bluuebunny/crossref_metadata_2025 huggingface dataset:
Doublecortin-Like Kinase 1 (DCLK1) Is a Novel NOTCH Pathway Signaling Regulator in Head and Neck Squamous Cell Carcinoma
Authors: Broner Esther C. , Trujillo Jonathan A. , Korzinkin Michael , Subbannayya Tejaswini , Agrawal Nishant , Ozerov Ivan V. , Zhavoronkov Alex , Rooper Lisa , Kotlov Nikita , Shen Le , Pearson Alexander T. , Rosenberg Ari J. , Savage Peter A. , Mishra Vasudha , Chatterjee Aditi , Sidransky David , Izumchenko Evgeny
Published: July 2021

Despite recent advancements, the 5 year survival of head and neck squamous cell carcinoma (HNSCC) hovers at 60%. DCLK1 has been shown to regulate epithelial-to-mesenchymal transition as well as serving as a cancer stem cell marker in colon, pancreatic and renal cancer. Although it was reported that DCLK1 is associated with poor prognosis in oropharyngeal cancers, very little is known about the molecular characterization of DCLK1 in HNSCC. In this study, we performed a comprehensive transcriptome-based computational analysis on hundreds of HNSCC patients from TCGA and GEO databases, and found that DCLK1 expression positively correlates with NOTCH signaling pathway activation. Since NOTCH signaling has a recognized role in HNSCC tumorigenesis, we next performed a series of in vitro experiments in a collection of HNSCC cell lines to investigate the role of DCLK1 in NOTCH pathway regulation. Our analyses revealed that DCLK1 inhibition, using either a pharmacological inhibitor or siRNA, resulted in substantially decreased proliferation, invasion, migration, and colony formation. Furthermore, these effects paralleled downregulation of active NOTCH1, and its downstream effectors, HEY1, HES1 and HES5, whereas overexpression of DCLK1 in normal keratinocytes, lead to an upregulation of NOTCH signaling associated with increased proliferation. Analysis of 233 primary and 40 recurrent HNSCC cancer biopsies revealed that high DCLK1 expression was associated with poor prognosis and showed a trend towards higher active NOTCH1 expression in tumors with elevated DCLK1. Our results demonstrate the novel role of DCLK1 as a regulator of NOTCH signaling network and suggest its potential as a therapeutic target in HNSCC.
Pyrotinib in the Treatment of Women With HER2-Positive Advanced Breast Cancer: A Multicenter, Prospective, Real-World Study
Authors: Zhang Lili , Wu Xiaohong , Zhou Jun , Zhu Mingzhen , Yu Hao , Zhang Yusong , Zhao Yutian , Han Zhengxiang , Guo Yujiang , Guan Xiaoqing , Wang Xufen , Xu Hong , Sun Li , Zhang Jiaxin , Zhuang Min , Xie Li , Yu Shiyou , Chen Ping , Feng Jifeng
Published: July 2021

Background

HER2-positive breast cancer was aggressive, resulting in a poorer prognosis. This multicenter study analyzed the real-world data of women treated with pyrotinib-based therapy, aiming to describe their characteristics, treatment regimens, and to investigate the clinical outcomes.

Methods

A total of 141 patients with HER2-positive breast cancer were enrolled from February 2019 to April 2020. Last follow-up time was February 2021. All patients were treated with pyrotinib-based therapy in 21-day cycles. The primary endpoint was progression-free survival (PFS).

Results

The median PFS (mPFS) for pyrotinib-based therapy was 12.0 months (95%CI 8.1-17.8) in all patients. Among the patients with liver metastases, mPFS was 8.7 months (95%CI, 6.3-15.4) compared to 12.3 months (95%CI, 8.8-23.3) for patients without liver metastases (P=0.172). In addition, patients receiving pyrotinib-based therapy as their >2 lines treatment had a numerically lower mPFS than those receiving pyrotinib-based therapy as their ≤2 lines treatment [8.4 (95%CI, 5.9-15.4) vs. 15.1 (95%CI, 9.3-22.9) months, P=0.107]. The mPFS was 12.2 months (95%CI, 7.9-18.8) in patients with previous exposure to trastuzumab and 11.8 months (95%CI, 6.8-22.9) in patients without previous exposure to trastuzumab (P=0.732). Moreover, mPFS in patients receiving regimens with and without capecitabine were 15.1 months (95%CI, 10.0-18.8) and 8.4 months (95%CI, 6.7-22.9), respectively (P=0.070). Furthermore, in patients with brain metastases, estimated 6-month PFS rate was 70.0%, and rate at 12 months was 60.0%. Seventy patients with measurable lesions were evaluable for response. The objective response rate was 38.6% and disease control rate was 85.7%. The most common adverse event was diarrhea (85.0%).

