bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Graphite Powder on the Mechanical and Acoustic Emission Characteristics of Concrete
Authors: He Wei , Hao Wenru , Meng Xia , Zhang Pengchong , Sun Xu , Shen Yinlan
Published: December 2021

In this paper, uniaxial compressive strength (UCS) test and three-point bending (TPB) test, together with an acoustic emission (AE) system, were performed to investigate the mechanical properties and AE characteristic changes of concrete with different graphite powder (GP) content. The results show that: (1) Poor adhesion and low interlocking of graphite with cement stone increase the initial defects of concrete, reducing its elastic modulus and the cyclo-hoop effect, and thus weakening the compressive strength. (2) For concrete with a low graphite content, the second sharp rise in ringing counts or energy released during the compressive process can be regarded as a failure alarm. However, as GP content increases, the second sharp rise fades away, while the first sharp rise becomes more visible. At high GP content, the first sharp rise is better for predicting failure. (3) The initial defects caused by GP significantly lower the initial fracture toughness, but its bridging effect greatly increases the critical crack mouth opening displacement and thus significantly enhances the unstable fracture toughness of concrete, by up to 9.9% at 9% GP content. (4) In contrast to compressive process, the sharp increase in AE signals preceding failure during the fracture process cannot be used to predict failure because it occurs too close to the ultimate load. However, as GP can significantly increase the AE signals and damage value in the stable period, such failure precursor information can provide a safety warning for damage development.
Does an Endometrial Cancer Diagnosis among Asymptomatic Patients Improve Prognosis?
Authors: Vinklerová Petra , Ovesná Petra , Bednaříková Markéta , Minář Luboš , Felsinger Michal , Hausnerová Jitka , Weinberger Vít
Published: December 2021

Background: Endometrial cancer is the most common gynecological malignancy in developed countries with no screening available. There is still a tendency to provide invasive bioptic verification in asymptomatic women with abnormal ultrasound findings to diagnose carcinoma in a preclinical phase; even though, it is not supported by European guidelines. Our goal was to determine DFS (disease-free survival), OS (overall survival), and DSS (disease-specific survival) differences between symptom-free and symptomatic (bleeding, or spotting) endometrial cancer patients with similar stage and tumor/clinical characteristics. Methods: All of our patients with endometrial cancer following surgical treatment between 2006 and 2019 were assessed, evaluating risk factors for recurrence and death while focusing on bleeding using univariable and multivariable analysis. Results: 625 patients meeting the inclusion criteria were divided into asymptomatic (n = 144, 23%) and symptomatic (n = 481, 77%) groups. The median follow-up was 3.6 years. Using univariable analysis, symptomatic patients had a three times higher risk of recurrence (HR 3.1 (95% Cl 1.24–7.77), p = 0.016). OS (HR 1.35 (0.84–2.19), p = 0.219) and DSS (HR 1.66 (0.64–4.28), p = 0.3) were slightly worse without reaching statistical significance. In our multivariable analysis, symptomatology was deemed completely insignificant in all monitored parameters (DFS: HR 2.03 (0.79–5.24), p = 0.144; OS: HR 0.72 (0.43–1.21), p = 0.216). Conclusions: The symptomatic endometrial cancer patients risk factor of earlier recurrence and death is insignificantly higher when compared with the asymptomatic cohort. However, multivariable analysis verifies that prognosis worsens with other clinically relevant parameters, not by symptomatology itself. In terms of survival outcome in EC patients, we recognized symptomatology as a non-significant marker for the patient’s prognosis.
Interrelation between Spectral Online Monitoring and Postoperative T1-Weighted MRI in Interstitial Photodynamic Therapy of Malignant Gliomas
Authors: Aumiller Maximilian , Heckl Christian , Quach Stefanie , Stepp Herbert , Ertl-Wagner Birgit , Sroka Ronald , Thon Niklas , Rühm Adrian
Published: December 2021

In a former study, interstitial photodynamic therapy (iPDT) was performed on patients suffering from newly diagnosed glioblastoma (n = 11; 8/3 male/female; median age: 68, range: 40–76). The procedure includes the application of 5-ALA to selectively metabolize protoporphyrin IX (PpIX) in tumor cells and illumination utilizing interstitially positioned optical cylindrical diffuser fibers (CDF) (2–10 CDFs, 2–3 cm diffusor length, 200 mW/cm, 635 nm, 60 min irradiation). Intraoperative spectral online monitoring (SOM) was employed to monitor treatment light transmission and PpIX fluorescence during iPDT. MRI was used for treatment planning and outcome assessment. Case-dependent observations included intraoperative reduction of treatment light transmission and local intrinsic T1 hyperintensity in non-contrast-enhanced T1-weighted MRI acquired within one day after iPDT. Intrinsic T1 hyperintensity was observed and found to be associated with the treatment volume, which indicates the presence of methemoglobin, possibly induced by iPDT. Based on SOM data, the optical absorption coefficient and its change during iPDT were estimated for the target tissue volumes interjacent between evaluable CDF-pairs at the treatment wavelength of 635 nm. By spatial comparison and statistical analysis, it was found that observed increases of the absorption coefficient during iPDT were larger in or near regions of intrinsic T1 hyperintensity (p = 0.003). In cases where PpIX-fluorescence was undetectable before iPDT, the increase in optical absorption and intrinsic T1 hyperintensity tended to be less. The observations are consistent with in vitro experiments and indicate PDT-induced deoxygenation of hemoglobin and methemoglobin formation. Further investigations are needed to provide more data on the time course of the observed changes, thus paving the way for optimized iPDT irradiation protocols.
Novel Combinations of Human Immunomodulatory mAbs Lacking Cardiotoxic Effects for Therapy of TNBC
Authors: Vetrei Cinzia , Passariello Margherita , Froechlich Guendalina , Rapuano Lembo Rosa , Sasso Emanuele , Zambrano Nicola , De Lorenzo Claudia
Published: December 2021

