bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Numerical Method for Diffusion Equation with Time-Fractional Caputo–Fabrizio Derivative
Authors: Wang Hanxiao , Zhang Xindong , Luo Ziyang , Liu Juan
Published: May 2023

In this paper, we propose a high-precision discrete scheme for the time-fractional diffusion equation (TFDE) with Caputo-Fabrizio type. First, a special discrete scheme of C-F derivative is used in time direction and a compact difference operator is used in space direction. Second, we discuss the convergence of the proposed method in discrete

L

1

-norm and

L

2

-norm. The convergence order of our discrete scheme is

O

τ

2

+

h

4

, where

τ

and

h

are the temporal and spatial step sizes, respectively. The aim of this paper is to show that fractional operator without singular term is very useful for improving the accuracy of discrete scheme.
The Impact of Anaemia on Outcomes, Admissions, and Costs in Patients with Chronic Kidney Disease in Two Public Nephrology Practices in Queensland: A CKD.QLD Registry Study
Authors: Zhang Jianzhen , Diwan Vishal , Wang Zaimin , Healy Helen G. , Venuthurupalli Sree Krishna , Abeysekera Rajitha , Hoy Wendy E.
Published: May 2023

Aim. Anaemia among patients with chronic kidney disease (CKD) leads to poor overall outcomes. This study explores anaemia and its impact on nondialysis CKD (NDD-CKD) patients. Methods. 2,303 adults with CKD from two CKD.QLD Registry sites were characterised at consent and followed until start of kidney replacement therapy (KRT), death, or censor date. Mean follow-up was 3.9 (SD 2.1) years. Analysis explored the impact of anaemia on death, KRT start, cardiovascular events (CVE), admissions, and costs in these NDD-CKD patients. Results. At consent, 45.6% patients were anaemic. Males were more often anaemic (53.6%) than females, and anaemia was significantly more common over the age of 65 years. The prevalence of anaemia was highest among CKD patients with diabetic nephropathy (27.4%) and renovascular disease (29.2%) and lowest in patients with genetic renal disease (3.3%). Patients with admissions for gastrointestinal bleeding had more severe anaemia, but accounted for only the minority of cases overall. Administration of ESAs, iron infusions, and blood transfusions were all correlated with more severe degrees of anaemia. The number of hospital admissions, length of stay, and hospital costs were all strikingly higher with more severe degrees of anaemia. Adjusted hazard ratios (CI 95%) of patients with moderate and severe anaemia vs. no anaemia for subsequent CVE, KRT, and death without KRT were 1.7 (1.4–2.0), 2.0 (1.4–2.9), and 1.8 (1.5–2.3), respectively. Conclusion. Anaemia is associated with higher rates of CVE, progression to KRT and death in NDD- CKD patients, and with greater hospital utilisation and costs. Preventing and treating anaemia should improve clinical and economic outcomes.
A Novel, Hand‐Held, and Low‐Level Light Therapy Device for the Treatment of Acne Vulgaris: A Single‐Arm, Prospective Clinical Study
Authors: Chung Euy Hyun , Son Ji Won , Eun Yun Su , Yang Na Gyeong , Kim Jae Yoon , Lee Sulhee , Heo Nam Hun , Rhee Jinhui , Lee Sung Yul , Hwang Yongsung , Kim Jung Eun
Published: May 2023

There is an increasing demand for low‐level light therapy devices for the treatment of dermatologic conditions, such as acne, hair loss, undesirable body hair, and skin aging. This study evaluated the safety and effectiveness of a novel hand‐held low‐level light therapy device with a 680 nm red laser diode and a 450 nm blue light‐emitting diode for the treatment of mild‐to‐moderate acne. A prospective clinical study was conducted on 57 patients with mild‐to‐moderate acne and Fitzpatrick skin types II–IV. Treatments were self‐administered by the patients at home daily for 4 weeks. Conventional treatment was restricted during the study period. The number of inflammatory and noninflammatory lesion counts, Investigator’s Global Assessment grade, patients’ self‐assessment, and adverse events were measured every two weeks, and follow‐ups were performed until four weeks after the final treatment. Moreover, we evaluated the bactericidal effect of low‐level light therapy on Cutibacterium acnes, a causative agent of acne vulgaris, in vitro. The mean number of inflammatory acne lesions decreased statistically at weeks 4 ( ∗∗∗p < 0.001) and 8 ( ∗∗∗p < 0.001). The proportion of Investigator’s Global Assessment grade 3, indicating moderate acne severity, decreased significantly at the final visit. No severe adverse reactions were reported. Furthermore, there was a significant reduction in the viability of Cutibacterium acnes following low‐level light therapy exposure in vitro. The results of this study demonstrate that this novel, hand‐held, and low‐level light therapy device are safe and effective for the treatment of inflammatory acne, with good adherence.
Fatigue Damage Identification by a Global-Local Integrated Procedure for Truss-Like Steel Bridges
Authors: Crognale Marianna , Potenza Francesco , Gattulli Vincenzo
Published: May 2023

