bluuebunny/crossref_metadata_2025 huggingface dataset:
A Large-Scale Analysis of the Semantic Password Model and Linguistic Patterns in Passwords
Authors: Veras Rafael , Collins Christopher , Thorpe Julie
Published: April 2021

In this article, we present a thorough evaluation of semantic password grammars. We report multifactorial experiments that test the impact of sample size, probability smoothing, and linguistic information on password cracking. The semantic grammars are compared with state-of-the-art
probabilistic context-free grammar
(
PCFG
) and neural network models, and tested in cross-validation and
A vs. B
scenarios. We present results that reveal the contributions of part-of-speech (syntactic) and semantic patterns, and suggest that the former are more consequential to the security of passwords. Our results show that in many cases PCFGs are still competitive models compared to their latest neural network counterparts. In addition, we show that there is little performance gain in training PCFGs with more than 1 million passwords. We present qualitative analyses of four password leaks (Mate1, 000webhost, Comcast, and RockYou) based on trained semantic grammars, and derive graphical models that capture high-level dependencies between token classes. Finally, we confirm the similarity inferences from our qualitative analysis by examining the effectiveness of grammars trained and tested on all pairs of leaks.
Mobile, Divisible, and Safe E-Cash System
Authors: Huang Ting
Published: April 2021

Mobile, divisible, and safe e-cash system adapts on mobile terminals for e-payment which can circulate in multiple banks. The usage of the divisible e-cash does not need pass bank, which the bank has not the bottleneck of e-business. The author’s thesis discusses on the withdrawal protocol, payment protocol, transferable protocol, deposit protocol, and update of e-cash, based on elliptic curve cryptography (ECC).The system is simple, efficient, secure, and fit for the mobile e-payment terminals in which storage, power, operand capacity, and network bandwidth supply are extraordinarily restricted. The system can protect from double spending, non-frameability, eavesdropping, tampering, and “perfect crime” effectively too. It can save from mis-identity attacks, two-layer anonymity attacks, and linking attacks.
SLAM/SAP Decreased Follicular Regulatory T Cells in Patients with Graves’ Disease
Authors: Geng Lina , Yang Jun , Tang Xinyi , Peng Huiyong , Tian Jie , Hu Zhigang , Liu Yingzhao , Xu Huaxi , Wang Shengjun
Published: April 2021

Signaling lymphocytic activation molecule (SLAM) and SLAM-associated protein (SAP) play important role in inflammatory and autoimmune diseases. Our study is aimed at detecting the expression of SLAM and SAP in patients with Graves’ disease (GD) and analyzing the effect of SLAM/SAP on circulating blood CD4+CXCR5+Foxp3+ follicular regulatory T (Tfr) cells. The level of SAP in CD4+CXCR5+ T cells and the level of SLAM on CD19+ B cells were significantly increased in the patients with GD, but no significant difference in the level of SLAM on CD4+CXCR5+ T cells was observed between the patients with GD and the healthy controls. A decrease in the percentage of Foxp3+ cells in CD4+CXCR5+ T cells was observed following anti-SLAM treatment, but the percentages of IFN-γ+ cells, IL-4+ cells, and IL-17+ cells showed no obvious differences. The proportion of circulating Tfr cells was decreased in the patients with GD, and the proportion of circulating Tfr cells had a negative correlation with the level of SAP in CD4+CXCR5+ T cells and the levels of autoantibodies in the serum of the patients with GD. Our results suggested that the SLAM/SAP signaling pathway is involved in the decrease of circulating Tfr cells in Graves’ disease.
Transonic Static Aeroelastic Numerical Analysis of Flexible Complex Configuration Wing
Authors: Zhang Changrong , Guo Hongtao , Lv Binbin , Zha Jun , Yu Li
Published: April 2021

Diamond back wing is subjected to large deformation while gliding, which significantly changes characteristics of the lift as well as the static stability. For this reason, conventional rigid aircraft assumption cannot meet the requirements of the aerodynamic analysis of such aircrafts for accuracy. In this paper, based on CFD/CSD methods, the static aeroelasticity of a small diameter bomb with diamond back wing was studied. The results showed that static aeroelastic effects cause the slope of lift line to drop by 21% and the aerodynamic centre to move backwards by a 1.5% bomb body length, which will deviate the actual flight performance from the design point, thereby decreasing the cruise efficiency and the cruise range.
Yu-Ping-Feng Formula Exerts Antilung Cancer Effects by Remodeling the Tumor Microenvironment through Regulating Myeloid-Derived Suppressor Cells
Authors: Wang Yuli , Sun Ningyang , Luo Yingbin , Fang Zhihong , Fang Yuan , Tian Jianhui , Yu Yongchun , Wu Jianchun , Li Yan
Published: April 2021

