bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initial opioid prescription characteristics and risk of opioid misuse, poisoning and dependence: retrospective cohort study
Authors: García-Sempere Aníbal , Hurtado Isabel , Robles Celia , Llopis-Cardona Fran , Sánchez-Saez Francisco , Rodriguez-Bernal Clara , Peiró-Moreno Salvador , Sanfélix-Gimeno Gabriel 
Published: July 2023

ObjectiveTo identify individual and initial prescription-related factors associated with an increased risk for opioid-related misuse, poisoning and dependence (MPD) in patients with non-cancer pain.MethodsCohort study linking several databases covering 5 million inhabitants of the region of Valencia, Spain, including all adults initiating prescription opioids in the period 2012–2018. To ascertain the association between the characteristics of the initial prescription choice and the risk of opioid MPD, we used shared frailty Cox regression models. We additionally considered death as a competing risk in sensitivity analyses.Results958 019 patients initiated opioid prescription from 2012 to 2018, of which 0.13% experienced MPD. Most patients were prescribed tramadol as initial opioid (76.7%) followed by codeine (16.3%), long-acting opioids (6.7%), short-acting opioids (0.2%) and ultrafast opioids (0.1%). Initiation with ultrafast (HR 7.2; 95% CI 4.1 to 12.6), short-acting (HR 4.8; 95% CI 2.3 to 10.2) and long-acting opioids (HR 1.5; 95% CI 1.2 to 1.9) were associated with a higher risk of MPD when compared with tramadol. Initial prescriptions covering 4–7 days (HR 1.3; 95% CI 1.0 to 1.8), 8–14 days (HR 1.4; 95% CI 1.0 to 1.9), 15–30 days (HR 1.7; 95% CI 1.2 to 2.3) and more than one a month (HR 1.8; 95% CI 1.3 to 2.5) were associated with more MPD risk than initial prescriptions for 1–3 days. Treatments with >120 daily morphine milligram equivalents (MME) increased MPD risk (vs <50 MME, HR 1.6; 95% CI 1.1 to 2.2). Main individual factors associated with increased risk of MPD risk were male sex (HR 2.4; 95% CI 2.1 to 2.7), younger age (when compared with patients aged 18–44 years, patients aged 45–64 years, HR 0.4; 95% CI 0.4 to 0.5; patients aged 65–74 years, HR 0.4; 95% CI 0.3 to 0.5 and patients aged 75 years old and over, HR 0.7; 95% CI 0.6 to 0.8), lack of economic resources (2.1; 95% CI 1.8 to 2.5) and registered misuse of alcohol (2.9; 95% CI 2.4 to 3.5). Sensitivity analyses yielded overall comparable results.ConclusionsOur study identifies riskier patterns of opioid prescription initiation for non-cancer indications, as well as patient subgroups with higher risk of misuse, poisoning and dependence.
Bacterial contamination of endoscopist and assistant face visors during gastrointestinal endoscopy: a pilot study
Authors: Nylander David , Leeds John , Perry John , Narayanan Manjusha , Dipper Chris , Gunn Mel , Nayar Manu , Speight Ally , Oppong Kofi W 
Published: July 2023

