bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Molecular Mechanism for Understanding the Actuated Strain of Dielectric Elastomers and Their Impacts
Authors: Wu Wenjie , Wang Zhong Lin , Zhang Liqun
Published: June 2022

Dielectric elastomers (DEs) are a special material that deform responding to an electric field. The induced strain is known as actuated strain (AS). This phenomenon is totally different from electrostriction, for there is no crystal lattice in elastomers and the AS of DEs is much greater. The most accepted mechanism holds the view that the AS of DEs is induced by the Maxwell stress. According to this mechanism, materials exhibiting similar ratios of permittivity and Young's modulus should have similar ASs, while the experimental AS isn't relevant to the ideal value, contradicting this mechanism. The direction of uniaxial pre‐strained DE's AS cannot be explained by this mechanism either. The electric field and DE are only regarded as a source of stress and a deformable body respectively in this mechanism, which ignores the interaction between those two. Recently, a new molecular mechanism for AS is proposed, in which the electric field first orient dipoles of chains, therefore the conformation of chains will be changed, finally leading to AS. With thermodynamical derivation and experiment, entropy‐dominated elasticity is found to account for more during AS. This mechanism is systematically introduced in this perspective and presents current challenges and outlooks of DE.
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

The 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

Objectives

Both 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).

Methods

After 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.

Results

After 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.

Conclusions

The 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

Purpose

To enable a fast and automatic deep learning–based QSM reconstruction of tissues with diverse chemical shifts, relevant to most regions outside the brain.

Methods

A 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.

Results

The 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.

Conclusions

Deep 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

This 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

In 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

Introduction

Most 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.

Objective

We 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 Methods

Combined 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.

Results

All 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.

Conclusion

Our 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

Difficulty 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

Background

Image‐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.

Objective

To 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 Design

Cross‐sectional study.

Setting

Tertiary care academic center.

Participants

600 consecutive patients with available magnetic resonance imaging (MRI) of the hips, knees, and shoulders (100 males and 100 females for each joint).

Methods

The 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.

Results

The 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.

Conclusions

Patient 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

Mutations 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.
The influence of packaging colour on consumer expectations of coffee using free word association
Authors: Sant'Anna Alexia Carvalho , dos Santos Alves Maria Jaízia , Moraes Monteiro Carla Roana , Ribeiro Gagliardi Talita , Ayala Valencia Germán
Published: June 2022

Coffee packaging colour is a factor used to attract consumer attention and generate sensory and hedonic expectations. This study aimed to understand the effect of colour packaging on consumer expectations. A cross‐sectional study with 432 volunteers was carried out using coffee packaging with black, red, green and yellow colours. Each coffee packaging was compared with another similar coffee packaging having the opposite colour in the chromatic circle (white, light blue, pink and dark blue colours). Results from volunteers using free word association show that important attributes related to coffee could be induced in the volunteers using food packaging with black, red and green colours. Furthermore, the white colour can also be used in coffee packaging; however, this colour was not correlated with warm products as expected in coffee. Finally, coffee packaging having pink, light and dark blue, as well as yellow colours was rejected by the volunteers, suggesting that those colours should be avoided in packaged coffee.
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

Pulmonary 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.
‘We need to engage with rather than alienate those who criticise the farming industry‘
Authors: Craven Emily
Published: June 2022

Emily Craven argues that, when considering the vegan debate, farm animal practitioners should seek to understand and work with those who criticise the industry to drive improvements in farming standards, rather than alienate and dismiss them.
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

Background

Inflammatory 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.

Methods

Pilot 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.

Results

Twenty 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.

Conclusion

The 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

Parotidectomy 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

Background

Otologic 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.

Objective

The 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 Evidence

Pub Med, APAMed Central, Herdin, CINAHL, Scopus, Springer Link, ProQuest Coronavirus Research Database, and Google Scholar were searched for the articles to be included.

Eligibility Criteria

Studies 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.

Results

The 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.

Conclusions

Otologic 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

Objective

Nonspecific 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.

