bluuebunny/crossref_metadata_2025_split huggingface dataset:
Organizational and Individual Contributing Factors to Safety Climate in Healthcare Industries—Bayesian Network Predictive Modeling Approach
Authors: He Yimin , Lee Jin , Huang Yueng-Hsiang , Hu Changya 
Published: August 2024

Objectives
The current study aims to identify individual and joint drivers that significantly influence the safety climate in healthcare industries by using Bayesian network (BN) simulations for an in-depth analysis.

Methods
Survey data were collected from 452 employees from two branches of one hospital in China for a study about workplace safety. The original English surveys were translated into Chinese using the back-translation procedure recommended by Brislin. Employees were asked to complete two online surveys with 1 month in between each administration. The sample was 42% doctors and 58% nurses. A BN model, based on theory, was updated and complemented with expert knowledge. A graphical model based on expert knowledge and data-driven machine learning approaches was used to refine the BN structure, representing interrelationships among all studied variables. The BN model was employed to identify the best key drivers and joint strategies for safety climate improvement.

Results
The BN model demonstrated a good overall fit. The Euclidean distance metric was used to assess the influence between connected variables, with interpersonal trust and locus of control having the strongest independent effects on safety climate among the five contributing factors. Joint strategies, particularly joint optimization of error disclosure culture and interpersonal trust, as well as error disclosure culture and self-efficacy, were most effective in promoting a safe climate.

Conclusions
The findings suggest that hospital safety climate can be improved by providing a psychologically safe error disclosure culture and enhancing interpersonal trust among employees and their self-efficacy.
Implications of frailty before and after intensive care unit admission
Authors: Gordon Joshua I. , Brummel Nathan E. 
Published: August 2024

Purpose of review
In the decade since the first publications related to frailty in those with critical illness, the study of frailty has rapidly increased. The purpose of this review is to update the reader on recent advances across several important areas of frailty research: how best to identify frailty in those with critical illness, studies describing the relationship between frailty and delirium, and how frailty affects outcomes for those with coronavirus disease 2019 (COVID-19), which, despite rates and severity of acute infection declining, still tremendously impacts patients long after the acute infection, resulting in symptoms of long COVID-19.

Recent findings
A number of frailty assessment tools exist, to date, the Clinical Frailty Scale based on the deficit accumulation approach to defining frailty, is the most commonly used in ICU studies. Several novel frailty instruments for the ICU are being developed. Because tools assessing frailty by the phenotypic and deficit accumulation approaches identify different populations, careful choice of a frailty assessment tool is warranted.
Frailty and delirium are hypothesized to represent different clinical expressions of a similar underlying vulnerability, thus identifying frailty may be a useful means by which to identify patients at high risk of becoming delirious. Recent studies show that frailty at ICU admission is a predictor of the development of delirium.
Finally, frailty and its outcomes were studied in patients with COVID-19. As with other causes of critical illness, frailty was highly prevalent in those admitted to the ICU and is associated with greater mortality. Frailty was also associated with increased decisions to limit life support treatments, but these decisions were not different among those admitted with COVID-19 or for other reasons.

Summary
Frailty in those with critical illness is an emerging field of study. Future work to define the optimal means by which to identify this syndrome and how best to manage critically ill patients with frailty are needed.
Progress in physiologically based pharmacokinetic-pharmacodynamic models of amino acids in humans
Authors: McColl Taylor J. , Clarke David C. 
Published: August 2024

Purpose of review
Amino acids are critical to health, serving both as constituents of proteins and in signaling and metabolism. Amino acids are consumed as nutrients, supplements, and nutraceuticals. Much remains to be learned about amino acid function. Physiologically based pharmacokinetic and pharmacodynamic (PBPK-PD) modeling is an emerging tool for studying their complex biology. This review highlights recent PBPK-PD models developed to study amino acid physiology and metabolism and discusses their potential for addressing unresolved questions in the field.

