bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract LB192: Demethylation, DNA damage and antitumor activity of DNA methyltransferase inhibitors in models with intact and disrupted DNMT1 gene
Authors: Laranjeira Angelo B. , Hollingshead Melinda , Nguyen Dat , Kinders Robert , Difilippantonio Michael , Doroshow James H. , Yang Sherry X.
Published: June 2022

DNA methyltransferase (DNMT) 1 is an enzyme responsible for maintaining DNA methylation pattern during DNA replication. However, its role on the methylation of tumor suppressor genes and DNA damage in relation to antitumor activity of DNMT inhibitors remains controversial. Here, we investigated the effects of DNMT inhibitors in human colorectal and breast cancer cell lines and animal models with intact (DNMT1+/+) and disrupted DNMT1 (DNMT1-/-) gene. Treatment with 5 µM of 4’-thio-5-aza-2’-deoxycytidine (aza-TdC), decitabine and azacytidine all inhibited DNMT1 expression and cell growth (94.0%/97.1%, 39.9%/58.6% and 69.2/91.3), and induced apoptosis (66.9%/62.5%, 30.9%/23.8% and 66.2/43.1%) in DNMT1+/+ HCT116/MCF7 cells; in contrast, the DNMT inhibitors had less/little activities in DNMT1-/- HCT116/MCF7 cells (P<0.001 each). γH2AX and G2/M cell-cycle arrest were induced by the inhibitors and greater degree of induction was produced by aza-TdC than decitabine in DNMT1+/+ cells (P<0.001), with activation of checkpoint kinase 1 and upregulation of p21. Both demethylation and increased acetylation of CDKN2A and CDKN2B gene promoters together with re-expression of p16INK4A and p15INK4B proteins were detected in DNMT1-/- versusDNMT1+/+ (demethylation only) cells upon exposure to decitabine for 72h. Compared with saline treatment, tumor growth was significantly inhibited by aza-TdC (90%; n=18 mice) and decitabine (62%; n=18) in DNMT1+/+ colorectal xenograft tumors, alongside decreasing expression of DNMT1 (51% and 44%) and an increase in p21 (85% and 48%). Similarly, tumor growth delays (86%; n=15 and 57%; n=14) were associated with the reduction of DNMT1 and augmentation of p21 in bladder PDX tumors. The findings suggest that DNMT inhibitors induce DNA damage and higher anti-tumor activity of aza-TdC is proportional to a greater magnitude of induction of DNA damage, p21 and cell cycle arrest without reactivating the expression of p16INK4A and p15INK4B. The gene re-expression coupled to demethylation and acetylation corresponds to the less anti-tumor activity by decitabine in DNMT1-/- cells. Thus, it is the DNA damage effects, rather than re-expression of the tumor suppressors, that are associated with antitumor activity of the DNMT inhibitors in cancer cells and/or xenograft and PDX tumors.

Citation Format: Angelo B. Laranjeira, Melinda Hollingshead, Dat Nguyen, Robert Kinders, Michael Difilippantonio, James H. Doroshow, Sherry X. Yang. Demethylation, DNA damage and antitumor activity of DNA methyltransferase inhibitors in models with intact and disrupted DNMT1 gene [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB192.
Abstract LB203: Assessment of the safety, pharmacokinetics, and pharmacodynamics of a first-in-class cancer drug candidate E-602, a sialoglycan degrader, in non-human primates
Authors: Cao Lizhi , Che Jenny , Chesney Ali , Dixit Rakesh , Zheng Nancy , Zane Nicole , Broderick James , Peng Li
Published: June 2022

E-602 is a novel, first-in-class, engineered human sialidase (Neu2) Fc fusion developed for cancer treatment by enhancing antitumor immunity through desialylating immunosuppressive sialoglycans. We have previously shown that E-602 cleaves off terminal sialic acids from surface sialoglycans on tumor and immune cells, restores the immune function of exhausted-like T cells, and enhances dendritic cell priming and activation of naïve T cells. E-602 has also demonstrated antitumor activity as a single agent in multiple syngeneic mouse tumor models. To support clinical development, we conducted a Good Laboratory Practice one-month repeat-dose toxicity study to evaluate E-602’s pharmacokinetic (PK) parameters, pharmacodynamic (PD) effects, and safety profiles in cynomolgus monkeys via weekly intravenous infusion of E-602 at 5, 30, 100, and 200 mg/kg for five doses. E-602 showed an apparent half-life (t1/2) of 4-6 hours and the terminal t1/2 of 10-30 hours with dose linearity from 30 mg/kg to 200 mg/kg. E-602 produced dose-dependent PD effects of desialylation of immune cells, such as T cells, monocytes, and dendritic cells, as monitored by flow cytometry. Despite the short half-life of E-602, the PD effect of immune cell desialylation sustained up to seven days for T cells, consistent with E-602’s enzymatic mechanism of action. Generally, E-602 was well tolerated up to 100 mg/kg with no dose-limiting adverse E-602-related changes in body weight, ophthalmology, neurological/musculoskeletal assessments, electrocardiogram parameters, respiratory rate, coagulation, urinalysis, organ weights, and histopathology. Animals in the 200 mg/kg dose group survived but showed isolated adverse histopathological changes with an uncertain relationship to E-602 administration. Therefore, the no-observed-adverse-effect-level (NOAEL) of E-602 was determined as 100 mg/kg in cynomolgus monkeys. In conclusion, the PK and PD data have supported the selection of cynomolgus monkeys as the toxicity species to evaluate E-602’s safety profile. E-602 has demonstrated sustained PD effects of immune cell desialylation up to seven days postdose and a wide safety margin with NOAEL of 100 mg/kg in cynomolgus monkeys.

