bluuebunny/crossref_metadata_2025 huggingface dataset:
Vertical Distribution of Aerosols during Deep-Convective Event in the Himalaya Using WRF-Chem Model at Convection Permitting Scale
Authors: Singh Prashant , Sarawade Pradip , Adhikary Bhupesh
Published: August 2021

The Himalayan region is facing frequent cloud bursts and flood events during the summer monsoon season. The Kedarnath flooding of 2013 was one of the most devastating recent events, which claimed thousands of human lives, heavy infrastructure, and economic losses. Previous research reported that the combination of fast-moving monsoon, pre-existing westerlies, and orographic uplifting were the major reasons for the observed cloud burst over Kedarnath. Our study illustrates the vertical distribution of aerosols during this event and its possible role using the Weather Research and Forecasting model coupled with chemistry (WRF-Chem) simulations. Model performance evaluation shows that simulations can capture the spatial and temporal patterns of observed precipitation during this event. Model simulation at 25 km and 4 km horizontal grid resolution, without any changes in physical parameterization, shows a very minimal difference in precipitation. Simulation at convection-permitting scale shows detailed information related to parcel motion compared to coarser resolution. This indicates that the parameterization at different resolutions needs to be further examined for a better outcome. The modeled result shows changes of up to 20–50% in the rainfall over the area near Kedarnath due to the presence of aerosols. Simulation at both resolutions shows the significant vertical transport of natural (increases by 50%+) and anthropogenic aerosols (increases by 200%+) during the convective event, which leads to significant changes in cloud properties, rain concentration, and ice concentration in the presence of these aerosols. Simulations can detect changes in important instability indices such as convective available potential energy (CAPE), convective inhibition energy (CIN), vorticity, etc., near Kedarnath due to aerosol–radiation feedback.
Survival in the Three Common Variants of Primary Progressive Aphasia: A Retrospective Study in a Tertiary Memory Clinic
Authors: Tastevin Maud , Lavoie Monica , de la Sablonnière Justine , Carrier-Auclair Julie , Laforce Robert
Published: August 2021

Knowledge on the natural history of the three main variants of primary progressive aphasia (PPA) is lacking, particularly regarding mortality. Moreover, advanced stages and end of life issues are rarely discussed with caregivers and families at diagnosis, which can cause more psychological distress. We analyzed data from 83 deceased patients with a diagnosis of PPA. We studied survival in patients with a diagnosis of logopenic variant (lvPPA), semantic variant (svPPA), or non-fluent variant (nfvPPA) and examined causes of death. From medical records, we retrospectively collected data for each patient at several time points spanning five years before the first visit to death. When possible, interviews were performed with proxies of patients to complete missing data. Results showed that survival from symptom onset and diagnosis was significantly longer in svPPA than in lvPPA (p = 0.002) and nfvPPA (p < 0.001). No relevant confounders were associated with survival. Mean survival from symptom onset was 7.6 years for lvPPA, 7.1 years for nfvPPA, and 12 years for svPPA. The most common causes of death were natural cardio-pulmonary arrest and pneumonia. Aspiration pneumonia represented 23% of deaths in nfvPPA. In conclusion, this pilot study found significant differences in survival between the three variants of PPA with svPPA showing the longest and nfvPPA showing more neurologically-related causes of death.
Intermittent Theta Burst Stimulation to the Primary Motor Cortex Reduces Cortical Inhibition: A TMS-EEG Study
Authors: Bai Zhongfei , Zhang Jiaqi , Fong Kenneth N. K.
Published: August 2021

Introduction: The aim of this study was to reveal the effects of intermittent theta burst stimulation (iTBS) in modulating cortical networks using transcranial magnetic stimulation and electroencephalography (TMS-EEG) recording. Methods: Eighteen young adults participated in our study and received iTBS to the primary motor cortex (M1), supplementary motor area, and the primary visual cortex in three separate sessions. A finger tapping task and ipsilateral single-pulse TMS-EEG recording for the M1 were administrated before and after iTBS in each session. The effects of iTBS in motor performance and TMS-evoked potentials (TEPs) were investigated. Results: The results showed that iTBS to the M1, but not supplementary motor area or the primary visual cortex, significantly reduced the N100 amplitude of M1 TEPs in bilateral hemispheres (p = 0.019), with a more prominent effect in the contralateral hemisphere than in the stimulated hemisphere. Moreover, only iTBS to the M1 decreased global mean field power (corrected ps < 0.05), interhemispheric signal propagation (t = 2.53, p = 0.030), and TMS-induced early α-band synchronization (p = 0.020). Conclusion: Our study confirmed the local and remote after-effects of iTBS in reducing cortical inhibition in the M1. TMS-induced oscillations after iTBS for changed cortical excitability in patients with various neurological and psychiatric conditions are worth further exploration.
Inhibitors of Lipoxygenase and Cyclooxygenase-2 Attenuate Trimethyltin-Induced Neurotoxicity through Regulating Oxidative Stress and Pro-Inflammatory Cytokines in Human Neuroblastoma SH-SY5Y Cells
Authors: Song Woo-Ju , Yun Jang-Hyuk , Jeong Myeong-Seon , Kim Kil-Nam , Shin Taekyun , Kim Hyoung-Chun , Wie Myung-Bok
Published: August 2021

