bluuebunny/crossref_metadata_2025 huggingface dataset:
Bargaining-Based Profit Allocation Model for Fixed Return Investment Water-Saving Management Contract
Authors: Liu Shize , Wang Xiaosheng , Li Wei
Published: December 2022

Fixed Return Investment (FRI) is one of the main operating modes of a Water-Saving Management Contract (WSMC). Aiming at the critical profit allocation of FRI WSMC projects, a new profit allocation model based on bargaining theory is proposed. First, the net present value is adopted to determine the profit interval to be allocated. Second, the bargaining process is divided into two levels. The first-level bargaining process is between a water user and an alliance, which consists of a Water Service Company (WSCO) and a financial institution. The second-level bargaining process is between the WSCO and the financial institution. Given the imbalance caused by offering first, the number of bargaining stages and sunk cost are introduced, and the equilibrium offers of the two parties in different bargaining stages are determined by using backward induction and mathematical induction. According to the feature that the number of bargaining stages is an integer in practice, the deterrence discount factors are introduced to redistribute the remaining part, and sixteen situations of profit allocation among participants are given. Third, the model analysis shows that the profit allocation of participants is closely related to the minimum profit requirements, deterrence discount factors, the number of bargaining stages, and sunk cost. Finally, the effectiveness of the model and the influence of various factors on profit allocation are verified by an example. The example shows that in the early stage of FRI WSMC, the water users enjoy more profits.
Quantitative Design for the Battery Equalizing Charge/Discharge Controller of the Photovoltaic Energy Storage System
Authors: Chao Kuei-Hsiang , Huang Bing-Ze
Published: December 2022

The purpose of this paper is to develop a photovoltaic module array with an energy storage system that has equalizing charge/discharge controls for regulating the power supply to the grid. Firstly, the boost converter is used in conjunction with maximum power point tracking (MPPT) such that the photovoltaic module array (PVMA) can output maximum power at any time. The battery equalizing charge/discharge architecture is composed of multiple sets of bidirectional buck–boost soft-switching converters in serial connection in order to achieve zero-voltage switching (ZVS) and zero-current switching (ZCS) so that when the charge/discharge power is above 150 W, the converter efficiency can be increased by 3%. The voltage and current signals from the battery are captured and input into the digital signal processor (DSP) to establish an equalizing charge/discharge control rule. For the output voltage control of the bidirectional buck–boost soft-switching converter, the dynamic mode is derived by first using the step response at chosen operating point, then quantitatively designing the controller parameters for the converter, so that the output voltage response can meet the pre-defined performance specifications. Finally, actual test results prove that the equalizing charge/discharge time of the quantitative design controller is shortened by more than 10% when compared to the traditional proportional-integral (P-I) controller regardless of charging or discharging; this also proves that the design of the photovoltaic module array with an energy storage system (ESS) that has equalizing charge/discharge controls is valid.
Overview and Comparative Study of Energy Management Strategies for Residential PV Systems with Battery Storage
Authors: Wu Xiangqiang , Tang Zhongting , Stroe Daniel-Ioan , Kerekes Tamas
Published: December 2022

PV and battery systems have been widely deployed in residential applications due to increasing environmental concerns and fossil energy prices. Energy management strategies play an important role in reducing energy bills and maximize profits. This paper first reviews the state of energy management problems, including commonly used objectives, constraints, and solutions for PV and battery applications. Then, a comparative study of different energy management strategies is conducted based on a real applied product and household profile. Moreover, results are discussed, and suggestions are given for different scenarios. Finally, conclusions and insights into future directions are also provided.
An Advanced Big Data Quality Framework Based on Weighted Metrics
Authors: Elouataoui Widad , El Alaoui Imane , El Mendili Saida , Gahi Youssef
Published: December 2022

While big data benefits are numerous, the use of big data requires, however, addressing new challenges related to data processing, data security, and especially degradation of data quality. Despite the increased importance of data quality for big data, data quality measurement is actually limited to few metrics. Indeed, while more than 50 data quality dimensions have been defined in the literature, the number of measured dimensions is limited to 11 dimensions. Therefore, this paper aims to extend the measured dimensions by defining four new data quality metrics: Integrity, Accessibility, Ease of manipulation, and Security. Thus, we propose a comprehensive Big Data Quality Assessment Framework based on 12 metrics: Completeness, Timeliness, Volatility, Uniqueness, Conformity, Consistency, Ease of manipulation, Relevancy, Readability, Security, Accessibility, and Integrity. In addition, to ensure accurate data quality assessment, we apply data weights at three data unit levels: data fields, quality metrics, and quality aspects. Furthermore, we define and measure five quality aspects to provide a macro-view of data quality. Finally, an experiment is performed to implement the defined measures. The results show that the suggested methodology allows a more exhaustive and accurate big data quality assessment, with a more extensive methodology defining a weighted quality score based on 12 metrics and achieving a best quality model score of 9/10.
Shedding Light on the Dentition and Venom Delivery System of the Rear-Fanged Snake, Galvarinus chilensis chilensis (Serpentes: Dipsadidae: Tachymenini) from Chile
Authors: Herrera Yarela , Fuentes-Retamal Sebastián , Kemmerling Ulrike , Peichoto María Elisa , Ortiz Juan Carlos , Urra Félix A.
Published: December 2022

