Myelodysplastic syndromes (MDS) are diseases that occur when blood-producing cells in the bone marrow are damaged; such damage can affect one or more types of blood cells. Common types of MDS are refractory anemia with ring sideroblasts and refractory anemia with excess blasts (MDS-RS and MDS-EB, respectively). This work analyzed the proteomics of the medullary plasma of 10 patients with MDS-RS and MDS-EB compared to healthy control people. Overexpressed proteins that may be potential candidates for biological markers for the evaluation, study, and diagnosis of these diseases have been identified. These samples were subjected to immunodepleting, concentrated, and digested for further analysis by mass spectrometry. The ratios between selected groups and healthy people were calculated. Seven overexpressed proteins in both syndromes were identified as potential biomarker candidates: vitronectin (VTN), (2) fibrinogen (FGA), (3) pregnancy zone protein (PZP), (4) kininogen (KNG1), (5) immunoglobulin lambda chain (IGLL1), (6) complement factor C4b, and (7) hemopexin (HPX). A modified affinity chromatographic column with lectin frutalin (FTL) was used for non-depleted samples. Immunoglobulin M (IgM) was expressed in the samples from both syndromes. Surprisingly, IgM from patients with syndromes was over retained on the frutalin (FTL) column when compared with the control group. We further hypothesized that over retention of this protein by the FTL is due to the presence of α-galactosidic residues in the IgM of MDS-RS and MDS-EB patients. Differential recognition of proteins on non-depleted samples from the use of FTL appears to be a powerful tool for proteomic analysis.

Failaka Island is located 20 kilometers east of the Kuwait mainland. The island includes archaeological sites dating back to the Bronze, Hellenistic, Christian, and Islamic ages. To develop the island as a tourist attraction the state is pursuing a new urban plan based on the island's environmental potential. This study is the basis of the urban plan depends on environmental criteria from the view of Geoarchaeology. The study analysis the land-use and land-cover changes of Failaka Island between 1958- 2018. It provides a topographic survey of the island's coastline and a classification of its geomorphological features and a state of the art identification of its archaeological sites by using a drone to make a terrain model. The study used a medium to high-resolution image analysis of the land-use and land-cover changes: WorldView2-50cm 2010 and 2018; Landsat 8; aerial photography; Drone images and a digital elevation model (DEM), to analysis the expected sea level changes by the end of this century. This study also created a geodatabase of the island that can be adapted for future studies. The results emphasize the importance of preserving the historical and ecological features of the island while developing its infrastructure.

Objectives: Metabolic interactions amongst mutated genes in myelodysplastic syndrome (MDS) offer promising avenues for novel anticancer treatments. Our comprehensive study delves into these mutational and transcriptomic landscapes, pinpointing hallmark gene mutations and deregulated gene expression that could influence MDS patients’ metabolomes. Methods: The study utilized a retrospective, cross-sectional approach, employing mutational data on the cBio Cancer Genomics Portal conducted and reported by the University of Tokyo in 2011 and multi-center MDS cohorts regulated by Wellcome Trust Sanger Institute, United Kingdom, all in 2020. For transcriptomic data, we selected three publicly accessible independent cohorts on the Gene Expression Omnibus (GEO) database (GSE114922 in Wellcome Trust Centre for Human Genetics, United Kingdome, GSE63569 in University of Oxford, United Kingdome, and GSE183328 in CIMA, Spain) held in 2015, 2018, and 2022, respectively. To compile clinical, mutational, and transcriptomic data on MDS patients from multiple datasets and studies. This meta-analysis included genomic data derived from cellular genomics sources to assess mutations in specific genes, alongside an examination of transcriptomic data from three separate datasets that have been previously published. Results: DNMT3A presented a 20% mutation frequency, playing a pivotal role in MDS metabolomics. The DNMT3A gene mutations displayed significant mutual exclusivity with the SRSF2, ASXL1, JAK2, and TP53 genes. The mutational analysis also showed that the gene expression landscape in MDS is associated with alterations to DNA methylation pathways. Conclusion: This analysis suggests a potential therapeutic niche. Identifying signature genes in MDS that have metabolic and methylation affiliations could illuminate the disease's intricate biology and inspire novel treatments.

(1) Background: Myelodysplastic syndromes (MDS) are a group of diseases that affect the morphology and function of neutrophils. Rapid diagnosis of MDS is crucial for the initiation of treatment that can vastly improve disease outcome. (2) methods: In this work, we present a new approach for detecting morphological differences between neutrophils isolated from blood samples of high risk MDS patients and that for patients and blood bank donors (BBDs). First, using fluorescent flow cytometry CD66b positive cells were stained with 2′,7′-dichlorofluorescin diacetate (DCF) and Hoechst. Secondly, we imaged the cells using interferometric phase microscopy (IPM) without utilizing cell staining. (3) Results: flow cytometry results show MDS patients present different dispersion patterns compared to BBDs. BBDs present two distinct subpopulations (one of these are the H cells constituting 16% for neutrophils) whereas MDS patients present only 4% of this subpopulation. IPM results are consistent with this pattern: ~20% of BBDs neutrophils were characterized as H cells and whereas MDS patients present only ~4% of these cells. (5) Conclusion- IPM can be utilized for diagnosis of complex hematological pathologies such as MDS.

Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) originate from preleukemic hematopoietic conditions, such as clonal hematopoiesis of indeterminate potential (CHIP) or clonal cytopenia of undetermined significance (CCUS) and have desolate outcomes. The prognosis is worse in patients with TP53 mutations which are often linked to complex karyotypes and contribute to worse responses to induction therapy, demethylating agents or venetoclax-based treatments. Survival of patients with TP53 gene mutations is often less than one year. Therefore, TP53-mutated MDS and AML are now classified separately in the unfavorable risk category. In the clinical setting, the wild-type p53 is reactivated pharmacologically by targeting p53/MDM2/MDM4 interactions and mutant p53 reactivation is achieved by refolding the DNA binding domain to wild-type-like conformation or via targeted degradation of the mutated protein. This review discusses our current understanding of p53 biology in MDS and AML and the promises and failures of p53 reactivation in the clinical trial setting.

Flash flooding is one of the most devastating natural events that leads to enormous and recurring loss of life. Kuwait was subjected to severe rainstorms in the winter of 2018 and 2020 followed by an extreme violent flood that had not been known in Kuwait since 1976. It resulted in several geomorphological and environmental impacts in urban and desert areas. This produced some positive results, such as geomorphological activity in landforms, the flow of some valleys and the prosperity of wildlife in the Kuwaiti desert. Negative results included some problems in the metropolitan area and destruction of some road networks that intersect the main valleys, and which were not equipped with crossings for avoiding floods. There was also the emergence of some problems in the infrastructure. Study of flash floods requires the involvement of all scientific and executive bodies to avoid environmental risk. The study aims to: 1- Monitor geomorphological and environmental changes. 2- Assess the impact of floods in the urban areas and on infrastructure. 3- Modeling the impact. 4- Creating solutions and adaptions to the flash flood. The study uses several methods such as remote sensing (RS), geographic information systems (GIS), hydrologic modeling and fieldwork to evaluate the impact of flash flood hazards on the sustainable urban development of Kuwait state. This approach is rarely used in Kuwait. We propose a novel method that could help decision-makers and planners in determining inundated flood zones before planning future urban developments in Kuwait, and help them to manage flood water, by identifying the most appropriate places for storage to exploit water in agriculture and drinking.

Recent years witnessed progressive broadening of the practical use of 3D-printed aluminium alloy parts, in particular for specific aerospace applications where weight saving is of great importance. Selective laser melting (SLM) is an intrinsically multi-parametric fabrication technology that offers multiple means of controlling mechanical properties (elastic moduli, yield strength, ductility) through the control over grains size, shape, and orientation. Ultimately, this approach implies that structural elements can be purposefully fabricated to reinforce specific zones and directions where higher mechanical loads are anticipated by design. Targeted control over mechanical properties is achieved through the tuning of 3D-printing parameters and may even obviate the need of heat treatment or mechanical post-processing. Systematic studies of grain structure for different printing orientation with the help of EBSD techniques in combination with mechanical testing at different dimensional levels are the necessary first steps to implement this agenda. Samples of 3D-printable Al-Mg-Si RS-333 alloy were fabricated in 3 orientations with respect to the principal build direction and the fast laser beam scanning direction. Sample structure and proper-ties were investigated using a number of techniques, including EBSD, in situ SEM tensile testing, roughness measurements and nanoindentation. The as-printed samples we found to display strong variation in Young’s modulus values from nanoindentation (from 43 to 66 GPa) and tensile tests (from 54 to 75 GPa), yield stress and ultimate tensile strength (100…195 and 130…220 MPa) in different printing orientations, and almost constant hardness of about 0.8 GPa. A further preliminary study was conducted of the effect of surface finishing on the mechanical performance. Surface polishing appears to reduce Young’s modulus and yield strength, but improves ductility, whereas the influence of sand blasting is more controversial. The experimental results are dis-cussed in connection with the grain morphology and orientation.

Choosing the optimal location for a city based on sound environmental geomorphology planning is of the utmost importance to achieving environmental sustainability, as it can spare the State and other decision-making entities a great deal of stress in the long run. GIS offers great potential for environmental planners to choose the most appropriate places for the cities of the future, especially when coupled with environmental geomorphological analyses. The State of Kuwait seeks sustainable development through the implementation of clear and specific urban plans, some of which suffer from a severe lack of geomorphological and spatially based environmental planning. This study aims to: 1) Conduct suitability modelling for establishing new cities in Kuwait, 2) Assess the current 2005-2030 urban plan, and 3) Propose possible recommendations and solutions for potential urban problems. The study relies on integrating several methods to devise a framework that will aid researchers and decision-makers in selecting optimal locations for built structures based on analysis and modelling (e.g., digital elevation model, geologic mapping, geomorphology, natural hazards, heritage/archaeological sites, military areas, oil fields, soils). Using this methodology in choosing city sites contributes to achieving sustainable development, reducing city problems, saving countries’ budgets, and saving lives. Results from this study enhance understanding of how environmental geomorphology, when combined with GIS, can be harnessed to achieve sustainable urban development in the Arabian Gulf countries and other desert countries.

