Trial: Zanubrutinib, a Next-Generation Bruton Tyrosine Kinase Inhibitor, Demonstrates Safety and Efficacy in Relapsed/Refractory Marginal Zone Lymphoma
Authors: Opat Stephen , Tedeschi Alessandra , Linton Kim , McKay Pamela , Hu Bei , Chan Henry , Jin Jie , Sobieraj-Teague Magdalena , Zinzani Pier Luigi , Coleman Morton , Thieblemont Catherine , Browett Peter , Ke Xiaoyan , Sun Mingyuan , Marcus Robert , Portell Craig A. , Ardeshna Kirit , Bijou Fontanet , Walker Patricia , Hawkes Eliza A. , Mapp Sally , Ho Shir-Jing , Talaulikar Dipti , Zhou Ke-Shu , Co Melannie , Li Xiaotong , Zhou Wenxiao , Cappellini Massimo , Tankersley Chris , Huang Jane , Trotman Judith 
Published: September 2021

Abstract

Purpose:
Marginal zone lymphoma (MZL) is an uncommon non–Hodgkin lymphoma with malignant cells that exhibit a consistent dependency on B-cell receptor signaling. We evaluated the efficacy and safety of zanubrutinib, a next-generation selective Bruton tyrosine kinase inhibitor, in patients with relapsed/refractory (R/R) MZL.

Patients and Methods:
Patients with R/R MZL were enrolled in the phase II MAGNOLIA (BGB-3111–214) study. The primary endpoint was overall response rate (ORR) as determined by an independent review committee (IRC) based on the Lugano 2014 classification.

Results:
Sixty-eight patients were enrolled. After a median follow-up of 15.7 months (range, 1.6 to 21.9 months), the IRC-assessed ORR was 68.2% and complete response (CR) was 25.8%. The ORR by investigator assessment was 74.2%, and the CR rate was 25.8%. The median duration of response (DOR) and median progression-free survival (PFS) by independent review was not reached. The IRC-assessed DOR rate at 12 months was 93.0%, and IRC-assessed PFS rate was 82.5% at both 12 and 15 months. Treatment was well tolerated with the majority of adverse events (AE) being grade 1 or 2. The most common AEs were diarrhea (22.1%), contusion (20.6%), and constipation (14.7%). Atrial fibrillation/flutter was reported in 2 patients; 1 patient had grade 3 hypertension. No patient experienced major hemorrhage. In total, 4 patients discontinued treatment due to AEs, none of which were considered treatment-related by the investigators.

Conclusions:
Zanubrutinib demonstrated high ORR and CR rate with durable disease control and a favorable safety profile in patients with R/R MZL.
NARX-based water quality index model of Air Busuk River using chemical parameter measurements
Authors: Hasnan Muhammad Ierfan , Jaffar Azhar , Thamrin Norashikin M. , Misnan Mohamad Farid , Yassin Ahmad Ihsan Mohd , Megat Ali Megat Syahirul Amin 
Published: September 2021

<p>Water quality plays a major role in issues related to public health and marine life. Hence, monitoring river for contaminations is vital for ensuring safe and sustainable water resources. Conventional method for assessing water quality index is costly as it requires considerable amount of time and laboratory resources. Therefore, this study proposes a water quality index model based on artificial neural network. A six-year data for Air Busuk River is obtained from the Department of Environment. Dissolved oxygen, biological oxygen demand, and ammoniacal nitrogen has shown high correlation with water quality index. The water quality index model is then developed based on these parameters, employing the non-linear autoregressive with exogeneous input structure. Generally, the model which is based on three chemical parameters has shown satisfactory performance with overall regression of 0.8767 and passed the correlation function tests. The model offers a potentially efficient method for assessing water quality with cost-saving benefits for government agencies and monitoring authorities.</p>
Deontology, Consequentialism and Reciprocity in Contemporary Just War Thinking
Authors: Brown Chris 
Published: September 2021

Abstract
There has always been a degree of tension between, on the one hand, the writings of philosophers, theologians and lawyers on the ethics of war, and, on the other, the moral approach of soldiers, those actually engaged in combat. The former base their thinking on deontological reasoning, albeit with occasional reluctant gestures towards notions such as ‘military necessity’, while the latter are by temperament consequentialist, stressing, in particular, the importance of reciprocity. This tension is controllable in the implausible context of war between liberal, Western European countries, but comes to the surface in situations where regular Western armies are in combat with the armed forces of non-liberal states, or in situations of asymmetric warfare. The question is posed – can the notion of a just war survive in the absence of reciprocity?
Long-Term Opioid Use in Post-Surgical Management of Patients With Head and Neck Cancer
Authors: Wang Judy J. , Rubin Samuel J. , Devaiah Anand K. , Faden Daniel L. , Salama Andrew R. , Edwards Heather A. 
Published: September 2021