Although the rear-fanged snake Galvarinus chilensis chilensis (formerly named Tachymenis ch. chilensis) causes ophidian accidents with clinical importance in Chile, the anatomical and histological characterizations of the venom delivery system (venom gland and fang) of this species still remain unknown. This study describes the dentition and characteristics of fangs and their ontogenetic variations in G. ch. chilensis. Moreover, histological and histochemistry analyses of the venom glands of this species are presented. Using micro-computed tomography and scanning electron microscopy, the dentitions of neonates, juveniles, and adults were analyzed, and no ontogenetic variations in teeth length and number present in the dentary and maxilla were observed. Moreover, we found three types of basic teeth, with distributional patterns conserved in all ontogenetic categories. The fangs exhibited a groove from the base to the middle. At the end of the groove, prominent ridges are formed. The fang and groove lengths were significantly distinct between ontogenetic categories. No differences between females and males were observed. Histologically, we found that the venom gland is close to the fangs and has a seromucous composition. Our results describe, for the first time, the distributional pattern and characteristics of the dentition and venom delivery system of the poorly studied snake G. ch. chilensis.
Functional Resilience of Mutually Repressing Motifs Embedded in Larger Networks
Authors: Harlapur Pradyumna , Duddu Atchuta Srinivas , Hari Kishore , Kulkarni Prakash , Jolly Mohit Kumar
Published: December 2022

Elucidating the design principles of regulatory networks driving cellular decision-making has important implications for understanding cell differentiation and guiding the design of synthetic circuits. Mutually repressing feedback loops between ‘master regulators’ of cell fates can exhibit multistable dynamics enabling “single-positive” phenotypes: (high A, low B) and (low A, high B) for a toggle switch, and (high A, low B, low C), (low A, high B, low C) and (low A, low B, high C) for a toggle triad. However, the dynamics of these two motifs have been interrogated in isolation in silico, but in vitro and in vivo, they often operate while embedded in larger regulatory networks. Here, we embed these motifs in complex larger networks of varying sizes and connectivity to identify hallmarks under which these motifs maintain their canonical dynamical behavior. We show that an increased number of incoming edges onto a motif leads to a decay in their canonical stand-alone behaviors. We also show that this decay can be exacerbated by adding self-inhibition but not self-activation loops on the ‘master regulators’. These observations offer insights into the design principles of biological networks containing these motifs and can help devise optimal strategies for the integration of these motifs into larger synthetic networks.
Neural Signatures of Error Processing in Depressed Adolescents with Comorbid Non-Suicidal Self-Injury (NSSI)
Authors: Malejko Kathrin , Hafner Stefan , Brown Rebecca C. , Plener Paul L. , Grön Georg , Graf Heiko , Abler Birgit
Published: December 2022

Non-suicidal self-injury (NSSI), as a highly prevalent psychiatric symptom in adolescents and young adults, is defined as the deliberate destruction of body tissue without suicidal intent. Impulsivity and dysfunctional response inhibition have been suggested to play a central role in adolescents’ vulnerability to self-harm. To investigate the potentially distinct neurobiology of NSSI, we used a well-established Go/No Go task in which activation of the inferior frontal gyrus (IFG) and dorsal anterior cingulate cortex (dACC) is interpreted as a neural correlate of processing failed response inhibition. Task-based functional magnetic resonance imaging data were obtained from 14 adolescents with a diagnosis of major depression and a history of NSSI (MD-NSSI), 13 depressed adolescents without NSSI (MD-only), and 14 healthy controls (HC). In line with hypotheses of dysfunctional response inhibition, we observed increased rates of commission errors in MD-NSSI along with significantly reduced error-related activations of the dACC and IFG. Intact response inhibition, as reflected by low commission error rates not different from HC, was observed in MD-only, along with increased activation of the error-processing network. Our findings support the hypothesis of a distinct neurobiological signature of NSSI. Further research on biomarkers of NSSI could focus on behavioral and neural correlates of failed response inhibition.
Cutaneous and Developmental Effects of CARD14 Overexpression in Zebrafish
Authors: Baniel Avital , Ziv Limor , Ben-Moshe Zohar , Sarig Ofer , Mohamad Janan , Peled Alon , Rechavi Gideon , Gothilf Yoav , Sprecher Eli
Published: December 2022

Background: Gain-of-function mutations in CARD14 have recently been shown to be involved in the pathogenesis of psoriasis and pityriasis rubra pilaris (PRP). Those mutations were found to activate the NF-kB signaling pathway. Objective: Zebrafish is often used to model human diseases in general, and in skin disorders more particularly. In the present study, we aimed to examine the effect of CARD14 overexpression in zebrafish with the aim to validate this model for future translational applications. Methods: We used light microscopy, scanning electron microscopy, histological analysis and whole mount in situ hybridization as well as real-time PCR to ascertain the effect of CARD14 overexpression in the developing zebrafish. Results: Overexpression of human CARD14 had a marked morphological and developmental effect on the embryos. Light microscopy demonstrated a characteristic cutaneous pattern including a granular surface and a spiky pigment pattern. In situ hybridization revealed keratinocytes of uneven size and shape. Scanning electron microscopy showed aberrant production of actin microridges and a rugged keratinocyte cell surface, reminiscent of the human hyperkeratotic phenotype. Developmentally, overexpression of CARD14 had a variable effect on anterior-posterior axis symmetry. Similar to what has been observed in humans with psoriasis or PRP, NF-kB expression was higher in CARD14-overexpressing embryos compared to controls. Conclusions: Overexpression of CARD14 results in a distinct cutaneous pattern accompanied by hyperactivation of the NF-kB pathway, suggesting that the zebrafish represents a useful system to model CARD14-associated papulosquamous diseases.
Label-Free Myoglobin Biosensor Based on Pure and Copper-Doped Titanium Dioxide Nanomaterials
Authors: Umar Ahmad , Haque Mazharul , Ansari Shafeeque G. , Seo Hyung-Kee , Ibrahim Ahmed A. , Alhamami Mohsen A. M. , Algadi Hassan , Ansari Zubaida A.
Published: December 2022