Methods

Original 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.

Results

In 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.

Conclusions

In 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.
Survival differences of low‐grade versus high‐grade head and neck pleomorphic dermal sarcomas and a review of a scalp case
Authors: Janz Tyler A. , Long Barry D. , Joshi Rohan R. , Coblens Orly M.
Published: June 2022

Objective

To examine survival by tumor grade of pleomorphic dermal sarcomas (PDS) of the head and neck (H&N) and review a scalp PDS case.

Methods

Patients in the Surveillance, Epidemiology, and End Results (SEER) database were included from 1980 to 2016 based on a diagnosis of H&N PDS. Survival estimates were performed using Kaplan–Meier analysis. Additionally, a case of a grade III H&N PDS is presented.

Results

Two hundred‐seventy cases of PDS were identified. The mean age at diagnosis was 75.1 years (SD: 13.5). Two hundred‐thirty‐four (86.7%) patients were male. Eighty‐seven percent of patients received surgery as a part of their care. The 5‐year overall survival rates for grades I, II, III, and IV PDSs were 69%, 60%, 50%, and 42%, respectively (P = 0.03).

Conclusions

H&N PDS occurs most commonly in older‐age males. Surgical management is frequently a part of H&N PDS care. Survival rates significantly decline based on tumor grade.
Simulation Modeling
Authors: Loucks Daniel P.
Published: June 2022

An introduction to deterministic and stochastic system simulation modeling and various statistical measures of their outputs.
A Framework for Digital Transformation for Research and Practice: Putting Things into Perspective
Authors: Mikalef Patrick , Parmiggiani Elena
Published: June 2022

The past years of researching digital transformation and the accumulated experience of practitioners in deploying projects of novel digital technologies have allowed us to gain much valuable insight about the process. From this assembly of knowledge, there is a lot we can learn about how to conduct future research, as well as a depth of knowledge regarding best practices that can aid practitioners. In this chapter, we provide some key input on how research and practice can approach digital transformation and discuss some ideas that are likely to be central in the near future. We draw on some streams of literature which have yet to be fully integrated in the current discourse of digital transformation research and provide some practical guidelines that can aid practitioners at different levels. We conclude with a brief overview of some key technologies which are likely to be in the spotlight of attention in the upcoming years and discuss their implications for research and practice.
Infection of lung megakaryocytes and platelets by SARS-CoV-2 anticipate fatal COVID-19
Authors: Zhu Aiwei , Real Fernando , Capron Claude , Rosenberg Arielle R. , Silvin Aymeric , Dunsmore Garett , Zhu Jaja , Cottoignies-Callamarte Andréa , Massé Jean-Marc , Moine Pierre , Bessis Simon , Godement Mathieu , Geri Guillaume , Chiche Jean-Daniel , Valdebenito Silvana , Belouzard Sandrine , Dubuisson Jean , Lorin de la Grandmaison Geoffroy , Chevret Sylvie , Ginhoux Florent , Eugenin Eliseo A. , Annane Djillali , Bordé Elisabeth Cramer , Bomsel Morgane
Published: June 2022

SARS-CoV-2, although not being a circulatory virus, spread from the respiratory tract resulting in multiorgan failures and thrombotic complications, the hallmarks of fatal COVID-19. A convergent contributor could be platelets that beyond hemostatic functions can carry infectious viruses. Here, we profiled 52 patients with severe COVID-19 and demonstrated that circulating platelets of 19 out 20 non-survivor patients contain SARS-CoV-2 in robust correlation with fatal outcome. Platelets containing SARS-CoV-2 might originate from bone marrow and lung megakaryocytes (MKs), the platelet precursors, which were found infected by SARS-CoV-2 in COVID-19 autopsies. Accordingly, MKs undergoing shortened differentiation and expressing anti-viral IFITM1 and IFITM3 RNA as a sign of viral sensing were enriched in the circulation of deadly COVID-19. Infected MKs reach the lung concomitant with a specific MK-related cytokine storm rich in VEGF, PDGF and inflammatory molecules, anticipating fatal outcome. Lung macrophages capture SARS-CoV-2-containing platelets in vivo. The virus contained by platelets is infectious as capture of platelets carrying SARS-CoV-2 propagates infection to macrophages in vitro, in a process blocked by an anti-GPIIbIIIa drug. Altogether, platelets containing infectious SARS-CoV-2  alter COVID-19 pathogenesis and provide a powerful fatality marker. Clinical targeting of platelets might prevent viral spread, thrombus formation and exacerbated inflammation at once and increase survival in COVID-19.
Preclinical models of epithelial ovarian cancer: practical considerations and challenges for a meaningful application
Authors: Ciucci Alessandra , Buttarelli Marianna , Fagotti Anna , Scambia Giovanni , Gallo Daniela
Published: June 2022