Citation Format: Lizhi Cao, Jenny Che, Ali Chesney, Rakesh Dixit, Nancy Zheng, Nicole Zane, James Broderick, Li Peng. Assessment of the safety, pharmacokinetics, and pharmacodynamics of a first-in-class cancer drug candidate E-602, a sialoglycan degrader, in non-human primates [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB203.
Abstract LB519: Bimodality of gene expression in cancer patients as interpretable biomarkers for drug sensitivity
Authors: Haibe-Kains Benjamin , Ba-alawi Wail
Published: June 2022

Identifying biomarkers predictive of cancer cells’ response to drug treatment constitutes one of the main challenges in precision oncology. Recent large-scale cancer pharmacogenomic studies have opened new avenues of research to develop predictive biomarkers by profiling thousands of human cancer cell lines at the molecular level and screening them with hundreds of approved drugs and experimental chemical compounds. Many studies have leveraged these data to build predictive models of response using various statistical and machine learning methods. However, a common challenge in these methods is the lack of interpretability as to how they make the predictions, hindering the clinical translation of these models. To alleviate this issue, we used the recent logic modeling approach to develop a new machine learning pipeline that explores the space of bimodally expressed genes in multiple large in vitro pharmacogenomic studies and builds multivariate, nonlinear, yet interpretable logic-based models predictive of drug response. We showcased the performance of the approach in a compendium of the three largest in vitro pharmacogenomic data sets to build robust and interpretable models for 101 drugs that span 17 drug classes with high validation rate in independent datasets. These results along with in vivo validation support a better translation of gene expression biomarkers between model systems using bimodal genes.

Citation Format: Benjamin Haibe-Kains, Wail Ba-alawi. Bimodality of gene expression in cancer patients as interpretable biomarkers for drug sensitivity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB519.
Abstract LB528: A microglia associated gene signature predicts survival risk in glioma patients
Authors: Jiang Chongming , Schaafsma Evelien , Zhao Yanding , Nguyen Thinh , Zhu Kenneth , Cheng Chao
Published: June 2022

Background: Gliomas are common tumors that affect the brain and spinal cord. A complex tumor microenvironment is one of the leading reasons for a poor prognosis in glioma patients. Microglia, as part of the immune microenvironment of gliomas, may facilitate glioma growth and invasion. However, the correlation between the microglia abundance and glioma prognosis has not been clarified.

Method: Our goal was to examine the relationship between microglia abundance and glioma prognosis. We analyzed the single-cell RNA sequences of human and mouse glioma cells to identify microglia marker genes. Then, we built a LASSO Cox regression model of microglia abundance signatures in gliomas. The Cancer Genome Atlas (TCGA) dataset (Low-grade gliomas, LGG) was used as the training cohort. The Repository of Molecular Brain Neoplasia Data (REMBRANDT) dataset and Chinese Glioma Genome Atlas (CGGA) dataset was used to validate the model as the validation cohorts.

Findings: Overall survival was significantly lower in those with a high level of microglia infiltration. Additionally, we found that microglia could interact with the tumor microenvironment and genomic features of gliomas, making microglia abundance negatively associated with the prognosis of glioma patients. Microglia abundance was positively correlated with immune genes expression and immune-related pathways. By applying our LASSO Cox regression model to gliomas, we found that patients with high-risk scores had significantly shorter overall survival (OS) than those with low-risk scores.

Conclusions: Taken together, our findings suggest that microglia abundance may be negatively associated with survival in gliomas. Based on the novel microglia abundance signatures, we developed a high accuracy LASSO Cox regression model. In this study, we demonstrated that the model accurately predicted the prognosis of glioma patients and could offer new therapeutic targets for microglial-directed therapies.

Keywords: Gliomas; Microglia abundance; LASSO Cox regression; TCGA; Signature.- 1 -

Citation Format: Chongming Jiang, Evelien Schaafsma, Yanding Zhao, Thinh Nguyen, Kenneth Zhu, Chao Cheng. A microglia associated gene signature predicts survival risk in glioma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB528.
Abstract LB541: The cysteine rich protein 61 (Cyr61) contributes to tumor proliferation and invasion via HGF (hepatocyte growth factor) mediated NFkB signaling pathway in human hepatocellular carcinoma
Authors: Jung Jiyoon , Koh sungae , Lee Kyunghee , Kim Jaeryong
Published: June 2022

Background: CCN growth factor family regulates a variety of biological events such as cell proliferation, cell invasion, cell differentiation, apoptosis, and growth inhibition. Cysteine-rich protein 61 (Cyr61) is one of six secreted proteins in the CCNs. It has been shown that Cyr61 plays an important role in tumorigenesis and carcinogenesis in glioma, breast cancer, and gastric cancer, and others. However, Cyr61 has not yet been elucidated on the tumorigenesis, proliferation, and invasion of hepatocellular carcinoma, and needs to be researched and discovered. In this study, the HGF-mediated association of Cyr61, interleukin-8 (IL-8), and NF-κB (Nuclear factor kappa-light-chain-enhancer of activated B cells) and cancer cell proliferation and invasion were investigated in two types of hepatoma cell lines.