Conclusion

Pyrotinib-based therapy showed promising efficacy in patients with HER2-positive breast cancer and was well tolerated, especially in patients treated with pyrotinib as ≤2 lines treatment and receiving regimens with capecitabine. The results of this real-world study further confirmed the intriguing efficacy of pyrotinib.
Siglec-15 Promotes Tumor Progression in Osteosarcoma via DUSP1/MAPK Pathway
Authors: Fan Meng-ke , Zhang Guo-chuan , Chen Wei , Qi Li-li , Xie Ming-fang , Zhang Yue-yao , Wang Ling , Zhang Qi
Published: July 2021

Recurrence and metastasis are important features of osteosarcoma (OS) that cause its poor prognosis. Aberrant expression of Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) has been reported in various kinds of cancers. However, the expression and function of Siglec-15 in OS remain unclear. In cultured OS cells (143B cells and MNNG/HOS cells) and their xenograft mouse models, we found that downregulation of Siglec-15 could inhibit the proliferation, migration and invasion of by inducing epithelial-mesenchymal transition (EMT) in vitro and in vivo. Conversely, Siglec-15 overexpression promoted the growth, migration and invasion of OS cells in a significant manner. Then, we screened a number of differentially expressed genes (DEGs) between Siglec-15-knockdown group and control group by RNA-Seq assay. Among these DEGs, we found that dual-specificity phosphatase 1 (DUSP1/MKP1) was significantly downregulated after Siglec-15 silencing. We investigated the DUSP1 functions in influencing OS cells’ biology, and found that the proliferation, migration and invasion of OS cells were promoted by overexpressing DUSP1 and crucially, the proliferation, migration and invasion of Siglec-15-knockdown OS cells were rescued by overexpressing DUSP1. Mechanically, we further showed that DUSP1-mediated inhibition of p38/MAPK and JNK/MAPK expression was attenuated when Siglec-15 expression was inhibited, suggesting that Siglec-15 promotes the malignant progression of OS cells by suppressing DUSP1-mediated suppression of the MAPK pathway. Moreover, we showed that both Siglec-15 and DUSP1 were highly expressed in human OS tissues by immunohistochemistry. High Siglec-15 expression was associated with OS lung metastasis, and high DUSP1 expression was associated with the high Enneking stage. Kaplan–Meier analysis indicated that high expression of Siglec-15 could predict poor prognosis of OS patients. Altogether, these results showed that Siglec-15 expression promoted OS development and progression by activating DUSP1 and might be a novel target in OS treatment.
Real-World Analysis of Survival and Clinical Events in a Cohort of Italian Perinatally HIV-1 Infected Children From 2001 to 2018
Authors: Chiappini Elena , Larotonda Francesca , Lisi Catiuscia , Giacomet Vania , Erba Paola , Bernardi Stefania , Zangari Paola , Di Biagio Antonio , Taramasso Lucia , Giaquinto Carlo , Rampon Osvalda , Gabiano Clara , Garazzino Silvia , Tagliabue Claudia , Esposito Susanna , Bruzzese Eugenia , Badolato Raffaele , Zanaboni Domenico , Cellini Monica , Dedoni Maurizio , Mazza Antonio , Pession Andrea , Giannini Anna Maria , Salvini Filippo , Dodi Icilio , Carloni Ines , Cazzato Salvatore , Tovo Pier Angelo , de Martino Maurizio , Galli Luisa
Published: July 2021

Background:Combined antiretroviral therapy (cART) has been associated with a steep decrease in mortality and morbidity in HIV-1 infected children. New antiretroviral molecules and drug classes have been developed and the management of HIV-infected children has improved, but recent data on survival are limited.

Methods:An observational retrospective study investigating changes in mortality and morbidity was conducted on 1,091 perinatally HIV-1 infected children enrolled in the Italian Register for HIV Infection in Children and followed-up from 2001 to 2018.

Results:Three hundred and fifty-four (32%) AIDS events and 26 (2%) deaths occurred overtime. Mortality rates decreased from 0.4/100 person-years in 2001–2006 to 0.27/100 person-years in 2007–2012 and 0.07/100 person-years in 2013–2018. Notably, 92% of the dead children were born in Italy, but only 50% were followed-up since birth or within three months of age. Seventy three percent of children had started cART at age ≥6 months; 23% were treated for <30 days before death. B and C clinical events progressively decreased (P< 0.0001). Opportunistic infections significantly decreased over time, but still were the most common events in all the periods (6.76/100 person-years in 2013–2018). In the last period, severe bacterial infections were the most common ones. Cancer rates were 0.07/100; 0.17/100; 0.07/100 person-years in the three periods, respectively.

Conclusions:Progressive reductions both in mortality and in rates of class B and C clinical events and OIs have been observed during the cART era. However, deaths were still registered; more than half of dead children were enrolled after birth and had belatedly started cART.
Physiological and Biochemical Response of Tropical Fruits to Hypoxia/Anoxia
Authors: Benkeblia Noureddine
Published: July 2021

Aerobic respiration and oxygen consumption are indicators of routine metabolic rate, and dissolved oxygen in plant tissues is one of the most important environmental factors affecting their survival. The reduction of available O2leads to hypoxia which causes a limitation of the oxidative phosphorylation; when O2is absent, tissues generate ATP by activating the fermentative glycolysis to sustain glycolysis in the absence of mitochondrial respiration, which results in the production of lactate. Overall, hypoxia was reported to often decrease the respiration rate (O2uptake) and delay the climacteric rise of ethylene in climacteric fruits by inhibiting action, thus delaying their ripening. Much research has been done on the application of postharvest hypoxia and anoxia treatment to temperate fresh crops (controlled or modified atmosphere), however, very few reported on tropical commodities. Indeed, the physiological mode of action of low or absence of oxygen in fresh crops is not well understood; and the physiological and biochemical bases of the effects low or absence of O2are also yet to be clarified. Recent investigations using omics technologies, however, have provided useful information on the response of fresh fruits and vegetables to this abiotic stress. The aims of this review are to (i) report on the oxygen exchange in the crops tissue, (ii) discuss the metabolic responses to hypoxia and anoxia, and (iii) report the physiological and biochemical responses of crops tissues to these abiotic stresses and the potential benefits of these environmental conditions.
Do Histories of Painful Life Experiences Affect the Expression of Empathy Among Young Adults? An Electroencephalography Study
Authors: Yaghoubi Jami Parvaneh , Han Hyemin , Thoma Stephen J. , Mansouri Behzad , Houser Rick
Published: July 2021

