bluuebunny/crossref_metadata_2025 huggingface dataset:
Androgen-Induced MIG6 Regulates Phosphorylation of Retinoblastoma Protein and AKT to Counteract Non-Genomic AR Signaling in Prostate Cancer Cells
Authors: Schomann Tim , Mirzakhani Kimia , Kallenbach Julia , Lu Jing , Rasa Seyed Mohammad Mahdi , Neri Francesco , Baniahmad Aria
Published: July 2022

The bipolar androgen therapy (BAT) includes the treatment of prostate cancer (PCa) patients with supraphysiological androgen level (SAL). Interestingly, SAL induces cell senescence in PCa cell lines as well as ex vivo in tumor samples of patients. The SAL-mediated cell senescence was shown to be androgen receptor (AR)-dependent and mediated in part by non-genomic AKT signaling. RNA-seq analyses compared with and without SAL treatment as well as by AKT inhibition (AKTi) revealed a specific transcriptome landscape. Comparing the top 100 genes similarly regulated by SAL in two human PCa cell lines that undergo cell senescence and being counteracted by AKTi revealed 33 commonly regulated genes. One gene, ERBB receptor feedback inhibitor 1 (ERRFI1), encodes the mitogen-inducible gene 6 (MIG6) that is potently upregulated by SAL, whereas the combinatory treatment of SAL with AKTi reverses the SAL-mediated upregulation. Functionally, knockdown of ERRFI1 enhances the pro-survival AKT pathway by enhancing phosphorylation of AKT and the downstream AKT target S6, whereas the phospho-retinoblastoma (pRb) protein levels were decreased. Further, the expression of the cell cycle inhibitor p15INK4b is enhanced by SAL and ERRFI1 knockdown. In line with this, cell senescence is induced by ERRFI1 knockdown and is enhanced slightly further by SAL. Treatment of SAL in the ERRFI1 knockdown background enhances phosphorylation of both AKT and S6 whereas pRb becomes hypophosphorylated. Interestingly, the ERRFI1 knockdown does not reduce AR protein levels or AR target gene expression, suggesting that MIG6 does not interfere with genomic signaling of AR but represses androgen-induced cell senescence and might therefore counteract SAL-induced signaling. The findings indicate that SAL treatment, used in BAT, upregulates MIG6, which inactivates both pRb and the pro-survival AKT signaling. This indicates a novel negative feedback loop integrating genomic and non-genomic AR signaling.
Glioblastoma Stem-Like Cells (GSCs) with Mesenchymal Signature: Lipid Profiles of Mobile Lipids Obtained with MRS before and after Radio/Chemical Treatments
Authors: Grande Sveva , Palma Alessandra , Luciani Anna Maria , Anello Pasqualino , Ricci-Vitiani Lucia , Buccarelli Mariachiara , D’Alessandris Quintino Giorgio , Pallini Roberto , Guidoni Laura , Viti Vincenza , Rosi Antonella
Published: July 2022

Glioblastoma is the most common and lethal primary malignant brain tumor in adults. Glioblastoma stem cells (GSCs) promote and are responsible for glioblastoma intratumoral heterogeneity and therapy resistance, due to their two main features: self-renewal and differentiation. Lipids have important biological and physiological functions that are critical for understanding the regulation and control of stem cell fate; lipid metabolism and related unsaturation levels play a possible role as the target of therapeutics to overcome glioblastoma radioresistance. This paper aimed at an in-depth analysis of 13 GSC mesenchymal (MES) lines, two subclones, and a stabilized glioblastoma line (T98G) by magnetic resonance spectroscopy (MRS). Particularly, 2D MRS was used to investigate lipid unsaturation behavior during growth in culture and after treatment with etomoxir and photon beams. MES lines, although belonging to the same genetic and metabolic cluster, showed metabolic heterogeneity when observed by MRS, focusing on lipid signals. Nonetheless, the observed unsaturation level stability for two representative lines after stressful treatments suggests unusual robustness of the unsaturation levels for each line, as a peculiar and intrinsic characteristic of GSCs.
Clinical and Pathological Tools for Predicting Recurrence and/or Metastasis in Patients with Pheochromocytoma and Paraganglioma
Authors: Bima Chiara , Bioletto Fabio , Lopez Chiara , Bollati Martina , Arata Stefano , Procopio Matteo , Gesmundo Iacopo , Ghigo Ezio , Maccario Mauro , Parasiliti-Caprino Mirko
Published: July 2022

Pheochromocytomas and paragangliomas are endocrine tumors belonging to the family of neural crest cell-derived neoplasms. They have an extremely variable clinical course, characterized by a non-negligible percentage of relapse and/or metastasis after radical surgery. To date, there are no reliable methods to predict the metastatic potential of these neoplasms, despite several clinical, molecular, and histopathological factors that have been extensively studied in the literature as predictors of the recurrence and/or metastasis in these neoplasms with different performances and results. In this review, we aimed to discuss and analyze the most important clinical and histopathological tools for predicting recurrence risk in patients affected by pheochromocytomas or paragangliomas. Thus, we compared the main available predictive models, exploring their applications in stratifying patients’ risks. In conclusion, we underlined the importance of simple and validated tools to better define disease aggressiveness and establish tailored patients’ treatments and follow-ups.
A nop56 Zebrafish Loss-of-Function Model Exhibits a Severe Neurodegenerative Phenotype
Authors: Quelle-Regaldie Ana , Folgueira Mónica , Yáñez Julián , Sobrido-Cameán Daniel , Alba-González Anabel , Barreiro-Iglesias Antón , Sobrido María-Jesús , Sánchez Laura
Published: July 2022