Methods: In this study, cell culture, cDNA microarray analysis, western blotting, Real-time Polymerase chain reaction, Zymography, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Cyr61 knock-down with short hairpin RNA (shRNA), chromatin immunoprecipitation assay, Standard two chamber invasion assay.

Results: First, we confirmed that the expression level of Cyr61 was up-regulated by HGF (hepatocyte growth factor) in hepatoma cells. To identify associated pathway of HGF-induced Cyr61 about IL-8, NF-κB expression, the cells were treated with PI3K (Phosphoinositide 3-kinase) inhibitor (LY294002) and then analyzed by Western blotting. The HGF-mediated IL-8 and NF-κB levels were decreased with LY294002. The role for Cyr61 associated with IL-8 and NF-κB was determined by knock down cell of Cyr61. Cyr61-sh RNA cells showed a decreased level of IL-8 and NF-κB. HGF-mediated cell proliferation and invasion were decreased in Cyr61 knock down cell.

Conclusions: These results suggest that Cry61 plays an important role in cell proliferation and metastasis in hepatocellular carcinoma, and Cry61 may be a novel target for the prevention of progression and treatment of hepatocellular carcinoma.

Citation Format: Jiyoon Jung, sungae Koh, Kyunghee Lee, Jaeryong Kim. The cysteine rich protein 61 (Cyr61) contributes to tumor proliferation and invasion via HGF (hepatocyte growth factor) mediated NFkB signaling pathway in human hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB541.
Plasma Oxytocin Is Not Associated with Social Cognition or Behavior in Frontotemporal Dementia and Alzheimer’s Disease Syndromes
Authors: Johnson Emma G. , Kuiper Wytse , Ahmed Rebekah M. , Halliday Glenda M. , Burrell James R. , Hodges John R. , Guastella Adam J. , Piguet Olivier , Kumfor Fiona
Published: June 2022

Introduction: Changes in social behavior and emotion processing are common in frontotemporal dementia (FTD) and semantic dementia (SD), and less so in Alzheimer’s disease (AD). Recent research has investigated oxytocin as a potential treatment for these symptoms; however, whether plasma oxytocin is associated with social-emotional symptoms of dementia remains underexplored. Methods: Thirty behavioral-variant FTD (bvFTD), 28 SD, 39 AD, and 24 controls underwent blood sampling to measure oxytocin. Participants completed an emotion processing battery. Carers completed the Cambridge Behavioral Inventory and the Neuropsychiatric Inventory. Results: Patients with bvFTD were severely impaired in emotion processing and behavioral ratings, with milder impairment in SD and AD. No difference in plasma oxytocin was observed between groups (p = 0.632). No significant associations were found between oxytocin and social behavior or emotion processing (r values between −0.241 and 0.227, all p values >0.099). Conclusion: Our results indicate that plasma oxytocin is not reduced in dementia and is unrelated to social, emotional, and behavioral features. We noted high interindividual variability in our data; hence, future investigations should consider methodological influences such as serum versus saliva and diurnal variation on oxytocin function. These results demonstrate that current measurement measures of plasma oxytocin have limited utility in determining the role of oxytocin in FTD. Alternative oxytocin measures may prove more sensitive and should be considered when conducting clinical trials.
The Role of MRI in the Treatment of Drug-Resistant Focal Epilepsy
Authors: Bernasconi Andrea , Bernasconi Neda
Published: June 2022

Background: Epilepsy is a prevalent chronic condition affecting about 50 million people worldwide. A third of patients with focal epilepsy suffer from seizures unresponsive to medication. Uncontrolled seizures damage the brain, are associated with cognitive decline, and have negative impact on well-being. For these patients, the surgical resection of the brain region that gives rise to seizures is the most effective treatment. Summary: Magnetic resonance imaging (MRI) plays a central role in detecting epileptogenic brain lesions. In this review, we critically discuss advances in neuroimaging acquisition, analytical post-acquisition techniques, and machine leaning methods for the detection of epileptogenic lesions, prediction of clinical outcomes, and identification of disease subtypes. Key Message: MRI is a mandatory investigation for diagnosis and treatment of epilepsy, particularly when surgery is being considered. Continuous progress in imaging techniques, combined with machine learning, will continue to push the boundaries of lesion visibility and provide increasingly precise predictors of clinical outcomes. Current efforts aiming at strengthening the competences of epileptologists in neuroimaging will ultimately reduce the need for invasive diagnostics.
Long Noncoding RNA Brain Cytoplasmic RNA 1 Induces Cisplatin-Resistance of Cervical Cancer Cells by Sponging MicroRNA-330-5p and Upregulating High-Mobility Group Box 3
Authors: Sun Dan , Cao Rui , Han Lu , Yu Xiaohui , Wang Huali , Wang Xiuying , Chen Xuelian
Published: June 2022