Objective: This study aims to identify clinical and socioeconomic factors associated with long-term, post-surgical opioid use in the head and neck cancer population. Methods: A single center retrospective study was conducted including patients diagnosed with head and neck cancer between January 1, 2014 and July 1, 2019 who underwent primary surgical management. The primary outcome measure was continued opioid use 6 months after treatment completion. Both demographic and cancer-related variables were recorded to determine what factors were associated with prolonged opioid use. Univariate analysis was performed using chi-squared test for categorical variables and 2-sample t-test for continuous variables. Multivariate analysis was performed using logistic regression. Results: A total of 359 patients received primary surgical management. Forty-five patients (12.53%) continued to take opioids 6 months after treatment completion. Using univariate analysis, patients less than 65 years of age ( P = .0126), adjuvant chemoradiation (n = 25, P < .001), and overall length of hospital stay (8.60 ± 8.58 days, P = .0274) were significantly associated with long term opioid use. Multivariate logistic regression showed that adjuvant chemoradiation (OR = 3.446, 95% CI [1.742, 6.820], P = .0004) and overall length of hospital stay (OR = 0.949, 95% CI [0.903, 0.997], P = .0373) to be significantly associated with opioid use 6 months after head and neck cancer treatment. Conclusion: Long-term postoperative opioid use in head and neck cancer patients is significantly associated with adjuvant chemoradiation, and patients with longer length of hospital stay. Therefore, future research should focus on interventions to better manage opioid use during the acute treatment period to decrease long-term use.
Global Production System, Textile Industry and Wage Disparity: Evidence from South India
Authors: Ramamurthy Nandini 
Published: September 2021

This article discusses the root causes of wage disparity in the textile industry. The study argues that wage disparity arises through direct and indirect approaches. Both create pressure on suppliers and leads to low wage payment, depriving workers of social security benefits, unpaid holidays and leaves. Hyper-consumerism, free on board (FoB) price, and flexibility have created competition among suppliers and other stakeholders. Suppliers flexibilise rules and re-organise work arrangements to meet on-time production by increasing working hours, introducing wage penalty, strict supervising, and increasing surveillance. JEL Codes: J3, J31, J41, J46, J81, J82, J83
Monocyte to high density lipoprotein ratio in patients with acute kidney injury after cardiac surgery
Authors: Huang Wenjuan , Wang Lei , Wan Xin 
Published: September 2021

Background: The Monocyte to high density lipoprotein ratio (MHR) has been postulated as a novel parameter associated with adverse renal and cardiovascular outcomes. In this study we investigated the association of MHR with cardiac surgery-associated acute kidney injury (CSA-AKI). Methods: In this retrospective study, we analyzed the data pertaining to 1505 patients undergoing cardiopulmonary bypass (CPB) surgery. The CSA-AKI, which was defined using Kidney Disease Improving Global Outcomes criteria. Concurrently, a retrospective scan of patient files was conducted and information relevant to nephropathy such as the level of their serum creatinine (SCr), Blood urea nitrogen (BUN), uric acid (UA), serum cystatin C (Cys-C), total cholesterol (TC), triglycerides (TG), glucose and MHR, ejection fraction, CPB duration time, and other indicators. Results: About 1505 patients were studied of whom 195 developed AKI. MHR was significantly higher in the AKI patients (p = 0.001). In multivariate logistic regression analysis, MHR, UA, Cys-C, age, glucose, and history of chronic kidney disease or hypertension were independently correlated with CSA-AKI. Conclusions: As a laboratory index, the elevated MHR is convenient, independent, and a useful predictor for CSA-AKI.
Suicide in French Polynesia: a retrospective analysis based on medicolegal documents and interview with family
Authors: Amadéo Stephane , Rereao Moerani , Vanquin David Germaine , Nguyen NgocLam , Séguin Monique , Beauchamp Guy , Favro Patrick , Trouche Heimana , Malogne Aurélia , Goodfellow Benjamin , Gokalsing Erick , Spodenkiewicz Michel , Sy Aminata , Bocage-Barthélémy Yvana , Sebti Johan , Tuheiava Annie , Jehel Louis , De Leo Diego 
Published: September 2021