Yu-Ping-Feng (YPF) formula is a classical prescription used for enhancing the body’s immunity function in traditional Chinese medicine (TCM). In clinical practice, the YPF formula has been reported to exhibit antilung cancer and immunomodulatory effect. However, the relationship between them remains unclear. The present study aimed to investigate the antilung cancer effect of the YPF formula and its immune-related mechanisms. The C57BL/6 tumor-bearing mice model was established and randomly divided into the YPF group and the control group. Tumor volume, spleen weight, and survival in both groups were measured and evaluated during 28 days of consecutive intervention. Flow cytometry was used to detect the proportion of immune cell subsets. Myeloid-derived suppressor cells (MDSCs) were induced in vitro from bone marrow cells. After intervention by the YPF formula, CCK-8 and flow cytometry analyses were performed to detect proliferation and apoptosis of MDSCs. A coculture system containing T cells and MDSCs was established to further study the role of MDSCs in the regulation of T-cell subsets proportion by the YPF formula. The expressions of MDSCs-related genes and proteins were detected by RT-PCR and Western blotting. The results showed the YPF formula inhibited tumor growth, reduced spleen weight, and prolonged the survival of mice. Besides, the proportions of MDSCs subsets and Regulatory T (Treg) in the YPF group decreased, whereas those of CD4+T and CD8+T increased both in vitro and in vivo. CCK-8 and flow cytometry demonstrated that the YPF formula could inhibit proliferation and promote apoptosis of MDSCs. The coculture experiments further confirmed that MDSCs served a critical role in regulating the tumor microenvironment by the YPF formula. RT-PCR and Western blotting indicated that the levels of MDSCs’ activation and proliferation-related proteins and genes were downregulated in the YPF group. Therefore, our results demonstrated that the YPF formula could promote apoptosis and inhibit the proliferation of MDSCs. As a result, the negative regulatory effect on the positive immune cells induced by MDSCs was weakened, thus achieving the antilung cancer effect by remodeling the tumor microenvironment.
The Keap1‐Nrf2 System: A Mediator between Oxidative Stress and Aging
Authors: Yu Chao , Xiao Jian-Hui
Published: April 2021

Oxidative stress, a term that describes the imbalance between oxidants and antioxidants, leads to the disruption of redox signals and causes molecular damage. Increased oxidative stress from diverse sources has been implicated in most senescence‐related diseases and in aging itself. The Kelch‐like ECH‐associated protein 1‐ (Keap1‐) nuclear factor‐erythroid 2‐related factor 2 (Nrf2) system can be used to monitor oxidative stress; Keap1‐Nrf2 is closely associated with aging and controls the transcription of multiple antioxidant enzymes. Simultaneously, Keap1‐Nrf2 signaling is also modulated by a more complex regulatory network, including phosphoinositide 3‐kinase (PI3K)/protein kinase B (Akt), protein kinase C, and mitogen‐activated protein kinase. This review presents more information on aging‐related molecular mechanisms involving Keap1‐Nrf2. Furthermore, we highlight several major signals involved in Nrf2 unbinding from Keap1, including cysteine modification of Keap1 and phosphorylation of Nrf2, PI3K/Akt/glycogen synthase kinase 3β, sequestosome 1, Bach1, and c‐Myc. Additionally, we discuss the direct interaction between Keap1‐Nrf2 and the mammalian target of rapamycin pathway. In summary, we focus on recent progress in research on the Keap1‐Nrf2 system involving oxidative stress and aging, providing an empirical basis for the development of antiaging drugs.
Effects of a Traditional Caraway Formulation on Experimental Models of Vitiligo and Mechanisms of Melanogenesis
Authors: Abuduaini Abudujilili , Lu Xueying , Zang Deng , Wu Tao , Aisa Haji Akbar
Published: April 2021

Background. Kursi Karwiya or caraway tablet (CWT), a traditional medicine formula, is widely used in Xinjiang, China, for treating vitiligo, a common autoimmune disease for which there is currently no satisfactory cure. Clinical interventions include pharmacological treatment with psoralens, often in conjunction with UVA radiation, but toxic side effects limit this application. Studies on the activities and mechanisms of CWT are scarce. Objective. To investigate the in vitro and in vivo effects of CWT in B16 cell line and in animal models of vitiligo, further exploring its mechanisms of regulating melanogenesis. Methods. Effects of CWT on melanin synthesis in B16 cells and mushroom tyrosinase activity were investigated in vitro. The signaling pathway of melanogenesis in murine B16 melanoma cells was examined by Western blotting. Two different animal models were used, vitiligo induced by hydroquinone in the mouse model and by hydrogen peroxide in the guinea pig model. Relevant biochemical parameters in blood and skin tissue were measured, and visual inspection, histopathology, and immunohistochemical analysis of treated areas were carried out. Results. CWT produced changes in biochemical parameters including TYR, MDA, MAO, AChE, IL-6, INF-α, β-EP, and cAMP in blood and/or skin tissue and in regulating melanogenesis. After treatment with CTW, skin color, melanin containing hair follicles, and expression of TYR, TRP-1, and TRP-2 in the skin of animals were significantly affected. Conclusions. CWT alleviated many of detrimental effects in both models of vitiligo. Tyrosinase activity and melanin content in B16 cells were increased, at least in part, via activation of the PKA p38 MAPK signaling pathways. Our results show that CWT produces beneficial effects on parameters of vitiligo and is worthy of further investigation for use in this distressing autoimmune disorder which currently has no effective cure.
COVID-19 in Children with Congenital Heart Diseases: A Multicenter Case Series from Iran
Authors: Esmaeeli Hassan , Ghaderian Mehdi , Zanjani Keyhan Sayadpour , Ghalibafan Seyyedeh Fatemeh , Mahdizadeh Mehrzad , Aelami Mohammad Hassan
Published: April 2021

Background. Promptly discovering and counteracting COVID-19 is critical as it could have catastrophic effects. As an asymptomatic group, children are highly susceptible to be misdiagnosed, especially those suffering from underlying diseases. Furthermore, discriminating the direct effects of the virus from those of the underlying diseases can pose a dilemma to physicians. This case series aims to determine the relationship between COVID-19 and various types of congenial heart disease among children. Patients and Methods. Seven patients from three different medical centers were enrolled. Their detailed demographic information, past medical history, symptoms, type of congenital heart diseases, imaging tests, laboratory tests, medications, and outcomes were analyzed. Results. The patients included 4 infants, 1 child, and 2 adolescents, with a median age of 9 months and a majority of boys. All of them had either obstructive lesions (right or left ventricular outflow tracts) or significant pulmonary hypertension. The more common clinical symptoms were cough, dyspnea, and fever. Two patients did not survive the illness. Conclusion. Prompt treatment of patients with a combination of COVID-19 and severe obstructive cardiac pathology or pulmonary hypertension is essential due to a risk for serious and/or fatal consequences.
Large Eddy Simulation and Flow Field Analysis of Car on the Bridge under Turbulent Crosswind
Authors: Ding Juyue , Yin Weitan , Ma Yongqi
Published: April 2021

