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Simple Summary: Current recommendations suggest setting two parallel cytogenetic cultures with 12-O-tetradecanoly-phorpol-13-acetate (TPA) and IL2+DSP30 as a mitogen to detect complex karyotypes (CKs) in chronic lymphocytic leukemia (CLL). However, studies comparing CK detection concordance between both methods in the same cohort are lacking. Herein, we evaluated the performance of two parallel cultures in a CLL cohort of 255 patients, specifically comparing CK detection (globally and in each individual patient). The CK detection rates and their prognostic impacts were similar for both mitogens. However, nearly one-third of CKs were only identified in one culture, mainly due to the detection of a normal karyotype or no metaphases in the other. In summary, the assessment of parallel cytogenetic cultures is the best strategy to detect CKs in CLL. Nonetheless, as IL2+DSP30 achieved the best performance, it should be prioritized above TPA if a single analysis is required to optimize cytogenetic assessment in routine practice. Current CLL guidelines recommend a two parallel cultures assessment using TPA and IL2+DSP30 mitogens for complex karyotype (CK) detection. Studies comparing both mitogens for CK identification in the same cohort are lacking. We analyzed the global performance, CK detection, and concordance in the complexity assessment of two cytogenetic cultures from 255 CLL patients. IL2+DSP30 identified more altered karyotypes than TPA (50 vs. 39%, p = 0.031). Moreover, in 71% of those abnormal by both, IL2+DSP30 identified more abnormalities and/or abnormal metaphases. CK detection was similar for TPA and IL2+DSP30 (10% vs. 11%). However, 11/33 CKs (33%) were discordant, mainly due to the detection of a normal karyotype or no metaphases in the other culture. Patients requiring treatment within 12 months after sampling (active CLL) displayed significantly more CKs than those showing a stable disease (55% vs. 12%, p < 0.001). Disease status did not impact cultures' concordance (κ index: 0.735 and 0.754 for stable and active). Although CK was associated with shorter time to first treatment (TTFT) using both methods, IL2+DSP30 displayed better accuracy than TPA for predicting TTFT (C-index: 0.605 vs. 0.580, respectively). In summary, the analysis of two parallel cultures is the best option to detect CKs in CLL. Nonetheless, IL2+DSP30 could be prioritized above TPA to optimize cytogenetic assessment in clinical practice. [ABSTRACT FROM AUTHOR]

With the growing concern worldwide regarding greenhouse gas (GHG) emissions and their impacts on human health and the environment, transportation has become a central theme in their mitigation, responsible for 15% of anthropogenic GHG, 23% of global energy-related, and 8.7 Gt CO2-eq emissions. This study's objective was to comprehensively review the current state of carbon mitigation in the transportation sector. This was conducted through a systematic literature review based on the multi-level perspective of socio-technical transition theory and structural contingency theory. In total, 30 review papers covering 3561 original articles were selected for full-text examination. The main findings were related to the fact that in order to build resilience against climate change, transportation services must adapt to the current scenario and act quickly to avert future changes. Enablers, barriers, benefits, disadvantages, and metrics in carbon emission reduction were identified. A comprehensive framework and a dynamic co-word analysis emphasised the interrelationships among the dimensions of sustainability transition in transportation. Important trade-offs among the transition dimensions are context-dependent and should be adapted to different countries and transport modes to succeed. The study sheds light on the need to investigate mitigation's often-neglected consequences and disadvantages. [ABSTRACT FROM AUTHOR]

Simple Summary: Genome complexity, detected by chromosome banding analysis or chromosomal microarray analysis, is a poor prognostic factor for chronic lymphocytic leukemia (CLL). Herein, we aimed to assess the performance of optical genome mapping (OGM) for the cytogenomic characterization of CLL patients, with a special focus on risk stratification based on genomic complexity. A cohort of 42 patients enriched in complex karyotypes was assessed by OGM, and the results were compared with those obtained from current methods. Moreover, clinical–biological characteristics and time to first treatment were analyzed according to the OGM-defined complexity. Globally, OGM identified 90% of the known alterations and provided novel structural information about these aberrations in 55% of patients. Regarding genomic complexity, OGM allowed us to identify a complex group (≥10 alterations) displaying enrichment of TP53 abnormalities and poorer evolution. Altogether, we confirmed that OGM is a valuable tool for the cytogenomic assessment and prognostic stratification of CLL patients. Novel treatments in chronic lymphocytic leukemia (CLL) have generated interest regarding the clinical impact of genomic complexity, currently assessed by chromosome banding analysis (CBA) and chromosomal microarray analysis (CMA). Optical genome mapping (OGM), a novel technique based on imaging of long DNA molecules labeled at specific sites, allows the identification of multiple cytogenetic abnormalities in a single test. We aimed to determine whether OGM is a suitable alternative to cytogenomic assessment in CLL, especially focused on genomic complexity. Cytogenomic OGM aberrations from 42 patients were compared with CBA, FISH, and CMA information. Clinical–biological characteristics and time to first treatment (TTFT) were analyzed according to the complexity detected by OGM. Globally, OGM identified 90.3% of the known alterations (279/309). Discordances were mainly found in (peri-)centromeric or telomeric regions or subclonal aberrations (<15–20%). OGM underscored additional abnormalities, providing novel structural information on known aberrations in 55% of patients. Regarding genomic complexity, the number of OGM abnormalities had better accuracy in predicting TTFT than current methods (C-index: 0.696, 0.602, 0.661 by OGM, CBA, and CMA, respectively). A cut-off of ≥10 alterations defined a complex OGM group (C-OGM, n = 12), which included 11/14 patients with ≥5 abnormalities by CBA/CMA and one patient with chromothripsis (Kappa index = 0.778; p < 0.001). Moreover, C-OGM displayed enrichment of TP53 abnormalities (58.3% vs. 3.3%, p < 0.001) and a significantly shorter TTFT (median: 2 vs. 43 months, p = 0.014). OGM is a robust technology for implementation in the routine management of CLL patients, although further studies are required to define standard genomic complexity criteria. [ABSTRACT FROM AUTHOR]

