bluuebunny/crossref_metadata_2025 huggingface dataset:
PKC-ζ mediated reduction of the extracellular vesicles-associated TGF-β1 overcomes radiotherapy resistance in breast cancer
Authors: Zhang Fayun , Zheng Zifeng , Wang Luoyang , Zeng Wenfeng , Wei Wenjing , Zhang Chunling , Zhao Ziran , Liang Wei
Published: April 2023

Background

Radiotherapy is widely applied in breast cancer treatment, while radiotherapy resistance is inevitable. TGF-β1 has been considered to be an endogenous factor for the development of radiotherapy resistance. As a large portion of TGF-β1 is secreted in an extracellular vesicles-associated form (TGF-β1EV), particularly in radiated tumors. Thus, the understanding of the regulation mechanisms and the immunosuppressive functions of TGF-β1EV will pave a way for overcoming the radiotherapy resistance in cancer treatment.

Methods

The superoxide-Zinc-PKC-ζ-TGF-β1EV pathway in breast cancer cells was identified through sequence alignments of different PKC isoforms, speculation and experimental confirmation. A series of functional and molecular studies were performed by quantitative real-time PCR, western blot and flow cytometry analysis. Mice survival and tumor growth were recorded. Student’s t test or two-way ANOVA with correction was used for comparisons of groups.

Results

The radiotherapy resulted in an increased expression of the intratumoral TGF-β1 and an enhanced infiltration of the Tregs in the breast cancer tissues. The intratumoral TGF-β1 was found mainly in the extracellular vesicles associated form both in the murine breast cancer model and in the human lung cancer tissues. Furthermore, radiation induced more TGF-β1EV secretion and higher percentage of Tregs by promoting the expression and phosphorylation of protein kinase C zeta (PKC-ζ). Importantly, we found that naringenin rather than 1D11 significantly improved radiotherapy efficacy with less side effects. Distinct from TGF-β1 neutralizing antibody 1D11, the mechanism of naringenin was to downregulate the radiation-activated superoxide-Zinc-PKC-ζ-TGF-β1EV pathway.

Conclusions

The superoxide-zinc-PKC-ζ-TGF-β1EV release pathway was elucidated to induce the accumulation of Tregs, resulting in radiotherapy resistance in the TME. Therefore, targeting PKC-ζ to counteract TGF-β1EV function could represent a novel strategy to overcome radiotherapy resistance in the treatment of breast cancer or other cancers.

Trial registration: The using of patient tissues with malignant Non-Small Cell Lung Cancer (NSCLC) was approved by the ethics committees at Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (NCC2022C-702, from June 8th, 2022).
Synthesis and adsorption performance of functionalized chitosan and carboxyethylsilanetriol hybrids
Authors: Salama Ahmed , El-Sakhawy Mohamed
Published: April 2023

A novel adsorbent from cationic chitosan derivative and anionic silica precursor was fabricated to remove methylene blue (MB). The hybrid material was prepared from N-guanidinium chitosan acetate (GChi) and carboxyethylsilanetriol sodium salt by a simple ionic interaction followed by sol–gel approach. Multiple characterization methods were used to analyze the morphology and the structure of the well-prepared functionalized material. Batch experiments were conducted to optimize the various operational parameters. The Langmuir isotherm was used to fit the data, and it predicted monolayer adsorption with a maximum capacity of 334 mg g−1. A pseudo-second-order equation fit the adsorption process well. Chitosan/silica hybrids containing carboxylic groups are efficient and cost-effective adsorbents for cationic dyes adsorption from aqueous solutions.
QSAR and molecular docking studies of isatin and indole derivatives as SARS 3CLpro inhibitors
Authors: Soleymani Niousha , Ahmadi Shahin , Shiri Fereshteh , Almasirad Ali
Published: April 2023

The 3C-like protease (3CLpro), known as the main protease of SARS-COV, plays a vital role in the viral replication cycle and is a critical target for the development of SARS inhibitor. Comparative sequence analysis has shown that the 3CLpro of two coronaviruses, SARS-CoV-2 and SARS-CoV, show high structural similarity, and several common features are shared among the substrates of 3CLpro in different coronaviruses. The goal of this study is the development of validated QSAR models by CORAL software and Monte Carlo optimization to predict the inhibitory activity of 81 isatin and indole-based compounds against SARS CoV 3CLpro. The models were built using a newer objective function optimization of this software, known as the index of ideality correlation (IIC), which provides favorable results. The entire set of molecules was randomly divided into four sets including: active training, passive training, calibration and validation sets. The optimal descriptors were selected from the hybrid model by combining SMILES and hydrogen suppressed graph (HSG) based on the objective function. According to the model interpretation results, eight synthesized compounds were extracted and introduced from the ChEMBL database as good SARS CoV 3CLpro inhibitor. Also, the activity of the introduced molecules further was supported by docking studies using 3CLpro of both SARS-COV-1 and SARS-COV-2. Based on the results of ADMET and OPE study, compounds CHEMBL4458417 and CHEMBL4565907 both containing an indole scaffold with the positive values of drug-likeness and the highest drug-score can be introduced as selected leads.
Comprehensive analyses of molecular features, prognostic values, and regulatory functionalities of m6A-modified long non-coding RNAs in lung adenocarcinoma
Authors: Ping Yili , Huang Jingjuan , Zhu Jichao , Sun Zujun , Shang Anquan , Chen Chen , Liu Wenfang , Li Dong
Published: April 2023

Background

Lung adenocarcinoma (LUAD) has a high incidence and recurrence rate. N6-methyladenosine (m6A) modification of RNA has become a promising epigenetic marker in tumors. The dysregulation of both RNA m6A levels and m6A regulator expression levels reportedly affects essential biological processes in various tumors. Long non-coding RNAs (lncRNAs), a subgroup of RNAs over 200 nucleotides in length that do not code for protein, can be modified and regulated by m6A, but the relevant profile in LUAD remains unclear.

