bluuebunny/crossref_metadata_2025_split huggingface dataset:
“As safe as possible”: a qualitative study of opioid withdrawal and risk behavior among people who use illegal opioids
Authors: Frank David , Elliott Luther , Cleland Charles M. , Walters Suzan M. , Joudrey Paul J. , Russell Danielle M. , Meyerson Beth E. , Bennett Alex S. 
Published: October 2023

AbstractBackgroundOpioid withdrawal is a regular occurrence among many people who use illicit opioids (PWUIO) that has also been shown to increase their willingness to engage in risk-involved behavior. The proliferation of fentanyl in the illicit opioid market may have amplified this relationship, potentially putting PWUIO at greater risk of negative health outcomes. Understanding the relationship between withdrawal and risk-involved behavior may also have important implications for the ways that problematic drug use is conceptualized, particularly in disease models of addiction, which position risk behavior as evidence of pathology that helps to justify ontological distinctions between addicts and non-addicts. Examining withdrawal, and its role in PWUIO’s willingness to engage in risk, may aid in the development of alternative theories of risk involvement and create discursive spaces for de-medicalizing and de-othering people who use illegal drugs.MethodsThis article is based on 32 semi-structured interviews with PWUIO in the New York City area who also reported recent withdrawal experience. Interviews were conducted remotely between April and August 2022 and recorded for later transcription. Data were then coded and analyzed based on a combination of inductive and deductive coding strategies and informed by the literature.ResultsParticipants described a strong relationship between withdrawal and their willingness to engage in risk-involved behavior that was exacerbated by the proliferation of fentanyl. Yet, their descriptions did not align with narratives of risk as a product of bad decisions made by individuals. Rather, data demonstrated the substantial role of social and structural context, particularly drug policies like prohibition and criminalization, in the kinds of risks that PWUIO faced and their ability to respond to them.ConclusionsWithdrawal should be taken more seriously both from an ethical perspective and as an important catalyst of risk behavior. However, theories that position activities taken to avoid withdrawal as irrational and as evidence of pathology are poorly aligned with the complexity of PWUIO’s actual lives. We recommend the use of less deterministic and less medicalized theories of risk that better account for differences between how people view the world, and for the role of socio-structural forces in the production of risk.
Live birth rates after resolution of endometrial cavity fluid in frozen embryo transfer cycles
Authors: Nguyen Vincent , Jackson Aaron , Gale Jenna 
Published: October 2023

Abstract
Research question
Are live birth rates affected in frozen embryo transfer cycles that develop transient endometrial cavity fluid that resolves by day of embryo transfer?

Design
The first frozen blastocyst transfer cycle between January 1st, 2016 and December 31st, 2019 were included in this retrospective cohort study at an academic fertility center. The presence or absence of endometrial cavity fluid (ECF) detected on initial ultrasound and at time of transfer was recorded. Patients who had persistent ECF at time of transfer were excluded from the study. The primary outcome was live birth rate in the group with resolved ECF relative to the group without ECF.

Results
A total of 1034 frozen blastocyst transfer cycles were included, 54 with resolved ECF and 980 without ECF. Adjusted analyses were performed using a log-binomial regression model. Live birth rates were 35.2% and 34.2%, adjusted risk ratio 1.00 [95% CI 0.70-1.50] in the two groups, respectively.

Conclusion
Live birth rates in frozen embryo transfer cycles are equivalent between patients with resolved endometrial cavity fluid compared to those who never had endometrial cavity fluid. Our findings suggest that the presence of endometrial cavity fluid is likely not detrimental to live birth rates if the fluid spontaneously resolves by the time of embryo transfer.
Venous thromboembolic disease in admitted blunt trauma patients: what matters?
Authors: Lineberry Camille , Alexis Dimitri , Mukhi Ambika , Duh Kevin , Tharakan Mathew , Vosswinkel James A. , Jawa Randeep S. 
Published: October 2023

Abstract
Background
Venous thromboembolic events (VTE) are a significant cause of morbidity and mortality following traumatic injury. We examined demographic characteristics, chemoprophylaxis, and outcomes of VTE patients with blunt trauma requiring hospitalization.

Methods
A retrospective review of adult blunt trauma hospitalizations with and without VTE between 2012 and 2019 was conducted. Deaths in the emergency department were excluded. Univariate and multivariable analyses, including machine learning classification algorithms for VTE, were performed.