In this study, using pure and copper-doped titanium dioxide (Cu-TiO2) nanostructures as the base matrix, enzyme-less label free myoglobin detection to identify acute myocardial infarction was performed and presented. The Cu-TiO2 nanomaterials were prepared using facile sol–gel method. In order to comprehend the morphologies, compositions, structural, optical, and electrochemical characteristics, the pure and Cu-TiO2 nanomaterials were investigated by several techniques which clearly revealed good crystallinity and high purity. To fabricate the enzyme-less label free biosensor, thick films of synthesized nanomaterials were applied to the surface of a pre-fabricated gold screen-printed electrode (Au-SPE), which serves as a working electrode to construct the myoglobin (Mb) biosensors. The interference study of the fabricated biosensor was also carried out with human serum albumin (HSA) and cytochrome c (cyt-c). Interestingly, the Cu-doped TiO2 nanomaterial-based Mb biosensor displayed a higher sensitivity of 61.51 µAcm−2/nM and a lower detection limit of 14 pM with a response time of less than 10 ms.
Effect of Upper Limb Motor Rehabilitation on Cognition in Parkinson’s Disease: An Observational Study
Authors: Varalta Valentina , Evangelista Elisa , Righetti Anna , Morone Giovanni , Tamburin Stefano , Picelli Alessandro , Fonte Cristina , Tinazzi Michele , Di Vico Ilaria Antonella , Waldner Andreas , Filippetti Mirko , Smania Nicola
Published: December 2022

Parkinson’s disease is characterized by motor and cognitive deficits that usually have an impact on quality of life and independence. To reduce impairment, various rehabilitation programs have been proposed, but their effects on both cognitive and motor aspects have not been systematically investigated. Furthermore, most intervention is focused on lower limb treatment rather than upper limbs. In the present study, we investigated the effect of 3-week upper limb vibratory stimulation training on cognitive functioning in 20 individuals with Parkinson’s disease. We analyzed cognitive (Montreal Cognitive Assessment, Trial Making Test, Digit Symbol, Digit Span Forward and Backward and Alertness) and motor performance (Unified Parkinson’s Disease Rating Scale—part III; Disability of the Arm, Shoulder and Hand Questionnaire) before treatment, at the end of treatment and one month post treatment. After rehabilitation, a statistically significant improvement was observed in terms of global cognitive status, attention, global motor functioning and disability. The results suggest an impact of upper limb motor rehabilitation on cognition in Parkinson’s disease. Future studies on neuromotor interventions should investigate their effects on cognitive functioning to improve understanding of cognitive motor interaction in Parkinson’s disease.
Win and Loss Responses in the Monetary Incentive Delay Task Mediate the Link between Depression and Problem Drinking
Authors: Chen Yu , Dhingra Isha , Le Thang M. , Zhornitsky Simon , Zhang Sheng , Li Chiang-Shan R.
Published: December 2022

Depression and alcohol misuse, frequently comorbid, are associated with altered reward processing. However, no study has examined whether and how the neural markers of reward processing are shared between depression and alcohol misuse. We studied 43 otherwise-healthy drinking adults in a monetary incentive delay task (MIDT) during fMRI. All participants were evaluated with the Alcohol Use Disorders Identification Test (AUDIT) and Beck’s Depression Inventory (BDI-II) to assess the severity of drinking and depression. We performed whole brain regressions against each AUDIT and BDI-II score to investigate the neural correlates and evaluated the findings at a corrected threshold. We performed mediation analyses to examine the inter-relationships between win/loss responses, alcohol misuse, and depression. AUDIT and BDI-II scores were positively correlated across subjects. Alcohol misuse and depression shared win-related activations in frontoparietal regions and parahippocampal gyri (PHG), and right superior temporal gyri (STG), as well as loss-related activations in the right PHG and STG, and midline cerebellum. These regional activities (β’s) completely mediated the correlations between BDI-II and AUDIT scores. The findings suggest shared neural correlates interlinking depression and problem drinking both during win and loss processing and provide evidence for co-morbid etiological processes of depressive and alcohol use disorders.
Complexity, Performance, and Search Efficiency: An Eye-Tracking Study on Assembly-Based Tasks among Construction Workers (Pipefitters)
Authors: Al-Haddad Sara , Sears Matthew , Alruwaythi Omar , Goodrum Paul M.
Published: December 2022

Past studies have used eye-tracking glasses to analyze people’s perception of visual stimuli, usually regarding wayfinding, safety, or visual appeal. Some industries, such as the automotive industry, studied the effects of visual stimuli on task completion. However, the architecture and construction industries have mainly conducted eye-tracking experiments with surveys or search tasks instead of performing a task. This paper uses eye-tracking glasses to analyze people’s perception of visual stimuli while completing tangible tasks that simulate real-world applications. This research studies how people look at visual stimuli that influence their ability to interpret drawings with varying degrees of complexity, assess task completion performance, and inspect how people search for information. Twenty pipefitters wore eye-tracking glasses to record their eye movement patterns while completing a model pipe spool assembly. The eye-tracking glasses and Visual Eyes software measured visit metrics, fixations, fixation durations, convex hull coverage, assembly time, rework, and errors. Unlike previous studies, convex hull areas are calculated and used to measure search efficiency. This research found that people interacted more frequently with more complex visual stimuli but did not necessarily require more time to complete a task. People with lower search efficiency visited the drawings more frequently than people with higher search efficiency. People with higher search efficiency made fewer mistakes, redid less work, and completed tasks quicker than those with lower search efficiency. Search efficiency was found to be a good predictor of task performance.
Geo-Environmental Hazard Assessment of Archaeological Sites and Archaeological Domes—Fatimid Tombs—Aswan, Egypt
Authors: Khalil Mona M. E. , Khodary Safia M. , Youssef Youssef M. , Alsubaie Mohammad S. , Sallam Ahmed
Published: December 2022