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer characterized by a higher mortality rate among breast cancer subtypes. Poly(ADP-ribose) polymerase (PARP) inhibitors are used in clinics to treat a subgroup of TNBC patients, but other targeted therapies are urgently needed. Programmed death-ligand 1 (PD-L1), involved in tumor immune escape, was recently identified as a target for TNBC; accordingly, the anti-PD-L1 monoclonal antibody (mAb), atezolizumab, has been approved by FDA in combination with Paclitaxel for the therapy of metastatic TNBC. Here, we tested novel combinations of fully human immunomodulatory mAbs, including anti-PD-L1 mAbs generated in our laboratory and atezolizumab, on TNBC and other tumor cell lines. We evaluated their anti-tumor efficacy when used as single agents or in combinatorial treatments with anti-CTLA-4 mAbs in in vitro co-cultures of hPBMCs with tumor cells, by measuring tumor cell lysis and IL-2 and IFNγ cytokines secretion by lymphocytes. In parallel, by using co-cultures of hPBMCs and cardiomyocytes, we analyzed the potential cardiotoxic adverse side effects of the same antibody treatments by measuring the cardiac cell lysis and the secretion of pro-inflammatory cytokines. We identified novel combinations of immunomodulatory mAbs endowed with more potent anti-cancer activity on TNBC and lower cardiotoxic side effects than the combination of atezolizumab and ipilimumab.
Immunotherapy in Patients with Advanced Non-Small Cell Lung Cancer Lacking Driver Mutations and Future Perspectives
Authors: De Mello Ramon Andrade Bezerra , Voscaboinik Rafael , Luciano João Vittor Pires , Cremonese Rafaela Vilela , Amaral Giovanna Araujo , Castelo-Branco Pedro , Antoniou Georgios
Published: December 2021

From a complete literature review, we were able to present in this paper what is most current in the treatment with immunotherapy for advanced non-small cell lung cancer (NSCLC). Especially the use of immunotherapy, particularly inhibitors of PD-1 (programmed cell death protein 1), PDL-1 (programmed cell death protein ligand 1), and CTLA-4 (cytotoxic T-lymphocyte antigen 4). Since 2015, these drugs have transformed the treatment of advanced NSCLC lacking driver mutations, evolving from second-line therapy to first-line, with excellent results. The arrival of new checkpoint inhibitors such as cemiplimab and the use of checkpoint inhibitors earlier in the therapy of advanced and metastatic cancers has been making the future prospects for treating NSCLC lacking driver mutations more favorable and optimistic. In addition, for those patients who have low PDL-1 positivity tumors, the combination of cytotoxic chemotherapy, VEGF inhibitor, and immunotherapy have shown an important improvement in global survival and progression free survival regardless the PDL-1 status. We also explored the effectiveness of adding radiotherapy to immunotherapy and the most current results about this combination. One concern that cannot be overlooked is the safety profile of immune checkpoint inhibitors (ICI) and the most common toxicities are described throughout this paper as well as tumor resistance to ICI.
Genomic and Transcriptomic Underpinnings of Melanoma Genesis, Progression, and Metastasis
Authors: Cherepakhin Olga S. , Argenyi Zsolt B. , Moshiri Ata S.
Published: December 2021

Melanoma is a deadly skin cancer with rapidly increasing incidence worldwide. The discovery of the genetic drivers of melanomagenesis in the last decade has led the World Health Organization to reclassify melanoma subtypes by their molecular pathways rather than traditional clinical and histopathologic features. Despite this significant advance, the genomic and transcriptomic drivers of metastatic progression are less well characterized. This review describes the known molecular pathways of cutaneous and uveal melanoma progression, highlights recently identified pathways and mediators of metastasis, and touches on the influence of the tumor microenvironment on metastatic progression and treatment resistance. While targeted therapies and immune checkpoint blockade have significantly aided in the treatment of advanced disease, acquired drug resistance remains an unfortunately common problem, and there is still a great need to identify potential prognostic markers and novel therapeutic targets to aid in such cases.
Perineural Invasion in Vulvar Squamous-Cell Carcinoma Is an Independent Risk Factor for Cancer-Specific Survival, but Not for Locoregional Recurrence: Results from a Single Tertiary Referral Center
Authors: Micheletti Leonardo , Borella Fulvio , Preti Mario , Frau Valentina , Cosma Stefano , Privitera Sebastiana , Bertero Luca , Benedetto Chiara
Published: December 2021