Trimethyltin (TMT) is an environmental neurotoxin that mediates dopaminergic neuronal injury in the brain. In this study, we characterized the toxic mechanism and possible protective compounds against TMT-induced neurotoxicity in human dopaminergic neuroblastoma SH-SY5Y cells. Antioxidants such as melatonin, N-acetylcysteine (NAC), α-tocopherol, and allopurinol alleviated TMT toxicity. Apoptosis induced by TMT was identified by altered expression of cleaved caspase-3, Bax, Bcl-2, and Bcl-xL through Western blot analysis. The iron chelator deferoxamine ameliorated the alteration of apoptosis-related proteins through TMT exposure. TMT also induced delayed ultrastructural necrotic features such as mitochondrial swelling and cytoplasmic membrane rupture; NAC reduced these necrotic injuries. Esculetin, meloxicam, celecoxib, and phenidone decreased TMT toxicity. Elevation of the pro-inflammatory cytokines IL-1β, TNF-α, and NF-ĸB and reduction of the antioxidant enzymes catalase and glutathione peroxidase-1 (GPx-1) were induced by TMT and ameliorated by inhibitors of LOX and COX-2 enzymes. Both NMDA and non-NMDA antagonists attenuated TMT toxicity. The free calcium ion modulators nimodipine and BAPTA/AM contributed to neuronal survival against TMT toxicity. Inhibitors of the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathway, an autophagy regulator, decreased TMT toxicity. These results imply that TMT neurotoxicity is the chief participant in LOX- and COX-2-mediated apoptosis, partly via necrosis and autophagy in SH-SY5Y cells.
Mindful Coping Power: Comparative Effects on Children’s Reactive Aggression and Self-Regulation
Authors: Boxmeyer Caroline L. , Miller Shari , Romero Devon E. , Powell Nicole P. , Jones Shannon , Qu Lixin , Tueller Stephen , Lochman John E.
Published: August 2021

Coping Power (CP) is an evidence-based preventive intervention for youth with disruptive behavior problems. This study examined whether Mindful Coping Power (MCP), a novel adaptation which integrates mindfulness into CP, enhances program effects on children’s reactive aggression and self-regulation. A pilot randomized design was utilized to estimate the effect sizes for MCP versus CP in a sample of 102 child participants (fifth grade students, predominantly low-middle income, 87% Black). MCP produced significantly greater improvement in children’s self-reported dysregulation (emotional, behavioral, cognitive) than CP, including children’s perceived anger modulation. Small to moderate effects favoring MCP were also observed for improvements in child-reported inhibitory control and breath awareness and parent-reported child attentional capacity and social skills. MCP did not yield a differential effect on teacher-rated reactive aggression. CP produced a stronger effect than MCP on parent-reported externalizing behavior problems. Although MCP did not enhance program effects on children’s reactive aggression as expected, it did have enhancing effects on children’s internal, embodied experiences (self-regulation, anger modulation, breath awareness). Future studies are needed to compare MCP and CP in a large scale, controlled efficacy trial and to examine whether MCP-produced improvements in children’s internal experiences lead to improvements in their observable behavior over time.
Molecular Biomarkers of Electroconvulsive Therapy Effects and Clinical Response: Understanding the Present to Shape the Future
Authors: Maffioletti Elisabetta , Carvalho Silva Rosana , Bortolomasi Marco , Baune Bernhard T. , Gennarelli Massimo , Minelli Alessandra
Published: August 2021

Electroconvulsive therapy (ECT) represents an effective intervention for treatment-resistant depression (TRD). One priority of this research field is the clarification of ECT response mechanisms and the identification of biomarkers predicting its outcomes. We propose an overview of the molecular studies on ECT, concerning its course and outcome prediction, including also animal studies on electroconvulsive seizures (ECS), an experimental analogue of ECT. Most of these investigations underlie biological systems related to major depressive disorder (MDD), such as the neurotrophic and inflammatory/immune ones, indicating effects of ECT on these processes. Studies about neurotrophins, like the brain-derived neurotrophic factor (BDNF) and the vascular endothelial growth factor (VEGF), have shown evidence concerning ECT neurotrophic effects. The inflammatory/immune system has also been studied, suggesting an acute stress reaction following an ECT session. However, at the end of the treatment, ECT produces a reduction in inflammatory-associated biomarkers such as cortisol, TNF-alpha and interleukin 6. Other biological systems, including the monoaminergic and the endocrine, have been sparsely investigated. Despite some promising results, limitations exist. Most of the studies are concentrated on one or few markers and many studies are relatively old, with small sample sizes and methodological biases. Expression studies on gene transcripts and microRNAs are rare and genetic studies are sparse. To date, no conclusive evidence regarding ECT molecular markers has been reached; however, the future may be just around the corner.
Melatonin: From Neurobiology to Treatment
Authors: Biggio Giovanni , Biggio Francesca , Talani Giuseppe , Mostallino Maria Cristina , Aguglia Andrea , Aguglia Eugenio , Palagini Laura
Published: August 2021

Melatonin, the major regulator of the sleep/wake cycle, also plays important physiological and pharmacological roles in the control of neuronal plasticity and neuroprotection. Accordingly, the secretion of this hormone reaches the maximal extent during brain development (childhood-adolescence) while it is greatly reduced during aging, a condition associated to altered sleep pattern and reduced neuronal plasticity. Altogether, these properties of melatonin have allowed us to demonstrate in both experimental models and clinical studies the great chronobiotic efficacy and sleep promoting effects of exogenous melatonin. Thus, the prolonged release formulation of melatonin, present as a drug in the pharmaceutical market, has been recently recommended for the treatment of insomnia in over 55 years old subjects.
Biomarker in Active Surveillance for Prostate Cancer: A Systematic Review
Authors: Manceau Cécile , Fromont Gaëlle , Beauval Jean-Baptiste , Barret Eric , Brureau Laurent , Créhange Gilles , Dariane Charles , Fiard Gaëlle , Gauthé Mathieu , Mathieu Romain , Renard-Penna Raphaële , Roubaud Guilhem , Ruffion Alain , Sargos Paul , Rouprêt Morgan , Ploussard Guillaume ,   on behalf of the CC-AFU, Cancerology Committee of the Association Française d’Urologie
Published: August 2021

