bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Bioactive Components from Ruellia tuberosa L. on Improving Glucose Uptake in TNF‐α‐Induced Insulin‐Resistant Mouse FL83B Hepatocytes
Authors: Xu Jian-Hua , Lo Yangming Martin , Chang Wen-Chang , Huang Da-Wei , Wu James Swi-Bea , Jhang Yu-Yuan , Huang Wen-Chung , Ko Chih-Yuan , Shen Szu-Chuan
Published: December 2020

Ruellia tuberosa L. (RTL) has been used as a folk medicine to cure diabetes in Asia. RTL was previously reported to alleviate hyperglycemia, insulin resistance (IR), abnormal hepatic detoxification, and liver steatosis. However, the potential bioactive compounds of RTL have still not been identified. The aim of this study was to investigate the bioactive compounds in RTL ethyl acetate (EA) fractions by using a glucose uptake assay in TNF‐α‐treated mouse FL83B hepatocytes to discover a mechanism by which to improve IR. The bioactive compounds were identified by the high‐performance liquid chromatography (HPLC) assay. Using the Sephadex LH20 gel packing chromatography column, the EAF5 fraction was isolated from RTL and significantly increased glucose uptake in TNF‐α‐treated FL83B cells. Moreover, the MCI gel packing chromatography column separated EAF5 into five subfractions and had no significant cytotoxic effect in FL83B cells when treated at the concentration of 25 μg/ml. Among the subfractions, EAF5‐5 markedly enhanced glucose uptake in TNF‐α‐treated FL83B cells. The possible bioactive compounds of the EAF5‐5 fraction that were identified by the HPLC assay include syringic acid, p‐coumaric acid, and cirsimaritin. The bioactive compound with the best effect of increasing glucose uptake was p‐coumaric acid, but its effect alone was not as good as the combined effect of all three compounds of the EAF5‐5 fraction. Thus, we speculate that the antidiabetic effect of RTL may be the result of multiple active ingredients.
Periapical Microsurgery with an Endoscope and Microscope of Two Upper Central Incisors Already Subjected to Periapical Surgery 25 Years Ago
Authors: Glera-Suarez Pablo , Serra-Pastor Blanca , Peñarrocha-Oltra David , Peñarrocha-Diago Miguel , Gay-Escoda Cosme
Published: December 2020

Introduction. The present clinical case describes periapical microsurgery with an endoscope and microscope in a patient already treated 25 years ago due to persistent periapical disease of the two central upper incisors, restored with poorly adapted crowns. Clinical Case. The first periapical surgery had been performed with silver amalgam as a retrograde filler material, causing grayish staining of the buccal mucosa. Periapical surgery was performed raising a submarginal flap with ostectomy and apicoectomy, retrograde cavity preparation with ultrasound tips, and filling with mineral trioxide aggregate (MTA). After soft tissue healing and complete bone regeneration of the lesion, retreatment of the incisors with a fixed prosthesis was carried out, adopting the biologically oriented preparation technique (BOPT). Conclusions. The described periapical microsurgery approach with magnification and illumination of the surgical field was found to be effective, avoiding the need to extract the two central upper incisors.
Enhanced Antitumor Immunity via Endocrine Therapy Prevents Mammary Tumor Relapse and Increases Immune Checkpoint Blockade Sensitivity
Authors: Sequeira Gonzalo R. , Sahores Ana , Dalotto-Moreno Tomás , Perrotta Ramiro M. , Pataccini Gabriela , Vanzulli Silvia I. , Polo María L. , Radisky Derek C. , Sartorius Carol A. , Novaro Virginia , Lamb Caroline A. , Rabinovich Gabriel A. , Salatino Mariana , Lanari Claudia
Published: December 2020

The role of active antitumor immunity in hormone receptor–positive (HR+) breast cancer has been historically underlooked. The aim of this study was to determine the contribution of the immune system to antiprogestin-induced tumor growth inhibition using a hormone-dependent breast cancer model. BALB/c-GFP+ bone marrow (BM) cells were transplanted into immunodeficient NSG mice to generate an immunocompetent NSG/BM-GFP+ (NSG-R) mouse model. Treatment with the antiprogestin mifepristone (MFP) inhibited growth of 59–2-HI tumors with similar kinetics in both animal models. Interestingly, MFP treatment reshaped the tumor microenvironment, enhancing the production of proinflammatory cytokines and chemokines. Tumors in MFP-treated immunocompetent mice showed increased infiltration of F4/80+ macrophages, natural killer, and CD8 T cells, displaying a central memory phenotype. Mechanistically, MFP induced immunogenic cell death (ICD) in vivo and in vitro, as depicted by the expression and subcellular localization of the alarmins calreticulin and HMGB-1 and the induction of an ICD gene program. Moreover, MFP-treated tumor cells efficiently activated immature dendritic cells, evidenced by enhanced expression of MHC-II and CD86, and induced a memory T-cell response, attenuating tumor onset and growth after re-challenge. Finally, MFP treatment increased the sensitivity of HR+ 59–2-HI tumor to PD-L1 blockade, suggesting that antiprogestins may improve immunotherapy response rates. These results contribute to a better understanding of the mechanisms underlying the antitumor effect of hormonal treatment and the rational design of therapeutic combinations based on endocrine and immunomodulatory agents in HR+ breast cancer.

