bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluorophores Use in Pituitary Surgery: A Pharmacokinetics and Pharmacodynamics Appraisal
Authors: Bongetta Daniele , Tartara Fulvio , Pagella Fabio , Somma Teresa , Cavaliere Marilou , Di Perna Giuseppe , Zenga Francesco , Cofano Fabio , Garbossa Diego , Zoia Cesare
Published: April 2021

(1) Background: Despite many surgical and technological advances, pituitary adenoma surgery is still burdened by non-negligible rates of incomplete tumor resection, mainly due to difficulties in differentiating pathology from normal pituitary tissue. Some fluorescent agents have been recently investigated as intraoperative contrast agents in pituitary surgery. The aim of this study is to evaluate the actual knowledge about the usefulness of such fluorophores with a particular focus on both the pharmacokinetics and pharmacodynamics issues of the pituitary gland. (2) Methods: We reviewed the current literature about fluorophores use in pituitary surgery and reported the first fully endoscopic experience with fluorescein. (3) Results: The studies investigating 5-ALA use reported contrasting results. ICG showed encouraging results, although with some specificity issues in identifying pathological tissue. Low-dose fluorescein showed promising results in differentiating pathology from normal pituitary tissue. Apart from the dose and timing of administration, both the fluorophores’ volume of distribution and the histological variability of the interstitial space and vascular density played a crucial role in optimizing intraoperative contrast enhancement. (4) Conclusions: Both pharmacokinetics and pharmacodynamics issues determine the potential usefulness of fluorophores in pituitary surgery. ICG and fluorescein showed the most promising results, although further studies are needed.
Speech Analysis Using Artificial Intelligence as a Peri-Operative Evaluation: A Case Report of a Patient with Temporal Lobe Epilepsy Secondary to Tuberous Sclerosis Complex Who Underwent Epilepsy Surgery
Authors: Niimi Keiko , Fujimoto Ayataka , Kano Yoshinobu , Otsuki Yoshiro , Enoki Hideo , Okanishi Tohru
Published: April 2021

Background: Improved conversational fluency is sometimes identified postoperatively in patients with epilepsy, but improvements can be difficult to assess using tests such as the intelligence quotient (IQ) test. Evaluation of pre- and postoperative differences might be considered subjective at present because of the lack of objective criteria. Artificial intelligence (AI) could possibly be used to make the evaluations more objective. The aim of this case report is thus to analyze the speech of a young female patient with epilepsy before and after surgery. Method: The speech of a nine-year-old girl with epilepsy secondary to tuberous sclerosis complex is recorded during interviews one month before and two months after surgery. The recorded speech is then manually transcribed and annotated, and subsequently automatically analyzed using AI software. IQ testing is also conducted on both occasions. The patient remains seizure-free for at least 13 months postoperatively. Results: There are decreases in total interview time and subjective case markers per second, whereas there are increases in morphemes and objective case markers per second. Postoperatively, IQ scores improve, except for the Perceptual Reasoning Index. Conclusions: AI analysis is able to identify differences in speech before and after epilepsy surgery upon an epilepsy patient with tuberous sclerosis complex.
Music as Add-On Therapy in the Rehabilitation Program of Parkinson’s Disease Patients—A Romanian Pilot Study
Authors: Fodor Dana Marieta , Breda Xenia-Melania , Valean Dan , Marta Monica Mihaela , Perju-Dumbrava Lacramioara
Published: April 2021

Music has been proven to have therapeutic potential in neurological disorders, especially Parkinson’s disease (PD), since rhythmic auditory cueing can partially replace the progressive loss of rhythmicity and automaticity. Several reports have highlighted improvements in motor outcomes in PD patients undergoing music therapy, but only a few studies have evaluated non-motor outcomes, such as quality of life (QoL), which deteriorates with disease progression. The current pilot study aims to examine the effects of a multimodal rehabilitation program centered on physical therapy combined with listening to music on self-reported QoL in people with PD, compared to the same rehabilitation program alone. The study was conducted on patients with idiopathic PD who attended a specific rehabilitation program with a duration of 2.5 h daily for 14 days. The patients were divided into the study group (16 patients), who listened to background music during the rehabilitation program sessions, and the control group who did not listen to music during sessions. The patients were assessed using the self-report Parkinson’s Disease Questionnaire (PDQ-39) at the beginning of the program and 1 month after its initiation. The patients in the study group registered greater improvements in five of the eight areas of life assessed by PDQ-39 compared to the control group. In conclusion, listening to music combined with a multimodal rehabilitation program centered on physical therapy may be beneficial for the patients’ quality of life.
Expect the Worst! Expectations and Social Interactive Decision Making
Authors: Giorgetta Cinzia , Grecucci Alessandro , Graffeo Michele , Bonini Nicolao , Ferrario Roberta , Sanfey Alan G.
Published: April 2021