As more long-span bridges continue to be completed and opened to traffic, the safety of cars driving across the bridge has attracted more and more attention, especially when the car is suddenly affected by the crosswind, the car is likely to have direction deviation or even a rollover accident. In this paper, the large eddy simulation method is used to study the flow field characteristics and safety of the car on the bridge under the turbulent crosswind. The numerical simulation model is established by referring to the Donghai Bridge, and the correctness of the car model is validated by combining with the data of wind tunnel test. The influence of factors such as the porosity and height of the bridge guardrail and the Reynolds number of airflow on the flow field characteristics is analyzed. The study shows that, in order to ensure the safety of cars on the bridge, the bridge guardrail porosity should be small, 35.8% is more suitable, the guardrail height should be more suitable within the range of 1.5–1.625 meters, and the Reynolds number should not be 3.51e + 5. The research results of this paper will provide reference for the optimal design of bridge guardrail.
An Indoor Vehicle-in-the-Loop Simulation Platform Testing Method for Autonomous Emergency Braking
Authors: Gao Ying , Zhao Xiangmo , Xu Zhigang , Cheng Jingjun , Wang Wenwei
Published: April 2021

Autonomous vehicle (AV) is expected to be the ultimate solution for traffic safety, while autonomous emergency braking (AEB), as a crucial and fundamental active safety function of AV, has excellent potential for reducing fatalities and improving road safety. Although AV has the ability to cope with harsh conditions, it is supposed to be tested fully, systematically, and rigorously before it is officially commercialized. This study developed a novel indoor AV-in-the-loop (AVIL) simulation platform based on Client-Server (C/S) architecture for real full-scale AV testing. The proposed AVIL simulation platform consists of three parts: physical hardware components, software components, and various electrical interfaces that ensure the bidirectional virtual reality (VR) interaction. To validate the functionality and performance of the platform, this paper then adopted the Udwadia–Kalaba (U-K) approach to build the AEB system based on a typical driving situation due to the explicitness and simplicity of the U-K approach. Further, a group of real road-based experiments and AVIL-based experiments were conducted. The experimental results showed that the testing data obtained from the proposed AVIL platform have a high similarity to those of the real road tests, which means that the proposed AVIL platform is capable of simulating the AV running condition when it performs linear emergency braking on the road, thus confirming the feasibility and effectiveness of the AVIL platform for AV AEB testing. Simultaneously, the testing time and repeatability of the latter performed better. The findings of this study provide a new safe, effective, and fast solution to AV testing, and the practicability of this method has been verified.
Heterogeneity and Environmental Preferences Shape the Evolution of Cooperation in Supply Networks
Authors: Mu Dong , Yue Xiongping
Published: April 2021

Supply networks as complex systems are significant challenges for decision‐makers in predicting the evolution of cooperation among firms. The impact of environmental heterogeneity on firms is critical. Environment‐based preference selection plays a pivotal role in clarifying the existence and maintenance of cooperation in supply networks. This paper explores the implication of the heterogeneity of environment and environment‐based preference on the evolution of cooperation in supply networks. Cellular automata are considered to examine the synchronized evolution of cooperation and defection across supply networks. The Prisoner’s Dilemma Game and Snowdrift Game reward schemes have been formed, and the heterogeneous environment and environmental preference have been applied. The results show that the heterogeneous environment’s degree leads to higher cooperation for both Prisoner’s Dilemma Game and Snowdrift Game. We also probe into the impact of the environmental preference on the evolution of cooperation, and the results of which confirm the usefulness of preference of environment. This work offers a valuable perspective to improve the level of cooperation among firms and understand the evolution of cooperation in supply networks.
Cancer Mortality Disparities among Asian American and Native Hawaiian/Pacific Islander Populations in California
Authors: Medina Heidy N. , Callahan Karen E. , Morris Cyllene R. , Thompson Caroline A. , Siweya Adugna , Pinheiro Paulo S.
Published: April 2021

Background:

Asian American and Native Hawaiian/Pacific Islanders (AANHPI) are the fastest growing minority in the United States. Cancer is the leading cause of death for AANHPIs, despite relatively lower cancer morbidity and mortality. Their recent demographic growth facilitates a detailed identification of AANHPI populations with higher cancer risk.

Methods:

Age-adjusted, sex-stratified, site-specific cancer mortality rates from California for 2012 to 2017 were computed for AANHPI groups: Chinese, Filipino, South Asian, Vietnamese, Korean, Japanese, Southeast Asian (i.e., Cambodian, Hmong, Laotian, Thai), and Native Hawaiian and Other Pacific Islander (NHOPI). Regression-derived mortality rate ratios (MRR) were used to compare each AANHPI group to non-Hispanic whites (NHW).

Results:

AANHPI men and women (total 40,740 deaths) had lower all-sites-combined cancer mortality rates (128.3 and 92.4 per 100,000, respectively) than NHWs (185.3 and 140.6) but higher mortality for nasopharynx, stomach, and liver cancers. Among AANHPIs, both NHOPIs and Southeast Asians had the highest overall rates including for colorectal, lung (men only), and cervical cancers; South Asians had the lowest. NHOPI women had 41% higher overall mortality than NHWs (MRR = 1.41; 95% CI, 1.25–1.58), including for breast (MRR = 1.33; 95% CI, 1.08–1.65) and markedly higher for endometrial cancer (MRR = 3.34; 95% CI, 2.53–4.42).