NOP56 belongs to a C/D box small nucleolar ribonucleoprotein complex that is in charge of cleavage and modification of precursor ribosomal RNAs and assembly of the 60S ribosomal subunit. An intronic expansion in NOP56 gene causes Spinocerebellar Ataxia type 36, a typical late-onset autosomal dominant ataxia. Although vertebrate animal models were created for the intronic expansion, none was studied for the loss of function of NOP56. We studied a zebrafish loss-of-function model of the nop56 gene which shows 70% homology with the human gene. We observed a severe neurodegenerative phenotype in nop56 mutants, characterized mainly by absence of cerebellum, reduced numbers of spinal cord neurons, high levels of apoptosis in the central nervous system (CNS) and impaired movement, resulting in death before 7 days post-fertilization. Gene expression of genes related to C/D box complex, balance and CNS development was impaired in nop56 mutants. In our study, we characterized the first NOP56 loss-of-function vertebrate model, which is important to further understand the role of NOP56 in CNS function and development.
Pain and Opioid-Induced Gut Microbial Dysbiosis
Authors: Thomas Karen R. , Watt Jacob , Wu Chuen Mong J. , Akinrinoye Adejoke , Amjad Sairah , Colvin Lucy , Cowe Rachel , Duncan Sylvia H. , Russell Wendy R. , Forget Patrice
Published: July 2022

Opioid-induced dysbiosis (OID) is a specific condition describing the consequences of opioid use on the bacterial composition of the gut. Opioids have been shown to affect the epithelial barrier in the gut and modulate inflammatory pathways, possibly mediating opioid tolerance or opioid-induced hyperalgesia; in combination, these allow the invasion and proliferation of non-native bacterial colonies. There is also evidence that the gut-brain axis is linked to the emotional and cognitive aspects of the brain with intestinal function, which can be a factor that affects mental health. For example, Mycobacterium, Escherichia coli and Clostridium difficile are linked to Irritable Bowel Disease; Lactobacillaceae and Enterococcacae have associations with Parkinson’s disease, and Alistipes has increased prevalence in depression. However, changes to the gut microbiome can be therapeutically influenced with treatments such as faecal microbiota transplantation, targeted antibiotic therapy and probiotics. There is also evidence of emerging therapies to combat OID. This review has collated evidence that shows that there are correlations between OID and depression, Parkinson’s Disease, infection, and more. Specifically, in pain management, targeting OID deserves specific investigations.
Autophagy: Guardian of Skin Barrier
Authors: Kim Hyun Jee , Park Jisoo , Kim Sun Kyeon , Park Hyungsun , Kim Jung Eun , Lee Seongju
Published: July 2022

Autophagy is a major degradation pathway that removes harmful intracellular substances to maintain homeostasis. Various stressors, such as starvation and oxidative stress, upregulate autophagy, and the dysregulation of autophagy is associated with various human diseases, including cancer and skin diseases. The skin is the first defense barrier against external environmental hazards such as invading pathogens, ultraviolet rays, chemical toxins, and heat. Although the skin is exposed to various stressors that can activate autophagy, the roles of autophagy in the skin have not yet been fully elucidated. Accumulating evidence suggests that autophagy is closely associated with pathogenesis and the treatment of immune-related skin diseases. In this study, we review how autophagy interacts with skin cells, including keratinocytes and immune cells, enabling them to successfully perform their protective functions by eliminating pathogens and maintaining skin homeostasis. Furthermore, we discuss the implications of autophagy in immune-related skin diseases, such as alopecia areata, psoriasis, and atopic dermatitis, and suggest that a combination of autophagy modulators with conventional therapies may be a better strategy for the treatment of these diseases.
Relationship between the Soluble F11 Receptor and Annexin A5 in African Americans Patients with Type-2 Diabetes Mellitus
Authors: Adedayo Ajibola , Eluwole Ayobami , Tedla Fasika , Kremer Arye , Khan Muhammad , Mastrogiovanni Nicole , Rosenberg Carl , Dreizen Paul , La Rosa John , Salciccioli Louis , Boutjdir Mohamed , Banerji Mary Ann , Brown Clinton , Lazar Jason , Salifu Moro , Bakillah Ahmed
Published: July 2022

Type 2 diabetes mellitus (T2DM) is characterized by endothelial dysfunction, increased thrombogenicity, and inflammation. The soluble human F11 receptor (sF11R) and annexin A5 (ANXA5) play crucial roles in inflammatory thrombosis and atherosclerosis. We examined the relationship between circulating sF11R and ANXA5 and their impact on endothelial function. The study included 125 patients with T2DM. Plasma levels of sF11R and ANXA5 were quantified by ELISA. Microvascular function was assessed using the vascular reactivity index (VRI). Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Carotid intima-media thickness (CIMT) was assessed by B-mode ultrasound imaging. The mean age of patients in the study was 59.7 ± 7.8 years, 78% had hypertension, 76% had dyslipidemia, and 12% had CKD. sF11R correlated positively with ANXA5 levels (β = 0.250, p = 0.005), and correlated inversely with VRI and total nitic oxide (NO), (β = −0.201, p = 0.024; β = −0.357, p = 0.0001, respectively). Multivariate regression analysis revealed that sF11R was independently associated with ANXA5 in the total population and in patients with HbA1c > 6.5% (β = 0.366, p = 0.007; β = 0.425, p = 0.0001, respectively). sF11R and ANXA5 were not associated with vascular outcome, suggesting that they may not be reliable markers of vascular dysfunction in diabetes. The clinical significance of sF11R/ANXA5 association in diabetes warrants further investigation in a larger population.
Small Nucleolar Derived RNAs as Regulators of Human Cancer
Authors: Coley Alexander Bishop , DeMeis Jeffrey David , Chaudhary Neil Yash , Borchert Glen Mark
Published: July 2022