Objectives: The aim of the study was to find out the function of long noncoding RNA brain cytoplasmic RNA 1 (BCYRN1) in cisplatin (DDP)-resistance of cervical cancer (CC) cells. Design and Materials, Setting, Methods: BCYRN1 expression in CC and DDP-resistant cells was evaluated, with the association of BCYRN1 and prognosis analyzed. Then, DDP-resistant cells with BCYRN1 knockdown were established and the DDP-resistance of these cells was assessed. BCYRN1 subcellular localization was detected and confirmed. Besides, the binding relations of BCYRN1 and microRNA (miR)-330-5p and between miR-330-5p and high-mobility group box 3 (HMGB3) were examined and verified. Moreover, the role of miR-330-5p and HMGB3 in the mechanism of BCYRN1 modulating DDP-resistance of CC cells was detected. In addition, xenograft transplantation was conducted to confirm the effect of BCYRN1 in CC cell DDP-resistance. Results: BCYRN1 was overexpressed in CC, which resulted in poor prognosis and DDP-resistance. BCYRN1 knockdown in DDP-resistant cells downregulated DDP-resistance. Mechanically, BCYRN1 sponged miR-330-5p to strengthen HMGB3 mRNA level. Besides, miR-330-5p underexpression or HMGB3 overexpression reversed the function of BCYRN1 knockdown in inhibiting DDP-resistance of CC cells. Eventually, BCYRN1 knockdown reduced the DDP-resistance of CC cells in vivo. Limitations: There are still some deficiencies in the research; for example, whether there are other miRs working as the downstream genes of BCYRN1 in the competing endogenous RNA interaction is not fully clarified, nor the other downstream mechanisms of miR-330-5p. Besides, the experimental findings and their application into practice need extensive validation. Conclusions: BCYRN1 knockdown could disrupt the DDP-resistance of CC cells through upregulating miR-330-5p to suppress HMGB3 mRNA level.
Association of Common and Rare Genetic Variation in the 3‐Hydroxy‐3‐Methylglutaryl Coenzyme A Reductase Gene and Cataract Risk
Authors: Ghouse Jonas , Ahlberg Gustav , Skov Anne Guldhammer , Bundgaard Henning , Olesen Morten S.
Published: June 2022

Background

Results from animal models and observational studies have raised concerns regarding the potential cataractogenic effects of statin treatment. We investigated whether common and rare genetic variants in
HMGCR
are associated with cataract risk, to gauge the likely long‐term effects of statin treatment on lenticular opacities.

Methods and Results

We used genotyping data and exome sequencing data of unrelated European individuals in the UK Biobank to test the association between genetically proxied inhibition of
HMGCR
and cataract risk. First, we constructed an
HMGCR
genetic score consisting of 5 common variants weighted by their association with low‐density lipoprotein cholesterol. Second, we analyzed exome sequencing data to identify carriers of predicted loss‐of‐function mutations in
HMGCR
. Common and rare variants in aggregate were then tested for association with cataract and cataract surgery. In an analysis of >402 000 individuals, a 38.7 mg/dL (1 mmol/L) reduction in low‐density lipoprotein C by the
HMGCR
genetic score was associated with higher risk for cataract (odds ratio, 1.14 [95% CI, 1.00–1.39],
P
=0.045) and cataract surgery (odds ratio, 1.25 [95% CI, 1.06–1.48],
P
=0.009). Among 169 172 individuals with
HMGCR
sequencing data, we identified 32 participants (0.02%), who carried a rare
HMGCR
predicted loss‐of‐function variant. Compared with noncarriers, heterozygous carriers of
HMGCR
predicted loss‐of‐function had a higher risk of developing cataract (odds ratio, 4.54 [95% CI, 1.96–10.53],
P
=0.001) and cataract surgery (odds ratio, 5.27 [95% CI, 2.27–12.25]
, P
=5.37×10
−4
). In exploratory analyses, we found no significant association between genetically proxied inhibition of
PCSK9, NPC1L1
, or circulating low‐density lipoprotein cholesterol levels (
P
>0.05 for all) and cataract risk.

Conclusions

We found that genetically proxied inhibition of the
HMGCR
gene mimicking long‐term statin treatment associated with higher risk of cataract. Clinical trials with longer follow‐up are needed to confirm these findings.
Neural Reinstatement Tracks Spread of Attention between Object Features in Working Memory
Authors: Printzlau Frida A. B. , Myers Nicholas E. , Manohar Sanjay G. , Stokes Mark G.
Published: June 2022

Attention can be allocated in working memory (WM) to select and privilege relevant content. It is unclear whether attention selects individual features or whole objects in WM. Here, we used behavioral measures, eye-tracking, and EEG to test the hypothesis that attention spreads between an object's features in WM. Twenty-six participants completed a WM task that asked them to recall the angle of one of two oriented, colored bars after a delay while EEG and eye-tracking data were collected. During the delay, an orthogonal “incidental task” cued the color of one item for a match/mismatch judgment. On congruent trials (50%), the cued item was probed for subsequent orientation recall; on incongruent trials (50%), the other memory item was probed. As predicted, selecting the color of an object in WM brought other features of the cued object into an attended state as revealed by EEG decoding, oscillatory α-power, gaze bias, and improved orientation recall performance. Together, the results show that attentional selection spreads between an object's features in WM, consistent with object-based attentional selection. Analyses of neural processing at recall revealed that the selected object was automatically compared with the probe, whether it was the target for recall or not. This provides a potential mechanism for the observed benefits of nonpredictive cueing in WM, where a selected item is prioritized for subsequent decision-making.
A Gamma Parameterization for Precipitating Particle Size Distributions Containing Snowflake Aggregates Drawn from Five Field Experiments
Authors: Duffy George , Posselt Derek J.
Published: June 2022

In this study, we investigate the tendencies of gamma parameters for particle size distributions (PSDs) containing snowflake aggregates in orographic, convective, and stratiform clouds, above snowstorms and above rainstorms, in temperatures ranging from 0° to −45°C. We find a strong relationship between μ and Λ but no dependence on temperature. Higher μ are observed during the experiments sampling winter snowstorms, and lower μ are observed during experiments sampling frozen clouds above convective and orographic storms. We find that a gamma function with a μ of −1.25 provides the best average representation of PSD shape and the most accurate representation of PSD moments related to mass and reflectivity. We also provide a lookup table of maximum particle size boundaries that can be used to parameterize incomplete gamma functions with negative μ values.

