bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol and apolipoprotein B for cardiovascular care
Authors: Bilgic Selin , Sniderman Allan D. 
Published: November 2023

Purpose of review
Some experts and consensus groups continue to argue that apolipoprotein B (apoB) should not be introduced broadly into clinical care. But, too often, the present approach to clinical care is not succeeding. An important reason for this failure, we believe, is that the conventional approach limits what the expert clinician can accomplish and is too complex, confusing, and contradictory for primary care physicians to apply effectively in their practise.

Recent findings
There are four major reasons that apoB should be measured routinely in clinical care. First, apoB is a more accurate marker of cardiovascular risk than LDL-C or non-HDL-C. Second, the measurement of apoB is standardized whereas the measurements of LDL-C and non-HDL-C are not. Third, with apoB and a conventional lipid panel, all the lipid phenotypes can be simply and accurately distinguished. This will improve the care of the expert. Fourth, apoB, as the single measure to evaluate the success of therapy, would simplify the process of care for primary care physicians.

Summary
By introducing apoB broadly into clinical care, the process of care will be improved for both the expert and the primary care physician, and this will improve the outcomes of care.
The Impact of Resilience and Perceived Autonomy Support on Medication Adherence Among Rural Older Adults With Hypertension
Authors: Besel Jamie M. , Insel Kathleen C. , Williams Geoffrey C. 
Published: November 2023

Background
Adherence to antihypertension medications has been explored in previous studies; however, these studies generally focus on individuals who reside in urban areas. Improved understanding is needed regarding rural older adults who are self-managing medications for hypertension and the motivational factors that may influence adherence.

Objectives
The purpose of this study was to examine medication adherence among rural older adults with hypertension and the association with motivational factors as defined in self-determination theory, including quality of motivation (autonomous vs controlled), perceived competence, perceived autonomy support, and basic psychological needs satisfaction. Rural nursing theory was also used to explore the concept of resilience.

Methods
This cross-sectional study involved 80 older adults (≥65 years old) self-managing at least 1 prescribed medication for managing their hypertension. Participants ranged in age from 65 to 89 (mean [SD], 74.04 [6.18]) years from rural areas in the northwest. Participants completed a demographic questionnaire, a measure of medication adherence, and questionnaires to assess perceived autonomy support, basic needs satisfaction, autonomous and controlled motivation, perceived competence, and resilience.

Results
Correlational analysis and multiple regression were used to examine associations and predict adherence. Perceived autonomy support, resilience, cost of medication, and medication regimen complexity were the only variables significantly associated with medication adherence and predicted adherence. Resilience mediated the relationship between perceived autonomy support and medication adherence.

Conclusions
Overall, findings indicate high levels of adherence. Interventions that enhance perceptions of autonomy support and resilience may be useful in managing hypertension.
Pediatric interventional bronchoscopy: from early limitations to achievable opportunities
Authors: Januska Megan N. , Kaspy Kimberley , Bozkanat Kubra M. , Vicencio Alfin G. 
Published: November 2023

Purpose of review
The rapid evolution of bronchoscopy equipment and technologies, from the introduction of the 1.1 mm flexible cryoprobe to the use of navigational and robotic bronchoscopy, has afforded unprecedented opportunities for pediatric advanced diagnostic and interventional bronchoscopy. While there is growing interest among pediatric pulmonologists to incorporate these new techniques into their practice, the current pediatric landscape is characterized by few practicing interventional bronchoscopists, scant published literature, and no formal training programs.

Recent findings
While the majority of the published literature consists of case reports and small case series, the increased application of new techniques is starting to yield larger and more structured studies that will be able to provide more objective commentary on the proposed indications, safety, and efficacy of such techniques in the pediatric population.