In the past decade, RNA fragments derived from full-length small nucleolar RNAs (snoRNAs) have been shown to be specifically excised and functional. These sno-derived RNAs (sdRNAs) have been implicated as gene regulators in a multitude of cancers, controlling a variety of genes post-transcriptionally via association with the RNA-induced silencing complex (RISC). In this review, we have summarized the literature connecting sdRNAs to cancer gene regulation. SdRNAs possess miRNA-like functions and are able to fill the role of tumor-suppressing or tumor-promoting RNAs in a tissue context-dependent manner. Indeed, there are many miRNAs that are actually derived from snoRNA transcripts, meaning that they are truly sdRNAs and as such are included in this review. As sdRNAs are frequently discarded from ncRNA analyses, we emphasize that sdRNAs are functionally relevant gene regulators and likely represent an overlooked subclass of miRNAs. Based on the evidence provided by the papers reviewed here, we propose that sdRNAs deserve more extensive study to better understand their underlying biology and to identify previously overlooked biomarkers and therapeutic targets for a multitude of human cancers.
Comparative Proteomic Assessment of Normal vs. Polyhydramnios Amniotic Fluid Based on Computational Analysis
Authors: Navakauskienė Rūta , Baronaitė Sandra , Matuzevičius Dalius , Krasovskaja Natalija , Treigytė Gražina , Arlauskienė Audronė , Navakauskas Dalius
Published: July 2022

Mass spectrometry-based proteomics have become a valued tool for conducting comprehensive analyses in amniotic fluid samples with pathologies. Our research interest is the finding and characterization of proteins related to normal vs. polyhydramnios (non-immune hydrops) pregnancy. Proteomic analysis was performed on proteins isolated from fresh amniotic fluid samples. Proteins were fractionated by 2DE using a different pI range (pI 3–11, pI 4–7) and analyzed with MALDI-TOF-MS. Furthermore, by using computational analysis, identified proteins in protein maps specific to normal vs. polyhydramnios pregnancy were compared and the quantities of expressed proteins were evaluated mathematically. Comparative analysis of proteome characteristic for the same polyhydramnios pregnancy fractionated by 2DE in different pI range (3–11 and 4–7) was performed and particular protein groups were evaluated for the quantification of changes within the same protein level. Proteins of normal and polyhydramnios pregnancies were fractionated by 2DE in pI range 3–11 and in pI range 4–7. Mass spectrometry analysis of proteins has revealed that the quantity changes of the main identified proteins in normal vs. polyhydramnios pregnancy could be assigned to immune response and inflammation proteins, cellular signaling and regulation proteins, metabolic proteins, etc. Specifically, we have identified and characterized proteins associated with heart function and circulatory system and proteins associated with abnormalities in prenatal medicine. The following are: serotransferrin, prothrombin, haptoglobin, transthyretin, alpha-1-antitrypsin, zinc-alpha-2-glycprotein, haptoglobin kininogen-1, hemopexin, clusterin, lumican, afamin, gelsolin. By using computational analysis, we demonstrated that some of these proteins increased a few times in pathological pregnancy. Computer assistance analysis of 2DE images suggested that, for the better isolation of the proteins’ isoforms, those levels increased/decreased in normal vs. polyhydramnios pregnancy, and the fractionation of proteins in pI rage 3–11 and 4–7 could be substantial. We analyzed and identified by MS proteins specific for normal and polyhydramnios pregnancies. Identified protein levels increased and/or modification changed in case of non-immune hydrops fetus and in cases of cardiovascular, anemia, growth restriction, and metabolic disorders. Computational analysis for proteomic characterization empower to estimate the quantitative changes of proteins specific for normal vs. polyhydramnios pregnancies.
How Chemotherapy Affects the Tumor Immune Microenvironment: A Narrative Review
Authors: Merlano Marco Carlo , Denaro Nerina , Galizia Danilo , Ruatta Fiorella , Occelli Marcella , Minei Silvia , Abbona Andrea , Paccagnella Matteo , Ghidini Michele , Garrone Ornella
Published: July 2022

Chemotherapy is much more effective in immunocompetent mice than in immunodeficient ones, and it is now acknowledged that an efficient immune system is necessary to optimize chemotherapy activity and efficacy. Furthermore, chemotherapy itself may reinvigorate immune response in different ways: by targeting cancer cells through the induction of cell stress, the release of damage signals and the induction of immunogenic cell death, by targeting immune cells, inhibiting immune suppressive cells and/or activating immune effector cells; and by targeting the host physiology through changes in the balance of gut microbiome. All these effects acting on immune and non-immune components interfere with the tumor microenvironment, leading to the different activity and efficacy of treatments. This article describes the correlation between chemotherapy and the immune changes induced in the tumor microenvironment. Our ultimate aim is to pave the way for the identification of the best drugs or combinations, the doses, the schedules and the right sequences to use when chemotherapy is combined with immunotherapy.
Viro-Immunological, Clinical Outcomes and Costs of Switching to BIC/TAF/FTC in a Cohort of People Living with HIV: A 48-Week Prospective Analysis
Authors: Mazzitelli Maria , Trunfio Mattia , Putaggio Cristina , Sasset Lolita , Leoni Davide , Lo Menzo Sara , Mengato Daniele , Cattelan Anna Maria
Published: July 2022