Despite many improvements in ovarian cancer diagnosis and treatment, until now, conventional chemotherapy and new biological drugs have not been shown to cure the disease, and the overall prognosis remains poor. Over 90% of ovarian malignancies are categorized as epithelial ovarian cancers (EOC), a collection of different types of neoplasms with distinctive disease biology, response to chemotherapy, and outcome. Advances in our understanding of the histopathology and molecular features of EOC subtypes, as well as the cellular origins of these cancers, have given a boost to the development of clinically relevant experimental models. The overall goal of this review is to provide a comprehensive description of the available preclinical investigational approaches aimed at better characterizing disease development and progression and at identifying new therapeutic strategies. Systems discussed comprise monolayer (2D) and three-dimensional (3D) cultures of established and primary cancer cell lines, organoids and patient-derived explants, animal models, including carcinogen-induced, syngeneic, genetically engineered mouse, xenografts, patient-derived xenografts (PDX), humanized PDX, and the zebrafish and the laying hen models. Recent advances in tumour-on-a-chip platforms are also detailed. The critical analysis of strengths and weaknesses of each experimental model will aid in identifying opportunities to optimize their translational value.
Acidosis significantly alters immune checkpoint expression profiles of T cells from oesophageal adenocarcinoma patients
Authors: Davern Maria , Donlon Noel E. , O’Connell Fiona , Gaughan Caoimhe , O’Donovan Cillian , Habash Mohammed , Sheppard Andrew D. , MacLean Michael , Dunne Margaret R. , Moore Jenny , Temperley Hugo , Conroy Melissa J. , Butler Christine , Bhardwaj Anshul , Ravi Narayanasamy , Donohoe Claire L. , Reynolds John V. , Lysaght Joanne
Published: June 2022

Tumour acidosis contributes to cancer progression by inhibiting anti-tumour immunity. However, the effect of acidosis on anti-tumour T cell phenotypes in oesophageal adenocarcinoma (OAC) is unknown. Therefore, this study investigated the effect of acidosis on anti-tumour T cell profiles and if immune checkpoint blockade (ICB) could enhance anti-tumour T cell immunity under acidosis. Acidic conditions substantially altered immune checkpoint expression profiles of OAC patient-derived T cells, upregulating TIM-3, LAG-3 and CTLA-4. Severe acidosis (pH 5.5) significantly decreased the percentage of central memory CD4+ T cells, an effect that was attenuated by ICB treatment. ICB increased T cell production of IFN-γ under moderate acidosis (pH 6.6) but not severe acidosis (pH 5.5) and decreased IL-10 production by T cells under severe acidic conditions only. A link between lactate and metastasis was also depicted; patients with nodal metastasis had higher serum lactate levels (p = 0.07) which also positively correlated with circulating levels of pro-angiogenic factor Tie-2. Our findings establish that acidosis-induced upregulation of immune checkpoints on T cells may potentially contribute to immune evasion and disease progression in OAC. However, acidic conditions curtailed ICB efficacy, supporting a rationale for utilizing systemic oral buffers to neutralize tumour acidity to improve ICB efficacy.

