bluuebunny/crossref_metadata_2025 huggingface dataset:
Total Reflection X-Ray Fluorescence Spectroscopy (TXRF) Method Validation: Determination of Heavy Metals in Dietary Supplements
Authors: Beltrán Blanca G. , Ramos-Sanchez Victor , Chávez-Flores David , Rodríguez-Maese Rogelio , Palacio Edwin
Published: December 2020

Dietary supplements may contain heavy metals with the property of bioaccumulation in humans. The aim of this research was to validate and apply two analytical methods to determine Pb, As, Cr, and Hg in dietary supplements by Total Reflection X-ray Fluorescence Spectroscopy (TXRF). Methods validation was conducted through a multivariate analysis using a central composite design (CCD) and a desirability function. Critical values for each study variable were established. The TXRF_DS_1 method was proposed for Pb, As, and Cr determinations, while the TXRF_DS_2 was established for Hg analysis. The digestion method with an acid mixture (HNO3 + HCl + H2O2) was used to break down the organic material of dietary supplements. A solution of 10 μg L−1 Ga was used as an internal standard. Excellent analytical performance was obtained as LODs of 0.59, 0.41, 0.57, and 0.75 μg L−1 and LOQs of 1.95, 1.35, 1.90, and 2.50 μgL −1 for Pb, As, Cr, and Hg, respectively. Calibration curves showed a good linearity for all elements (R2>0.999). Excellent accuracy and precision in measurements (% RSD) was achieved. The real and spiked samples analysis demonstrated the applicability of the TXRF technique (percentage recovery 91–108%). Besides, two samples were analyzed in a comparison study between the TXRF_DS_1 method and the ICP-OES method. The results obtained showed good agreement between both techniques. The TXRF technique allows the analysis of toxic heavy metals in dietary supplements, which are marketed in a wide variety of presentations.
GroupTracer: Automatic Attacker TTP Profile Extraction and Group Cluster in Internet of Things
Authors: Wu Yixin , Huang Cheng , Zhang Xing , Zhou Hongyi
Published: December 2020

As Advanced Persistent Threat (APT) becomes increasingly frequent around the world, security experts are starting to look at how to observe, predict, and mitigate the damage from APT attacks. In the meantime, the Internet of things devices are also risky and heavily exposed to the Internet, making them more easily used by hacker organizations to launch APT attacks. An excellent attacker can take down millions of Internet of things devices in a short time. Once the IoT botnet is built, attackers can use it to launch complex attacks which could damage Internet infrastructure and cause network disconnection. This paper proposes GroupTracer, a framework for observing and predicting the Internet of things attacks. GroupTracer is designed to automatically extract the TTP profiles (i.e., tactics, techniques, and procedures) that can describe the behavior of attackers through their tactics, techniques, and processes and dig out the potential attacker groups behind complex attacks. Firstly, it captures attacks by IoT honeypots and extracts relevant fields from logs. Then, attack behaviors are automatically mapped to the ATT&CK framework to achieve automatic TTP profiles extraction. After that, GroupTracer presents four feature groups, including TTP profiles, Time, IP, and URL features, a total of 18 features, mines potential attack groups through hierarchical clustering algorithm, and compares the clustering results with two baseline algorithms. As the ground truth labels are unknown, we apply three internal validation indexes to evaluate the cluster quantity. Experimental results showed that the proposed framework has achieved an excellent performance in exploiting potential groups as the Calinski–Harabasz index reaches 3416.93. Eventually, attack trees are generated for each cluster where nodes indicate attack commands and edges represent command sequences. These attack trees could help better understand each attack group’s actions and techniques.
MDMX Recruits UbcH5c to Facilitate MDM2 E3 Ligase Activity and Subsequent p53 Degradation In Vivo
Authors: Yang Jing , Jin Aiwen , Han Jing , Chen Xin , Zheng Junnian , Zhang Yanping
Published: December 2020

MDM2 regulates p53 degradation by functioning as an E3 ubiquitin ligase. The role of MDMX, an MDM2 homolog that lacks E3 ligase activity, in the regulation of p53 degradation remains incompletely understood and sometime controversial. This confusion is due at least in part to studies of p53 degradation mainly carried out in in vitro settings, as elimination of either MDM2 or MDMX from mice results in p53-dependent embryonic lethality, thus obfuscating in vivo studies of the individual roles of MDM2 and MDMX in p53 degradation. To overcome this problem, we generated mice expressing an inducible p53 allele under various MDM2 and MDMX deletion and mutation statuses and studied in vivo p53 degradation. Degradation of p53 in vivo was largely prevented in mice and mouse embryonic fibroblast retaining MDM2 but lacking MDMX. Although MDM2 and MDMX interacted with p53 in the absence of each other, they bound p53 more efficiently as a heterodimer. MDMX, but not MDM2, interacted with ubiquitin-conjugating enzyme UbcH5c, an interaction that was essential for MDMX to enable MDM2 E3 ligase activity for p53 degradation. Grafting the C-terminal residues of MDMX to the C-terminus of MDM2 allowed MDM2 to interact with UbcH5c and enhanced MDM2-mediated p53 degradation in the absence of MDMX. Together, these data indicate that MDMX plays an essential role for p53 degradation in vivo by recruiting UbcH5c to facilitate MDM2 E3 ligase function.