Background and aimDuring the COVID-19 pandemic, health workers’ facial exposure to pathogens has been brought into focus. In this study, we aimed to determine the occurrence and degree of facial contamination to both endoscopists and their assistants during endoscopic procedures to help inform future safety measures.MethodsNon-sterile visors worn by endoscopist, assistant and room control visors from 50 procedures were swabbed post procedure for culture. Procedure type, therapy, duration and evidence of visible visor contamination were recorded. After 48-hour incubation, all bacterial colonies were identified using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry. Organisms were classified into skin/environmental, oronasal and enteric.ResultsA total of 104 visors were available for assessment (93 staff; 11 control). In worn visors, skin/environmental flora were isolated from 70, oronasal flora from 8, and enteric flora from 3 with an average colony count of >9.5. Notably, bacteria of enteric origin (Escherichia coliandEnterobacter cloacae) were isolated from three worn visors. In room control, skin/environmental flora were isolated from seven and oronasal flora from one with average colony count of five. No room control visors grew enteric flora. Overall, 9.1% room control and 10.8% worn visors were contaminated with organisms that could possibly have originated from patients. However, enteric flora were only obtained from worn visors. No visors were visibly contaminated.ConclusionThis pilot study demonstrates risk of contamination to faces of endoscopists and assistants. Larger studies are required to determine degree of risk and to give guidance on facial protection during gastrointestinal endoscopy.
Updated definition of pulmonary hypertension and outcome after transcatheter aortic valve implantation
Authors: Cardaioli Francesco , Nai Fovino Luca , Fabris Tommaso , Masiero Giulia , Arturi Federico , Trevisanello Aurora , Zuccarelli Vittorio , Napodano Massimo , Fraccaro Chiara , Continisio Saverio , Tarantini Giuseppe 
Published: July 2023

ObjectiveThe European Society of Cardiology guidelines have recently defined new cut-offs for pulmonary hypertension (PH) and pulmonary vasculature resistance (PVR; median pulmonary artery pressure (mPAP) >20 instead of 25 mm Hg and PVR >2 instead of 3 Wood unit). The prognostic value of this updated classification after transcatheter aortic valve implantation (TAVI) is unknown.Methods579 consecutive patients treated by TAVI with preprocedural right heart catheterisation evaluation were included. Patients were grouped as: (1) no PH, (2) isolated precapillary/combined (I-PreC/Co) PH and (3) isolated postcapillary PH (I-PoC). All-cause death, cardiovascular death and hospitalisations for heart failure (HF) were evaluated at follow-up. We also analysed the prognostic role of residual postprocedural PH.ResultsOut of 579 patients, 299 (52%) had PH according to the new criteria compared with 185 (32%) according to the previous ones. Overall median age was 82 years, while 55.3% patients were male. Patients with PH were more frequently diagnosed with chronic obstructive pulmonary disease and atrial fibrillation and were characterised by higher surgical risk as compared with patients without PH.At a median follow-up of 2.9 years, the presence of PH according to previous definition was associated with worse survival (p<0.001) and HF hospitalisation (p=0.002) rates, irrespective of PVR values. With newer cut-offs, PH was associated with worse outcomes only in patients with increased PVR, while no differences were found between patients with PH and normal PVR values and those without PH. Postprocedural mPAP normalisation was observed in 45% of the cases, but it was associated with improved long-term survival only in the I-PoC PH group.ConclusionsNew ESC PH cut-offs increased the number of PH diagnoses. The presence of PH, particularly in the setting of increased PVR, identify patients at higher risk for postprocedural mortality and rehospitalisation. Normalisation of PH was associated with better survival only in I-PoC group.
CDF-II W boson mass in the Dirac scotogenic model
Authors: Chuliá Salvador Centelles , Srivastava Rahul , Yadav Sushant 
Published: July 2023

The Dirac scotogenic model provides an elegant mechanism which explains small Dirac neutrino masses and neutrino mixing, with a single symmetry simultaneously protecting the “Diracness” of the neutrinos and the stability of the dark matter candidate. Here, we explore the phenomenological implications of the recent CDF-II measurement of the W boson mass in the Dirac scotogenic framework. We show that, in the scenario where the dark matter is mainly a [Formula: see text] scalar doublet, it can satisfy all the theoretical and experimental constraints along with the CDF-II W boson mass for the mass range of 58–86 GeV. However, unlike the Majorana scotogenic model, the Dirac version also has a “dark sector” SU(2)L singlet scalar. We show that if the singlet scalar is the lightest dark sector particle, i.e. the dark matter then all neutrino physics and dark matter constraints along with the constraints from oblique S, T and U parameters can be concurrently satisfied for W boson mass in the CDF-II mass range, where the singlet dark matter mass is constrained up to around 500 GeV.
Hospitalizations and Cost of Inpatient Care for Physical Diseases in Survivors of Childhood Cancer in Western Australia: A Longitudinal Matched Cohort Study
Authors: Abdalla Tasnim , Walwyn Thomas , White Daniel , Choong Catherine S. , Bulsara Max , Preen David B. , Ohan Jeneva L. 
Published: July 2023

