bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biofabrication approaches and regulatory framework of metastatic tumor‐on‐a‐chip models for precision oncology
Authors: Nieto Daniel , Jiménez Gema , Moroni Lorenzo , López‐Ruiz Elena , Gálvez‐Martín Patricia , Marchal Juan Antonio 
Published: June 2022

AbstractThe complexity of the tumor microenvironment (TME) together with the development of the metastatic process are the main reasons for the failure of conventional anticancer treatment. In recent years, there is an increasing need to advance toward advanced in vitro models of cancer mimicking TME and simulating metastasis to understand the associated mechanisms that are still unknown, and to be able to develop personalized therapy. In this review, the commonly used alternatives and latest advances in biofabrication of tumor‐on‐chips, which allow the generation of the most sophisticated and optimized models for recapitulating the tumor process, are presented. In addition, the advances that have allowed these new models in the area of metastasis, cancer stem cells, and angiogenesis are summarized, as well as the recent integration of multiorgan‐on‐a‐chip systems to recapitulate natural metastasis and pharmacological screening against it. We also analyze, for the first time in the literature, the normative and regulatory framework in which these models could potentially be found, as well as the requirements and processes that must be fulfilled to be commercially implemented as in vitro study model. Moreover, we are focused on the possible regulatory pathways for their clinical application in precision medicine and decision making through the generation of personalized models with patient samples. In conclusion, this review highlights the synergistic combination of three‐dimensional bioprinting systems with the novel tumor/metastasis/multiorgan‐on‐a‐chip systems to generate models for both basic research and clinical applications to have devices useful for personalized oncology.
Development and initial validation of a reliable German self‐report measure to assess acute cannabis intoxication‐effects (CanTox‐17)
Authors: Schüler Merle , Moritz Steffen , Schnell Thomas 
Published: June 2022

AbstractObjectivesBoth positive and negative including psychotic‐like cannabis intoxication effects are well‐established. Yet, consequences for consumption patterns, addictive behavior or psychotic developments are poorly researched in general, in Germany not at all. Thus, objective was to develop the first German‐language questionnaire operationalizing acute cannabis intoxication effects, based on the original “Cannabis Experience Questionnaire” (CEQ).MethodsAfter expert translation of the CEQ, items related to acute intoxication effects were presented to a sample of 537 cannabis users. Four‐ and five‐factorial solutions of explorative factor analysis with a randomly split sub‐sample 1 were cross‐validated by confirmatory factor analysis on sub‐sample 2.ResultsAfter content review of factors and analysis of external validity, a 17 item four‐factorial model was approved. Factors are (1) “paranoia/dysphoria”, (2) “confusion/disorientation”, (3) “euphoria/creativity”, (4) “psychosis‐like/loss of reality”. Model fit is satisfactory (RMSEA = 0.058, SRMR = 0.065, CFI = 0.929, TLI = 0.914). Correlations with corresponding external measures support construct validity.ConclusionsThe present questionnaire is a time‐efficient, valid and reliable instrument. Thus, predictors of different cannabis intoxication effects can be analysed for the first time in German‐speaking area, as well as their significance for substance use or psychosis risk.
Deep learning–based quantitative susceptibility mapping (QSM) in the presence of fat using synthetically generated multi‐echo phase training data
Authors: Hanspach Jannis , Bollmann Steffen , Grigo Johanna , Karius Andre , Uder Michael , Laun Frederik B. 
Published: June 2022

PurposeTo enable a fast and automatic deep learning–based QSM reconstruction of tissues with diverse chemical shifts, relevant to most regions outside the brain.MethodsA UNET was trained to reconstruct susceptibility maps using synthetically generated, unwrapped, multi‐echo phase data as input. The RMS error with respect to synthetic validation data was computed. The method was tested on two in vivo knee and two pelvis data sets. Comparisons were made to a conventional fat–water separation pipeline by applying a commonly used graph‐cut algorithm, both without and with an extended mask for background field removal (FWS‐CONV‐QSM and FWS‐MASK‐CONV‐QSM, respectively). Several regions of interest were segmented and compared. Furthermore, the approach was tested on a prostate cancer patient receiving low‐dose‐rate brachytherapy, to detect and localize the seeds by MRI.ResultsThe RMS error was 0.292 ppm with FWS‐CONV‐QSM and 0.123 ppm for the UNET approach. Susceptibility maps were reconstructed much faster (< 10 s) and completely automatically (no background masking needed) by the UNET compared with the other applied techniques (5 min 51 s and 22 min 44 s for CONV‐QSM and FWS‐MASK‐CONV‐QSM, respectively. Background artifacts, fat–water swaps, and hypointense artifacts between I‐125 seeds of a patient receiving low‐dose brachytherapy in the prostate were largely reduced in the UNET approach.ConclusionsDeep learning–based QSM reconstruction, trained solely with synthetic data, is well‐suited to rapidly reconstructing high‐quality susceptibility maps in the presence of fat without needing masking for background field removal.
Freezing‐induced stiffness and strength anisotropy in freezing clayey soil: Theory, numerical modeling, and experimental validation
Authors: Yin Qing , Andò Edward , Viggiani Gioacchino , Sun WaiChing 
Published: June 2022