Previous research suggests that prior experience of pain affects the expression of empathy. However, most of these studies attended to physical pain despite evidence indicating that other forms of pain may also affect brain activity and emotional states in similar ways. To address this limitation, we compared empathic responses of 33 participants, some of whom had experienced a personal loss, across three conditions: observing strangers in physical pain, psychological pain, and a non-painful condition. We also examined the effect of presence of prior painful experience on empathic reactions. In addition, we examined the stimulation type, prior experience, and ERPs in the early Late Positive Potential (300–550 ms), late Late Positive Potential (550–800 ms), and very late Late Positive Potential (VLLPP; 800–1,050 ms) time windows. Behavioral data indicated that participants who had personally experienced a loss scored significantly higher on perspective taking in the psychological-pain condition. ERP results also indicated significantly lower intensity in Fp2, an electrode in the prefrontal region, within VLLPP time window for participants experiencing a loss in the psychological-pain condition. The results of both behavioral and ERP analysis indicated that prior experience of psychological pain is related to cognitive empathy, but not affective empathy. The implication of these findings for research on empathy, for the study of psychological pain, and the moderating influence of prior painful experiences are discussed.
Socially Shared Feelings of Imminent Recall: More Tip-of-the-Tongue States Are Experienced in Small Groups
Authors: Rousseau Luc , Kashur Nathalie
Published: July 2021

Tip-of-the-tongue (TOT) states are typically defined as feelings of imminent recall for known, but temporarily inaccessible target words. However, TOTs are not merely instances of retrieval failures. Clues that increase the subjective likelihood of retrieval success, such as cue familiarity and target-related information, also have been shown to elicit feelings of imminent recall, supporting a metacognitive, inferential etiology of the TOT phenomenon. A survey conducted on our university campus provided anecdotal evidence that TOTs are occasionally shared among people in small groups. Although shared TOTs may suggest the influence of social contagion, we hypothesized that metacognitive appraisal of group recall efficiency could be involved. There should be more instances of remembering in several heads than in one. From this, we conjectured that people remembering together entertain the inference that successful retrieval is more likely in group recall than in a single-person recall situation. Such a metacognitive appraisal may drive a stronger feeling of closeness with the target word and of recall imminence, precipitating one (or more people) into a TOT state. We used general knowledge questions to elicit TOTs. We found that participants reported more TOTs when remembering in small groups than participants remembering alone. Critically, the experimental manipulation selectively increased TOTs without affecting correct recall, suggesting that additional TOTs observed in small groups were triggered independently from the retrieval process. Near one third (31%) of the TOTs in small groups were reported by two or more participants for the same items. However, removing common TOTs from the analyses did not change the basic pattern of results, suggesting that social contagion was not the main factor involved in the observed effect. We argue that beyond social contagion, group recall magnifies the inference that target words will be successfully retrieved, prompting the metacognitive monitoring system to launch more near-retrieval success “warning” (TOT) signals than in a single-person recall situation.
Effectiveness and Acceptance of a Smartphone-Based Virtual Agent Screening for Alcohol and Tobacco Problems and Associated Risk Factors During COVID-19 Pandemic in the General Population
Authors: Auriacombe Marc , Fournet Lucie , Dupuy Lucile , Micoulaud-Franchi Jean-Arthur , de Sevin Etienne , Moriceau Sarah , Baillet Emmanuelle , Alexandre Jean-Marc , Serre Fuschia , Philip Pierre
Published: July 2021

Background: During the current COVID-19 pandemic, alcohol, and tobacco are the most available substances for managing stress and can induce a risk of addiction. KANOPEE is a smartphone application available to the general population using an embodied conversational agent (ECA) to screen for experiences of problems with alcohol/tobacco use and to provide follow-up tools for brief intervention.

Objectives: This study aimed to determine if the smartphone KANOPEE application could identify people at risk for alcohol and/or tobacco use disorders in the context of the current COVID-19 pandemic, to assess adherence to a 7-day follow-up use diary, and to evaluate trust and acceptance of the application.

Methods: The conversational agent, named Jeanne, interviewed participants about perceived problems with the use of alcohol and tobacco since the pandemic and explored risk for tobacco and alcohol use disorder with the five-item Cigarette Dependence Scale (CDS-5) and “Cut Down, Annoyed, Guilty, Eye-opener” (CAGE) questionnaire and experience of craving for each substance. Descriptive, univariate, and multivariate analyses were performed to specify personalized associations with reporting a problem with alcohol/tobacco use; descriptive analysis reported the experience with the intervention and acceptance and trust in the application.

Results: From April 22 to October 26, 2020, 1,588 French participants completed the KANOPEE interview, and 318 answered the acceptance and trust scales. Forty-two percent of tobacco users and 27% of alcohol users reported problem use since the pandemic. Positive screening with CDS-5 and CAGE and craving were associated with reported problem use (p < 0.0001). Lockdown period influenced alcohol (p < 0.0005) but not tobacco use (p > 0.05). Eighty-eight percent of users reported that KANOPEE was easy to use, and 82% found Jeanne to be trustworthy and credible.