Results

The m6A levels of total RNA were decreased in LUAD tumor tissues and cells. Multiple m6A regulators were abnormally expressed at both the RNA and protein levels, and were related in expression patterns and functionally synergistic. Our microarray revealed 2846 m6A-modified lncRNA transcripts as well as its molecular features, 143 of which were differentially m6A-modified and manifested a negative correlation between expression levels and m6A modification levels. More than half of the differentially m6A-modified lncRNAs associated with dysregulated expression. The 6-MRlncRNA risk signature was a reliable indicator for assessing survival time of LUAD patients. The competitive endogenous regulatory network suggested a potential m6A-induced pathogenicity in LUAD.

Conclusions

These data have demonstrated that differential RNA m6A modification and m6A regulator expression levels were identified in LUAD patients. In addition, this study provides evidence increasing the understanding of molecular features, prognostic values, and regulatory functionalities of m6A-modified lncRNAs in LUAD.
Presacral malakoplakia presenting as foot drop: a case report
Authors: Yates Tom A. , Devlin Katie , Arnaout Abed , Hurt William , Stone Neil , Everett Kate V. , Pittman Alan , Patel Hardik , Heenan Susan , Hart Paul , Harrison Thomas S.
Published: April 2023

Background

Malakoplakia is a rare condition characterized by inflammatory masses with specific histological characteristics. These soft tissue masses can mimic tumors and tend to develop in association with chronic or recurrent infections, typically of the urinary tract. A specific defect in innate immunity has been described. In the absence of randomized controlled trials, management is based on an understanding of the biology and on case reports.

Case presentation

Here we describe a case of presacral malakoplakia in a British Indian woman in her late 30s, presenting with complex unilateral foot drop. Four years earlier, she had suffered a protracted episode of intrapelvic sepsis following a caesarean delivery. Resection of her presacral soft tissue mass was not possible. She received empiric antibiotics, a cholinergic agonist, and ascorbic acid. She responded well to medical management both when first treated and following a recurrence of symptoms after completing an initial 8 months of therapy. Whole exome sequencing of the patient and her parents was undertaken but no clear causal variant was identified.

Conclusions

Malakoplakia is uncommon but the diagnosis should be considered where soft tissue masses develop at the site of chronic or recurrent infections. Obtaining tissue for histological examination is key to making the diagnosis. This case suggests that surgical resection is not always needed to achieve a good clinical and radiological outcome.
Coronavirus disease 2019-associated nephropathy in an African American patient: a case report and review of the literature
Authors: Dhillon Vijaypal S. , Alkashash Ahmad , Viquez-Beita Karolina
Published: April 2023

Background

Acute kidney injury is now recognized as a common complication of coronavirus disease 2019, affecting up to 46% of patients, with acute tubular injury as the most common etiology. Recently, we have seen an increase in cases of collapsing glomerulonephritis in patients with coronavirus disease 2019, also known as coronavirus disease 2019-associated nephropathy. It has been noted to be seen with a higher incidence in African American patients who are carriers of the APOL1 variant allele.

Case presentation

A 47-year-old African American male with a past medical history of asthma presented to the emergency department with complaints of intermittent chest pain, shortness of breath, and worsening confusion. On admission, he was found to be hemodynamically stable, but labs were significant for elevated creatinine and blood urea nitrogen, signifying acute kidney injury. He was admitted and taken for emergent dialysis. During his hospitalization, he was found to be positive for coronavirus disease 2019. Renal biopsy was done, which showed collapsing glomerulopathy, and the patient continues to require outpatient dialysis after discharge.

Conclusion

Collapsing glomerulonephritis has emerged as a complication in patients with coronavirus disease 2019. This condition should be particularly suspected in African American patients who present with acute kidney injury, nephrotic-range proteinuria, and who are positive for coronavirus disease 2019. Current treatment options are limited to supportive treatment and renal replacement therapy. More clinical cases and trials are needed to better understand and improve therapeutic outcomes in these patients.
Bioengineered tissue and cell therapy products are efficiently cryopreserved with pathogen-inactivated human platelet lysate-based solutions
Authors: Martín-López María , Rosell-Valle Cristina , Arribas-Arribas Blanca , Fernández-Muñoz Beatriz , Jiménez Rosario , Nogueras Sonia , García-Delgado Ana Belén , Campos Fernando , Santos-González Mónica
Published: April 2023

Background

There remains much interest in improving cryopreservation techniques for advanced therapy medicinal products (ATMPs). Recently, human platelet lysate (hPL) has emerged as a promising candidate to replace fetal bovine serum (FBS) as a xeno-free culture supplement for the expansion of human cell therapy products. Whether hPL can also substitute for FBS in cryopreservation procedures remains poorly studied. Here, we evaluated several cryoprotective formulations based on a proprietary hPL for the cryopreservation of bioengineered tissues and cell therapy products.