To date, therapeutic switches are performed to reduce and prevent toxicity, improve adherence, promote virological control, and save costs. Drug switches are a daily challenge in the management of people living with HIV (PLWH), especially in those with multiple comorbidities and on polypharmacy. The objectives of this prospective analysis were: (I) to evaluate the viro-immunological efficacy of BIC/FTC/TAF in a cohort of PLWH who switched to this regimen from any other previous, at the Infectious and Tropical Diseases Unit of the Padua University Hospital; (II) to assess the impact on body weight, lipids, and renal function parameters at week 48; and (III) to evaluate daily costs changes, adherence, and the rate and causes of discontinuation of the regimen. We included all adult PLWH who switched to BIC/FTC/TAF from 1 February 2020 to 31 October 2021. We collected demographic, clinical, and laboratory data at baseline and week 48 after the switch. In addition, the estimated cART-related cost changes over the follow-up period were calculated. Over the study period, 290 individuals who switched to BIC/FTC/TAF, 76.9% were males, with a median age of 52 years, and 94.8% had an undetectable baseline HIV viremia. After a median time of 35 days (IQR: 1–55), 41 (14.1%) individuals discontinued the regimen. Factors significantly associated with discontinuation were switching from dual regimens, and neurological disorders. At week 48, we detected a significant increase in body weight, BMI, CD4 T-cell count, and CD4/CD8 ratio, and a significant reduction in triglycerides and costs; all patients had undetectable HIV RNA. Our results showed that switching to BIC/FTC/TAF may favor slightly immunological recovery and cost saving (−4.2 EUR/day from baseline to week 48, equivalent to a mean saving of 1533 EUR/year/person). The reduction in triglycerides does not appear to be clinically relevant, even if statistically significant, nor do both the increase in body weight and BMI (+1 kg and +0.29 BMI, respectively) and the increase in CD4 T-cell count (+45 cells/mmc). Further studies are needed to confirm our results.
The Role of Vitamin D in Alzheimer’s Disease: A Transcriptional Regulator of Amyloidopathy and Gliopathy
Authors: Kang Jiseung , Park Mincheol , Lee Eunkyung , Jung Jieun , Kim Tae
Published: July 2022

Alzheimer’s disease (AD) is characterized by amyloid-beta (Aβ) accumulation and cognitive mental decline. Epidemiological studies have suggested an association between low serum vitamin D levels and an increased risk of AD. Vitamin D regulates gene expression via the vitamin D receptor, a nuclear ligand-dependent transcription factor. However, the molecular mechanism underlying the pathogenic and therapeutic effects of vitamin D on AD is not fully understood yet. To better understand how vitamin D regulates the expression of genes related to AD pathology, first, we induced vitamin D deficiency in 5xFAD mice by providing a vitamin-D-deficient diet and observed the changes in the mRNA level of genes related to Aβ processing, which resulted in an increase in the Aβ load in the brain. The vitamin D-deficient diet also suppressed the expression of genes for microglial Aβ phagocytosis. Interestingly, vitamin D deficiency in the early stage of AD resulted in earlier memory impairment. In addition, we administered vitamin D intraperitoneally to 5xFAD mice with a normal diet and found lower Aβ levels with the suppressed expression of genes for Aβ generation and observed improved memory function, which may be potentially associated with reduced MAO-B expression. These findings strongly suggest the role of vitamin D as a crucial disease-modifying factor that may modulate the amyloid pathology with regard to reducing AD symptoms.
Present and Future Opportunities in Imaging the Ubiquitin System (Ub-System)
Authors: Mortati Leonardo , Pergolizzi Barbara , Panuzzo Cristina , Bracco Enrico
Published: July 2022

From yeast to mammalian cells, ubiquitination is one of the most conserved, and reversible, eukaryotic post-translational modifications (PTMs) responsible for controlling nearly all cellular processes. Potentially, every single eukaryotic cell can accomplish different ubiquitination processes at once, which in turn control the execution of specific cellular events in time and space with different biological significance (e.g., protein degradation or protein–protein interaction). Overall, all these signals are highly dynamic and need to be finely integrated to achieve a proper cellular response. Altogether, ubiquitination appears to be an extremely complex process, likely more than any other PTMs. Until a few years ago, the prevailing experimental approaches to investigate the different aspects of the ubiquitin system entailed genetic and biochemical analysis. However, recently, reagents and technologies have been developed enabling microscopy-based imaging of ubiquitination to enter the scene. In this paper, we discuss the progress made with conventional (confocal fluorescence microscopy) and non-conventional non-linear microscopy (Atomic Force Microscopy—AFM, Coherent Anti-Stokes Raman Scattering—CARS, Stimulated Raman Scattering—SRS) and we speculate on future developments.
Seasonal Differences in Expression of Neuropeptide Y (NPY) in Visual Centers of Spotted Munia (Lonchura punctulata)
Authors: Naseem Asma , Vaish Vaibhav , Rani Sangeeta , Malik Shalie
Published: July 2022

The visual perception of birds is an incredibly exciting subject of research. Birds have significantly higher visual acuity than most other animals, which helps them stay safe in flight and detect their prey. Understanding how the eyes send information to the brain for additional processing is crucial. The brain has sections (nuclei) that accept input from the retina. The key areas where information is processed are the hyperpallium apicale (HA), hippocampus (HP), optic tectum (TeO), nucleus rotundus (RoT), and the geniculatus lateralis ventralis (Glv); among these, the RoT is one of the most investigated nuclei for vision. This study looked at how the visual centers of non-photoperiodic songbirds (Spotted Munia) adapt in different life history stages by looking at NPY expression. We immunohistochemically quantified NPY expression in four different seasons, including pre-breeding (June), breeding (September), post-breeding (December), and regressed (March) in the brain of Spotted Munia. We evaluated changes in the expression levels of the peptide throughout the year, by determining the expression at four different periods throughout the year. Peptide expression levels were projected to fluctuate within photoperiod-induced seasons. It was discovered that the parts of the brain related to vision (RoT, HA, and HP) have a higher number of immunoreactive cells during their mating season, i.e., during the summer. The appearance of NPY, a non-photic marker, in brain areas linked with light perception, was fascinating. Indirectly, NPY aids avian reproduction in a variety of ways. These findings demonstrate the importance of these nuclei in the process of reproduction, as well as the involvement of NPY in the visual brain areas of Spotted Munia.
Comment on Chow, J.W.; Stokic, D.S. Longitudinal Changes in Temporospatial Gait Characteristics during the First Year Post-Stroke. Brain Sci. 2021, 11, 1648
Authors: Daly Janis J.
Published: July 2022