Results
Of 10,926 admitted adult blunt trauma patients, 177 had VTE events. VTE events occurred at a median of 6 [IQR 3–11] days, with 7.3% occurring within 1 day of admission. VTE patients were more often male, and more often underwent surgery. They had higher injury severity as well as longer intensive care unit and hospital lengths of stay. While VTE occurred throughout the spectrum of injury severity, 27.7% had low injury severity (ISS < = 9). In multivariable analyses, both heparin and enoxaparin had reduced adjusted odds ratios for VTE.

Conclusion
Approximately 7.3% of VTE events occurred within one day of admission. A substantial proportion of VTE events occurred in patients with low injury severity (ISS < = 9). Subcutaneous unfractionated heparin and enoxaparin chemoprophylaxis were both inversely associated with VTE. These findings underscore the need for vigilance for VTE identification in blunt trauma patients throughout their hospitalization and VTE prevention efforts.
Supporting translation of research evidence into practice—the use of Normalisation Process Theory to assess and inform implementation within randomised controlled trials: a systematic review
Authors: Williams Allison , Lennox Laura , Harris Matthew , Antonacci Grazia 
Published: October 2023

AbstractBackgroundThe status of randomised controlled trials (RCTs) as the ‘gold standard’ for evaluating efficacy in healthcare interventions is increasingly debated among the research community, due to often insufficient consideration for implementation. Normalisation Process Theory (NPT), which focuses on the work required to embed processes into practice, offers a potentially useful framework for addressing these concerns. While the theory has been deployed in numerous RCTs to date, more work is needed to consolidate understanding of if, and how, NPT may aid implementation planning and processes within RCTs. Therefore, this review seeks to understand how NPT contributes to understanding the dynamics of implementation processes within RCTs. Specifically, this review will identify and characterise NPT operationalisation, benefits and reported challenges and limitations in RCTs.MethodsA qualitative systematic review with narrative synthesis of peer-reviewed journal articles from eight databases was conducted. Studies were eligible for inclusion if they reported sufficient detail on the use of NPT within RCTs in a healthcare domain. A pre-specified data extraction template was developed based on the research questions of this review. A narrative synthesis was performed to identify recurrent findings.ResultsSearches identified 48 articles reporting 42 studies eligible for inclusion. Findings suggest that NPT is primarily operationalised prospectively during the data collection stage, with limited sub-construct utilisation overall. NPT is beneficial in understanding implementation processes by aiding the identification and analysis of key factors, such as understanding intervention fidelity in real-world settings. Nearly three-quarters of studies failed to report the challenges and limitations of utilising NPT, though coding difficulties and data falling outside the NPT framework are most common.ConclusionsNPT appears to be a consistent and generalisable framework for explaining the dynamics of implementation processes within RCTs. However, operationalisation of the theory to its full extent is necessary to improve its use in practice, as it is currently deployed in varying capacities. Recommendations for future research include investigation of NPT alongside other frameworks, as well as earlier operationalisation and greater use of NPT sub-constructs.Trial RegistrationThe protocol for this systematic review was accepted for public registration on PROSPERO (registration number: CRD42022345427) on 26 July 2022.
Serial assessments of cardiac output and mixed venous oxygen saturation in comatose patients after out-of-hospital cardiac arrest
Authors: Grand Johannes , Hassager Christian , Schmidt Henrik , Mølstrøm Simon , Nyholm Benjamin , Høigaard Henrik Frederiksen , Dahl Jordi S. , Meyer Martin , Beske Rasmus P. , Obling Laust , Kjaergaard Jesper , Møller Jacob E. 
Published: October 2023

Abstract
Aim
To assess the association with outcomes of cardiac index (CI) and mixed venous oxygen saturation (SvO2) in comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA).

Methods
In the cohort study of 789 patients included in the “BOX”-trial, 565 (77%) patients were included in this hemodynamic substudy (age 62 ± 13 years, male sex 81%). Pulmonary artery catheters were inserted shortly after ICU admission. CI and SvO2 were measured as soon as possible in the ICU and until awakening or death. The endpoints were all-cause mortality at 1 year and renal failure defined as need for renal replacement therapy.