The Fatimid state was established in Egypt in 969 and lasted until the end of the dynasty in 1171. During the Fatimid rule in Egypt, a large set of monuments were erected. A significant portion of these monuments were shrines dedicated to the descendants of the Prophet Muhammed, especially in Aswan. Groundwater rising, at present, has introduced severe deterioration to the ancient earthen mud-brick architecture of the Fatimid tombs in Aswan city (Egypt). However, monitoring the influence of anthropogenic and environmental aspects on the deterioration issues in Fatimid tombs has not yet been considered. To this end, the scope of this pilot study is to investigate the structural stability and weathering vulnerability of the building materials of mud-brick structures in the Fatimid Cemetery before restoration labor. This was achieved using an integration of remote sensing (Landsat 8 and SRTM-DEM) and hydrogeological datasets in the Geographic Information System (GIS), along with a physicochemical and mineralogical analysis of various materials (the bearing soil, wall plasters, and Muqarnas) from the affected cemeteries. The morphological and mineralogical compositions of the collected samples were analytically examined by using X-ray diffraction (XRD) and scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM/EDX) and CT scan. Moreover, geotechnical studies were conducted for the perched soil water and subsoil, including the analysis of the physiochemical composition and heavy metals using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The results of multitemporal analysis of land use/land cover (LULC) changes displayed the growth and appearance of wetlands near the Fatimid tombs area over the last decades, boosting the geo-environmental risks from soil water rising. Furthermore, the detailed analytical investigations of building materials and soil foundations showed that this unique and substantial ancient Islamic archaeological site of Egypt shows weak geotechnical properties, and it is highly sensitive to natural and anthropogenic stressors. This innovative methodology can produce novel recommendations and results to the Ministry of Antiquities in Egypt and the Heritage Commission in Saudi Arabia for the adequate restoration of monuments.
Effects of Different Frequency Sensitivity Models of a Viscoelastic Damper on Wind-Induced Response of High-Rise Buildings
Authors: Sato Daiki , Chang Ting-Wei , Chen Yinli
Published: December 2022

The fractional derivative (FD) model is one kind of numerical model of viscoelastic (VE) damper, which can describe the behavior of the frequency sensitivity of VE damper well with some empirical parameters. However, the FD model is difficult to apply to practice design because of its complex calculation. Compared with the FD model, the integer derivative (ID) models are widely used as the VE damper equipped in the high-rise building. However, ID models lack consideration of frequency sensitivity, which significantly affects their accuracy. To consider frequency sensitivity in the ID model, this study attempted to use the 4-element and 6-element models of ID models to approximate the FD model, easily describing the VE characteristic of the damper. The wind forces of 500-year-return periods were employed to analyze the influence of the frequency sensitivity of the VE damper on wind-induced responses and energy dissipation. The results of this study showed that the 4-element and 6-element models not only matched frequency sensitivities well to the FD model in the low-frequency region of wind excitation but also had good agreements with the FD model in wind-induced responses and energy dissipation. Based on the findings in this study, the 4-element and 6-element models were recommended as numerical models for the wind-resistant design of high-rise buildings with VE dampers. It helps improve the wind-induced behavior simulation of VE dampers considering their frequency sensitivity in high accuracy without massive experimental cost.
Lightweight Composite Partitions with High Sound Insulation in Hotel Interior Spaces: Design and Application
Authors: Qu Ting , Wang Bo , Min Hequn
Published: December 2022

Sound insulation performance of partitions is one of the key factors contributing to the comfort of the hotel interior spaces. Based on the theory of constrained layer damping, this study proposed the light-weight composite partition structure with high sound insulation, which was composed of gypsum boards of different thicknesses and an isobutylene isoprene rubber board. The normal incidence sound transmission loss of the structure was evaluated through finite element simulations as well as experiments, which were conducted in a standing wave tube. The results show that the simulation and experimental results of two kinds of lightweight high sound insulation multi-layer composite partition walls are closely aligned; the surface density of the optimized partition wall was less than 42 kg/m2, although the normal incidence STL exceeded 51.8 dB at 200 Hz and at 1/3 octave of 1000 Hz with the maximum value of 58.5 dB. The lightweight composite partition wall with high sound insulation has a huge application potential in enhancing the sound environment quality of hotels.
N6-Isopentenyladenosine Impairs Mitochondrial Metabolism through Inhibition of EGFR Translocation on Mitochondria in Glioblastoma Cells
Authors: Pagano Cristina , Coppola Laura , Navarra Giovanna , Avilia Giorgio , Bruzzaniti Sara , Piemonte Erica , Galgani Mario , Della Monica Rosa , Chiariotti Lorenzo , Cuomo Mariella , Buonaiuto Michela , Torelli Giovanni , Caiazzo Pasquale , Laezza Chiara , Bifulco Maurizio
Published: December 2022