Conclusion: KANOPEE was able to screen for risk factors for substance use disorder (SUD) and was acceptable to users. Reporting craving and being at risk for SUD seem to be early markers to be identified. Alcohol problem use seems to be more reliant on contextual conditions such as confinement. This method is able to offer acceptable, brief, and early intervention with minimal delay for vulnerable people.
Prevalence and Incidence of Sexually Transmitted Infection in Injectable Progestin Contraception Users in South Africa
Authors: Noguchi Lisa M. , Marrazzo Jeanne M. , Richardson Barbara , Hillier Sharon L. , Balkus Jennifer E. , Palanee-Phillips Thesla , Nair Gonasagrie , Panchia Ravindre , Piper Jeanna , Gomez Kailazarid , Ramjee Gita , Chirenje Z. Mike
Published: July 2021

Introduction: Whether intramuscular depot medroxyprogesterone acetate (DMPA-IM) and norethisterone enanthate (NET-EN) have a differential impact on the incidence of sexually transmitted infection (STI) remains unclear. In the Vaginal and Oral Interventions to Control the Epidemic (VOICE) trial, HIV-1 acquisition was higher for DMPA-IM users vs. NET-EN users. We compared DMPA-IM and NET-EN users with regard to chlamydia, gonorrhea, trichomoniasis, syphilis, and herpes simplex virus type 2 (HSV-2) infection.

Materials and Methods: Prospective data were analyzed from VOICE, a randomized trial of HIV-1 chemoprophylaxis. Participants were evaluated annually and as indicated for chlamydia, gonorrhea, trichomoniasis, and syphilis. Stored specimens were tested for HSV-2. Proportional hazards models compared the risk of STI between DMPA-IM and NET-EN users.

Results: Among 2,911 injectable contraception users in South Africa, 1,800 (61.8%) used DMPA-IM and 1,111 used NET-EN (38.2%). DMPA-IM and NET-EN users did not differ in baseline chlamydia: 15.1 vs. 14.3%, p = 0.54; gonorrhea: 3.4 vs. 3.7%, p = 0.70; trichomoniasis: 5.7 vs.5.0%, p = 0.40; or syphilis: 1.5 vs. 0.7%, p = 0.08; but differed for baseline HSV-2: (51.3 vs. 38.6%, p < 0.001). Four hundred forty-eight incident chlamydia, 103 gonorrhea, 150 trichomonas, 17 syphilis, and 48 HSV-2 infections were detected over 2,742, 2,742, 2,783, 2,945, and 756 person-years (py), respectively (chlamydia 16.3/100 py; gonorrhea 3.8/100 py; trichomoniasis 5.4/100 py; syphilis 0.6/100 py; HSV-2 6.4/100 py). Comparing DMPA-IM with NET-EN users, no difference was noted in the incidence of chlamydia, gonorrhea, trichomoniasis, syphilis, or HSV-2 infections, including when adjusted for confounders [chlamydia (aHR 1.03, 95% CI 0.85–1.25), gonorrhea (aHR 0.88, 95% CI 0.60–1.31), trichomoniasis (aHR 1.07, 95% CI 0.74–1.54), syphilis (aHR 0.41, 95% CI 0.15–1.10), and HSV-2 (aHR 0.83, 95% CI 0.45–1.54, p = 0.56)].

Discussion: Among South African participants enrolled in VOICE, DMPA-IM and NET-EN users differed in prevalence of HSV-2 at baseline but did not differ in the incidence of chlamydia, gonorrhea, trichomoniasis, syphilis, or HSV-2 infection. Differential HIV-1 acquisition, previously demonstrated in this cohort, does not appear to be explained by differential STI acquisition. However, the high incidence of multiple STIs reinforces the need to accelerate access to comprehensive sexual and reproductive health services.
Alteration of the Canine Metabolome After a 3-Week Supplementation of Cannabidiol (CBD) Containing Treats: An Exploratory Study of Healthy Animals
Authors: Morris Elizabeth M. , Kitts-Morgan Susanna E. , Spangler Dawn M. , Ogunade Ibukun M. , McLeod Kyle R. , Harmon David L.
Published: July 2021

Despite the increased interest and widespread use of cannabidiol (CBD) in humans and companion animals, much remains to be learned about its effects on health and physiology. Metabolomics is a useful tool to evaluate changes in the health status of animals and to analyze metabolic alterations caused by diet, disease, or other factors. Thus, the purpose of this investigation was to evaluate the impact of CBD supplementation on the canine plasma metabolome. Sixteen dogs (18.2 ± 3.4 kg BW) were utilized in a completely randomized design with treatments consisting of control and 4.5 mg CBD/kg BW/d. After 21 d of treatment, blood was collected ~2 h after treat consumption. Plasma collected from samples was analyzed using CIL/LC-MS-based untargeted metabolomics to analyze amine/phenol- and carbonyl-containing metabolites. Metabolites that differed — fold change (FC) ≥ 1.2 or ≤ 0.83 and false discovery ratio (FDR) ≤ 0.05 — between the two treatments were identified using a volcano plot. Biomarker analysis based on receiver operating characteristic (ROC) curves was performed to identify biomarker candidates (area under ROC ≥ 0.90) of the effects of CBD supplementation. Volcano plot analysis revealed that 32 amine/phenol-containing metabolites and five carbonyl-containing metabolites were differentially altered (FC ≥ 1.2 or ≤ 0.83, FDR ≤ 0.05) by CBD; these metabolites are involved in the metabolism of amino acids, glucose, vitamins, nucleotides, and hydroxycinnamic acid derivatives. Biomarker analysis identified 24 amine/phenol-containing metabolites and 1 carbonyl-containing metabolite as candidate biomarkers of the effects of CBD (area under ROC ≥ 0.90;P< 0.01). Results of this study indicate that 3 weeks of 4.5 mg CBD/kg BW/d supplementation altered the canine metabolome. Additional work is warranted to investigate the physiological relevance of these changes.
The Interplay between S-Glutathionylation and Phosphorylation of Cardiac Troponin I and Myosin Binding Protein C in End-Stage Human Failing Hearts
Authors: Budde Heidi , Hassoun Roua , Tangos Melina , Zhazykbayeva Saltanat , Herwig Melissa , Varatnitskaya Marharyta , Sieme Marcel , Delalat Simin , Sultana Innas , Kolijn Detmar , Gömöri Kamilla , Jarkas Muhammad , Lódi Mária , Jaquet Kornelia , Kovács Árpád , Mannherz Hans Georg , Sequeira Vasco , Mügge Andreas , Leichert Lars I. , Sossalla Samuel , Hamdani Nazha
Published: July 2021