Active surveillance (AS) in prostate cancer (PCa) represents a curative alternative for men with localised low-risk PCa. Continuous improvement of AS patient’s selection and surveillance modalities aims at reducing misclassification, simplifying modalities of surveillance and decreasing need for invasive procedures such repeated biopsies. Biomarkers represent interesting tools to evaluate PCa diagnosis and prognosis, of which many are readily available or under evaluation. The aim of this review is to investigate the biomarker performance for AS selection and patient outcome prediction. Blood, urinary and tissue biomarkers were studied and a brief description of use was proposed along with a summary of major findings. Biomarkers represent promising tools which could be part of a more tailored risk AS strategy aiming to offer personalized medicine and to individualize the treatment and monitoring of each patient. The usefulness of biomarkers has mainly been suggested for AS selection, whereas few studies have investigated their role during the monitoring phase. Randomized prospective studies dealing with imaging are needed as well as larger prospective studies with long-term follow-up and strong oncologic endpoints.
Cisplatin Resistance in Epstein–Barr-Virus-Associated Gastric Carcinoma Acquired through ATM Methylation
Authors: Lee Sun Hee , Choi Su Jin , Choi Wonhyeok , Cho Subin , Cho Miyeon , Kim Dong Sun , Kang Byung Woog , Kim Jong Gwang , Lee You Mie , Cho Hyosun , Kang Hyojeung
Published: August 2021

Epstein–Barr-virus-associated gastric carcinoma (EBVaGC), first reported in 1992, currently accounts for 10% of all gastric carcinoma worldwide. EBVaGC has unique DNA hypermethylation phenotypes that allow for higher proportions of DNA methylation than any other gastric cancer. CpG islands in the gene promoter region are one of the major regions in which DNA methylation controls gene transcription. Despite cisplatin-based chemotherapy being one of the standard treatment regimens for advanced gastric cancer, including EBVaGC, cisplatin alone or in combination with 5-fluorouracil has been limited by its less potent anticancer activity and the occurrence of cisplatin resistance. Accordingly, the current study evaluated the anticancer activities of a combination of cisplatin and 5-Azacytidine (5-AZA) against EBVaGC. Our findings showed that cisplatin upregulated the DNMT3A gene, whereas shRNA-targeted removal of DNMT3A mRNA contributed to cisplatin-mediated EBV lytic reactivation. Moreover, the removal of DNMT3A mRNA upregulated the ATM gene through DNA demethylation on the ATM promoter. Furthermore, CRISPR/Cas9-targeted removal of the ATM gene resulted in significantly reduced cell susceptibility and EBV lytic reactivation by a combination of cisplatin and DNMT3A inhibitor 5-AZA. Finally, 5-AZA exhibited a synergistic effect with cisplatin in anti-EBV and anti-EBVaGC activities by increasing drug susceptibility and EBV lytic reactivation. The aforementioned results suggest that cisplatin combined with DNA methylation inhibitors could be a novel therapeutic approach for EBVaGC.
Comparative Analyses of Liquid-Biopsy MicroRNA371a-3p Isolation Protocols for Serum and Plasma
Authors: Timmerman Dennis M. , Gillis Ad J. M. , Mego Michal , Looijenga Leendert H. J.
Published: August 2021

MicroRNAs (miRNAs) are short, non-coding RNAs involved in translation regulation. Dysregulation has been identified in cancer cells. miRNAs can be secreted and detectable in body fluids; therefore, they are potential liquid-biopsy biomarkers. The miR-371a-3 cluster members are an example, monitoring the presence of malignant germ cell tumors based on patient serum/plasma analyses. However, a large variety of isolation techniques on sample types (serum vs. plasma) are reported, hampering interstudy comparisons. Therefore, we analyzed the impact of using the miRNeasy Serum/Plasma Kit (cell-free total RNA purification) Qiagen extraction kit and the TaqMan anti-miRNA bead-capture procedure of ThermoFisher for miRNA isolation. Ten normal male matched serum and plasma samples and seventeen testicular germ cell tumor patient serum samples were investigated. The Qiagen kit requires a higher input volume (200 µL vs. 50 µL), resulting in higher sensitivity. Serum and plasma comparison demonstrated high similarity in miRNA levels. Titration experiments showed that the bead-capture procedure is superior in cases of lower starting volumes (<100 µL). This study highlights the strengths and limitations of two different isolation protocols, relevant for in vivo analysis with small starting volumes. In summary, miRNA detection levels results varied little between plasma and serum, whereas for low volumes the bead capture isolation method is preferable.
Inhibitory Receptors and Immune Checkpoints Regulating Natural Killer Cell Responses to Cancer
Authors: Buckle Irina , Guillerey Camille
Published: August 2021