Psychological studies have demonstrated that expectations can have substantial effects on choice behavior, although the role of expectations on social decision making in particular has been relatively unexplored. To broaden our knowledge, we examined the role of expectations on decision making when interacting with new game partners and then also in a subsequent interaction with the same partners. To perform this, 38 participants played an Ultimatum Game (UG) in the role of responders and were primed to expect to play with two different groups of proposers, either those that were relatively fair (a tendency to propose an equal split—the high expectation condition) or unfair (with a history of offering unequal splits—the low expectation condition). After playing these 40 UG rounds, they then played 40 Dictator Games (DG) as allocator with the same set of partners. The results showed that expectations affect UG decisions, with a greater proportion of unfair offers rejected from the high as compared to the low expectation group, suggesting that players utilize specific expectations of social interaction as a behavioral reference point. Importantly, this was evident within subjects. Interestingly, we also demonstrated that these expectation effects carried over to the subsequent DG. Participants allocated more money to the recipients of the high expectation group as well to those who made equal offers and, in particular, when the latter were expected to behave unfairly, suggesting that people tend to forgive negative violations and appreciate and reward positive violations. Therefore, both the expectations of others’ behavior and their violations play an important role in subsequent allocation decisions. Together, these two studies extend our knowledge of the role of expectations in social decision making.
Neuropsychological Evaluations in Limbic Encephalitis
Authors: Witt Juri-Alexander , Helmstaedter Christoph
Published: April 2021

Limbic encephalitis (LE) can cause dynamic and permanent impairment of cognition and behavior. In clinical practice, the question arises as to which cognitive and behavioral domains are affected by LE and which assessment is suited to monitor the disease progress and the success of treatment. Current findings on cognition and behavior in LE are reviewed and discussed based on current guidelines and consensus papers. In addition, we outline approaches for the neuropsychological monitoring of LE and its treatment. Dependent on disease acuity and severity, LE leads to episodic long-term memory dysfunction in different variants (e.g., anterograde memory impairment, accelerated long-term forgetting, and affection of autobiographical memory) and executive deficits. In addition, affective disorders are very common. More severe psychiatric symptoms may occur as well. In the course of the disease, dynamic phases with functional recovery must be differentiated from residual defect states. Evidence-based neuropsychological diagnostics should be conducted ideally before treatment initiation and reassessments are indicated when any progress is suggested, and when decisive anti-seizure or immunomodulatory treatment changes are made. Cognition and behavior may but must not run in synchrony with seizures, MRI pathology, or immune parameters. Cognitive and behavioral problems are integral aspects of LE and represent important biomarkers of disease acuity, progress, and therapy response beyond and in addition to parameters of immunology, neurological symptoms, and brain imaging. Thus, evidence-based neuropsychological assessments are essential for the diagnostic workup of patients with suspected or diagnosed limbic encephalitis, for treatment decisions, and disease and treatment monitoring.
Structured Reporting of Rectal Cancer Staging and Restaging: A Consensus Proposal
Authors: Granata Vincenza , Caruso Damiano , Grassi Roberto , Cappabianca Salvatore , Reginelli Alfonso , Rizzati Roberto , Masselli Gabriele , Golfieri Rita , Rengo Marco , Regge Daniele , Lo Re Giuseppe , Pradella Silvia , Fusco Roberta , Faggioni Lorenzo , Laghi Andrea , Miele Vittorio , Neri Emanuele , Coppola Francesca
Published: April 2021

Background: Structured reporting (SR) in oncologic imaging is becoming necessary and has recently been recognized by major scientific societies. The aim of this study was to build MRI-based structured reports for rectal cancer (RC) staging and restaging in order to provide clinicians all critical tumor information. Materials and Methods: A panel of radiologist experts in abdominal imaging, called the members of the Italian Society of Medical and Interventional Radiology, was established. The modified Delphi process was used to build the SR and to assess the level of agreement in all sections. The Cronbach’s alpha (Cα) correlation coefficient was used to assess the internal consistency of each section and to measure the quality analysis according to the average inter-item correlation. The intraclass correlation coefficient (ICC) was also evaluated. Results: After the second Delphi round of the SR RC staging, the panelists’ single scores and sum of scores were 3.8 (range 2–4) and 169, and the SR RC restaging panelists’ single scores and sum of scores were 3.7 (range 2–4) and 148, respectively. The Cα correlation coefficient was 0.79 for SR staging and 0.81 for SR restaging. The ICCs for the SR RC staging and restaging were 0.78 (p < 0.01) and 0.82 (p < 0.01), respectively. The final SR version was built and included 53 items for RC staging and 50 items for RC restaging. Conclusions: The final version of the structured reports of MRI-based RC staging and restaging should be a helpful and promising tool for clinicians in managing cancer patients properly. Structured reports collect all Patient Clinical Data, Clinical Evaluations and relevant key findings of Rectal Cancer, both in staging and restaging, and can facilitate clinical decision-making.
Development of an Objective Scoring System for Endoscopic Assessment of Radiation-Induced Upper Gastrointestinal Toxicity
Authors: Lin Daniel , Moningi Shalini , Abi Jaoude Joseph , Singh Ben S. , Cazacu Irina M. , Kouzy Ramez , Nogueras Gonzalez Graciela M. , Angsuwatcharakon Phonthep , Herman Joseph M. , Bhutani Manoop S. , Taniguchi Cullen M.
Published: April 2021