Significance:

This study provides the first in vivo evidence of MDMX facilitating MDM2-mediated p53 degradation, clarifying its role in the regulation of this critical tumor suppressor.
KIF15-Mediated Stabilization of AR and AR-V7 Contributes to Enzalutamide Resistance in Prostate Cancer
Authors: Gao Lin , Zhang Wenbo , Zhang Jing , Liu Junmei , Sun Feifei , Liu Hui , Hu Jing , Wang Xin , Wang Xueli , Su Peng , Chen Shouzhen , Qu Sifeng , Shi Benkang , Xiong Xueting , Chen Weiwen , Dong Xuesen , Han Bo
Published: December 2020

The new generation androgen receptor (AR) pathway inhibitor enzalutamide can prolong the survival of patients with metastatic prostate cancer. However, resistance to enzalutamide inevitably develops in these patients, and the underlying mechanisms of this resistance are not fully defined. Here we demonstrate that the kinesin family member 15 (KIF15) contributes to enzalutamide resistance by enhancing the AR signaling in prostate cancer cells. KIF15 directly bound the N-terminus of AR/AR-V7 and prevented AR/AR-V7 proteins from degradation by increasing the protein association of ubiquitin-specific protease 14 (USP14) with AR/AR-V7. In turn, the transcriptionally active AR stimulated KIF15 expression. KIF15 inhibitors alone or in combination with enzalutamide significantly suppressed enzalutamide-resistant prostate cancer cell growth and xenograft progression. These findings highlight a key role of KIF15 in enabling prostate cancer cells to develop therapy resistance to enzalutamide and rationalize KIF15 as a potential therapeutic target.

Significance:

These findings demonstrate how reciprocal activation between KIF15 and AR contributes to enzalutamide resistance in prostate cancer and highlights cotargeting KIF15 and AR as a therapeutic strategy for these tumors.
Simplified Breast Risk Tool Integrating Questionnaire Risk Factors, Mammographic Density, and Polygenic Risk Score: Development and Validation
Authors: Rosner Bernard , Tamimi Rulla M. , Kraft Peter , Gao Chi , Mu Yi , Scott Christopher , Winham Stacey J. , Vachon Celine M. , Colditz Graham A.
Published: December 2020

Background:

Clinical use of breast cancer risk prediction requires simplified models. We evaluate a simplified version of the validated Rosner–Colditz model and add percent mammographic density (MD) and polygenic risk score (PRS), to assess performance from ages 45–74. We validate using the Mayo Mammography Health Study (MMHS).

Methods:

We derived the model in the Nurses' Health Study (NHS) based on: MD, 77 SNP PRS and a questionnaire score (QS; lifestyle and reproductive factors). A total of 2,799 invasive breast cancer cases were diagnosed from 1990–2000. MD (using Cumulus software) and PRS were assessed in a nested case–control study. We assess model performance using this case–control dataset and evaluate 10-year absolute breast cancer risk. The prospective MMHS validation dataset includes 21.8% of women age <50, and 434 incident cases identified over 10 years of follow-up.

Results:

In the NHS, MD has the highest odds ratio (OR) for 10-year risk prediction: ORper SD = 1.48 [95% confidence interval (CI): 1.31–1.68], followed by PRS, ORper SD = 1.37 (95% CI: 1.21–1.55) and QS, ORper SD = 1.25 (95% CI: 1.11–1.41). In MMHS, the AUC adjusted for age + MD + QS 0.650; for age + MD + QS + PRS 0.687, and the NRI was 6% in cases and 16% in controls.

Conclusion:

A simplified assessment of QS, MD, and PRS performs consistently to discriminate those at high 10-year breast cancer risk.

Impact:

This simplified model provides accurate estimation of 10-year risk of invasive breast cancer that can be used in a clinical setting to identify women who may benefit from chemopreventive intervention.

See related commentary by Tehranifar et al., p. 587
Effect of Metabolic Health and Obesity Phenotype on the Risk of Pancreatic Cancer: A Nationwide Population-Based Cohort Study
Authors: Chung Hye Soo , Lee Ji Sung , Song Eyun , Kim Jung A , Roh Eun , Yu Ji Hee , Kim Nam Hoon , Yoo Hye Jin , Seo Ji A , Kim Sin Gon , Kim Nan Hee , Baik Sei Hyun , Choi Kyung Mook
Published: December 2020

Background:

Recently, a few studies have reported different results regarding the relationship between metabolic health and obesity phenotype and several cancers. We examined the effects of metabolic health and obesity phenotype on pancreatic cancer using a nationwide population-based cohort database.

Methods:

Using the Korean National Health Insurance Service–Health Screening Cohort, we enrolled 347,434 Korean adults who underwent a health examination between 2009 and 2010 and were followed until 2015. This population was divided into four groups based on metabolically healthy status and body mass index (BMI): metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO).

Results:

Over a median follow-up of 6.1 (5.5–6.5) years, 886 individuals were diagnosed with pancreatic cancer. The adjusted HRs for incident pancreatic cancer were 1.52 [95% confidence interval (CI) 1.27–1.81] and 1.34 (95% CI, 1.12–1.61) for the MUNW and MUO phenotypes (compared with the MHNW phenotype) after adjusting for various confounding factors. However, compared with the MHNW phenotype, the MHO phenotype did not show an elevated risk of pancreatic cancer. Moreover, the HR for pancreatic cancer gradually increased with an increase in number of metabolically unhealthy components, even after adjusting for BMI (Ptrend < 0.001).