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor and is poorly susceptible to cytotoxic therapies. Amplification of the epidermal growth factor receptor (EGFR) and deletion of exons 2 to 7, which generates EGFR variant III (vIII), are the most common molecular alterations of GBMs that contribute to the aggressiveness of the disease. Recently, it has been shown that EGFR/EGFRvIII-targeted inhibitors enhance mitochondrial translocation by causing mitochondrial accumulation of these receptors, promoting the tumor drug resistance; moreover, they negatively modulate intrinsic mitochondria-mediated apoptosis by sequestering PUMA, leading to impaired apoptotic response in GBM cells. N6-isopentenyladenosine (i6A or iPA), a cytokinin consisting of an adenosine linked to an isopentenyl group deriving from the mevalonate pathway, has antiproliferative effects on numerous tumor cells, including GBM cells, by inducing cell death in vitro and in vivo. Here, we observed that iPA inhibits the mitochondrial respiration in GBM cells by preventing the translocation of EGFR/EGFRvIII to the mitochondria and allowing PUMA to interact with them by promoting changes in mitochondrial activity, thus playing a critical role in cell death. Our findings clearly demonstrate that iPA interferes with mitochondrial bioenergetic capacity, providing a rationale for an effective strategy for treating GBM.
Particle Therapy in Adult Patients with Pelvic Ewing Sarcoma—Tumor and Treatment Characteristics and Early Clinical Outcomes
Authors: Schmid Maximilian P. , Harrabi Semi , Herfarth Klaus , Bruland Øyvind S. , Welzel Thomas , Haberer Thomas , Ellerbrock Malte , Debus Jürgen , Uhl Matthias , Seidensaal Katharina
Published: December 2022

Purpose: To report dosimetric characteristics and early clinical outcomes in patients with pelvic Ewing sarcoma undergoing particle therapy. Methods: Patients ≥ 18 years old with pelvic Ewing sarcoma treated in adjuvant or definitive settings were considered for this retrospective analysis. Proton therapy was carried out with 45–60 Gy (RBE) (1.5–2 Gy (RBE) per fraction) and carbon ion therapy for recurrent disease with 51 Gy (RBE) (3 Gy (RBE) per fraction). Local control (LC), disease control (DC) and overall survival (OS) were calculated using the Kaplan–Meier method. Results: For our sample, 21 patients were available, 18 of whom were treated for primary, 3 for locally recurrent and 16 for inoperable disease. The median CTV and PTV were 1215 cm3 and 1630 cm3. Median Dmean values for the PTV, bladder and rectum and median V40 Gy for the bowel for patients undergoing proton therapy were 56 Gy (RBE), 0.6 Gy (RBE), 9 Gy (RBE) and 15 cm3, respectively. At the end of particle therapy, G 1–2 skin reactions (n = 16/21) and fatigue (n = 9/21) were the main reported symptoms. After a median follow-up of 21 months, the 2-year LC, DC and OS were 76%, 56% and 86%, respectively. Conclusions: Particle therapy in adult pelvic Ewing sarcoma is feasible and provides excellent dosimetric results. First clinical outcomes are promising; however, further long-term follow-up is needed.
ARDS after Pneumonectomy: How to Prevent It? Development of a Nomogram to Predict the Risk of ARDS after Pneumonectomy for Lung Cancer
Authors: Mazzella Antonio , Mohamed Shehab , Maisonneuve Patrick , Borri Alessandro , Casiraghi Monica , Bertolaccini Luca , Petrella Francesco , Lo Iacono Giorgio , Spaggiari Lorenzo
Published: December 2022

(1) Background: The cause of ARDS after pneumonectomy is still unclear, and the study of risk factors is a subject of debate. (2) Methods: We reviewed a large panel of pre-, peri- and postoperative data of 211 patients who underwent pneumonectomy during the period 2014–2021. Univariable and multivariable logistic regression was used to quantify the association between preoperative parameters and the risk of developing ARDS, in addition to odds ratios and their respective 95% confidence intervals. A backward stepwise selection approach was used to limit the number of variables in the final multivariable model to significant independent predictors of ARDS. A nomogram was constructed based on the results of the final multivariable model, making it possible to estimate the probability of developing ARDS. Statistical significance was defined by a two-tailed p-value < 0.05. (3) Results: Out of 211 patients (13.3%), 28 developed ARDS. In the univariate analysis, increasing age, Charlson Comorbidity Index and ASA scores, DLCO < 75% predicted, preoperative C-reactive protein (CRP), lung perfusion and duration of surgery were associated with ARDS; a significant increase in ARDS was also observed with decreasing VO2max level. Multivariable analysis confirmed the role of ASA score, DLCO < 75% predicted, preoperative C-reactive protein and lung perfusion. Using the nomogram, we classified patients into four classes with rates of ARDS ranking from 2.0% to 34.0%. (4) Conclusions: Classification in four classes of growing risk allows a correct preoperative stratification of these patients in order to quantify the postoperative risk of ARDS and facilitate their global management.
GD2 Expression in Medulloblastoma and Neuroblastoma for Personalized Immunotherapy: A Matter of Subtype
Authors: Paret Claudia , Ustjanzew Arsenij , Ersali Sara , Seidmann Larissa , Jennemann Richard , Ziegler Nicole , Malki Khalifa El , Russo Alexandra , Wingerter Arthur , Ortmüller Franziska , Bornas Angelina , Wehling Pia Charlotte , Lepădatu Adina , Ottenhausen Malte , Roth Wilfried , Sommer Clemens , Fliss Barbara , Frauenknecht Katrin B. M. , Sandhoff Roger , Faber Jörg
Published: December 2022