Abstract

Background:
The long-term effects of childhood cancer are unclear in the Australian context. We examined hospitalization trends for physical diseases and estimated the associated inpatient care costs in all 5-year childhood cancer survivors (CCS) diagnosed in Western Australia (WA) from 1982 to 2014.

Methods:
Hospitalization records for 2,938 CCS and 24,792 comparisons were extracted from 1987 to 2019 (median follow-up = 12 years, min = 1, max = 32). The adjusted hazard ratio (aHR) of hospitalization with 95% confidence intervals (CI) was estimated using the Andersen–Gill model for recurrent events. The cumulative burden of hospitalizations over time was assessed using the mean cumulative count method. The adjusted mean cost of hospitalization was estimated using the generalized linear models.

Results:
We identified a higher risk of hospitalization for all-cause (aHR, 2.0; 95% CI, 1.8–2.2) physical disease in CCS than comparisons, with the highest risk for subsequent malignant neoplasms (aHR, 15.0; 95% CI, 11.3–19.8) and blood diseases (aHR, 6.9; 95% CI, 2.6–18.2). Characteristics associated with higher hospitalization rates included female gender, diagnosis with bone tumors, cancer diagnosis age between 5 and 9 years, multiple childhood cancer diagnoses, multiple comorbidities, higher deprivation, increased remoteness, and Indigenous status. The difference in the mean total hospitalization costs for any disease was significantly higher in survivors than comparisons (publicly funded $11,483 United States Dollar, P &lt; 0.05).

Conclusions:
The CCS population faces a significantly higher risk of physical morbidity and higher cost of hospital-based care than the comparisons.

Impact:
Our study highlights the need for long-term follow-up healthcare services to prevent disease progression and mitigate the burden of physical morbidity on CCS and hospital services.
Hierarchical Phosphorylation of HOXB13 by mTOR Dictates Its Activity and Oncogenic Function in Prostate Cancer
Authors: Chen Yonghong , Dufour Catherine R. , Han Lingwei , Li Ting , Xia Hui , Giguère Vincent 
Published: July 2023

Abstract

Dysregulation of mTOR signaling plays a critical role in promoting prostate cancer growth. HOXB13, a homeodomain transcription factor, is known to influence the androgen response and prostate cancer development. Recently, HOXB13 was found to complex with mTOR on chromatin. However, the functional crosstalk between HOXB13 and mTOR remains elusive. We now report that mTOR directly interacts with and hierarchically phosphorylates HOXB13 at threonine 8 and 41 then serine 31 to promote its interaction with the E3 ligase SKP2 while enhancing its oncogenic properties. Expression of HOXB13 harboring phosphomimetic mutations at the mTOR-targeted sites stimulates prostate cancer cellular growth both in vitro and in murine xenografts. Transcriptional profiling studies revealed a phospho-HOXB13–dependent gene signature capable of robustly discriminating between normal prostate tissues, primary and metastatic prostate cancer samples. This work uncovers a previously unanticipated molecular cascade by which mTOR directly phosphorylates HOXB13 to dictate a specific gene program with oncogenic implications in prostate cancer.