Recent findings
PBPK-PD models provided several insights. They revealed the interplay between the mechanisms by which leucine governs skeletal muscle protein metabolism in healthy adults. The models also identified optimal dosing regimens of amino acid supplementation to treat sickle-cell disease and recurrent hypoglycemia, and to minimize drug side effects in seizure disorders. Additionally, they characterized the effects of novel anticancer drugs that seek to deprive cancer cells of amino acids. Future models may inform treatment strategies for sarcopenia, characterize distinctions between animal- and plant-based nutrition, and inform nutrient-drug interactions in Parkinson's disease.

Summary
PBPK-PD models are powerful tools for studying amino acid physiology and metabolism, with applications to nutrition, pharmacology, and their interplay.
Regurgitation, eructation, and supragastric belch: retrograde esophageal motility, disorders, and treatment
Authors: Patel Pooja , Layne Sabrina , Leiman David A. 
Published: August 2024

Purpose of review
This review describes pathologic conditions of retrograde flow into the esophagus along with recent therapeutic advances and treatment options.

Recent findings
The esophagus facilitates anterograde and retrograde movement of contents, the latter of which is mediated by transient lower esophageal sphincter relaxations (TLESRs). Gastroesophageal reflux disease (GERD) often includes esophageal-specific symptoms such as heartburn or regurgitation. Volume regurgitation responds less frequently to acid suppression with proton pump inhibitors (PPIs) than heartburn, given its relationship with incompetence of the esophagogastric junction (EGJ) and increased frequency of TLESRs. Therefore, although the refluxate pH can be altered with PPIs, the frequency of reflux episodes is generally not reduced and surgical and endoscopic treatments may be favored. Other instances of abnormal retrograde esophageal flow respond better to medical therapy, or lifestyle interventions. Compared to gastric belching because of increased stomach distension, supragastric belching is caused by intake of air from pharynx into the esophagus followed by rapid expulsion of air. These conditions can be distinguished on esophageal tests such as high-resolution manometry and are likely to respond to behavioral modifications.

Summary
Retrograde flow into the esophagus can be a normal occurrence, but diagnostic testing to distinguish causes can guide appropriate intervention.
The Brussels Breast Surgery Fellowship | A Three-Month Experience in Advancing Skills in Breast Surgery
Authors: Kyriazidis Ioannis 
Published: August 2024

Abstract
The Brussels Breast Surgery Fellowship at Brussels University Hospital offers a unique 3-month clinical immersion in reconstructive and aesthetic breast surgery. Under the guidance of fellowship director Prof. Moustapha Hamdi and his esteemed colleagues, the fellow is exposed to a high volume and wide breadth of cases spanning autologous and implant-based breast reconstruction, oncoplastic surgery, breast reduction and mastopexy, implant augmentation, revision breast surgery, and fat grafting. The multidisciplinary team approach, involving close collaboration with breast surgeons, provides valuable experience in oncoplastic planning and execution. In addition to time in the operating theater, the fellow gains knowledge through outpatient clinics, didactic teaching sessions, and clinical research opportunities leveraging the department's extensive prospective database. As the 2023 fellowship awardee, I had the privilege of learning directly from Prof. Dr. Moustapha Hamdi and participating in over 130 cases across the reconstructive and aesthetic spectrum. Unique features of the fellowship included exposure to lymphedema surgery utilizing the Symani robotic system, advanced techniques like the internal bra, volume distribution mastopexies, observation of private aesthetic clinic cases, and optional participation in academic workshops. This fellowship represents an outstanding opportunity to refine one's skills in breast surgery and microsurgery while experiencing the rich culture of Belgium.
Does Inter-Eye Asymmetry of Disc Area Explain Differences in Onset of Nonarteritic Anterior Ischemic Optic Neuropathy?
Authors: Singh Shonar , Guillot Florian H. , Henderson Amanda D. , Carey Andrew R. 
Published: August 2024

Background:
Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common acute optic neuropathy in individuals over the age of 50 years. It is associated with conventional vascular risk factors and structural vulnerabilities including “disc-at-risk.” We aim to ascertain if a correlation exists between optic nerve head size and the onset of NAION.

Methods:
We performed a retrospective chart review of patients with an ICD-10 diagnosis of unilateral or bilateral NAION who underwent optical coherence tomography (OCT) and visual field testing. The primary outcome measure was the disc area as measured on OCT at a follow-up (minimum 6 months after acute vision loss) of the involved (or first involved for bilateral cases) vs fellow eye. The secondary outcome was the cup-to-disc ratio (CDR) of the first vs fellow eye.