Conclusions:

Regardless of BMI, metabolically unhealthy phenotype demonstrated significantly increased risk of pancreatic cancer, whereas obese individuals with metabolically healthy phenotype did not.

Impact:

These findings suggest that metabolically unhealthy phenotype might represent a potential risk factor for pancreatic cancer occurrence independent of obesity.
The Histone Methyltransferase Gene G9A Is Regulated by Nuclear Receptor 4A1 in Alveolar Rhabdomyosarcoma Cells
Authors: Shrestha Rupesh , Mohankumar Kumaravel , Jin Un-ho , Martin Gregory , Safe Stephen
Published: December 2020

The histone methyltransferase G9A (EHMT2) gene catalyzes methylation of histone 3 lysine 9 (H3K9), and this gene silencing activity contributes to the tumor promoter–like activity of G9A in several tumor types including alveolar rhabdomyosarcoma (ARMS). Previous studies show the orphan nuclear receptor 4A1 (NR4A1, Nur77) is overexpressed in rhabdomyosarcoma and exhibits pro-oncogenic activity. In this study, we show that knockdown of NR4A1 in ARMS cells decreased expression of G9A mRNA and protein. Moreover, treatment of ARMS cells with several bis-indole–derived NR4A1 ligands (antagonists) including 1,1-bis(3′-indolyl)-1-(4-hydroxyphenyl)methane (CDIM8), 3,5-dimethyl (3,5-(CH3)2), and 3-bromo-5-methoxy (3-Br-5-OCH3) analogs also decreased G9A expression. Furthermore, NR4A1 antagonists also decreased G9A expression in breast, lung, liver, and endometrial cancer cells confirming that G9A is an NR4A1-regulated gene in ARMS and other cancer cell lines. Mechanistic studies showed that the NR4A1/Sp1 complex interacted with the GC-rich 511 region of the G9A promoter to regulate G9A gene expression. Moreover, knockdown of NR4A1 or treatment with NR4A1 receptor antagonists decreased overall H3K9me2, H3K9me2 associated with the PTEN promoter, and PTEN-regulated phospho-Akt. In vivo studies showed that the NR4A1 antagonist (3-Br-5-OCH3) inhibited tumor growth in athymic nude mice bearing Rh30 ARMS cells and confirmed that G9A was an NR4A1-regulated gene that can be targeted by NR4A1 receptor antagonists.
Optimization of Erlotinib Plus Sulindac Dosing Regimens for Intestinal Cancer Prevention in an Apc-Mutant Model of Familial Adenomatous Polyposis (FAP)
Authors: Ulusan Ahmet M. , Rajendran Praveen , Dashwood Wan Mohaiza , Yavuz Omer F. , Kapoor Sabeeta , Gustafson Trace A. , Savage Michelle I. , Brown Powel H. , Sei Shizuko , Mohammed Altaf , Vilar Eduardo , Dashwood Roderick H.
Published: December 2020

A clinical trial in patients with familial adenomatous polyposis (FAP) demonstrated that sulindac plus erlotinib (SUL+ERL) had good efficacy in the duodenum and colon, but toxicity issues raised concerns for long-term prevention. We performed a biomarker study in the polyposis in rat colon (Pirc) model, observing phosphorylated Erk inhibition in colon polyps for up to 10 days after discontinuing ERL+SUL administration. In a follow-up study lasting 16 weeks, significant reduction of colon and small intestine (SI) tumor burden was detected, especially in rats given 250 ppm SUL in the diet plus once-a-week intragastric dosing of ERL at 21 or 42 mg/kg body weight (BW). A long-term study further demonstrated antitumor efficacy in the colon and SI at 52 weeks, when 250 ppm SUL was combined with once-a-week intragastric administration of ERL at 10, 21, or 42 mg/kg BW. Tumor-associated matrix metalloproteinase-7 (Mmp7), tumor necrosis factor (Tnf), and early growth response 1 (Egr1) were decreased at 16 weeks by ERL+SUL, and this was sustained in the long-term study for Mmp7 and Tnf. Based on the collective results, the optimal dose combination of ERL 10 mg/kg BW plus 250 ppm SUL lacked toxicity, inhibited molecular biomarkers, and exhibited effective antitumor activity. We conclude that switching from continuous to once-per-week ERL, given at one-quarter of the current therapeutic dose, will exert good efficacy with standard-of-care SUL against adenomatous polyps in the colon and SI, with clinical relevance for patients with FAP before or after colectomy.

Prevention Relevance:

This investigation concludes that switching from continuous to once-per-week erlotinib, given at one-quarter of the current therapeutic dose, will exert good efficacy with standard-of-care sulindac against adenomatous polyps in the colon and small intestine, with clinical relevance for patients with FAP before or after colectomy.
Tumor-Infiltrating Natural Killer Cells
Authors: Cózar Beatriz , Greppi Marco , Carpentier Sabrina , Narni-Mancinelli Emilie , Chiossone Laura , Vivier Eric
Published: December 2020

Because of their potent antitumor activity and their proinflammatory role, natural killer (NK) cells are at the forefront of efforts to develop immuno-oncologic treatments. NK cells participate in immune responses to tumors by killing target cells and producing cytokines. However, in the immunosuppressive tumor microenvironment, NK cells become dysfunctional through exposure to inhibitory molecules produced by cancer cells, leading to tumor escape. We provide an overview of what is known about NK tumor infiltration and surveillance and about the mechanisms by which NK cells become dysfunctional.

