bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic Delay in Human Papillomavirus Negative Oropharyngeal Squamous Cell Carcinoma
Authors: Karp Emily E. , Yin Linda X. , O'Byrne Thomas Jamie , Lu Lauren Y. , Routman David M. , Lester Scott C. , Neben Wittich Michelle A. , Ma Daniel J. , Price Katharine A. , Chintakuntlawar Ashish V. , Tasche Kendall K. , Price Daniel L. , Moore Eric J. , Van Abel Kathryn M. 
Published: July 2022

ObjectiveFailure to recognize symptoms of non‐human papillomavirus‐associated oropharyngeal squamous cell carcinoma (HPV(−)OPSCC) at presentation can delay diagnosis and treatment. We aim to identify patient factors and provider practice patterns that delay presentation and care in HPV(−)OPSCC.MethodsRetrospective review at a tertiary care center. Patients with HPV(−)OPSCC receiving treatment from 2006 to 2016. Patients were excluded if their date of symptom onset or diagnosis was unknown after thorough review of the electronic medical record or their tissue was not tested for HPV or p16. Clinical data, workup, and care timelines were abstracted. Univariate and multivariable linear regressions were performed to determine associations between patient and provider factors and delays in care.ResultsOf 70 included patients, 52 (74%) were male and mean age was 60.5 (SD = 9.0). Median time to diagnosis was 69 days (IQR = 32–127 days), with a median latency of 30 days (IQR = 12–61 days) from symptom onset to first presentation and 19.5 days (IQR = 4–46 days) from the first presentation to diagnosis. Most patients visited at least 2 providers (n = 52, 74%) before diagnosis. Evaluation by 3 or more providers prior to diagnosis was associated with significant delays in diagnosis of nearly a year (357.7 days, p < 0.001) and being treated or prescribed analgesia prior to diagnosis was significantly associated with delays in diagnosis (p = 0.004) on univariate regression analysis.ConclusionsDelays in care related to evaluations by multiple providers and misdiagnosis prolonged time to diagnosis in HPV(−)OPSCC. Improved patient and provider education is necessary to expedite the diagnosis of HPV(−)OPSCC.Level of Evidence4 Laryngoscope, 133:1394–1401, 2023
A compositional analysis study of body composition and cardiometabolic risk factors
Authors: Janssen Ian , Miller Erin , Dzongowski Erin , Miakisheva Kristina , Ross Robert 
Published: July 2022

AbstractObjectiveThis cross‐sectional study used compositional data analysis (CoDA) to do the following: 1) analyze the relative associations between fat and lean tissues with cardiometabolic risk factors; and 2) estimate how these risk factors would change if equivalent mass was displaced from one tissue to another. Differences between CoDA and traditional regression were explored.MethodsA total of 397 adults with overweight or obesity were studied. Body composition consisted of visceral fat, abdominal subcutaneous fat, peripheral subcutaneous fat, other fat depots, skeletal muscle, and other lean tissues. The outcomes were a continuous metabolic syndrome score (primary outcome) and eight other cardiometabolic risk factors (secondary outcomes). Associations were examined using CoDA and traditional linear regression.ResultsVisceral fat mass, relative to the mass of the remaining tissues, was significantly associated with the metabolic syndrome score and five of eight remaining risk factors (p < 0.05). The relative contribution of the remaining tissues was not consistently associated with the study outcomes. Displacing equivalent mass from visceral fat into the remaining tissues was associated with meaningful decreases in the metabolic syndrome score. Regression estimates for CoDA and traditional regression differed in size and statistical significance.ConclusionsThese CoDA findings reinforce that excess visceral fat contributes to less‐favorable cardiometabolic risk factors.
Hydrophilic shape memory polymer hydrogels with virous pore structures and shape changing performance
Authors: Lv Yang , Chen Xiaohu , Zhang Peicong , Zhou Shiyi , Li Junfeng , Bai Ruqing , Wang Li 
Published: July 2022