Results
First measured CI was median 1.7 (1.4–2.1) l/min/m2, and first measured SvO2 was median 67 (61–73) %. CI < median with SvO2 > median was present in 222 (39%), and low SvO2 with CI < median was present in 59 (11%). Spline analysis indicated that SvO2 value < 55% was associated with poor outcome. Low CI at admission was not significantly associated with mortality in multivariable analysis (p = 0.14). SvO2 was significantly inversely associated with mortality (hazard ratioadjusted: 0.91 (0.84–0.98) per 5% increase in SvO2, p = 0.01). SvO2 was significantly inversely associated with renal failure after adjusting for confounders (ORadjusted: 0.73 [0.62–0.86] per 5% increase in SvO2, p = 0.001). The combination of lower CI and lower SvO2 was associated with higher risk of mortality (hazard ratioadjusted: 1.54 (1.06–2.23) and renal failure (ORadjusted: 5.87 [2.34–14.73].

Conclusion
First measured SvO2 after resuscitation from OHCA was inversely associated with mortality and renal failure. If SvO2 and CI were below median, the risk of poor outcomes increased significantly.

Registration
The BOX-trial is registered at clinicaltrials.gov (NCT03141099, date 2017–30–04, retrospectively registered).

Graphical abstract
Ten-year risk assessment for cardiovascular diseases using ASCVD risk estimator plus: outcomes from hypertension and diabetes patients
Authors: Osoro Ian , Kumar Ranjeet , Sharma Amit 
Published: October 2023

Abstract
Background
Cardiovascular risk prediction models encompass numerous CVD risk factors. Available prediction models were developed from non-Asian cohorts hence we decided to evaluate the performance of the ASCVD risk estimator model and the associated 10-year CVD predisposing factors in Punjab.

Methods
We carried out a cross-sectional study among patients having hypertension and diabetes mellitus in a tertiary hospital in Punjab, India. 201 participants without ASCVD who were ≥ 40 years old and had been admitted to the medical ward were assessed. a pre-validated questionnaire was used to collect data on the socio-demographics and behavioral patterns. Lipid profile and blood pressure measurements were collected as per standard protocols. The respondents’ CVD risk was assessed using ASCVD Risk Estimator Plus. Data were analyzed using IBM SPSS version 26; bivariate analysis was done using Chi-square and binary logistic regression was used to identify the predictors of 10-year risk for CVD at a 5% level of significance.
Measurements.
We examined the stratification of the predicted outcomes and evaluated the associations between individual risk factors and the predicted cardiovascular events. Our study categorized the results of these outcomes into 4 categories: low category (1–5%), borderline category (6–9%) intermediate category (10–20%), and high category (21–95%).

Results
Out of the 201 participants that enrolled in our study, the majority 76 (37.8%) were in the intermediate category, 56 (27.9%) were in the high category, 41 (20.4%) were in the borderline category, 28 (13.9%) were in the low category. The median ASCVD percentage was 14.20%. Respondents who were alcoholics, smokers, and drug abusers (OR = 5.8, 95% CI 0.397–83.584) were associated with the highest likelihood of developing CVDs. Furthermore, males had a significantly higher mean predicted CVD outcome % (M = 23.18%) compared to females (M = 14.91%).

Conclusion
According to our prediction study, it was discovered that 145 (72.1%) participants were not likely to have had an ASCVD in the next 10 years. However, middle-aged males should be more cautious with their lifestyle habits, particularly in dealing with risk factors that can expose them to CVDs.
Multi-tissue epigenetic analysis identifies distinct associations underlying insulin resistance and Alzheimer’s disease at CPT1A locus
Authors: Sarnowski Chloé , Huan Tianxiao , Ma Yiyi , Joehanes Roby , Beiser Alexa , DeCarli Charles S. , Heard-Costa Nancy L. , Levy Daniel , Lin Honghuang , Liu Ching-Ti , Liu Chunyu , Meigs James B. , Satizabal Claudia L. , Florez Jose C. , Hivert Marie-France , Dupuis Josée , De Jager Philip L. , Bennett David A. , Seshadri Sudha , Morrison Alanna C. 
Published: October 2023