Methods

We tested different xenogeneic-free, pathogen-inactivated hPL (ihPL)- and non-inactivated-based formulations for cryopreserving bioengineered tissue (cellularized nanostructured fibrin agarose hydrogels (NFAHs)) and common cell therapy products including bone marrow-derived mesenchymal stromal cells (BM-MSCs), human dermal fibroblasts (FBs) and neural stem cells (NSCs). To assess the tissue and cellular properties post-thaw of NFAHs, we analyzed their cell viability, identity and structural and biomechanical properties. Also, we evaluated cell viability, recovery and identity post-thaw in cryopreserved cells. Further properties like immunomodulation, apoptosis and cell proliferation were assessed in certain cell types. Additionally, we examined the stability of the formulated solutions. The formulations are under a bidding process with MD Bioproducts (Zurich, Switzerland) and are proprietary.

Results

Amongst the tissue-specific solutions, Ti5 (low-DMSO and ihPL-based) preserved the viability and the phenotype of embedded cells in NFAHs and preserved the matrix integrity and biomechanical properties similar to those of the standard cryopreservation solution (70% DMEM + 20% FBS + 10% DMSO). All solutions were stable at − 20 °C for at least 3 months. Regarding cell-specific solutions, CeA maintained the viability of all cell types > 80%, preserved the immunomodulatory properties of BM-MSCs and promoted good recovery post-thaw. Besides, both tested solutions were stable at − 20 °C for 18 months. Finally, we established that there is a 3-h window in which thawed NFAHs and FBs maintain optimum viability immersed in the formulated solutions and at least 2 h for BM-MSCs.

Conclusions

Our results show that pathogen-inactivated solutions Ti5 allocated for bioengineered tissues and CeA allocated for cells are efficient and safe candidates to cryopreserve ATMPs and offer a xenogeneic-free and low-DMSO alternative to commercially available cryoprotective solutions.
Human adipose tissue-derived small extracellular vesicles promote soft tissue repair through modulating M1-to-M2 polarization of macrophages
Authors: Dong Jia , Wu Bin , Tian Weidong
Published: April 2023

Background

Successful regenerative medicine strategies need the manipulation and control of macrophages’ phenotypic switching. Our previous study indicated that rat and porcine adipose tissue-derived small extracellular vesicles could successfully promote soft tissue repair. However, whether human adipose tissue-derived small extracellular vesicles (h-sEV-AT) showed the same ability to promote soft tissue regeneration and whether adipose tissue-derived small extracellular vesicles (sEV-AT) contribute to modulating the polarization of macrophages were unknown.

Methods

In this study, we, for the first time, isolated h-sEV-AT from liposuction adipose tissue and characterized the morphology, size distribution, and marker protein. In vitro, we treated adipose-derived stromal/stem cells (ASCs), endothelial cells (ECs), and M1 macrophages with h-sEV-AT. In vivo, the ability of h-sEV-AT to promote soft tissue regeneration and polarize macrophages was investigated.

Results

The results indicated that h-sEV-AT possessed the characteristics of small extracellular vesicles (sEVs). In vitro, an obvious increase in adipogenesis and angiogenesis was induced by h-sEV-AT. In vivo, h-sEV-AT successfully induced the regeneration of adipose tissue and effectively accelerated full-thickness skin wound healing. Besides, we found that h-sEV-AT showed the ability to increase the percentage of M2 macrophages both in vivo and in vitro, which had been reported to contribute to tissue repair and regeneration.

Conclusions

Taken together, these results suggested that h-sEV-AT showed the ability to induce soft tissue repair supported by not only the differentiation of ASCs and ECs but also the polarization of macrophages. Considering the abundant sources, high yield, and guaranteed effectiveness, this study provided a cell-free strategy for soft tissue regeneration that directly isolated small extracellular vesicles from human liposuction adipose tissue.
An improved monarch butterfly spectrum allocation algorithm for multi-source data stream in complex electromagnetic environment
Authors: Liu Yuchao , Cao Chenggang , Han Yu
Published: April 2023

In the era of the Internet of Everything, various wireless devices and sensors use spectrum, which is a precious and non-renewable resource, to communication. Due to the characteristics of massive, heterogeneous, and multi-source, the generated multi-source data stream brings difficulties to spectrum cognition. As a result, unreasonable spectrum allocation strategy leads to low utilization of spectrum resources. Optimizing spectrum allocation strategy can effectively improve spectrum utilization. Aiming at the problem of trapped local optimum solution in the genetic algorithm (GA) and particle swarm optimization algorithm (PSO), an improved monarch butterfly algorithm is proposed. Firstly, this paper employs the simulated annealing algorithm to select the migration rate, which increases the diversity of monarch butterfly population. Secondly, chaos mapping algorithm is utilized to improve the optimization ability and convergence speed. Finally, in the view of the problem that the monarch butterfly algorithm is easy to fall into the local optimal solution, there is no better way to escape from the local optimal solution. The Wolf pack updating operator is selected to improve the diversity of the population to generate new monarch butterflies. This method updates the population by generating new monarch butterfly individuals, so as to increasing the diversity of the population. The experimental results show that the improved monarch butterfly algorithm outperforms the other two algorithms in terms of convergence speed and system revenue.
Effective path-loss compensation model based on multipath exploitation for through-the-wall radar imaging
Authors: Mkemwa Florian , Abdalla Abdi T. , Maiseli Baraka , Amour Idrissa , Muqaibel Ali
Published: April 2023