The discovery of immune checkpoints provided a breakthrough for cancer therapy. Immune checkpoints are inhibitory receptors that are up-regulated on chronically stimulated lymphocytes and have been shown to hinder immune responses to cancer. Monoclonal antibodies against the checkpoint molecules PD-1 and CTLA-4 have shown early clinical success against melanoma and are now approved to treat various cancers. Since then, the list of potential candidates for immune checkpoint blockade has dramatically increased. The current paradigm stipulates that immune checkpoint blockade therapy unleashes pre-existing T cell responses. However, there is accumulating evidence that some of these immune checkpoint molecules are also expressed on Natural Killer (NK) cells. In this review, we summarize our latest knowledge about targetable NK cell inhibitory receptors. We discuss the HLA-binding receptors KIRS and NKG2A, receptors binding to nectin and nectin-like molecules including TIGIT, CD96, and CD112R, and immune checkpoints commonly associated with T cells such as PD-1, TIM-3, and LAG-3. We also discuss newly discovered pathways such as IL-1R8 and often overlooked receptors such as CD161 and Siglecs. We detail how these inhibitory receptors might regulate NK cell responses to cancer, and, where relevant, we discuss their implications for therapeutic intervention.
A New Story of the Three Magi: Scaffolding Proteins and lncRNA Suppressors of Cancer
Authors: Kotelevets Larissa , Chastre Eric
Published: August 2021

Scaffolding molecules exert a critical role in orchestrating cellular response through the spatiotemporal assembly of effector proteins as signalosomes. By increasing the efficiency and selectivity of intracellular signaling, these molecules can exert (anti/pro)oncogenic activities. As an archetype of scaffolding proteins with tumor suppressor property, the present review focuses on MAGI1, 2, and 3 (membrane-associated guanylate kinase inverted), a subgroup of the MAGUK protein family, that mediate networks involving receptors, junctional complexes, signaling molecules, and the cytoskeleton. MAGI1, 2, and 3 are comprised of 6 PDZ domains, 2 WW domains, and 1 GUK domain. These 9 protein binding modules allow selective interactions with a wide range of effectors, including the PTEN tumor suppressor, the β-catenin and YAP1 proto-oncogenes, and the regulation of the PI3K/AKT, the Wnt, and the Hippo signaling pathways. The frequent downmodulation of MAGIs in various human malignancies makes these scaffolding molecules and their ligands putative therapeutic targets. Interestingly, MAGI1 and MAGI2 genetic loci generate a series of long non-coding RNAs that act as a tumor promoter or suppressor in a tissue-dependent manner, by selectively sponging some miRNAs or by regulating epigenetic processes. Here, we discuss the different paths followed by the three MAGIs to control carcinogenesis.
Piperlongumine, a Potent Anticancer Phytotherapeutic, Induces Cell Cycle Arrest and Apoptosis In Vitro and In Vivo through the ROS/Akt Pathway in Human Thyroid Cancer Cells
Authors: Kung Fang-Ping , Lim Yun-Ping , Chao Wen-Ying , Zhang Yi-Sheng , Yu Hui-I , Tai Tsai-Sung , Lu Chieh-Hsiang , Chen Shu-Hsin , Li Yi-Zhen , Zhao Pei-Wen , Yen Yu-Pei , Lee Ying-Ray
Published: August 2021

Thyroid cancer (TC) is the most common endocrine malignancy, and its global incidence has steadily increased over the past 15 years. TC is broadly divided into well-differentiated, poorly differentiated, and undifferentiated types, depending on the histological and clinical parameters. Thus far, there are no effective treatments for undifferentiated thyroid cancers or advanced and recurrent cancer. Therefore, the development of an effective therapeutic is urgently needed for such patients. Piperlongumine (PL) is a naturally occurring small molecule derived from long pepper; it is selectively toxic to cancer cells by generating reactive oxygen species (ROS). In this study, we demonstrate the potential anticancer activity of PL in four TC cell lines. For this purpose, we cultured TC cell lines and analyzed the following parameters: Cell viability, colony formation, cell cycle, apoptosis, and cellular ROS induction. PL modulated the cell cycle, induced apoptosis, and suppressed tumorigenesis in TC cell lines in a dose- and time-dependent manner through ROS induction. Meanwhile, an intrinsic caspase-dependent apoptosis pathway was observed in the TC cells under PL treatment. The activation of Erk and the suppression of the Akt/mTOR pathways through ROS induction were seen in cells treated with PL. PL-mediated apoptosis in TC cells was through the ROS-Akt pathway. Finally, the anticancer effect and safety of PL were also demonstrated in vivo. Our findings indicate that PL exhibits antitumor activity and has the potential for use as a chemotherapeutic agent against TC. This is the first study to show the sensitivity of TC cell lines to PL.
Meningioma–Brain Crosstalk: A Scoping Review
Authors: Borch Josefine de Stricker , Haslund-Vinding Jeppe , Vilhardt Frederik , Maier Andrea Daniela , Mathiesen Tiit
Published: August 2021

Background: In recent years, it has become evident that the tumoral microenvironment (TME) plays a key role in the pathogenesis of various cancers. In meningiomas, however, the TME is poorly understood, and it is unknown if glia cells contribute to meningioma growth and behaviour. Objective: This scoping review investigates if the literature describes and substantiates tumour–brain crosstalk in meningiomas and summarises the current evidence regarding the role of the brain parenchyma in the pathogenesis of meningiomas. Methods: We identified studies through the electronic database PubMed. Articles describing glia cells and cytokines/chemokines in meningiomas were selected and reviewed. Results: Monocytes were detected as the most abundant infiltrating immune cells in meningiomas. Only brain-invasive meningiomas elicited a monocytic response at the tumour–brain interface. The expression of cytokines/chemokines in meningiomas has been studied to some extent, and some of them form autocrine loops in the tumour cells. Paracrine interactions between tumour cells and glia cells have not been explored. Conclusion: It is unknown to what extent meningiomas elicit an immune response in the brain parenchyma. We speculate that tumour–brain crosstalk might only be relevant in cases of invasive meningiomas that disrupt the pial–glial basement membrane.
Treatment Regimens for Immunocompetent Elderly Patients with Primary Central Nervous System Lymphoma: A Scoping Review
Authors: Schorb Elisabeth , Isbell Lisa Kristina , Illerhaus Gerald , Ihorst Gabriele , Meerpohl Joerg J. , Grummich Kathrin , Nagavci Blin , Schmucker Christine
Published: August 2021