Conclusions:

AANHPI populations present with considerable heterogeneous cancer mortality patterns. Heightened mortality for infection, obesity, and tobacco-related cancers in Southeast Asians and NHOPI populations highlight the need for differentiated priorities and public health interventions among specific AANHPI populations.

Impact:

Not all AANHPIs have favorable cancer profiles. It is imperative to expand the focus on the currently understudied populations that bear a disproportionate cancer burden.
Anemia May Increase the Overall Risk of Cancer: Findings from a Cohort Study with a 12-Year Follow-up Period in South Korea
Authors: Oh Tak Kyu , Song In-Ae
Published: April 2021

Background:

No previous study has assessed cancer risk in individuals with anemia diagnosed based on hemoglobin levels. Thus, we aimed to investigate whether anemia increases the risk of cancer.

Methods:

Adult individuals who underwent a standardized medical examination during 2002 and 2003 in South Korea were included, and their cancer status was evaluated between January 2004 and December 2015 (12 years) as a primary endpoint. Anemia was defined as serum hemoglobin levels of <12 and <13 g/dL for women and men, respectively.

Results:

A total of 454,304 adults were included in the final analysis. Among them, 41,947 (9.2%) and 412,357 (90.8%) individuals constituted the anemia and control groups, respectively. After propensity score matching, a total of 83,886 individuals (41,943 per group) were included in the analysis. Cox regression revealed that the risk of cancer in the anemia group was 3% higher than that in the control group (HR, 1.03; 95% confidence interval, 1.01–1.05; P = 0.023). Specifically, relative to the control group, the anemia group was at an increased risk of gastric (HR, 1.29), esophageal (HR, 1.37), lung (HR, 1.14), and thyroid cancers (HR, 1.14), neoplasms of breast and genital organs (HR, 1.12), and lymphoma or leukemia (HR, 1.63).

Conclusions:

Anemia was independently associated with an increased overall risk of cancer. Further research is required to clarify the associated mechanism.

Impact:

Anemia was independently associated with an increased overall risk of cancer in the South Korean population.
Clinical and Immunologic Responses to a B-Cell Epitope Vaccine in Patients with HER2/neu-Overexpressing Advanced Gastric Cancer—Results from Phase Ib Trial IMU.ACS.001
Authors: Wiedermann Ursula , Garner-Spitzer Erika , Chao Yee , Maglakelidze Marina , Bulat Iurie , Dechaphunkul Arunee , Arpornwirat Wichit , Charoentum Chaiyut , Yen Chia-Jui , Yau Thomas Cheung , Tanasanvimon Suebpong , Maneechavakajorn Jedzada , Sookprasert Aumkhae , Bai Li-Yuan , Chou Wen-Chi , Ungtrakul Teerapat , Drinic Mirjana , Tobias Joshua , Zielinski Christoph C. , Chong Leslie , Ede Nicholas J. , Marino Mark T. , Good Anthony J.
Published: April 2021

Purpose:

HER2/neu is overexpressed in up to 30% of gastroesophageal adenocarcinomas (GEA) and linked to poor prognosis. Recombinant mAbs to treat HER2/neu-overexpressing cancers are effective with limitations, including resistance and toxicity. Therefore, we developed a therapeutic B-cell epitope vaccine (IMU-131/HER-Vaxx) consisting of three fused B-cell epitopes from the HER2/neu extracellular domain coupled to CRM197 and adjuvanted with Montanide. This phase Ib study aimed to evaluate the optimal/safe dose leading to immunogenicity and clinical responses (https//clinicaltrials.gov/ct2/show/NCT02795988).

Patients and Methods:

A total of 14 patients with HER2/neu-overexpressing GEA were enrolled, and dose escalation (10, 30, 50 μg) was performed in three cohorts (C). Immunogenicity was evaluated by HER2-specific Abs and cellular responses, clinical responses by CT scans according to RECIST version 1.1.

Results:

IMU-131 was safe without vaccine-related significant local/systemic reactions or serious adverse events. A total of 11 of 14 patients were evaluable for changes in tumor size and vaccine-specific immune responses. One patient showed complete, 5 partial responses, and 4 stable diseases as their best response. HER2-specific IgG levels were dose dependent. In contrast to patients in C1 and C2, all patients in C3 mounted substantial HER2-specific Ab levels. In addition, cellular vaccine responses, such as Th1-biased cytokine ratios and reduced regulatory T cell numbers, were generated. Progression-free survival was prolonged in C3, correlating with the vaccine-specific humoral and cellular responses.

Conclusions:

IMU-131 was well tolerated and safe. The induced HER2-specific Abs and cellular responses were dose dependent and correlated with clinical responses. The highest dose (50 μg) was recommended for further evaluation in a phase II trial, with chemotherapy + IMU-131 or chemotherapy alone, which is currently ongoing.
PCA062, a P-cadherin Targeting Antibody–Drug Conjugate, Displays Potent Antitumor Activity Against P-cadherin–expressing Malignancies
Authors: Sheng Qing , D'Alessio Joseph A. , Menezes Daniel L. , Karim Christopher , Tang Yan , Tam Angela , Clark Suzanna , Ying Chi , Connor Anu , Mansfield Keith G. , Rondeau Jean-Michel , Ghoddusi Majid , Geyer Felipe C. , Gu Jane , McLaughlin Margaret E. , Newcombe Rick , Elliot GiNell , Tschantz William R. , Lehmann Sylvie , Fanton Christie P. , Miller Kathy , Huber Thomas , Rendahl Katherine G. , Jeffry Ursula , Pryer Nancy K. , Lees Emma , Kwon Paul , Abraham Judith A. , Damiano Jason S. , Abrams Tinya J.
Published: April 2021