The State of Kuwait seeks sustainable development through implementation of clear and specific urban plans, some of which suffer from a severe lack of geomorphological and spatially-based environmental planning, such as the use of geographic information systems (GIS). Choosing the optimal location for a city based on sound environmental planning is of the utmost importance to achieving environmental sustainability, as it can spare the State and other decision-making entities a great deal of stress in the long run. GIS, in particular, offers great potential for the environmental planner and decision-maker to choose the most appropriate places for the cities of the future, especially when coupled with geomorphological analyses. To achieve the Vision of Kuwait 2035, one of the State’s planning objectives focuses on Urban Planning for the Establishment of Environmental Cities that Achieve (UPEECA) environmental sustainability criteria. To gain a more holistic analysis related to the Vision, this study aims to: 1) Conduct suitability modelling for establishing new cities in Kuwait, 2) Assess the current 2005-2030 urban plan, and 3) Propose possible recommendations and solutions for potential urban problems. The study relies on integrating several methods to devise a framework that will aid researchers and decision-makers in selecting optimal locations for built structures based on analysis and modelling (e.g., digital elevation model, geologic mapping, geomorphology, natural hazards, heritage/archaeological sites, military areas, oil fields, soils)

This is study follows environmental diversity assessment for geotourism development in Asir region. Geotourism seeks to supporting the tourism landscape in its interaction with the historical and archaeological, architectural or immaterial heritage, and requires diversification in terms of product, market and geographical potential. The study is based on various tourist facades and environmental diversity in Asir. As tourism development is a comprehensive undertaking involving many sectors, and these are the challenges to which the country’s tourism industry should respond to promote domestic tourism. quality and spatial pattern of tourism resources, climate comfort, and natural disaster possibility. Based on analyze multi-source datasets collected, geomorphological features of this area, we created a GIS database comprising geologic and topographic maps, and satellite images using these datasets. The findings of the study provided valuable insights into the role of environmental diversity in achieving tourism. The study examined the interrelationship between tourism and environmental diversity.

In the last three decades the presence of phospholipids in the nucleus has been shown and thoroughly investigated. A great interest raised about nuclear inositol lipids mainly because of their role in signalling acting. Here we review the main issues of nuclear phospholipid localization and the role of nuclear inositol lipids and their related enzymes in cellular signaling both in physiological and pathological conditions.

Myelodysplastic neoplasm (MDS) is a heterogenous clonal disorder of hemopoietic stem cells charac-terized by cytomorphologic dysplasia, ineffective hematopoiesis, peripheral cytopenias and risk of pro-gression to Acute Myeloid Leukemia (AML). Our understanding of this disease has continued to evolve over the last century. More recently prognostication and treatment are determined by cytogenetic and molecular data. Specific genetic abnormalities such as 5q deletion (del 5q), TP53 inactivation and SF3B1 mutation, are increasingly associated with disease phenotype and outcomes, as reflected in the recently updated 5th edition of the World Health Organization Classification of Hematolymphoid Tumors (WHO5) and International Consensus Classification 2022 (ICC 2022) classifications. Treatments are in-creasingly being tailored for patient specific phenotypes, and trials exploring the efficacy of targeted treatments are ongoing in this era of precision medicine.

Due to the proliferation of genetic testing, pathogenic germline variants predisposing to hereditary hematological malignancy syndrome (HHMS) have been identified in an increasing number of genes. Consequently, the field of HHMS is gaining recognition among clinicians and scientists worldwide. Patients with germline genetic abnormalities often have poor outcomes and are candidates for allogeneic hematopoietic stem cell transplantation (HSCT). However, HSCT using blood from a related donor should be carefully considered because of the risk that the patient may inherit a pathogenic variant. At present, we now face the challenge of incorporating these advances into clinical practice for patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) and optimizing the management and surveillance of patients and asymptomatic carriers, with the limitation that evidence-based guidelines are often inadequate. The 2016 revision of the WHO classification added a new section on myeloid malignant neoplasms, including MDS and AML with germline predisposition. The main syndromes can be classified into three groups. Those without pre-existing disease or organ dysfunction; DDX41, TP53, CEBPA, those with pre-existing platelet disorders; ANKRD26, ETV6, RUNX1, and those with other organ dysfunctions; SAMD9/SAMD9L, GATA2, and inherited bone marrow failure syndromes. In this review, we will outline the role of the genes involved in HHMS in order to clarify our understanding of HHMS.

Purpose: Myelodysplastic syndromes (MDS) are caused by a stem cell failure, but the relationship between immune dysregulation and the course of disease has not yet been analyzed in detail. Experimental design: To get insights into the pathophysiologic and clinical relevance of the histotopography of immune cell subpopulations in this process, the immune cell infiltrate with focus on its spatial distribution was determined by multispectral imaging (MSI) in 147 bone marrow biopsies from MDS or secondary acute myeloid leukemia (sAML) patients and healthy controls (HC). In addition, the data were correlated to genetic alterations and clinical features of these patients including therapy response. Results: A high inter-tumoral heterogeneity in the frequency and spatial distribution of CD3⁺CD8⁺, CD3⁺CD8^-, CD3⁺FOXP3⁺ T cell subsets, MUM1p⁺CD3^- post-germinal B/plasma cells and CD34⁺ blasts was found in MDS and sAML samples. In HC only few B cells/plasma cells, but no T cell subpopulations were detected in the proximity to CD34⁺ blasts. In contrast, the frequency of these lymphocytes was increased in proximity to CD34⁺ blasts in both MDS and sAML independent of the karyotype, genetic alterations frequently detected in MDS, clinical risk stratification systems or treatment response to hypomethylating agents. Furthermore, an increased frequency of CD3⁺CD8⁺ T cells and MUM1p⁺ CD3^- B cells was found in responders to epigenetic drugs. Conclusions: Thus, we conclude that (i) T cell subsets do not belong to the normal stem cell niche, (ii) the presence of T and B cell subpopulations not directly affect the course of MDS, (iii) lymphocytes in the proximity to CD34⁺ blasts might indicate defective stem cell properties and (iv) the number of lymphocytes is a predictor of therapy response to hypomethylating agents.