Oxidative stress is defined as an imbalance between the antioxidant defense system and the production of reactive oxygen species (ROS). At low levels, ROS are involved in the regulation of redox signaling for cell protection. However, upon chronical increase in oxidative stress, cell damage occurs, due to protein, DNA and lipid oxidation. Here, we investigated the oxidative modifications of myofilament proteins, and their role in modulating cardiomyocyte function in end-stage human failing hearts. We found altered maximum Ca2+-activated tension and Ca2+ sensitivity of force production of skinned single cardiomyocytes in end-stage human failing hearts compared to non-failing hearts, which was corrected upon treatment with reduced glutathione enzyme. This was accompanied by the increased oxidation of troponin I and myosin binding protein C, and decreased levels of protein kinases A (PKA)- and C (PKC)-mediated phosphorylation of both proteins. The Ca2+ sensitivity and maximal tension correlated strongly with the myofilament oxidation levels, hypo-phosphorylation, and oxidative stress parameters that were measured in all the samples. Furthermore, we detected elevated titin-based myocardial stiffness in HF myocytes, which was reversed by PKA and reduced glutathione enzyme treatment. Finally, many oxidative stress and inflammation parameters were significantly elevated in failing hearts compared to non-failing hearts, and corrected upon treatment with the anti-oxidant GSH enzyme. Here, we provide evidence that the altered mechanical properties of failing human cardiomyocytes are partially due to phosphorylation, S-glutathionylation, and the interplay between the two post-translational modifications, which contribute to the development of heart failure.
Agent-Based Simulation to Measure the Effectiveness of Citizen Sensing Applications—The Case of Missing Children
Authors: Michalitsi-Psarrou Ariadni , Papageorgiou Iason Lazaros , Ntanos Christos , Psarras John
Published: July 2021

Citizen sensing applications need to have a number of users defined that ensures their effectiveness. This is not a straightforward task because neither the relationship between the size of the userbase or its effectiveness is easily quantified, nor is it clear which threshold for the number of users would make the application ‘effective’. This paper presents an approach for estimating the number of users needed for location-based crowdsourcing applications to work successfully, depending on the use case, the circumstances, and the criteria of success. It circumvents various issues, ethical or practical, in performing real-world controlled experiments and tackles this challenge by developing an agent-based modelling and simulation framework. This framework is tested on a specific scenario, that of missing children and the search for them. The search is performed with the contribution of citizens being made aware of the disappearance through a mobile application. The result produces an easily reconfigurable testbed for the effectiveness of citizen sensing mobile applications, allowing the study of the marginal utility of new users of the application. The resulting framework aims to be the digital twin of a real urban scenario, and it has been designed to be easily adapted and support decisions on the feasibility, evaluation, and targeting of the deployment of spatial crowdsourcing applications.
Impact of HPC and Automated CFD Simulation Processes on Virtual Product Development—A Case Study
Authors: Lange Christopher , Barthelmäs Patrick , Rosnitschek Tobias , Tremmel Stephan , Rieg Frank
Published: July 2021

High-performance computing (HPC) enables both academia and industry to accelerate simulation-driven product development processes by providing a massively parallel computing infrastructure. In particular, the automation of high-fidelity computational fluid dynamics (CFD) analyses aided by HPC systems can be beneficial since computing time decreases while the number of significant design iterations increases. However, no studies have quantified these effects from a product development point of view yet. This article evaluates the impact of HPC and automation on product development by studying a formula student racing team as a representative example of a small or medium-sized company. Over several seasons, we accompanied the team, and provided HPC infrastructure and methods to automate their CFD simulation processes. By comparing the team’s key performance indicators (KPIs) before and after the HPC implementation, we were able to quantify a significant increase in development efficiency in both qualitative and quantitative aspects. The major aerodynamic KPI increased up to 115%. Simultaneously, the number of expedient design iterations within one season increased by 600% while utilizing HPC. These results prove the substantial benefits of HPC and automation of numerical-intensive simulation processes for product development.
Empowering Advanced Parametric Modes Clustering from Topological Data Analysis
Authors: Frahi Tarek , Falco Antonio , Mau Baptiste Vinh , Duval Jean Louis , Chinesta Francisco
Published: July 2021