The field of neurorehabilitation has moved considerably beyond a narrow use of gait speed [...]
Prediction of Higher Ki-67 Index in Pituitary Adenomas by Pre- and Intra-Operative Clinical Characteristics
Authors: Wang Xuanzhi , Li Mingwu , Jiang Xiaofeng , Wang Fei , Ling Shiying , Niu Chaoshi
Published: July 2022

Objective: The Ki-67 index is an indicator of the active proliferation and aggressive behavior of pituitary adenomas (PAs). Appropriate pre- and intra-operatives of the Ki-67 index can help surgeons develop better and more personalized treatment strategies for patients with PAs. This study aimed to investigate the influence factors for predicting the Ki-67 index in PAs. Methods: Data of 178 patients with PAs confirmed by pathology were retrospectively analyzed. According to the Ki-67 index, the patients were divided into the Ki-67 < 3% and Ki-67 ≥ 3% cohorts. Patient data, including age, sex, postoperative immunohistochemical pituitary hormone positive index, Knosp grade, tumor breaking through the sellar floor, rich blood supply to the tumor, tumor located inside the sella, erosion of the dorsum sellae bone, and pituitary-specific transcription factor, were collected. A univariate logistic analysis was used to evaluate the influence factors for a high Ki-67 index. Multiple regression and receiver operating characteristic (ROC) curve were used to analyze the factors with p < 0.05. The mutant status of Ki-67 index was predicted by nomogram. Results: Multivariate regression analysis showed that rich blood supply to the tumor and erosion of the dorsum sellae bone were independent risk factors for the Ki-67 proliferation index. The ROC curves demonstrated that age, rich blood supply to the tumor, and erosion of the dorsum sellae bone can predict the occurrence of a high Ki-67 index. Together, the three risk factors provide a stronger ability to predict the Ki-67 index. The nomogram was developed and validated. Conclusion: Age, rich blood supply to the tumor, and erosion of the dorsum sellae bone are influencing factors for predicting the Ki-67 index. Suitable nomogram prediction models were developed and validated, and there is potential for personalized treatment for PA patients.
The Influence of Psychopathy on Incarcerated Inmates’ Cognitive Empathy
Authors: Flórez Gerardo , Ferrer Ventura , García Luis , Crespo María , Pérez Manuel , Saiz Pilar
Published: July 2022

(1) Background: there is an ongoing debate about whether psychopathic traits increase or decrease cognitive empathy/Theory of Mind. (2) Methods: using a representative sample of 204 Spanish convicted inmates incarcerated at the Pereiro de Aguiar Penitentiary in Ourense, Spain, we investigated the relationship between two tools for the assessment of psychopathy, the Psychopathy Checklist-Revised (PCL-R) and the Comprehensive Assessment of Psychopathic Personality (CAPP), and the Reading the Mind in the Eyes Test (RMET), a well-known measure of cognitive empathy. (3) Results: The results showed no clear connection between the scores on the psychopathy assessment tools and RMET performance. This lack of association was stronger when the age variable was included in the multivariate analysis. (4) Conclusions: the results of this study failed to detect any clear link between psychopathy and cognitive empathy performance. Accordingly, our results indicate that psychopathy neither improves nor worsens cognitive empathy.
Study on Damping Performance of Hyperboloid Damper with SMA-Negative Stiffness
Authors: Chang Huahui , Liu Leifei , Jing Li , Lu Jingyan , Cao Sasa
Published: July 2022

To improve the limiting capacity of isolation bearings and reduce residual deformation, a new material shape memory alloy (SMA) was introduced into the damping device. SMA shape memory materials have shape memory effect, superelastic effect, and damping properties of metal alloys. Although the SMA isolation bearing can improve the self-resetting ability of the bridge, it will increase the internal force response of the substructure compared with the ordinary isolation bearing. To solve this problem, a new type of SMA negative stiffness hyperboloid shock absorber is proposed. The device is provided with restoring force by SMA cables, negative rigidity by two friction pendulum supports with opposite curved surfaces, and energy dissipation capacity by friction between the slider and the upper and lower steel plates. Theoretical derivation and finite element analysis results show that the damping device can not only provide the self-resetting ability of the bridge but also partially reduce the internal force response of the SMA damping bridge structural system on the premise of reducing the displacement response of the bridge.
Waste Durian Husk Fibers as Natural Sound Absorber: Performance and Acoustic Characterization
Authors: Putra Azma , Othman Muhammad Nur , Oliveira Thaynan , Souli M’hamed , Kassim Dg Hafizah , Irianto  , Herawan Safarudin
Published: July 2022