Accurate estimations of actual evapotranspiration (ETa) are fundamental for various environmental issues. Artificial Intelligence-based models are considered a promising alternative to the most common direct ETa estimation techniques and indirect methods by remote sensing (RS)-based surface energy balance models. Artificial Neural Networks (ANN) are proven to be suitable for predicting reference evapotranspiration and ETa based on RS data. The aim of this study is to develop a methodology based on ANNs for estimating daily ETa values using NDVI and land surface temperature, coupled with limited site-specific climatic variables at a large irrigation catchment. Two scenarios were implemented by the ANN model. Data from only the 38 days of satellite overpass dates was selected in Scenario-I, while the 769-day data included the satellite overpass dates and other days located between two satellite overpass acquisitions in Scenario-II. An irrigation scheme in the Mediterranean region of Turkiye was selected, and a total of 38 Landsat images, and local climatic data were used in 2021 and 2022. Results showed that R2 values in Scenario-I and II were acknowledgeably high for training (0.79 and 0.86), testing (0.75 and 0.81), and the entire dataset (0.76 and 0.84), respectively. Results of the new model in two scenarios showed acceptable agreement with ETa-METRIC values. The proposed ANN model demonstrated the potential of obtaining daily ETa using limited climatic data and RS imagery.

This study focused on the impact of the treatment with the hypomethylating agent 5-Azacitidine on the redox status and inflammation in 24 MDS patients. Clinical and genetic features of MDS patients were recorded and peripheral blood samples were used to determine the activity of the endogenous antioxidant defense system (superoxide dismutase, SOD, catalase, CAT, glutathion peroxidase, GPx, and reductase, GRd, activities), markers of oxidative damage (lipid peroxidation, LPO, and advanced oxidation protein products, AOPP). Moreover, pro-inflammatory cytokines and plasma nitrite plus nitrate levels as markers of inflammation, and CoQ10 plasma levels, were also measured. Globally, MDS patients showed less redox status in terms of a reduction in the GSSG/GSH ratio and in the LPO levels, and increased CAT activity compared with healthy subjects, with not changes in SOD, GPx and GRd activities, and AOPP levels. When analyzed the evolution from early- to advanced stages of the disease, the GPx activity, GSSG/GSH ratio, LPO and AOPP increased, with a reduction in CAT. GPx changes were related with the presence of risk factors such as high-risk IPSS-R or mutational score. Besides, there was an increase in IL-2, IL-6, IL-8 and TNF-α plasma levels, with further increase of IL-2 and IL-10 from early to advanced stage of the disease. However, we did not observe any association between inflammation and oxidative stress. Finally, 5-azacitidine treatment generates oxidative stress in MDS patients, without affecting inflammation levels, suggesting that oxidative status and inflammation are two independent processes.

Researchers need to delineate the shoreline for different applications with no access to costly resources such as topographic maps and high-resolution satellite images. With the increase of open source data, this study aims to present a methodology to use open source data in the best possible way to map the shoreline. Several methods have been tested using open source remote sensing data (Landsat and Aster), such as supervised classification, unsupervised classification, manual mapping, and by applying some spectral indices, among others. The accuracy of the extracted shoreline data was verified using high-resolution open database images (such as Google Earth basemap). The results showed that the manually mapped shoreline through applying spectral index (green- near infrared/green+ near infrared) is the most accurate, although it remains important to modify it using high-resolution images of open databases. Open-source data showed acceptable accuracy in mapping the shoreline.

Etiological factors involved in myelodysplastic syndrome (MDS) include immunologic, oxidative stress, and inflammatory factors, among others, and these are targets for microRNAs (miRNs). Here, we evaluated whether some miRNs may affect the tumor development comparing untreated and 5-azacitidine (5-AZA) MDS-treated patients. Peripheral blood samples were collected from 20 controls and 24 MDS patients, and selected miRNs related to redox balance and inflammation, including miR-18a, miR-21, miR-34a and miR-146a, were isolated and measured by quantitative real-time polymerase chain reaction (qRTPCR). A differential expression profile of miRNs was detected in untreated MDS patients and 5-AZA group. MiR-18a, miR-21, miR-34a and miR-146a were significantly overexpressed in untreated MDS, compared to controls. However, we did not observe any miRNs profile alteration during the progression of the disease. On the other hand, 5-AZA treatment tends to restore miRNs expression levels. Relating to prognostic risk factors, high risk MDS groups (high IPSS-R, high cytogenetic risk, high molecular risk (HMR) mutations tended to be related with higher expression levels of miR-18a and miR-34a. Higher miRNs expression is correlated with lower glutathione peroxidase activity, while they are related with a higher profile of pro-inflammatory cytokines (IL-2, IL-6, IL-8, TNF-α). Although our study was limited by the low number of MDS patients included, we identified miRNs deregulation involved in the MDS development, that could regulate redox sensors and inflammatory responses. Finally, 5-AZA treatment is related with lower miRNs expression levels in MDS patients.