We developed and implemented an objective toxicity scoring system to be used during endoscopic evaluation of the upper gastrointestinal (GI) tract in order to directly assess changes in toxicity during the radiation treatment of pancreatic cancer. We assessed and validated the upper GI toxicity of 19 locally advanced pancreatic cancer trial patients undergoing stereotactic body radiation therapy (SBRT). Wilcoxon-signed rank tests were used to compare pre- and post-SBRT scores. Comparison of the toxicity scores measured before and after SBRT revealed a mild increase in toxicity in the stomach and duodenum (p < 0.005), with no cases of severe toxicity observed. Kappa and AC1 statistics analysis were used to evaluate interobserver agreement. Our toxicity scoring system was reliable in determining GI toxicity with a good overall interobserver agreement for pre-treatment scores (stomach, κ = 0.71, p < 0.005; duodenum, κ = 0.88, p < 0.005) and post-treatment scores (stomach, κ = 0.71, p < 0.005; duodenum, κ = 0.76, p < 0.005). The AC1 statistics yielded similar results. With future usage, we hope this scoring system will be a useful tool for objectively and reliably assessing changes in GI toxicity during the treatment of pancreatic cancer and for GI toxicity assessments and comparisons during radiation therapy research trials.
Phenotypic Characteristics of the Tumour Microenvironment in Primary and Secondary Hepatocellular Carcinoma
Authors: Fessas Petros , Spina Paolo , Boldorini Renzo L. , Pirisi Mario , Minisini Rosalba , Mauri Francesco A. , Simpson Fraser , Olivieri Paola , Gennari Alessandra , Wong Ching Ngar , Siddique Abdul , Goldin Robert D. , Akarca Ayse U. , Marafioti Teresa , Pinato David J.
Published: April 2021

(1) Background: The intra-tumoural heterogeneity (ITH) of hepatocellular carcinoma (HCC) and its microenvironment (TME) across primary and secondary disease is poorly characterised. (2) Methods: Intra-tumoural (IT) and peri-tumoural (PT) staining of matched primary and secondary samples was conducted to evaluate the distribution of CD4+/FOXP3+ and CD8+/PD1+ T-cells. Samples underwent PD-L1/2 immunostaining, tumour mutational burden (TMB) evaluation, and high-resolution T-cell receptor (TCR) sequencing to derive T-cell clonality and targeted transcriptomics. (3) Results: We analysed 24 samples from matched primary (n = 11) and secondary (n = 13; 5 synchronous, 6 metachronous) deposits, 11 being extrahepatic (84.6%). IT CD8+ density was lower than PT in both primary (p = 0.005) and secondary deposits (p = 0.01), consistent with immune exclusion. PD-L1+ tumours displayed higher IT and PT CD8+/PD1+ cell density compared to PD-L1- (p < 0.05), and primary IT infiltrate was enriched in CD4+/FOXP3+ cells, compared to PT regions (p = 0.004). TCR-sequencing demonstrated enrichment of the top T-cell clonotype in secondary versus primary HCC (p = 0.02), without differences in overall productive clonality (p = 0.35). TMB was similar across primary versus secondary HCC (p = 0.95). While directed gene set analysis demonstrated the uniformity of transcriptional signatures of individual immune cell types, secondary deposits demonstrated higher COLEC12 (p = 0.004), CCL26 (p = 0.02), CD1E (p = 0.02) and CD36 (p = 0.03) expression with downregulation of CXCL1 (p = 0.03), suggesting differential regulation of innate immunity. (4) Conclusion: Immune exclusion is a defining feature of the HCC TME. Despite evidence of homogeneity in somatic TMB, secondary HCC is characterised by the expansion of a distinct T-cell clonotype and differential regulation of innate immune pathways.
Wound Fluid from Breast Cancer Patients Undergoing Intraoperative Radiotherapy Exhibits an Altered Cytokine Profile and Impairs Mesenchymal Stromal Cell Function
Authors: Wuhrer Anne , Uhlig Stefanie , Tuschy Benjamin , Berlit Sebastian , Sperk Elena , Bieback Karen , Sütterlin Marc
Published: April 2021

Intraoperative radiotherapy (IORT) displays an increasingly used treatment option for early breast cancer. It exhibits non-inferiority concerning the risk of recurrence compared to conventional external irradiation (EBRT) in suitable patients with early breast cancer. Since most relapses occur in direct proximity of the former tumor site, the reduction of the risk of local recurrence effected by radiotherapy might partially be due to an alteration of the irradiated tumor bed’s micromilieu. Our aim was to investigate if IORT affects the local micromilieu, especially immune cells with concomitant cytokine profile, and if it has an impact on growth conditions for breast cancer cells as well as mammary mesenchymal stromal cells (MSC), the latter considered as a model of the tumor bed stroma.42 breast cancer patients with breast-conserving surgery were included, of whom 21 received IORT (IORT group) and 21 underwent surgery without IORT (control group). Drainage wound fluid (WF) was collected from both groups 24 h after surgery for flow cytometric analysis of immune cell subset counts and potential apoptosis and for multiplex cytokine analyses (cytokine array and ELISA). It served further as a supplement in cultures of MDA-MB 231 breast cancer cells and mammary MSC for functional analyses, including proliferation, wound healing and migration. Furthermore, the cytokine profile within conditioned media from WF-treated MSC cultures was assessed. Flow cytometric analysis showed no group-related changes of cell count, activation state and apoptosis rates of myeloid, lymphoid leucocytes and regulatory T cells in the WF. Multiplex cytokine analysis of the WF revealed group-related differences in the expression levels of several cytokines, e.g., oncostatin-M, leptin and IL-1β. The application of WF in MDA-MB 231 cultures did not show a group-related difference in proliferation, wound healing and chemotactic migration. However, WF from IORT-treated patients significantly inhibited mammary MSC proliferation, wound healing and migration compared to WF from the control group. The conditioned media collected from WF-treated MSC-cultures also exhibited altered concentrations of VEGF, RANTES and GROα. IORT causes significant changes in the cytokine profile and MSC growth behavior. These changes in the tumor bed could potentially contribute to the beneficial oncological outcome entailed by this technique. The consideration whether this alteration also affects MSC interaction with other stroma components presents a promising gateway for future investigations.
Challenges and Novel Opportunities of Radiation Therapy for Brain Metastases in Non-Small Cell Lung Cancer
Authors: Jablonska Paola Anna , Bosch-Barrera Joaquim , Serrano Diego , Valiente Manuel , Calvo Alfonso , Aristu Javier
Published: April 2021