Significance:

Antiprogestin therapy induces immunogenic tumor cell death in PRA-overexpressing tumors, eliciting an adaptive immune memory response that protects mice from future tumor recurrence and increases sensitivity to PD-L1 blockade.
Cyclophosphamide and Vinorelbine Activate Stem-Like CD8+ T Cells and Improve Anti-PD-1 Efficacy in Triple-Negative Breast Cancer
Authors: Falvo Paolo , Orecchioni Stefania , Hillje Roman , Raveane Alessandro , Mancuso Patrizia , Camisaschi Chiara , Luzi Lucilla , Pelicci PierGiuseppe , Bertolini Francesco
Published: December 2020

Checkpoint inhibitors (CI) instigate anticancer immunity in many neoplastic diseases, albeit only in a fraction of patients. The clinical success of cyclophosphamide (C)-based haploidentical stem-cell transplants indicates that this drug may re-orchestrate the immune system. Using models of triple-negative breast cancer (TNBC) with different intratumoral immune contexture, we demonstrate that a combinatorial therapy of intermittent C, CI, and vinorelbine activates antigen-presenting cells (APC), and abrogates local and metastatic tumor growth by a T-cell–related effect. Single-cell transcriptome analysis of >50,000 intratumoral immune cells after therapy treatment showed a gene signature suggestive of a change resulting from exposure to a mitogen, ligand, or antigen for which it is specific, as well as APC-to-T-cell adhesion. This transcriptional program also increased intratumoral Tcf1+ stem-like CD8+ T cells and altered the balance between terminally and progenitor-exhausted T cells favoring the latter. Overall, our data support the clinical investigation of this therapy in TNBC.

Significance:

A combinatorial therapy in mouse models of breast cancer increases checkpoint inhibition by activating antigen-presenting cells, enhancing intratumoral Tcf1+ stem-like CD8+ T cells, and increasing progenitor exhausted CD8+ T cells.
Balancing and Differentiating p53 Activities toward Longevity and No Cancer?
Authors: Horikawa Izumi
Published: December 2020

Aging and death of cells (cellular senescence and apoptosis, respectively), triggered by or associated with cellular stress and DNA damage, impair organ function and homeostasis, leading to organismal aging and death. On the other hand, defects in physiologic regulations of cellular aging and death (escape from cellular senescence and failed apoptosis of severely damaged cells) contribute to uncontrolled cell division and genetic instability in cancer. In an oversimplified scenario, p53, an inducer of cellular senescence and apoptosis, may thus unfavorably contribute to aging and favorably suppress tumorigenesis. However, physiologic mechanisms should exist and therapeutic approaches may be developed to balance between aging and tumor suppression, for example, by differentially regulating cellular senescence, apoptosis, and other p53-mediated biological processes, such as DNA repair, autophagy, and energy metabolism. Possible mechanisms for such differential regulation of different subsets of p53 target genes may involve posttranslational modifications (e.g., phosphorylation and acetylation) and DNA binding cooperativity of p53. In this issue of Cancer Research, Timofeev and colleagues show that a previously uncharacterized phosphorylation in the p53 core DNA-binding domain regulates the DNA binding cooperativity and transcriptional activity of p53. Their mice deficient for this p53 phosphorylation were resistant to spontaneous and induced tumorigenesis, while they had shortened lifespan, but did not show progeria-like phenotypes. Prompted by this study, research on p53, aging, and cancer will explore balancing and differentiating different p53 activities toward a challenging goal of achieving longevity with no cancer.

See related article by Timofeev et al., p. 5231
Dissemination and Implementation Research at the National Cancer Institute: A Review of Funded Studies (2006–2019) and Opportunities to Advance the Field
Authors: Neta Gila , Clyne Mindy , Chambers David A.
Published: December 2020

Background:

To ensure investment in cancer research reaches populations who can benefit, the NCI has funded implementation science grants since the Dissemination and Implementation Research in Health (DIRH) funding opportunities launched in 2006. We analyzed NCI-funded DIRH grants to provide a snapshot of implementation science conducted across the cancer care continuum and highlight areas ripe for exploration.

Methods:

NCI-funded DIRH grants between fiscal years 2006 and 2019 were identified using the iSearch database. Two coders classified each grant by topic, populations studied, intervention and setting characteristics, strategies tested, study designs and methods used, and outcomes measured.

Results:

Seventy-one grants were awarded addressing cancer prevention (n = 33), screening (n = 33), diagnosis (n = 4), treatment (n = 9), and/or survivorship (n = 11). Colorectal (n = 20), breast (n = 15), and cervical (n = 11) were the most studied cancers. Most grants focused on delivery of guidelines (n = 36) or behavioral change interventions (n = 18) in health care settings (n = 47), studying implementation processes (n = 37) and/or testing implementation strategies (n = 43) using experimental (n = 35) and quasi-experimental (n = 6) designs. Few studied sustainability (n = 7), scale-up (n = 2), deimplementation (n = 4), measure development (n = 6), or policy-level implementation (n = 6).

Conclusions:

Current funding suggests researchers are studying implementation of cancer control interventions across the care continuum. However, research gaps remain in strategies for sustainability, scale-up, and deimplementation. More emphasis is needed on cancer treatment and survivorship. Additional focus on policy implementation and measure development is warranted.