The cell surface glycoprotein P-cadherin is highly expressed in a number of malignancies, including those arising in the epithelium of the bladder, breast, esophagus, lung, and upper aerodigestive system. PCA062 is a P-cadherin specific antibody–drug conjugate that utilizes the clinically validated SMCC-DM1 linker payload to mediate potent cytotoxicity in cell lines expressing high levels of P-cadherin in vitro, while displaying no specific activity in P-cadherin–negative cell lines. High cell surface P-cadherin is necessary, but not sufficient, to mediate PCA062 cytotoxicity. In vivo, PCA062 demonstrated high serum stability and a potent ability to induce mitotic arrest. In addition, PCA062 was efficacious in clinically relevant models of P-cadherin–expressing cancers, including breast, esophageal, and head and neck. Preclinical non-human primate toxicology studies demonstrated a favorable safety profile that supports clinical development. Genome-wide CRISPR screens reveal that expression of the multidrug-resistant gene ABCC1 and the lysosomal transporter SLC46A3 differentially impact tumor cell sensitivity to PCA062. The preclinical data presented here suggest that PCA062 may have clinical value for treating patients with multiple cancer types including basal-like breast cancer.
BRAF
V600E Mutation in Cell-Free DNA, Rather than in Lesion Tissues, at Diagnosis Is An Independent Prognostic Factor in Children with Langerhans Cell Histiocytosis
Authors: Wang Chan-Juan , Cui Lei , Ma Hong-Hao , Wang Dong , Zhang Li , Lian Hong-Yun , Li Wei-Jing , Zhang Qing , Wang Tian-You , Li Zhi-Gang , Zhang Rui
Published: April 2021

The aim of this study was to investigate the prognostic significance of BRAFV600E in cell-free (cf) DNA (cfBRAFV600E) and lesion tissues (ltBRAFV600E) in pediatric Langerhans cell histiocytosis (LCH). This study included a total of 140 patients with successfully detected cfBRAFV600E and ltBRAFV600E at diagnosis. Treatment response at week 6 was correlated with both cfBRAFV600E and ltBRAFV600E. Moreover, the patients with positive cfBRAFV600E had a much lower 3-year progression-free survival (PFS) rate and a higher progression/reactivation rate than those with negative cfBRAFV600E (47.1% ± 7.6% vs. 78.4% ± 5.1%, P < 0.0001; 44.6% vs. 19.0%, P = 0.001, respectively). However, no significant difference was found in the 3-year PFS rate or progression/reactivation rate between patients with positive and negative ltBRAFV600E (P = 0.348 and 0.596, respectively). In addition, after patients were divided into group A (both cfBRAFV600E and ltBRAFV600E positive, n = 56), group B (ltBRAFV600E positive and cfBRAFV600E negative, n = 28), and group C (both cfBRAFV600E and ltBRAFV600E negative, n = 56), there was a significant difference in the 3-year PFS rate and progression/reactivation rate among the three groups (47.1% ± 7.6%, 92.9% ± 6.1%, and 72.2% ± 6.1%, P < 0.001; 44.6%, 3.6%, and 26.8%, P < 0.001, respectively). In the multivariate analysis, cfBRAFV600E and age at diagnosis remained independent prognostic factors for 3-year PFS in childhood LCH. Therefore, cfBRAFV600E was more closely associated with important clinical characteristics, treatment response at week 6, and prognosis than ltBRAFV600E.
Independent and Joint Effects of Testosterone Replacement Therapy and Statins use on the Risk of Prostate Cancer Among White, Black, and Hispanic Men
Authors: Lopez David S. , Polychronopoulou Efstathia , Tsilidis Konstantinos K. , Khera Mohit , Su L. Joseph , Fowke Jay H. , Peek M.K. , Kuo Yong-Fang , Markides Kyriakos , Canfield Steven
Published: April 2021

The associations of testosterone therapy (TTh) and statins use with prostate cancer remain conflicted. However, the joint effects of TTh and statins use on the incidence of prostate cancer, stage and grade at diagnosis, and prostate cancer-specific mortality (PCSM) have not been studied.

We identified White (N = 74,181), Black (N = 9,157), and Hispanic (N = 3,313) men diagnosed with prostate cancer in SEER-Medicare 2007–2016. Prediagnostic prescription of TTh and statins was ascertained for this analysis. Weighted multivariable-adjusted conditional logistic and Cox proportional hazards models evaluated the association of TTh and statins with prostate cancer, including statistical interactions between TTh and statins.

We found that TTh (OR = 0.74; 95% CI, 0.68–0.81) and statins (OR = 0.77; 95% CI, 0.0.75–0.88) were inversely associated with incident prostate cancer. Similar inverse associations were observed with high-grade and advanced prostate cancer in relation to TTh and statins use. TTh plus statins was inversely associated with incident prostate cancer (OR = 0.53; 95% CI, 0.48–0.60), high-grade (OR = 0.43; 95% CI, 0.37–0.49), and advanced prostate cancer (OR = 0.44; 95% CI, 0.35–0.55). Similar associations were present in White and Black men, but among Hispanics statins were associated with PCSM.

Prediagnostic use of TTh or statins, independent or combined, was inversely associated with incident and aggressive prostate cancer overall and in NHW and NHB men. Findings for statins and aggressive prostate cancer are consistent with previous studies. Future studies need to confirm the independent inverse association of TTh and the joint inverse association of TTh plus statins on risk of prostate cancer in understudied populations.