AbstractThis paper presents a combined experimental‐modeling effort to interpret the coupled thermo‐hydro‐mechanical behaviors of the freezing soil, where an unconfined, fully saturated clay is frozen due to a temperature gradient. By leveraging the rich experimental data from the microCT images and the measurements taken during the freezing process, we examine not only how the growth of ice induces volumetric changes of the soil in the fully saturated specimen but also how the presence and propagation of the freezing fringe front may evolve the anisotropy of the effective media of the soil–ice mixture that cannot be otherwise captured phenomenologically in the isotropic saturation‐dependent critical state models for plasticity. The resultant model is not only helpful for providing a qualitative description of how freezing affects the volumetric responses of the clayey material, but also provide a mean to generate more precise predictions for the heaving due to the freezing of the ground.
A new search scheme using multi‐bee‐colony elite learning method for unmanned aerial vehicles in unknown environments
Authors: Yue Wei , Li Chaofan , Liu Zhongchang , Li Lili , Wang Liyuan 
Published: June 2022

AbstractIn this research, a cooperative search for multiple dynamic targets in an unknown marine environment by multiple unmanned aerial vehicles is studied based on a novel multi‐bee‐colony (MBC) elite learning algorithm. First, a specialized searching model is established which includes the UAV dynamics, the sensor model, the target probability and environmental certainty at different flight altitudes. Then, a new search strategy, which consists of rough search and accurate search, is proposed by maximizing the multiobjective utility function with the dynamic changing of the flight altitude. In order to solve the optimization problem, an improved MBC algorithm based on elite learning is designed, which can improve the adaptability and computation speed of the standard artificial bee colony (ABC) algorithm under different search missions. Finally, extensive simulations are conducted to show the effectiveness and superiority of the proposed search strategy.
Response surface modeling and optimization of the extraction conditions using lactic acid‐based deep eutectic solvents as green alternative extraction media for Mentha pulegium
Authors: Kaoui Soukaina , Chebli Bouchra , Ait Baddi Ghita , Basaid Khadija , Mir Youssef 
Published: June 2022

AbstractIntroductionMost recurrently available organic solvents are toxic and inflammable and pose high risks to human health. Natural deep eutectic solvents (NADESs) have been developed as promising green alternatives.ObjectiveWe aimed to extract polyphenolic compounds from Mentha pulegium using lactic acid‐based deep eutectic solvents. Extraction parameters were optimized by response surface methodology.Material and MethodsCombined with ultrasound‐assisted extraction, three different lactic acid‐based deep eutectic solvents were investigated for the extraction of polyphenols. Methanol (80%, v/v) was used for comparison. The optimized influencing factors were: water content in solvent, extraction time, and temperature. The design was adopted including 17 experiments with three center points.ResultsAll NADESs tested showed an excellent extraction efficacy compared to 80% methanol. Under the optimized conditions, with 45% of water, at 30°C, and for extraction 90 min, the highest extraction yields were recorded using lactic acid:sodium acetate (3:1), achieving 173.35 ± 0.02 mg gallic acid equivalents (GAE)/g dry weight (dw) of polyphenols and 95 ± 0.09% antioxidant activity. After extraction for 90 min at 80°C with 18% of water, we obtained 164.06 ± 0.01 mg GAE/g dw and 94 ± 0.02% antioxidant activity using lactic acid:glucose (5:1). Efficient recovery (64.92 ± 0.01 mg GAE/g dw and 97 ± 0.1% antioxidant activity) was achieved using lactic acid:glycine (3:1) with 31% of water, at 35°C, and extraction for 30 min.ConclusionOur results indicate that with optimized parameters, the proposed natural solvents are excellent alternatives to chemical ones for the extraction of phenolic compounds.
Parents' voices matter: A mixed‐method study on the dyslexia diagnosis process
Authors: Denton Kenneth , Coneway Betty , Simmons Michelle , Behl Malvika , Shin Mikyung 
Published: June 2022