Significance Statement

In many weather models and satellite retrieval algorithms, frozen clouds and precipitation are governed by the same assumptions even though they develop through different growth processes. This paper provides recommendations for snowflake aggregate size distributions that reflect natural conditions, and these recommended assumptions are demonstrated to improve estimates of mass and radar reflectivity. We studied a variety of storms, such as thunderstorms, snow storms, and winter rainstorms, and we found that our model for snowflake aggregates was nearly identical in all observed conditions.
The Impact of Primary Care Physicians on the Surgical Presentation and Outcomes of Colorectal Cancer in Vulnerable Populations
Authors: Balan Naveen , Braschi Caitlyn , Kirkland Patrick , Kaji Amy H. , Chen Kathryn T.
Published: June 2022

Background

Multiple socioeconomic and clinical factors have been implicated in the health disparities that exist amongst vulnerable populations with colorectal cancer. Efforts have been directed toward addressing these factors to improve outcomes. We evaluate the impact of primary care physicians (PCP) on the surgical presentation and outcomes of colorectal cancer at a safety-net hospital.

Methods

A retrospective chart review of 331 patients diagnosed with colorectal adenocarcinoma between 2014 and 2020 at a single-institution urban county medical center.

Results

The cohort was predominantly male (59%) and Hispanic (52.1%). Thirty-two percent of patients had a PCP at time of diagnosis. Patients with PCPs compared to those without PCPs had significantly lower rates of acute presentation (perforation or obstruction) (17.0 vs 38.1%, P < .001), higher rates of surgical resection (83.0 vs 70.7%, P = .016), and were less likely to have metastatic disease at presentation (20.4 vs 33.5%, P = .02). Overall, having a PCP also improved probability of survival (HR 1.36, P < .04).

Conclusion

Having a PCP at the time of colorectal cancer diagnosis is associated with improved outcomes in a safety-net population, with significant differences in surgical presentation and resection.
Off-Label Use of Ciprofloxacin/Dexamethasone Drops in the Pediatric Upper Airway: Case Presentation and Review of Adverse Effects
Authors: Ben-Dov Tom , Yang Jackie , April Max M.
Published: June 2022

Objective:

This report describes a new observation of hyperglycemia in a child with Type 1 diabetes after off-label use of otic ciprofloxacin/dexamethasone drops in the nasal passage and reviews previous reports of adverse endocrine effects from intranasal corticosteroids in pediatric patients.

Methods:

We describe the clinical case and conducted a literature review of MEDLINE (PubMed) and EMBASE.

Results:

A 9-month-old female with a history of Type 1 diabetes who underwent unilateral choanal atresia repair was started on 1 week of ciprofloxacin 0.3%/dexamethasone 0.1% otic drops twice a day for choanal obstruction with granulation tissue. While the patient’s airway patency improved, average daily blood glucose increases by 40 to 50 points were noted on the patient’s continuous glucose monitor. The hyperglycemia resolved within 2 days after switching to mometasone furoate 0.05% spray. We also review 21 pediatric otolaryngology cases of iatrogenic Cushing’s syndrome associated with on- and off-label use of topical steroid suspensions in the airway. Patients ranged from 3 months to 16 years in age and used doses of 50 μg/day to 2 mg/day.

Conclusion:

This is the first reported pediatric case of increased blood glucose levels associated with intranasal steroid suspensions, to the best of our knowledge. Counseling families on precise dose administration and potential endocrine disturbances is critical when prescribing these medications for off-label use in infants and small children, particularly among patients with underlying endocrine disorders such as diabetes.
The 2020 Vertical Merger Guidelines: Some Suggestions for Revision
Authors: Alderman Brianna L. , Blair Roger D.
Published: June 2022

In 2020, the Department of Justice and the Federal Trade Commission (FTC) published their Vertical Merger Guidelines (VM Guidelines). The Guidelines were intended to reveal the principal analytical techniques, practices, and enforcement policies employed by the two Agencies, but they were short-lived at the FTC. In 2021, the VM Guidelines were rescinded by the FTC. Even before they were rescinded, their general language and some of the illustrative examples were not fully specified, which made them misleading. As work begins on reconstructing the VM Guidelines, we illustrate some of the weaknesses of the 2020 version and offer some suggestions for their revision. In this article, we will demonstrate why the incomplete specification can lead to some analytical difficulties. In addition, we will offer some clarifications and corrections. Our goal is to suggest refinements to the 2020 VM Guidelines so that they will be more useful in developing future guidelines for antitrust enforcement policy.
Vertical Merger Guidelines and the Rule of Law
Authors: Werden Gregory J.
Published: June 2022