Graphical abstract

Study schematic—PBMCs were isolated from OAC patients (A) and expanded ex vivo for 7 days using anti-CD3/28 +IL-2 T cell activation protocol (B) and further cultured for 48 h under increasing acidic conditions in the absence or presence of immune checkpoint blockade (nivolumab, ipilimumab or dual nivolumab + ipilimumab) (C). Immunophenotyping was then carried out to assess immune checkpoint expression profiles and anti-tumour T cell phenotypes (D). Serum lactate was assessed in OAC patients (E–F) and levels were correlated with patient demographics (G) and the levels of circulating immune/pro-angiogenic cytokines that were determined by multiplex ELISA (H). Key Findings—severe acidic conditions upregulated multiple immune checkpoints on T cells (I). Efficacy of ICB was curtailed under severe acidic conditions (J). Circulating lactate levels positively correlated with circulating levels of pro-angiogenic factor tie-2 and higher serum lactate levels were found in patients who had nodal metastasis (K).
Working conditions in low risk nulliparous women in The Netherlands: are legislation and guidelines a guarantee for a healthy working environment? A cohort study
Authors: van Beukering Monique D. M. , Schuster Heleen J. , Peelen Myrthe J. C. S. , Schonewille Marit E. A. , Hajenius Petra J. , Duijnhoven Ruben G. , Brand Teus , Painter Rebecca C. , Kok Marjolein
Published: June 2022

Objective

Hazardous working conditions increase the risk of adverse pregnancy outcomes. In this study, we examine adherence to legislation and guidelines aimed at improving working conditions in pregnancy.

Methods

Between 2014 and 2016, we recruited a prospective cohort of low-risk nulliparous pregnant women in paid employment or self-employed in 16 community midwifery practices in The Netherlands. Participants completed two questionnaires concerning demographics, education, general health and working conditions between 10–16 and 20–24 weeks of pregnancy. We calculated the proportion of participants with work-related risk factors not in accordance with legislation and/or guidelines.

Results

Of 269 participants included, 214 (80%) completed both questionnaires. At 10–16 weeks 110 (41%) participants and at 20–24 weeks 129 (63%) participants continued to work under circumstances that did not meet recommendations. Employers provided mandated information on work adjustment to 37 (15%) participants and 96 (38%) participants received no information about the potential hazards while working with biological and chemical hazards. Participants with lower educational attainment (aOR 2.2 95%CI 1.3–3.9), or employment in healthcare (aOR 4.5, 95%CI 2.2–9.0), education/childcare and social service (aOR 2.6, 95%CI 1.1–6.0 2),, catering (aOR 3.6, 95%CI 1.1–12) and industry, construction and cleaning (aOR 3.3, 95%CI 1.1–10.3) more often continued work which did not meet recommendations.

Conclusion

There is poor adherence to national legislation and guidelines for safe working in pregnancy in The Netherlands: 50% of the pregnant women worked under hazardous conditions. Given the impact on adverse pregnancy outcomes as well as on the public purse, action to improve compliance must be taken by all stakeholders.
Activity of isoflavone biochanin A in chronic experimental toxoplasmosis: impact on inflammation
Authors: Aboukamar Wafaa A. , Elhenawy Abeer A. , Elmehankar Manar S. , Elzoheiry Manal A. , El-Gamal Randa , Elabbasy Lamiaa M. , Hany Heba , Nabih Nairmen
Published: June 2022