Through-the-wall radar imaging (TWRI) has attracted a great deal of attention in several sensitive applications, including rescue missions and military operations. Notwithstanding its broad range of applications, TWRI suffers from path-loss because distant targets experience more attenuation of signal power than those closer to the transceiver. This challenge may lead to missed targets with important information necessary for analysis and informed decision making. Responding to the challenge, we have developed a signal model with an effective path-loss compensator incorporating a free space exponent. Furthermore, multipath exploitation and compressive sensing techniques were employed to develop an effective algorithm for isolating residual clutter that may corrupt real targets. The proposed signal model integrates contributions from the front wall, multipath returns, and path-loss. Compared with the state-of-the-art model under the same experimental conditions, simulation results show that the proposed model achieves improved signal-to-clutter ratio, relative clutter peak, and probability of detection by 13.1%, 17.4% and 33.6%, respectively, suggesting that our model can represent the scene more accurately.
Approximate controllability of second-order impulsive neutral stochastic differential equations with state-dependent delay and Poisson jumps
Authors: Huang Hao , Wu Zheng , Su Xiaofeng
Published: April 2023

We consider the approximate controllability for a class of second-order impulsive neutral stochastic differential equations with state-dependent delay and Poisson jumps in a real separable Hilbert space. Under the sufficient conditions, we obtain approximate controllability results by virtue of the theory of a strongly continuous cosine family of bounded linear operators combined with stochastic inequality technique and the Sadovskii fixed point theorem. Finally, we illustrate the main results by an example.
Response patterns of simulated corn yield and soil nitrous oxide emission to precipitation change
Authors: Kaur Navneet , Hui Dafeng , Riccuito Daniel M. , Mayes Melanie A. , Tian Hanqin
Published: April 2023

Background

Precipitation plays an important role in crop production and soil greenhouse gas emissions. However, how crop yield and soil nitrous oxide (N2O) emission respond to precipitation change, particularly with different background precipitations (dry, normal, and wet years), has not been well investigated. In this study, we examined the impacts of precipitation changes on corn yield and soil N2O emission using a long-term (1981–2020, 40 years) climate dataset as well as seven manipulated precipitation treatments with different background precipitations using the DeNitrification-DeComposition (DNDC) model.

Results

Results showed large variations of corn yield and precipitation but small variation of soil N2O emission among 40 years. Both corn yield and soil N2O emission showed near linear relationships with precipitation based on the long-term precipitation data, but with different response patters of corn yield and soil N2O emission to precipitation manipulations. Corn yield showed a positive linear response to precipitation manipulations in the dry year, but no response to increases in precipitation in the normal year, and a trend of decrease in the wet year. The extreme drought treatments reduced corn yield sharply in both normal and wet years. In contrast, soil N2O emission mostly responded linearly to precipitation manipulations. Decreases in precipitation in the dry year reduced more soil N2O emission than those in the normal and wet years, while increases in precipitation increased more soil N2O emission in the normal and wet years than in the dry year.

Conclusions

This study revealed different response patterns of corn yield and soil N2O emission to precipitation and highlights that mitigation strategy for soil N2O emission reduction should consider different background climate conditions.
Prevalence and correlates of destructive behaviors in the US Naval Surface Forces from 2010–2020
Authors: Lai Kevin , Jameson Jason T. , Russell Dale W.
Published: April 2023

Purpose

To estimate the prevalence of domestic violence, sexual assault, and suicide for United States Navy (USN) personnel between 2010 and 2020 and identify potential associated factors.

Methods

Official report data were used to calculate prevalence rates and odds ratios, accounting for sample and general USN population demographic data to assess differences in over- or underrepresentation of destructive behaviors.

Results

Domestic violence and sexual assault offenders tended to be younger lower-ranked males. For sexual assaults, offenders were three times more likely to be senior to the victim, which was not the case for domestic violence. Females were overrepresented in terms of suicidal ideation and attempts relative to the USN population, while males accounted for more actual suicides. The relative rates of suicidal ideation and attempts for females exceeded those for males (i.e., comparing the sample rate against the USN male and female populations), but the sample proportion for completed suicides (compared to the USN population) were greater for males than for females. Those in the junior enlisted (E1–E3) paygrades exhibited greater odds of suicide attempts versus suicidal ideations relative to those in the Petty Officers (E4–E6) paygrades, although E4–E6s completed more suicides.