Prevention Relevance:

The study investigates a potential interaction between TTh and statin and its effect on incident and aggressive prostate cancer in men of different racial and ethnic backgrounds. These results suggest that among NHW and non-Hispanic Black men TTh plus statins reduced the odds of incident prostate cancer, high-grade and advance stage prostate cancer.
Insulin ist notwendig, aber nicht ausreichend: Paradigmenwechsel in der Behandlung des Typ-1-Diabetes
Authors: Lord Sandra , Greenbaum Carla J.
Published: April 2021

Ungeachtet der eindeutigen Belege dafür, dass Typ-1-Diabetes (T1D) bereits deutlich vor einer Manifestation von Hyperglykämie beginnt, stehen keine krankheitsmodifizierenden Therapien für die Behandlung der Erkrankung im Frühstadium zur Verfügung. Nach den hoch interessanten Ergebnissen der Teplizumab Prevention Studie – der ersten Studie, die nachweisen konnte, dass sich ein manifester T1D durch eine Immuntherapie hinauszögern lässt – steigt die Hoffnung wieder, dass T1D in Zukunft vor Entwicklung einer Hyperglykämie behandelt werden kann. Es bedarf eines Paradigmenwechsels, da die Mehrheit der Menschen mit T1D die glykämischen Zielwerte nicht erreicht, die mit einem niedrigeren Risiko für T1D-Komplikationen verbunden sind, und bei denen daher weiterhin die Gefahr von Komplikationen und einer verkürzten Lebenserwartung besteht. Die folgende Übersichtsarbeit beschäftigt sich mit der Geschichte und dem aktuellen Stand der Immuntherapie bei T1D und beleuchtet einige Herausforderungen und Ideen für die Zukunft. Auch wenn diese Anstrengungen weltweit unternommen werden, konzentrieren wir uns hier vor allem auf die 2004 aufgelegten Forschungsaktivitäten des Diabetes TrialNet, eines Konsortiums der US-amerikanischen National Institutes of Health.
Role of Adenylate Cyclase 9 in the Pharmacogenomic Response to Dalcetrapib
Authors: Rhainds David , Packard Chris J. , Brodeur Mathieu R. , Niesor Eric J. , Sacks Frank M. , Jukema J. Wouter , Wright R. Scott , Waters David D. , Heinonen Therese , Black Donald M. , Laghrissi-Thode Fouzia , Dubé Marie-Pierre , Pfeffer Marc A. , Tardif Jean-Claude
Published: April 2021

Following the neutral results of the dal-OUTCOMES trial, a genome-wide study identified the rs1967309 variant in the adenylate cyclase type 9 (
ADCY9
) gene on chromosome 16 as being associated with the risk of future cardiovascular events only in subjects taking dalcetrapib, a CETP (cholesterol ester transfer protein) modulator. Homozygotes for the minor A allele (AA) were protected from recurrent cardiovascular events when treated with dalcetrapib, while homozygotes for the major G allele (GG) had increased risk. Here, we present the current state of knowledge regarding the impact of rs1967309 in
ADCY9
on clinical observations and biomarkers in dalcetrapib trials and the effects of mouse
ADCY9
gene inactivation on cardiovascular physiology. Finally, we present our current model of the interaction between dalcetrapib and
ADCY9
gene variants in the arterial wall macrophage, based on the intracellular role of CETP in the transfer of complex lipids from endoplasmic reticulum membranes to lipid droplets. Briefly, the concept is that dalcetrapib would inhibit CETP-mediated transfer of cholesteryl esters, resulting in a progressive inhibition of cholesteryl ester synthesis and free cholesterol accumulation in the endoplasmic reticulum. Reduced ADCY9 activity, by paradoxically leading to higher cyclic AMP levels and in turn increased cellular cholesterol efflux, could impart cardiovascular protection in rs1967309 AA patients. The ongoing dal-GenE trial recruited 6145 patients with the protective AA genotype and will provide a definitive answer to whether dalcetrapib will be protective in this population.
Cardiac Magnetic Resonance–Derived Extracellular Volume Mapping for the Quantification of Hepatic and Splenic Amyloid
Authors: Chacko Liza , Boldrini Michele , Martone Raffaele , Law Steven , Martinez-Naharrro Ana , Hutt David F. , Kotecha Tushar , Patel Rishi K. , Razvi Yousuf , Rezk Tamer , Cohen Oliver C. , Brown James T. , Srikantharajah Mukunthan , Ganesananthan Sharmananthan , Lane Thirusha , Lachmann Helen J. , Wechalekar Ashutosh D. , Sachchithanantham Sajitha , Mahmood Shameem , Whelan Carol J. , Knight Daniel S. , Moon James C. , Kellman Peter , Gillmore Julian D. , Hawkins Philip N. , Fontana Marianna
Published: April 2021

Background:

Systemic amyloidosis is characterized by amyloid deposition that can involve virtually any organ. Splenic and hepatic amyloidosis occurs in certain types, in some patients but not others, and may influence prognosis and treatment. SAP (serum amyloid P component) scintigraphy is uniquely able to identify and quantify amyloid in the liver and spleen, thus informing clinical management, but it is only available in 2 centers globally. The aims of this study were to examine the potential for extracellular volume (ECV) mapping performed during routine cardiac magnetic resonance to: (1) detect amyloid in the liver and spleen and (2) estimate amyloid load in these sites using SAP scintigraphy as the reference standard.

Methods:

Five hundred thirty-three patients referred to the National Amyloidosis Centre, London, between 2015 and 2017 with suspected systemic amyloidosis who underwent SAP scintigraphy and cardiac magnetic resonance with T1 mapping were studied.