Summary
For many decades, progress in pediatric advanced diagnostic and interventional bronchoscopy was slow and deliberate, limited by the lack of appropriately sized equipment and experienced interventional bronchoscopists. The current opportunities afforded require equal, or perhaps even more, vigilance as pediatric pulmonologists employ new equipment and technologies and define new practices and standards of care. Importantly, this review is meant to serve as a general conspectus of pediatric advanced diagnostic and interventional bronchoscopy and not a consensus guideline for the performance of advanced or even routine bronchoscopy in the pediatric population. For technical standards of pediatric bronchoscopy, refer to existing guidelines [1,2].
The effect of psychological factors on pain outcomes: lessons learned for the next generation of research
Authors: Crombez Geert , Veirman Elke , Van Ryckeghem Dimitri , Scott Whitney , De Paepe Annick 
Published: November 2023

Abstract
Big data and machine learning techniques offer opportunities to investigate the effects of psychological factors on pain outcomes. Nevertheless, these advances can only deliver when the quality of the data is high and the underpinning causal assumptions are considered. We argue that there is room for improvement and identify some challenges in the evidence base concerning the effect of psychological factors on the development and maintenance of chronic pain. As a starting point, 3 basic tenets of causality are taken: (1) cause and effect differ from each other, (2) the cause precedes the effect within reasonable time, and (3) alternative explanations are ruled out. Building on these tenets, potential problems and some lessons learned are provided that the next generation of research should take into account. In particular, there is a need to be more explicit and transparent about causal assumptions in research. This will lead to better research designs, more appropriate statistical analyses, and constructive discussions and productive tensions that improve our science.
Dental Rehabilitation of the Unilateral Cleft Dental Gap: A Single Institution Experience With Long-Term Follow-Up
Authors: Lee Kevin C. , Yau Vicky , Khoshnevisan Mohammad A. , Eisig Sidney B. 
Published: November 2023

Objective:
The purpose of this study was to identify factors associated with the management of the cleft dental gap after alveolar bone grafting.

Methods:
This was a retrospective cohort study of patients with unilateral cleft lip and alveolus or palate who had successful alveolar bone grafting. Our primary study outcome was alveolar cleft management (orthodontic closure or space maintenance). Our secondary study outcome was the rate of fixed dental rehabilitation. Univariate comparisons were made with SAS 9.4.

Results:
The final study sample consisted of 54 patients. Most patients were treated with orthodontic closure (55.6%). Patients missing multiple teeth (P < 0.01) were less likely to receive orthodontic closure. Orthodontic closure was not associated with differences in intermaxillary midline coincidence (P = 0.22) or the need for LeFort advancement (P = 0.15). Only 41.7% of patients who were managed with space maintenance obtained a fixed prosthesis. Hispanic ethnicity (P < 0.01) and Medicaid insurance (P < 0.01) were associated with lower rates of fixed dental rehabilitation.

Conclusions:
Orthodontic closure was the most common approach, and it did not result in significant maxillary midline distortion. Less than half of patients treated with space maintenance obtained fixed restorations. Socioeconomic barriers are likely preventing access to definitive dental rehabilitation in patients with unilateral cleft lip and alveolus or palate.
Eliminating the benzos: A benzodiazepine-sparing approach to preventing and treating alcohol withdrawal syndrome
Authors: McCullough Mary Alyce , Miller Preston R. , Martin Tamriage , Rebo Kristin A. , Stettler Gregory R. , Martin Robert Shayn , Cantley Morgan , Shilling Elizabeth H. , Hoth James J. , Nunn Andrew M. 
Published: November 2023

BACKGROUND
Alcohol withdrawal syndrome (AWS) represents significant cost to the hospitalized trauma population from a clinical and financial perspective. Historically, AWS has been managed with benzodiazepines. Despite their efficacy, benzodiazepines carry a heavy adverse effect profile. Recently, benzodiazepine-sparing protocols for the prophylaxis and treatment of AWS have been used in medical patient populations. Most existing benzodiazepine-sparing protocols use phenobarbital, while ours primarily uses gabapentin and clonidine, and no such protocol has been developed and examined for safety and efficacy specifically within a trauma population.