Conclusion

The descriptive profile of destructive behaviors in a representative sample of USN personnel provides an overview of the possible factors associated with destructive behaviors and includes an exploration of the relational dynamics and nature of the incidents. The results suggest that sexual assault and domestic violence are characterized by unique relational dynamics and that these destructive behaviors should not necessarily be classified together as male-oriented aggressions (i.e., mainly perpetrated by males against female victims). Those in the E1–E3 and E4–E6 paygrades displayed different patterns in suicidal ideation, attempts, and actual suicides. The results highlight individual characteristics to help inform the development of targeted policies, practices, and interventions for military and other hierarchical organizations (e.g., police).
Exogenous interleukin 33 enhances the brain’s lymphatic drainage and toxic protein clearance in acute traumatic brain injury mice
Authors: Liu Mingqi , Huang Jinhao , Liu Tao , Yuan Jiangyuan , Lv Chuanxiang , Sha Zhuang , Wu Chenrui , Jiang Weiwei , Liu Xuanhui , Nie Meng , Chen Yupeng , Dong Shiying , Qian Yu , Gao Chuang , Fan Yibing , Wu Di , Jiang Rongcai
Published: April 2023

The persistent dysregulation and accumulation of poisonous proteins from destructive neural tissues and cells activate pathological mechanisms after traumatic brain injury (TBI). The lymphatic drainage system of the brain, composed of the glymphatic system and meningeal lymphatic vessels (MLVs), plays an essential role in the clearance of toxic waste after brain injury. The neuroprotective effect of interleukin 33 (IL-33) in TBI mice has been demonstrated; however, its impact on brain lymphatic drainage is unclear. Here, we established a fluid percussion injury model to examine the IL-33 administration effects on neurological function and lymphatic drainage in the acute brain of TBI mice. We verified that exogenous IL-33 could improve the motor and memory skills of TBI mice and demonstrated that in the acute phase, it increased the exchange of cerebrospinal and interstitial fluid, reversed the dysregulation and depolarization of aquaporin-4 in the cortex and hippocampus, improved the drainage of MLVs to deep cervical lymph nodes, and reduced tau accumulation and glial activation. We speculate that the protective effect of exogenous IL-33 on TBI mice’s motor and cognitive functions is related to the enhancement of brain lymphatic drainage and toxic metabolite clearance from the cortex and hippocampus in the acute stage. These data further support the notion that IL-33 therapy may be an effective treatment strategy for alleviating acute brain injury after TBI.
Cost of diabetes and its complications: results from a STEPS survey in Punjab, India
Authors: Kansra Pooja , Oberoi Sumit
Published: April 2023

Background

Diabetes mellitus is an obtrusive universal health emergency in developed and developing countries, including India. With the exponential rise of epidemiological conditions, the costs of treating and managing diabetes are on an upsurge. This study aimed to estimate the cost of diabetes and determine the determinants of the total cost among diabetic patients.

Methods

This cross-sectional study was executed in the northern state of Punjab, India. It involves the multi-stage area sampling technique and data was collected through a self-structured questionnaire adapted following the “WHO STEPS Surveillance” manual. Mann–Whitney U and Kruskal–Wallis tests were performed to compare the cost differences in socio-demographic variables. Lastly, multiple linear regression was conducted to determine and evaluate the association of the dependent variable with numerous influential determinants.

Results

The urban respondents' average direct and indirect costs are higher than rural respondents. Age manifests very eccentric results; the highest mean direct outpatient care expenditure of ₹52,104 was incurred by the respondents below 20 years of age. Gender, complications, income, history of diabetes and work status were statistically significant determinants of the total cost. Study reports a rapid increase in the median annual direct and indirect cost from ₹15,460 and ₹3572 in 1999 to ₹34,100 and ₹4200 in 2021.

Conclusions

The present study highlights that the economic jeopardy of diabetes can be managed by educating people about diabetes and its associated risk factors. The economic burden of diabetes could be restrained by formulating new health policies and promoting the use of generic medicines. The result of the study directs that expenditure on outpatient care is to be reimbursed under the ‘Ayushman Bharat-Sarbat Sehat Bima Yojana’.
Scientific and technological research on the use of wine lees
Authors: de Andrade Bulos Roberta Barreto , da Gama Paz Francine , Machado Ciro Gomes , Tavares Pedro Paulo Lordelo Guimarães , de Souza Carolina Oliveira , Umsza-Guez Marcelo Andrés
Published: April 2023

Background

Wine lees are defined as the residue formed at the bottom of the container during the wine fermentation stage. It consists of a solid phase composed of yeasts and bacteria responsible for vinification. In general, wine lees, despite being a material rich in polyphenols, are underused or discarded. In this context, the aim of this review is to present an overview of the use of wine lees in the food industry and other sectors, by means of scientific and technological surveys.

Methodology

Bibliographical searches of the main works published on wine lees or grapes were carried out in articles selected in the Scopus and SciELO databases, while the search for the technology protected or described in patent documents involving wine lees and their main applications was carried out through the Espacenet online database combined with the private platform from Questel company: Orbit®.

Main text

Wine lees represent an important fraction of winemaking by-products and contain several high-value components with potential to be exploited in industrial sectors, such as phenolic compounds. Through the Technological Prospection, it was demonstrated that wine lees are still poorly studied, with few patents filed on the technological/nutritional properties of wine lees. In 2016, there was a peak of patent filing growth and China was the country with the highest number of patents, totaling 31 deposits. Regarding the area of application, agriculture was the most common, followed by beverage production. Most of the inventors are of Asian origin, corroborating the results previously discussed regarding the distribution of patents per country, and this might probably be related to the high investment of these countries in various stages of education and technological research.