AbstractBackgroundInsulin resistance (IR) is a major risk factor for Alzheimer’s disease (AD) dementia. The mechanisms by which IR predisposes to AD are not well-understood. Epigenetic studies may help identify molecular signatures of IR associated with AD, thus improving our understanding of the biological and regulatory mechanisms linking IR and AD.MethodsWe conducted an epigenome-wide association study of IR, quantified using the homeostatic model assessment of IR (HOMA-IR) and adjusted for body mass index, in 3,167 participants from the Framingham Heart Study (FHS) without type 2 diabetes at the time of blood draw used for methylation measurement. We identified DNA methylation markers associated with IR at the genome-wide level accounting for multiple testing (P < 1.1 × 10−7) and evaluated their association with neurological traits in participants from the FHS (N = 3040) and the Religious Orders Study/Memory and Aging Project (ROSMAP,N = 707). DNA methylation profiles were measured in blood (FHS) or dorsolateral prefrontal cortex (ROSMAP) using the Illumina HumanMethylation450 BeadChip. Linear regressions (ROSMAP) or mixed-effects models accounting for familial relatedness (FHS) adjusted for age, sex, cohort, self-reported race, batch, and cell type proportions were used to assess associations between DNA methylation and neurological traits accounting for multiple testing.ResultsWe confirmed the strong association of blood DNA methylation with IR at three loci (cg17901584–DHCR24, cg17058475–CPT1A, cg00574958–CPT1A, and cg06500161–ABCG1). In FHS, higher levels of blood DNA methylation at cg00574958 and cg17058475 were both associated with lower IR (P = 2.4 × 10−11andP = 9.0 × 10–8), larger total brain volumes (P = 0.03 andP = 9.7 × 10−4), and smaller log lateral ventricular volumes (P = 0.07 andP = 0.03). In ROSMAP, higher levels of brain DNA methylation at the same twoCPT1Amarkers were associated with greater risk of cognitive impairment (P = 0.005 andP = 0.02) and higher AD-related indices (CERAD score:P = 5 × 10−4and 0.001; Braak stage:P = 0.004 andP = 0.01).ConclusionsOur results suggest potentially distinct epigenetic regulatory mechanisms between peripheral blood and dorsolateral prefrontal cortex tissues underlying IR and AD atCPT1Alocus.
Progressive mechanical and structural changes in anterior cerebral arteries with Alzheimer’s disease
Authors: Liu Xiaozhu , Halvorsen Samuel , Blanke Nathan , Downs Margaret , Stein Thor D. , Bigio Irving J. , Zaia Joseph , Zhang Yanhang 
Published: October 2023

AbstractAlzheimer's disease (AD) is a neurodegenerative disease and the main cause for dementia. The irreversible neurodegeneration leads to a gradual loss of brain function characterized predominantly by memory loss. Cerebrovascular changes are common neuropathologic findings in aged subjects with dementia. Cerebrovascular integrity is critical for proper metabolism and perfusion of the brain, as cerebrovascular remodeling may render the brain more susceptible to pulse pressure and may be associated with poorer cognitive performance and greater risk of cerebrovascular events. The objective of this study is to provide understanding of cerebrovascular remodeling with AD progression. Anterior cerebral arteries (ACAs) from a total of 19 brain donor participants from controls and pathologically diagnosed AD groups (early—Braak stages I-II; intermediate—Braak stages III-IV; and advanced—Braak stages V-VI) were included in this study. Mechanical testing, histology, advanced optical imaging, and mass spectrometry were performed to study the progressive structural and functional changes of ACAs with AD progression. Biaxial extension-inflation tests showed that ACAs became progressively less compliant, and the longitudinal stress in the intermediate and advanced AD groups was significantly higher than that from the control group. With pathological AD development, the inner and outer diameters of the ACAs remained almost unchanged; however, histology study revealed progressive smooth muscle cell atrophy and loss of elastic fibers which led to compromised structural integrity of the arterial wall. Multiphoton imaging demonstrated elastin degradation at the media-adventitia interface, which led to the formation of an empty band of 21.0 ± 15.4 μm and 32.8 ± 9.24 μm in width for the intermediate and advanced AD groups, respectively. Furthermore, quantitative birefringence microscopy showed disorganized adventitial collagen with AD development. Mass spectrometry analysis provided further evidence of altered collagen content and other extracellular matrix (ECM) molecule and smooth muscle cell changes that were consistent with the mechanical and structural alterations. Collectively, our study provides understanding of the mechanical and structural cerebrovascular deterioration in cerebral arteries with AD, which may be related to neurodegenration and pathology in the brain.
PACAP–Sirtuin3 alleviates cognitive impairment through autophagy in Alzheimer’s disease
Authors: Wang Qing , Wang Yue , Li Shiping , Shi Jiong 
Published: October 2023

Abstract
Background
Autophagy is vital in the pathogenesis of neurodegeneration. Thus far, no studies have specifically investigated the relationship between pituitary adenylate cyclase-activating polypeptide (PACAP) and autophagy, particularly in the context of Alzheimer’s disease (AD). This study used in vitro and in vivo models, along with clinical samples, to explore interactions between PACAP and autophagy in AD.