Toxoplasma gondiiis a worldwide prevalent parasite. The infection has been linked to variable inflammatory effects including neuroinflammation. Biochanin A (BCA) is an isoflavone, known for its anti-inflammatory and anti-oxidative properties. In this study, we examined the effect of BCA on the brain and liver inflammatory lesions in a murine model with chronic toxoplasmosis. Mice were divided in to six groups: non-infected control, non-infected BCA-treated, and four infected groups withToxoplasmagondiiMe49-type II cystogenic strain: infected control, BCA (50 mg/kg/day)-treated, combined BCA/cotrimoxazole-treated and cotrimoxazole (370 mg/kg/day) alone-treated. Gene expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and inducible nitric oxide synthase (iNOS) was evaluated by quantitative real-time PCR in the brain and liver tissues. In the infected control group, an upregulation of TNF-α and IL-1β mRNA expression levels was found. However, a downregulation of iNOS expression was detected in the brain of infected control mice. In both BCA- and combined-treated groups, the brain and liver tissues showed significantly reduced inflammatory lesions compared to the infected control mice with inhibited TNF-α and IL-1β mRNA levels. The iNOS expression levels in the brain tissues of BCA group were significantly higher than the levels of the infected control group. BCA alone or combined significantly reducedT. gondiicyst count in the brain tissues. In conclusion, the anti-inflammatory activity of BCA was demonstrated in the brain tissues of mice with chronic toxoplasmosis with decreased TNF-α and IL-1β expression levels and increased iNOS expression levels.
Generation of hemipelvis surface geometry based on statistical shape modelling and contralateral mirroring
Authors: Krishna Praveen , Robinson Dale L. , Bucknill Andrew , Lee Peter Vee Sin
Published: June 2022

Personalised fracture plates manufactured using 3D printing offer an improved treatment option for unstable pelvic ring fractures that may not be adequately secured using off-the-shelf components. To design fracture plates that secure the bone fragments in their pre-fracture positions, the fractures must be reduced virtually using medical imaging-based reconstructions, a time-consuming process involving segmentation and repositioning of fragments until surface congruency is achieved. This study compared statistical shape models (SSMs) and contralateral mirroring as automated methods to reconstruct the hemipelvis using varying amounts of bone surface geometry. The training set for the geometries was obtained from pelvis CT scans of 33 females. The root-mean-squared error (RMSE) was quantified across the entire surface of the hemipelvis and within specific regions, and deviations of pelvic landmarks were computed from their positions in the intact hemipelvis. The reconstruction of the entire hemipelvis surfaced based on contralateral mirroring had an RMSE of 1.21 ± 0.29 mm, whereas for SSMs based on the entire hemipelvis surface, the RMSE was 1.11 ± 0.29 mm, a difference that was not significant (p = 0.32). Moreover, all hemipelvis reconstructions based on the full or partial bone geometries had RMSEs and landmark deviations from contralateral mirroring that were significantly lower (p < 0.05) or statistically equivalent to the SSMs. These results indicate that contralateral mirroring tends to be more accurate than SSMs for reconstructing unilateral pelvic fractures. SSMs may still be a viable method for hemipelvis fracture reconstruction in situations where contralateral geometries are not available, such as bilateral pelvic factures, or for highly asymmetric pelvic anatomies.
Effect of biochar on desiccation of marine soils under constant and cyclic temperatures
Authors: Puspanathan Thellen Kumar , Jayawardane Vihan Shenal , Paul Suvash Chandra , Ying Kong Sih , Shukla Sanjay Kumar , Anggraini Vivi
Published: June 2022

Biochar has recently been gaining increasing attention as a stable and sustainable soil amendment material. However, the effect of biochar amendment on the desiccation behaviour of coastal soils has not yet been examined. Consequently, the present study primarily investigated the effect of exposing biochar-amended marine soil (BAS) to constant and cyclic temperatures on its swell–shrink, evaporation and desiccation cracking characteristics. Biochar contents of 1%, 2%, 4% and particle size ranges of PS-1 (600 μm < D ≤ 2000 μm), PS-2 (300 μm < D ≤ 600 μm), PS-3 (D ≤ 75 μm) (D: biochar particle diameter) were employed. It was revealed that the absolute volumetric shrinkage of both unamended and biochar-amended specimens increased as the number of thermal cycles increased. Under continuous heat exposure, 4% (PS-3) BAS in compacted state achieved the maximum reduction in volumetric shrinkage which was 42%. Moreover, under continuous heat exposure, 2% (PS-1) BAS in slurry state achieved the highest reduction in desiccation cracking, which was 73%. The present study highlights the importance of identifying the most effective combination of biochar content and particle size required to achieve a desired outcome, in order to gain the maximum benefit of biochar as an amendment material at the lowest possible cost.
Autophagy Dysfunction in ALS: from Transport to Protein Degradation
Authors: Cozzi Marta , Ferrari Veronica
Published: June 2022