Background: Most patients diagnosed with primary central nervous system lymphoma (PCNSL) are older than 60 years. Despite promising treatment options for younger patients, prognosis for the elderly remains poor and efficacy of available treatment options is limited. Materials and Methods: We conducted a scoping review to identify and summarize the current study pool available evaluating different types and combinations of (immuno) chemotherapy with a special focus on HCT-ASCT in elderly PCNSL. Relevant studies were identified through systematic searches in the bibliographic databases Medline, Web of Science, Cochrane Library and ScienceDirect (last search conducted in September 2020). For ongoing studies, we searched ClinicalTrials.gov, the German study register and the WHO registry. Results: In total, we identified six randomized controlled trials (RCT) with 1.346 patients, 26 prospective (with 1.366 patients) and 24 retrospective studies (with 2.629 patients). Of these, only six studies (one completed and one ongoing RCT (with 447 patients), one completed and one ongoing prospective single arm study (with 65 patients), and two retrospective single arm studies (with 122 patients)) evaluated HCT-ASCT. Patient relevant outcomes such as progression-free and overall survival and (neuro-)toxicity were adequately considered across almost all studies. The current study pool is, however, not conclusive in terms of the most effective treatment options for elderly. Main limitations were (very) small sample sizes and heterogeneous patient populations in terms of age ranges (particularly in RCTs) limiting the applicability of the results to the target population (elderly). Conclusions: Although it has been shown that HCT-ASCT is probably a feasible and effective treatment option, this approach has never been investigated within a RCT including a wide range of elderly patients. A RCT comparing conventional (immuno) chemotherapy with HCT-ASCT is crucial to evaluate benefit and harms in an un-biased manner to eventually provide older PCNSL patients with the most effective treatment.
Development of Discordant Hypermetabolic Prostate Cancer Lesions in the Course of [177Lu]PSMA Radioligand Therapy and Their Possible Influence on Patient Outcome
Authors: Hartrampf Philipp E. , Lapa Constantin , Serfling Sebastian E. , Buck Andreas K. , Seitz Anna Katharina , Meyer Philipp T. , Ruf Juri , Michalski Kerstin
Published: August 2021

Introduction: Positron emission tomography/computer tomography (PET/CT) targeting the prostate-specific membrane antigen (PSMA) is crucial for the assessment of adequate PSMA expression in patients with metastatic castration-resistant prostate cancer (mCRPC) prior to PSMA radioligand therapy (PSMA RLT). Moreover, initial dual tracer staging using combined PSMA and [18F]fluorodeoxyglucose (FDG) PET/CT provides relevant information, since discordant FDG-positive but PSMA-negative (FDG+/PSMA−) lesions constitute a negative prognostic marker of overall survival (OS) after PSMA RLT. However, little is known about the prognostic implications of dual tracer imaging for restaging at follow-up. The aim of this analysis was to investigate the prognostic implications of new FDG+/PSMA− lesions during or after PSMA RLT. Methods: This bicentric analysis included 32 patients with mCRPC who underwent both FDG and PSMA PET/CT imaging after two or four cycles of PSMA RLT. Patients with FDG+/PSMA− lesions prior to PSMA RLT were not considered. The presence of FDG+/PSMA− lesions was assessed with follow-up dual tracer imaging of patients after two or four cycles of PSMA RLT. Patients with at least one new FDG+/PSMA− lesion were compared to patients without any FDG+/PSMA− lesions at the respective time points. A log-rank analysis was used to assess the difference in OS between subgroups. Results: After two cycles of PSMA RLT, four of 32 patients (13%) had FDG+/PSMA− metastases. No significant difference in OS was observed (p = 0.807), as compared to patients without FDG+/PSMA− lesions. Follow-up dual tracer imaging after the 4th cycle of PSMA RLT was available in 18 patients. Of these, four patients presented with FDG+/PSMA− findings (n = 2 already after two cycles). After the fourth cycle of PSMA RLT, no significant difference in OS was observed between patients with and without FDG+/PSMA− lesions (p = 0.442). Conclusion: This study shows that FDG+/PSMA− lesions develop in a limited number of patients undergoing PSMA RLT. Further studies are needed to establish the clinical relevance of such lesions.
Radiomics of MRI for the Prediction of the Pathological Response to Neoadjuvant Chemotherapy in Breast Cancer Patients: A Single Referral Centre Analysis
Authors: Pesapane Filippo , Rotili Anna , Botta Francesca , Raimondi Sara , Bianchini Linda , Corso Federica , Ferrari Federica , Penco Silvia , Nicosia Luca , Bozzini Anna , Pizzamiglio Maria , Origgi Daniela , Cremonesi Marta , Cassano Enrico
Published: August 2021