AbstractThe preparation of a porous shape memory hydrogel with excellent shape changing performance is a hot research topic at present. In this paper, hydrophilic hydrogels were synthesized using polypropylene glycol (PPG) and polyethylene glycol (PEG) as raw materials and hexamethylene diisocyanate (HDI) as crosslinking agent. The pore structures were developed by gas foaming and salt leaching methods. The results showed that the hydrophilicity of hydrogel and the swelling rate in phosphate buffered saline (PBS) increased with the increase of PEG mass fraction, the shape changing performance of hydrogels varied as well with high shape recovery rate ≥90%. The recovery speed in aqueous environment was faster than in the air. After embedding hydroxyapatite (HA) particles, the materials exhibited appropriate degradable properties and good in vitro mineralization performance. Therefore, the obtained PPG/PEG system hydrogels is expected to become an ideal platform for tissue engineering and other applications in the biomedical field.
Who benefits from an eHealth‐based stress management intervention in advanced prostate cancer? Results from a randomized controlled trial
Authors: Benzo Roberto M. , Moreno Patricia I. , Noriega‐Esquives Blanca , Otto Amy K. , Penedo Frank J. 
Published: July 2022

AbstractObjectiveConduct a secondary analysis to examine the effects of a tablet‐delivered, group‐based cognitive‐behavioral stress management (CBSM) intervention for reducing symptom burden among men with advanced prostate cancer (APC) and elevated baseline levels of symptom burden.MethodsA total of 192 men with APC were randomized to either a CBSM or a health promotion condition and followed for one year. Six analytical samples were included in our study, each including participants who reported elevated levels of burden for the corresponding outcome at baseline. Outcomes included five domains of symptom‐related quality of life (urinary incontinence n = 98; urinary irritation n = 61; bowel function n = 43; sexual function n = 177; and hormonal function n = 149) and depression (n = 31). Repeated measures mixed models were used to detect within‐ and between‐group changes in outcomes.ResultsRegardless of condition, participants with elevated symptom burden or mild‐to‐severe depression showed short‐term (6‐month) improvements in urinary irritation, bowel function, hormonal function, and depression scores. Only participants in the CBSM condition showed short‐term (6‐month) improvements in urinary incontinence, and long‐term (12‐month) improvements in urinary irritation, bowel function, hormonal function, and depression scores.ConclusionsOur findings suggest that targeting a web‐based CBSM intervention to recipients most likely to benefit (elevated levels of symptom burden) can improve several domains of symptom‐related quality of life and depressive symptoms in men with APC.
Machine learning‐guided covariate selection for time‐to‐event models developed from a small sample of real‐world patients receiving bevacizumab treatment
Authors: Karatza Eleni , Papachristos Apostolos , Sivolapenko Gregory B. , Gonzalez Daniel 
Published: July 2022

AbstractTherapeutic outcomes in patients with metastatic colorectal cancer (mCRC) receiving bevacizumab treatment are highly variable, and a reliable predictive factor is not available. Progression‐free survival (PFS) and overall survival (OS) were recorded from an observational, prospective study after 5 years of follow‐up, including 46 patients with mCRC receiving bevacizumab treatment. Three vascular endothelial growth factor (VEGF)‐A and two intercellular adhesion molecule‐1 genes polymorphisms, age, gender, weight, dosing scheme, and co‐treatments were collected. Given the relatively small number of events (37 [80%] for the PFS and 26 [57%] for the OS), to study the effect of these covariates on PFS and OS, a covariate analysis was performed using statistical and supervised machine learning techniques, including Cox regression, penalized Cox regression techniques (least absolute shrinkage and selection operator [LASSO], ridge regression, and elastic net), survival trees, and survival forest. The predictive performance of each method was evaluated in bootstrapped samples, using prediction error curves and the area under the curve of the receiver operating characteristic. The LASSO penalized Cox‐regression model showed the best overall performance. Nonlinear mixed effects (NLME) models were developed, and a conventional stepwise covariate search was performed. Then, covariates identified as important by the LASSO model were included in the base NLME models developed for PFS and OS, resulting in improved models as compared to those obtained with the stepwise covariate search. It was shown that having gene polymorphisms in VEGFA (rs699947 and rs1570360) and ICAM1 (rs1799969) are associated with a favorable clinical outcome in patients with mCRC receiving bevacizumab treatment.
Determination and enantioselective separation of zilpaterol in human urine after mimicking consumption of contaminated meat using high‐performance liquid chromatography with tandem mass spectrometry techniques
Authors: Euler Luisa , Wagener Felicitas , Thomas Andreas , Thevis Mario 
Published: July 2022