Neuroblastoma (NBL) and medulloblastoma (MB) are aggressive pediatric cancers which can benefit from therapies targeting gangliosides. Therefore, we compared the ganglioside profile of 9 MB and 14 NBL samples by thin layer chromatography and mass spectrometry. NBL had the highest expression of GD2 (median 0.54 nmol GD2/mg protein), and also expressed complex gangliosides. GD2-low samples expressed GD1a and were more differentiated. MB mainly expressed GD2 (median 0.032 nmol GD2/mg protein) or GM3. Four sonic hedgehog-activated (SHH) as well as one group 4 and one group 3 MBs were GD2-positive. Two group 3 MB samples were GD2-negative but GM3-positive. N-glycolyl neuraminic acid-containing GM3 was neither detected in NBL nor MB by mass spectrometry. Furthermore, a GD2-phenotype predicting two-gene signature (ST8SIA1 and B4GALNT1) was applied to RNA-Seq datasets, including 86 MBs and validated by qRT-PCR. The signature values were decreased in group 3 and wingless-activated (WNT) compared to SHH and group 4 MBs. These results suggest that while NBL is GD2-positive, only some MB patients can benefit from a GD2-directed therapy. The expression of genes involved in the ganglioside synthesis may allow the identification of GD2-positive MBs. Finally, the ganglioside profile may reflect the differentiation status in NBL and could help to define MB subtypes.
Prognostic Impact and Clinical Implications of Unfavorable Upgrading in Low-Risk Prostate Cancer after Robot-Assisted Radical Prostatectomy: Results of a Single Tertiary Referral Center
Authors: Porcaro Antonio Benito , Panunzio Andrea , Bianchi Alberto , Sebben Marco , Gallina Sebastian , De Michele Mario , Orlando Rossella , Serafin Emanuele , Mazzucato Giovanni , Vidiri Stefano , D’Aietti Damiano , Princiotta Alessandro , Montanaro Francesca , Marafioti Patuzzo Giulia , De Marco Vincenzo , Brunelli Matteo , Pagliarulo Vincenzo , Cerruto Maria Angela , Tafuri Alessandro , Antonelli Alessandro
Published: December 2022

Objective: to evaluate predictors and the prognostic impact of favorable vs. unfavorable tumor upgrading among low-risk prostate cancer (LR PCa) patients treated with robot-assisted radical prostatectomy (RARP). Methods: From January 2013 to October 2020, LR PCa patients treated with RARP at our institution were identified. Unfavorable tumor upgrading was defined as the presence of an International Society of Urological Pathology (ISUP) grade group at final pathology > 2. Disease relapse was coded as biochemical recurrence and/or local recurrence and/or presence of distant metastases. Regression analyses tested the association between clinical and pathological features and the risk of unfavorable tumor upgrading and disease relapse. Results: Of the 237 total LR PCa patients, 60 (25.3%) harbored unfavorable tumor upgrading. Disease relapse occurred in 20 (8.4%) patients. Unfavorable upgrading represented an independent predictor of disease relapse, even after adjustment for other clinical and pathological variables. Conversely, favorable tumor upgrading did not show any statistically significant association with PCa relapse. Unfavorable tumor upgrading was associated with tumors being larger (OR: 1.03; p = 0.031), tumors extending beyond the gland (OR: 8.54, p < 0.001), age (OR: 1.07, p = 0.009), and PSA density (PSAD) ≥ 0.15 ng/mL/cc (OR: 1.07, p = 0.009). Conclusions: LR PCa patients with unfavorable upgrading at final pathology were more likely to be older, to have PSAD ≥ 0.15 ng/mL/cc, and to experience disease relapse. Unfavorable tumor upgrading is an issue to consider when counseling these patients to avoid delayed treatments, which may impair cancer-specific survival.
Deploying Indocyanine Green Fluorescence-Guided Navigation System in Precise Laparoscopic Resection of Pediatric Hepatoblastoma
Authors: Qiu Ronglin , Wu Yaohao , Su Jianhang , Chen Luping , Liao Minyi , Zhao Zhuangjie , Lu Zijie , Xiong Xiangang , Jin Shikai , Deng Xiaogeng
Published: December 2022

Background: Hepatoblastoma (HB) is the most common form of liver cancer in children. To date, complete tumor resection is still the gold standard for treating HB. Indocyanine green (ICG) has been identified as a sensitive adjunct that is highly effective in the identification and surgical management of local and metastatic HB. It has thus becomes an increasingly popular choice among surgeons in HB resection surgeries that are fluorescence-guided. However, laparotomy remains the preferred choice in most cases since the applications and limitations of fluorescence-guided laparoscopic surgery in treating HB remain unclear. In this study, the characteristics and outcomes of laparoscopic HB resections that were guided by intraoperative ICG fluorescent imaging were investigated. Methods: Seven HB patients underwent ICG-guided laparoscopic HB resection surgery from August 2019 to December 2021. ICG was intravenously administered to the patients at a dosage of 0.5 mg/kg 48 h prior to the scheduled operation. During operation, tumor localization and resection boundary were guided by fluorescence visualization. The data on surgical and clinical features were collected retrospectively. Results: The resection area and tumor boundary could be clearly viewed in real-time under the ICG fluorescence imaging navigation system during operation, except for one patient who had received interventional chemoembolization before surgery. The image produced by laparoscopic fluorescence navigation was clear since it was not affected by ambient light. All tumors were completely resected as confirmed by negative margins for HB during postoperative pathological examination. No residual or recurrence were also found through computed tomography during follow-up visits from 9 to 37 months. Conclusions: ICG fluorescence-guided laparoscopic surgery is safe and effective in treating HB due to its ability to provide clear information on tumor localization and delineate tumor margins in real-time.
High-Dose Intermittent Treatment with the Multikinase Inhibitor Sunitinib Leads to High Intra-Tumor Drug Exposure in Patients with Advanced Solid Tumors
Authors: Gerritse Sophie , Labots Mariette , ter Heine Rob , Dekker Henk , Poel Dennis , Tauriello Daniele , Nagtegaal Iris , Van Den Hombergh Erik , Van Erp Nielka , Verheul Henk
Published: December 2022