Objectives: We aimed to determine whether radiomic features extracted from a highly homogeneous database of breast MRI could non-invasively predict pathological complete responses (pCR) to neoadjuvant chemotherapy (NACT) in patients with breast cancer. Methods: One hundred patients with breast cancer receiving NACT in a single center (01/2017–06/2019) and undergoing breast MRI were retrospectively evaluated. For each patient, radiomic features were extracted within the biopsy-proven tumor on T1-weighted (T1-w) contrast-enhanced MRI performed before NACT. The pCR to NACT was determined based on the final surgical specimen. The association of clinical/biological and radiomic features with response to NACT was evaluated by univariate and multivariable analysis by using random forest and logistic regression. The performances of all models were assessed using the areas under the receiver operating characteristic curves (AUC) with 95% confidence intervals (CI). Results: Eighty-three patients (mean (SD) age, 47.26 (8.6) years) were included. Patients with HER2+, basal-like molecular subtypes and Ki67 ≥ 20% presented a pCR to NACT more frequently; the clinical/biological model’s AUC (95% CI) was 0.81 (0.71–0.90). Using 136 representative radiomics features selected through cluster analysis from the 1037 extracted features, a radiomic score was calculated to predict the response to NACT, with AUC (95% CI): 0.64 (0.51–0.75). After combining the clinical/biological and radiomics models, the AUC (95% CI) was 0.83 (0.73–0.92). Conclusions: MRI-based radiomic features slightly improved the pre-treatment prediction of pCR to NACT, in addiction to biological characteristics. If confirmed on larger cohorts, it could be helpful to identify such patients, to avoid unnecessary treatment.
The Role of Cost-Effectiveness Analysis in Patient-Centered Cancer Care in the Era of Precision Medicine
Authors: Toscano Fabrizio , Vera Alberto , Kim Eleanor , Golinelli Davide , Vila-Reyes Helena , Bteich Fernand , Schernberg Antoine , Seban Romain-David , Yeh Randy , Dercle Laurent
Published: August 2021

Over the last few decades, changes in diagnostic and treatment paradigms have greatly advanced cancer care and improved outcomes [...]
HIV Increases the Inhibitory Impact of Morphine and Antiretrovirals on Autophagy in Primary Human Macrophages: Contributions to Neuropathogenesis
Authors: Barbaro John M. , Cuervo Ana Maria , Berman Joan W.
Published: August 2021

HIV enters the CNS early after peripheral infection, establishing reservoirs in perivascular macrophages that contribute to development of HIV-associated neurocognitive disorders (HAND) in 15–40% of people with HIV (PWH) despite effective antiretroviral therapy (ART). Opioid use may contribute to dysregulated macrophage functions resulting in more severe neurocognitive symptoms in PWH taking opioids. Macroautophagy helps maintain quality control in long-lived cell types, such as macrophages, and has been shown to regulate, in part, some macrophage functions in the CNS that contribute to HAND. Using Western blotting and confocal immunofluorescence in primary human macrophages, we demonstrated that morphine and a commonly prescribed ART regimen induce bulk autophagy. Morphine and ART also inhibited completion of autophagy. HIV infection increased these inhibitory effects. We also examined two types of selective autophagy that degrade aggregated proteins (aggrephagy) and dysfunctional mitochondria (mitophagy). Morphine and ART inhibited selective autophagy mediated by p62 regardless of HIV infection, and morphine inhibited mitophagic flux in HIV-infected cells demonstrating potential mitotoxicity. These results indicate that inhibition of autophagy, both in bulk and selective, in CNS macrophages may mediate neurocognitive dysfunction in PWH using opioids. Increasing autophagic activity in the context of HIV may represent a novel therapeutic strategy for reducing HAND in these individuals.
Perilipin 5 Ameliorates Hepatic Stellate Cell Activation via SMAD2/3 and SNAIL Signaling Pathways and Suppresses STAT3 Activation
Authors: Cierpka Rafael , Weiskirchen Ralf , Asimakopoulos Anastasia
Published: August 2021

Comprehending the molecular mechanisms underlying hepatic fibrogenesis is essential to the development of treatment. The hallmark of hepatic fibrosis is the development and deposition of excess fibrous connective tissue forcing tissue remodeling. Hepatic stellate cells (HSC) play a major role in the pathogenesis of liver fibrosis. Their activation via the transforming growth factor-β1 (TGF-β1) as a key mediator is considered the crucial event in the pathophysiology of hepatic fibrogenesis. It has been shown that Perilipin 5 (PLIN5), known as a lipid droplet structural protein that is highly expressed in oxidative tissue, can inhibit such activation through various mechanisms associated with lipid metabolism. This study aimed to investigate the possible influence of PLIN5 on TGF-β1 signaling. Our findings confirm the importance of PLIN5 in maintaining HSC quiescence in vivo and in vitro. PLIN5 overexpression suppresses the TGF-β1-SMAD2/3 and SNAIL signaling pathways as well as the activation of the signal transducers and activators of transcription 3 (STAT3). These findings derived from experiments in hepatic cell lines LX-2 and Col-GFP, in which overexpression of PLIN5 was able to downregulate the signaling pathways SMAD2/3 and SNAIL activated previously by TGF-β1 treatment. Furthermore, TGF-β1-mediatedinduction of extracellular matrix proteins, such as collagen type I (COL1), Fibronectin, and α-smooth muscle actin (α-SMA), was suppressed by PLIN5. Moreover, STAT3, which is interrelated with TGF-β1 was already basally activated in the cell lines and inhibited by PLIN5 overexpression, leading to a further reduction in HSC activity shown by lowered α-SMA expression. This extension of the intervening mechanisms presents PLIN5 as a potent and pleiotropic target in HSC activation.
Is Pediatric Dentistry a Topic of Interest for Pediatric Journals? A Scoping Review
Authors: Cagetti Maria Grazia , Balian Araxi , Cirio Silvia , Camoni Nicole , Salerno Claudia , Tartaglia Gianluca Martino
Published: August 2021