Conclusion

The study suggests that different applications should aim at developing an integrated approach aimed at extracting from wine lees the highest number and quantities of compounds with possible applications in different sectors.

Graphical Abstract
Aortic stenosis: a review on acquired pathogenesis and ominous combination with diabetes mellitus
Authors: Wal Pranay , Rathore Shruti , Aziz Namra , Singh Yash Kumar , Gupta Arpit
Published: April 2023

Background

Aortic stenosis (AS) is a progressive disease, with no pharmacological treatment. The prevalence of diabetes mellitus (DM) among AS patients is higher than in the general population. DM significantly increases the risk of AS development and progression from mild to severe. The interplay between AS and DM's mechanism is not entirely known yet.

Main Body

The increased accumulation of advanced glycation end products (AGEs) was linked to increased valvular oxidative stress, inflammation, expression of coagulation factors, and signs of calcification, according to an analysis of aortic stenotic valves. It is interesting to note that in diabetic AS patients, valvular inflammation did not correlate with serum glucose levels but rather only with long-term glycemic management markers like glycated haemoglobin and fructosamine. Transcatheter aortic valve replacement, which has been shown to be safer than surgical aortic valve replacement, is advantageous for AS patients who also have concurrent diabetes. Additionally, novel anti-diabetic medications have been proposed to lower the risk of AS development in DM patients, including sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonist that target reduction of AGEs-mediated oxidative stress.

Conclusions

There are little data on the effects of hyperglycemia on valvular calcification, but understanding the interactions between them is essential to develop a successful treatment strategy to stop or at least slow the progression of AS in DM patients. There is a link among AS and DM and that DM negatively impacts the quality of life and longevity of AS patients. The sole successful treatment, despite ongoing efforts to find new therapeutic modalities, involves aortic valve replacement. More research is required to find methods that can slow the advancement of these conditions, enhancing the prognosis and course of people with AS and DM.

Graphical Abstract
Recent advances in therapeutic CRISPR-Cas9 genome editing: mechanisms and applications
Authors: Zhou Lifang , Yao Shaohua
Published: April 2023

Recently, clustered regularly interspaced palindromic repeats (CRISPR)-Cas9 derived editing tools had significantly improved our ability to make desired changes in the genome. Wild-type Cas9 protein recognizes the target genomic loci and induced local double strand breaks (DSBs) in the guidance of small RNA molecule. In mammalian cells, the DSBs are mainly repaired by endogenous non-homologous end joining (NHEJ) pathway, which is error prone and results in the formation of indels. The indels can be harnessed to interrupt gene coding sequences or regulation elements. The DSBs can also be fixed by homology directed repair (HDR) pathway to introduce desired changes, such as base substitution and fragment insertion, when proper donor templates are provided, albeit in a less efficient manner. Besides making DSBs, Cas9 protein can be mutated to serve as a DNA binding platform to recruit functional modulators to the target loci, performing local transcriptional regulation, epigenetic remolding, base editing or prime editing. These Cas9 derived editing tools, especially base editors and prime editors, can introduce precise changes into the target loci at a single-base resolution and in an efficient and irreversible manner. Such features make these editing tools very promising for therapeutic applications. This review focuses on the evolution and mechanisms of CRISPR-Cas9 derived editing tools and their applications in the field of gene therapy.
Tumor-Naïve Circulating Tumor DNA as an Early Response Biomarker for Patients Treated With Immunotherapy in Early Phase Clinical Trials
Authors: Sanz-Garcia Enrique , Genta Sofia , Chen Xiaoxi , Ou Qiuxiang , Araujo Daniel V. , Abdul Razak Albiruni R. , Hansen Aaron R. , Spreafico Anna , Bao Hua , Wu Xue , Siu Lillian L. , Bedard Philippe L.
Published: April 2023

PURPOSE

To evaluate early circulating tumor DNA (ctDNA) kinetics using a tumor-naïve assay and correlate it with clinical outcomes in early phase immunotherapy (IO) trials.

METHODS

Plasma samples were analyzed using a 425-gene next-generation sequencing panel at baseline and before cycle 2 (3-4 weeks) in patients with advanced solid tumors treated with investigational IO agents. Variant allele frequency (VAF) for mutations in each gene, mean VAF (mVAF) from all mutations, and change in mVAF between both time points were calculated. Hyperprogression (HyperPD) was measured using Matos and Caramella criteria.

RESULTS

A total of 162 plasma samples were collected from 81 patients with 27 different tumor types. Patients were treated in 37 different IO phase I/II trials, 72% of which involved a PD-1/PD-L1 inhibitor. ctDNA was detected in 122 plasma samples (75.3%). A decrease in mVAF from baseline to precycle 2 was observed in 24 patients (37.5%) and was associated with longer progression-free survival (hazard ratio [HR], 0.43; 95% CI, 0.24 to 0.77; P < .01) and overall survival (HR, 0.54; 95% CI, 0.3 to 0.96; P = .03) compared with an increase. These differences were more marked if there was a >50% decrease in mVAF for both progression-free survival (HR, 0.29; 95% CI, 0.13 to 0.62; P < .001) and overall survival (HR, 0.23; 95% CI, 0.09 to 0.6; P = .001). No differences in mVAF changes were observed between the HyperPD and progressive disease patients.