Civil steel structures and infrastructures, such as truss railway bridges, are often subject to potential damage, mainly due to fatigue phenomena and corrosion. Therefore, damage detection algorithms should be designed and appropriately implemented to increase their structural health. Today, the vast amount of information provided by data processing techniques and measurements coming from a monitoring system constitutes a possible tool for damage identification in terms of both detection and description. For this reason, the research activity aims to develop a methodology for a preliminary description of the damage in steel railway bridges induced by fatigue phenomena. The proposed approach is developed through an integration of global and local procedures. At the global scale, vibration-based procedures will be applied to improve a forecast numerical model and, subsequently, to identify the zones most involved in fatigue problems. At the local scale, careful and refined local identification will be pursued via image processing techniques whose evidence will be analyzed and described through nonlinear numerical models. A case study of a historical railway bridge in Spain will illustrate the methodology’s performance, potentiality, and critical issue.
Reduced Gravity and Magnetohydrodynamic Effects on Transient Mixed Convection Flow Past a Magnetized Heated Cone Embedded in Porous Medium
Authors: Nabwey Hossam A. , Ullah Zia , Ilyas Asifa , Ashraf Muhammad , Rashad Ahmed M. , Alshber Sumayyah I. , Abu Hawsah Miad
Published: May 2023

The effects of reduced gravity on the periodic behavior of convective heat transfer characteristics of fluid flow along the magnetized heated cone embedded in porous medium is studied in the current contribution. The mathematical form of the nonlinear partial differential equations subject to the boundary conditions for the proposed unsteady model is presented. By employing appropriate dimensionless quantities, the mathematical equations are transformed into dimensionless form to get the numerical solutions of the proposed model. The dimensionless form is further condensed to a form that is more straightforward for smooth numerical computations. Later, large simulations are run using the implicit finite difference method for appropriate range of parameters values included in the flow model. The effect of reduced gravity parameter

R

g

, the Richardson parameter or mixed convection parameter

λ

, the Prandtl number Pr, and the porosity parameter

Ω

, on chief physical quantities, that is, velocity profile, temperature distribution, magnetic intensity, transient skin friction, transient rate of heat transfer, and transient current density are simulated and highlighted graphically. Additionally, via careful examination and intentional discussion of physical reasoning, the physical impacts of various factors on the material qualities are examined. Applications that motivate the present work is the reduced gravity effects due to which the other nongravity forces such as thermal volume expansion, density difference, and magnetic field can induce the fluid motion.
Incidence and Mortality Rates for Childhood Acute Lymphoblastic Leukemia in Puerto Rican Hispanics, 2012–2016
Authors: Montes-Rodríguez Ingrid M. , Soto-Salgado Marievelisse , Torres-Cintrón Carlos R. , Tomassini-Fernandini Jonnalie C. , Suárez Erick , Clavell Luis A. , Cadilla Carmen L.
Published: May 2023

Background:

Acute lymphoblastic leukemia (ALL) accounts for 80% of all leukemias diagnosed in children. Although ALL age patterns are consistent across racial/ethnic groups, their incidence and mortality rates are highly variable. We assessed the age-standardized ALL incidence and mortality rates of Puerto Rican Hispanic (PRH) children and compared them with those of US mainland Hispanics (USH), non-Hispanic Whites (NHW), non-Hispanic Blacks (NHB), and Non-Hispanic Asian or Pacific Islanders (NHAPI).

Methods:

Differences between racial/ethnic groups were assessed by estimating the standardized rate ratio (SRR) for 2010 to 2014. Secondary data analyses of the Puerto Rico Central Cancer Registry and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) databases were performed for the 2001 to 2016 period.

Results:

PRH children had 31% lower incidence rates than USH, but 86% higher incidence rates than NHB. In addition, the incidence trends of ALL increased significantly from 2001 to 2016 among PRH and USH, with 5% and 0.9% per year, respectively. Moreover, PRH have a lower 5-year overall survival (81.7%) when compared with other racial/ethnic groups.

Conclusions:

PRH children were found to have disparities in ALL incidence and mortality rates compared with other racial/ethnic groups in the US. Additional research is warranted to identify the genetic and environmental risk factors that may be associated with the disparities observed.

Impact:

This is the first study reporting the incidence and mortality rates of childhood ALL for PRH and making comparisons with other racial/ethnic groups in the US.

See related commentary by Mejía-Aranguré and Núñez-Enríquez, p. 999
Data from Loss of LGR5 through Therapy-induced Downregulation or Gene Ablation Is Associated with Resistance and Enhanced MET-STAT3 Signaling in Colorectal Cancer Cells
Authors: Posey Tressie A. , Jacob Joan , Parkhurst Ashlyn , Subramanian Shraddha , Francisco Liezl E. , Liang Zhengdong , Carmon Kendra S.
Published: May 2023

Abstract
Leucine-rich repeat-containing, G protein-coupled receptor 5 (LGR5) is highly expressed in colorectal cancer and cancer stem cells (CSCs) that play important roles in tumor initiation, progression, and metastasis. Loss of LGR5 has been shown to enhance therapy resistance. However, the molecular mechanisms that mediate this resistance remain elusive. In this study, we demonstrate conversion of LGR5+ colorectal cancer cells to an LGR5− state in response to chemotherapy, LGR5− targeted antibody–drug conjugates (ADCs), or LGR5 gene ablation led to activation of STAT3. Further investigation revealed increased STAT3 activation occurred as a result of increased mesenchymal epithelial transition (MET) factor receptor activity. LGR5 overexpression decreased MET-STAT3 activity and sensitized colorectal cancer cells to therapy. STAT3 inhibition suppressed MET phosphorylation, while constitutively active STAT3 reduced LGR5 levels and increased MET activity, suggesting a potential feedback mechanism. Combination treatment of MET-STAT3 inhibitors with irinotecan or antibody–drug conjugates (ADCs) substantiated synergistic effects in colorectal cancer cells and tumor organoids. In colorectal cancer xenografts, STAT3 inhibition combined with irinotecan enhanced tumor growth suppression and prolonged survival. These findings suggest a mechanism by which drug-resistant LGR5− colorectal cancer cells acquire a survival advantage through activation of MET-STAT3 and provide rationale for new treatment strategies to target colorectal cancer.
Data from Novel Arginase Inhibitor, AZD0011, Demonstrates Immune Cell Stimulation and Antitumor Efficacy with Diverse Combination Partners
Authors: Doshi Aatman S. , Cantin Susan , Hernandez Marylens , Srinivasan Srimathi , Tentarelli Sharon , Griffin Matthew , Wang Yanjun , Pop-Damkov Petar , Prickett Laura B. , Kankkonen Cecilia , Shen Minhui , Martin Maryann San , Wu Song , Castaldi M. Paola , Ghadially Hormas , Varnes Jeffrey , Gales Sonya , Henry David , Hoover Clare , Mele Deanna A. , Simpson Iain , Gangl Eric T. , Mlynarski Scott N. , Finlay M. Raymond V. , Drew Lisa , Fawell Stephen E. , Shao Wenlin , Schuller Alwin G.
Published: May 2023