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting upper and lower motor neurons (MNs). Since the identification of the first ALS mutation in 1993, more than 40 genes have been associated with the disorder. The most frequent genetic causes of ALS are represented by mutated genes whose products challenge proteostasis, becoming unable to properly fold and consequently aggregating into inclusions that impose proteotoxic stress on affected cells. In this context, increasing evidence supports the central role played by autophagy dysfunctions in the pathogenesis of ALS. Indeed, in early stages of disease, high levels of proteins involved in autophagy are present in ALS MNs; but at the same time, with neurodegeneration progression, autophagy-mediated degradation decreases, often as a result of the accumulation of toxic protein aggregates in affected cells. Autophagy is a complex multistep pathway that has a central role in maintaining cellular homeostasis. Several proteins are involved in its tight regulation, and importantly a relevant fraction of ALS-related genes encodes products that directly take part in autophagy, further underlining the relevance of this key protein degradation system in disease onset and progression. In this review, we report the most relevant findings concerning ALS genes whose products are involved in the several steps of the autophagic pathway, from phagophore formation to autophagosome maturation and transport and finally to substrate degradation.
Inferior Vena Cava Collapsibility Index: A Precise, Noninvasive Tool for Evaluation of Edema in Children with Nephrotic Syndrome
Authors: El-Halaby Hanan , Bakr Ashraf , El-Assmy Mohamed , Abdalla Hussein Abdelaziz , Salem Marwa , Eid Riham
Published: June 2022

This study aimed to evaluate available volume status assessment tools in nephrotic syndrome (NS). Sixty children with INS were subdivided into hypovolemic and nonhypovolemic groups based on fractional excretion of sodium (FeNa%); all were studied for inferior vena cava collapsibility index (IVCCI), plasma atrial natriuretic peptide (ANP), and body composition monitor (BCM). Forty-four patients had nonhypovolemic and 16 had hypovolemic states. ANP did not differ between both groups. IVCCI was higher in hypovolemic group (p < 0.001) with sensitivity 87.5% and specificity 81.8% for hypovolemia detection, while BCM overhydration (BCM-OH) values were higher in nonhypovolemic group (p = 0.04) with sensitivity = 68.2% and specificity = 75% for detection of hypervolemia. FeNa% showed negative correlation with IVCCI (r =  −0.578, p < 0.001) and positive correlation with BCM-OH (r = 0.33, p = 0.018), while FeNa% showed nonsignificant correlation to ANP concentration. IVCCI is a reliable tool for evaluating volume status in NS and is superior to BCM.
Measuring positive memories of home and family during childhood: The development and initial validation of the ‘Memories of Home and Family Scale’
Authors: Shevlin Mark , Redican Enya , McElroy Eoin , Ben-Ezra Menachem , Karatzias Thanos , Hyland Philip
Published: June 2022

There is a burgeoning evidence base highlighting the positive influence of benevolent childhood experiences (BCEs), even in the context of adversity. However, few measures are available to assess BCEs. The current study sought to develop and validate a measure which assesses positive recollections of experiences and emotions at home and with family during childhood called the ‘Memories of Home and Family Scale’(MHFS). Confirmatory factor analysis (CFA) was employed to test the latent structure of the preliminary MHFS item scores in a sample of university students from the United Kingdom (N = 624). Following selection of the best-fitting model and final items for inclusion in the scale, total and subscale scores were correlated with a range of mental health outcomes. CFA results indicated that the latent structure of the MHFS items was best represented by a correlated six-factor first-order model.The final MHFS demonstrated high levels of internal reliability and convergent validity.