Significance:

The functions of tumor-infiltrating NK cells may be impaired. This review aims to describe the various mechanisms by which tumors alter NK-cell functions.
The Influence of Altitude on Erythropoietin Resistance Index in Maintenance Hemodialysis Patients: Data from Tibetan Plateau
Authors: Wang Yan , Dang Zong-hui , Gan Liang-ying , Luobu Ciren , Zhang Lei , Li Guo-liang , Zuo Li
Published: December 2020

Background: It is known that hypoxia influences many of the biologic processes involved in erythropoiesis; therefore, the high-altitude hypoxia may affect erythropoietin (EPO) responsiveness in maintenance hemodialysis (MHD) patients. This study aimed to evaluate the impact of altitude on EPO responsiveness in MHD patients. Methods: In this retrospective study, MHD patients from Tibet Autonomous Region People’s Hospital (3,650 m above sea level) and Peking University People’s Hospital (43.5 m above sea level) were recruited between May 2016 and December 2018. Patients were divided into 2 groups according to altitude. Variables including age, sex, dialysis vintage, dialysis modality, duration of EPO use, EPO doses, and laboratory tests were collected and analyzed. EPO responsiveness was measured in terms of the EPO resistance index (ERI). ERI was defined as the weekly weight-adjusted dose of EPO (IU/kg/week) divided by hemoglobin concentration (g/dL). The association between ERI and altitude was estimated using a multivariable linear regression model. Results: Sixty-two patients from Tibet Autonomous Region People’s Hospital (high-altitude [HA] group) and 102 patients from Peking University People’s Hospital (low-altitude [LA] group) were recruited. The ERI for HA group and LA group was 6.9 ± 5.1 IU w−1 kg−1 (g/dL)−1 and 11.5 ± 6.4 IU w−1 kg−1 (g/dL)−1, respectively. After adjusting for covariates by multivariable regression, altitude was independently associated with ERI (R2 = 0.245, p < 0.001). Conclusion: Altitude had an independent negative correlation with ERI. This result supported the hypothesis that altitude-associated hypoxia improved EPO responsiveness in MHD patients.
Anesthesia-Related Factors Associated with Preterm Labor and Delivery after Open Fetal Surgery
Authors: Aina Titilopemi A.O. , Zhu Huirong , Kim Jonathan , Wiafe Kobby A. , Nassr Ahmed A. , Olutoye Olutoyin A.
Published: December 2020

Background: Fetal surgery, such as for meningomyelocele repair, has a clear clinical fetal benefit. In patients who undergo in utero repair of meningomyelocele, for example, there is reduced long-term disease morbidity. However, despite the beneficial effects of early intervention, women who undergo fetal interventions have an increased risk of preterm labor and delivery. Several surgery-related factors have been described but no specific anesthesia-related factors. Objective: The aim of this study was to determine if any aspects of the perioperative anesthetic management influenced maternal complications following in utero surgery. Methods: This was a retrospective chart review of the anesthetic management of mothers and fetuses who presented for open and fetoscopic myelomeningocele repair, between 2011 and 2015, at Texas Children’s Fetal Center®. Results: Forty-six women underwent open or fetoscopic repair of neural tube defects at our institution. We found the maternal heart rate in the postoperative period to be associated with a higher likelihood of preterm labor, but not delivery. The odds of having preterm delivery was higher for nulliparous patients and those with lower intraoperative diastolic pressure. Conclusions: Our findings confirm what has been previously reported regarding the association of nulliparity with preterm delivery. Additionally, this study highlights the importance of maintaining stable perioperative hemodynamics during the intraoperative and postoperative phases of care for patients undergoing in utero surgery.
COVID-19-Associated Systemic Thromboembolism: A Case Report and Review of the Literature
Authors: Mahajan Pranav , Dass Bhagwan , Radhakrishnan Nila , McCullough Peter A.
Published: December 2020

Introduction: Coronavirus disease 2019 (COVID-19) is a pandemic that has affected >188 countries, involved >24 million people, and caused >840,000 deaths. COVID-19, in its severe form, presents as acute respiratory distress syndrome (ARDS), shock, and multiorgan failure. Thrombotic microangiopathy of the lungs and kidneys has been observed in these patients. Elevated D-dimer levels have been observed in people with serious COVID-19 illness, and this could be helpful in guiding treatment with anticoagulation in these patients. Objective: To analyze the role of anticoagulation as a treatment modality for COVID-19. Methods: We present the unique case of a COVID-19 patient who developed sepsis, ARDS, acute kidney injury, and deep-vein thrombosis (DVT), who was deteriorating clinically. She was treated with anticoagulation. Results: There was rapid recovery after treatment with systemic anticoagulation. Conclusions: Systemic anticoagulation could prove to be essential in the treatment of CO­VID-19. Further studies are required to assess its role in improving long-term morbidity and mortality in these patients.
“Door to Treatment” Outcomes of Cancer Patients during the COVID-19 Pandemic
Authors: Ak Naziye , Vatansever Sezai
Published: December 2020