The paper presents the sound absorption coefficient of acoustic absorbers fabricated from natural durian husk fibers, which are currently still considered as agricultural wastes, especially in Malaysia. Samples were fabricated with different fiber densities and thicknesses and the sound absorption performance was measured using the impedance tube method. The results reveal that the durian husk fibers can have absorption coefficient of more than 0.5 above 1 kHz for a minimum thick sample of 20 mm and with minimum density of 160 kg/m3. The optimised macroscopic parameters for various densities were calculated using the inverse method employing the well-known Johnson-Champoux-Allard (JCA) model for porous material.
Experimental Investigation of Novel Angle Bracket Connection in Cold-Formed Steel Structures
Authors: Lukačević Lazar , Krolo Paulina , Bakran Antonio
Published: July 2022

In this study, an innovative fabricated angle bracket connection for joining cold-formed steel structures is presented and investigated. The innovation lies in the especially designed and manufactured angle bracket and in the method of connecting the angle bracket for the C-profile using clinch pressing. This novel angle bracket can be used to connect cold-formed steel elements such as beam trusses at the ends of the chords or for anchoring the column base. Five specimens were fabricated and experimentally tested under monotonic tensile loading until failure. A specific tool was developed to properly hold C-profiles. Three displacement measurement procedures were performed, and the appropriate method was used to analyse the test results. The main failure mechanism of the angle bracket connection determined by the tests was pull-through of the M12 bolt, whose resistance is compared with the calculated values according to the AISI S100-16 and EN 1993-1-3 standards. There was no bearing failure in the innovative connection between the C-profile and the angle bracket, which indicates an increase in the bearing capacity of the connection.
Energy Analysis and Forecast of a Major Modern Hospital
Authors: Liu Aaron , Ma Yunlong , Miller Wendy , Xia Bo , Zedan Sherif , Bonney Bruce
Published: July 2022

Healthcare buildings often have high energy use intensity, which is potentially influenced by a few factors, such as occupancy and climate. A suite of data analysis methods, including principal component analysis and regressions, is applied to analyse monthly electricity data of a modern major hospital in subtropical Australia. The analysis shows that occupancy is not highly correlated with the hospital’s electricity use, nor is it important for building energy modelling. However, outdoor environment temperature is highly correlated with the hospital’s electricity use. Then, the hospital’s electricity uses in 2030 to 2090 scenarios are forecast with future climate files. The impacts are analysed in terms of bill increases and renewable capacity needed to offset the increased electricity use. This study has established a process to predict future hospital energy use using data-driven energy modelling. This succinct article provides vital evidence to support the healthcare sector to continuously improve energy efficiency for health buildings, which is a major asset to adapt to the changing climate.
Thermal and Physico-Chemical Characteristics of Plaster Reinforced with Wheat Straw for Use as Insulating Materials in Building
Authors: Saad Azzem Lokmane , Bellel Nadir
Published: July 2022

In this paper, a new material consisting of plaster and wheat straw was studied with the purpose of reducing energy consumption. The aim of this study is to test this new compound for use as an insulation material in buildings, where the samples were prepared by mixing wheat straw after grinding it in different proportions from 0% to 15%. On the other hand, the physico-chemical properties and thermal conductivity of the samples were experimentally investigated, and the time lag and energy savings for the samples were also studied. The results showed that the addition of wheat straw leads to an increase in the time lag and also to a decrease in the thermal conductivity, which leads to an improvement in the thermal resistance and energy savings. As well, fiber addition has no effect on the chemical composition of the matrix, as shown by FTIR and XRD analyses.The findings of the DSC and TGA analysis indicate that the inclusion of wheat straw fibers has an effect on the thermal characteristics of the matrix. This new biocomposite can be used as an additive to plaster to create environmentally friendly composite materials for thermal insulation in buildings.
Outcomes of Minimally Invasive and Robot-Assisted Esophagectomy for Esophageal Cancer
Authors: Banks Kian C. , Hsu Diana S. , Velotta Jeffrey B.
Published: July 2022

With the evolution of minimally invasive esophagectomy (MIE) and robot-assisted minimally invasive esophagectomy (RAMIE), questions remain regarding the benefits and indications of these methods. Given that set indications do not exist, this article aims first to review the reported outcomes of MIE, RAMIE, and open esophagectomy. Then, considerations based on the reported outcomes are discussed to guide surgeons in selecting the best approach. MIE and RAMIE offer the potential to improve outcomes for esophagectomy patients; however, surgeon experience as well as individual patient factors play important roles when deciding upon the surgical approach.
FOXD1 Is a Transcription Factor Important for Uveal Melanocyte Development and Associated with High-Risk Uveal Melanoma
Authors: van den Bosch Quincy C. C. , Nguyen Josephine Q. N. , Brands Tom , van den Bosch Thierry P. P. , Verdijk Robert M. , Paridaens Dion , Naus Nicole C. , de Klein Annelies , Kiliç Emine , Brosens Erwin
Published: July 2022

Uveal melanoma (UM) is a deadly ocular malignancy, originating from uveal melanocytes. Although much is known regarding prognostication in UM, the exact mechanism of metastasis is mostly unknown. Metastatic tumor cells are known to express a more stem-like RNA profile which is seen often in cell-specific embryonic development to induce tumor progression. Here, we identified novel transcription regulators by reanalyzing publicly available single cell RNA sequencing experiments. We identified five transcription regulators of interest: ELL2, KDM5B, REXO4, RBFOX2 and FOXD1. Our most significant finding is FOXD1, as this gene is nearly exclusively expressed in high-risk UM and its expression is associated with a poor prognosis. Even within the BAP1-mutated UM, the expression of FOXD1 is correlated with poor survival. FOXD1 is a novel factor which could potentially be involved in the metastatic capacity of high-risk UM. Elucidating the function of FOXD1 in UM could provide insight into the malignant transformation of uveal melanocytes, especially in high-risk UM.
Tumor-Treating Fields in Glioblastomas: Past, Present, and Future
Authors: Guo Xiaopeng , Yang Xin , Wu Jiaming , Yang Huiyu , Li Yilin , Li Junlin , Liu Qianshu , Wu Chen , Xing Hao , Liu Penghao , Wang Yu , Hu Chunhua , Ma Wenbin
Published: July 2022