Abstract
Antitumor immunity can be hampered by immunosuppressive mechanisms in the tumor microenvironment, including recruitment of arginase (ARG) expressing myeloid cells that deplete l-arginine essential for optimal T-cell and natural killer cell function. Hence, ARG inhibition can reverse immunosuppression enhancing antitumor immunity. We describe AZD0011, a novel peptidic boronic acid prodrug to deliver an orally available, highly potent, ARG inhibitor payload (AZD0011-PL). We demonstrate that AZD0011-PL is unable to permeate cells, suggesting that this compound will only inhibit extracellular ARG. In vivo, AZD0011 monotherapy leads to arginine increases, immune cell activation, and tumor growth inhibition in various syngeneic models. Antitumor responses increase when AZD0011 is combined with anti–PD-L1 treatment, correlating with increases in multiple tumor immune cell populations. We demonstrate a novel triple combination of AZD0011, anti–PD-L1, and anti-NKG2A, and combination benefits with type I IFN inducers, including polyI:C and radiotherapy. Our preclinical data demonstrate AZD0011’s ability to reverse tumor immunosuppression and enhance immune stimulation and antitumor responses with diverse combination partners providing potential strategies to increase immuno-oncology therapies clinically.
Data from IMiDs augment CD3-bispecific antibody induced CD8+ cell cytotoxicity and expansion by enhancing IL-2 production
Authors: Li Ji , Slaga Dionysos , Johnston Jennifer , Junttila Teemu T.
Published: May 2023

Abstract
Although CD3-bispecific antibodies have demonstrated promising activity in the treatment of hematological cancers, insufficient T cell co-stimulation may limit long-term responses.
Immunomodulatory drugs (IMiDs), routinely used in treating multiple myeloma (MM), possess pleiotropic anti-myeloma properties and have been described to enhance T cell responses similar to co-stimulatory signaling and may therefore have synergistic effects when combined with T cell bispecifics. In this report, we demonstrate that IMiDs substantially enhance tumor cell killing induced by CD3-bispecifics and increase CD8+ T cell proliferation and expansion. We further show that the beneficial effects of IMiDs on T cell function and expansion are mediated by enhanced IL-2 production by CD4+ T cells. Our studies provide mechanistic insight into the co-stimulatory properties of IMiDs and support combination treatments with T cell agonist therapies in a broad spectrum of indications.
Data from Pharmacokinetic/Pharmacodynamic Analysis of Savolitinib Plus Osimertinib in an EGFR-Mutation Positive, MET-Amplified Non-Small Cell Lung Cancer Model
Authors: Jones Rhys D.O. , Petersson Klas , Tabatabai Areya , Bao Larry , Tomkinson Helen , Schuller Alwin G.
Published: May 2023

Abstract
Osimertinib is a third-generation, irreversible, oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), recommended as first-line treatment for patients with locally advanced/metastatic EGFR-mutation positive (EGFRm) non-small cell lung cancer (NSCLC). However, MET-amplification/overexpression is a common acquired osimertinib resistance mechanism. Savolitinib is an oral, potent, and highly selective MET-TKI; preliminary data suggest that combining osimertinib with savolitinib may overcome MET-driven resistance.
A patient-derived xenograft (PDX) mouse model with EGFRm, MET-amplified NSCLC was tested with a fixed osimertinib dose (10 mg/kg, for exposures equivalent to [≈] 80 mg), combined with doses of savolitinib (0–15 mg/kg, ≈0–600 mg once-daily), both with 1-aminobenzotriazole (to better match clinical half-life). After 20 days of oral dosing, samples were taken at various timepoints to follow the time-course of drug exposure in addition to phosphorylated MET and EGFR (pMET; pEGFR) change. Population pharmacokinetics, savolitinib concentration versus percentage inhibition from baseline in pMET, and the relationship between pMET and tumor growth inhibition (TGI) were also modeled.
As single agents, savolitinib (15 mg/kg) showed significant anti-tumor activity, reaching ~84% TGI and osimertinib (10 mg/kg) showed no significant anti-tumor activity (34% TGI, P>0.05 vs. vehicle). Upon combination, at a fixed dose of osimertinib, significant savolitinib dose-related anti-tumor activity was shown, ranging from 81% TGI (0.3 mg/kg) to 84% tumor regression (15 mg/kg). Pharmacokinetic-pharmacodynamic modeling showed that the maximum inhibition of both pEGFR and pMET increased with increasing savolitinib doses.
Savolitinib demonstrated exposure-related combination anti-tumor activity when combined with osimertinib in the EGFRm MET-amplified NSCLC PDX model.
Data from Addressing Tumor Heterogeneity by Sensitizing Resistant Cancer Cells to T cell–Secreted Cytokines
Authors: Ito Yoshinaga , Pan Deng , Zhang Wubing , Zhang Xixi , Juan Tiffany Y. , Pyrdol Jason W. , Kyrysyuk Oleksandr , Doench John G. , Liu X. Shirley , Wucherpfennig Kai W.
Published: May 2023