AbstractDifficulty learning to read presents many struggles for children and their families, and evaluation of parental perspectives of the dyslexia assessment process within the United States represents an under‐researched area. This study sought to investigate how parental perspectives change during their child's dyslexia assessment. Six hundred one parents of children experiencing reading difficulties provided both Likert scale and open‐ended responses to an online survey regarding their experiences throughout the dyslexia assessment and diagnosis process. Participants' responses were analyzed through thematic coding, sentiment analysis, and regression analysis. Parent perspectives were largely positive but revealed three important areas for investigation: shift in parental perspectives and lifestyles, assessment timelines, and parental advocacy and support. The assessment timeline predicted parental satisfaction. Results indicate a desire for clarity in the assessment process and ongoing needs for advocacy, support, and intervention. Implications for educational assessments, parent/family support, and suggestions for future research are discussed.
Statistically based nomograms for the minimal needle length required to achieve intra‐articular fluoroscopic‐guided injections of the shoulder, hip, and knee
Authors: Sebro Ronnie , De la Garza‐Ramos Cynthia 
Published: June 2022

AbstractBackgroundImage‐guided intra‐articular injections are commonly performed to reduce pain in patients with arthritis or other joint‐related pathology. Utilizing a needle length that is too short could lead to increased patient discomfort, increased procedural time, and extra‐articular injections.ObjectiveTo predict the minimum needle length required for fluoroscopic‐guided intra‐articular injections of the hips, knees, and shoulders based on patient age, gender, height and weight, or body mass index (BMI) and to evaluate whether this varies by gender.Study DesignCross‐sectional study.SettingTertiary care academic center.Participants600 consecutive patients with available magnetic resonance imaging (MRI) of the hips, knees, and shoulders (100 males and 100 females for each joint).MethodsThe distance from the skin to the joint (glenohumeral, hip and knee) and the thickness of the subcutaneous fat pad (distance from the skin to the muscle) along the injection path were measured. Multivariable linear ridge regression with 10‐fold cross‐validation was used to predict the distance from the skin to the hip, knee, and glenohumeral joints using age, gender, weight, and height or using age, gender, and BMI.ResultsThe data show that the subcutaneous fat thickness and the distance from the skin to all joints increase with weight (p < .001) and BMI (p < .001). Subcutaneous fat pads around the anterior shoulder (p < .02) and knee (<.001) are thicker in women than in men.ConclusionsPatient habitus, in particular weight and BMI, are strong predictors of the thickness of the subcutaneous fat pads and consequently strong predictors of the distance from the skin to the joint. Subcutaneous fat pad thickness around the shoulders and knees varies by gender. Nomograms showing the minimal needle length required to achieve intra‐articular injections of the hip, knee and glenohumeral joints are presented.
Structural and functional determinants inferred from deep mutational scans
Authors: Bajaj Priyanka , Manjunath Kavyashree , Varadarajan Raghavan 
Published: June 2022

AbstractMutations that affect protein binding to a cognate partner primarily occur either at buried residues or at exposed residues directly involved in partner binding. Distinguishing between these two categories based solely on mutational phenotypes is challenging. The bacterial toxin CcdB kills cells by binding to DNA Gyrase. Cell death is prevented by binding to its cognate antitoxin CcdA, at an extended interface that partially overlaps with the GyrA binding site. Using the CcdAB toxin–antitoxin (TA) system as a model, a comprehensive site‐saturation mutagenesis library of CcdB was generated in its native operonic context. The mutational sensitivity of each mutant was estimated by evaluating the relative abundance of each mutant in two strains, one resistant and the other sensitive to the toxic activity of the CcdB toxin, through deep sequencing. The ability to bind CcdA was inferred through a RelE reporter gene assay, since the CcdAB complex binds to its own promoter, repressing transcription. By analyzing mutant phenotypes in the CcdB‐sensitive, CcdB‐resistant, and RelE reporter strains, it was possible to assign residues to buried, CcdA interacting or GyrA interacting sites. A few mutants were individually constructed, expressed, and biophysically characterized to validate molecular mechanisms responsible for the observed phenotypes. Residues inferred to be important for antitoxin binding, are also likely to be important for rejuvenating CcdB from the CcdB–Gyrase complex. Therefore, even in the absence of structural information, when coupled to appropriate genetic screens, such high‐throughput strategies can be deployed for predicting structural and functional determinants of proteins.
Pirfenidone ameliorates pulmonary arterial pressure and neointimal remodeling in experimental pulmonary arterial hypertension by suppressing NLRP3 inflammasome activation
Authors: Mavrogiannis Emmanouil , Hagdorn Quint A. J. , Bazioti Venetia , Douwes Johannes M. , Van Der Feen Diederik E. , Oberdorf‐Maass Silke U. , Westerterp Marit , Berger Rolf M. F. 
Published: June 2022