Mid-1960s Supreme Court decisions undermined the rule of law by giving the government unbridled discretion in enforcing Section 7 of the Clayton Act. Since 1968, the government has promoted the rule of law through guidelines limiting discretion. The Vertical Merger Guidelines, however, place no meaningful limits on agency discretion. They articulate theories under which mergers can be harmful but neither specific nor general standards. They set out no principles for determining when a merger harms competition, rather than a competitor, and no criteria for determining when harm to competition is likely, rather than merely possible. Nor do they convey the agencies’ general attitude toward vertical mergers.
How Adverse Childhood Experiences and Gender Shape Perceptions of Synthetic Drug Use and Desistance in Yunnan, China
Authors: Monk-Turner Elizabeth , Fu Hongyun , Li Jianghong , Yang Xiushi
Published: June 2022

Past research on illicit drug use and desistance has primarily been conducted in western countries, relied on quantitative data, and given little attention to potential gender differentiation. Utilizing qualitative data, we explore gender differences in how illicit drug users perceive the onset of use, whether or not they connect this to adverse childhood experiences (ACEs), and why they quit. The work is based on a sample of 24 informants from Yunnan. Women link onset of use to adverse childhood experiences (ACE) and report quitting primarily for their children. Men found support from their families helpful in ending illicit drug use. This adds qualitative support to theoretical work done by Wu and colleagues, Zhang, and Zhang and Demant who argue that familial attachment is critical in desistance. Utilizing a gendered lens, we gain and nuanced understanding of illicit drug use and links to ACEs which may better inform intervention programs.
Rational Inattention as an Empirical Framework for Discrete Choice and Consumer-Welfare Evaluation
Authors: Joo Joonhwi
Published: June 2022

The conventional discrete-choice model of demand assumes that consumers are fully informed about every available product alternative. This assumption is at odds with the large body of literature studying incomplete information and the role of the consumer's “evoked set” or “consideration set.” The author develops a novel empirical discrete-choice demand model derived from an underlying theory of consumers' rational inattention. The model distinguishes between factors that shift demand through the utility function, such as prices and product attributes, and factors that shift demand through the consumer's information “evaluation costs.” The author conducts an empirical case study of the laundry detergent category. Using a set of exclusion restrictions based on retail promotional instruments, specification tests select the rational inattention model over the conventional full-information discrete-choice model. Exploiting the launch of Tide Pods midway through the sample, the author demonstrates the role of evaluation costs for the measured value creation from a new product. A conventional discrete-choice model always assigns positive incremental consumer value from new products. However, the rational inattention model developed herein finds a decrease in overall consumer welfare from the new Tide Pods’ entry, with the increased friction in information associated with the larger choice set offsetting the potential gains from higher match value.
Special Section: Relationships Between Executive Function and Sports / Exercise
Authors: Ball J.D.
Published: June 2022

This short article is a commentary on this special section of Perceptual and Motor Skills entitled Relationships between Executive Function and Sports/Exercise. Given the vast executive function research in sports already published, this moment is opportune for highlighting (a) progress to date, (b) research limitations yet to address, and (c) inspirational new findings. The articles that follow illustrate these themes.
The centralization and rapid deployment of police agency information technologies: An appraisal of real-time crime centers in the U.S.
Authors: Przeszlowski Kimberly , Guerette Rob T , Lee-Silcox Joelle , Rodriguez Jose , Ramirez Jaime , Gutierrez Alejandro
Published: June 2022

The newfound ability to deliver information to police in rapid timeframes has resulted in Real-Time Crime Centers (RTCCs) across the United States. Despite their emergence, little is known collectively about them. This study appraised the nature of RTCCs through a national survey of 44 police agencies. Findings revealed that (1) RTCCs have recently begun to diffuse rapidly but are still in an early innovation/adoption phase, (2) there is no single model of their use, (3) most procure a wide variety of technologies and information sources, and (4) most allow for information to be shared with partners in real-time.
An island of sanity during COVID-19 pandemic: Does pet attachment support buffer employees’ stress due to job insecurity?
Authors: Wan Min (Maggie) , Kelemen Thomas K. , Zhang Yejun , Matthews Samuel H.
Published: June 2022

Drawing on the transactional theory of stress, the current study investigates whether employee job insecurity triggers employee behavioral strain reactions (i.e., alcohol use, marijuana use, and cigarette use) and psychological strain reactions (i.e., emotional exhaustion and depression) through stress during the COVID-19 pandemic. In addition, we integrate social support theory and expect the moderating role of pet attachment support in the above relationships. By collecting two-wave data from 187 employees with pets in the United States, we found that during the COVID-19 pandemic, stress mediated the relationships between job insecurity and predicted behavioral and psychological reactions. Moreover, pet attachment support buffered the relationships between stress and these behavioral and psychological strain reactions (all except cigarette use). Pet attachment support also alleviated the conditional indirect effects job insecurity had on the two types of strain reactions via stress. We discuss theoretical and practical implications of this study.
The Association Between Perceptions of Neighborhood Conditions and the Employment of Emerging Adults Formerly Involved in the Juvenile Justice System
Authors: Lee Lewis H. , Kim Minseop , Carlson Catherine , Ellis Taylor , Johnson Karen , Pretz Angela
Published: June 2022