Approximately 20% patients with non-small cell lung cancer (NSCLC) present with CNS spread at the time of diagnosis and 25–50% are found to have brain metastases (BMs) during the course of the disease. The improvement in the diagnostic tools and screening, as well as the use of new systemic therapies have contributed to a more precise diagnosis and prolonged survival of lung cancer patients with more time for BMs development. In the past, most of the systemic therapies failed intracranially because of the inability to effectively cross the blood brain barrier. Some of the new targeted therapies, especially the group of tyrosine kinase inhibitors (TKIs) have shown durable CNS response. However, the use of ionizing radiation remains vital in the management of metastatic brain disease. Although a decrease in CNS-related deaths has been achieved over the past decade, many challenges arise from the need of multiple and repeated brain radiation treatments, which carry along not insignificant risks and toxicity. The combination of stereotactic radiotherapy and systemic treatments in terms of effectiveness and adverse effects, such as radionecrosis, remains a subject of ongoing investigation. This review discusses the challenges of the use of radiation therapy in NSCLC BMs in view of different systemic treatments such as chemotherapy, TKIs and immunotherapy. It also outlines the future perspectives and strategies for personalized BMs management.
Proteomic Studies of Primary Acute Myeloid Leukemia Cells Derived from Patients Before and during Disease-Stabilizing Treatment Based on All-Trans Retinoic Acid and Valproic Acid
Authors: Hernandez-Valladares Maria , Wangen Rebecca , Aasebø Elise , Reikvam Håkon , Berven Frode S. , Selheim Frode , Bruserud Øystein
Published: April 2021

All-trans retinoic acid (ATRA) and valproic acid (VP) have been tried in the treatment of non-promyelocytic variants of acute myeloid leukemia (AML). Non-randomized studies suggest that the two drugs can stabilize AML and improve normal peripheral blood cell counts. In this context, we used a proteomic/phosphoproteomic strategy to investigate the in vivo effects of ATRA/VP on human AML cells. Before starting the combined treatment, AML responders showed increased levels of several proteins, especially those involved in neutrophil degranulation/differentiation, M phase regulation and the interconversion of nucleotide di- and triphosphates (i.e., DNA synthesis and binding). Several among the differentially regulated phosphorylation sites reflected differences in the regulation of RNA metabolism and apoptotic events at the same time point. These effects were mainly caused by increased cyclin dependent kinase 1 and 2 (CDK1/2), LIM domain kinase 1 and 2 (LIMK1/2), mitogen-activated protein kinase 7 (MAPK7) and protein kinase C delta (PRKCD) activity in responder cells. An extensive effect of in vivo treatment with ATRA/VP was the altered level and phosphorylation of proteins involved in the regulation of transcription/translation/RNA metabolism, especially in non-responders, but the regulation of cell metabolism, immune system and cytoskeletal functions were also affected. Our analysis of serial samples during the first week of treatment suggest that proteomic and phosphoproteomic profiling can be used for the early identification of responders to ATRA/VP-based treatment.
Prion Protein of Extracellular Vesicle Regulates the Progression of Colorectal Cancer
Authors: Yun Chul-Won , Lee Jun-Hee , Go Gyeongyun , Jeon Juhee , Yoon Sungtae , Lee Sang-Hun
Published: April 2021

Colorectal cancer (CRC) is one of the leading causes of cancer-related death due to its aggressive metastasis in later stages. Although there is a growing interest in the tumorigenic role of cellular prion protein (PrPC) in the process of metastasis, the precise mechanism behind the cellular communication involving prion proteins remains poorly understood. This study found that hypoxic tumor microenvironment increased the PrPC-expressing exosomes from CRC, and these exosomes regulate the CRC cell behavior and tumor progression depending on the expression of PrPC. Hypoxic exosomes from CRC cells promoted sphere formation, the expression of tumor-inducing genes, migration, invasion, and tumor growth. Furthermore, these exosomes increased endothelial permeability, migration, invasion, and angiogenic cytokine secretion. These effects were associated with PrPC expression. Application of anti-PrPC antibody with 5-fluorouracil significantly suppressed the CRC progression in a murine xenograft model. Taken together, these findings indicate that PrP-expressing exosomes secreted by hypoxic CRC cells are a key factor in the tumorigenic CRC-to-CRC and CRC-to-endothelial cell communication. Significance: These findings suggest that inhibiting PrPC in hypoxic exosomes during chemotherapy may be an effective therapeutic strategy in colorectal cancer.
Using Genomics Feature Selection Method in Radiomics Pipeline Improves Prognostication Performance in Locally Advanced Esophageal Squamous Cell Carcinoma—A Pilot Study
Authors: Xie Chen-Yi , Hu Yi-Huai , Ho Joshua Wing-Kei , Han Lu-Jun , Yang Hong , Wen Jing , Lam Ka-On , Wong Ian Yu-Hong , Law Simon Ying-Kit , Chiu Keith Wan-Hang , Fu Jian-Hua , Vardhanabhuti Varut
Published: April 2021