Implications:
Control of HOXB13 transcriptional activity via its direct phosphorylation by the mTOR kinase is a potential therapeutic avenue for the management of advanced prostate cancer.
p53 Regulates the Extent of Fibroblast Proliferation and Fibrosis in Left Ventricle Pressure Overload
Authors: Liu Xiaoyi , Burke Ryan M. , Lighthouse Janet K. , Baker Cameron D. , Dirkx Ronald A. , Kang Brian , Chakraborty Yashoswini , Mickelsen Deanne M. , Twardowski Jennifer J. , Mello Stephano S. , Ashton John M. , Small Eric M. 
Published: July 2023

BACKGROUND:
Cardiomyopathy is characterized by the pathological accumulation of resident cardiac fibroblasts that deposit ECM (extracellular matrix) and generate a fibrotic scar. However, the mechanisms that control the timing and extent of cardiac fibroblast proliferation and ECM production are not known, hampering the development of antifibrotic strategies to prevent heart failure.

METHODS:

We used the Tcf21 (transcription factor 21)
MerCreMer
mouse line for fibroblast-specific lineage tracing and
p53
(tumor protein p53) gene deletion. We characterized cardiac physiology and used single-cell RNA-sequencing and in vitro studies to investigate the p53-dependent mechanisms regulating cardiac fibroblast cell cycle and fibrosis in left ventricular pressure overload induced by transaortic constriction.

RESULTS:

Cardiac fibroblast proliferation occurs primarily between days 7 and 14 following transaortic constriction in mice, correlating with alterations in p53-dependent gene expression. p53 deletion in fibroblasts led to a striking accumulation of Tcf21-lineage cardiac fibroblasts within the normal proliferative window and precipitated a robust fibrotic response to left ventricular pressure overload. However, excessive interstitial and perivascular fibrosis does not develop until after cardiac fibroblasts exit the cell cycle. Single-cell RNA sequencing revealed
p53
null fibroblasts unexpectedly express lower levels of genes encoding important ECM proteins while they exhibit an inappropriately proliferative phenotype. in vitro studies establish a role for p53 in suppressing the proliferative fibroblast phenotype, which facilitates the expression and secretion of ECM proteins. Importantly,
Cdkn2a
(cyclin-dependent kinase inhibitor 2a) expression and the p16
Ink4a
-retinoblastoma cell cycle control pathway is induced in
p53
null cardiac fibroblasts, which may eventually contribute to cell cycle exit and fulminant scar formation.

CONCLUSIONS:
This study reveals a mechanism regulating cardiac fibroblast accumulation and ECM secretion, orchestrated in part by p53-dependent cell cycle control that governs the timing and extent of fibrosis in left ventricular pressure overload.
Extracellular Vesicle–Encapsulated Adeno-Associated Viruses for Therapeutic Gene Delivery to the Heart
Authors: Li Xisheng , La Salvia Sabrina , Liang Yaxuan , Adamiak Marta , Kohlbrenner Erik , Jeong Dongtak , Chepurko Elena , Ceholski Delaine , Lopez-Gordo Estrella , Yoon Seonghun , Mathiyalagan Prabhu , Agarwal Neha , Jha Divya , Lodha Shweta , Daaboul George , Phan Anh , Raisinghani Nikhil , Zhang Shihong , Zangi Lior , Gonzalez-Kozlova Edgar , Dubois Nicole , Dogra Navneet , Hajjar Roger J. , Sahoo Susmita 
Published: July 2023

BACKGROUND:
Adeno-associated virus (AAV) has emerged as one of the best tools for cardiac gene delivery due to its cardiotropism, long-term expression, and safety. However, a significant challenge to its successful clinical use is preexisting neutralizing antibodies (NAbs), which bind to free AAVs, prevent efficient gene transduction, and reduce or negate therapeutic effects. Here we describe extracellular vesicle–encapsulated AAVs (EV-AAVs), secreted naturally by AAV-producing cells, as a superior cardiac gene delivery vector that delivers more genes and offers higher NAb resistance.