Modal analysis is widely used for addressing NVH—Noise, Vibration, and Hardness—in automotive engineering. The so-called principal modes constitute an orthogonal basis, obtained from the eigenvectors related to the dynamical problem. When this basis is used for expressing the displacement field of a dynamical problem, the model equations become uncoupled. Moreover, a reduced basis can be defined according to the eigenvalues magnitude, leading to an uncoupled reduced model, especially appealing when solving large dynamical systems. However, engineering looks for optimal designs and therefore it focuses on parametric designs needing the efficient solution of parametric dynamical models. Solving parametrized eigenproblems remains a tricky issue, and, therefore, nonintrusive approaches are privileged. In that framework, a reduced basis consisting of the most significant eigenmodes is retained for each choice of the model parameters under consideration. Then, one is tempted to create a parametric reduced basis, by simply expressing the reduced basis parametrically by using an appropriate regression technique. However, an issue remains that limits the direct application of the just referred approach, the one related to the basis ordering. In order to order the modes before interpolating them, different techniques were proposed in the past, being the Modal Assurance Criterion—MAC—one of the most widely used. In the present paper, we proposed an alternative technique that, instead of operating at the eigenmodes level, classify the modes with respect to the deformed structure shapes that the eigenmodes induce, by invoking the so-called Topological Data Analysis—TDA—that ensures the invariance properties that topology ensure.
Bias Effects on g- and s-Factors in Westcott Convention
Authors: Harada Hideo
Published: July 2021

For accuracy improvement of neutron activation analysis and neutron capture cross sections, bias effects are investigated on g- and s-factors in the Westcott convention. As origins of biases, a joining function shape, neutron temperature, and sample temperature have been investigated. Biases are quantitatively deduced for two 1/v isotopes (197Au, 59Co) and six non-1/v isotopes (241Am, 151Eu, 103Rh, 115In, 177Hf, 226Ra). The s-factor calculated with a joining function deduced recently by a detailed Monte Carlo simulation is compared to s-factors calculated with traditional joining functions by Westcott. The results show the bias induced by the sample temperature is small, in the order of 0.1% for the g-factor and in the order of 1% for the s-factor. On the other hand, the bias size induced by a joining function shape for the s-factor depends significantly on both isotopes and neutron temperature. As a result, the reaction rates are also affected significantly. The bias size for the reaction rate is given in the case of an epithermal neutron index r = 0.1, for the eight isotopes.
Soft Bio-Integrated Multifunctional Devices Using an Intrinsically Stretchable Conducting Nanomembrane
Authors: Lee Sangkyu , Kang Kyumin , Choi Heewon , Yoon Jiyong , Kim Yewon , An Soojung , Jung Hyunjin , Seong Duhwan , Park Kyuha , Baac Hyoungwon , Son Donghee
Published: July 2021

Soft bioelectronic systems with a unique mechanical property, namely modulus matching between human skin (or tissue) and the device, have gained widespread attention. This is because of their closed-loop strain-insensitive electrical performance ranging from application in the long-term stable measurements of physiological signals and feedback modulation to human skin (or organs). Various materials and integration/fabrication strategies such as buckled, rigid islands, and wavy designs addressed for soft bioelectronic systems require complex device fabrication with time-consuming packaging and integration processes. In this study, we developed a soft bio-integrated multifunctional device (SBMD) fabricated through the simple thermal evaporation and transfer processes. The intrinsically stretchable Au–SEBS film composed of thermally evaporated gold (Au) nanomembranes and an elastomeric substrate was applied to various functional modules that are capable of sensing the strain (up to ~300%), temperature (with a thermal sensitivity of ~0.6 Ω/°C), chemicals (at a concentration of NaCl of ~0.5 wt%), and even electrophysiological cardiac/muscle signals and showing thermal actuations (80 °C at 9 V). Specifically, such multifunctions of the SBMD were stably performed even on skin. Thus, we believe the SBMD would be a promising candidate for realizing soft bioelectronic systems.
Biphasic Effects of Blue Light Irradiation on Human Umbilical Vein Endothelial Cells
Authors: Kan Kejia , Mu Yifei , Bouschbacher Marielle , Sticht Carsten , Kuch Natalia , Sigl Martin , Rahbari Nuh , Gretz Norbert , Pallavi Prama , Keese Michael
Published: July 2021

Blue light regulates biological function in various cells, such as proliferation, oxidative stress, and cell death. We employed blue light illumination on human umbilical vein endothelial cells utilizing a LED device at 453 nm wavelength and revealed a novel biphasic response on human umbilical vein endothelial cells (HUVECs). The results showed that low fluence blue light irradiation promoted the fundamental cell activities, including cell viability, migration and angiogenesis by activating the angiogenic pathways such as the VEGF signaling pathway. In contrast, high fluence illumination caused the opposite effect on those activities by upregulating pro-apoptotic signaling cascades like ferroptosis, necroptosis and the p53 signaling pathways. Our results provide an underlying insight into photobiomodulation by blue light and may help to implement potential treatment strategies for treating angiogenesis-dependent diseases.
Evaluation of T2-Weighted MRI for Visualization and Sparing of Urethra with MR-Guided Radiation Therapy (MRgRT) On-Board MRI
Authors: Pham Jonathan , Savjani Ricky R. , Gao Yu , Cao Minsong , Hu Peng , Sheng Ke , Low Daniel A. , Steinberg Michael , Kishan Amar U. , Yang Yingli
Published: July 2021