Purpose: To evaluate the prognostic value of baseline and restaging CT-based radiomics with features associated with gene expression in esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiation (nCRT) plus surgery. Methods: We enrolled 106 ESCC patients receiving nCRT from two institutions. Gene expression profiles of 28 patients in the training set were used to detect differentially expressed (DE) genes between patients with and without relapse. Radiomic features that were correlated to DE genes were selected, followed by additional machine learning selection. A radiomic nomogram for disease-free survival (DFS) prediction incorporating the radiomic signature and prognostic clinical characteristics was established for DFS estimation and validated. Results: The radiomic signature with DE genes feature selection achieved better performance for DFS prediction than without. The nomogram incorporating the radiomic signature and lymph nodal status significantly stratified patients into high and low-risk groups for DFS (p < 0.001). The areas under the curve (AUCs) for predicting 5-year DFS were 0.912 in the training set, 0.852 in the internal test set, 0.769 in the external test set. Conclusions: Genomics association was useful for radiomic feature selection. The established radiomic signature was prognostic for DFS. The radiomic nomogram could provide a valuable prediction for individualized long-term survival.
Exosomes in Liquid Biopsy: The Nanometric World in the Pursuit of Precision Oncology
Authors: Valencia Karmele , Montuenga Luis M.
Published: April 2021

Among the different components that can be analyzed in liquid biopsy, the utility of exosomes is particularly promising because of their presence in all biological fluids and their potential for multicomponent analyses. Exosomes are extracellular vesicles with an average size of ~100 nm in diameter with an endosomal origin. All eukaryotic cells release exosomes as part of their active physiology. In an oncologic patient, up to 10% of all the circulating exosomes are estimated to be tumor-derived exosomes. Exosome content mirrors the features of its cell of origin in terms of DNA, RNA, lipids, metabolites, and cytosolic/cell-surface proteins. Due to their multifactorial content, exosomes constitute a unique tool to capture the complexity and enormous heterogeneity of cancer in a longitudinal manner. Due to molecular features such as high nucleic acid concentrations and elevated coverage of genomic driver gene sequences, exosomes will probably become the “gold standard” liquid biopsy analyte in the near future.
PPARs and Tumor Microenvironment: The Emerging Roles of the Metabolic Master Regulators in Tumor Stromal–Epithelial Crosstalk and Carcinogenesis
Authors: Cheng Hong Sheng , Yip Yun Sheng , Lim Eldeen Kai Yi , Wahli Walter , Tan Nguan Soon
Published: April 2021

Peroxisome proliferator-activated receptors (PPARs) have been extensively studied for more than three decades. Consisting of three isotypes, PPARα, γ, and β/δ, these nuclear receptors are regarded as the master metabolic regulators which govern many aspects of the body energy homeostasis and cell fate. Their roles in malignancy are also increasingly recognized. With the growing interest in crosstalk between tumor stroma and epithelium, this review aims to highlight the current knowledge on the implications of PPARs in the tumor microenvironment. PPARγ plays a crucial role in the metabolic reprogramming of cancer-associated fibroblasts and adipocytes, coercing the two stromal cells to become substrate donors for cancer growth. Fibroblast PPARβ/δ can modify the risk of tumor initiation and cancer susceptibility. In endothelial cells, PPARβ/δ and PPARα are pro- and anti-angiogenic, respectively. Although the angiogenic role of PPARγ remains ambiguous, it is a crucial regulator in autocrine and paracrine signaling of cancer-associated fibroblasts and tumor-associated macrophages/immune cells. Of note, angiopoietin-like 4 (ANGPTL4), a secretory protein encoded by a target gene of PPARs, triggers critical oncogenic processes such as inflammatory signaling, extracellular matrix derangement, anoikis resistance and metastasis, making it a potential drug target for cancer treatment. To conclude, PPARs in the tumor microenvironment exhibit oncogenic activities which are highly controversial and dependent on many factors such as stromal cell types, cancer types, and oncogenesis stages. Thus, the success of PPAR-based anticancer treatment potentially relies on innovative strategies to modulate PPAR activity in a cell type-specific manner.
Evaluation of Glutaminase Expression in Prostate Adenocarcinoma and Correlation with Clinicopathologic Parameters
Authors: Myint Zin W. , Sun Ramon C. , Hensley Patrick J. , James Andrew C. , Wang Peng , Strup Stephen E. , McDonald Robert J. , Yan Donglin , St. Clair William H. , Allison Derek B.
Published: April 2021