RationaleThe synthetic β‐adrenoreceptor agonist zilpaterol is legitimately used as an animal feed supplement in selected countries due to its known effects on lipolysis and protein biosynthesis. These pharmacological characteristics of zilpaterol have contributed to its classification as doping agent in sport by the World Anti‐Doping Agency. However, the use as a feed supplement can lead to residues of the drug in edible tissues and, possibly, also in the urine of consumers.MethodsTo provide urinary elimination profiles of microdosed zilpaterol and to determine whether the ingestion of zilpaterol below or at the acceptable daily intake level of 0.04 μg/kg bodyweight can result in an adverse analytical finding (AAF) in doping controls, healthy volunteers were administered single or multiple oral doses of 0.5 μg or 3 μg zilpaterol to mimic ingestion of contaminated cattle meat. Urine samples were collected and analyzed using a validated high‐performance liquid chromatography‐electrospray ionization‐tandem mass spectrometry (HPLC‐ESI‐MS/MS) method and a newly developed chiral high‐performance liquid chromatography–atmospheric pressure chemical ionization–tandem mass spectrometry (HPLC‐APCI‐MS/MS) method.ResultsUrinary peak concentrations of zilpaterol were observed for all volunteers 1.5–12.5 h after ingestion, and maximum levels >5 ng/mL, which would constitute an AAF in doping controls, were found after the intake of 3 μg of zilpaterol on five consecutive days in one out of five study participants. Noteworthy, the enantiomeric ratio of excreted zilpaterol remained constant over time.ConclusionThis study provides first insights into the urinary excretion of microdosed zilpaterol. Furthermore, a method was successfully developed and applied for the separation of the zilpaterol enantiomers with mass spectrometric detection.
On the conformal spin dependence of the perturbative QCD vacuum singularity
Authors: Chachamis Grigorios , Vera Agustín Sabio 
Published: July 2022

Abstract
We study the four-gluon scattering amplitude in the high energy limit of QCD written in terms of its conformal expansion. We highlight the need to include both even and odd conformal spin contributions in order to map it to an iterative representation in rapidity and transverse momentum space which we have evaluated numerically. By Fourier expanding in a set of three azimuthal angles, we find a new form for the amplitude in terms of 4F3 hypergeometric functions. An alternative formulation is possible when connecting this Fourier expansion with Bessel kernels studied in analytic number theory.
Surgical Management of Amiodarone‐associated Thyrotoxicosis: Too Risky or Too Effective?
Authors: Hamoir Etienne , Meurisse Michel , Defechereux Thierry , Joris Jean , Vivario Janine , Hennen Georges 
Published: July 2022

AbstractAmiodarone‐associated thyrotoxicosis, often clinically mild and resolutive after amiodarone discontinuation or under medical therapy, is sometimes drug unresponsive and not uncommonly follows a dramatic, even fatal course. Therefore, we considered a surgical solution in 15 severely amiodarone‐associated thyrotoxic patients. Twelve men and three women (mean age 68 years, range 50–84 years) underwent radical thyroidectomy for clinical and biologically proved amiodarone‐associated thyrotoxicosis. In six surgery was the first‐line therapeutic option. In the other nine thyroidectomy seemed unavoidable considering the unresponsiveness to medical therapy and rapid deterioration of the patients’ clinical condition, with life‐threatening cardiac failure in three. In every patient surgery was conducted without immediate or delayed complications. Total thyroidectomy proved uniformly, definitively, and rapidly effective in controlling thyrotoxicosis in all patients, with a spectacular reversal of cardiac failure in the three most critical cases. Surgery was beneficial to our 15 patients and undoubtedly life‐saving in the three most worrying cases. These results suggest that thyroidectomy should be more liberally regarded as an interesting alternative to conventional, but unpredictably effective, medical therapies.
Does tranexamic acid reliably reduce blood loss in proximal femur fracture surgery?
Authors: Fenwick A. , Antonovska I. , Pfann M. , Mayr J. , Wiedl A. , Nuber S. , Förch S. , Mayr E. 
Published: July 2022

Abstract
Purpose
The aim of our study was to investigate the use of tranexamic acid in patients with proximal femoral fractures and compare the total blood loss, transfusion rates, complications, and the application method.

Methods
A retrospective single center cohort study (level I trauma center) with 1479 patients treated operatively for a proximal femoral fracture between January 2016 and June 2020 was performed. 1 g of tranexamic acid was applied (systemic, topic or combined application). Patient data, surgical procedure, complications, and mortality were assessed. Hemoglobin levels, blood loss and transfusion rates for patients with and without tranexamic acid and the application methods were compared.