Impact:

Understanding the breadth of NCI-funded implementation science can inform future efforts to build the knowledge base on how to improve dissemination and implementation of evidence in cancer control.
Obstructive Sleep Apnea and Incident Cancer: A Large Retrospective Multicenter Clinical Cohort Study
Authors: Kendzerska Tetyana , Povitz Marcus , Leung Richard S. , Boulos Mark I. , McIsaac Daniel I. , Murray Brian J. , Bryson Gregory L. , Talarico Robert , Hilton John F. , Malhotra Atul , Gershon Andrea S.
Published: December 2020

Background:

To examine the association between the severity of obstructive sleep apnea (OSA) and nocturnal hypoxemia with incident cancer.

Methods:

This was a multicenter retrospective clinical cohort study using linked clinical and provincial health administrative data on consecutive adults who underwent a diagnostic sleep study between 1994 and 2017 in four academic hospitals (Canada) who were free of cancer at baseline. Cancer status was derived from the Ontario Cancer Registry. Cox cause–specific regressions were utilized to address the objective and to calculate the 10-year absolute risk difference (ARD) in the marginal probability of incident cancer and the number needed to harm (NNH).

Results:

Of 33,997 individuals considered, 33,711 with no missing OSA severity were included: median age, 50 years; 58% male; and 23% with severe OSA (apnea-hypopnea index >30). Of the 18,458 individuals with information on sleep time spent with oxygen saturation (SaO2) <90%, 5% spent >30% of sleep with SaO2 <90% (severe nocturnal hypoxemia). Over a median of 7 years, 2,498 of 33,711 (7%) individuals developed cancer, with an incidence rate of 10.3 (10.0–10.8) per 1,000 person-years. Controlling for confounders, severe OSA was associated with a 15% increased hazard of developing cancer compared with no OSA (HR = 1.15, 1.02–1.30; ARD = 1.28%, 0.20–2.37; and NNH = 78). Severe hypoxemia was associated with about 30% increased hazard (HR = 1.32, 1.08–1.61; ARD = 2.38%, 0.47–4.31; and NNH = 42).

Conclusions:

In a large cohort of individuals with suspected OSA free of cancer at baseline, the severity of OSA and nocturnal hypoxemia was independently associated with incident cancer.

Impact:

These findings suggest the need for more targeted cancer risk awareness in individuals with OSA.
Provider Discussion about Lifestyle by Cancer History: A Nationally Representative Survey
Authors: Arem Hannah , Duan Xuejing , Ehlers Diane K. , Lyon Maureen E. , Rowland Julia H. , Mama Scherezade K.
Published: December 2020

Background:

Providers are uniquely positioned to encourage health-promoting behaviors, particularly among cancer survivors where patients develop trust in providers.

Methods:

We utilized the National Health Interview Survey to identify adults who reported a visit to a provider in the prior year (44,385 individuals with no cancer history and 4,792 cancer survivors), and reported prevalence of provider discussions on weight loss, physical activity, diet, and smoking. We used generalized linear mixed models to examine predicted prevalence of provider lifestyle discussions by cancer history overall, and among those who do not meet body mass index (BMI), activity, or smoking guidelines.

Results:

Among those with a BMI of 25–<60 kg/m2, 9.2% of those with a cancer history and 11.6% of those without a cancer history reported being told to participate in a weight loss program (P < 0.001). Overall, 31.7% of cancer survivors and 35.3% of those with no cancer history were told to increase their physical activity (P < 0.001). Only 27.6% of cancer survivors and 32.2% of those with no cancer history reported having a general discussion of diet (P < 0.001). Among smokers, 67.3% of cancer survivors and 69.9% of those with no cancer history reported counseling on smoking (P = 0.309).

Conclusions:

Fewer cancer survivors, who are at increased risk for health complications, are reporting provider discussions about critical lifestyle issues than those with no cancer history.

Impact:

Our nationally representative results suggest that providers are missing an opportunity for influencing patient lifestyle factors, which could lead to mitigation of late and long-term effects of treatment.
Combinatorial Efficacy of Olaparib with Radiation and ATR Inhibitor Requires PARP1 Protein in Homologous Recombination–Proficient Pancreatic Cancer
Authors: Parsels Leslie A. , Engelke Carl G. , Parsels Joshua , Flanagan Sheryl A. , Zhang Qiang , Tanska Daria , Wahl Daniel R. , Canman Christine E. , Lawrence Theodore S. , Morgan Meredith A.
Published: December 2020