Results:
Seventy-three patients were included, of which 58 (79%) had unilateral and 15 (21%) had bilateral NAION, with a median follow-up of 23 months. Between the first eye involved and the fellow eye, there were no statistically significant differences in the mean disc area (1.69 ± 0.29 vs 1.71 ± 0.29, P = 0.7). However, average CDR (0.41 ± 0.20 vs 0.28 ± 0.18, P < 0.001) and vertical CDR (0.42 ± 0.20 vs 0.28 ± 0.19, P < 0.0001) were significantly larger in the involved eye.

Conclusions:
Despite no statistically significant differences in the disc area between the affected eye and the fellow eye, CDR was larger in eyes with a history of NAION compared with fellow eyes. Further research is required to elucidate local factors that may increase the risk of NAION in one eye relative to the other.
The bioavailability of compounded and generic rapamycin in normative aging individuals: A retrospective study and review with clinical implications
Authors: Harinath Girish , Lee Virginia , Nyquist Andy , Moel Mauricio , Wouters Maartje , Hagemeier Jesper , Verkennes Brandon , Tacubao Colleen , Kauppi Krister , Morgan Stefanie L. , Isman Anar , Zalzala Sajad 
Published: August 2024

AbstractRapamycin, also known as sirolimus, has demonstrated great potential for application in longevity medicine. However, the bioavailability of generic and compounded rapamycin at longevity doses in normative aging individuals remains unknown. We conducted a retrospective, real-world study determining the 24-hour blood rapamycin levels to establish the relative bioavailability, dose-to-blood level linearity and inter-individual heterogeneity in a normative aging cohort. Participants received either compounded rapamycin (n = 23, dosages 5, 10, or 15 mg) or generic rapamycin (n= 44, dosages 2, 3, 6, or 8 mg) once per week, and were asked to obtain a sirolimus level blood draw 24 hours after dose self-administration. Similar blood rapamycin levels and a linear dose-to-blood level relationship were observed for both formulations, although a higher bioavailability per milligram of rapamycin was noted for the generic formulation (compounded averaged 0.287 (28.7%) bioavailability relative to generic rapamycin in (ng/mL) / mg rapamycin). While substantial inter-individual heterogeneity in blood rapamycin levels was observed for both formulations, repeat tests for individuals demonstrated high test-retest reliability. As we detected no significant association between bioavailability and measures of body mass index (BMI), sex, age, or length of time taking rapamycin, we suggest that individualized dosing and routine monitoring of blood rapamycin levels should be applied to ensure optimal longevity efficacy. Finally, we contextualize our data with a brief review of the literature on the currently available knowledge of rapamycin’s bioavailability in normative aging populations, and provide implications for the clinical use of rapamycin in longevity medicine moving forward.
Comparison of four intensive care scores in prediction of outcome after Veno-Arterial ECMO: A single center retrospective study
Authors: Sudarsanan Suraj , Sivadasan Praveen , Chandra Prem , Omar Amr S , Atuel Kathy Lynn Gaviola , Lone Hafeez Ulla , Ragab Hany O , Ehsan Irshad , Carr Cornelia S , Pattath Abdulrasheed , Al khulaifi Abdulaziz , Shouman Yasser Mahfouz Eltokhy , Al Mulla A/Wahid Mahmoud A.A. 
Published: August 2024