Although prior research finds that poor neighborhood conditions are negatively associated with employment, little study has focused on emerging adults who formerly had contact with the juvenile justice system and are frequently engaged in informal job markets. Using a hybrid model and three waves from panel data with formerly juvenile justice-involved emerging adults (18–24 at T1, 20–25 at T2, 20–26 at T3) collected in Philadelphia and Phoenix ( N = 947), we find an inter-individual increase in the degree of disorder within the neighborhood decreases weeks worked for community jobs (between-effect), whereas an intra-individual increase in neighborhood condition scores increases weeks worked for under-the-table jobs among emerging adults (within-effect). Some time-variant and invariant sociodemographic factors, including perceived opportunity for work, mental health, substance use, gang membership, race, and education, are significantly related to employment. Our findings reiterate justice-involved young people may have difficulty sustaining formal employment partially due to neighborhood conditions.
Associations Between COVID-19 Vaccine Hesitancy and Socio-Spatial Factors in NYC Transit Workers 50 Years and Older
Authors: Meltzer Gabriella Y. , Harris Jordan , Hefner Michelle , Lanternier Paula , Gershon Robyn R.M. , Vlahov David , Merdjanoff Alexis A.
Published: June 2022

This analysis investigates how age, race/ethnicity, and geographic location contributed to vaccine hesitancy in a sample of 645 New York City (NYC) Transport Workers Union (TWU), Local 100 members surveyed in August 2020. Union members ages 50+ were 46% less likely to be vaccine hesitant than their younger counterparts (OR 0.64; 95% CI 0.42, 0.97). Non-Whites (OR 3.95; 95% 2.44, 6.39) and those who did not report their race (OR 3.10; 95% CI 1.87, 5.12) were significantly more likely to be vaccine hesitant than Whites. Those who were not concerned about contracting COVID-19 in the community had 1.83 greater odds (95% CI 1.12, 2.98) of being vaccine hesitant than those who were concerned. Older respondents tended to reside in Queens while vaccine hesitant and non-White respondents were clustered in Brooklyn. General trends observed in COVID-19 vaccine hesitancy persist in a population of high risk, non-healthcare essential workers.
Technical Violations and Their Effects on Pretrial/Bond Supervision Outcomes
Authors: Zettler Haley R. , Martin Kelli D.
Published: June 2022

The use of pretrial and bond supervision commonly referred to as supervised release has increased over the last several decades due to burgeoning jail and prison populations. Much research has been conducted on these release mechanisms but has yet to examine the effects of types of technical violations on pretrial failure. The current study examined the effects of technical violations committed by individuals under a felony “bond” supervision program, which included both pretrial releasees and individuals being supervised on bond awaiting a probation revocation hearing, in a large metropolitan area. The results demonstrate while technical violations are associated with pretrial failure, the effects vary by violation type. Furthermore, the findings illustrate differences in risk factors for technical violations while on pretrial/bond supervision. Relevant policy implications of the research are provided.
Ractopamine residues in meat might reduce the risk of type 2 diabetes
Authors: Fan Frank S
Published: June 2022

Background: The overall prevalence of diabetes in the world has risen substantially in the past several decades, so have complications and mortalities associated with it. Aim: Prevention strategies for diabetes thus become an urgent public health need for reducing the burden of diabetes. Methods: Ractopamine, a β1/2-adrenergic receptor agonist, has been approved for use in finishing swine, cattle, and turkey in countries where meat exporting brings tremendous economic benefits. This leanness enhancer is recently found to be a full agonist at trace amine-associated receptor 1 also. A thorough literature review was performed to assess possible effects of ractopamine on glucose metabolism. Results: Activating β-adrenoceptor could lead to glucose-lowering effects independent of insulin while activation on trace amine-associated receptor 1 induces an incretin-like signaling on insulin-secreting pancreatic β-cells. Conclusion: Accordingly, it is hypothesized that long-term consuming meat containing ractopamine might lower the risk of type 2 diabetes.
The relationship between height and fruit/vegetable intakes in adults: A nationwide cross-sectional study
Authors: Rosário Rafaela , Agostinis-Sobrinho Cesar , Padrão Patrícia , Lopes Oscar , Moreira Pedro
Published: June 2022

Background: Worldwide, fruit and vegetable intake is below recommendations. There is increasing evidence to suggest an association between height and diet. Aim: to analyse the associations of fruit and vegetable intake with attained height in Portuguese adults. Methods: A representative sample of 17 480 Portuguese adults (56.7% women) participated in this cross-sectional study. The survey comprised sociodemographic characteristics and self-reported height and weight. We performed regression models to assess the associations between height and fruit and vegetable consumption. Results: Compared with no intakes, those men with higher fruit and vegetables intake had 0.54 cm (95% CI 0.04; 1.04) greater height. Also, women with higher intakes of vegetables, fruit and vegetables combined were directly associated with a greater height of 0.29 cm (95% CI 0.03; 0.56 in vegetables) and 0.51 cm (95% CI 0.09; 0.93 in fruit and vegetables combined). Conclusion: Greater consumption of fruit and vegetables was directly associated with higher height in adults. From a health promotion perspective, intervention programmes aiming at improving fruit and vegetable intake should be highlighted so that full height potential is achieved.
The Better By Moving study: A multifaceted intervention to improve physical activity in adults during hospital stay
Authors: Geelen Sven JG , Giele Boukje M , Veenhof Cindy , Nollet Frans , Engelbert Raoul HH , van der Schaaf Marike
Published: June 2022

Objective

‘Better By Moving’ is a multifaceted intervention developed and implemented in collaboration with patients and healthcare professionals to improve physical activity in hospitalized adults. This study aimed to understand if, how and why ‘Better By Moving’ resulted in higher levels of physical activity by evaluating both outcomes and implementation process.