Background: The novel coronavirus disease 2019 has become a worldwide threat. We aimed to explore reflections of these unexpected changes to newly diagnosed cancer patients. Method: We searched the 2 months after the index case of our country. The first admission day and the first day of intravenous treatment of newly diagnosed patients were recorded. Results: In the 60 days measured during the pandemic, the total number of patients on polyclinics was 159/weekdays, and the total applied chemotherapy cycles were 276/week. For comparison, the total numbers in the previous year were 267/weekday and 363/week for polyclinic and applied chemotherapy cycles, respectively. The total number of newly admitted patients in 2020 was 283. For comparison, the number of new patients in the same 60-day period in 2019 was 495. Patients who were admitted for adjuvant treatment required a median of 8 days for the first course, those who were admitted for neoadjuvant treatment required 12 days, and metastatic patients required 14 days; there were no significant differences between treatment types (p = 0.233). However, the median treatment time was 11.5 and 17 days, in 2020 and in 2019, respectively. A significant difference was observed between the 2 groups (p < 0.001). Conclusion: The effective shift of workers and accurate regulations have not resulted in apparent delays in patient care. While a decrease in the number of patients has detected, faster healthcare service was introduced to newly diagnosed patients. The reason for the decrease in the number of patients should be investigated with new studies.
Association of Tumor Necrosis Factor-Alpha-308 G/A and -238 G/A Polymorphism with Diabetic Retinopathy: A Systematic Review and Updated Meta-Analysis
Authors: Gao Wenna , Zhu Ruilin , Yang Liu
Published: December 2020

Background: Mounting evidence has suggested that tumor necrosis factor-alpha (TNF-α) can promote the development of diabetic retinopathy (DR), and TNF-α gene variants may influence DR risk. However, the results are quite different. Objectives: To comprehensively address this issue, we performed the meta-analysis to evaluate the association of TNF-α-308 G/A and -238 G/A polymorphism with DR. Method: Data were retrieved in a systematic manner and analyzed using STATA Statistical Software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Allelic and genotypic comparisons between cases and controls were evaluated. Results: For the TNF-α-308 G/A polymorphism, overall analysis suggested a marginal association with DR (the OR [95% CI] of [GA vs. GG], [GA + AA] vs. GG, and [A vs. G] are 1.21 [1.04, 1.41], 1.20 [1.03, 1.39], and 1.14 [1.01, 1.30], respectively). And the subgroup analysis indicated an enhanced association among the European population. For the TNF-α-238 G/A polymorphism, there was a mild correlation in the entire group (the OR [95% CI] of [GA vs. GG] is 1.55 [1.14, 2.11]), which was strengthened among the Asian population. Conclusion: The meta-analysis suggested that -308 A and -238 A allele in TNF-α gene potentially increased DR risk and showed a discrepancy in different ethnicities.
Phase 1b Study to Evaluate Safety, Tolerability, and Maximum Tolerated Dose of PF-05230907 for Intracerebral Hemorrhage
Authors: Silva Blas Yolanda , Diringer Michael N. , Lo Benjamin , Masjuan Jaime , Pérez de la Ossa Natalia , Cardinal Matthew , Yong Florence , Zhu Tong , Li Gang , Arkin Steven
Published: December 2020

Background and Purpose:

This study aimed to determine the maximum tolerated dose and to evaluate the overall safety and tolerability of single doses of PF-05230907 in subjects with acute intracerebral hemorrhage.

Methods:

Individuals presenting with intracerebral hemorrhage were enrolled in a phase 1, multicenter, open-label clinical trial. A Bayesian modified continual reassessment method design based on treatment-emergent thromboembolic or ischemic events was adopted. Sequential dosing, an external data monitoring committee, and prespecified stopping rules were incorporated as safeguards.

Results:

Twenty-one subjects received PF-05230907. The mean (±SD) age in years and intracerebral hemorrhage volume in mL at baseline were 62 (±9) and 18 (±11), respectively. Two treatment-emergent thromboembolic or ischemic events occurred (deep vein thrombosis and cerebral ischemia), in the 30 μg/kg dose group. There were no other clear drug-related toxicities at dose levels ranging from 5 to 30 μg/kg. At the time of study termination, the maximum tolerated dose was estimated to be 24 μg/kg, with a mean fitted dose-toxicity estimate of 11.9% (95% CI, 1.2%–27.4%).

Conclusions:

Single doses of PF-05230907 appeared to be tolerated across a range of doses in the intracerebral hemorrhage population, with thrombotic events observed only at the highest dose level tested. Recruitment within the recommended therapeutic window of opportunity remains a challenge.

Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02687191.
Commerce and Consumers: The Ubiquitous Chest of the Late Middle Ages
Authors: Wilson Katherine Anne
Published: December 2020

Contrary to their ubiquity within written, visual, and material sources, chests have largely remained overlooked in studies of the late Middle Ages. Bill Brown’s “thing theory” helps to explicate the ways in which chests can transform from unnoticed “things” in the background to meaningful “objects” when viewed through their entanglements with commercial, consumer, political, and moral concerns. The interdisciplinary study of chests in the late Middle Ages brings together a range of evidence including inventories, guild accounts, court pleas, contemporary writings, images, and material culture from Burgundy, France, and England.
Homicide in Victoria: Female Perpetrators of Murder and Manslaughter, 1860 to 1920
Authors: Nagy Victoria
Published: December 2020

Records from the Central Register of Female Prisoners permit a longitudinal analysis of ninety-five women convicted of murder and manslaughter in Victoria between 1860 and 1920. The data show the similarities and differences between the women convicted of these homicide offenses. An examination of the women’s socioeconomic profiles, occupations, ages, migrations, and victims reveals the links between their crimes and their punishment.
Caste and Higher Education in India
Authors: Lardinois Roland
Published: December 2020