CONCLUSION

A decrease in ctDNA within 4 weeks of treatment was associated with treatment outcomes in patients in early phase IO trials. Tumor-naïve ctDNA assays may be useful for identifying early treatment benefits in phase I/II IO trials.
bakR: uncovering differential RNA synthesis and degradation kinetics transcriptome-wide with Bayesian hierarchical modeling
Authors: Vock Isaac W. , Simon Matthew D.
Published: April 2023

Differential expression analysis of RNA sequencing (RNA-seq) data can identify changes in cellular RNA levels, but provides limited information about the kinetic mechanisms underlying such changes. Nucleotide recoding RNA-seq methods (NR-seq; e.g., TimeLapse-seq, SLAM-seq, etc.) address this shortcoming and are widely used approaches to identify changes in RNA synthesis and degradation kinetics. While advanced statistical models implemented in user-friendly software (e.g., DESeq2) have ensured the statistical rigor of differential expression analyses, no such tools that facilitate differential kinetic analysis with NR-seq exist. Here, we report the development of Bayesian analysis of the kinetics of RNA (bakR;https:// github.com/simonlabcode/bakR), an R package to address this need. bakR relies on Bayesian hierarchical modeling of NR-seq data to increase statistical power by sharing information across transcripts. Analyses of simulated data confirmed that bakR implementations of the hierarchical model outperform attempts to analyze differential kinetics with existing models. bakR also uncovers biological signals in real NR-seq data sets and provides improved analyses of existing data sets. This work establishes bakR as an important tool for identifying differential RNA synthesis and degradation kinetics.
THE INTERMEDIATE SPACE
Authors: Kangelaris Fotis
Published: April 2023

Starting from the question of why things have a form, we develop the concept of the “Intermediate Space” as a procedure during which the “thing” assumes its form as a word or as a picture. However, this intermediate space can constitute itself its final form.Looking into, in the first place, the concept of the “Intermediate Space” as a basic structural function of psychopathology, we focus, later, on three examples on which we base our aspect.The Garden as the “Intermediate Space” of the countryside-city/nature-civilisation, unconscious-conscious.The Architecture as the “Intermediate Space” between matter and spirit as for its agony to be art. In this unit, after the initial observations, there is a focus on the concepts of “rurbain” and the “ladder”.“Non finito” in art where the route of the “thing” to its form as art crystallizes before its final shaping. Towards this, we look into different appearances of art and we expand on relevant philosophical comments.In the final part of our study, we attempt through questions an elevation of the human's life to a “Non finito” work. The “thing”, as far as this study is concerned, has to be heard in the concept of the lacanian topology and the freudian “Das Ding”.
ERT 2013
Authors: Vardopoulos Panos
Published: April 2023

In June 2013, the memorandum Greek government decided to shut down the public radio and television broadcaster, ERT. This is a photographic documentary of the anti-government protests in the courtyard of ERT headquarters, during the occupation of the premises by the majority of employees, trying to keep the voice of public broadcaster alive.
NON-DESTRUCTIVE INVESTIGATION OF PAINTINGS ON DIFFERENT SUBSTRATES. METHODOLOGY, ACHIEVEMENTS AND LIMITATIONS.
Authors: Kaminari Agathi , Banou Penelope , Moutsatsou Anna , Alexopoulou Athena
Published: April 2023

Today, non-destructive testing includes diagnostic methods that provide significant information for art historians, conservators and researchers. The quick in situ application, the absence of expensive consumables, the inspection of entire surfaces and the ability for mapping make these methods attractive to users. Additionally, they provide the advantage of examining large areas of work of art, supporting a multidisciplinary approach, documentation, analysis and protection of visual arts’ works. The case studies presented here involve the application of methodology on paintings on wood, canvas and paper substrate, while the constraints and particular requirements that different structures and special conditions dictate are discussed. Through these case studies the authors intend to highlight that the application of modern non-destructive methods offer many possibilities to the end user, making feasible the revelation of the painting technique, the characterization of the materials and supporting the decision making for conservation.
THE CHALLENGE OF THE EMERGENCY REMOTE TEACHING IN THE EDUCATION OF ART CONSERVATORS. EXPERIENCES AND REFLECTIONS
Authors: Alexopoulou Athena
Published: April 2023

COVID-19 pandemic and the measures to constrain it have influenced, among others, every dimension of the cultural heritage; from research, conservation and preservation projects to training and education. The closure of training buildings and campuses, the cancellation of face-to-face classes and labs and other learning experiences forced a shift to emergency remote teaching. Especially, for art conservators education, as the field of heritage conservation is powered by art history, technology and science, any deceleration has an important impact on it.  Moreover, conservators have to be in contact with the real object, to be present physically in the archaeological sites, to interact with the material of the monuments and traditionally they work very close to them.  The closure of the education domain deprived conservation students from the physical contact with the objects, but had fostered the digital transformation of the heritage sector, as well as the academic conservation education. The goal of this paper is to discuss advantages and weaknesses of emergency remote teaching comparing to face-to-face teaching and online teaching too, as well as to record the experience of the remote teaching in the Department of Conservation of Antiquities and Artworks and the opportunities emerged for the curricula of the Department.
PIRAEUS: A NEW CITY FOUNDED AT THE DAWN OF THE 19TH CENTURY, AROUND THE BIRTH OF THE GREEK STATE
Authors: Moira Maria
Published: April 2023