PARP inhibitor monotherapy (olaparib) was recently FDA approved for the treatment of BRCA1/2-mutant, homologous recombination (HR) repair-deficient pancreatic cancer. Most pancreatic cancers, however, are HR proficient and thus resistant to PARP inhibitor monotherapy. We tested the hypothesis that combined therapy with radiation and ataxia telangiectasia and Rad3-related (ATR) inhibitor (AZD6738) would extend the therapeutic indication of olaparib to HR-proficient pancreatic cancers. We show that olaparib combined with AZD6738 significantly reduced radiation survival relative to either agent alone, regardless of HR status. Whereas catalytic inhibition of PARP with low concentrations of olaparib radiosensitized HR-deficient models, maximal sensitization in HR-proficient models required concentrations of olaparib that induce formation of PARP1–DNA complexes. Furthermore, CRISPR-Cas9–mediated PARP1 deletion failed to recapitulate the effects of olaparib on radiosensitivity and negated the combinatorial efficacy of olaparib and AZD6738 on radiosensitization, suggesting that PARP1–DNA complexes, rather than PARP catalytic inhibition, were responsible for radiosensitization. Mechanistically, therapeutic concentrations of olaparib in combination with radiation and AZD6738 increased DNA double-strand breaks. DNA fiber combing revealed that high concentrations of olaparib did not stall replication forks but instead accelerated replication fork progression in association with an ATR-mediated replication stress response that was antagonized by AZD6738. Finally, in HR-proficient tumor xenografts, the combination of olaparib, radiation, and AZD6738 significantly delayed tumor growth compared with all other treatments. These findings suggest that PARP1–DNA complexes are required for the therapeutic activity of olaparib combined with radiation and ATR inhibitor in HR-proficient pancreatic cancer and support the clinical development of this combination for tumors intrinsically resistant to PARP inhibitors.
A Pilot Study of Galunisertib plus Stereotactic Body Radiotherapy in Patients with Advanced Hepatocellular Carcinoma
Authors: Reiss Kim A. , Wattenberg Max M. , Damjanov Nevena , Prechtel Dunphy Elizabeth , Jacobs-Small Mona , Lubas M. Judy , Robinson James , Dicicco Lisa , Garcia-Marcano Luis , Giannone Michael A. , Karasic Thomas B. , Furth Emma E. , Carpenter Erica L. , Wojcieszynski Andrzej P. , Vonderheide Robert H. , Beatty Gregory L. , Ben-Josef Edgar
Published: December 2020

TGFβ is a pleiotropic cytokine with immunosuppressive activity. In preclinical models, blockade of TGFβ enhances the activity of radiation and invokes T-cell antitumor immunity. Here, we combined galunisertib, an oral TGFβ inhibitor, with stereotactic body radiotherapy (SBRT) in patients with advanced hepatocellular carcinoma (HCC) and assessed safety, efficacy, and immunologic correlatives. Patients (n = 15) with advanced HCC who progressed on, were intolerant of, or refused sorafenib were treated with galunisertib (150 mg orally twice a day) on days 1 to 14 of each 28-day cycle. A single dose of SBRT (18-Gy) was delivered between days 15 to 28 of cycle 1. Site of index lesions treated with SBRT included liver (9 patients), lymph node (4 patients), and lung (2 patients). Blood for high-dimensional single cell profiling was collected. The most common treatment-related adverse events were fatigue (53%), abdominal pain (46.6%), nausea (40%), and increased alkaline phosphatase (40%). There were two instances of grade 2 alkaline phosphatase increase and two instances of grade 2 bilirubin increase. One patient developed grade 3 achalasia, possibly related to treatment. Two patients achieved a partial response. Treatment with galunisertib was associated with a decrease in the frequency of activated T regulatory cells in the blood. Distinct peripheral blood leukocyte populations detected at baseline distinguished progressors from nonprogressors. Nonprogressors also had increased CD8+PD-1+TIGIT+ T cells in the blood after treatment. We found galunisertib combined with SBRT to be well tolerated and associated with antitumor activity in patients with HCC. Pre- and posttreatment immune profiling of the blood was able to distinguish patients with progression versus nonprogression.
Progressive Fibrosing Interstitial Lung Diseases: Prevalence and Characterization in Two Italian Referral Centers
Authors: Faverio Paola , Piluso Martina , De Giacomi Federica , Della Zoppa Matteo , Cassandro Roberto , Harari Sergio , Luppi Fabrizio , Pesci Alberto
Published: December 2020

Background: The prevalence and natural history of progressive fibrosing interstitial lung diseases (PF-ILDs), and their response to commonly used treatments in real life are largely unknown. Objectives: The aim of the study was to describe the prevalence, clinical characteristics, management, and outcomes of PF-ILD patients attending 2 Italian referral centers (San Gerardo Hospital, Monza, and San Giuseppe Hospital, Milan) from January 1, 2011, to July 31, 2019. Methods: From a cohort of non-idiopathic pulmonary fibrosis fibrosing ILD patients with at least 2-year follow-up, we selected only those with progressive disease, defined as per the INBUILD trial, collecting their demographical, clinical, and functional data. Results: Out of the 245 fibrosing ILD patients, 75 (31%) were classified as PF-ILDs (median age 66 years, 60% males), most frequently idiopathic non-specific interstitial pneumonia (28%), followed by connective tissue disease-associated ILD (20%), chronic hypersensitivity pneumonitis, and sarcoidosis (17% each). Most patients (81%) were categorized as PF-ILDs because of forced vital capacity (FVC) decline ≥10%, while 19% experienced a marginal FVC decline (between 5 and 10%) associated with worsening respiratory symptoms or increasing extent of fibrotic changes on high-resolution computed tomography. Disease progression occurred after a median of 18 months from ILD diagnosis. The vast majority (93%) of PF-ILD patients received prednisolone, alone (40%) or associated with steroid-sparing agents (52%), and 35% of treated patients developed treatment-related adverse events. After ILD progression, the median survival was 3 (interquartile range (IQR) 2–5) years, with a 2- and 3-year mortality rate of 4 and 20%, respectively. Conclusions: In a real-life setting, approximately one-third of the fibrosing ILD patients showed a progressive course despite treatment. Studies aimed to better phenotype this subgroup of patients are needed.
CT-Derived Pulmonary Artery Diameters to Preselect for Echocardiography in COPD Patients Eligible for Bronchoscopic Treatments
Authors: van der Molen Marieke C. , Hartman Jorine E. , Klooster Karin , Kerstjens Huib A.M. , van Melle Joost , Willems Tineke P. , Slebos Dirk-Jan
Published: December 2020