The aims of this study were to assess the prevalence of perineural invasion (PNI) in vulvar squamous cell carcinoma (VSCC) and its prognostic role in locoregional recurrence (LRR) and cancer-specific survival (CSS). We performed a retrospective analysis of 223 consecutive stage IB–IIIC surgically treated VSCCs at S. Anna Hospital, University of Turin, from 2000 to 2019. We identified 133/223 (59.6%) patients with PNI-positive VSCCs. PNI was associated with aggressive biological features (i.e., advanced FIGO stage, larger tumor diameter, greater depth of invasion, a higher number of metastatic lymph nodes, and lymphovascular invasion) and shorter 5-year CSS (78% vs. 90%, log-rank p = 0.02) compared with PNI-negative VSCCs. Multivariate analysis showed that PNI (HR 2.99 CI 95% 1.17–7.63; p = 0.02) and the presence of tumor cells on pathological surgical margins (HR 3.13 CI 95% 1.37–7.13; p = 0.007) are independent prognostic factors for CSS. PNI does not appear to be related to LRR, but is an independent prognostic factor for worse survival outcomes. Future studies are necessary to explore the possible value of PNI in tailoring the choice of adjuvant treatment.
A Chemerin Peptide Analog Stimulates Tumor Growth in Two Xenograft Mouse Models of Human Colorectal Carcinoma
Authors: Friebus-Kardash Justa , Schulz Petra , Reinicke Sandy , Karthaus Cordula , Schefer Quirino , Bandholtz Sebastian , Grötzinger Carsten
Published: December 2021

Background: Chemerin plasma concentration has been reported to be positively correlated with the risk of colorectal cancer. However, the potential regulation of CRC tumorigenesis and progression has not yet been investigated in an experimental setting. This study addresses this hypothesis by investigating proliferation, colony formation, and migration of CRC cell lines in vitro as well as in animal models. Methods: In vitro, microscopic assays to study proliferation, as well as a scratch-wound assay for migration monitoring, were applied using the human CRC cell lines HCT116, HT29, and SW620 under the influence of the chemerin analog CG34. The animal study investigated HCT116-luc and HT29-luc subcutaneous tumor size and bioluminescence during treatment with CG34 versus control, followed by an ex-vivo analysis of vessel density and mitotic activity. Results: While the proliferation of the three CRC cell lines in monolayers was not clearly stimulated by CG34, the chemerin analog promoted colony formation in three-dimensional aggregates. An effect on cell migration was not observed. In the treatment study, CG34 significantly stimulated both growth and bioluminescence signals of HCT116-luc and HT29-luc xenografts. Conclusions: The results of this study represent the first indication of a tumor growth-stimulating effect of chemerin signaling in CRC.
Relapsed Medulloblastoma in Pre-Irradiated Patients: Current Practice for Diagnostics and Treatment
Authors: Hill Rebecca M. , Plasschaert Sabine L. A. , Timmermann Beate , Dufour Christelle , Aquilina Kristian , Avula Shivaram , Donovan Laura , Lequin Maarten , Pietsch Torsten , Thomale Ulrich , Tippelt Stephan , Wesseling Pieter , Rutkowski Stefan , Clifford Steven C. , Pfister Stefan M. , Bailey Simon , Fleischhack Gudrun
Published: December 2021

Relapsed medulloblastoma (rMB) accounts for a considerable, and disproportionate amount of childhood cancer deaths. Recent advances have gone someway to characterising disease biology at relapse including second malignancies that often cannot be distinguished from relapse on imaging alone. Furthermore, there are now multiple international early-phase trials exploring drug–target matches across a range of high-risk/relapsed paediatric tumours. Despite these advances, treatment at relapse in pre-irradiated patients is typically non-curative and focuses on providing life-prolonging and symptom-modifying care that is tailored to the needs and wishes of the individual and their family. Here, we describe the current understanding of prognostic factors at disease relapse such as principal molecular group, adverse molecular biology, and timing of relapse. We provide an overview of the clinical diagnostic process including signs and symptoms, staging investigations, and molecular pathology, followed by a summary of treatment modalities and considerations. Finally, we summarise future directions to progress understanding of treatment resistance and the biological mechanisms underpinning early therapy-refractory and relapsed disease. These initiatives include development of comprehensive and collaborative molecular profiling approaches at relapse, liquid biopsies such as cerebrospinal fluid (CSF) as a biomarker of minimal residual disease (MRD), modelling strategies, and the use of primary tumour material for real-time drug screening approaches.
Prediction of Chemotoxicity, Unplanned Hospitalizations and Early Death in Older Patients with Colorectal Cancer Treated with Chemotherapy
Authors: Feliu Jaime , Espinosa Enrique , Basterretxea Laura , Paredero Irene , Llabrés Elisenda , Jiménez-Munárriz Beatriz , Antonio-Rebollo Maite , Losada Beatriz , Pinto Alvaro , Custodio Ana Belén , del Mar Muñoz María , Gómez-Mediavilla Jenifer , Torregrosa María-Dolores , Soler Gema , Cruz Patricia , Higuera Oliver , Molina-Garrido María-José
Published: December 2021