METHODS:
We developed a 2-step density-gradient ultracentrifugation method to isolate highly purified EV-AAVs. We compared the gene delivery and therapeutic efficacy of EV-AAVs with an equal titer of free AAVs in the presence of NAbs, both in vitro and in vivo. In addition, we investigated the mechanism of EV-AAV uptake in human left ventricular and human induced pluripotent stem cell-derived cardiomyocytes in vitro and mouse models in vivo using a combination of biochemical techniques, flow cytometry, and immunofluorescence imaging.

RESULTS:
Using cardiotropic AAV serotypes 6 and 9 and several reporter constructs, we demonstrated that EV-AAVs deliver significantly higher quantities of genes than AAVs in the presence of NAbs, both to human left ventricular and human induced pluripotent stem cell-derived cardiomyocytes in vitro and to mouse hearts in vivo. Intramyocardial delivery of EV-AAV9–sarcoplasmic reticulum calcium ATPase 2a to infarcted hearts in preimmunized mice significantly improved ejection fraction and fractional shortening compared with AAV9–sarcoplasmic reticulum calcium ATPase 2a delivery. These data validated NAb evasion by and therapeutic efficacy of EV-AAV9 vectors. Trafficking studies using human induced pluripotent stem cell–derived cells in vitro and mouse hearts in vivo showed significantly higher expression of EV-AAV6/9–delivered genes in cardiomyocytes compared with noncardiomyocytes, even with comparable cellular uptake. Using cellular subfraction analyses and pH-sensitive dyes, we discovered that EV-AAVs were internalized into acidic endosomal compartments of cardiomyocytes for releasing and acidifying AAVs for their nuclear uptake.

CONCLUSIONS:
Together, using 5 different in vitro and in vivo model systems, we demonstrate significantly higher potency and therapeutic efficacy of EV-AAV vectors compared with free AAVs in the presence of NAbs. These results establish the potential of EV-AAV vectors as a gene delivery tool to treat heart failure.
A Promising Break in the “Black Box”: Agency of Competencies and Interpretation in Istanbul Maker Ecologies
Authors: Dilek Özgün , Kaya Cigdem 
Published: July 2023

Abstract
This article reflects an inquiry into the agency in Istanbul maker ecologies by employing phenomenological research through the perspective of Actor-Network Theory. The originally generated onto-phenomenological approach in this article attributes agency to the competencies and the interpretation. Socioeconomic effects that emerged as an outcome of the agency in maker-thing assemblages are reflected as a part of this inquiry. Agency in local maker practices is exposed to show how they are different from the global maker movement through the criticism of it in the discussion.
VEGF Mediates Tumor Growth and Metastasis by Affecting the Expression of E-Cadherin and N-Cadherin Promoting Epithelial to Mesenchymal Transition in Gastric Cancer
Authors: Zhang Yue , Wang Yanyan , Zhao Menglin , Li Xinwei , Li Huiyuan , Tang Mingyue , Geng Zhijun , Zuo Lugen , Song Xue , Wang Zishu , Wang Qiang , Su Fang 
Published: July 2023

Background: Gastric cancer (GC) is the fifth leading cancer in the world, and there is a high mortality rate in China. Exploring the relationship between the prognosis of GC and the expression of related genes is helpful to further understand the common characteristics of the occurrence and development of GC and provide a new method for the identification of early GC, so as to provide the best therapeutic targets. Methods: Vascular endothelial growth factor (VEGF) and markers of epithelial-mesenchymal transition (EMT) were investigated immunohistochemically using tumor samples obtained from 196 GC tissues and adjacent tumor tissues. The correlation of the expression level with histopathologic features and survival was investigated. Results: Here, we show that VEGF and EMT markers expression were significantly correlated with depth of tumor invasion and GC stage ( P < .05), degree of differentiation and lymph node metastasis ( P < .001). We found that the rate of VEGF positivity in GC tissues was 52.05%, which was significantly higher than that in adjacent cancer tissues (16.84%). In GC, the association between VEGF and E-cadherin was negative ( r = −0.188, P < .05), whereas VEGF and N-cadherin were positively correlated ( r = 0.214, P < .05). Furthermore, the Kaplan-Meier analysis and a Cox regression model were used to analyze the effect of VEGF and EMT marker expression on the survival of the patients. We found that the overall survival of GC patients was correlated with VEGF ( P < .001), N-cadherin ( P < .001), E-cadherin ( P = .002) expression, and some histopathologic features. Conclusions: Vascular endothelial growth factor and EMT markers exist side by side and play a part together in the development of GC, which provides new ideas for evaluating the prognosis of GC and researching targeted drugs.
Outcomes of Frontal Sinus Stenting With Steroid Impregnated Microsponge Versus Steroid-Eluting Implant
Authors: Brar Tripti , Brown Adam , Miglani Amar , Lal Devyani , Marino Michael J. 
Published: July 2023