Results
667 femoral neck fractures, 701 pertrochanteric and 109 subtrochanteric fractures were included. Mean age was 80.8 years. 274 patients received tranexamic acid. At admission average hemoglobin was 12.2 g/l. Hemoglobin drop postoperatively was less after tranexamic acid (9.72 vs. 9.35 g/dl). Transfusion rates were lowered significantly by 17.1% after tranexamic acid. Blood loss was reduced for all patients after tranexamic acid independent of fracture morphology. The combination of 1 g i.v. and 1 g topical-applied tranexamic acid seems to be more effective. Complication rates did not differ.

Conclusion
Tranexamic acid is effective in reducing blood loss and transfusion rates, without increasing the risk of thromboembolic events after proximal femoral fractures. For open reduction and nailing and arthroplasty in fracture setting combined topical and single i.v. application seems most effective and closed reduction with nailing can be treated by single dose i.v. application of 1 g tranexamic acid.
Exploring the concept of Cognitive Digital Twin from model-based systems engineering perspective
Authors: Jinzhi Lu , Zhaorui Yang , Xiaochen Zheng , Jian Wang , Dimitris Kiritsis 
Published: July 2022

AbstractDigital Twin technology has been widely applied in various industry domains. Modern industrial systems are highly complex consisting of multiple interrelated systems, subsystems and components. During the lifecycle of an industrial system, multiple digital twin models might be created related to different domains and lifecycle phases. The integration of these relevant models is crucial for creating higher-level intelligent systems. The Cognitive Digital Twin (CDT) concept has been proposed to address this challenge by empowering digital twins with augmented semantic capabilities. It aims at identifying the dynamics and interrelationships of virtual models, thus to enhance complexity management capability and to support decision-making during the entire system lifecycle. This paper aims to explore the CDT concept and its core elements following a systems engineering approach. A conceptual architecture is designed according to the ISO 42010 standard to support CDT development; and an application framework enabled by knowledge graph is provided to guide the CDT applications. In addition, an enabling tool-chain is proposed corresponding to the framework to facilitate the implementation of CDT. Finally, a case study is conducted, based on simulation experiments as a proof-of-concept.
Optimization and automation of rapid and selective analysis of fatty acid methyl esters from aqueous samples by headspace SPME arrow extraction followed by GC–MS/MS analysis
Authors: Tintrop Lucie K. , Jochmann Maik A. , Beesley Thomas , Küppers Marco , Brunstermann Ruth , Schmidt Torsten C. 
Published: July 2022

AbstractThe analysis of fatty acid methyl esters (FAMEs) is of high relevance for monitoring and control of various industrial processes and biological systems. In this study, a novel, green analytical approach for the determination of 24 FAMEs from aqueous samples is proposed, which is based on a headspace solid-phase microextraction (SPME) arrow followed by gas chromatography coupled to tandem mass spectrometry (GC–MS/MS). The method was substantially accelerated to a run time of 44 min per sample by thorough optimization and automation of the relevant parameters. The limiting parameters, mostly based on expediting equilibrium attainment, were found to be parameters of extraction: material, pH, time, and temperature, which were optimized to divinylbenzene polydimethylsiloxane (DVB-PDMS), pH 2, 20 min, and 70 °C, respectively. The optimization and automation of the method led to low method detection limits (9–437 ng L−1) and high selectivity. Evaluation of the method on real samples was done by analyzing the aqueous phase of a bioreactor, whereby the matrix effect could be greatly reduced due to dilution and headspace sampling. The rapid, sensitive, selective, and matrix-reduced approach is found to be not only a novel method for water analysis but is promising for further applications, e.g., with solid and gaseous samples containing FAMEs.
Graphical abstract
Influence of N-acetyltransferase 2 (NAT2) genotype/single nucleotide polymorphisms on clearance of isoniazid in tuberculosis patients: a systematic review of population pharmacokinetic models
Authors: Thomas Levin , Raju Arun Prasath , Chaithra  , M Sonal Sekhar , Varma Muralidhar , Saravu Kavitha , Banerjee Mithu , SV Chidananda Sanju , Mallayasamy Surulivelrajan , Rao Mahadev 
Published: July 2022

Abstract
Purpose
Significant pharmacokinetic variabilities have been reported for isoniazid across various populations. We aimed to summarize population pharmacokinetic studies of isoniazid in tuberculosis (TB) patients with a specific focus on the influence of N-acetyltransferase 2 (NAT2) genotype/single-nucleotide polymorphism (SNP) on clearance of isoniazid.