Purpose: To evaluate urethral contours from two optimized urethral MRI sequences with an MR-guided radiotherapy system (MRgRT). Methods: Eleven prostate cancer patients were scanned on a MRgRT system using optimized urethral 3D HASTE and 3D TSE. A resident radiation oncologist contoured the prostatic urethra on the patients’ planning CT, diagnostic 3T T2w MRI, and both urethral MRIs. An attending radiation oncologist reviewed/edited the resident’s contours and additionally contoured the prostatic urethra on the clinical planning MRgRT MRI (bSSFP). For each image, the resident radiation oncologist, attending radiation oncologist, and a senior medical physicist qualitatively scored the prostatic urethra visibility. Using MRgRT 3D HASTE-based contouring workflow as baseline, prostatic urethra contours drawn on CT, diagnostic MRI, clinical bSSFP and 3D TSE were evaluated relative to the contour on 3D HASTE using 95th percentile Hausdorff distance (HD95), mean-distance-to-agreement (MDA), and DICE coefficient. Additionally, prostatic urethra contrast-to-noise-ratios (CNR) were calculated for all images. Results: For two out of three observers, the urethra visibility score for 3D HASTE was significantly higher than CT, and clinical bSSFP, but was not significantly different from diagnostic MRI. The mean HD95/MDA/DICE values were 11.35 ± 3.55 mm/5.77 ± 2.69 mm/0.07 ± 0.08 for CT, 7.62 ± 2.75 mm/3.83 ± 1.47 mm/0.12 ± 0.10 for CT + diagnostic MRI, 5.49 ± 2.32 mm/2.18 ± 1.19 mm/0.35 ± 0.19 for 3D TSE, and 6.34 ± 2.89 mm/2.65 ± 1.31 mm/0.21 ± 0.12 for clinical bSSFP. The CNR for 3D HASTE was significantly higher than CT, diagnostic MRI, and clinical bSSFP, but was not significantly different from 3D TSE. Conclusion: The urethra’s visibility scores showed optimized urethral MRgRT 3D HASTE was superior to the other tested methodologies. The prostatic urethra contours demonstrated significant variability from different imaging and workflows. Urethra contouring uncertainty introduced by cross-modality registration and sub-optimal imaging contrast may lead to significant treatment degradation when urethral sparing is implemented to minimize genitourinary toxicity.
Ten Years (2011–2021) of the Italian Lombardy ADHD Register for the Diagnosis and Treatment of Children and Adolescents with ADHD
Authors: Bonati Maurizio , Scarpellini Francesca , Cartabia Massimo , Zanetti Michele ,   on behalf of the Lombardy ADHD Group
Published: July 2021

Background: The purpose of this article is to update the diagnostic assessment, therapeutic approach, and 12–18 month follow-up of patients added to the Italian Lombardy Attention Deficit Hyperactivity Disorder (ADHD) Register. Methods: Medical records of patients added to the Registry from 2011 to 2021 were analysed. Results: 4091 of 5934 patients met the criteria for a diagnosis of ADHD, and 20.3% of them presented a familiarity with the disorder. A total of 2879 children (70.4%) had at least one comorbidity disorder, in prevalence a learning disorder (39%). Nearly all (95.9%) received at least one psychological prescription, 17.9% of them almost one pharmacological treatment, and 15.6% a combination of both. Values of ≥5 of the Clinical Global Impression—Severity scale (CGI-S) are more commonly presented by patients with a pharmacological prescription than with a psychological treatment (p < 0.0001). A significant improvement was reported in half of the patients followed after 1 year, with Clinical Global Impression—Improvement scale (CGI-I) ≤ 3. In all, 233 of 4091 are 18-year-old patients. Conclusions: A ten-year systematic monitoring of models of care was a fruitful shared and collaborative initiative in order to promote significant improvement in clinical practice, providing effective and continuous quality of care. The unique experience reported here should spread.
Is ABO-Incompatible Living Donor Liver Transplantation Really a Good Alternative for Pediatric Recipients?
Authors: de Magnée Catherine , Brunée Louise , Tambucci Roberto , Pire Aurore , Scheers Isabelle , Sokal Etienne M. , Baldin Pamela , Zech Francis , Eeckhoudt Stéphane , Reding Raymond , Stephenne Xavier
Published: July 2021

Background: ABO-incompatible (ABOi) living donor liver transplantation (LDLT) has been proposed to compensate for donor shortage. To date, few studies have reported detailed ABOi LDLT results in large series of pediatric patients. C4d complement deposition in graft capillaries has been reported to be associated with antibody-mediated rejection in solid organ transplantation. Methods: A retrospective case–control study was conducted, comparing clinical outcomes of each of 34 consecutive pediatric ABOi LDLT recipients with those of 2 non-ABOi pairs (n = 68), matched according to pre-transplant diagnostic criteria, age, and date of transplantation. In addition, we studied the C4d immunostaining pattern in 22 ABOi and in 36 non-ABOi recipients whose liver biopsy was performed within the first 4 post-transplant weeks for suspected acute rejection. Results: The incidence of biliary complications was higher in ABOi recipients (p < 0.05), as were the incidence of acute humoral rejection (p < 0.01) and the incidence of retransplantation (p < 0.05). All children who required retransplantation were older than 1 year at the time of ABOi LDLT. Positive C4d immunostaining was observed in 13/22 (59%) ABOi recipients versus 3/36 (8.3%) non-ABOi recipients (p < 0.0001). Conclusions: ABOi LDLT is a feasible option for pediatric end-stage liver disease but carries increased risks for the recipient, especially for children older than 1 year, even with a specific preparation protocol. C4d immunostaining may be a hallmark of acute humoral rejection in ABOi liver transplantation.
HE4 in the Diagnostic Approach of Endometrial Cancer in Patients with Postmenopausal Bleeding, the METRODEC Protocol: Protocol for a Multicenter Prospective Study
Authors: Degez Manon , Caillon Hélène , Chauviré-Drouard Anne , Leroy Maxime , Lair David , Winer Norbert , Thubert Thibault , Le Floch Pauline , Desroys du Roure Valérie , Randet Mélanie , Ducarme Guillaume , Dochez Vincent
Published: July 2021