Background Mometasone-eluting poly-L-lactide-coglycolide (MPLG) is available commercially for frontal sinus ostium (FSO) stenting. An alternative chitosan polymer-based drug delivery microsponge is also available at a lower cost per unit. Objective To compare the outcomes of MPLG stents versus triamcinolone-impregnated chitosan polymer (TICP) microsponge in frontal sinus surgery. Methods Patients who underwent endoscopic sinus surgery from December 2018 to February 2022 were reviewed to identify those with the intraoperative placement of TICP microsponge or MPLG stent in the FSO. FSO patency was evaluated by endoscopy at follow-up. Twenty-two-item sinonasal outcome test (SNOT-22) was also recorded, and complications were noted. Results A total of 68 subjects and 96 FSOs were treated. TICP was first used in August 2021 and MPLG in December 2018. MPLG placement in a Draf 3 cavity was excluded since TICP had not been used during Draf 3 procedure. Both cohorts (TICP 20 subjects, 35 FSOs; MPLG 26 subjects, 39 FSOs) had similar clinical characteristics. At a mean total follow-up of 249.2 days for TICP and 490.4 days for MPLG, FSO patency was 82.9% and 87.1%, respectively ( P = .265). At an equivalent follow-up of 130.6 days in TICP and 154.0 days in MPLG, patency was 94.3% and 89.7%, respectively ( P = .475). Both groups showed significant reductions in SNOT-22 ( P < .001). MPLG demonstrated crusting within the FSO at 1 month (none in TICP). Conclusion FSO patency for both stents was similar, although TICP had significantly lower costs per unit. Additional comparative trials may be helpful for guiding clinicians on the appropriate clinical situations for the use of these devices.
The Experience of Working Nurses Attending Graduate School During COVID-19: A Hermeneutic Phenomenology Study
Authors: DeGrande Heather , Seifert Madison , Painter Elizabeth 
Published: July 2023

Introduction There has been unprecedented uncertainty involved in the COVID-19 pandemic, especially for working nurses. Nurses working while attending graduate school faced additional unique challenges including working extended hours while also home-schooling young children, managing a family life while also navigating pandemic-related changes affecting students’ educational paths. Objectives The purpose of this study was to explore the lived experiences of working nurses attending graduate school during the COVID-19 pandemic. The central research question was: What is the lived experience of working nurses attending graduate school during COVID-19? Methods The exploration of the lived experience of working nurses attending graduate school during a pandemic required a research methodology delving into the meaning of lived experience as it has been lived, temporally, and contextually (during a pandemic). Qualitative hermeneutic phenomenology was used to explore the meaning of lived experience from an interpretational stance. Results The overall meaning of the experience was a paradigm shift of existence across the three realms of work, home, and school. The themes associated with the shift were rapid change, uncertainty, fear, and support persons. Stress was a resulting overarching theme. Conclusions To support working nurses further their education during times of crisis, nurse leaders and educators should put processes in place to mitigate change and stress through strategic communication and supportive work environments.