Secondary acute myeloid leukemia (sAML) is a heterogeneous malignant hematopoietic disease that arises either from an antecedent hematologic disorder (AHD) including myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), aplastic anemia (AA), or as a result of exposure to genotoxic chemotherapeutic agents or radiotherapy (therapy related AML, tAML). sAML is diagnosed when the number of blasts is ≥20% in the bone marrow or peripheral blood, and it is characterized by poor prognosis, resistance to therapy and low overall survival rate. With the recent advances in next generation sequencing technologies, our understanding of the molecular events associated with sAML evolution has significantly increased and opened new perspectives for the development of novel therapies. The genetic aberrations that are associated with sAML affect genes involved in processes such as splicing, chromatin modification and genome integrity. Moreover, non-coding RNAs’ emerged as an important contributing factor to leukemogenesis. For decades, the standard treatment for secondary AML has been the 7 + 3 regimen of cytarabine and daunorubicin which prolongs survival for several months, but modifications in either dosage or delivery has significantly extended that time. Apart from traditional chemotherapy, hematopoietic stem cell transplantation, CAR-T cell therapy and small molecule inhibitors have also emerged to treat sAML.

Myelodysplastic syndromes and myeloproliferative neoplasms both represent hematologic diseases associated with bone marrow failure often resulting in anemia. For those patients, transfusion of red blood cell (RBC) units is essential, but results in iron overload (IOL) that may affect various organ functions. Therefore, iron chelation therapy plays a major role in anemic patients, not only because it reduces IOL, but also because it may improve hematopoietic function by increasing hemoglobin or diminishing requirement of RBC transfusions. To assess the utility, efficacy and safety of the different iron chelation medication approved in Germany as well as to examine the effect of chelation on hematopoietic insufficiency, a prospective, multicenter, non-interventional study named EXCALIBUR was designed. In total, 502 patients from 106 German hospitals and medical practices were enrolled. A large proportion of patients switched from deferasirox dispersible tablet to deferasirox film-coated tablet, mainly due to more convenient application which was reflected in the treatment satisfaction questionnaire for medication scores. Iron chelation was effective in lowering serum ferritin levels, with the observed adverse drug reactions being in line with the known safety profile. Hematologic response occurred in a few patients, comparable to other studies that examined hematologic improvement in patients with MDS.

This study explores the Edaravone solubility space encompassing both neat and binary dissolution media. The efforts were made toward revealing the concentration limits inherently associated with common pure and mixed solvents. For this purpose, the published solubility data of the title drug were scrupulously inspected and cured. This enabled to make the dataset consistent and coherent. However, the lack of some important types of solvents in the collection called for an extension of the available pool of Edaravone solubility data. Hence, new measurements were performed for collecting Edaravone solubility in polar non-protic and polar di-protic media. Such an extended set of data was used for tuning the parameters of regressors models and formulating the ensemble for predicting new data. In both phases, namely the model training and ensemble formulation, close attention was paid not only to minimizing the deviation of computed values from the experimental ones but also to ensuring the high predictive power and computing solubility for new systems. Furthermore, the environmental friendliness characteristics determined based on the common green solvent selection criteria was included in the analysis. Our applied protocol led to the conclusion that the solubility space defined by ordinary solvents is limited, and it is unlikely to find solvents that are more suited for Edaravone dissolution than those depicted in this manuscript. The theoretical framework presented in this study provides a precise guide for conducting experiments, saving time and resources in the pursuit of new findings.

3D-printed aluminium alloy fabrications made by selective laser melting (SLM) offer a promising route for the production of small series of custom-designed heat exchangers with complex geometry and shape and miniature size. Alloy composition and printing parameters need to be optimized to mitigate fabrication defects (pores and microcracks) and enhance the part performance. The deformation response needs to be studied with adequate characterization techniques at relevant dimensional scale capturing the peculiarities of micro-mechanical behavior relevant to the particular article and specimen dimensions. Purposefully designed Al-Si-Mg 3D-printable RS-333 alloy was investigated with a number of microscopy techniques including in situ mechanical testing with a Deben Microtest 1 kN stage integrated and synchronized with Tescan Vega3 SEM to acquire high resolution image datasets for Digital Image Correlation (DIC) analysis. Dog bone specimens were 3D-printed in different orientation of gauge zone cross-section with respect to the fast laser beam scanning and growth directions. This corresponds to varying local conditions of metal solidification and cooling. Specimens show variation in mechanical properties, namely, Young’s modulus (65…78 GPa), yield stress (80–150 MPa), ultimate tensile strength (115–225 MPa) and elongation at break (0,75–1,4 %). Furthermore, the failure localization and character was altered with the change of gauge cross-section orientation. DIC analysis allowed correct strain evaluation that overcame the load frame compliance effect and helped to identify the unevenness of deformation distribution (plasticity waves) that ultimately resulted in exceptionally high strain localization near the ultimate failure crack position.

The search for economical and sustainable sources of PUFAs within the framework of the circular economy is encouraged by their proven beneficial effects on health. The extraction of monkfish liver oil (MLO) for the synthesis of omega-3 ethyl esters was performed evaluating two blending systems and four green solvents. Moreover, the potential solubility of the MLO in green solvents was studied using the predictive simulation software COSMO-RS. The production of the ethyl esters was performed by one or two step reactions. Novozym 435, two resting cells (Aspergillus flavus and Rhizopus oryzae) obtained in our laboratory and mix of them were used as biocatalysts in a solvent-free system. The yields for Novozym 435, R. oryzae and A. flavus in the one-step esterification were 63%, 61% and 46%, respectively. The hydrolysis step in the two-step reaction led to 83%, 88% and 93% of free fatty acids (FFA) for Novozym 435, R. oryzae and A. flavus respectively. However, Novozym 435 showed the highest yield in the esterification step (85%) followed by R. oryzae (65%) and A. flavus (41%). Moreover, selectivity in front of polyunsaturated fatty acids of R. oryzae lipase was evidenced, since it did slightly esterified docosahexaenoic acid (DHA) in all the esterification reactions tested.