Abstract
Tumor heterogeneity is a major barrier to cancer therapy, including immunotherapy. Activated T cells can efficiently kill tumor cells following recognition of MHC class I (MHC-I)–bound peptides, but this selection pressure favors outgrowth of MHC-I–deficient tumor cells. We performed a genome-scale screen to discover alternative pathways for T cell–mediated killing of MHC-I–deficient tumor cells. Autophagy and TNF signaling emerged as top pathways, and inactivation of Rnf31 (TNF signaling) and Atg5 (autophagy) sensitized MHC-I–deficient tumor cells to apoptosis by T cell–derived cytokines. Mechanistic studies demonstrated that inhibition of autophagy amplified proapoptotic effects of cytokines in tumor cells. Antigens from apoptotic MHC-I–deficient tumor cells were efficiently cross-presented by dendritic cells, resulting in heightened tumor infiltration by IFNγ-and TNFα-producing T cells. Tumors with a substantial population of MHC-I–deficient cancer cells could be controlled by T cells when both pathways were targeted using genetic or pharmacologic approaches.
Significance:
Tumor heterogeneity is a major barrier to immunotherapy. We show that MHC-I–deficient tumor cells are forced into apoptosis by T cell–derived cytokines when TNF signaling and autophagy pathways are targeted. This approach enables T cell–mediated elimination of tumors with a substantial population of resistant, MHC-I–deficient tumor cells.

This article is highlighted in the In This Issue feature, p. 1027
Data from Reprogramming Cancer into Antigen-Presenting Cells as a Novel Immunotherapy
Authors: Linde Miles H. , Fan Amy C. , Köhnke Thomas , Trotman-Grant Aaron C. , Gurev Sarah F. , Phan Paul , Zhao Feifei , Haddock Naomi L. , Nuno Kevin A. , Gars Eric J. , Stafford Melissa , Marshall Payton L. , Dove Christopher G. , Linde Ian L. , Landberg Niklas , Miller Lindsay P. , Majzner Robbie G. , Zhang Tian Yi , Majeti Ravindra
Published: May 2023

Abstract
Therapeutic cancer vaccination seeks to elicit activation of tumor-reactive T cells capable of recognizing tumor-associated antigens (TAA) and eradicating malignant cells. Here, we present a cancer vaccination approach utilizing myeloid-lineage reprogramming to directly convert cancer cells into tumor-reprogrammed antigen-presenting cells (TR-APC). Using syngeneic murine leukemia models, we demonstrate that TR-APCs acquire both myeloid phenotype and function, process and present endogenous TAAs, and potently stimulate TAA-specific CD4+ and CD8+ T cells. In vivo TR-APC induction elicits clonal expansion of cancer-specific T cells, establishes cancer-specific immune memory, and ultimately promotes leukemia eradication. We further show that both hematologic cancers and solid tumors, including sarcomas and carcinomas, are amenable to myeloid-lineage reprogramming into TR-APCs. Finally, we demonstrate the clinical applicability of this approach by generating TR-APCs from primary clinical specimens and stimulating autologous patient-derived T cells. Thus, TR-APCs represent a cancer vaccination therapeutic strategy with broad implications for clinical immuno-oncology.
Significance:
Despite recent advances, the clinical benefit provided by cancer vaccination remains limited. We present a cancer vaccination approach leveraging myeloid-lineage reprogramming of cancer cells into APCs, which subsequently activate anticancer immunity through presentation of self-derived cancer antigens. Both hematologic and solid malignancies derive significant therapeutic benefit from reprogramming-based immunotherapy.

This article is highlighted in the In This Issue feature, p. 1027
MDM2-PROTAC versus MDM2 Inhibitors: Beyond p53 Reactivation
Authors: Peuget Sylvain , Selivanova Galina
Published: May 2023

In this issue of Cancer Discovery, Adams and colleagues present the discovery of a potent PROTAC, MDM2 degrader, which activates wild-type p53 leading to cancer cell death. Importantly, in a number of in vitro and in vivo experiments, the authors show that the depletion of MDM2 by PROTAC kills p53-mutant or p53-null cancer cells.