Results:

The diagnostic performance of ECV to detect splenic and hepatic amyloidosis was high for both organs (liver: area under the curve, −0.917 [95% CI, 0.880–0.954]; liver ECV cutoff, 0.395; sensitivity, 90.7%; specificity, 77.7%;
P
<0.001; spleen: area under the curve, −0.944 [95% CI, 0.925–0.964]; spleen ECV cutoff, 0.385; sensitivity, 93.6%; specificity, 87.5%;
P
<0.001). There was good correlation between liver and spleen ECV and amyloid load assessed by SAP scintigraphy (r=0.504,
P
<0.001; r=0.693,
P
<0.001, respectively). There was high interobserver agreement for both the liver and spleen (ECV liver intraclass correlation coefficient, 0.991 [95% CI, 0.984–0.995];
P
<0.001; ECV spleen intraclass correlation coefficient, 0.995 [95% CI, 0.991–0.997];
P
<0.001) with little bias across a wide range of ECV values.

Conclusions:

Our study demonstrates that ECV measurements obtained during routine cardiac magnetic resonance scans in patients with suspected amyloidosis can identify and measure the magnitude of amyloid infiltration in the liver and spleen, providing important clues to amyloid type and offering a noninvasive measure of visceral amyloid burden that can help guide and track treatment.
Pregnancy in the Cardiac Catheterization Laboratory
Authors: Cheney Amy E. , Vincent Logan L. , McCabe James M. , Kearney Kathleen E.
Published: April 2021

Concerns over radiation exposure are ubiquitous to all interventional cardiologists; however, fear of exposure during childbearing years disproportionately deters women from entering the field. This review summarizes the available data on occupational radiation exposure during pregnancy with an emphasis on radiation quantification, the impact of exposure at various stages of fetal development, societal recommendations for safe levels of exposure during gestation, threshold levels necessary to induce fetal harm, and safe practices for the pregnant interventionalist. Reconciling the available information, we conclude that pregnancy in the cardiac catheterization laboratory is both safe and feasible. This review also highlights new technologies that may augment standard radiation safety techniques and are of particular interest to the pregnant interventional cardiologist. Finally, we propose steps to improve female representation in this field, underscoring the importance of a sex-balanced workforce.
Water and Warfare: The Evolution and Operation of the Water Taboo
Authors: Grech-Madin Charlotte
Published: April 2021

For much of human history, water was a standard weapon of war. In the post–World War II period, however, nation-states in international conflict have made concerted efforts to restrain the weaponization of water. Distinct from realist and rationalist explanations, the historical record reveals that water has come to be governed by a set of intersubjective standards of behavior that denounce water's involvement in conflict as morally taboo. How did this water taboo develop, and how does it matter for nation-states? Focused process-tracing illuminates the taboo's development from the 1950s to the 2010s, and indicates that (1) a moral aversion to using water as a weapon exists; (2) this aversion developed through cumulative mechanisms of taboo evolution over the past seventy years; and (3) the taboo influences states at both an instrumental level of compliance, and, in recent decades, a more internalized level. These findings offer new avenues for research and policy to better understand and uphold this taboo into the future.
Once More a Weasel
Authors: Farmer Matthew C.
Published: April 2021

At the premiere of Euripides’ Orestes in 408 BCE, the actor Hegelochos, playing the part of Orestes, made a small but destructive error in his performance: while attempting to deliver the line ‘after the storm I see once more a calm’, he said instead, ‘after the storm I see once more a weasel’. The comic poets Strattis, Sannyrion, and Aristophanes each present versions of this error in their plays; this paper contextualizes their treatment of Hegelochos within the portrayal of tragic actors in comedy generally, and argues that they portray Hegelochos’ mistake as an act of instantaneous tragic parody.
Dealing with the unexpected: the effect of environmental variability on behavioural flexibility in a Mediterranean lizard
Authors: De Meester Gilles , Sfendouraki-Basakarou Alkyoni , Pafilis Panayiotis , Van Damme Raoul
Published: April 2021

Harsh and variable environments have been hypothesized to both drive and constrain the evolution towards higher cognitive abilities and behavioural flexibility. In this study, we compared the cognitive abilities of island and mainland Aegean wall lizards (Podarcis erhardii), which were expected to live in respectively a more variable and a more stable habitat. We used four proxies of behavioural flexibility: a neophobia assay, a problem-solving test and a spatial + reversal learning task. Surprisingly, the two populations did not differ in neophobia or problem-solving. Insular lizards, however, outperformed mainland conspecifics in an initial spatial learning task, but were less successful during the subsequent reversal learning. Our results thus seem to indicate that the effect of environmental variability on cognition is complex, as it may favour some, but not all aspects of behavioural flexibility.
Description of Leurocyclus tuberculosus (Decapoda, Brachyura) for northern Chilean Patagonian inner seas (41°S, Puerto Montt, Chile)
Authors: De los Ríos-Escalante Patricio , Ibáñez-Arancibia Eliana
Published: April 2021

The brachyuran crab, Leurocyclus tuberculosus (H. Milne Edwards & Lucas, 1842) is widely distributed along the Atlantic coast of South America, but there are no precise records about its occurrence on the Chilean Pacific coast. The present study is a description of four juvenile specimens of L. tuberculosus collected from an intertidal prairie of Gracilaria sp. in an inner sea in Chile (41°S, Puerto Montt). According to existing literature, the specimens would be juvenile individuals belonging to L. tuberculosus that, in accordance with the literature, was described as probably inhabiting the Chilean coasts without more details. The literature revealed that this species is widely distributed along the Atlantic coasts of South America, and can also, probably due to dynamic oceanographic processes, be present on the southern Pacific coast.
A Double-Plated Cosmos? Gen 1’s Cosmology, the Baal Stele, and the Logic of a Firmament of the Earth
Authors: Boyd Samuel L.
Published: April 2021