Purpose: To identify risk factors for toxicity, unplanned hospitalization (UH) and early death (ED) in older patients with colorectal carcinoma (CRC) initiating chemotherapy. Methods: 215 patients over 70 years were prospectively included. Geriatric assessment was performed before treatment, and tumor and treatment variables were collected. The association between these factors and grade 3–5 toxicity, UH and ED (<6 months) was examined by using multivariable logistic regression. Score points were assigned to each risk factor. Results: During the first 6 months of treatment, 33% of patients developed grade 3–5 toxicity, 31% had UH and 23% died. Risk factors were, for toxicity, instrumental activities of daily living, creatinine clearance, weight loss and MAX2 index; for UH, Charlson Comorbidity Score, creatinine clearance, weight loss, serum albumin, and metastatic disease; and for ED, basic activities in daily living, weight loss, metastatic disease, and hemoglobin levels. Predictive scores were built with these variables. The areas under receiver operation characteristic (ROC) curves for toxicity, UH and ED were 0.70 (95% CI: 0.64–0.766), 0.726 (95% IC: 0.661–0.799) and 0.74 (95% IC: 0.678–0.809), respectively. Conclusion: Simple scores based on geriatric, tumor and laboratory characteristics predict severe toxicity, UH and ED, and may help in treatment planning.
Actionable Molecular Alterations Are Revealed in Majority of Advanced Non-Small Cell Lung Cancer Patients by Genomic Tumor Profiling at Progression after First Line Treatment
Authors: Frank Malene Støchkel , Bodtger Uffe , Gehl Julie , Ahlborn Lise Barlebo
Published: December 2021

Background: Genomic profiling in advanced Non-Small Cell Lung cancer (NSCLC) can reveal Actionable Molecular Alterations (AMAs). Our study aims to investigate clinical relevance of re-biopsy after first line treatment, by reporting on acquired and persistent AMAs and potential targeted treatments in a real-time cohort of NSCLC patients. Methods: Patients with advanced NSCLC receiving first-line treatment were prospectively included in an observational study (NCT03512847). Genomic profiling was performed by TruSight Oncology 500 HT gene panel on tumor tissue collected at diagnosis and at time of progression. Results: The 92 patients re-biopsied at progression had received immunotherapy (n = 44), chemotherapy (n = 44), or combination treatment (n = 4). In 87 of these patients (95%), successful genomic profiling was performed at both the diagnostic biopsy and the re-biopsy. In 74 patients (85%), ≥1 AMA were found. The AMAs were acquired in 28%. The most frequent AMAs were observed in TP53 (45%), KRAS (24%), PIK3CA (6%), and FGFR1 (6%). Only five patients (5%) received targeted treatment mainly due to deterioration in performance status. Conclusions: Re-biopsy at progression revealed acquired AMAs in approximately one third of patients, and 85% had at least one AMA with the potential of receiving targeted treatment, thus strengthening the clinical relevance of re-biopsy.
Fast Adaptive Temperature-Based Re-Optimization Strategies for On-Line Hot Spot Suppression during Locoregional Hyperthermia
Authors: Kok H. Petra , Crezee Johannes
Published: December 2021

Background: Experience-based adjustments in phase-amplitude settings are applied to suppress treatment limiting hot spots that occur during locoregional hyperthermia for pelvic tumors. Treatment planning could help to further optimize treatments. The aim of this research was to develop temperature-based re-optimization strategies and compare the predicted effectiveness with clinically applied protocol/experience-based steering. Methods: This study evaluated 22 hot spot suppressions in 16 cervical cancer patients (mean age 67 ± 13 year). As a first step, all potential hot spot locations were represented by a spherical region, with a user-specified diameter. For fast and robust calculations, the hot spot temperature was represented by a user-specified percentage of the voxels with the largest heating potential (HPP). Re-optimization maximized tumor T90, with constraints to suppress the hot spot and avoid any significant increase in other regions. Potential hot spot region diameter and HPP were varied and objective functions with and without penalty terms to prevent and minimize temperature increase at other potential hot spot locations were evaluated. Predicted effectiveness was compared with clinically applied steering results. Results: All strategies showed effective hot spot suppression, without affecting tumor temperatures, similar to clinical steering. To avoid the risk of inducing new hot spots, HPP should not exceed 10%. Adding a penalty term to the objective function to minimize the temperature increase at other potential hot spot locations was most effective. Re-optimization times were typically ~10 s. Conclusion: Fast on-line re-optimization to suppress treatment limiting hot spots seems feasible to match effectiveness of ~30 years clinical experience and will be further evaluated in a clinical setting.
A Model-Based Framework to Identify Optimal Administration Protocols for Immunotherapies in Castration-Resistance Prostate Cancer
Authors: Coletti Roberta , Pugliese Andrea , Lunardi Andrea , Caffo Orazio , Marchetti Luca
Published: December 2021

Prostate cancer (PCa) is one of the most frequent cancer in male population. Androgen deprivation therapy is the first-line strategy for the metastatic stage of the disease, but, inevitably, PCa develops resistance to castration (CRPC), becoming incurable. In recent years, clinical trials are testing the efficacy of anti-CTLA4 on CRPC. However, this tumor seems to be resistant to immunotherapies that are very effective in other types of cancers, and, so far, only the dendritic cell vaccine sipuleucel-T has been approved. In this work, we employ a mathematical model of CRPC to determine the optimal administration protocol of ipilimumab, a particular anti-CTLA4, as single treatment or in combination with the sipuleucel-T, by considering both the effect on tumor population and the drug toxicity. To this end, we first introduce a dose-depending function of toxicity, estimated from experimental data, then we define two different optimization problems. We show the results obtained by imposing different constraints, and how these change by varying drug efficacy. Our results suggest administration of high-doses for a brief period, which is predicted to be more efficient than solutions with prolonged low-doses. The model also highlights a synergy between ipilimumab and sipuleucel-T, which leads to a better tumor control with lower doses of ipilimumab. Finally, tumor eradication is also conceivable, but it depends on patient-specific parameters.
Effects of Red Blood Cell Transfusions on Distant Metastases of Oral Squamous Cell Carcinomas
Authors: Brandenburg Leonard Simon , Metzger Marc Christian , Poxleitner Philipp , Voss Pit Jacob , Vach Kirstin , Hell Johannes , Hasel Konstantin , Weingart Julia Vera , Schwarz Steffen Jochen , Ermer Michael Andreas
Published: December 2021