Tumor-treating fields (TTFields), a noninvasive and innovative therapeutic approach, has emerged as the fourth most effective treatment option for the management of glioblastomas (GBMs), the most deadly primary brain cancer. According to on recent milestone randomized trials and subsequent observational data, TTFields therapy leads to substantially prolonged patient survival and acceptable adverse events. Clinical trials are ongoing to further evaluate the safety and efficacy of TTFields in treating GBMs and its biological and radiological correlations. TTFields is administered by delivering low-intensity, intermediate-frequency, alternating electric fields to human GBM function through different mechanisms of action, including by disturbing cell mitosis, delaying DNA repair, enhancing autophagy, inhibiting cell metabolism and angiogenesis, and limiting cancer cell migration. The abilities of TTFields to strengthen intratumoral antitumor immunity, increase the permeability of the cell membrane and the blood–brain barrier, and disrupt DNA-damage-repair processes make it a promising therapy when combined with conventional treatment modalities. However, the overall acceptance of TTFields in real-world clinical practice is still low. Given that increasing studies on this promising topic have been published recently, we conducted this updated review on the past, present, and future of TTFields in GBMs.
CD109 Is a Critical Determinant of EGFR Expression and Signaling, and Tumorigenicity in Squamous Cell Carcinoma Cells
Authors: Zhou Shufeng , Hassan Amani , Kungyal Tenzin , Tabariès Sebastien , Luna José , Siegel Peter , Philip Anie
Published: July 2022

(1) Background: Squamous cell carcinoma (SCC) is one of the leading causes of cancer-related deaths worldwide. CD109 is overexpressed in many cancers including SCC. Although a pro-tumorigenic role for CD109 has been shown in non-SCC cancers, and in one type of SCC, the mechanisms and signaling pathways reported are discrepant. (2) Methods: The CD109-EGFR interaction and CD109-mediated regulation of EGFR expression, signaling, and stemness were studied using microarray, immunoblot, immunoprecipitation, qPCR, immunofluorescence, and/or spheroid formation assays. The role of CD109 in tumor progression and metastasis was studied using xenograft tumor growth and metastatic models. (3) Results: We establish the in vivo tumorigenicity of CD109 in vulvar SCC cells and demonstrate that CD109 is an essential regulator of EGFR expression at the mRNA and protein levels and of EGFR/AKT signaling in vulvar and hypopharyngeal SCC cells. Furthermore, we show that the mechanism involves EGFR-CD109 heteromerization and colocalization, leading to the stabilization of EGFR levels. Additionally, we demonstrate that the maintenance of epithelial morphology and in vitro tumorigenicity of SCC cells require CD109 localization to the cell surface. (4) Conclusions: Our study identifies an essential role for CD109 in vulvar SCC progression. We demonstrate that CD109 regulates SCC cellular stemness and epithelial morphology via a cell-surface CD109-EGFR interaction, stabilization of EGFR levels and EGFR/AKT signaling.
Circulating Exhausted PD-1+CD39+ Helper CD4 T Cells Are Tumor-Antigen-Specific and Predict Response to PD-1/PD-L1 Axis Blockade
Authors: Martinez-Gomez Carlos , Michelas Marie , Scarlata Clara-Maria , Salvioni Anna , Gomez-Roca Carlos , Sarradin Victor , Lauzéral-Vizcaino Françoise , Féliu Virginie , Dupret-Bories Agnès , Ferron Gwénaël , Sarini Jérôme , Devaud Christel , Delord Jean-Pierre , Balança Camille-Charlotte , Martinez Alejandra , Ayyoub Maha
Published: July 2022

Tumor-infiltrating exhausted PD-1hiCD39+ tumor-antigen (Ag)-specific CD4 T cells contribute to the response to immune checkpoint blockade (ICB), but their circulating counterparts, which could represent accessible biomarkers, have not been assessed. Here, we analyzed circulating PD-1+CD39+ CD4 T cells and show that this population was present at higher proportions in cancer patients than in healthy individuals and was enriched in activated HLA-DR+ and ICOS+ and proliferating KI67+ cells, indicative of their involvement in ongoing immune responses. Among memory CD4 T cells, this population contained the lowest proportions of cells producing effector cytokines, suggesting they were exhausted. In patients with HPV-induced malignancies, the PD-1+CD39+ population contained high proportions of HPV Ag-specific T cells. In patients treated by ICB for HPV-induced tumors, the proportion of circulating PD-1+CD39+ CD4 T cells was predictive of the clinical response. Our results identify CD39 expression as a surrogate marker of circulating helper tumor-Ag-specific CD4 T cells.
Application of Elastin-like Polypeptide in Tumor Therapy
Authors: Shi Xianggang , Chen Dongfeng , Liu Guodong , Zhang Hailing , Wang Xiaoyan , Wu Zhi , Wu Yan , Yu Feng , Xu Qinggang
Published: July 2022