The cosmology as described in the creation account in Gen 1:1–2:4a has occasioned endless commentary. One of the more perceptive studies of this text was published by Baruch Halpern in 2003. In this article, I review Halpern’s argument and add evidence from iconography at Ugarit. The Baal Stele (Louvre catalog number AO 15775), in which the deity holds lightning and stands with the king, also displays a cosmology that has intriguing connections with Halpern’s thesis about an “expanse of the earth.” After connecting Halpern’s thesis to this visual representation of cosmology from Ugarit, I explore the ways in which both text and image are mutually illuminating and help to interpret one another, extending the analysis to so-called Deutero-Isaiah and Ps 136 as well.
On the History and Evolution of Qws: The Portrait of a First Millennium BCE Deity Explored through Community Identity
Authors: Danielson Andrew J.
Published: April 2021

This article explores the history and evolution of the deity Qws through a study of the communities affiliated with Qws, presenting also a current collection of all inscriptional references to this deity. Diachronic and spatial analyses of the references reveal nuanced insights into how Qws was understood by his adherents, as well as the patterns of behavior, linguistic practices, and identities that marked these communities. The attestations of Qws demonstrate the deity’s relative obscurity during the Late Bronze Age, a rapid rise in inscriptional popularity among persons associated with the region of Edom during the late Iron Age, and a regional perpetuation of attestation following the dissolution of the Iron Age southern Levantine polities. Furthermore, attestations of Qws among diasporic community’s present insights into the shifting identities and cultic practices of the immigrant communities affiliated with the deity.
‘A Hussy Who Rode on Horseback in Sexy Underwear in Front of the Prisoners’: the Trials of Buchenwald’s Ilse Koch
Authors: Drumbl Mark , Mouthaan Solange
Published: April 2021

Ilse Koch’s trials for her role in atrocities at the Nazi Buchenwald concentration camp served as visual spectacles and primed her portrayal in media and public spaces. Koch’s conduct was credibly rumored to be one of frequent affairs, simultaneous lovers, and the sexual humiliation of prisoners. The gendered construction of her sexual identity played a distortive role in her intersections with law and with post-conflict Germany. Koch’s trials revealed two different dynamics. Koch’s actions were refracted through a patriarchal lens which spectacularized female violence and served as an optical space to (re)establish appropriate feminine mores. Feminist critiques of Koch’s trials furthermore also spun problematic narratives of womanly innocence and victimized powerlessness, or at times ignored her as a perpetrator. In the end Koch’s actual story—‘her’ story—becomes lost amid prurience, politics, and burlesque.
The Reception of Receptive Ecumenism
Authors: Ryan Gregory A.
Published: April 2021

Receptive Ecumenism (re) has been presented as a distinctive ecumenical approach for nearly fifteen years, and it is eight years since Paul Avis asked the critical question, ‘Are we Receiving Receptive Ecumenism?’ The main part of this essay addresses that question by surveying the different ways in which re has been received in the academy, in ecumenical bodies, and in the life of the churches. A shorter section then outlines a proposal for viewing re in a wider ecclesiological context, rather than simply as an ecumenical practice. The essay primarily focuses on resources developed since 2012 in order to assess the breadth and depth of contemporary reception of re, and potential future developments.
Fonctionnement sémantique du connecteur coréen -ko : temporalité, aspectualité et manière
Authors: Son Hyunjung , Nam Kishim
Published: April 2021

This article aims to examine the Korean connective -ko, which is generally considered an equivalent of the French connective et. The connective -ko is semantically polyvalent, having several interpretations such as enumeration, temporal succession, simultaneity, causality, and manner. In this article, we examine the expression of “manner” by the connective -ko on the hypothesis that such interpretation is derived from the temporal function of simultaneity of -ko. We introduce two main functions of -ko, temporal connection and simple connection by contiguity and then show how the temporal function interacts with the aspectual properties of propositions connected by -ko to generate the interpretation of manner.
Cuba Through A New Lens
Authors: Stubbs Jean
Published: April 2021

[First paragraph]The Origins of the Cuban Revolution Reconsidered. Samuel Farber. Chapel Hill: University of North Carolina Press, 2006. x + 212 pp. (Paper US$ 19.95)Cuba: A New History. Ric hard Gott . New Haven: Yale University Press, 2005. xii + 384 pp. (Paper US$ 17.00)Havana: The Making of Cuban Culture. Antoni Kapcia. Oxford: Berg Publishers, 2005. xx + 236 pp. (Paper US$ 24.95) Richard Gott, Antoni Kapcia, and Samuel Farber each approach Cuba through a new lens. Gott does so by providing a broad-sweep history of Cuba, which is epic in scope, attaches importance to social as much as political and economic history, and blends scholarship with flair. Kapcia homes in on Havana as the locus for Cuban culture, whereby cultural history becomes the trope for exploring not only the city but also Cuban national identity. Farber revisits his own and others’ interpretations of the origins of the Cuban Revolution.
Toward a Carribean cultural political economy
Authors: Sheller Mimi
Published: April 2021

[First paragraph]The Caribbean Postcolonial: Social Equality, Post-Nationalism and Cultural Hybridity. Shalini Puri. New York: Palgrave Macmillan, 2004. ix + 300 pp. (Paper US$ 24.95)Miraculous Weapons: Revolutionary Ideology in Caribbean Culture. Joy A.I. Mahabir. New York: Peter Lang, 2003. ix + 167 pp. (Cloth US$ 58.95)The relation between cultural production and political struggle, and between the aesthetic and the material as expressions of social relations, are absolutely central themes within Caribbean studies in all of its disciplinary and interdisciplinary guises. A key question for the field as a whole is what role it might play in generating new approaches to “cultural political economy,” which is emerging as an effective bridging concept at the intersections of anthropology, sociology, economics, political theory, and literary and cultural studies.