AbstractPulmonary arterial hypertension (PAH) is a fatal disease characterized by increased pulmonary arterial pressure, inflammation, and neointimal remodeling of pulmonary arterioles. Serum levels of interleukin (IL)‐1β and IL‐18 are elevated in PAH patients and may enhance proinflammatory neointimal remodeling. NLRP3 inflammasome activation induces cleavage of the cytokines IL‐1β and IL‐18, required for their secretion. Pirfenidone (PFD), an antifibrotic and anti‐inflammatory drug, has been suggested to inhibit NLRP3 inflammasome activation. We hypothesized that PFD delays the progression of PAH by suppressing NLRP3 inflammasome activation. We assessed the effects of PFD treatment in a rat model for neointimal PAH induced by monocrotaline and aortocaval shunt using echocardiographic, hemodynamic, and vascular remodeling parameters. We measured inflammasome activation by NLRP3 immunostaining, Western blots for caspase‐1, IL‐1β, and IL‐18 cleavage, and macrophage IL‐1β secretion. PFD treatment ameliorated pulmonary arterial pressure, pulmonary vascular resistance, and pulmonary vascular remodeling in PAH rats. In PAH rats, immunostaining of NLRP3 in pulmonary arterioles and caspase‐1, IL‐1β, and IL‐18 cleavage in lung homogenates were increased compared to controls, reflecting NLRP3 inflammasome activation in vivo. PFD decreased IL‐1β and IL‐18 cleavage, as well as macrophage IL‐1β secretion in vitro. Our studies show that PFD ameliorates pulmonary hemodynamics and vascular remodeling in experimental PAH. Although PFD did not affect all NLRP3 inflammasome parameters, it decreased IL‐1β and IL‐18 cleavage, the products of NLRP3 inflammasome activation that are key to its downstream effects. Our findings thus suggest a therapeutic benefit of PFD in PAH via suppression of NLRP3 inflammasome activation.
A pilot prospective prevalence study of chronic rhinosinusitis associated with inflammatory bowel disease
Authors: Dhillon India , Ham Jennifer , Maul Ximena , Rosenfeld Gregory , Thamboo Andrew 
Published: June 2022

AbstractBackgroundInflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. Extra‐intestinal manifestations such as pulmonary diseases have been reported. Chronic rhinosinusitis (CRS), an inflammatory condition of the sinonasal mucosa, has been associated with several lung diseases. Given the relationship between lung and intestinal pathologies, and lung and sinus pathologies, we aimed to determine the prevalence of IBD among CRS patients.MethodsPilot prevalence study. Ninety‐two CRS patients were screened for IBD symptoms from October 2018 to January 2020. Patient‐reported disease symptoms and overall quality of life were evaluated using the Sino‐Nasal Outcome Test 22 (SNOT‐22), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and EuroQol 5 Dimension 5 Level (EQ‐5D‐5L) questionnaires. The Modified Lund–Kennedy (MLK) endoscopic and Lund–Mackay (LM) grading systems were used to confirm CRS diagnoses. Individuals who reported subjective symptoms of IBD were referred to a gastroenterologist clinic for further diagnostics.ResultsTwenty of the 92 (20.2%, 95% CI: 12.6%–29.8%) CRS patients reported symptoms of IBD and four individuals (4.26%, 95% CI: 1.17%–10.50%) were subsequently diagnosed with IBD. Compared to patients without IBD symptoms (n = 72), those with symptoms (n = 20) reported significantly worse SNOT‐22 (P = 0.002), SIBDQ (P < 0.05), and EQ‐5D‐3L (P = 0.0063) scores. However, these patients did not exhibit significantly different MLK (P = 0.81) or LM (P = 0.04) scores.ConclusionThe prevalence of IBD may be elevated among individuals with CRS relative to the general Canadian population. This pilot study suggests that CRS with IBD is associated with lower quality of life. Further cross‐sectional studies with larger sample sizes are required.
Patient safety and quality improvements in parotid surgery
Authors: Talati Vidit , Brown Hannah J. , Losenegger Tasher , Revenaugh Peter , Al‐Khudari Samer 
Published: June 2022