See related article by Adams et al., p. 1210 (5).
Breast Cancer Stem Cell–Derived Tumors Escape from γδ T-cell Immunosurveillance In Vivo by Modulating γδ T-cell Ligands
Authors: Raute Katrin , Strietz Juliane , Parigiani Maria Alejandra , Andrieux Geoffroy , Thomas Oliver S. , Kistner Klaus M. , Zintchenko Marina , Aichele Peter , Hofmann Maike , Zhou Houjiang , Weber Wilfried , Boerries Melanie , Swamy Mahima , Maurer Jochen , Minguet Susana
Published: May 2023

There are no targeted therapies for patients with triple-negative breast cancer (TNBC). TNBC is enriched in breast cancer stem cells (BCSC), which play a key role in metastasis, chemoresistance, relapse, and mortality. γδ T cells hold great potential in immunotherapy against cancer and might provide an approach to therapeutically target TNBC. γδ T cells are commonly observed to infiltrate solid tumors and have an extensive repertoire of tumor-sensing mechanisms, recognizing stress-induced molecules and phosphoantigens (pAgs) on transformed cells. Herein, we show that patient-derived triple-negative BCSCs are efficiently recognized and killed by ex vivo expanded γδ T cells from healthy donors. Orthotopically xenografted BCSCs, however, were refractory to γδ T-cell immunotherapy. We unraveled concerted differentiation and immune escape mechanisms: xenografted BCSCs lost stemness, expression of γδ T-cell ligands, adhesion molecules, and pAgs, thereby evading immune recognition by γδ T cells. Indeed, neither promigratory engineered γδ T cells, nor anti–PD-1 checkpoint blockade, significantly prolonged overall survival of tumor-bearing mice. BCSC immune escape was independent of the immune pressure exerted by the γδ T cells and could be pharmacologically reverted by zoledronate or IFNα treatment. These results pave the way for novel combinatorial immunotherapies for TNBC.
EGFR Inhibition by Cetuximab Modulates Hypoxia and IFN Response Genes in Head and Neck Squamous Cell Carcinoma
Authors: Chaudhary Ritu , Slebos Robbert J.C. , Noel Leenil C. , Song Feifei , Poole Maria I. , Hoening Dirk S. , Hernandez-Prera Juan C. , Conejo-Garcia Jose R. , Guevara-Patino Jose A. , Wang Xuefeng , Xie Mengyu , Tan Aik Choon , Chung Christine H.
Published: May 2023

Head and neck squamous cell carcinoma (HNSCC) has one of the most hypoxic and immunosuppressive tumor microenvironments (TME) among solid tumors. However, there is no proven therapeutic strategy to remodel the TME to be less hypoxic and proinflammatory. In this study, we classified tumors according to a Hypoxia-Immune signature, characterized the immune cells in each subgroup, and analyzed the signaling pathways to identify a potential therapeutic target that can remodel the TME. We confirmed that hypoxic tumors had significantly higher numbers of immunosuppressive cells, as evidenced by a lower ratio of CD8+ T cells to FOXP3+ regulatory T cells, compared with nonhypoxic tumors. Patients with hypoxic tumors had worse outcomes after treatment with pembrolizumab or nivolumab, anti-programmed cell death-1 inhibitors. Our expression analysis also indicated that hypoxic tumors predominantly increased the expression of the EGFR and TGFβ pathway genes. Cetuximab, an anti-EGFR inhibitor, decreased the expression of hypoxia signature genes, suggesting that it may alleviate the effects of hypoxia and remodel the TME to become more proinflammatory. Our study provides a rationale for treatment strategies combining EGFR-targeted agents and immunotherapy in the management of hypoxic HNSCC.

Significance:

While the hypoxic and immunosuppressive TME of HNSCC has been well described, comprehensive evaluation of the immune cell components and signaling pathways contributing to immunotherapy resistance has been poorly characterized. We further identified additional molecular determinants and potential therapeutic targets of the hypoxic TME to fully leverage currently available targeted therapies that can be administered with immunotherapy.
Adolescent Hypertension Is Associated With Stroke in Young Adulthood: A Nationwide Cohort of 1.9 Million Adolescents
Authors: Fishman Boris , Bardugo Aya , Zloof Yair , Bendor Cole D. , Libruder Carmit , Zucker Inbar , Lutski Miri , Ram Amit , Hershkovitz Yael , Orr Omri , Omer Ma’ayan , Furer Ariel , Goldman Adam , Yaniv Gal , Tanne David , Derazne Estela , Tzur Dorit , Afek Arnon , Grossman Ehud , Twig Gilad
Published: May 2023

Background:

Adult hypertension is a well-established risk factor for stroke in young adults (aged <55 years), and the effects are even more deleterious than at an older age. However, data are limited regarding the association between adolescent hypertension and the risk of stroke in young adulthood.

Methods:

A nationwide, retrospective cohort study of adolescents (aged 16–19 years) who were medically evaluated before compulsory military service in Israel during 1985 to 2013. For each candidate for service, hypertension was designated after constructed screening, and the diagnosis was confirmed through a comprehensive workup process. The primary outcome was ischemic and hemorrhagic stroke incidence as registered at the national stroke registry. Cox proportional-hazards models were used. We conducted sensitivity analyses by excluding people with a diabetes diagnosis at adolescence or a new diabetes diagnosis during the follow-up period, analysis of adolescents with overweight, and adolescents with baseline unimpaired health status.

Results:

The final sample included 1 900 384 adolescents (58% men; median age, 17.3 years). In total, 1474 (0.08%) incidences of stroke (1236 [84%] ischemic) were recorded, at a median age of 43 (interquartile range, 38–47) years. Of these, 18 (0.35%) occurred among the 5221 people with a history of adolescent hypertension. The latter population had a hazard ratio of 2.4 (95% CI, 1.5–3.9) for incident stroke after adjustment for body mass index and baseline sociodemographic factors. Further adjustment for diabetes status yielded a hazard ratio of 2.1 (1.3–3.5). We found similar results when the outcome was ischemic stroke with a hazard ratio of 2.0 (1.2–3.5). Sensitivity analyses for overall stroke, and ischemic stroke only, yielded consistent findings.