Objective To analyse the epidemiological data on suicide in French Polynesia (FP). Methods Data on suicides were collected from the Public Health Direction, Judicial Police Investigations Court of Justice records, the Centre d’Opérations et de Renseignements de la Gendarmerie, patient records for those hospitalized in psychiatry and from psychological autopsies. Results The dataset consisted of 316 suicide cases in FP over 25 years (1992–2016). In FP, suicide was more frequent in men (sex ratio 3.2:1), young people (mean age, 34.4 years) and individuals with previously diagnosed psychiatric disorders (100 of 316; 31.6%) The most common method of suicide was hanging (276 of 316; 87.3%). A history of previous suicide attempts was found in 25 of 56 (44.6%) of suicide cases, when documented. The most common potential triggering factors for suicide were emotional problems. The suicide rates have remained stable during 1992–2016 (mean 10.6/100 000 inhabitants per year), with periods of economic crises increasing suicide rates. Conclusions These results provide valuable information to enable the effective targeting of suicide prevention strategies toward those at high risk. Economic crises had larger impacts in the French overseas territories than mainland France. Given the unprecedented economic impact of the Covid-19 pandemic in FP, there is an urgent need to implement suicide epidemiological surveillance and prevention programmes.
Time course of efficacy of atogepant for the preventive treatment of migraine: Results from the randomized, double-blind ADVANCE trial
Authors: Schwedt Todd J , Lipton Richard B , Ailani Jessica , Silberstein Stephen D , Tassorelli Cristina , Guo Hua , Lu Kaifeng , Dabruzzo Brett , Miceli Rosa , Severt Lawrence , Finnegan Michelle , Trugman Joel M 
Published: September 2021

Background Atogepant is an oral, small-molecule, calcitonin gene–related peptide receptor antagonist for the preventive treatment of migraine. Methods In the double-blind, phase 3 ADVANCE trial, participants with 4–14 migraine days/month were randomized to atogepant 10 mg, 30 mg, 60 mg, or placebo once daily for 12 weeks. We evaluated the time course of efficacy of atogepant for the preventive treatment of migraine. Analyses included change from baseline in mean monthly migraine days during each of the three 4-week treatment periods, change in weekly migraine days during weeks 1–4, and proportion of participants with a migraine on each day during the first week. Results We analyzed 873 participants (n = 214 atogepant 10 mg, n = 223 atogepant 30 mg, n = 222 atogepant 60 mg, n = 214 placebo). For weeks 1–4, mean change from baseline in mean monthly migraine days ranged from −3.1 to −3.9 across atogepant doses vs −1.6 for placebo ( p < 0.0001). For weeks 5–8 and 9–12, reductions in mean monthly migraine days ranged from −3.7 to −4.2 for atogepant vs −2.9 for placebo ( p ≤ 0.012) and −4.2 to −4.4 for atogepant vs −3.0 for placebo ( p < 0.0002), respectively. Mean change from baseline in weekly migraine days in week 1 ranged from −0.77 to −1.03 for atogepant vs −0.29 with placebo ( p < 0.0001). Percentages of participants reporting a migraine on post-dose day 1 ranged from 10.8% to 14.1% for atogepant vs 25.2% with placebo ( p ≤ 0.0071). Conclusion Atogepant demonstrated treatment benefits as early as the first full day after treatment initiation, and sustained efficacy across each 4-week interval during the 12-week treatment period. Clinical trial registration: ClinicalTrials.gov identifier: NCT03777059
Teaching Methods in Undergraduate Intermediate Theory, Statistics and Econometrics, and Other Upper-Division Economics Courses: Results From a Sixth National Quinquennial Survey
Authors: Harter Cynthia , Asarta Carlos J. 
Published: September 2021

This article is an extension of a recent article published in The American Economist (Asarta et al., 2021) and presents the second report of basic findings from the 2020 online administration of the sixth national quinquennial survey on teaching and assessment methods in economics. Consistent with the results from the first report, we find that “chalk and talk” remains the staple method of instruction across the entire undergraduate economics curriculum. Lessons, activities, and references that address diversity, inclusion, or gender issues are almost never used in intermediate theory, statistics and econometrics, and other upper-division field courses. There has been notable growth in the use of cooperative learning/small-group assignments, as well as in instructor-led and “student(s) with student(s)” discussions over the past 25 years. Overall, however, there have been minimal changes in teaching methods over time. JEL Classifications: A20, A22
Thanatopolitics and colonial logics in Blade Runner 2049
Authors: Taşkale Ali Rıza 
Published: September 2021

This article critically engages with Denis Villeneuve’s Blade Runner 2049, focusing on the relationship between colonial logics and biological engineering that understands the natural world as property. First, it discusses the connections between the film and the shifting status of biopolitics becoming thanatopolitics, prompted by advances in synthetic biology. It argues that the film’s preoccupation with the reproductive capacity of its replicants retraces a racialized (post) colonialism and reconfigured slavery, or the voluntary labour of the occupied – as normalized in synthetic biology and the ongoing processes of devaluing of some lives over others for socioeconomic reasons. Second, and relatedly, the film reveals how deeply the thanatopolitics of a biopolitical economy is rooted in an intensification of racialized and colonial logics. The film thus doubles as a medium in which to grasp the centrality of colonial and racial logics to the ongoing real subsumption of life by capital, and the ways in which it continues to shape the present.