AbstractBackgroundAssess the ability of APACHE II (acute physiology and chronic health evaluation II), SOFA (sequential organ failure assessment scores), Cardiac Surgery Score (CASUS) and SAVE (Survival after VA-ECMO) to predict outcomes in a cohort of patients undergoing Veno-Arterial ECMO (VA-ECMO).MethodsObservational retrospective study of all patients admitted to Cardiothoracic Intensive Care Unit (CTICU) for a minimum duration of 24 hours after undergoing VA-ECMO insertion between years 2015 to 2022. Scores for APACHE II, SOFA and CASUS were calculated at 24 after ICU admission. SAVE score was calculated from the last available patient details within 24 hours of ECMO insertion. Demographic, clinical, and laboratory data relevant for the study was retrieved from electronic patient records.ResultsPre-ECMO serum levels of lactates and creatinine were significantly associated with mortality. Lower ECMO flow rates at 4 hours and 12 hours after ECMO cannulation was significantly associated with survival to discharge. Development of arrythmias, acute kidney injury (AKI) and need of continuous renal replacement therapy (CRRT) while on ECMO were significantly associated with mortality. The APACHE-II, SOFA and CASUS, calculated at 24 hours of ICU admission were significantly higher amongst non-survivors. Following categorization of risk scores using ROC curve analysis, it was found that APACHE-II, SOFA and CASUS calculated at 24 hours of ICU admission after ECMO insertion demonstrated moderate predictive ability for mortality whereas SAVE score failed to predict mortality. APACHE-II >27 (AUC of 0.66) calculated at 24 hours of ICU admission after ECMO insertion, demonstrated the greatest predictive ability, for mortality. Multivariate logistic regression analysis of the four scores showed that APACHE-II > 27 and SOFA > 14 calculated at 24 hours of ICU admission after ECMO insertion, were independently significantly predictive of mortality.ConclusionsThe APACHE-II, SOFA and CASUS, calculated at 24 hours of ICU admission were significantly higher amongst non-survivors as compared to survivors. APACHE-II demonstrated the best mortality predictive ability. APACHE-II scores of 27 or above, and SOFA of 14 or above at 24 hours of ICU admission after ECMO cannulation can predict mortality and will aid physicians in decision making.
A hollow fiber membrane-based liver organoid-on-a-chip model for examining drug metabolism and transport
Authors: Myszczyszyn Adam , Münch Anna , Lehmann Vivian , Sinnige Theo , van Steenbeek Frank G. , Bouwmeester Manon , Samsom Roos-Anne , Keuper-Navis Marit , van der Made Thomas K. , Kogan Daniel , Braem Sarah , van der Laan Luc J. W. , Amirabadi Hossein Eslami , van de Steeg Evita , Masereeuw Rosalinde , Spee Bart 
Published: August 2024

AbstractLiver-on-a-chip models predictive for both metabolism as well as canalicular and blood transport of drug candidates in humans are lacking. Here, we established an advanced, bioengineered and animal component-free hepatocyte-like millifluidic system based on 3D hollow fiber membranes (HFMs), recombinant human laminin 332 coating and adult human stem cell-derived organoids. Organoid fragments formed polarized and tight monolayers on HFMs with improved hepatocyte-like maturation, as compared to standard 3D organoid cultures in Matrigel from matched donors. Gene expression profiling and immunofluorescence revealed that hepatocyte-like monolayers expressed a broad panel of phase I (e.g., CYP3A4, CYP2D6) and II (UGTs, SULTs) drug-metabolizing enzymes and drug transporters (e.g., OATP1B3, MDR1 and MRP3). Moreover, statically cultured monolayers displayed phase I and II metabolism of a cocktail of six relevant compounds, including midazolam and 7-hydroxycoumarin. We also demonstrated the disposition of midazolam in the basal/blood-like circulation and apical/canalicular-like compartment of the millifluidic chip. Finally, we connected the system to the other two PK/ADME-most relevant organ systems,i.e.small intestine- and kidney proximal tubule-like to study the bioavailability of midazolam and coumarin, and excretion of metformin. In conclusion, we generated a proof-of-concept liver organoid-on-a-chip model for examining metabolism and transport of drugs, which can be further developed to predict PK/ADME profiles in humans.
The role of mitochondrial complex I in the proinflammatory response to polylactide implants
Authors: Maduka Chima V. , Makela Ashley V. , Tundo Anthony , Ural Evran , Stivers Katlin B. , Alhaj Mohammed , Narayan Ramani , Goodman Stuart B. , Ashammakhi Nureddin , Elisseeff Jennifer H. , Hankenson Kurt D. , Contag Christopher H. 
Published: August 2024