Patients with advanced cancer refractory to standard treatment were treated with sunitinib at a dose of 300 mg once every week (Q1W) or 700 mg once every two weeks (Q2W). Tumor, skin and plasma concentrations were measured and immunohistochemical staining for tumor cell proliferation (TCP), microvessel density (MVD) and T-cell infiltration was performed on tumor biopsies before and after 17 days of treatment. Oral administration of 300 mg sunitinib Q1W or 700 mg Q2W resulted in 19-fold (range 5–35×) and 37-fold higher (range 10–88×) tumor drug concentrations compared to parallel maximum plasma drug concentrations, respectively. Patients with higher tumor sunitinib concentrations had favorable progression-free and overall survival than those with lower concentrations (p = 0.046 and 0.024, respectively). In addition, immunohistochemistry of tumor biopsies revealed an induction of T-cell infiltration upon treatment. These findings provide pharmacological and biological insights in the clinical benefit from high-dose intermittent sunitinib treatment. It emphasizes the potential benefit from reaching higher tumor drug concentrations and the value of measuring TKI tumor- over plasma-concentrations. The finding that reaching higher tumor drug concentrations provides most clinical benefit in patients with treatment refractory malignancies indicates that the inhibitory potency of sunitinib may be enforced by a high-dose intermittent treatment schedule. These results provide proof of concept for testing other clinically available multitargeted tyrosine kinase inhibitors in a high-dose intermittent treatment schedule.
Phosphorylation-Mediated Activation of β-Catenin-TCF4-CEGRs/ALCDs Pathway Is an Essential Event in Development of Aggressive Hepatoblastoma
Authors: Gulati Ruhi , Hanlon Margaret A. , Lutz Maggie , Quitmeyer Tyler , Geller James , Tiao Gregory , Timchenko Lubov , Timchenko Nikolai
Published: December 2022

Background and Aims: Hepatoblastoma (HBL), a deadly malignancy in children, is the most common type of pediatric liver cancer. We recently demonstrated that β-catenin, phosphorylated at S675 (ph-S675-β-catenin), causes pathological alterations in fibrolamellar hepatocellular carcinoma (FLC), by activating oncogenes and fibrotic genes via human genomic regions, known as cancer-enhancing genomic regions or aggressive liver cancer domains (CEGRs/ALCDs). The aim of this study was to determine the role of the ph-S675-β-catenin-TCF4-CEGRs/ALCDs pathway in HBL. Methods: The ph-S675-β-catenin-TCF4-CEGRs/ALCDs pathway was examined in a large cohort of HBL specimens, in HBL cell lines HepG2 and Huh6, and in patient-derived xenografts (PDXs). Results: β-catenin is phosphorylated at S675 in a large portion of tested HBL patients. In these patients, ph-S675-β-catenin forms complexes with TCF4 and opens CEGRs/ALCDs-dependent oncogenes for transcription, leading to a massive overexpression of the oncogenes. The inhibition of the β-catenin-TCF4-CEGRs/ALCDs axis inhibits the proliferation of cancer cells and tumor growth in HBL cell lines and HBL-PDXs. The ph-S675-β-catenin is abundant in mitotic cells. We found that markers of HBL Glypican 3 (GPC3) and Alpha Fetoprotein (AFP) are increased in HBL patients by β-catenin-TCF4-p300 complexes. Conclusions: The phosphorylation-mediated activation of the β-catenin-TCF4-p300-CEGRs/ALCDs pathway increases oncogene expression in patients with aggressive liver cancer and promotes the development of hepatoblastoma.
Divulging a Pleiotropic Role of Succinate Receptor SUCNR1 in Renal Cell Carcinoma Microenvironment
Authors: Najm Rania , Hachim Mahmood Yaseen , Kandasamy Richard K.
Published: December 2022

The succinate receptor, SUCNR1, has been attributed to tumor progression, metastasis, and immune response modulation upon its activation via the oncometabolite succinate. Nonetheless, little is known about the prognostic relevance of SUCNR1 and its association with tumor immune infiltrates and microbiota in renal cell carcinoma (RCC). Herein, publicly available platforms including Human Protein Atlas, cBioPortal, TIMER2.0, and TISIDB were utilized to depict a divergent implication of SUCNR1 in the immune microenvironment of clear cell RCC (KIRC) and papillary RCC (KIRP); the two major subtypes of RCC. Our results showed that the SUCNR1 expression level was augmented in RCC compared to other solid cancers, yet with opposite survival rate predictions in RCC subtypes. Consequently, a higher expression level of SUCNR1 was associated with a good disease-specific survival rate (p = 5.797 × 10−5) in KIRC patients albeit a poor prognostic prediction in KIRP patients (p = 1.9282 × 10−3). Intriguingly, SUCNR1 was mainly correlated to immunomodulators and diverse immune infiltrates in KIRP. Additionally, the SUCNR1 was mostly associated with a repertoire of microbes including beneficial bacteria that likely influenced a better disease-specific survival rate in KIRC. Our findings illustrate a significant novel subtype-specific role of SUCNR1 in RCC which potentially modulates tumor immune infiltration and microbiome signature, hence altering the prognosis of cancer patients.
NEO212, a Perillyl Alcohol-Temozolomide Conjugate, Triggers Macrophage Differentiation of Acute Myeloid Leukemia Cells and Blocks Their Tumorigenicity
Authors: Chen Thomas C. , Minea Radu O. , Swenson Steve , Yang Zhuoyue , Thein Thu Zan , Schönthal Axel H.
Published: December 2022