The power of the river does not always work to the benefit of living things; rather, it has the ability to destroy human society and has negative effects on the environment. River Teesta has a prodigious significance on the riverine dweller and its changing precarious behaviour has repercussions on the lives of millions. Utilizing satellite images and 41 years of temporal analysis, the mapping of channel extraction and channel shifting has been demonstrated. Delineating the exact channel boundary is a laborious operation, but MNDWI technique is really valuable in this situation to produce valuable results. Descriptive statistics are used to analyze the Teesta River's active flow line migration trend and channel migration behaviour. A particular river's oscillating character over time has both beneficial and detrimental power, destroying important resources for environmental sustainability and human society while also providing fertile mother earth as a source of wealth. As a result, another goal of the current study was to determine how vulnerable riverine residents were. A livelihood vulnerability index (LVI) based on the riverine inhabitants' exposure, sensitivity, and capacity for adaptation was created. According to the findings, the river's erratic behaviour is putting the people who live beside it in danger. Therefore, it is vitally necessary to implement a capable management strategy to stop bank failure at the Teesta-Dharala confluence in order to save the riverine residents.

Up to 50% of patients with high-risk myeloid malignancies die of relapse after allogeneic stem cell transplantation. Current sequential conditioning regimens like the FLAMSA protocol combine intensive induction therapy with TBI or alkylators. Venetoclax has synergistic effects to chemotherapy. In a retrospective survey among German transplant centers, we identified 61 patients with myeloid malignancies that had received FLAMSA based sequential conditioning with Venetoclax between 2018 and 2022 as an individualized treatment approach. Sixty patients (98%) had active disease at transplant and 74% had genetic high-risk features. Patients received allografts from matched unrelated, matched related or mismatched donors. Tumor lysis syndrome occurred in two patients but no significant non-hematologic toxicity related to Venetoclax was observed. At day +30, 55 patients (90%) were in complete remission. Acute GvHD II°-IV° occurred in 17 (28%) and moderate/severe chronic GvHD in 7 patients (12%). Event-free survival and overall survival were 64% and 80% at 1 year as well as 57% and 75% at 2 years, respectively. The combination of sequential FLAMSA-RIC with Venetoclax appears to be safe and highly effective. To further validate these insights and enhance the idea of smart conditioning, a controlled prospective clinical trial has been initiated in 07/2023.

Management of urinary tract infection is challenged by increasing antimicrobial re-sistance (AMR) worldwide. In this study we describe the trends in antimicrobial re-sistance of uropathogens isolated from the largest private sector laboratory in Ghana over a five-year period. We reviewed positive urine cultures at the MDS Lancet Laboratories from 2017 to 2021. Proportions of uropathogens with antimicrobial resistance to oral and parenteral antimicrobials recommended by the Ghana standard treatment guidelines were determined. The proportion of multi-drug resistant isolates, ESBL and car-bapenemase-producing phenotypes were determined. Of 94,134 urine specimens submitted for culture, 20,010 (22.1%) were culture positive. Enterobacterales were the commonest group of organisms, E. coli (70.6) being the commonest isolate and Enterococcus spp. the commonest gram positive (1.3%) organisms. Among oral antimicrobials the highest resistance was observed to ciprofloxacin (62.3%) and cefuroxime (60.2) %) and the least resistance to Fosfomycin (1.9%). The least resistance among parenteral antimicrobials was to meropenem ( 0.3%). Highest multi-drug resistance levels were observed among Klebsiella spp. (68.6%) and E. coli (64.0%). ESBL positivity was highest in Klebsiella spp. (58.6%) and E. coli (50.0%). There may be a need to review the Ghana standard treatment guidelines to reflect increased resistance among uropathogens to recom-mended antimicrobials

Parkinson’s Disease (PD) is a neurodegenerative and progressive disease that impacts the nerve cells in the brain and varies from person to person. The exact cause of PD is still unknown, and the diagnosis of PD does not include a specific objective test with certainty. Although deep learning has made great progress in medical neuroimaging analysis, these methods are very susceptible to biases present in neuroimaging datasets. An innovative decorrelated deep learning technique is introduced to mitigate class bias and scanner bias while simultaneously focusing on finding distinguishing characteristics in resting-state functional MRI (rs-fMRI) data, which assist in recognizing the PD with good accuracy. The decorrelation function reduces the non-linear correlation between features and bias in order to learn bias-invariant features. The Parkinson’s Progression Markers Initiative (PPMI) dataset, referred to as a single scanner imbalanced dataset in this study used to validate our method. The imbalanced dataset problem affects the performance of the deep learning framework by overfitting to the majority class. To resolve this problem, we propose a new Decorrelated Convolutional Neural Networks (DcCNN) framework by applying decorrelation-based optimization to Convolutional Neural Networks(CNN). An analysis of evaluation metrics comparisons shows that integrating the decorrelation function boosts the performance of PD recognition by removing class bias. Specifically, our DcCNN model performs significantly better than existing traditional approaches to tackle the imbalance problem. Finally, the same framework can be extended to create scanner invariant features without significantly impacting the performance of a model. The obtained dataset is a multi-scanner dataset which leads to scanner bias due to the differences in acquisition protocols and scanners. The multi-scanner dataset is a combination of two datasets, namely PPMI and FTLDNI - frontotemporal lobar degeneration neuroimaging initiative (NIFD) dataset. The results of t-distributed stochastic neighbor embedding (t-SNE) and scanner classification accuracy of our proposed Feature Extraction-DcCNN (FE-DcCNN) model validated the effective removal of scanner bias. Our method achieves an average accuracy of 77.80% on a multi-scanner dataset for differentiating PD from healthy control, which is superior to the DcCNN model trained on a single scanner imbalanced dataset.