Conclusions:

Adolescent hypertension is associated with an increased risk of stroke, particularly ischemic stroke, in young adulthood.
Effect of an Educational Intervention for Primary Stroke Risk Reduction in Ghana and Nigeria: Pilot Randomized Controlled Trial
Authors: Sarfo Fred Stephen , Akinyemi Joshua Odunayo , Obiako Reginald , Nichols Michelle , Fakunle Adekunle Gregory , Adusei Nathaniel , Ampofo Michael , Arulogun Oyedunni , Jenkins Carolyn , Akpa Onoja M. , Aribisala Benjamin , Abdulrasaq Saheed , Akinyemi Rufus , Ovbiagele Bruce , Owolabi Mayowa O.
Published: May 2023

Background:

Using tailored mobile health interventions to improve global vascular risk awareness and control is yet to be investigated for primary stroke prevention in Africa.

Methods:

This 2-arm pilot randomized controlled trial involved 100 stroke-free adults with at least 2 vascular risk factors for stroke. Eligible participants were assigned randomly to a control arm offering 1-time counseling (n=50) or a 2-month educational intervention arm (n=50) comprising a stroke video and riskometer app aimed at improving stroke risk factor awareness and health-seeking behavioral modification to control total vascular risk. Reduction in total stroke risk score was the primary outcome while feasibility and process measures were secondary outcomes.

Results:

All enrolled participants completed the 2-month follow-up (retention rate=100%). The mean (SD) age of participants was 59.5 (±12.5) years, 38% were males. The mean change in stroke risk score at 2 months was −11.9% (±14.2) in the intervention arm versus −1.2% (±9.1) in the control arm,
P
=0.0001. Stroke risk awareness improved by 16.1% (±24.7) in the intervention arm versus 8.9% (±24.7) in the control arm,
P
=0.08. The intervention arm had 11.1 mm Hg reduction in systolic blood pressure compared with 4.8 mm Hg reduction in the control arm.

Conclusions:

The intervention demonstrated a positive signal of effect over a 2-month period. A definitive clinical trial with a longer duration of follow-up is warranted on the premise of these promising findings from this pilot randomized clinical trial.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT05619406.
Cannabis Regulation Through the “Without Right” Clause in Article 2(1) of EU Framework Decision 2004/757/jha on Illicit Drug Trafficking
Authors: van Kempen Piet Hein , Fedorova Masha
Published: May 2023

Several EU states have shown initiatives towards a more lenient approach to the regulation of cannabis cultivation and trade for recreational use. One possibility that is being investigated is whether a national regulatory system for controlled trade of recreational cannabis can be developed in accordance of the EU Framework Decision 2004/757/jha. The ‘without right’ -clause in Article 2(1) of this decision, from a linguistic point of view, does seem to allow the introduction of such a licensing system. In fact, such a system would not cross the system or the purpose of the Framework Decision, if such licensing system does not result in cross-border effects or the hindering of transnational cooperation in combatting cross-border drug trafficking. However, this possibility is only of theoretical nature considering the clear and strict obligations ensuing from the UN narcotic drugs conventions. In order to regulate recreational cannabis within the boundaries of public international law, states can: (1) denounce the UN narcotic drugs conventions; (2) deviate from the obligations of the UN conventions on the basis of positive human rights obligations; (3) create an inter se agreement between like-minded states that deviates from the UN conventions; and (4) denounce the UN drugs conventions and re-access subsequently with a reservation allowing for regulation of recreational cannabis. We argue that these options can have a combined strengthening effect and indeed present a legally sound and politically viable opportunity to regulate recreational cannabis without denouncing the whole UN drug control system.
First description of nymphal stages of Hoplopleura edentula (Anoplura: Hoplopleuridae) and a global checklist of the Hoplopleura associated with Clethrionomys
Authors: Kozina Paulina , Izdebska Joanna N.
Published: May 2023

We present the first record of the characteristics of the three nymphal stages of Hoplopleura edentula, one of the common Eurasian species of the genus Hoplopleura. Lastly, a list of all species of Hoplopleura parasitizing the host genus Clethrionomys is provided. The descriptions of sucking louse species usually lack the features of the nymphal stages. In addition, it is impossible to determine whether the host is the main one or an accidental when there is a co-occurance of two or more lice species, unless we observe nymphs of the same species. As a result, data on the host cycle, the range of host specificity and other aspects of parasite-host system functioning, the possibility of transfer between hosts, and the possibility of transmission of pathogens, are incomplete. This study examines 114 specimens of the bank vole Clethrionomys glareolus, in which 38 Hoplopleura edentula were found.
Margin-Negative en Bloc Resection of a Large Retroperitoneal Melanoma Including Reconstruction of the Infra-renal Inferior Vena Cava
Authors: Slutsky Hanna L. , Johnson Douglas B. , Stone Patrick , Tan Marcus C. B.
Published: May 2023

The management and outcomes for patients with metastatic melanoma have been revolutionized by immunotherapy. This case report highlights the role of surgery as an adjuvant to systemic therapies when there is oligoprogressive disease. We describe a 74-year-old man with metastatic melanoma who initially had a complete radiographic response after dual agent immunotherapy but subsequently developed a large metastasis in the retroperitoneum. After multidisciplinary discussion, he underwent margin negative resection that required en bloc segmental resection of the infra-renal inferior vena cava. To our knowledge, this is the first reported resection of a melanoma metastasis in this location.
Small Rotational Changes of the Chest on Portable Chest Films Produce Large Displacements of Test Projectiles in the Cardiac Box
Authors: Leavitt Justin , Carballo Christopher , Mentzer Caleb , Bokhari Faran , Yon James R.
Published: May 2023