Methods
AD model mice were administered 6 μl of 0.1 mg/ml PACAP liquid intranasally for 4 weeks, then subjected to behavioral analyses to assess the benefits of PACAP treatment. The underlying mechanisms of PACAP-induced effects were investigated by methods including real-time quantitative polymerase chain reaction, RNA sequencing, immunofluorescence, and western blotting. Exosomes were extracted from human serum and subjected to enzyme-linked immunosorbent assays to examine autophagy pathways. The clinical and therapeutic implications of PACAP and autophagy were extensively investigated throughout the experiment.

Results
Impaired autophagy was a critical step in amyloid β (Aβ) and Tau deposition; PACAP enhanced autophagy and attenuated cognitive impairment. RNA sequencing revealed three pathways that may be involved in AD progression: PI3K-AKT, mTOR, and AMPK. In vivo and in vitro studies showed that sirtuin3 knockdown diminished the ability of PACAP to restore normal autophagy function, resulting in phagocytosis dysregulation and the accumulation of pTau, Tau, and Aβ. Additionally, the autophagic biomarker MAP1LC3 demonstrated a positive association with PACAP in human serum.

Conclusions
PACAP reverses AD-induced cognitive impairment through autophagy, using sirtuin3 as a key mediator. MAP1LC3 has a positive relationship with PACAP in humans. These findings provide insights regarding potential uses of intranasal PACAP and sirtuin3 agonists in AD treatment.

Trial registration
NCT04320368.
Refractory drug-induced systemic small-vessel vasculitis with two varied extracutaneous manifestations: a case report and review of the literature
Authors: Jovanovic Mark , Sabovic Miso 
Published: October 2023

Abstract
Background
Clopidogrel and ticagrelor are rarely reported to cause vasculitis via drug hypersensitivity reaction, largely mediated by T cells and immunoglobulin E (IgE). Despite therapeutic advances, the etiology of refractory vasculitides remains incompletely understood. Recently, (non)immunological mechanisms bypassing T cells and IgE have been proposed to explain resistance to standard immunosuppressants. Herein, we report a case of refractory drug-induced systemic small-vessel vasculitis with varied extracutaneous manifestations and incorporate multiple sources of data to provide detailed accounts of complex (non)immunological phenomena involved in this case. Study objectives are to provide an insight about rare presentations of commonly used drugs, upgrade the pathophysiological concepts of drug-induced vasculitis, raise need for further investigation to define causes and risk factors for refractory vasculitis, and discuss most of the current knowledge suggesting novel therapeutic approaches to treat this vasculitis. To our knowledge, this is the first case of the two flares of systemic small-vessel vasculitis in a single patient in response to clopidogrel and ticagrelor exposure, respectively. However, this report is limited by attribution/observer bias.

Case presentation
We herein report a 24-year-old Caucasian male student with a medical history of mild seasonal allergic rhinoconjunctivitis, tension-type headaches, posttraumatic arterial stenosis, and previous exposure to ibuprofen, acetylsalicylic acid, and mRNA coronavirus disease 2019 (COVID-19) vaccine who suffered largely from acute urticaria and dyspnea after 20 days of acetylsalicylic acid and clopidogrel introduction. A skin punch biopsy confirmed leukocytoclastic vasculitis. Serologic antibody testing, complement analysis, microbiologic testing, and cancer biomarkers revealed no abnormalities. Regarding the patient’s medical history, both acetylsalicylic acid and clopidogrel were exchanged for ticagrelor. Furthermore, the addition of naproxen, cyclosporine, bilastine, prednisolone, and montelukast resulted in complete recovery. After 7 days, diarrhea and hematuria occurred. Urinalysis and computed tomography showed reversible proteinuria with gross hematuria and hypodense changes in kidney medulla, respectively, associated with discontinuation of ticagrelor and naproxen. In addition, the patient recovered completely without any immunosuppression up-titration.

Conclusions
This case highlights the role of clopidogrel and ticagrelor as possible triggering agents for systemic small-vessel vasculitis and offers an insight into novel therapeutic strategies for refractory vasculitides. Further research is needed to build on the findings of a current report.