METHODS
In December of 2019, we implemented our benzodiazepine-sparing protocol for trauma patients identified at risk for alcohol withdrawal on admission. Trauma patients at risk for AWS admitted to an academic Level 1 trauma center before (conventional) and after (benzodiazepine-sparing [BS]) protocol implementation were compared. Outcomes examined include morphine milligram equivalent dosing rates and lorazepam equivalent dosing rates as well as the Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) scores, hospital length of stay, intensive care unit length of stay, and ventilator days.

RESULTS
A total of 387 conventional and 134 benzodiazepine sparing patients were compared. Injury Severity Score (13 vs. 16, p = 0.10) and admission alcohol levels (99 vs. 149, p = 0.06) were similar. Patients in the BS pathway had a lower maximum daily CIWA-Ar (2.7 vs. 1.5, p = 0.04). While mean morphine milligram equivalent per day was not different between groups (31.5 vs. 33.6, p = 0.49), mean lorazepam equivalents per day was significantly lower in the BS group (1.1 vs. 0.2, p < 0.01). Length of stay and vent days were not different between the groups.

CONCLUSION
Implementation of a benzodiazepine-sparing pathway that uses primarily clonidine and gabapentin to prevent and treat alcohol withdrawal syndrome in trauma patients is safe, reduces the daily maximum CIWA-Ar, and significantly decreases the need for benzodiazepines. Future studies will focus on outcomes affected by avoiding AWS and benzodiazepines in the trauma population.

LEVEL OF EVIDENCE
Therapeutic/Care Management; Level IV.
Integrated longitudinal multi-omics study identifies immune programs associated with COVID-19 severity and mortality in 1152 hospitalized participants
Authors: Gygi Jeremy P. , Maguire Cole , Patel Ravi K. , Shinde Pramod , Konstorum Anna , Shannon Casey P. , Xu Leqi , Hoch Annmarie , Jayavelu Naresh Doni , Network IMPACC , Haddad Elias K. , Reed Elaine F. , Kraft Monica , McComsey Grace A. , Metcalf Jordan , Ozonoff Al , Esserman Denise , Cairns Charles B. , Rouphael Nadine , Bosinger Steven E. , Kim-Schulze Seunghee , Krammer Florian , Rosen Lindsey B. , van Bakel Harm , Wilson Michael , Eckalbar Walter , Maecker Holden , Langelier Charles R. , Steen Hanno , Altman Matthew C. , Montgomery Ruth R. , Levy Ofer , Melamed Esther , Pulendran Bali , Diray-Arce Joann , Smolen Kinga K. , Fragiadakis Gabriela K. , Becker Patrice M. , Augustine Alison D. , Sekaly Rafick P. , Ehrlich Lauren I. R. , Fourati Slim , Peters Bjoern , Kleinstein Steven H. , Guan Leying 
Published: November 2023

AbstractHospitalized COVID-19 patients exhibit diverse clinical outcomes, with some individuals diverging over time even though their initial disease severity appears similar. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity. In this study, we carried out deep immunophenotyping and conducted longitudinal multi-omics modeling integrating ten distinct assays on a total of 1,152 IMPACC participants and identified several immune cascades that were significant drivers of differential clinical outcomes. Increasing disease severity was driven by a temporal pattern that began with the early upregulation of immunosuppressive metabolites and then elevated levels of inflammatory cytokines, signatures of coagulation, NETosis, and T-cell functional dysregulation. A second immune cascade, predictive of 28-day mortality among critically ill patients, was characterized by reduced total plasma immunoglobulins and B cells, as well as dysregulated IFN responsiveness. We demonstrated that the balance disruption between IFN-stimulated genes and IFN inhibitors is a crucial biomarker of COVID-19 mortality, potentially contributing to the failure of viral clearance in patients with fatal illness. Our longitudinal multi-omics profiling study revealed novel temporal coordination across diverse omics that potentially explain disease progression, providing insights that inform the targeted development of therapies for hospitalized COVID-19 patients, especially those critically ill.
Voltage-gated T-type calcium channel blockers reduce apoptotic body mediated SARS-CoV-2 cell-to-cell spread and subsequent cytokine storm
Authors: Phan Thanh Kha , Sheerin Dylan , Shi Bo , Dayton Merle , Mackewicz Liana , Ozkocak Dilara C. , Atkin-Smith Georgia , Peton Nashied , Audi Omar , Tixeira Rochelle , Ashdown George , Davidson Kathryn C. , Doerflinger Marcel , Coussens Anna K. , Poon Ivan K. H. 
Published: November 2023