There is no consensus on the effect of red blood cell (RBC) transfusions on patients with oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the association between RBC administration and the occurrence of distant metastases (M+) after surgical treatment of OSCC. All medical records of patients who underwent primary surgery for OSCC in our department (2003–2019) were analyzed retrospectively (n = 609). Chi and Cox regression models were used to analyze the influence of transfusion on the development of M+, and survival rates. Kaplan–Meier curves were used for graphical presentation. A multitude of patient-specific factors showed a statistical impact in univariate analysis (transfusion, age, gender, diabetes, pT, pN, L, V, Pn, G, UICC, adjuvant therapy, free microvascular transplant, preoperative hemoglobin level). Transfusion status and pN stage were the only variables that showed a significant correlation to M+ in the multivariate Cox model. The hazard ratios for the occurrence of M+ were 2.42 for RBC transfusions and 2.99 for pN+. Administration of RBC transfusions was identified as a significant prognostic parameter for the occurrence of distant metastases after surgical treatment of OSCC. Hence, the administration of RBC transfusions should be considered carefully in the perioperative management.
Synthesis of Atmospherically Stable Zero-Valent Iron Nanoparticles (nZVI) for the Efficient Catalytic Treatment of High-Strength Domestic Wastewater
Authors: Ansari Afzal , Siddiqui Vasi Uddin , Akram Md. Khursheed , Siddiqi Weqar Ahmad , Khan Anish , Al-Romaizan Abeer Nasser , Hussein Mahmoud A. , Puttegowda Madhu
Published: December 2021

Here, we report the fabrication of nZVI by the wet chemical technique in the presence of ethanol using ferric iron and sodium borohydride as the reducing agents under ambient conditions. The obtained nZVI particles are mainly in a zero-valent oxidation state and do not undergo significant oxidation for several weeks. The structural and morphological parameters of nZVI were investigated by using UV, XRD, SEM, EDX, TEM, and DLS analysis. The optical nature, bandgap energy, and absorption edge were all revealed by the UV–visible spectrum. The phase development and crystallinity of nZVI particles were shown by the XRD pattern. The morphological investigation revealed that the nanoparticles were spherical with an average size of 34–110 nm by using ImageJ software, and the elemental analysis was analyzed using EDX. Furthermore, the catalytic treatment performance of domestic wastewater was evaluated in terms of pH, COD (chemical oxygen demand) solubilization, total solids (TS), volatile solids (VS), phosphorous, and total nitrogen (TN) reduction under aerobic and anaerobic operating conditions. The effluent was subjected to a process evaluation with a different range (100–500 mg/L) of nZVI dosages. The COD solubilization and suspended solids reduction were significantly improved in the anaerobic condition in comparison to the aerobic condition. Furthermore, the effect of nZVI on phosphorous (PO43−) reduction was enhanced by the electrons of iron ions. The high concentration of nZVI dosing has a positive impact on COD solubilization and phosphorous removal regardless of the aeration condition with 400 mg/L of nZVI dosage.
Two Biotechnological Approaches to the Preparative Synthesis of Natural Dihydrocoumarin
Authors: Serra Stefano , Marzorati Stefano , Valentino Mattia
Published: December 2021

In this work, we describe two different biotechnological processes that provide the natural flavour dihydrocoumarin in preparative scale. Both the presented approaches are based on the enzyme-mediated reduction of natural coumarin. The first one is a whole-cell process exploiting the reductive activity of the yeast Kluyveromyces marxianus, a Generally Recognized As Safe (GRAS) microorganism that possesses high resistance to the substrate toxicity. Differently, the second is based on the reduction of natural coumarin by nicotinamide adenine dinucleotide phosphate (NADPH) and using the Old Yellow Enzyme reductase OYE2 as catalyst. NADPH is used in catalytic amount since the co-factor regeneration is warranted employing an enzymatic system based on glucose oxidation, in turn catalysed by a further enzyme, namely glucose dehydrogenase (GDH). Both processes compare favourably over the previously reported industrial method as they work with higher coumarin concentration (up to 3 g/L for the enzymatic process) yet allowing the complete conversion of the substrate. Furthermore, the two approaches have significant differences. The microbial reduction is experimentally simple but the isolated dihydrocoumarin yield does not exceed 60%. On the contrary, the enzymatic approach requires the use of two specially prepared recombinant enzymes, however, it is more efficient, affording the product in 90% of isolated yield.
Introgression of SbERD4 Gene Encodes an Early-Responsive Dehydration-Stress Protein That Confers Tolerance against Different Types of Abiotic Stresses in Transgenic Tobacco
Authors: Jha Rajesh Kumar , Mishra Avinash
Published: December 2021