Book review of Nikos Belavilas, History of the City of Piraeus. 19th and 20th century (in Greek), Alexandria Publications, Athens 2021, 599 pages.Piraeus is a charming seaside city, bustling and vibrant, filled with contradictions; a Mediterranean seaport of regional importance, with geophysical singularities and an extensive lace-like coastline; a major cultural and social urban hub of national importance, which played an instrumental role in the industrialization and economic growth of Greece. Piraeus was a newly-founded city that was designed and situated by the sea, in order to serve the maritime transportations of the newly established state. Piraeus developed around the core of the deep bay formed by the Piraeus peninsula, on the site of the ruined ancient settlement and around the humble medieval port facilities, which framed this natural anchorage, in a location that would offer the new Athenian capital the necessary sea link and the infrastructure required for the development of its maritime and commercial activities.In this thoroughly engaging book, both in terms of methodological composition but also as a reading experience, Nikos Belavilas retrieves from an interdisciplinary domain and offers the main axes along which the narrative evolves: the city, the port and the industry. Around them revolves the history of the rapid strategic residential development of Piraeus.
REPRESENTING THE PAST THROUGH THE MAGIC OF MINIATURES
Authors: Mențeanu Andrei
Published: April 2023

The visual magic of the miniature world allows the depiction of the past using a combination of advanced contemporary, as well as classical technologies. For the viewer to be transported back in time, the miniature must be a hyper-realistic representation that acts on the viewer's memory and imagination. A miniature, appreciable in size, in which the scenes turn out to be drawn from the reality of the past, constitutes an extremely effective method of actualizing a tragic episode of history. And since miniatures can transform reality into art, they are, simultaneously, artistic compositions.
SENSING THE PAST: AN EXPLORATION OF ART AND ARCHAEOLOGY
Authors: Poraj-Wilczynska Elizabeth
Published: April 2023

This portfolio deals with the work I have been undertaking for the past 20 years. Investigating sense of place at Belas Knap Neolithic long barrow, Cotswolds, England. I have taken an holistic approach in the creation of art that aims to bridge the sensory experience of archaeology, memory and culture. Over the last twenty years I have been responding through my art to place and memory, mapping, interpreting and connecting to the seasonal changes at Belas Knap, a laterally chambered Neolithic long barrow located in the Cotswold Hills, Gloucestershire, South West England (NGR: SP0209 2554).
FROM CAMERA AS PART OF THE BODY, TO CAMERA – THE BODY PART
Authors: Dimitrijevič Danica
Published: April 2023

The digital world is where 3.4 billion people communicate via digital images through social media. On average, each one of us spends 6 hours each day in front of a screen. The digital images rapidly appearing and disappearing under our scrolling fingers shape our perception, time and body movements, brain structure, and responses in a complex neurological way. The camera enables the formation of our identity, social development, aesthetic value, and cultural participation. Without this camera image, one is isolated, unable to speak. Moreover, without storage where we save images, we are exempt from personal history, narratives, and memory. Once we integrated a camera into the smartphone, we produced an extra organ. With the Orion visual cortical prosthesis medical study that implants a camera into the eyes to restore vision, face emotional surveillance project VibeCheck, and BeAnotherLab software, swooping through virtual reality the bodies, this article follows the socio-philosophical and technological shifts through the history of the camera and photography in object production, body perception, their definition, interaction, and final merge between body and camera object. Through the reference of the theoretical works of Roland Barthes, Maurice Merleau-Ponty, Karen Barad and Tim Ingold, the article follows how we have produced camera images through time and how camera images have been producing us. The camera transforms from a separate room or device to a prosthetic/inherent part of the body, without which the body is not fully functional. Today, a person without a phone camera is marginalized and handicapped. The deficit of not having an image-generating tool turns out to be a sensual deprivation, social limitation and discrepancy in identity.
BEAUTY IS…
Authors: Lasithiotaki Nina
Published: April 2023

Walter Benjamin aptly describes the dual role of photography, since its invention, saying that “photography stakes a claim to art as soon as it appears as a commodity”. Although fashion has become the subject of significant philosophical and sociological study over the past 150 years, it continues to be a taboo, or merely too lowly a subject for academic consideration – even in modern–day cultural studies. The reason is clear: fashion does not pose an argument; it entices and seduces, constantly looking for a new aesthetic paradigm that will embody the eternal polytheism of Beauty. Photographer Julia Hetta adopts many of the tools and practices of classical painting to capture the paradox and ambiguity of the concept of Beauty, which Victor Hugo likens to Death, noting that: “Death and beauty are two things profound, so of dark and azure, that one might say that they were two sisters terrible and fecund, possessing the one enigma, the one secret.” Hetta illustrates the dualism of the modernist subject with appeals to the imaginary of an insurmountable innocence and purity, as this is captured in depictions of the classical ideal; and precisely therein lies the originality of her gaze. She develops a personal style in photography, featuring strong elements of drama and theatrics. She illustrates the current, the innovative, the radical in the field of human presence and clothing, recalling the cultural deposits of times past, but also imbuing her creations with new rules that detect a subjective and complex beauty.