Background: Pediatric dentistry shares many skills with pediatrics. This review evaluates the amount of literature on pediatric dentistry in the first 30 pediatric journals classified by the Web of Science in 2019. The aim was to perform a quantitative analysis of the main dental topics addressed. Methods: A scoping review with the PRISMA-ScR criteria was performed. The Clarivate Analytics Journal Citation Report was consulted for journals ranked in the category “Pediatrics” in 2019. Papers were searched in PubMed using an ad hoc prepared string. Results: A total of 504 papers were included. Papers on dental hard tissues were the most prevalent (45.6%), followed by dental public health (23.2%), orofacial development (15.3%), soft tissues related conditions (12.3%), and orofacial trauma (3.6%). Increasing trends have been observed for total papers published (R2 = 0.9822) and total dental papers (R2 = 0.8862), with no statistically significant differences (χ2(6) = 0.051 p > 0.05). The majority of papers (n = 292, 57.9%) were cited between 1 and 10 times, whilst less than 7% of papers received more than 40 citations. Discussion: It is desirable that papers on pediatric dentistry increase in the pediatric scenario, allowing the two related disciplines to intertwine more in the future.
Segmental Assessment of Trunk Control in Moderate-to-Late Preterm Infants Related to Sitting Development
Authors: Sangkarit Noppharath , Keeratisiroj Orawan , Yonglitthipagon Ponlapat , Bennett Surussawadi , Siritaratiwat Wantana
Published: August 2021

(1) Background: The assessment of postural segment control in premature infants seems to be critical during the onset of upright gross motor development, especially sitting. Identifying correlations between postural segment control and the development of sitting milestones could help with promoting optimal gross motor movement. However, data on this topic in home-raised premature infants via longitudinal design are still limited. The purpose of this study was to examine relationships between postural segment control and sitting development through series assessments from the corrected age of 4 months until the early onset of independent sitting attainment. (2) Methods: 33 moderate-to-late premature infants were recruited. Their trunk segment control was assessed using the Segmental Assessment of Trunk Control (SATCo), and sitting development was examined by the Alberta Infant Motor Scale (AIMS). Relationships between SATCo and sitting scores were analysed using Spearman’s rank correlation (rs). (3) Results: significant fair-to-good correlations between segmental trunk control and sitting scales were found from 4 months (rs = 0.370–0.420, p < 0.05) to the age of independent sitting attainment (rs = 0.561–0.602, p < 0.01). (4) Conclusion: relationships between the trunk segment control and sitting ability of moderate-to-late preterm infants were increased in accordance with age.
Knowledge Levels and Educational Experiences among Dental Graduates in Saudi Arabia Regarding Child Abuse and Neglect: A National Study
Authors: Sulimany Ayman M. , Alsamhan Abdulaziz , Alawwad Abdulrahman Awwad , Aqueel Mohammad , Alzaid Nawaf , Bawazir Omar A. , Hamdan Hebah M.
Published: August 2021

Background: Child abuse and neglect (CAN) is considered a serious problem worldwide. Dentists have a significant role in recognizing and reporting CAN cases. Aim: The aim of this study was to assess the CAN-related knowledge and educational experiences among Saudi dental graduates. Design: Self-administered questionnaires were distributed to dental graduates from all dental schools in Saudi Arabia (n = 1552). Bivariate and multivariate logistic regression analyses were performed to assess the associations between knowledge level and different predictors. Results: A total of 988 dental graduates completed the questionnaire. The majority of them were dissatisfied with the amount of education they had received in their school (56.4%). Around 60% of the participants had inadequate knowledge regarding CAN. Graduates from government schools who received dental education about CAN and female participants had significantly higher odds of having adequate knowledge scores than others (odds ratio = 2.0, 3.1, and 1.7, respectively). Only 39.5% of the participants felt confident in their ability to identify CAN cases, and only 9.7% knew how to report such cases. Conclusions: Graduate dental students have insufficient knowledge about CAN. More time should be dedicated to educating students about this important topic in dental curricula.
Conservative Treatment of Complicated Crown Fracture and Crown-Root Fracture of Young Permanent Incisor—A Case Report with 24-Month Follow-Up
Authors: Marinčák David , Doležel Vojtěch , Přibyl Michal , Voborná Iva , Marek Ivo , Šedý Jiří , Žižka Radovan
Published: August 2021

The complicated crown-root fracture of young permanent teeth is an uncommon traumatic dental injury that is usually treated in a complex way and is demanding not only for the dentist but even for the treated child. In this case report, we present the conservative treatment of a maxillary central incisor in a 10-year-old boy after a traumatic dental injury. Treatment included partial pulpotomy and adhesive fragment reattachment after reflection of the mucoperiosteal flap. The patient was fully asymptomatic at 24-month follow-up, with an aesthetically acceptable outcome. Vital pulp therapy and adhesive fragment reattachment can be a viable treatment option for complicated crown-root fractures, especially when treating immature permanent teeth.
The Promise of Mutation Resistant Drugs for SARS-CoV-2 That Interdict in the Folding of the Spike Protein Receptor Binding Domain
Authors: Bergasa-Caceres Fernando , Rabitz Herschel A.
Published: August 2021