Subramanian’s The Caste of Merit addresses the issue of educational inequality in colonial and independent India, focusing on the Indian Institutes of Technology (iits) that have trained the engineering elites since the 1950s. The members of the high caste who initially comprised this group ascribed their personal success to merit, not to background. India’s policy of allowing disadvantaged caste groups to enter the (iits), however, challenged the high castes’ representation of their educational privilege as simply a matter of talent. Subramanian’s view of the upper-caste position as an attempt to forestall progress toward a more egalitarian Indian society opens a methodological debate about the fundamental epistemic demands that scholars must satisfy before they adopt social causes above and beyond the conveying of objective information.
Narcissus and Echo:Reflections on an Art-Science Collaboration
Authors: Steinman Dolores A. , Coppin Peter W. , Steinman David A.
Published: December 2020

More than a decade ago, the authors proposed establishing a basis for scientific exploration of blood-flow dynamics intertwined with the visual arts. Here they present a case study showing how paradigms they codeveloped for visually abstracting cerebral aneurysm blood flows were extrapolated to sonification and bimodal representations, and how a close interdisciplinary partnership was effected by guiding engineering students versed in the arts and artists adept with digital technology toward final outcomes greater than the sum of their parts.
The Choreography of the Creative Process: Drawing in Time and Space
Authors: Zoran Amit Raphael , Dick Nir , Glauber Naama
Published: December 2020

This article provides a new perspective on the contribution of computers to visual art, exploring how the visual product’s aesthetic qualities and the making process itself can render a hybrid artistic outcome. A medium that unifies the physical product with the spirit of the making process has innovative potential for computational artistic practice. The article demonstrates various techniques to visualize artists’ motor performance in activities such as drawing and carving. The authors digitally track artists’ movements and computer graphic tools to expose expressive performance, highlight working styles and bring their strokes’ hidden paths to the artwork’s forefront. The authors discuss contextual application of this form of visualization to new domains of visual art.
World Cinema, vod Platforms and the Western Demand
Authors: Parvulescu Constantin
Published: December 2020

The article explores the concept of world cinema as an other to global cinema from a marketing perspective. Special attention is given to the way the world cinema universe is presented on video-on-demand platforms in Western markets. To demonstrate that the stories, scope and concerns of this universe vary according to marketing objectives, the article compares presentations on three platforms with contrasting business models and marketing algorithms: Netflix, Filmin, and FilmDoo. This leads to an important conclustion: presentations on platforms with an apparently more ethical business model are not necessarily more progressive and more advantageous to world cinema in terms of avoiding its “genre-fication”.
Comparing the Prognostic Value of Hematological Indices in Patients With ST Segment Elevation Myocardial Infarction: “A Head to Head” Analysis
Authors: Sigirci Serhat , Ser Özgür Selim , Keskin Kudret , Yildiz Süleyman Sezai , Gurdal Ahmet , Kilickesmez Kadriye Orta
Published: December 2020

Although there are reviews and meta-analyses focusing on hematological indices for risk prediction of mortality in patients with ST segment elevation myocardial infarction (STEMI), there are not enough data with respect to direct to head-to-head comparison of their predictive values. We aimed to investigate which hematological indices have the most discriminatory capability for prediction of in-hospital and long-term mortality in a large STEMI cohort. We analyzed the data of 1186 patients with STEMI. In-hospital and long-term all-cause mortality was defined as the primary end point of the study. In-hospital mortality rate was 8.6% and long-term mortality rate 9.0%. Although the neutrophil to lymphocyte ratio (NLR) and age were found to be independent predictors of in-hospital mortality in the multivariate regression analyses; Cox regression analysis revealed that age, ejection fraction, red cell distribution width (RDW), and monocyte to high-density lipoprotein ratio (MHDLr) were independently associated with long-term mortality. Neutrophil to lymphocyte ratio had the highest area under curve value in the receiver operating characteristic curve analyses for prediction of in-hospital mortality. In conclusion, while NLR may be used for prediction of in-hospital mortality, RDW and MHDLr ratio are better hematological indices for long-term mortality prediction after STEMI than other most common indices.
FDI and Spillovers in India: Any Policy Lessons from Existing Studies?
Authors: Sasidharan Subash
Published: December 2020

During the past three decades, numerous policy changes were made by the policy makers to attract foreign direct investment (FDI) in India. An extensive body of studies using rich firm level panel data have analyzed how foreign firms presence affect the productivity/technology spillovers to domestic firms in India. These studies using recent methodological advancements distinguish between horizontal and vertical spillovers. Empirical analyses of productivity/technology spillovers from foreign firms offer inconclusive results with early studies reporting neutral and negative FDI spillovers, while more recent studies consistently providing evidence of positive vertical spillovers. Therefore, the main contribution of this paper is to review the literature on FDI spillovers in India and explore whether there are any policy lessons from the findings of these firm level studies.
Evolution of intersectional perceived discrimination and internalized stigma during COVID-19 lockdown among the general population in Spain
Authors: Ugidos Carolina , López-Gómez Aída , Castellanos Miguel Ángel , Saiz Jesús , González-Sanguino Clara , Ausín Berta , Muñoz Manuel
Published: December 2020

Background:

Stigma and discrimination have been associated with different diseases and pandemics, with negative consequences for the people who suffered them and for their communities. Currently, COVID-19 has become a new source of stigmatization.