AbstractDuring the foreign body response, immune cells are metabolically rewired after exposure to breakdown products of various biomaterials, including polylactide (PLA) and polyethylene. Particles of polyethylene interact with Toll-like receptor 4 on macrophages, resulting in increased oxygen consumption that forms reactive oxygen species at complex I of the mitochondrial electron transport chain (mETC). However, PLA degradation products bind to monocarboxylate transporters for downstream signaling with elevated oxygen consumption rates, whose functional implication is unclear and remains inferred from cellular responses to polyethylene biomaterials. By chemically probing the function of the mETC, we show that proinflammatory macrophages activated by exposure to amorphous PLA (aPLA) breakdown products rely on mitochondrial respiration for ATP production, independent of oxygen consumption rates. In contrast, macrophages activated by semi-crystalline PLA (cPLA) breakdown products exhibit a metabolic phenotype wherein ATP levels are unaffected by changing oxygen consumption rates. In subcutaneous implants, the incorporation of metformin in aPLA or cPLA to chemically inhibit complex I did not effectively modulate the proinflammatory response to biomaterials, suggesting that PLA degradation products elicit a distinct metabolic program, thus providing an alternative perspective on the role of mitochondrial respiration in the inflammatory response to biomaterials.
A compact prism-based microscope for high sensitive measurements in fluid biopsy
Authors: Perego Laura , Dallari Caterina , Falciani Chiara , Pini Alessandro , Gardini Lucia , Credi Caterina , Pavone Francesco Saverio 
Published: August 2024

ABSTRACTThe increasing demand for sensitive, portable, and cost-effective disease detection methods has raised significant interest in the development of biosensors for rapid and early-stage diagnosis, population mass-screening, and bedside monitoring. Although a certain number of sensing devices with high sensitivity has experienced considerable progress, their practical application has been hindered by challenges in replicating instrumental systems, obtaining rapid and multiplexed signals, and the high cost of manufacturing. In response, we present a streamlined prism-based Total Internal Reflection system which, in combination with surface functionalization techniques on gold nanoparticles, is capable of facilitating Evanescent Wave scattering for the highly sensitive and rapid detection of specific analytes in synthetic liquids and real human samples. The system achieves a remarkable limit of detection of 1 fg/mL concentration for the targeted pathological biomarker. Our innovative design addresses the limitations of existing technologies by reducing costs, minimising overall size, and ensuring swift biofluid analysis with remarkable sensitivity. To validate its efficacy, we conducted scattering experiments in synthetic and human serum samples, exploiting functionalized AuNPs to recognize bacterial lipopolysaccharides as biomarkers for sepsis disease. The cohesive integration of these techniques hopefully makes this biosensing setup a promising candidate for potential clinical deployment, meeting the pressing requirements for rapid personalised diagnosis, large-scale population screening and bed-monitoring.
Mesenchymal Meis2 controls whisker development independently from trigeminal sensory innervation
Authors: Kaplan Mehmet Mahsum , Hudacova Erika , Matejcek Miroslav , Tuaima Haneen , Krivanek Jan , Machon Ondrej 
Published: August 2024

AbstractHair follicle development is initiated by reciprocal molecular interactions between the placode-forming epithelium and the underlying mesenchyme. Cell fate transformation in dermal fibroblasts generates a cell niche for placode induction by activation of signaling pathways WNT, EDA, and FGF in the epithelium. These successive paracrine epithelial signals initiate dermal condensation in the underlying mesenchyme. Although epithelial signaling from the placode to mesenchyme is better described, little is known about primary mesenchymal signals resulting in placode induction. Here we show thatMeis2expression in cells derived from the neural crest is critical for whisker formation, and also for branching of trigeminal nerves. While whisker formation is independent of the trigeminal sensory innervation, MEIS2 in mesenchymal dermal cells orchestrates the initial steps of epithelial placode formation and subsequent dermal condensation. MEIS2 regulates the expression of transcription factorFoxd1, which is typical of pre-dermal condensation. However, deletion ofFoxd1does not affect whisker development. Overall, our data suggest an early role of mesenchymal MEIS2 during whisker formation and provide evidence that whiskers can normally develop in the absence of sensory innervation orFoxd1expression.