The Coastal Patrol and Surveillance Application (CPSA) is developed and deployed to detect, track and monitor water vessel traffic using automated devices. Latest advancements of marine technologies, including the Automatic Underwater Vehicles, have allowed the development of this type of applications. To facilitate their operations, installation of a Coastal Patrol and Surveillance Network (CPSN) is mandatory. One of the primary design objectives of this network is to deliver adequate amount of data within an effective time period. This is particularly essential for reporting a detection and notifying the current status of an intruder’s vessel through the adverse underwater communication channels. Additionally, intermittent connectivity of the nodes remain another important obstacle to overcome to allow smooth functioning of CPSA. Taking these objectives and obstacles into account, this work proposes a new protocol, named UDTN-RS, which is developed by ensembling forward error correction technique (namely Reed-Solomon codes or RS) in Underwater Delay Tolerant Network (UDTN) routing protocol with probabilistic spraying technique. In addition, the existing binary packet spraying technique is enhanced for supporting encoded packet exchange between the contacting nodes. A comprehensive simulation campaign is performed in identifying the effectiveness of the proposed protocol. The obtained results suggest that the proposed UDTN-RS protocol can be considered a suitable alternative of the existing protocols for sparse networks like CPSN.

This study aimed to use remote sensing and GIS to detect changes in surface water and wetlands in the Kumasi Metropolis over a period of 20 years (2002-2022). Landsat images were processed using the QGIS software, and the Maximum Likelihood Algorithm was used to perform supervised classification of land use land cover, while raster calculator aided in detecting wetlands by calculation for NDWI, MNDWI, and AWEI. The results showed that the majority of the landscape in the Kumasi metropolis was made up of built-up areas (79.4%), followed by agricultural lands (13.3%) and wetlands (7.3%). Over the 20-year period, built-up areas had gained 20.7% of the total landscape, while agricultural lands and wetlands had lost 16.7% and 4.0%, respectively. All water index methods recorded an increase in non-water cover and a loss of water cover over the period, with surface water decreasing by 5% and non-water land cover increasing by 5%. The study concludes that there have been significant changes in wetlands and surface water land use and land cover within the Kumasi Metropolis over the past 20 years, and recommends the enforcement of legislation on surface water protection in the area to protect wetlands

Published in July 2018, TAILORx aimed to establish non-inferiority of endocrine therapy (ET) compared to addition of chemotherapy (CHT-ET) in hormone receptor positive, human epidermal receptor 2 negative (HR+/HER2-) breast cancer (BC) patients with a 21-gene intermediate (11-25) recurrence score (RS). While this hypothesis proved correct, the study did show benefit of addition of chemotherapy (CHT) in a subgroup of women under 50 years of age, and particularly in the RS 16-25. The aim of this present study was to look at how TAILORx findings, including changes in RS categories, impacted CHT implementation at one oncologic center in Basel, Switzerland, and to identify main factors leading to these changes. Methods: We conducted a retrospective study on HR+/HER2-, BC patients who underwent 21-gene genomic testing between 2010-2021, at our center. Patients with metastatic disease were not included. We identified 326 eligible patients, of which 165 had a BC diagnosis before TAILORx (cohort A) and 161 after TAILORx publication (cohort B). Results: Demographic and tumor characteristics were similar in the two cohorts, although cohort B included significantly more women under the age of 50 when compared to A (34% vs. 24%, p<0.001). Median age and mean RS results were comparable 59 (IQR 16) in A and 58 (IQR 19) years in B and 17.72 (SD9.59) in A and 17.89 (SD9.53) in B, respectively. Patients in cohort A were slightly more overweight when compared to B (55% vs. 40% respectively, p<0.001). Most patients had stage II tumors of NST histologic type. Tumors in cohort B had higher Ki-67 than cohort A (39% vs. 32%, p=0.010). When compared based on manufacturer’s and based on TAILORx thresholds there were no significant differences in RS distribution. However, changes in score category led to shifts in patient population distribution, leading to a 40% drop in the low RS (from 60% to 20%), a doubling in the intermediate RS (from 30% to 60%) and an increase of 5% in the high RS (from 8-10% to 15%). Most patients had conservative surgery, adjuvant radiotherapy (RT) and ET. Overall CHT recommendation and application did not differ significantly in B vs. A. There was a reduction of 1% in the intermediate RS (11-25) and an increase of 13% CHT-ET application in the high RS (>26) category. In cohort B we noticed an increase in CHT-ET application among women <50 years old (by 12.5%), in lobular carcinomas (by 10%), grade 3 tumors (by 2%), node positive BC (by 3%) and node negative (by 2%). Tumor board recommendation for CHT dropped by 1% in the post TAILORx era, with a notable reduction of 5% in the intermediate RS (11-25) category. However, overall CHT administration rate was 19% in cohort A and 22% in B (p=0.763). Tumor Board recommended CHT for 90% of the BC patients that would have otherwise been assigned to CHT according to new RS guidelines in A and for 85% in B, showing a trend for undertreatment. Logistic regression analysis showed significance of age in both cohort A (OR 1.05, 95% CI 1.01-1.11, p=0.03) and cohort B (OR 0.89, 95% CI 0.84-0.94), p<0.001), and of nodal status in both cohort A (=R 3.32 95% CI 1.09-10-06, p=0.034) and cohort B (OR 3.31, 95% CI 1.29-8.53, p=0.013), while intermediate and high RS seem to be more relevant in cohort A (OR 0.12, 95% CI 0.03-0.43, p=0.01 and OR 0.04, 95% CI 0.01-0.21, p<0.01). Overall logistic regression analysis showed relevance of age (OR 0.93, 95% CI 0.08-0.97, p=0.001), pN (OR 4.77, 95% CI 2.03-11.22, p<0.001) and RS categories (RS 11-25: OR 0.02, 95% CI 0.01-0.07, p<0.001; RS>26: OR 617.93, 95% CI 57.97-6587.16, p<0.001). Conclusion: Our findings are similar to those reported across several studies: while tumor board recommendation for CHT decreases in the intermediate RS category, there is an increase being reported in the high RS category, leading to overall minor changes in CHT application. Administration of CHT-ET seems to be increasing among younger women, with unfavorable histo-pathological factors, such as lobular carcinoma and G3 histologic grade. Before TAILORx there is a tendency for undertreatment (-10%), especially among older BC patients, which seems to be maintained and even deepened (-15%) in the post TAILORx era, pointing to a personalized decision-making approach among Swiss oncologists.