Elastin-like polypeptides (ELPs) are stimulus-responsive artificially designed proteins synthesized from the core amino acid sequence of human tropoelastin. ELPs have good biocompatibility and biodegradability and do not systemically induce adverse immune responses, making them a suitable module for drug delivery. Design strategies can equip ELPs with the ability to respond to changes in temperature and pH or the capacity to self-assemble into nanoparticles. These unique tunable biophysicochemical properties make ELPs among the most widely studied biopolymers employed in protein purification, drug delivery, tissue engineering and even in tumor therapy. As a module for drug delivery and as a carrier to target tumor cells, the combination of ELPs with therapeutic drugs, antibodies and photo-oxidation molecules has been shown to result in improved pharmacokinetic properties (prolonged half-life, drug targeting, cell penetration and controlled release) while restricting the cytotoxicity of the drug to a confined infected site. In this review, we summarize the latest developments in the application methods of ELP employed in tumor therapy, with a focus on its conjugation with peptide drugs, antibodies and photosensitizers.
IKKε Inhibitor Amlexanox Promotes Olaparib Sensitivity through the C/EBP-β-Mediated Transcription of Rad51 in Castrate-Resistant Prostate Cancer
Authors: Gilbert Sophie , Péant Benjamin , Mes-Masson Anne-Marie , Saad Fred
Published: July 2022

The progression of prostate cancer (PC) is often characterized by the development of castrate-resistant PC (CRPC). Patients with CRPC are treated with a variety of agents including new generation hormonal therapies or chemotherapy. However, as the cancer develops more resistance mechanisms, these drugs eventually become less effective and finding new therapeutic approaches is critical to improving patient outcomes. Previously, we have shown that IKKε depletion and IKKε inhibitors, BX795 and Amlexanox, decrease CRPC cell proliferation in vitro and in vivo and that IKKε inhibitors induce a senescence phenotype accompanied by increased DNA damage and genomic instability in CRPC cells. Here, we describe a new role for IKKε in DNA damage repair involving Rad51 and examine the therapeutic potential of Amlexanox combined with the PARP inhibitor Olaparib in CRPC cell lines. Combining Amlexanox with Olaparib decreased CRPC cell proliferation and enhanced DNA damage through the inhibition of Olaparib-induced Rad51 recruitment and expression in CRPC cells or IKKε-depleted PC-3 cells. We demonstrated that Rad51 promoter activity, measured by luciferase assay, was decreased with Amlexanox treatment or IKKε depletion and that Amlexanox treatment decreased the occupancy of transcription factor C/EBP-β on the Rad51 promoter. Our mouse model also showed that Amlexanox combined with Olaparib inhibited tumor growth of CRPC xenografts. Our study highlights a new role for IKKε in DNA damage repair through the regulation of Rad51 transcription and provides a rationale for the combination of Amlexanox and Olaparib in the treatment of patients with CRPC.
Transfer Learning-Based Multi-Scale Denoising Convolutional Neural Network for Prostate Cancer Detection
Authors: Chui Kwok Tai , Gupta Brij B. , Chi Hao Ran , Arya Varsha , Alhalabi Wadee , Ruiz Miguel Torres , Shen Chien-Wen
Published: July 2022

Background: Prostate cancer is the 4th most common type of cancer. To reduce the workload of medical personnel in the medical diagnosis of prostate cancer and increase the diagnostic accuracy in noisy images, a deep learning model is desired for prostate cancer detection. Methods: A multi-scale denoising convolutional neural network (MSDCNN) model was designed for prostate cancer detection (PCD) that is capable of noise suppression in images. The model was further optimized by transfer learning, which contributes domain knowledge from the same domain (prostate cancer data) but heterogeneous datasets. Particularly, Gaussian noise was introduced in the source datasets before knowledge transfer to the target dataset. Results: Four benchmark datasets were chosen as representative prostate cancer datasets. Ablation study and performance comparison between the proposed work and existing works were performed. Our model improved the accuracy by more than 10% compared with the existing works. Ablation studies also showed average improvements in accuracy using denoising, multi-scale scheme, and transfer learning, by 2.80%, 3.30%, and 3.13%, respectively. Conclusions: The performance evaluation and comparison of the proposed model confirm the importance and benefits of image noise suppression and transfer of knowledge from heterogeneous datasets of the same domain.
Clinical Impact of Dual Time Point 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Fusion Imaging in Pancreatic Cancer
Authors: Einama Takahiro , Yamagishi Yoji , Takihata Yasuhiro , Konno Fukumi , Kobayashi Kazuki , Yonamine Naoto , Fujinuma Ibuki , Tsunenari Takazumi , Kouzu Keita , Nakazawa Akiko , Iwasaki Toshimitsu , Shinto Eiji , Ishida Jiro , Ueno Hideki , Kishi Yoji
Published: July 2022

We examined the value of preoperative dual time point (DTP) 18F-fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging (FDG PET/CT) as a predictor of early recurrence or the outcomes in patients with pancreatic cancer. Standardized uptake values (SUVs) in DTP FDG PET/CT were performed as preoperative staging. SUVmax1 and SUVmax2 were obtained in 60 min and 120 min, respectively. ΔSUVmax% was defined as (SUVmax2 − SUVmax1)/SUVmax1 × 100. The optimal cut-off values for SUVmax parameters were selected based on tumor relapse within 1 year of surgery. Optimal cut-off values for SUVmax1 and ΔSUVmax% were 7.18 and 24.25, respectively. The combination of SUVmax1 and ΔSUVmax% showed higher specificity and sensitivity, and higher positive and negative predictive values for tumor relapse within 1 year than SUVmax1 alone. Relapse-free survival (RFS) was significantly worse in the subgroups of high SUVmax1 and high ΔSUVmax% (median 7.0 months) than in the other subgroups (p < 0.0001). The multivariate Cox analysis of RFS identified high SUVmax1 and high ΔSUVmax% as independent prognostic factors (p = 0.0060). DTP FDG PET/CT may effectively predict relapse in patients with pancreatic cancer. The combination of SUVmax1 and ΔSUVmax% identified early recurrent patient groups more precisely than SUVmax1 alone.