Background: Currently, patients with COPD who are evaluated for bronchoscopic treatments are routinely screened for pulmonary hypertension (PH) and systolic left ventricle dysfunction by echocardiography. Objectives: We evaluated the prevalence of PH and systolic left ventricle dysfunction in this patient group and investigated if the previously proposed CT-derived pulmonary artery to aorta (PA:A) ratio >1 and PA diameter measurements can be used as alternative screening tools for PH. Methods: Two hundred fifty-five patients were included in this retrospective analysis (FEV1 25%pred, RV 237%pred). All patients received transthoracic echocardiography and chest CT scans on which diameters of the aorta and pulmonary artery were measured at the bifurcation and proximal to the bifurcation. Results: Following echocardiography, 3 patients (1.2%) had PH and 1 (0.4%) had systolic left ventricle dysfunction. Using a PA:A ratio >1, only 10.3% of the patients with a right ventricular systolic pressure (RVSP) ≥35 mm Hg were detected and none of the patients with an RVSP >50 mm Hg were detected. Patients with an RVSP ≥35 mm Hg had significantly higher PA diameters (29.5 vs. 27.5 mm; p = 0.02) but no significantly different PA:A ratios. All patients with an RVSP >50 mm Hg had PA diameters >30 mm. Conclusions: The prevalence of PH and systolic left ventricle dysfunction is low in this preselected cohort of patients with severe COPD. In this population, a PA:A ratio >1 is not a useful cardiac screening tool for PH. A PA diameter >30 mm could substitute for routinely performed echocardiography in the screening for PH in this patient group.
Early Cytokine Removal in Critical COVID-19 Patients with Extracorporeal Therapies (HA-380 plus High Volume Hemofiltration) May Prevent Progression of Acute Respiratory Distress Syndrome: Case Report
Authors: Ramírez-Guerrero Gonzalo , Torres Cifuentes Vicente , Baghetti Hernández Romyna , Villagrán Cortés Francisco , Rojas Doll Simón , Oliva Alarcón Rocio , Lucero Córdova Cristian , Flores Fernandez Pablo , Garay Coloma Osvaldo
Published: December 2020

We present the case of a patient who suffered from acute respiratory distress syndrome caused by pneumonia associated with COVID-19 and cytokine release syndrome. This patient received a high-volume hemofiltration plus adsorption, solving the hemodynamic deterioration, pulmonary infiltrates, and gas exchange. Our clinical case proposes that the extracorporeal therapies can have a role in the management of severe COVID-19.
End‐Organ Function and Exercise Performance in Patients With Fontan Circulation: What Characterizes the High Performers?
Authors: Weinreb Scott J. , Dodds Kathryn M. , Burstein Danielle S. , Huang Jing , Rand Elizabeth B. , Mancilla Edna , Heimall Jennifer R. , McBride Michael G. , Paridon Stephen M. , Goldberg David J. , Rychik Jack
Published: December 2020

Background

The physiologic hallmarks of the Fontan circulation—chronically elevated central venous pressures and low cardiac output—have significant effects not only on cardiovascular status but also impact other organ systems. Exercise capacity is limited in many and declines with age, accelerating in adolescence, but with wide variability. We explore the relationship between exercise performance and end‐organ function in outpatient subjects with a Fontan circulation.

Methods and Results

This is a cross‐sectional analysis of subject end‐organ characterization from our outpatient Fontan circulation clinic with peak oxygen consumption (peak V
o
2
) at cardiopulmonary exercise testing as the primary outcome. We perform linear regression to assess associations between clinical characteristics and peak V
o
2
as well as the magnitude of the association of clinical characteristics with peak V
o
2
. Of 265 subjects age 12.8 (9.5–16.4) years, there is a negative correlation between age and peak V
o
2
(−0.49,
P
<0.001). Of those undergoing ramp cycle exercise testing, 34% perform above 80% predicted peak V
o
2
. Variables positively associated with peak V
o
2
and their effect size include vitamin D sufficiency (+3.00,
P
=0.020) and absolute lymphocyte count (+0.23,
P
=0.005). Status as overweight/obese (−3.91,
P
=0.003) and hemoglobin (−0.77,
P
=0.003) are negatively associated. Neither ventricular morphology, timing of Fontan palliation, nor Fontan circulation type affect peak V
o
2
.

Conclusions

Higher peak V
o
2
in those with a Fontan circulation is associated with younger age, vitamin D sufficiency, absence of overweight/obese, lower hemoglobin, and a healthier hepatic profile. Whether exercise training or other initiatives can modify organ characteristics in those with a Fontan circulation is worthy of exploration.
Acoustic characteristics of the island-endemic Parapelophryne scalpta (Anura: Bufonidae) from Hainan Island, China
Authors: YEUNG HO YUEN , YANG JIAN-HUAN
Published: December 2020