Aims:

The aim of the present study is to analyze longitudinally the evolution of intersectional perceived discrimination and internalized stigma among the general population of Spain, at three points in time throughout the confinement.

Method:

Participants completed an online survey.

Results:

Results show an increase in both variables from the first to the second evaluation, and a slight decrease from the second to the third evaluation. Moreover, these changes are explained by depression, anxiety and family support.

Conclusions:

These findings indicate the factors that need to be considered to reduce the perception of discrimination and the internalization of stigma, and their detrimental consequences, during an especially stressful event such as the current pandemic outbreak.
Are the Criminogenic Effects of Incarceration Mediated by a Change in Criminal Thinking or a Change in Perceived Certainty?
Authors: Walters Glenn D.
Published: December 2020

The purpose of the current study was to determine whether a change in criminal thinking or a change in perceived certainty mediates the putative criminogenic effect of incarceration. A path analysis of 1,170 male delinquents revealed that incarceration prior to age 19 produced a negative rather than positive effect on offending behavior at age 20, although it did predict an increase in proactive criminal thinking (PCT) from age 18 to age 19. PCT, in turn, predicted a rise in past year offending. Perceived certainty of punishment, on the other hand, failed to mediate the effect of incarceration on future offending.
The Temporal Uses of Moral Things: Manifesting, Anchoring and Conserving Caring Relations within the Sensorium
Authors: Balmer Andrew , Meckin Robert , Abbott Owen
Published: December 2020

In this article we argue that menthol-containing products, like chewing gums, vapour rubs and mouthwashes, are used as moral things within everyday practices. They take on moral functions because of how their material qualities contribute to sensory experiences. Specifically, we focus on scenarios in which menthol products become associated with the moral work of care and highlight the temporal dimension of what people do with moral things. We review the literature on morality as a practical, everyday accomplishment and stress the embodied nature of caring practices to outline how care is bound up with sensory experience. We draw on rich qualitative data generated through creative methods, including film, photography and sketching, as part of object-elicitation interviews, focus groups, home tours and ‘pop-up stalls’. We develop three concepts regarding the function of moral things: manifesting, anchoring and conserving moral relations to describe how time, morality and the sensory are entwined.
The Mobilisation of AI in Education: A Bourdieusean Field Analysis
Authors: Davies Huw C , Eynon Rebecca , Salveson Cory
Published: December 2020

Artificial Intelligence (AI) is currently hailed as a ‘solution’ to perceived problems in education. Though few sociologists of education would agree with its deterministic claims, this AI solutionist thinking is gaining significant currency. In this article, using a relatively novel method for sociology – a knowledge graph – together with Bourdieusean theory, we critically examine how and why different stakeholders in education, educational technology and policy are valorising AI, the main concepts, such as personalisation, they collectively endorse and their incentives for doing so. Drawing on this analysis, we argue that AI is currently being mobilised in education in problematic ways and advocate for more systematic sociological thinking and research to re-orientate the field to account for society’s structural conditions.
Challenges to Religious Freedom in the USA: Some Lessons from Global Crises
Authors: Hollenbach David
Published: December 2020

Religious freedom is a focus of controversy in the United States today. The leaders of some religious communities, particularly Evangelicals and Roman Catholics, object to policies that challenge their beliefs, often their beliefs regarding sex and reproduction, by appealing to their right to religious freedom. This leads others to see religious freedom as a threat to moral changes they regard as progress. Religious liberty threatens to become a source of social division and conflict. This article analyzes these conflicts and considers how the USA can address them more effectively by reflecting on several international challenges to religious freedom. These global cases show that the religious freedom controversies in the USA today call both religious communities and those with secular worldviews to recognize that social unity and respect for freedom should go together. Social unity requires respect for freedom, including the freedom of those with whom one disagrees.
Beyond a Single Firm and Internal Focus Service Failure/Recovery: Multiple Providers and External Service Recoveries
Authors: Weber Karin , Hsu Cathy H. C.
Published: December 2020

Moving beyond the traditional focus on single service providers and internal service recoveries, this article extends service failure/recovery research by examining the effect on consumer evaluations and behavior of (1) a series of service failures that involve multiple entities in the creation of customer experiences; (2) an external service recovery, that is, a recovery implemented by a firm other than the one that caused the service failure; and (3) a joint service provider recovery, in contrast to the prevalent focus on a single firm service recovery. Employing two experiments, findings confirmed that a firm unaffiliated with the firm that caused the service failure benefits more from an external service recovery than an affiliated firm. Surprisingly, external recoveries by affiliated entities themselves, and compared to the internal recovery by the entity that caused the failure, did not significantly impact consumer evaluations and behavior. Study implications and future research directions are discussed.
Fake news as fake politics: the digital materialities of YouTube misinformation videos about Brazilian oil spill catastrophe
Authors: Lemos André Luiz Martins , Bitencourt Elias Cunha , dos Santos João Guilherme Bastos
Published: December 2020