In recent work, we proposed that effective therapeutic drugs aimed at treating the SARS-CoV-2 infection could be developed based on interdicting in the early steps of the folding pathway of key viral proteins, including the receptor binding domain (RBD) of the spike protein. In order to provide for a drug target on the protein, the earliest contact-formation event along the dominant folding pathway of the RBD spike protein was predicted employing the Sequential Collapse Model (SCM). The segments involved in the predicted earliest contact were suggested to provide optimal folding interdiction target regions (FITRs) for potential therapeutic drugs, with a focus on folding interdicting peptides (FIPs). In this paper, we extend our analysis to include 13 known single mutations of the RBD spike protein as well as the triple mutation B1.351 and the recent double mutation B1.617.2. The results show that the location of the FITR does not change in any of the 15 studied mutations, providing for a mutation-resistant drug design strategy for the RBD-spike protein.
Physical, Mechanical and Durability Properties of Ecofriendly Ternary Concrete Made with Sugar Cane Bagasse Ash and Silica Fume
Authors: Landa-Ruiz Laura , Landa-Gómez Aldo , Mendoza-Rangel José M. , Landa-Sánchez Abigail , Ariza-Figueroa Hilda , Méndez-Ramírez Ce Tochtli , Santiago-Hurtado Griselda , Moreno-Landeros Victor M. , Croche René , Baltazar-Zamora Miguel Angel
Published: August 2021

In the present investigation, the physical, mechanical and durability properties of six concrete mixtures were evaluated, one of conventional concrete (CC) with 100% Portland cement (PC) and five mixtures of Ecofriendly Ternary Concrete (ETC) made with partial replacement of Portland Cement by combinations of sugar cane bagasse ash (SCBA) and silica fume (SF) at percentages of 10, 20, 30, 40 and 50%. The physical properties of slump, temperature, and unit weight were determined, as well as compressive strength, rebound number, and electrical resistivity as a durability parameter. All tests were carried out according to the ASTM and ONNCCE standards. The obtained results show that the physical properties of ETC concretes are very similar to those of conventional concrete, complying with the corresponding regulations. Compressive strength results of all ETC mixtures showed favorable performances, increasing with aging, presenting values similar to CC at 90 days and greater values at 180 days in the ETC-20 and ETC-30 mixtures. Electrical resistivity results indicated that the five ETC mixtures performed better than conventional concrete throughout the entire monitoring period, increasing in durability almost proportionally to the percentage of substitution of Portland cement by the SCBA–SF combination; the ETC mixture made with 40% replacement had the highest resistivity value, which represents the longest durability. The present electrical resistivity indicates that the durability of the five ETC concretes was greater than conventional concrete. The results show that it is feasible to use ETC, because it meets the standards of quality, mechanical resistance and durability, and offers a very significant and beneficial contribution to the environment due to the use of agro-industrial and industrial waste as partial substitutes up to 50% of CPC, which contributes to reduction in CO2 emissions due to the production of Portland cement, responsible for 8% of total emissions worldwide.
Diagonalization Method to Hyperbolic Two-Temperature Generalized Thermoelastic Solid Sphere under Mechanical Damage Effect
Authors: Al-Lehaibi Eman A. N.
Published: August 2021

This study is the first to use the diagonalization method for the new modelling of a homogeneous, thermoelastic, and isotropic solid sphere that has been subjected to mechanical damage. The fundamental equations were derived using the hyperbolic two-temperature generalized thermoelasticity theory with mechanical damage taken into account. The outer surface of the sphere has been assumed to have been shocked thermally without cubical dilatation. The numerical results for the dynamical and conductive temperatures increment, strain, displacement, and average of the principal stresses components have been represented graphically with different values of the hyperbolic two-temperature parameter and mechanical damage parameters. The two-temperature model parameter and the mechanical damage parameter have significant effects. The propagations of the thermomechanical waves take place at finite speeds in the context of the hyperbolic two-temperature theory as well as in the usual context of the Lord–Shulman theory with one-temperature.
Trial Design of a Prospective Multicenter Diagnostic Accuracy Study of a Point-of-Care Test for the Detection of Taenia solium Taeniosis and Neurocysticercosis in Hospital-Based Settings in Tanzania
Authors: Trevisan Chiara , Damme Inge , Ngowi Bernard , Schmidt Veronika , Stelzle Dominik , Møller Karen , Kabululu Mwemezi , Makasi Charles , Magnussen Pascal , Bottieau Emmanuel , Abatih Emmanuel , Johansen Maria , Ngowi Helena , Ndawi Benedict , Mwape Kabemba , Zulu Gideon , Dorny Pierre , Winkler Andrea , Gabriël Sarah ,   on behalf of the SOLID Consortium
Published: August 2021

Taenia solium diagnosis is challenging as trained personnel, good diagnostic tools, and infrastructure is lacking in resource-poor areas. This paper aims to describe the study trial design adopted to evaluate a newly developed rapid point-of-care test that simultaneously detects taeniosis and neurocysticercosis (TS POC) in three district hospitals in Tanzania. The two-stage design included three types of patients: patients with specific neurological signs and symptoms (group 1); patients with complaints compatible with intestinal worm infections (group 2); patients with other symptom(s) (group 3). For group 1, all patients were tested using the TS POC test (stage 1), after which all positive, and a subset of negative, patients were selected for laboratory reference tests, clinical examination, and a brain computed tomography (CT) scan (stage 2). For groups 2 and 3, a similar design was adopted, but clinical examination and a brain CT scan (stage 2) were only performed in patients who were TS POC test-positive for cysticercosis. Due to the lack of a gold standard, a Bayesian approach was used to determine test accuracy for taeniosis and cysticercosis. For neurocysticercosis, a composite case definition was used as the reference standard. If successful, this study will help the future developments (commercialization and implementation) of the rapid test and improve patient management and disease prevention.