Background: Endometrial cancer is the most common pelvic gynecological cancer in France. The most frequent symptom is post-menopausal bleeding and is one of the primary reasons for consultation in gynecological emergencies. The treatment is very codified and consists of a surgical intervention for anatomopathological analysis. The latter is frequently reassuring. These interventions are often performed in mild situations and there is currently no element to be sufficiently reassuring to avoid surgery. This study aims to explore the sensitivity of an innovative marker: Human Epididymis 4 (HE4) in the diagnosis approach of endometrial cancer in case of postmenopausal bleedings. Methods: This is a prospective multicenter diagnostic study with three centers involved. Inclusion criteria are any patient with post-menopausal bleeding who is to undergo hysteroscopy, endometrial biopsy, or endometrial resection. In accordance with the recommendations for the management of post-menopausal bleedings, the medical conduct consists of performing a clinical examination, an ultrasound and, in general, even in case of paraclinical examination reassuring, an anatomopathological analysis. This pathological analysis can be obtained in several ways: biopsy, hysteroscopy-curettage (which is the most frequently performed surgery), and hysterectomy. Our protocol consists of taking a blood sample from each woman who will undergo one of the interventions mentioned above. The dosage of HE4 and CA125 requires the withdrawal of an additional heparinized tube during the preoperative assessment usually performed. This research is therefore classified as non-interventional. The primary outcome is to evaluate the sensitivity of the HE4 marker in patients with postmenopausal bleeding in the diagnosis of endometrial cancer. The secondary outcomes are other parameters (specificity, VPP, VPN) of HE4, Evaluating the diagnostic capabilities of the CA125 marker alone and associated with HE4, as well as those of the REM and REM-B algorithms. We aim to include 100 patients over a period of one year in three centers. Discussion: As of now, there is no biological marker used in routine practice in the diagnosis of endometrial cancer. The ultimate goal of HE4 in endometrial cancer is to avoid surgery for those who are identified as non-sick. This study is the precursor of others for use in routine practice, HE4 would represent a great help to diagnosis if our study demonstrates it as reliable in the management of these patients and avoid many unnecessary and risky surgeries.
Progress in Diagnosing Primary Ciliary Dyskinesia: The North American Perspective
Authors: O’Connor Michael Glenn , Horani Amjad , Shapiro Adam J.
Published: July 2021

Primary Ciliary Dyskinesia (PCD) is a rare, under-recognized disease that affects respiratory ciliary function, resulting in chronic oto-sino-pulmonary disease. The PCD clinical phenotype overlaps with other common respiratory conditions and no single diagnostic test detects all forms of PCD. In 2018, PCD experts collaborated with the American Thoracic Society (ATS) to create a clinical diagnostic guideline for patients across North America, specifically considering the local resources and limitations for PCD diagnosis in the United States and Canada. Nasal nitric oxide (nNO) testing is recommended for first-line testing in patients ≥5 years old with a compatible clinical phenotype; however, all low nNO values require confirmation with genetic testing or ciliary electron micrograph (EM) analysis. Furthermore, these guidelines recognize that not all North American patients have access to nNO testing and isolated genetic testing is appropriate in cases with strong clinical PCD phenotypes. For unresolved diagnostic cases, referral to a PCD Foundation accredited center is recommended. The purpose of this narrative review is to provide insight on the North American PCD diagnostic process, to enhance the understanding of and adherence to current guidelines, and to promote collaboration with diagnostic pathways used outside of North America.
Predictors of Newborn’s Weight for Height: A Machine Learning Study Using Nationwide Multicenter Ultrasound Data
Authors: Ahn Ki , Lee Kwang-Sig , Lee Se , Kwon Sung , Na Sunghun , Kim Kyongjin , Kang Hye , Lee Kyung , Won Hye-Sung , Kim Moon , Hwang Han , Park Mi ,   Korean Society of Ultrasound in Obstetrics Gynecology Research Group
Published: July 2021

There has been no machine learning study with a rich collection of clinical, sonographic markers to compare the performance measures for a variety of newborns’ weight-for-height indicators. This study compared the performance measures for a variety of newborns’ weight-for-height indicators based on machine learning, ultrasonographic data and maternal/delivery information. The source of data for this study was a multi-center retrospective study with 2949 mother–newborn pairs. The mean-squared-error-over-variance measures of five machine learning approaches were compared for newborn’s weight, newborn’s weight/height, newborn’s weight/height2 and newborn’s weight/hieght3. Random forest variable importance, the influence of a variable over average node impurity, was used to identify major predictors of these newborns’ weight-for-height indicators among ultrasonographic data and maternal/delivery information. Regarding ultrasonographic fetal biometry, newborn’s weight, newborn’s weight/height and newborn’s weight/height2 were better indicators with smaller mean-squared-error-over-variance measures than newborn’s weight/height3. Based on random forest variable importance, the top six predictors of newborn’s weight were the same as those of newborn’s weight/height and those of newborn’s weight/height2: gestational age at delivery time, the first estimated fetal weight and abdominal circumference in week 36 or later, maternal weight and body mass index at delivery time, and the first biparietal diameter in week 36 or later. These six predictors also ranked within the top seven for large-for-gestational-age and the top eight for small-for-gestational-age. In conclusion, newborn’s weight, newborn’s weight/height and newborn’s weight/height2 are more suitable for ultrasonographic fetal biometry with smaller mean-squared-error-over-variance measures than newborn’s weight/height3. Machine learning with ultrasonographic data would be an effective noninvasive approach for predicting newborn’s weight, weight/height and weight/height2.