AbstractParotidectomy is the mainstay treatment for tumors of the parotid gland. In an effort to improve clinical outcomes, several modern surgical techniques and perioperative interventions have been evaluated and refined. This review discusses current and actively debated perioperative interventions aimed at improving patient safety and the quality of parotidectomy. Relevant high‐impact literature pertaining to preoperative diagnostic modalities, intraoperative surgical techniques, and postoperative care will be described.
Otologic and vestibular symptoms in COVID‐19: A scoping review
Authors: Ong Kimberly Mae C. , Cruz Teresa Luisa G. 
Published: June 2022

AbstractBackgroundOtologic and vestibular symptoms have been seen in patients confirmed to have COVID‐19 disease. Further discussion of these symptoms may provide insight into short‐ and long‐term management for these patients.ObjectiveThe aim of this review was to describe the otologic and vestibular symptoms that present in patients with COVID‐19. The primary outcomes of this review were onset, duration and clinical outcomes of these symptoms.Sources of EvidencePub Med, APAMed Central, Herdin, CINAHL, Scopus, Springer Link, ProQuest Coronavirus Research Database, and Google Scholar were searched for the articles to be included.Eligibility CriteriaStudies included were those involving adult patients diagnosed with COVID‐19 who experienced hearing loss, ear pain, ear discharge, otitis media, vertigo, or tinnitus. Studies were eligible for inclusion if there was a description of the otologic dysfunction, specifically onset, duration, or clinical outcomes.ResultsThe majority of patients who experienced hearing loss (68%), tinnitus (88%), vertigo/dizziness (30%), ear pain (8%), and discharge (100%) did so within a month of experiencing the typical symptoms of COVID‐19. A majority also experienced complete resolution of their symptoms within 2 weeks. Standard treatment for COVID‐19 was usually provided but when specific diagnoses are made for these symptoms (e.g., sudden sensorineural hearing loss, otitis media, vestibular neuritis), they are treated in the same manner as one would for non‐COVID‐19 cases, in addition to the management for COVID‐19. In certain cases, there may be a need for additional work‐up to rule out other causes.ConclusionsOtologic and vestibular symptoms were present in COVID‐19 patients, majority as part of the systemic nature of the disease. The onset, duration, and course were consistent with the natural history of a systemic viral infection. COVID‐19 should be considered in any patient with a new‐onset hearing loss, tinnitus, or vertigo/dizziness, even in the absence of infectious or respiratory symptoms.
Vestibular and cochlear dysfunction in aging: Two sides of the same coin?
Authors: Azevedo Cátia , Vilarinho Sérgio , Sousa Menezes Ana , Milhazes Mar Fernando , Dias Luís 
Published: June 2022

AbstractObjectiveNonspecific complaints of hearing loss, vertigo, imbalance, and instability, without a defined etiology, are very prevalent in the elderly population, with a great impact on morbidity and mortality in this age group. The objectives of this study were to verify whether there is age‐related vestibular dysfunction and to test the association of vestibular dysfunction with presbycusis in the elderly population.MethodsOriginal retrospective analytical cross‐sectional study, carried out with 80 patients who underwent a videonystagmography and complete audiometric evaluation due to nonspecific vestibular complaints, without a specific vestibular disorder diagnosis. Patients were selected and divided into two distinct age groups (group A: >60 years; group B: 18–50 years) and, in both groups, we analyzed the caloric tests and the pure‐tone audiometry.ResultsIn the vestibular evaluation, we found that there was a statistically significant difference (P < 0.05) between groups in the prevalence of bilateral vestibular weakness (group A: 22.5%; group B: 5%), and that the increase in age, above 60 years, is negatively correlated with the mean total caloric response. Additionally, we obtained a reasonable negative and statistically significant correlation (r = −0.320, P < 0.05) between the mean bone conduction thresholds at high frequencies and total caloric responses in group A.ConclusionsIn patients with hearing loss, it is essential to perform a complete vestibular study to diagnose vestibular disorders and, consequently, prevent adverse outcomes that may result from these alterations.