Salicornia brachiata is an extreme halophyte that commonly grows on marsh conditions and is also considered a promising resource for drought and salt-responsive genes. To unveil a glimpse of stress endurance by plants, it is of the utmost importance to develop an understanding of stress tolerance mechanisms. ‘Early Responsive to Dehydration’ (ERD) genes are defined as a group of genes involved in stress tolerance and the development of plants. To increase this understanding, parallel to this expedited thought, a novel SbERD4 gene was cloned from S. brachiata, characterized, and functionally validated in the model plant tobacco. The study showed that SbERD4 is a plasma-membrane bound protein, and its overexpression in tobacco plants improved salinity and osmotic stress tolerance. Transgenic plants showed high relative water, chlorophylls, sugars, starch, polyphenols, proline, free amino acids, and low electrolyte leakage and H2O2 content compared to control plants (wild type and vector control) under different abiotic stress conditions. Furthermore, the transcript expression of antioxidant enzyme encoding genes NtCAT, NtSOD, NtGR, and NtAPX showed higher expression in transgenic compared to wild-type and vector controls under varying stress conditions. Overall, the overexpression of a novel early responsive to dehydration stress protein 4-encoding gene (SbERD4) enhanced the tolerance of the plant against multiple abiotic stresses. In conclusion, the overexpression of the SbERD4 gene mitigates plant physiology by enduring stress tolerance and might be considered as a promising key gene for engineering salinity and drought stress tolerance in crops.
Discovery of a Novel Leaf Rust (Puccinia recondita) Resistance Gene in Rye (Secale cereale L.) Using Association Genomics
Authors: Vendelbo Nikolaj Meisner , Mahmood Khalid , Sarup Pernille , Hovmøller Mogens S. , Justesen Annemarie Fejer , Kristensen Peter Skov , Orabi Jihad , Jahoor Ahmed
Published: December 2021

Leaf rust constitutes one of the most important foliar diseases in rye (Secale cereale L.). To discover new sources of resistance, we phenotyped 180 lines belonging to a less well-characterized Gülzow germplasm at three field trial locations in Denmark and Northern Germany in 2018 and 2019. We observed lines with high leaf rust resistance efficacy at all locations in both years. A genome-wide association study using 261,406 informative single-nucleotide polymorphisms revealed two genomic regions associated with resistance on chromosome arms 1RS and 7RS, respectively. The most resistance-associated marker on chromosome arm 1RS physically co-localized with molecular markers delimiting Pr3. In the reference genomes Lo7 and Weining, the genomic region associated with resistance on chromosome arm 7RS contained a large number of nucleotide-binding leucine-rich repeat (NLR) genes. Residing in close proximity to the most resistance-associated marker, we identified a cluster of NLRs exhibiting close protein sequence similarity with the wheat leaf rust Lr1 gene situated on chromosome arm 5DL in wheat, which is syntenic to chromosome arm 7RS in rye. Due to the close proximity to the most resistance-associated marker, our findings suggest that the considered leaf rust R gene, provisionally denoted Pr6, could be a Lr1 ortholog in rye.
Elucidating T Cell and B Cell Responses to SARS-CoV-2 in Humans: Gaining Insights into Protective Immunity and Immunopathology
Authors: Khanolkar Aaruni
Published: December 2021

The SARS-CoV-2 pandemic is an unprecedented epochal event on at least two fronts. Firstly, in terms of the rapid spread and the magnitude of the outbreak, and secondly, on account of the equally swift response of the scientific community that has galvanized itself into action and has successfully developed, tested and deployed highly effective and novel vaccines in record time to combat the virus. The sophistication and diversification of the scientific toolbox we now have at our disposal has enabled us to interrogate both the breadth and the depth of the immune response to a degree that is unparalleled in recent memory. In terms of our understanding of what is critical to contain the virus and mitigate the effects the pandemic, neutralizing antibodies to SARS-CoV-2 garner most of the attention, however, it is essential to recognize that it is the quality and the fitness of the virus-specific T cell and B cell response that lays the foundation and the backdrop for an effective neutralizing antibody response. In this report, we will review some of the key findings that have helped define and delineate some of the essential attributes of T and B cell responses in the setting of SARS-CoV-2 infection.
Pax-5 Protein Expression Is Regulated by Transcriptional 3′UTR Editing
Authors: Beauregard Annie-Pier , Hannay Brandon , Gharib Ehsan , Crapoulet Nicolas , Finn Nicholas , Guerrette Roxann , Ouellet Amélie , Robichaud Gilles A.
Published: December 2021

The Pax-5 gene encodes a transcription factor that is essential for B-cell commitment and maturation. However, Pax-5 deregulation is associated with various cancer lesions, notably hematopoietic cancers. Mechanistically, studies have characterized genetic alterations within the Pax-5 locus that result in either dominant oncogenic function or haploinsufficiency-inducing mutations leading to oncogenesis. Apart from these mutations, some examples of aberrant Pax-5 expression cannot be associated with genetic alterations. In the present study, we set out to elucidate potential alterations in post-transcriptional regulation of Pax-5 expression and establish that Pax-5 transcript editing represents an important means to aberrant expression. Upon the profiling of Pax-5 mRNA in leukemic cells, we found that the 3′end of the Pax-5 transcript is submitted to alternative polyadenylation (APA) and alternative splicing events. Using rapid amplification of cDNA ends (3′RACE) from polysomal fractions, we found that Pax-5 3′ untranslated region (UTR) shortening correlates with increased ribosomal occupancy for translation. These observations were also validated using reporter gene assays with truncated 3′UTR regions cloned downstream of a luciferase gene. We also showed that Pax-5 3′UTR editing has direct repercussions on regulatory elements such as miRNAs, which in turn impact Pax-5 protein expression. More importantly, we found that advanced staging of various hematopoietic cancer lesions relates to shorter Pax-5 3′UTRs. Altogether, our findings identify novel molecular mechanisms that account for aberrant expression and function of the Pax-5 oncogene in cancer cells. These findings also present new avenues for strategic intervention in Pax-5-mediated cancers.
Immunotherapy with Cell-Based Biological Drugs to Cure HIV-1 Infection
Authors: Siracusano Gabriel , Lopalco Lucia
Published: December 2021