Methods
A systematic search was conducted in PubMed and Embase for articles published in the English language from inception till February 2022 to identify population pharmacokinetic (PopPK) studies of isoniazid. Studies were included if patient population had TB and received isoniazid therapy, non-linear mixed effects modelling, and parametric approach was used for building isoniazid PopPK model and NAT2 genotype/SNP was tested as a covariate for model development.

Results
A total of 12 articles were identified from PubMed, Embase, and hand searching of articles. Isoniazid disposition was described using a two-compartment model with first-order absorption and linear elimination in most of the studies. Significant covariates influencing the pharmacokinetics of isoniazid were NAT2 genotype, body weight, lean body weight, body mass index, fat-free mass, efavirenz, formulation, CD4 cell count, and gender. Majority of studies conducted in adult TB population have reported a twofold or threefold increase in isoniazid clearance for NAT2 rapid acetylators compared to slow acetylators.

Conclusion
The variability in disposition of isoniazid can be majorly attributed to NAT2 genotype. This results in a trimodal clearance pattern with a multi-fold increase in clearance of NAT2 rapid acetylators compared to slow acetylators. Further studies exploring the generalizability/adaptability of developed PopPK models in different clinical settings are required.
Finite-Size Effects in Simulations of Peptide/Lipid Assembly
Authors: Jarin Zack , Agolini Olivia , Pastor Richard W. 
Published: July 2022

Abstract
Molecular dynamics simulations are an attractive tool for understanding lipid/peptide self-assembly but can be plagued by inaccuracies when the system sizes are too small. The general guidance from self-assembly simulations of homogeneous micelles is that the total number of surfactants should be three to five times greater than the equilibrium aggregate number of surfactants per micelle. Herein, the heuristic is tested on the more complicated self-assembly of lipids and amphipathic peptides using the Cooke and Martini 3 coarse-grained models. Cooke model simulations with 50 to 1000 lipids and no peptide are dominated by finite-size effects, with usually one aggregate (micelle or nanodisc) containing most of the lipids forming at each system size. Approximately 200 systems of different peptide/lipid (P/L) ratios and sizes of up to 1000 lipids yield a “finite-size phase diagram” for peptide driven self-assembly, including a coexistence region of micelles and discs. Insights from the Cooke model are applied to the assembly of dimyristoylphosphatidylcholine and the ELK-neutral peptide using the Martini 3 model. Systems of 150, 450, and 900 lipids with P/L = 1/6.25 form mixtures of lipid-rich discs that agree in size with experiment and peptide-rich micelles. Only the 150-lipid system shows finite-size effects, which arise from the long-tailed distribution of aggregate sizes. The general rule of three to five times the equilibrium aggregate size remains a practical heuristic for the Cooke and Martini 3 systems investigated here.

Graphical Abstract
Suture material choice can increase risk of hypersensitivity in hand trauma patients
Authors: Koppa Mayank , House Rosemary , Tobin Vicky , Rozen Warren M. , Hunter-Smith David J. , Goldie Stephen J. 
Published: July 2022

Abstract
Introduction
Hypersensitivity is an unfortunate potential outcome in patients undergoing surgery following traumatic injuries to their hands. In our practice, we noted that certain suture types may increase the risk of the patient developing hypersensitivity.

Methodology
We conducted a retrospective observational study to investigate if certain suture materials increase the risk of hypersensitivity when used to repair surgical wounds in hand trauma. Patients undergoing hand trauma surgery over a period of five consecutive months were included in the study. Ethics committee approval was obtained from Peninsula Health’s research office.

Results
184 patients were included in the study. Hypersensitivity was observed in 30 (16.3%) patients post-operatively. Chromic gut suture was used in 53.3% of the patients who experienced hypersensitivity. Patients who had chromic catgut used in their surgery were 2.82 times more likely to develop hypersensitivity than patients who did not have chromic gut used (p = 0.0015). If a patient had a nerve repaired and chromic gut sutured used, they were 6.50 times more likely to develop hypersensitivity (p < 0.0001).

Conclusion
Surgeons should be aware that this data indicates that suture choice in hand trauma patients can greatly impact the risk of the patient developing hypersensitivity.
Level of evidence: Level IV, risk/prognostic study.