High Glutaminase (GLS1) expression may have prognostic implications in colorectal and breast cancers; however, high quality data for expression in prostate cancer (PCa) are lacking. The purpose of this study is to investigate the status of GLS1 expression in PCa and correlated expression levels with clinicopathologic parameters. This study was conducted in two phases: an exploratory cohort analyzing RNA-Seq data for GLS1 from The Cancer Genome Atlas (TCGA) data portal (246 PCa samples) and a GLS1 immunohistochemical protein expression cohort utilizing a tissue microarray (TMA) (154 PCa samples; 41 benign samples) for correlation with clinicopathologic parameters. In the TCGA cohort, GLS1 mRNA expression did not show a statistically significant difference in disease-free survival (DFS) but did show a small significant difference in overall survival (OS). In the TMA cohort, there was no correlation between GLS1 expression and stage, Gleason score, DFS and OS. GLS1 expression did not significantly correlate with the clinical outcomes measured; however, GLS1 expression was higher in PCa cells compared to benign epithelium. Future studies are warranted to evaluate expression levels in greater numbers of high-grade and advanced PCa samples to investigate whether there is a rational basis for GLS1 targeted therapy in a subset of patients with prostate cancer.
Theoretical Study on the Lewis Acidity of the Pristine AlF3 and Cl-Doped α-AlF3 Surfaces
Authors: Becker Christian , Braun Thomas , Paulus Beate
Published: April 2021

In the past two decades, metal fluorides have gained importance in the field of heterogenous catalysis of bond activation reaction, e.g., hydrofluorination. One of the most investigated metal fluorides is AlF3. Together with its chlorine-doped analogon aluminiumchlorofluoride (AlClxF3−x, x = 0.05–0.3; abbreviated ACF), it has attracted much attention due to its application in catalysis. Various surface models for α-AlF3 and their chlorinated analogues (as representatives of amorphous ACF) are investigated with respect to their Lewis acidity of the active centres. First-principle density functional theory (DFT) methods with dispersion correction are used to determine the adsorption structure and energy of the probe molecules CO and NH3. The corresponding vibrational frequency shift agrees well with the measured values. With this insight we predict the local structure of the active sites and can clarify the importance of secondary interactions to the local anionic surrounding of the catalytic site.
Oxygen Evolution Activity of LaNbN2O-Based Photocatalysts Obtained from Nitridation of a Precursor Oxide Structurally Modified by Incorporating Volatile Elements
Authors: Ramu Shwetharani , Hisatomi Takashi , Domen Kazunari
Published: April 2021

The perovskite-type oxynitride LaNbN2O is a photocatalyst that can evolve oxygen from aqueous solutions in response to long-wavelength visible light. However, it is challenging to obtain active LaNbN2O because of the facile reduction of Nb5+ during the nitridation of the precursor materials. The present study attempted to synthesize a perovskite-type oxide La0.6Na0.4Zn0.4Nb0.6O3, containing equimolar amounts of La3+ and Nb5+ in addition to volatile Na+ and Zn2+, followed by the nitridation of this oxide to generate LaNbN2O. The obtained oxide was not the intended single-phase material but rather comprised a cuboid perovskite-type oxide similar to La0.5Na0.5Zn0.33Nb0.67O3 along with spherical LaNbO4 particles and other impurities. A brief nitridation was found to form a LaNbN2O-like shell structure having a light absorption onset of approximately 700 nm on the cuboid perovskite-type oxide particles. This LaNbN2O-based photocatalyst, when loaded with a CoOx cocatalyst, exhibited an apparent quantum yield of 1.7% at 420 nm during oxygen evolution reaction from an aqueous AgNO3 solution. This was more than double the values obtained from the nitridation products of LaNbO4 and LaKNaNbO5. The present work demonstrates a new approach to the design of precursor oxides that yield highly active LaNbN2O and suggests opportunities for developing efficient Nb-based perovskite oxynitride photocatalysts.
Optimizing Temperature Treatment of Copper Hollow Fibers for the Electrochemical Reduction of CO2 to CO
Authors: Hummadi Khalid Khazzal , Sustronk Anne , Kas Recep , Benes Nieck , Mul Guido
Published: April 2021

Copper hollow fibers were prepared via dry-wet spinning of a polymer solution of N-methylpyrrolidone, Polyetherimide, Polyvinyl Pyrolidone, and copper particles of sizes in the range of 1–2 µm. To remove template molecules and to sinter the copper particles, the time of calcination was varied in a range of 1–4 h at 600 °C. This calcination temperature was determined based on Thermal Gravimetric Analysis (TGA), showing completion of hydrocarbon removal at this temperature. Furthermore, the temperature of the subsequent treatment of the fibers in a flow of 4% H2 (in Ar) was varied in the range of 200 °C to 400 °C, at a fixed time of 1 h. Temperature programmed reduction experiments (TPR) were used to analyze the hydrogen treatment. The Faradaic Efficiency (FE) towards CO in electrochemical reduction of CO2 was determined at −0.45 V vs. RHE (Reversible Hydrogen Electrode), using a 0.3 M KHCO3 electrolyte. A calcination time of 3 h at 600 °C and a hydrogen treatment temperature of 280 °C were found to induce the highest FE to CO of 73% at these constant electrochemical conditions. Optimizing oxidation properties is discussed to likely affect porosity, favoring the CO2 gas distribution over the length of the fiber, and hence the CO2 reduction efficiency. Treatment in H2 in the range of 250 to 300 °C is proposed to affect the content of residual (subsurface) oxygen in Cu, which leads to favorable properties on the nanoscale.
ZnO Nanospheres Fabricated by Mechanochemical Method with Photocatalytic Properties
Authors: Zhou Zhou , Wang Jing , Jhun Chul Gyu
Published: April 2021