The Hainan Pygmy Toad Parapelophryne scalpta (Liu & Hu) is the single species of the genus Parapelophryne Fei, Ye & Jiang in the Family Bufonidae (Frost 2020) and is endemic to China’s Hainan Island, which lies within the tropics at 18°09′–20°10′N, 108°37′–111°03′E, with a land area of ca. 33,900 km2. The taxonomy status of this species has obtained much debates since its discovery: it was originally described by Liu et al. (1973) as a member of the genus Nectophryne Buchholz & Peters then allocated to Pelophryne Barbour by Ye & Fei (1978). On the basis of its unique morphological characters, Fei et al. (2003) erected a new genus Parapelophryne to discriminate P. scalpta from other bufonids. Some researchers, however, still listed the species under the genus Pelophryne (Stuart et al. 2008; Shi et al. 2011). Recently, the validity of the genus Parapelophryne is further confirmed by Matsui et al. (2015) on the basis of molecular analyses. Interestingly enough, Matsui et al. (2015)’s result showed that this extremely small-sized toad is a sister taxon of the large-sized toads of the genus Bufo Garsault, which is mainly distributed in temperate and subtropical regions of Eurasia (Frost 2020). Parapelophryne scalpta is a forest-dependent species and only inhabits in well-preserved evergreen broadleaf forests (Fei & Ye 2016). It is the smallest toad species in China with snout-vent length of 19–23 mm in adult males and 24–27 mm in females (Fei & Ye 2016). Due to their small size and elusive habits, little is known about the natural history of P. scalpta and its acoustic characteristics are still undocumented (Fei & Ye 2016). During a herpetological survey in Hainan in 2015, we luckily detected male calls of P. scalpta and obtained a short but clear record of the advertisement call of the species. Herein, we describe the acoustic characteristics and calling behavior of Parapelophryne scalpta.
A simple measure of beta-convergence revisited
Authors: Gray David
Published: December 2020

Convergence among regions to long-run, non-zero income differentials is predicted by mainstream and alternative spatial theories. A variety of convergence, considered by Sala-i-Martin, focuses on the rank order over time. As some must be growing faster than others, intra-distributional mobility implies convergence of regions. A measure of this from Boyle and McCarthy is the trend in rank concordance. As it is a measure of similarity between a given distribution and other sample periods, we propose that Kendall’s criterion ranking coefficient, combined with concordance, provides better insight into intra-distributional mobility and convergence. Agreement with a distribution can be traced over a series to highlight the mobility over time. This has the advantage of revealing whether mobility entails converging from, reverting to or converging to an order. Although there are phases of sigma-convergence and divergence, what is found in an analysis of regional house prices is that the rank-order is little affected by cycle phase. In trend, the UK price distribution appears to converge to a hierarchy, corresponding better with a very large monocentric urban model or Zipf-type, than a core–periphery-type distribution of prices. The broadening of price spreads is likely to be facilitated by the liberalisation of finance seen elsewhere, and by an appetite for greater mortgage debt.
Old, small and unwanted: Post-war housing and neighbourhood socioeconomic status
Authors: Rolheiser Lyndsey
Published: December 2020

Post-war neighbourhoods across the USA have declined in socioeconomic status over the past few decades. Over this same time period, the relative status of many of these neighbourhoods has dipped below that of older neighbourhoods. With the characteristics of post-war housing being arguably undesirable by current standards, extant literature claims the functional obsolescence of post-war housing is contributing to low and declining neighbourhood socioeconomic status. What remains unclear is whether the effect observed is due to housing age – post-war housing is vulnerable to physical depreciation given its age – or if there is a true post-war vintage effect influencing neighbourhood socioeconomic status beyond what age alone would predict. Using a panel model spanning 1990 to 2010, three main findings emerge. First, the presence of greater shares of post-war housing in neighbourhoods is associated with a small but significant decrease in neighbourhood status. Second, this effect varies across and within urban and suburban neighbourhoods. Third, there exists substantial heterogeneity in the effect across metropolitan areas that differ by housing supply growth and price. Together, these results imply that policymakers should consider the negative effects of functional obsolescence on top of the ills associated with ageing homes within certain spatial contexts.
Case Study Analysis of Hermeneutic Boundary Spanning During Policy Change and Transition
Authors: Zingale Nicholas C. , Higl Alexandra
Published: December 2020

Working through a lens of administrative governance, hermeneutics, and boundary spanning, we spent 18 months studying the Ohio Children’s Trust Fund (OCTF) as it began its transition from a county to a regional funding model. Using observations and interviews of regional directors and administrative teams, we were interested in learning more about the role of boundary spanning and hermeneutics during the transition process. In other words, attempting to answer the question on what makes boundary spanning work at the level of the boundary spanner? The case study research produced four primary findings: (a) state and regional administrators desired a transitional approach that meant dispersing and distributing power and decisions to regional leaders; (b) political, time, and budget constraints worked against these desires; (c) boundary spanning efforts failed to produce a resource network; and (d) seeking understanding between the macro deterministic goals of the state to the micro regional and local needs produced an exercise in philosophical hermeneutics—particularly at the boundaries of the region and the state, as actors interpreted what they saw, read, and thought. We concluded that public administrators might better cope with the uncertainties associated with program transitions by more fully developing a hermeneutic mind-set for exploratory bias over confirmatory bias when engaging in boundary spanning and forming collaborative networks.
Does Advanced Placement Economics Exam Participation and Performance Predict Undergraduate Economics Major Completion?
Authors: Ahlstrom Laura J.
Published: December 2020

Students who take an Advanced Placement (AP) Microeconomics and/or AP Macroeconomics exam may be more interested in economics than their non-AP exam peers and more likely to complete an economics major. Performance on AP exams in economics may also affect students’ economics major completion. This study uses binary probit estimations to assess how participation in and performance on AP exams in economics affects students’ completion of an economics major. The findings suggest students who take both AP exams in economics are significantly more likely to graduate with an economics major compared with non-AP students who complete their introductory economics coursework in college. In addition, strong performance on the AP Microeconomics exam significantly increases a student’s probability of earning an economics major. Receiving high scores on both AP Economics exams is also significantly and positively correlated with economics major completion.