The cardiac box has been used to guide the management of trauma patients for decades. However, improper imaging can lead to erroneous assumptions about operative management in this patient population. In this study, we used a thoracic model to demonstrate imaging’s effect on chest radiography. The data demonstrate that even small changes in rotation can lead to large discrepancies in results.
The Impact of Relocating a Trauma Center: Retrospective Observations on Payer Demographics and Cost-Analysis
Authors: Punja Viren , Capasso Thomas , Stokes Laura , Ray Kelley , Narveson Joel R. , Walters Ryan W. , Fernandez Carlos , Patel Neil D. , Ewing Kaily , Kuncir Eric
Published: May 2023

Background

Standardization of trauma centers improves quality of care, yet that comes with financial challenges. The decision to designate a trauma center typically focuses on access, quality of care, and the needs of the local community, but less often considers the financial viability of the trauma center. A level-1 trauma center was relocated in 2017 and this presented an opportunity to compare financial data at two separate locations in the same city.

Methods

A retrospective review was performed on the local trauma registry and billing database in all patients aged ≥19 years on the trauma service before and after the move.

Results

3041 patients were included (pre-move: 1151; post-move: 1890). After the move, patients were older (9.5 years), and more were females (14.9%) and white (16.5%). Increases in blunt injuries (7.6%), falls (14.8%), and motor vehicle accidents (1.7%) were observed after the move. After the move, patients were less likely to be discharged home (6.5%) and more likely to go to a skilled nursing facility (3%) or inpatient rehabilitation (5.5%). Post-move more patients had Medicare (12.6%) or commercial (8.5%) insurance and charges per patient decreased by $2,833, while charges collected per patient increased by $2425. Patients were seen from a broader distribution of zip codes post-move.

Discussion

Relocating a trauma center did improve financial viability for this institution. Future studies should consider the impact on the surrounding community and other trauma centers.

Level of evidence

Level IV.
Dietary Zinc Intakes Are Associated With Skeletal Muscle Mass and Strength in Children and Adolescents: Zinc and Muscle in Children
Authors: Kong Fan-Shuo , Ma Chun-Ming
Published: May 2023

The purpose of this study was to evaluate the relationship between dietary zinc intakes and skeletal muscle mass and strength in children and adolescents. A retrospective study was conducted using data on United States adolescents aged 8 to 19 years. Data were extracted from the National Health and Nutrition Examination Survey 2011-2014 cycles. Subjects were divided into 3 groups based on the tertiles of dietary zinc intakes. The levels of appendicular skeletal muscle mass divided by weight (ASM/Wt, %) and grip in subjects with the highest tertile were higher than those in subjects with the middle and lowest tertiles ( P < .05). Dietary zinc intakes were positively correlated with ASM/Wt ( r = .221, P < .001) and grip ( r = 0.169, P < .001). After a multivariate analysis, dietary zinc intakes were still significantly associated with ASM/Wt ( β = 0.059, P < .001) and grip ( β = 0.245, P < .001). The present study demonstrates that dietary zinc intakes were positively associated with skeletal muscle mass and strength in children and adolescents.
Quotidian crime, wartime violence and public goods preferences: Evidence from Liberia
Authors: Berens Sarah , Karim Sabrina
Published: May 2023

Much of the literature on victimization looks at the effect of organized violence (OV) on civilian perceptions and behaviour. Yet citizens in countries experience quotidian crime (QC) on a daily basis. QC differs from OV, the former being more isolated, while the latter is more of a collective experience. As such we develop a theoretical framework that explores the effects of both types of violence on preferences for public goods. Victims of OV may prefer welfare public goods for the entire community, whereas victims of QC may prefer security for themselves. We also test the effects of compound victimization on public goods’ preferences. We use original survey data from rural Liberia to test our hypotheses and find support for our argument. Our results show the importance of a disaggregated approach to understanding the effects of violence on preferences.
Research Should Focus on Improving Mathematics Proficiency for Students With Disabilities
Authors: Witzel Bradley , Myers Jonte , Root Jenny , Freeman-Green Shaqwana , Riccomini Paul , Mims Pamela
Published: May 2023

Students with disabilities experience differential levels of achievement in mathematics when compared with their nondisabled peers. Identifying and implementing evidence-based practices (EBPs) is essential to increase their mathematics achievement. However, an argument is re-emerging that calls into question the effectiveness of well-known EBPs, such as explicit/direct instruction. This argument is based on opinion and conjecture, rather than student outcome measures. In this commentary, we use research on explicit and direct instruction with mathematics to (a) highlight the confusion over theoretical implications, (b) call for researchers to reduce personal bias within research, and (c) emphasize the need for improving outcomes of students with disabilities that affect mathematics learning.
The Past, Present, and Future of Commercial Associations in China: Reflections on Theory and the Pathways of Practice
Authors: Zhao Shan
Published: May 2023