Many patients with acute myeloid leukemia (AML) are still dying from this disease. In the past, the alkylating agent temozolomide (TMZ) has been investigated for AML and found to be partially effective; however, the presence of O6-methylguanine DNA methyltransferase (MGMT; a DNA repair enzyme) in tumor cells confers profound treatment resistance against TMZ. We are developing a novel anticancer compound, called NEO212, where TMZ was covalently conjugated to perillyl alcohol (a naturally occurring monoterpene). NEO212 has revealed robust therapeutic activity in a variety of preclinical cancer models, including AML. In the current study, we investigated its impact on a panel of human AML cell lines and found that it exerted cytotoxic potency even against MGMT-positive cells that were highly resistant to TMZ. Furthermore, NEO212 strongly stimulated the expression of a large number of macrophage-associated marker genes, including CD11b/ITGAM. This latter effect could not be mimicked when cells were treated with TMZ or an equimolar mix of individual agents, TMZ plus perillyl alcohol. The superior cytotoxic impact of NEO212 appeared to involve down-regulation of MGMT protein levels. In a mouse model implanted with TMZ-resistant, MGMT-positive AML cells, two 5-day cycles of 25 mg/kg NEO212 achieved an apparent cure, as mice survived >300 days without any signs of disease. In parallel toxicity studies with rats, a 5-day cycle of 200 mg/kg NEO212 was well tolerated by these animals, whereas animals that were given 200 mg/kg TMZ all died due to severe leukopenia. Together, our results show that NEO212 exerts pleiotropic effects on AML cells that include differentiation, proliferation arrest, and eventual cell death. In vivo, NEO212 was well tolerated even at dosages that far exceed the therapeutic need, indicating a large therapeutic window. These results present NEO212 as an agent that should be considered for development as a therapeutic agent for AML.
Heterogeneous Catalysis as an Efficient Tool for Selective Hydrogenation of Oximes to Amines and Hydroxylamines
Authors: Redina Elena A. , Ivanova Inna I. , Arkhipova Natalia Y. , Kustov Leonid M.
Published: December 2022

The synthesis of many biologically active compounds is not complete without transforming the carbonyl group into an amino group, carried out by the reaction of nucleophilic substitution with hydroxylamine at the carbonyl carbon atom and further reduction of the C–N and N–O bonds. This method eliminates nitrating agents that exhibit oxidizing properties and may cause undesirable effects on other structural fragments of complex molecules. Selective hydrogenation of oximes over heterogeneous catalysts is still one of the most useful and challenging reactions in synthetic organic chemistry to obtain amines and hydroxylamines since the 1920s when the Adam’s catalyst was first used for this reaction. In this review, we focused on the application of heterogeneous catalysts for the hydrogenation of oximes in relation to the methods applied for pharmaceutical synthesis.
Comparative Study on the Scratch and Wear Resistance of Diamond-like Carbon (DLC) Coatings Deposited on X42Cr13 Steel of Different Surface Conditions
Authors: Siddiqui Shiraz Ahmed , Maros Maria Berkes
Published: December 2022

Tribological investigations are of great importance, especially in the case of novel combinations of materials used for the tribosystem. In the current research, multilayer diamond-like carbon coating deposited by plasma enhanced chemical vapour deposition on an X42Cr13 plastic mould tool steel is studied with two different surface conditions of the substrate. On the one hand, it is secondary hardened; on the other hand, it is additively plasma nitrided preceding the diamond-like carbon coating. This latter combined treatment, called duplex treatment, has an increasingly wide range of applications today. However, its effectiveness largely depends on applying the appropriate nitriding technology. The tribological behaviour was characterised by an instrumented scratch test and a reciprocating ball-on-plate wear test. The results demonstrate better scratch resistance for the duplex-treated samples, while they show weaker performance in the applied wear type of loading. The current comparative study reveals the reason for the unexpected behaviour and highlights some critical aspects of the heat treatment procedure. The architecture of the tested multilayer DLC coating is unique, and no tribological results have yet been published on tribosystems combined with an X42Cr13 steel substrate. The presented results may particularly interest tribologists and the materials research community.
Synthesis and Structural Analysis of a Nitrobenzofurazan Derivative of Dibenzo-18-Crown-6 Ether
Authors: Bujor Alexandru , Tecuceanu Victorita , Hanganu Anamaria , Ionita Petre
Published: December 2022

Nitrobenzofurazan derivatives are well known for their fluorescence, whilst crown ethers are known for their complexing capacity toward cationic species. In this study, we present the synthesis and structural characterization of a new derivative containing both nitrobenzofurazan moieties and a crown ether core. The new compound was obtained from dibenzo-18-crown-6 ether, which was first nitrated, reduced to the corresponding amine, and subsequently derivatized with NBD. Structural analyses performed by IR, NMR, UV–Vis, and MS confirmed its structure and physico-chemical behavior toward the complexation of alkaline cations.