JEL Classifications: A21, A22
‘Framing figures’ and the campaign for sex purchase criminalisation in Ireland: A Lakoffian analysis
Authors: Ward Eilís
Published: December 2020

If the concept of social justice posits equality and fairness between subjects in the social order, then the presence of those subjects within that order must first and foremost be acknowledged. In Ireland’s recent reform of prostitution law contained in the Criminal Law (Sexual Offences) Act 2017, the presence of the sex worker as a rights-bearing subject or citizen, with access to justice in that capacity, was denied. In this article I focus on the use of data by the neo-abolitionist ‘Turn off the Red Light’ campaign to ‘flatten out’ the complexity of sex workers lives and present the figure of the ‘vulnerable prostituted woman’ and the ‘trafficking victim’: tragic, abject, a necessarily violated person and in need of ‘protection’ from the state. I argue that this data, entering public and political discourse as uncontestable truth, constituted what I call, ‘framing figures’, framing an inevitable outcome and precluding certain subjects from the status of equality and fairness. The data allowed campaigners for the Sex Purchase Ban (SPB), and, in turn the state, to eclipse a social justice approach to sex work, such as proposed by the Sex Workers Alliance of Ireland and other actors.
Typologies and Correlates of Police Violence Against Female Sex Workers Who Inject Drugs at the México–United States Border: Limits of De Jure Decriminalization in Advancing Health and Human Rights
Authors: West Brooke S. , Henry Brandy F. , Agah Niloufar , Vera Alicia , Beletsky Leo , Rangel M Gudelia , Staines Hugo , Patterson Thomas L. , Strathdee Steffanie A.
Published: December 2020

Decriminalization of sex work is increasingly promoted as a structural measure to improve the health of vulnerable groups. In México, sex work is not illegal, but knowledge of policies’ street-level impact is limited. This study describes typologies of police violence against female sex workers who inject drugs (FSWID), identifying risk and protective factors for violence exposure to inform policy responses. Survey data were collected during 2008–2010 among HIV-negative FSWID in a behavioral intervention in Tijuana and Ciudad Juarez ( N = 584). Latent class analysis identified typologies of police violence in the past 6 months: asked for money, money taken, syringes taken, asked for sex, and sexually assaulted. Structural equation modeling (SEM) predicted latent class membership using sociodemographic, behavioral and risk environment factors, controlling for age, education, marital status, and city. Recent police violence was reported by 68% of FSWID, with three typologies emerging: Low (36.6%); Material (47.8%): having money/syringes taken or being asked for money; and Material/Sexual (15.7%): material violence and being asked for sex or sexually assaulted. In multivariable SEM, Material Violence was associated with: being jailed [adjusted Odds Ratio (aOR) = 4.34], HIV testing (aOR = 2.18), and trading sex indoors (aOR = 1.66). Factors associated with Material/Sexual Violence included: being jailed (aOR = 41.18), injecting with clients (aOR = 3.12), earning more money for sex without a condom (aOR = 2.88), being raped by a client (aOR = 2.13), drinking with clients (aOR = 2.03), receiving substance use treatment (aOR = 1.95), being <18 when first trading sex (aOR = .43), trading sex outdoors (aOR = .53), and poor working conditions (aOR = .56). Despite de jure decriminalization of sex work, police violence against FSWID at the México–United States border is pervasive with implications for sex- and drug-related harms. Closing gaps in policy implementation and mitigating material/sexual violence from police is imperative to decreasing economic vulnerability, risk of overdose and HIV, and improving engagement in HIV and harm reduction services.
Detached Attachment: Burnout and Commitment among Caregivers in the Immigrant Rights Movement
Authors: Márquez Alejandro
Published: December 2020

The increasing numbers of migrants and asylum seekers reaching the U.S.–Mexico border since 2014 has strained local nonprofit organizations helping them. Lack of material and human resources along with uncertain policy implementation by the government generates frustration and burnout among caregivers working in local nonprofits. Nonetheless, turnover as a result of burnout is surprisingly low. To answer why so few caregivers make efforts to help migrants and asylum seekers on the border, I analyze how caregivers respond to burnout in this resource-scarce context. I find that caregivers practice what I call detached attachment, the process of physically and emotionally distancing oneself from care work, while maintaining a cognitive attachment to it. Caregivers seek space to process their negative emotions and manage their relationships with care recipients to reduce intensity, while also reflecting on their normative attachments to the work. Paradoxically, then, the negative experience of burnout ends up renewing caregivers’ commitment to the immigrant rights movement. This article highlights the significance of everyday practices of care in sustaining social movement participation.
‘It’s Like a War Zone’: Jay’s Liminal Experience of Normal and Extreme Work in a UK Supermarket during the COVID-19 Pandemic
Authors: Cai Minjie , Tindal Scott , Tartanoglu Bennett Safak , Velu Jay
Published: December 2020

This article presents a UK supermarket worker’s experiences of work during the COVID-19 pandemic. Writing during a period of uncertainty, Jay’s narrative reveals how the sudden and constant transitions between mundanity and extremity on the shop floor evoke conflicting emotions and work intensification that disrupt and reconstruct normality. His accounts describe violent customer behaviours, absent management, a lack of clear organisational policies, and the different views of appropriate health and safety measures among colleagues. It illustrates how liminality in the workplace at a time of crisis can endanger employees whose seemingly mundane jobs become extreme.
Impacts of decarbonization on the automotive after sales sector: A review of evidence
Authors: Eslava-Bautista Jorge , Cottrill Caitlin D , Beecroft Mark
Published: December 2020