Since its discovery 35 years ago, there have been no therapeutic interventions shown to enable full HIV-1 remission. Combined antiretroviral therapy (cART) has achieved the sustained control of HIV-1 replication, however, the life-long treatment does not eradicate long-lived latently infected reservoirs and can result in multiple side effects including the development of multidrug-resistant escape mutants. Antibody-based treatments have emerged as alternative approaches for a HIV-1 cure. Here, we will review clinical advances in coreceptor-targeting antibodies, with respect to anti-CCR5 antibodies in particular, which are currently being generated to target the early stages of infection. Among the Env-specific antibodies widely accepted as relevant in cure strategies, the potential role of those targeting CD4-induced (CD4i) epitopes of the CD4-binding site (CD4bs) in eliminating HIV-1 infected cells has gained increasing interest and will be presented. Together, with approaches targeting the HIV-1 replication cycle, we will discuss the strategies aimed at boosting and modulating specific HIV-1 immune responses, highlighting the harnessing of TLR agonists for their dual role as latency reverting agents (LRAs) and immune-modulatory compounds. The synergistic combinations of different approaches have shown promising results to ultimately enable a HIV-1 cure.
The Impact of Sickle Cell Disease on Academic Performance among Affected Students
Authors: Alhazmi Abdulaziz , Hakami Khalid , Abusageah Faisal , Jaawna Essa , Khawaji Meshal , Alhazmi Essam , Zogel Basem , Qahl Salman , Qumayri Ghadeer
Published: December 2021

Background: Sickle cell disease (SCD) is a genetic disease that is highly prevalent in Jazan Province, Saudi Arabia, and is mostly characterized by many complications such as vaso-occlusive crises (VOC), acute chest syndrome (ACS) and well-documented neurological complications. These complications may affect patients’ academic performance. Methods: An observational, cross-sectional, retrospective study was conducted in Jazan Province. General and demographic data were collected and questions about academic performance of students with SCD were answered. Both t-tests and chi-square tests, along with multiple logistic regression, were used for analysis. Results: 982 participants were selected for this study with a mean age of 23 years (SD: 7). Most of the participants were female (64%). The number of participants with SCD was 339 (36%), of whom 42% were male. Students with SCD recorded lower grade point averages (GPA) and more absences compared to healthy participants. Further, about 60% of students with SCD thought they performed better than 40% of the participants without SCD during the COVID-19 pandemic when most of the educational activities were online. Conclusion: As has been previously reported, this study suggested that the academic performance of students with SCD is negatively affected compared to healthy individuals, and this is mostly due to complications associated with the disease. Further, students with SCD acknowledged better performance with online education, an option that should be considered to improve their academic performance. National studies on a larger population are required by health and education officials, and supportive online educational programs are warranted to enhance the academic performance of this population.
Questionnaire-Derived Sleep Habits and Academic Achievement in First Year University Students
Authors: Driller Matthew , Suppiah Haresh , Gastin Paul B. , Beaven Christopher M.
Published: December 2021

This study aimed to determine the effect of sleep quantity and quality via the Pittsburgh Sleep Quality Index (PSQI) on students’ academic achievement in their first year of university study. In this cross-sectional study, 193 students (102 female, 91 male, mean ± SD; age = 19.3 ± 2.9 y) from an undergraduate Health degree in New Zealand completed the PSQI four weeks prior to the end of the semester in their first year of university study. Results from three core subjects in the first semester were averaged and correlations between the PSQI and academic success were evaluated using Spearman’s rho (ρ). The group were also trichotomized using a PSQI global score of ≤5 as the threshold for “good” sleepers (n = 62, 32%), a score of 5–8 for “moderate” sleepers (n = 63, 33%) and a score ≥8 to characterize “poor” sleepers (n = 68, 35%). Overall, students averaged 7 h 37 min of self-reported sleep duration with an average bedtime of 22:55 p.m. and wake time of 8:01 a.m. There was a significant, small inverse relationship between academic performance and bedtime (p = 0.03, ρ = −0.14), with those going to bed earlier having superior academic success. The trichotomized data demonstrated no significant differences in academic performance between students with poor, moderate and good sleep quality (p = 0.92). Later bedtimes were associated with lower academic performance in a group of first year university students. However, there were no other relationships observed between academic success and self-reported sleep quality or quantity as determined by the PSQI. Enhancing awareness of the impact of sleep timing on academic success should be prioritized and strategies to improve sleep hygiene should be promoted to university students.
Facile Route to Effective Antimicrobial Aluminum Oxide Layer Realized by Co-Deposition with Silver Nitrate
Authors: Calovi Massimo , Furlan Berenice , Coroneo Valentina , Massidda Orietta , Rossi Stefano
Published: December 2021