Since the 1980s, three paradigms have dominated the historical study of commercial associations—class analysis, modernization, and “public sphere”/“civil society”—but all three are imbued with and insist upon a binary opposition between state and society. These paradigms produce an understanding of commercial associations as part of a Western-style “bourgeois public sphere,” itself part of “civil society,” standing in opposition to the state. These misinterpretations were only strengthened by the complete state-ification of commercial associations in China after 1949. Studies of the history of commercial associations, trapped in this theoretical pitfall, cannot produce convincing historical research, even with abundant empirical data, nor can they provide experiential models for the development of contemporary commercial associations. Instead, if we focus on practice, we discover that modern commercial associations were part of a “third sphere,” an in-between space within the paradoxical institutional framework of China’s highly centralized government and minimalist administrative system. The semiformal governance mechanism operative within the third sphere reflected the close relationship and mutual shaping at work between the state and local society rather than a binary opposition between them. Applying these insights on the history of commercial associations to the practices of contemporary “commercial consultative associations” allows us to see that the semiformal administrative traditions embedded in the “third sphere” continue to quietly operate, which has immense significance for the future development of commercial associations in China.
Caste, Social Capital and Precarity of Labour Market Intermediaries: The case of dalit labour contractors in India
Authors: Soundararajan Vivek , Sharma Garima , Bapuji Hari
Published: May 2023

Research on precarity predominantly adopts a monolithic view of labour market intermediaries and ignores the differential distribution of precarity based on social group membership. This omission not only hinders a nuanced understanding of precarity but also prevents our ability to address inequalities. To address this, we examined the influence of caste on differential experiences of precarity among labour contractors (LCs) in the garment industry in Tamil Nadu, India. We find that unequal distribution of social capital along caste lines leads to Dalit LCs experiencing greater precarity than their upper caste counterparts, and being stuck in such precarity. Specifically, caste-based dynamics of social capital threaten the survival of Dalit LCs by distorting their economic wellbeing and destabilizing their leadership, and hindering their upward occupational mobility by confining their spatial mobility, limiting resourceful connections, and thwarting growth opportunities. Our study shines new light on how societal inequalities differentially distribute precarity among actors in the same occupation and underscores the intersectional nature of occupational precarity as well as the contextual nature of social capital.
The Integration Paradox: A Review and Meta-Analysis of the Complex Relationship Between Integration and Reports of Discrimination
Authors: Schaeffer Merlin , Kas Judith
Published: May 2023

Social science research has produced evidence of an “integration paradox”: immigrants and their descendants who appear to have greater access to mainstream middle-class society, as indicated by their education or labor market success, often report experiencing more discrimination. Several explanations have been put forth to account for this counterintuitive pattern, supported by a wealth of empirical evidence. To assess the reliable insights generated by this line of research, this article presents a review and meta-analytic analysis of the integration paradox. The article reviews the major theoretical arguments advanced in literature, and derives crucial hypotheses concerning the phenomenon's overall nature, underlying mechanisms, and two key moderating conditions. Specifically, it discusses how factors like better education, which appear to signal improved integration into mainstream society, may also lead to greater exposure to mainstream members, heightened familiarity with exclusionary public discourse, or a heightened risk of downward social mobility. By increasing cognitive susceptibility to framing experiences in terms of discrimination or simply the opportunities to encounter discrimination, these mechanisms are expected to increase reports of discrimination. To test these propositions, the study summarizes and evaluates 280 statistical estimates published in 42 studies, utilizing recent developments in multilevel meta-analysis. The findings support the credibility of the integration paradox, particularly for immigrant minorities who are easily distinguishable from the mainstream and for those who reside in countries with a more open socio-political context of reception. However, the results also suggest that additional research is needed to fully comprehend the underlying mechanisms of the paradox.
A Moderated Model for the Effect of Human Resource Management Strategy on Organizational Outcomes
Authors: Mehmood Khawaja Khalid , Masood Samra , Hanaysha Jalal Rajeh
Published: May 2023

Much of the previous research has focused on the relationship between human resource practices and organizational outcomes. However, there is limited research investigating the effect of human resource strategy (accumulation, facilitation and utilization strategy) on organizational outcomes. This study addresses the research gap and aims to contribute to the stock of literature and theory by analysing the moderating effect of company age and company size on the relationship between human resource management strategy and organizational performance, competitive advantage and employee turnover in Pakistan’s hotel industry. Questionnaires were used to collect data from hotels located in Punjab province. Based on a final sample of 105 hotels, we found that the hotel age moderates the association between HRM strategy and employee turnover. The results reveal that the more the inclination towards an accumulation strategy, the better is organization’s performance and competitive advantage, and the lower the employee turnover. Other than contributing to the resource-based view and the contingency theory, this research provides suggestions to hotel managers regarding the effective use of HRM strategy. Specifically, by focusing on accumulation HR strategy, hotel managers could reduce employee turnover, generate competitive advantage and achieve high performance.
How Intense Language Hurts a Politician's Trustworthiness: Voter Norms of a Political Debate via Language Expectancy Theory
Authors: Clementson David E. , Zhao Wenqing , Park Sohyun
Published: May 2023

Incivility in U.S. political debates hurts democracy. But uncivil language is more entertaining, exciting, and arousing than civil language. Given the contradictory relationship between people's general aversion and the media attention to popularized incivility, insight can be gained through examining politicians’ language intensity, a relatively common yet scarcely explored phenomenon in political debates. In a preregistered multiple-message experimental design with an original stimulus filmed for this study, participants ( n = 538 registered U.S. voters) watch a debate featuring a real politician (with a real journalist moderating the debate). Participants are randomly assigned to high- or low-intensity language conditions. Inspired by language expectancy theory (LET), a multiple-mediation model is tested, whereby language intensity decreases a politician's trustworthiness through intense language being more uncivil than low-intensity language which is associated with voters’ normative expectancies. Discussion concerns the practical implications for politicians’ debate strategy and theoretical ramifications of LET via communication accommodation theory.