Earthquakes are one of the most catastrophic natural phenomena. After an earthquake, earthquake reconnaissance enables effective recovery by collecting building damage data and other impacts. This paper aims to identify state-of-the-art data sources for building damage assessment and provide guidance for more efficient data collection. We have reviewed 38 articles that indicate the sources used by different authors to collect data related to damage and post-disaster recovery progress after earthquakes between 2014 and 2021. The current data collection methods have been grouped into seven categories: fieldwork or ground surveys, omnidirectional imagery (OD), terrestrial laser scanning (TLS), remote sensing (RS), crowdsourcing platforms, social media (SM) and closed-circuit television videos (CCTV). The selection of a particular data source or collection technique for earthquake reconnaissance includes different criteria depending on what questions are to be answered by this data. We conclude that modern reconnaissance missions can not rely on a single data source and that different data sources should complement each other, validate collected data, or systematically quantify the damage. The recent increase in the number of crowdsourcing and SM platforms used to source earthquake reconnaissance data demonstrates that this is likely to become an increasingly important source of data.

Polycystic ovary syndrome (PCOS) is a complex hormonal disorder which impair ovarian function. The adherence to healthy dietary patterns and physical exercise are the first line of recommended treatment for PCOS patients, but it is no clear what type of diet is more adequate. In this case-control study, we explore the association between the adherence to five dietary quality indices widely used and PCOS. We enrolled 126 cases of PCOS and 159 controls (Murcia, Spain). Diagnostic of PCOS and its phenotypes were established following the Rotterdam criteria [hyperandrogenism (H), oligoanovulation (O), polycystic ovaries morphology (POM)]. We used a validated food frequency questionnaires to calculate the scores for five dietary indices: alternate Healthy Eating index (AHEI), AHEI-2010, relative Mediterranean Dietary Score (rMED), alternate Mediterranean Dietary Score (aMED) and Dietary Approaches to Stop Hypertension (DASH). We used multivariable logistic regression to estimate adjusted odds ratios and confidence intervals. In the multivariable analysis, AHEI-2010 index was inversely associated with “H+O” PCOS’ phenotype (ORQ3 VS Q1= 0.1; 95% CI :(0.0; 0.9); P for trend= 0.02). In conclusion, we did not find any statistical significative association between dietary indices and total, anovulatory and ovulatory PCOS, but it seems interesting explore these association among the diverse phenotypes of PCOS in studies with higher sample size.

Using multi-color flow cytometry analysis, we studied the immunophenotypical differences between leukemic blasts/LSCs from patients with AML/MDS and hematopoietic stem and progenitor cells (HSPCs) from patients in complete remission (CR) following their successful treatment. The panel of markers included CD34, CD38, CD45RA, CD123 as representatives for a hierarchical hematopoietic stem and progenitor cell (HSPC) classification as well as programmed death ligand 1 (PD-L1). Rather than restricting the evaluation on a 2- or 3-dimensional analysis, we applied a t-distributed stochastic neighbor embedding (t-SNE) approach to get a deeper insight and segregation between leukemic and normal HPSCs. For that purpose, we created a t-SNE map, which resulted in the visualization of 27 cell clusters based on their similarity concerning the composition and intensity of antigen expression. Two of these clusters were “leukemia-related” containing a great proportion of CD34⁺/CD38^- hematopoietic stem cells (HSCs) or CD34⁺ cells with a strong coexpression of CD45RA/CD123, respectively. CD34⁺ cells within the latter cluster were also highly positive for PD-L1 reflecting their immunosuppressive capacity. Beyond this proof of principle study, the inclusion of additional markers will be helpful to refine the differentiation between normal HSPCs and leukemic cells, particularly in the context of minimal disease detection and antigen-targeted therapeutic interventions. Furthermore, we suggest a protocol for the assignment of new cell ensembles in quantitative terms, via a numerical value, the Pearson coefficient, based on a similarity comparison of the t-SNE pattern with a reference.