The preparation of high specific area (86.5 m2/g) ZnO nanospheres with good photocatalytic efficiency via a simple, green and efficient mechanochemical method was reported in this work. The products were characterized by XRD, SEM, TEM, BET and UV–Vis. The ball milling parameters were improved to reduce the agglomeration hazard during the ball milling process, and the specific surface area, band gap and photocatalytic efficiency were investigated in relation to ball milling time. Our study developed the opportunity for the low-cost and facile synthesis of a high specific surface area photocatalyst on a large scale for future industrial applications.
Influence of Nutrient-Stress Conditions on Chlorella vulgaris Biomass Production and Lipid Content
Authors: Ratomski Patryk , Hawrot-Paw Małgorzata
Published: April 2021

Microalgal biomass and its cellular components are used as substrates for the production of fuels. A valuable group among the components of microalgal biomass is lipids, which act as a precursor for the production of biodiesel in the transesterification process. Some methods, including the creation of stressful conditions, are applied to increase the accumulation of lipids. This study aimed to determine the effect of limited nutrient access on the growth and development of the microalga Chlorella vulgaris and the amount of lipids stored in its cells. Aquaculture wastewater (AWW) was used in the study as a source of nutrients at doses of 20%, 40%, 60%, 80% and 100%. The amount of microalgal biomass, optical density, lipid content after extraction of the biomass in Soxhlet apparatus and chlorophyll a content were determined. It was observed that the microalgae efficiently used the nutrients contained in the AWW. The largest amount of biomass was obtained in AWW80 (727 ± 19.64 mg·L−1). The OD680 (0.492 ± 0.00) determined under the same conditions was almost five times higher in AWW than in the synthetic medium. Under nutrient-stress conditions, the content of lipids in biomass ranged from 5.75% (AWW80) to 11.81% (AWW20). The highest content of chlorophyll a in microalgal cells was obtained in AWW20 (206 ± 11.33 mg∙m−3).
Development of a Decellularized Porcine Esophageal Matrix for Potential Applications in Cancer Modeling
Authors: Chaitin Hersh , Lu Michael L. , Wallace Michael B. , Kang Yunqing
Published: April 2021

Many decellularized extracellular matrix-derived whole organs have been widely used in studies of tissue engineering and cancer models. However, decellularizing porcine esophagus to obtain decellularized esophageal matrix (DEM) for potential biomedical applications has not been widely investigated. In this study a modified decellularization protocol was employed to prepare a porcine esophageal DEM for the study of cancer cell growth. The cellular removal and retention of matrix components in the porcine DEM were fully characterized. The microstructure of the DEM was observed using scanning electronic microscopy. Human esophageal squamous cell carcinoma (ESCC) and human primary esophageal fibroblast cells (FBCs) were seeded in the DEM to observe their growth. Results show that the decellularization process did not cause significant loss of mechanical properties and that blood ducts and lymphatic vessels in the submucosa layer were also preserved. ESCC and FBCs grew on the DEM well and the matrix did not show any toxicity to cells. When FBS and ESCC were cocultured on the matrix, they secreted more periostin, a protein that supports cell adhesion on matrix. This study shows that the modified decellularization protocol can effectively remove the cell materials and maintain the microstructure of the porcine esophageal matrix, which has the potential application of studying cell growth and migration for esophageal cancer models.
Comparative Study between Exogenously Applied Plant Growth Hormones versus Metabolites of Microbial Endophytes as Plant Growth-Promoting for Phaseolus vulgaris L.
Authors: Ismail Mohamed A. , Amin Mohamed A. , Eid Ahmed M. , Hassan Saad El-Din , Mahgoub Hany A. M. , Lashin Islam , Abdelwahab Abdelrhman T. , Azab Ehab , Gobouri Adil A. , Elkelish Amr , Fouda Amr
Published: April 2021

Microbial endophytes organize symbiotic relationships with the host plant, and their excretions contain diverse plant beneficial matter such as phytohormones and bioactive compounds. In the present investigation, six bacterial and four fungal strains were isolated from the common bean (Phaseolus vulgaris L.) root plant, identified using molecular techniques, and their growth-promoting properties were reviewed. All microbial isolates showed varying activities to produce indole-3-acetic acid (IAA) and different hydrolytic enzymes such as amylase, cellulase, protease, pectinase, and xylanase. Six bacterial endophytic isolates displayed phosphate-solubilizing capacity and ammonia production. We conducted a field experiment to evaluate the promotion activity of the metabolites of the most potent endophytic bacterial (Bacillus thuringiensis PB2 and Brevibacillus agri PB5) and fungal (Alternaria sorghi PF2 and, Penicillium commune PF3) strains in comparison to two exogenously applied hormone, IAA, and benzyl adenine (BA), on the growth and biochemical characteristics of the P. vulgaris L. Interestingly, our investigations showed that bacterial and fungal endophytic metabolites surpassed the exogenously applied hormones in increasing the plant biomass, photosynthetic pigments, carbohydrate and protein contents, antioxidant enzyme activity, endogenous hormones and yield traits. Our findings illustrate that the endophyte Brevibacillus agri (PB5) provides high potential as a stimulator for the growth and productivity of common bean plants.
HDL in Immune-Inflammatory Responses: Implications beyond Cardiovascular Diseases
Authors: Bonacina Fabrizia , Pirillo Angela , Catapano Alberico L. , Norata Giuseppe D.
Published: April 2021