ABSTRACTSARS-CoV-2 typically utilises host angiotensin-converting enzyme 2 (ACE2) as a cellular surface receptor and host serine protease TMPRSS2 for the proteolytic activation of viral spike protein enabling viral entry. Although macrophages express low levels of ACE2, they are often found positive for SARS-CoV-2 in autopsied lungs from COVID-19 patients. As viral-induced macrophage inflammation and overwhelming cytokine release are key immunopathological events that drives exacerbated tissue damage in severe COVID-19 patients, insights into the entry of SARS-CoV-2 into macrophages are therefore critical to understand COVID-19 pathogenesis and devise novel COVID-19 therapies. Mounting evidence suggest that COVID-19 pathogenesis is associated with apoptosis, a type of programmed cell death that often leads to the release of numerous large extracellular vesicles (EVs) called apoptotic bodies (ApoBDs). Here, we showed that ApoBDs derived from SARS-CoV-2-infected cells carry viral antigens and infectious virions. Human monocyte-derived macrophages readily efferocytosed SARS-CoV-2-induced ApoBDs, resulting in SARS-CoV-2 entry and pro-inflammatory responses. To target this novel ApoBD-mediated viral entry process, we screened for ApoBD formation inhibitors and discovered that T-type voltage-gated calcium channel (T-channel) blockers can inhibit SARS-CoV-2-induced ApoBD formation. Mechanistically, T-channel blockers impaired the extracellular calcium influxes required for ApoBD biogenesis. Importantly, blockade of ApoBD formation by T-channel blockers were able to limit viral dissemination and virus-induced macrophage inflammationin vitroand in a pre-clinical mouse model of severe COVID-19. Our discovery of the ApoBD-efferocytosis-mediated viral entry reveals a novel route for SARS-CoV-2 infection and cytokine storm induction, expanding our understanding of COVID-19 pathogenesis and offering new therapeutic avenues for infectious diseases.
Do more food choices lead to bad decisions? A case study in predacious ladybird beetle,Propylea dissecta
Authors: Verma Lata , Mishra Geetanjali , Omkar  
Published: November 2023

AbstractUnderstanding why animals choose one food over another is one of the key questions underlying the fields of behaviour ecology. This study aims to test if ladybird beetles,Propylea dissectaMulsant (Coleoptera: Coccinellidae) can forage selectively for nutrients in order to redress specific nutritional imbalances to maximise their fitness. The general approach was, first, to manipulate the nutritional status of the predator by rearing them in five separate pre-treatment dietary groups from first instar larvae to newly emerged adult stage. Thereafter, we tested their feeding response to five different types of food, i.e.,Aphis craccivoraKoch,Aphis neriiBoyer de Fonsclombe, conspecific eggs, heterospecific eggs and mixed pollen grains, equidistantly placed in Petri dish. On the basis of newly emerged adults’ food choice, they were reared on the same diet for 10 days. Thereafter, adults were paired with their opposite sex (collected from stock culture reared onA.craccivora) and mating and reproductive parameters were recorded. Our results suggested that the variety of food did not affect the preference of ladybird beetle,P. dissecta. They tend to choose their natural diet,i.e., aphid in each dietary regime. We found that previous dietary regime significantly influences the mating and reproductive parameters of both the male and female except for the time to commence mating by the male. Food choices of adult beetles were found to significantly influence the time to commence mating, average fecundity and percent egg viability in males and the mating duration in females.
Activated NK Cells with Pro-inflammatory Features are Associated with Atherogenesis in Perinatally HIV-Acquired Adolescents
Authors: Alles Mario , Gunasena Manuja , Kettelhut Aaren , Ailstock Kate , Musiime Victor , Kityo Cissy , Richardson Brian , Mulhern Will , Tamilselvan Banumathi , Rubsamen Michael , Kasturiratna Dhanuja , Demberg Thorsten , Cameron Cheryl M. , Cameron Mark J. , Dirajlal-Fargo Sahera , Funderburg Nicholas T. , Liyanage Namal P.M. 
Published: November 2023