This article investigates misinformation chains – fake news and clickbait – related to the 2019 oil spill along the coast of Northeast Brazil. A link between the intensive use of misinformation on YouTube and the environmental impact of digital media and algorithmic performativity has been found by analyzing videos about the 2019 Brazilian oil spill. A total of 591 YouTube videos were extracted based on a search for the hashtags ‘oleononordeste’, ‘vazamentopetroleo’, and ‘greenpixe’. The data thus obtained suggest that most of the corpus (80.37%) consists of misinformation, of which 65.82% (389 videos) is clickbait and 14.55% (86 videos) fake news. YouTube misinformation videos produced around 1.42 MtCO2e, the equivalent of burning 3.30 barrels of oil. We argue that misinformation chains increase pollution and carbon footprint as a result of at least three factors: (a) the extra energy cost of feeding algorithms; (b) increased algorithmic resistance to the visibility of journalistic information; and (c) undermining public debate about environmental catastrophes in favor of private interests (fake politics).
Preclinical Safety Assessment of 2 Inhaled Single-Domain Antibodies in the Cynomolgus Monkey
Authors: Haworth Richard , Boyle Molly , Edwards Paul , Gupta Reenu , Fagg Rajni , Karantabias George , Price Mark
Published: December 2020

The safety of 2 single domain antibodies (dAbs) was evaluated by inhalation toxicology studies in the cynomolgus monkey. In the first case study, a 14-day repeat-dose study evaluating an anti-thymic stromal lymphopoietin (anti-TSLP) dAb resulted in minimal mononuclear inflammatory cell infiltrates in the lungs, increases in lymphocytes in bronchoalveolar lavage fluid, and development of antidrug antibodies (ADAs). In a 6-week inhalation study, there was an increase in incidence and/or severity of mononuclear cell infiltrates in the lung, increased cellularity in the tracheobronchial lymph node (TBLN), and development of ADA. The second case study evaluated a change in duration of inhalation dosing, a different route of exposure (intravenous or IV), and recovery following an off-dose period with an anti-tumor necrosis factor receptor 1 dAb. A 7-day repeat-dose inhalation study and a 14-day IV study produced no microscopic effects in the lung, whereas a 14-day inhalation study resulted in moderate increases in pulmonary perivascular/peribronchiolar/alveolar lymphocytic infiltrates and increased cellularity in the TBLN, with partial and full recovery, respectively, after 14 days. The lung and lymph node findings seen after inhalation of either dAb were considered secondary to the immunogenic response to a human protein and were considered nonadverse.
Rural politics in transitional China: Urban–rural disparity, national integration, and grassroots democracy
Authors: Huang Zhenhua
Published: December 2020

This essay reviews three books by Xu Yong that examine three critical historical processes of political transformation in rural China: the politicization of society due to urban–rural disparity, the government’s efforts to encourage political integration in rural areas, and the development of rural grassroots democracy. Urban–rural disparity has been a structural characteristic of China’s politicized society since the establishment of the monarchy. The analysis of this inequality focuses on uncovering grassroots society (as opposed to Chinese society’s upper echelons) and examining its evolutionary logic. Since 1949, China has faced the historical task of building a modern state. The government aggressively entered the countryside through large-scale political mobilization and social integration with the Chinese Communist Party as the driving force. The goal was to create a strongly integrated communist nation. Since the 1980s, the Chinese countryside has not only experienced economic liberalization but also received an opportunity for political democratization through the creation and practice of village autonomy. Self-government in autonomous villages has provided Chinese peasants with a wide range of democratic rights. In addition, calls for transformation and promotion of the democratic paradigm have increased. Xu’s three books effectively present many critical aspects of China’s rural political transformations. However, questions remain concerning the consistency of the theory and the accuracy of the analysis, which leaves room for further research and discussion.
Easily misdiagnosed intramuscular hemangioma: a case report
Authors: Li Yujia , Chou Ke , Xiong Jiepeng , Zhu Wei , Yu Min
Published: December 2020

An intramuscular hemangioma is a benign vascular tumor that often occurs in the lower extremities. We herein report a rare case of an intramuscular hemangioma that occurred in the gluteus medius muscle and was misdiagnosed as lumbar disc herniation. A 36-year-old woman presented with incidental and infrequent pain of the left buttock. She was diagnosed with lumbar disc herniation and underwent treatment. Although her pain was slightly relieved, relapse soon occurred. X-ray examination and magnetic resonance imaging revealed a mass in the gluteus medius muscle. The mass was suspected to be a malignant tumor and was therefore resected. The final diagnosis was an intramuscular hemangioma. Her pain completely disappeared thereafter and did not recur. Patients with intramuscular hemangiomas usually have no specific symptoms; therefore, this tumor is often misdiagnosed. When a satisfactory treatment effect is not obtained, the diagnosis should be reassessed in a timely manner.
Congenital absence of the right coronary artery with acute myocardial infarction: report of two cases and review of the literature
Authors: Chen Zhongbo , Yan Jinhua , Han Xiaorong , Adhikari Binay Kumar , Zhang Jin , Zhang Ying , Sun Jian , Wang Yonggang
Published: December 2020

Congenital absence of the right coronary artery (RCA) is a rare coronary anomaly. Few cases of this condition have been reported. Congenital absence of the RCA is considered as a benign anomaly. However, in certain cases, these patients may develop life-threatening clinical complications that include acute myocardial infarction, stroke, or sudden death. We report two patients who were diagnosed with congenital absence of the RCA and presented with acute myocardial infarction. We discuss our experience in diagnosis and treatment of this disease. Congenital absence of the RCA with acute myocardial infarction is an uncommon clinical emergency. Therefore, early detection, correct diagnosis, and appropriate treatment are important.