High density lipoproteins (HDL) are heterogeneous particles composed by a vast array of proteins and lipids, mostly recognized for their cardiovascular (CV) protective effects. However, evidences from basic to clinical research have contributed to depict a role of HDL in the modulation of immune-inflammatory response thus paving the road to investigate their involvement in other diseases beyond those related to the CV system. HDL-C levels and HDL composition are indeed altered in patients with autoimmune diseases and usually associated to disease severity. At molecular levels, HDL have been shown to modulate the anti-inflammatory potential of endothelial cells and, by controlling the amount of cellular cholesterol, to interfere with the signaling through plasma membrane lipid rafts in immune cells. These findings, coupled to observations acquired from subjects carrying mutations in genes related to HDL system, have helped to elucidate the contribution of HDL beyond cholesterol efflux thus posing HDL-based therapies as a compelling interventional approach to limit the inflammatory burden of immune-inflammatory diseases.
Advances in Wearable Chemosensors
Authors: Koralli Panagiota , Mouzakis Dionysios E.
Published: April 2021

In this review, the latest research on wearable chemosensors is presented. In focus are the results from open literature, mainly from the last three years. The progress in wearable chemosensors is presented with attention drawn to the measuring technologies, their ability to provide robust data, the manufacturing techniques, as well their autonomy and ability to produce power. However, from statistical studies, the issue of patients’ trust in these technologies has arisen. People do not trust their personal data be transferred, stored, and processed through the vastness of the internet, which allows for timely diagnosis and treatment. The issue of power consumption and autonomy of chemosensor-integrated devices is also studied and the most recent solutions to this problem thoroughly presented.
Sustained Inflation Reduces Pulmonary Blood Flow during Resuscitation with an Intact Cord
Authors: Nair Jayasree , Davidson Lauren , Gugino Sylvia , Koenigsknecht Carmon , Helman Justin , Nielsen Lori , Sankaran Deepika , Agrawal Vikash , Chandrasekharan Praveen , Rawat Munmun , Berkelhamer Sara K. , Lakshminrusimha Satyan
Published: April 2021

The optimal timing of cord clamping in asphyxia is not known. Our aims were to determine the effect of ventilation (sustained inflation–SI vs. positive pressure ventilation–V) with early (ECC) or delayed cord clamping (DCC) in asphyxiated near-term lambs. We hypothesized that SI with DCC improves gas exchange and hemodynamics in near-term lambs with asphyxial bradycardia. A total of 28 lambs were asphyxiated to a mean blood pressure of 22 mmHg. Lambs were randomized based on the timing of cord clamping (ECC—immediate, DCC—60 s) and mode of initial ventilation into five groups: ECC + V, ECC + SI, DCC, DCC + V and DCC + SI. The magnitude of placental transfusion was assessed using biotinylated RBC. Though an asphyxial bradycardia model, 2–3 lambs in each group were arrested. There was no difference in primary outcomes, the time to reach baseline carotid blood flow (CBF), HR ≥ 100 bpm or MBP ≥ 40 mmHg. SI reduced pulmonary (PBF) and umbilical venous (UV) blood flow without affecting CBF or umbilical arterial blood flow. A significant reduction in PBF with SI persisted for a few minutes after birth. In our model of perinatal asphyxia, an initial SI breath increased airway pressure, and reduced PBF and UV return with an intact cord. Further clinical studies evaluating the timing of cord clamping and ventilation strategy in asphyxiated infants are warranted.
Understanding Laboratory Testing for SARS-CoV-2
Authors: Cheema Ritu , Blumberg Dean A.
Published: April 2021

The SARS-CoV-2 pandemic has impacted millions of lives worldwide. Molecular assays and serological tests have been approved under EUA (emergency use authorization) by the FDA (food and drug administration), given these unprecedented times. These tests are not only critical for confirming the clinical diagnosis and making therapeutic decisions but also play an important role in the understanding of the epidemiology of the pandemic. There is limited experience with currently available tests and differences may exist among tests even using similar technology. The focus of this review is to improve clinicians’ understanding of SARS-CoV-2 test procedures including their limitations. We discuss the impact of different host and environmental factors on test results.
Audit of Psychosocial and Palliative Care Support for Children Having Allogeneic Stem Cell Transplants at the New Zealand National Allogeneic Transplant Centre
Authors: Evans Amanda M. , Thabrew Hiran , Arroll Bruce , Cole Nyree , Drake Ross
Published: April 2021

Psychosocial and palliative care support during stem cell transplants (SCT) is known to improve outcomes. Aim: evaluate the support provided to children and families at the New Zealand National Allogeneic Stem Cell Transplant unit (NATC). Method: the psychosocial and palliative care support for children who received SCT between December 2012 and April 2018 was audited. Results: of the 101 children who received SCT, 97% were reviewed by the social work team (SW) and 82% by the psychiatric consult liaison team (CLT) at least once during their illness. However, pre-transplant psychological assessment only occurred in 16%, and during the SCT admission, only 55% received SW support, and 67% received CLT support. Eight out of eighty-five families (9%) were offered support for siblings. Eight of the sixteen children who died were referred for pediatric palliative care (PPC) with all supported and half the families who experienced a death (n = 8; 50%) received bereavement follow up. Conclusion: although the majority received some social work and psychological support, auditing against the standards suggests the consistency of involvement could be improved. Referrals for PPC were inadequate and largely for end-of-life phase. Sibling support, in particular donor siblings, had insufficient psychological assessment and support. Key recommendations are provided to address this underperformance.