The emergence and spreading of the SARS-CoV-2 pandemic has forced the focus of attention on a significant issue: the realization of antimicrobial surfaces for public spaces, which do not require extensive use of disinfectants. Silver represents one of the most used elements in this context, thanks to its excellent biocidal performance. This work describes a simple method for the realization of anodized aluminum layers, whose antimicrobial features are ensured by the co-deposition with silver nitrate. The durability and the chemical resistance of the samples were evaluated by means of several accelerated degradation tests, such as the exposure in a salt spray chamber, the contact with synthetic sweat and the scrub test, highlighting the residual influence of silver in altering the protective behavior of the alumina layers. Furthermore, the ISO 22196:2011 standard was used as the reference protocol to set up an assay to measure the effective antibacterial activity of the alumina-Ag layers against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria, even at low concentrations of silver. Finally, the Ag-containing aluminum oxide layers exhibited excellent antimicrobial performances also following the chemical–physical degradation processes, ensuring good durability over time of the antimicrobial surfaces. Overall, this work introduces a simple route for the realization of anodized aluminum surfaces with excellent antibacterial properties.
Learn2Write: Augmented Reality and Machine Learning-Based Mobile App to Learn Writing
Authors: Opu Md. Nahidul Islam , Islam Md. Rakibul , Kabir Muhammad Ashad , Hossain Md. Sabir , Islam Mohammad Mainul
Published: December 2021

Augmented reality (AR) has been widely used in education, particularly for child education. This paper presents the design and implementation of a novel mobile app, Learn2Write, using machine learning techniques and augmented reality to teach alphabet writing. The app has two main features: (i) guided learning to teach users how to write the alphabet and (ii) on-screen and AR-based handwriting testing using machine learning. A learner needs to write on the mobile screen in on-screen testing, whereas AR-based testing allows one to evaluate writing on paper or a board in a real world environment. We implement a novel approach to use machine learning for AR-based testing to detect an alphabet written on a board or paper. It detects the handwritten alphabet using our developed machine learning model. After that, a 3D model of that alphabet appears on the screen with its pronunciation/sound. The key benefit of our approach is that it allows the learner to use a handwritten alphabet. As we have used marker-less augmented reality, it does not require a static image as a marker. The app was built with ARCore SDK for Unity. We further evaluated and quantified the performance of our app on multiple devices.
Activation of Blast Furnace Slag with CFB Fly Ash as a Supplementary Binder Material: Hydration Products and Effects of Sulfate Attack
Authors: Chen Guan-Yu , Huang Wei-Hsing
Published: December 2021

Circulating Fluidized Bed (CFB) combustion is a clean technology for burning, with advantages of adapting to a large variety of fuel, high combustion efficiency, lower NOx emissions, and stable operation. The residue collected from the ash-hoppers of the electrostatic precipitator of the CFB boiler is called CFB fly ash. This paper presents the hydration development on the application of CFB fly ash to activating blast furnace slag (BFS) as a supplementary binder material (SBM) for replacement of Portland cement in making concrete. Investigation of the hydration products of cement pastes prepared with combinations of BFS and CFB fly ash were conducted by means of X-ray diffraction, thermal gravimetric analysis, and scanning electronic microscope. Test results show that the main hydration products of the CFB fly ash-BFS blended pastes were found to be hydrated calcium silicate (C-S-H), ettringite, gypsum, and some portlandite. Considering that CFB fly ash produced from the combustion of high-sulfur coke has high SO3 contents, the volume stability of mortar made from CFB fly ash-activated BFS was subjected to tests in accordance with ASTM C1012 and ASTM C1038 for evaluating the internal and external sulfate attack, respectively. The results indicate that, due to the high sulfur (SO3) content of CFB fly ash, the expansion caused by internal sulfate attack (ISA) increased with increasing proportion of CFB fly ash in the mixture. In contrast, no significant expansion was observed in the external sulfate attack (ESA) test, regardless of the proportion of CFB fly ash in the mixture. In order for the CFB fly ash to serve as a supplementary binder material and to maintain adequate volume stability, the amount of CFB fly ash used for the activation of BFS is recommended to be no more than 20% of the SBM.
Specific Bile Microorganisms Caused by Intra-Abdominal Abscess on Pancreaticoduodenectomy Patients: A Retrospective Cohort Study
Authors: Lin Young-Jen , Ho Te-Wei , Wu Chien-Hui , Kuo Ting-Chun , Yang Ching-Yao , Wu Jin-Ming , Tien Yu-Wen
Published: December 2021

We retrospectively collected PD patients with a performance of bile culture between 2007 and 2019 in our institute. As to bile culture, we used a swab to do intraoperative bile cultures after transection of the CBD. IAA was defined as the documental bacteriological culture from either a turbid discharge from the intraoperatively placed drain in patients with a clinical picture consistent with infection or a postoperative fluid collection managed by CT-guided placement of drains. A total of 1244 PD patients were identified, and 539 (43.3%) subjects with bile sampling were included for analysis. Among these study patients, 433 (80.3%) developed bile contamination (positive bile culture). Bile contamination showed a significantly higher rate of IAA compared to non-bile contamination (17.1% vs. 0.9%, p < 0.001). The rate of co-shared microorganisms in both bile and abscess was 64.1%. On the multivariate analysis, age and specific bile microorganisms (Enterococcus species, Escherichia Coli, Streptococcus species, Citrobacter species, and Candida) are significantly associated with development of IAA. Specific bile microorganisms are the highly significant factors associated with development of IAA. The strategy to prevent bile spillage during PD should be considered to minimize afterward contamination of the abdominal cavity and prevent IAA.