Automotive after sales, which include provision of spare parts, customer service, and accessories sales, is one of the most profitable parts of the automotive industry and provides for an ongoing relationship with the customer. In times of recession, performance of after sales remains steady as it is highly independent of macroeconomic behaviors and keeps outstanding margins. Current automotive after sales are predominantly based on fossil fuel power train technologies, involving a significant number of replaceable working parts, lubricants, and supplies, and requiring ongoing manual labor. Current efforts to decarbonize the automotive industry, however, have the potential to disrupt this industry by shifting traditional after sales business models.

The objective of this paper is to review the background and development of policies and actions in relation to the decarbonization of transport with a particular focus upon the role of the automotive after sales sector. The review considers the role of a range of stakeholders including multilateral bodies setting targets for participating nations; national governments; and the automotive industry, operating at varying scales. Electrification of vehicles and discouragement of car use and ownership are identified as key decarbonization strategies that could significantly impact upon car manufacturers and the broader automotive industry, which will in turn impact upon the after sales market. The review concludes that there has been limited research about impacts on after sales markets from transport decarbonization strategies. Areas of impact identified include reduction of working parts, fewer additional units, longer service intervals, changes in labor needs, disruption in customer retention, and changes to the repurchase cycle. In order to explore these potential impacts, the development of alternative future scenarios under different power train technologies and regional factors is recommended as an area for further research.
Protective Effects of Human Nonrenal and Renal Stromal Cells and Their Conditioned Media in a Rat Model of Chronic Kidney Disease
Authors: Imberti Barbara , Cerullo Domenico , Corna Daniela , Rota Cinzia , Locatelli Monica , Pezzotta Anna , Introna Martino , Capelli Chiara , Carminati Claudia Elisa , Rabelink Ton J. , Leuning Danielle G. , Zoja Carlamaria , Morigi Marina , Remuzzi Giuseppe , Benigni Ariela , Luyckx Valerie
Published: December 2020

Mesenchymal stromal cells (MSCs) are emerging as a novel therapeutic option for limiting chronic kidney disease progression. Conditioned medium (CM) containing bioactive compounds could convey similar benefits, avoiding the potential risks of cell therapy. This study compared the efficacy of nonrenal and renal cell-based therapy with the corresponding CM in rats with renal mass reduction (RMR). Infusions of human kidney stromal cells (kPSCs) and CM-kPSCs, but not umbilical cord (uc) MSCs or CM-ucMSCs, reduced proteinuria and preserved podocyte number and nephrin expression in RMR rats. Glomerular fibrosis, microvascular rarefaction, and apoptosis were reduced by all treatments, while the peritubular microvascular loss was reduced by kPSCs and CM-kPSCs treatment only. Importantly, kPSCs and CM-kPSCs reduced NG2-positive pericytes, and all therapies reduced α-smooth muscle actin expression, indicating reduced myofibroblast expansion. Treatment with kPSCs also significantly inhibited the accumulation of ED1-positive macrophages in the renal interstitium of RMR rats. These findings demonstrate that the CM of ucMSCs and kPSCs confers similar renoprotection as the cells. kPSCs and CM-kPSCs may be superior in attenuating chronic renal injury as a cell source.
Evaluation of Extended-Interval Dabigatran Dosing in Older Patients With Non-Valvular Atrial Fibrillation
Authors: Ni Lianfang , Chen Xiahuan , Liu Meilin , Fan Yan , Fu Zhifang , Sun Dan , Zhao Zhijie
Published: December 2020

Objective:

To evaluate the safety and efficacy of extended-interval dabigatran dosing in older Chinese patients with non-valvular atrial fibrillation.

Methods:

We conducted an observational study on non-valvular atrial fibrillation patients administered dabigatran at different dosing intervals at the Department of Geriatrics, Peking University First Hospital, China. We enrolled 121 consecutive non-valvular atrial fibrillation patients aged ≥60 years on dabigatran therapy (mean age, 79.6 ± 7.4 years); they were administered conventional low-dose dabigatran (110 mg twice daily) or extended-interval dosing with dabigatran (110 mg every 16 h or every 24 h). All patients received follow-up care, and we evaluated the presence of bleeding and thromboembolic events.

Results:

All patients exhibited creatinine clearance greater than 30 mL/min with an average of 56.6 ± 17.3 mL/min. Sixty-two patients received extended-interval dosing with dabigatran at a mean dose of 117.1 ± 18.6 mg daily. Patients on extended-interval dosing were older; they exhibited lower creatinine clearance and bodyweight and higher CHA2DS2-VASc and HAS-BLED scores. The mean follow-up time was 25.8 ± 15.6 months. No significant differences were observed in the trough and peak values of the activated partial thromboplastin time and in thromboembolic or bleeding events between the 2 groups.

Conclusion:

Extended-interval dabigatran dosing in older patients with non-valvular atrial fibrillation and lower creatinine clearance can maintain activated partial thromboplastin time trough and peak values comparable to the conventional low dose. Physician-prescribed practices regarding dabigatran dosing intervals do not lead to worse outcomes in the above-mentioned population.