Design

Mixed-methods study informed by the Medical Research Council guidance.

Setting

Tertiary hospital.

Participants

Adult patients admitted to surgery, haematology, infectious diseases and cardiology wards, and healthcare professionals.

Measures

Physical activity was evaluated before and after implementation using the Physical Activity Monitor AM400 on one random day during hospital stay between 8 am and 8 pm. Furthermore, the time spent lying on bed, length of stay and discharge destination was investigated. The implementation process was evaluated using an audit trail, surveys and interviews.

Results

There was no significant difference observed in physical activity (median [IQR] 23 [12–51] vs 27 [17–55] minutes, P = 0.107) and secondary outcomes before-after implementation. The intervention components’ reach was moderate and adoption was low among patients and healthcare professionals. Patients indicated they perceived more encouragement from the environment and performed exercises more frequently, and healthcare professionals signalled increased awareness and confidence among colleagues. Support (priority, resources and involvement) was perceived a key contextual factor influencing the implementation and outcomes.

Conclusion

Although implementing ‘Better By Moving’ did not result in significant improvements in outcomes at our centre, the process evaluation yielded important insights that may improve the effectiveness of implementing multifaceted interventions aiming to improve physical activity during hospital stay.
Gut virome dysbiosis following focal cerebral ischemia in mice
Authors: Chelluboina Bharath , Kieft Kristopher , Breister Adam , Anantharaman Karthik , Vemuganti Raghu
Published: June 2022

Stroke leads to gut bacterial dysbiosis that impacts the post-stroke outcome. The gut microbiome also contains a high abundance of viruses which might play a crucial role in disease progression and recovery by modulating the metabolism of both host and host’s gut bacteria. We presently analyzed the virome composition (viruses and phages) by shotgun metagenomics in the fecal samples obtained at 1 day of reperfusion following transient focal ischemia in adult mice. Viral genomes, viral auxiliary metabolic genes, and viral protein networks were compared between stroke and sham conditions (stroke vs sham, exclusive to sham and exclusive to stroke). Following focal ischemia, abundances of 2 viral taxa decreased, and 5 viral taxa increased compared with the sham. Furthermore, the abundance of Clostridia-like phages and Erysipelatoclostridiaceae-like phages were altered in the stroke compared with the sham cohorts. This is the first report to show that the gut virome responds acutely to stroke.
Analysis of medical appointments for patients with overweight and obesity in a public hospital of Lima, Peru: a cross-sectional study of audio-recorded consultations
Authors: Torres-Nolasco Maria Felix , Ruiz Eloy F , Tarazona-Meza Carla , Lazo-Porras María , Málaga Germán
Published: June 2022

Objective

To describe the content of overweight and obesity counseling performed in a public Peruvian hospital.

Methods

We audio-recorded 40 visits of patients with overweight or obesity from the internal medicine, cardiology, endocrinology, and family medicine services at Cayetano Heredia Hospital. Fragments of the recordings in which counseling was performed were transcribed and codified. We established a checklist to score each counseling session and performed descriptive analyses.

Results

Complete counseling (including weight, nutrition, and physical activity) was performed in 32.5% of consultations. The average time spent in counseling was 1.72 minutes. Counseling on weight loss was performed in 65% of consultations, nutrition in 65%, and physical activity in 35%. On average, 8 of 26 checklist items were fulfilled per appointment. Weight loss goals were established in 15% of visits. The most frequent diet recommendations were eating more fruits and vegetables (32.5%) and eating fewer carbohydrates (30.0%). Suggested physical activities were walking (10.0%), running (7.5%), and playing any sport (7.5%).

Conclusions

Complete counseling was only addressed in one-third of the appointments, and most counseling was superficial without considering therapeutic goals. This suggests the need to include lifestyle counseling in consultations, regardless of the medical specialty or patient’s background condition.
On the Analytical Probabilistic Modeling of Flow Transmission Across Nodes in Transportation Networks
Authors: Lu Jing , Osorio Carolina
Published: June 2022

This paper focuses on the analytical probabilistic modeling of vehicular traffic. It formulates a stochastic node model. It then formulates a network model by coupling the node model with the link model of Lu and Osorio (2018), which is a stochastic formulation of the traffic-theoretic link transmission model. The proposed network model is scalable and computationally efficient, making it suitable for urban network optimization. For a network with [Formula: see text] links, each with a space capacity of one, the model has a complexity of [Formula: see text]. The network model yields the marginal distribution of link states. The model is validated versus a simulation-based network implementation of the stochastic link transmission model. The validation experiments consider a set of small networks with intricate traffic dynamics. For all scenarios, the proposed model accurately captures the traffic dynamics. The network model is used to address a signal control problem. Compared with the probabilistic link model of Lu and Osorio (2018) with an exogenous node model and a benchmark deterministic network loading model, the proposed network model derives signal plans with better performance. The case study highlights the added value of using between-link (i.e., across-node) interaction information for traffic management and accounting for stochasticity in the network.