AbstractHuman immunodeficiency virus (HIV) is associated with persistent immune activation and dysfunction in people with HIV despite treatment with antiretroviral therapy (ART). Modulation of the immune system may be driven by: low-level HIV replication, co-pathogens, gut dysbiosis /translocation, altered lipid profiles, and ART toxicities. In addition, perinatally acquired HIV (PHIV) and lifelong ART may alter the development and function of the immune system. Our preliminary data and published literature suggest reprogramming innate immune cells may accelerate aging and increase the risk for future end-organ complications, including cardiovascular disease (CVD). The exact mechanisms, however, are currently unknown. Natural killer (NK) cells are a highly heterogeneous cell population with divergent functions. They play a critical role in HIV transmission and disease progression in adults. Recent studies suggest the important role of NK cells in CVDs; however, little is known about NK cells and their role in HIV-associated cardiovascular risk in PHIV adolescents. Here, we investigated NK cell subsets and their potential role in atherogenesis in PHIV adolescents compared to HIV-negative adolescents in Uganda. Our data suggest, for the first time, that activated NK subsets in PHIV adolescents may contribute to atherogenesis by promoting plasma oxidized low-density lipoprotein (Ox-LDL) uptake by vascular macrophages.
HDL Particle Concentration and Size Predict Incident Coronary Artery Disease Events in People with Type 1 Diabetes
Authors: Costacou Tina , Vaisar Tomas , Miller Rachel G. , Davidson W. Sean , Heinecke Jay W. , Orchard Trevor J. , Bornfeldt Karin E. 
Published: November 2023

AbstractBackgroundCholesterol efflux capacity (CEC) negatively correlates with cardiovascular disease risk. Small HDL particles account almost quantitively for CEC, perhaps mediated through efflux of outer leaflet plasma membrane phospholipids by ABCA1. People with type 1 diabetes (T1D) are at increased risk of coronary artery disease (CAD) despite normal levels of HDL-cholesterol (HDL-C). We therefore tested the hypotheses that small HDL particles (HDL-P)—rather than HDL-C levels—predict incident CAD in T1D.MethodsIncident CAD (CAD death, myocardial infarction, and/or coronary revascularization) was determined in a cohort of 550 participants with childhood-onset T1D. HDL-P was quantified by calibrated ion mobility analysis. CEC and phospholipid efflux were quantified with validated assays.ResultsDuring a median follow-up of 26 years, 36.5% of the participants developed incident CAD. In multivariable Cox models, levels of HDL-C and apolipoprotein A-I (APOA1) did not predict CAD risk. In contrast, extra-small HDL particle levels strongly and negatively predicted risk (hazard ratio [HR]=0.25, 95% confidence interval [CI]=0.13–0.49). An increased concentration of total HDL particles (T-HDL-P) (HR=0.87, CI=0.82–0.92) and three other HDL sizes were weaker predictors of risk: small HDL (HR=0.80, 0.65-0.98), medium HDL (HR=0.78, CI=0.70–0.87) and large HDL (HR=0.72, CI=0.59–0.89). Although CEC negatively associated with incident CAD, that association disappeared after the model was adjusted for T-HDL-P. Isolated small HDLs strongly promoted ABCA1-dependent efflux of membrane outer leaflet phospholipids.ConclusionsLow concentrations of T-HDL-P and all four sizes of HDL subpopulations predicted incident CAD independently of HDL-C, APOA1, and other common CVD risk factors. Extra-small HDL was a much stronger predictor of risk than the other HDLs. Our data are consistent with the proposal that small HDLs play a critical role in cardioprotection in T1D, which might be mediated by macrophage plasma membrane outer leaflet phospholipid export and cholesterol efflux by the ABCA1 pathway.