The wide adoption of the recently coined fog and edge computing paradigms alongside conventional cloud computing creates a novel scenario, known as the cloud continuum, where services may benefit from the overall set of resources to optimize their execution. To operate successfully, such a cloud continuum scenario demands for novel management strategies, enabling a coordinated and efficient management of the entire set of resources, from the edge up to the cloud, designed in particular to address key edge characteristics, such as mobility, heterogeneity and volatility. The design of such a management framework poses many research challenges and has already promoted many initiatives worldwide at different levels. In this paper we present the results of one of these experiences driven by an EU H2020 project, focusing on the lessons learnt from a real deployment of the proposed management solution in three different industrial scenarios. We think that such a description may help understand the benefits brought in by a holistic cloud continuum management and also may help other initiatives in their design and development processes. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic cancer is a digestive tumor that is most difficult to treat and carries one of the worst prognoses. The anatomical location of the pancreas makes it very difficult to obtain enough tumor material to establish a molecular diagnosis, so knowing the biology of this tumor and implementing new targeted-therapies is still a pending issue. The use of liquid biopsy, a blood sample test to detect circulating-tumor DNA fragments (ctDNA), is key to overcoming this difficulty and improving the evolution of this tumor. Liquid biopsies are equally representative of the tissue from which they come and allow relevant molecular and diagnostic information to be obtained in a faster and less invasive way. One challenge related to ctDNA is the lack of consistency in the study design. Moreover, ctDNA accounts for only a small percentage of the total cell-free circulating DNA and prior knowledge about particular mutations is usually required. Thus, our aim was to understand the current role and future perspectives of ctDNA in pancreatic cancer using digital-droplet PCR technology. Pancreatic cancer (PC) is one of the most devastating malignant tumors, being the seventh leading cause of cancer-related death worldwide. Researchers and clinicians are endeavoring to develop strategies for the early detection of the disease and the improvement of treatment results. Adequate biopsy is still challenging because of the pancreas's poor anatomic location. Recently, circulating tumor DNA (ctDNA) could be identified as a liquid biopsy tool with huge potential as a non-invasive biomarker in early diagnosis, prognosis and management of PC. ctDNA is released from apoptotic and necrotic cancer cells, as well as from living tumor cells and even circulating tumor cells, and it can reveal genetic and epigenetic alterations with tumor-specific and individual mutation and methylation profiles. However, ctDNA sensibility remains a limitation and the accuracy of ctDNA as a biomarker for PC is relatively low and cannot be currently used as a screening or diagnostic tool. Increasing evidence suggests that ctDNA is an interesting biomarker for predictive or prognosis studies, evaluating minimal residual disease, longitudinal follow-up and treatment management. Promising results have been published and therefore the objective of our review is to understand the current role and the future perspectives of ctDNA in PC. [ABSTRACT FROM AUTHOR]

Aims: This study assessed the impact of acute hemoglobin (Hb) falls in heart failure (HF) patients. Methods: HF patients with repeated Hb values over time were included. Falls in Hb greater than 30% were considered to represent an acute episode of anemia and the risk of hospitalization and all-cause mortality after the first episode was assessed. Results: In total, 45,437 HF patients (54.9% female, mean age 74.3 years) during a follow-up average of 2.9 years were analyzed. A total of 2892 (6.4%) patients had one episode of Hb falls, 139 (0.3%) had more than one episode, and 342 (0.8%) had concomitant acute kidney injury (AKI). Acute heart failure occurred in 4673 (10.3%) patients, representing 3.6/100 HF patients/year. The risk of hospitalization increased with one episode (Hazard Ratio = 1.30, 95% confidence interval (CI) 1.19–1.43), two or more episodes (HR = 1.59, 95% CI 1.14–2.23, and concurrent AKI (HR = 1.61, 95% CI 1.27–2.03). A total of 10,490 patients have died, representing 8.1/100 HF patients/year. The risk of mortality was HR = 2.20 (95% CI 2.06–2.35) for one episode, HR = 3.14 (95% CI 2.48–3.97) for two or more episodes, and HR = 3.20 (95% CI 2.73–3.75) with AKI. In the two or more episodes and AKI groups, Hb levels at the baseline were significantly lower (10.2–11.4 g/dL) than in the no episodes group (12.8 g/dL), and a higher and significant mortality in these subgroups was observed. Conclusions: Hb falls in heart failure patients identified those with a worse prognosis requiring a more careful evaluation and follow-up. [ABSTRACT FROM AUTHOR]

Background: Breast cancer in very young women (BCVY) defined as <35 years old, presents with different molecular biology than in older patients. High HDAC5 expression has been associated with poor prognosis in breast cancer (BC) tissue. We aimed to analyze HDAC5 expression in BCVY and older patients and their correlation with clinical features, also studying the potential of HDAC5 inhibition in BC cell lines. Methods: HDAC5 expression in 60 BCVY and 47 older cases were analyzed by qRT-PCR and correlated with clinical data. The effect of the HDAC5 inhibitor, LMK-235, was analyzed in BC cell lines from older and young patients. We performed time and dose dependence viability, migration, proliferation, and apoptosis assays. Results: Our results correlate higher HDAC5 expression with worse prognosis in BCVY. However, we observed no differences between HDAC5 expression and pathological features. Our results showed greatly reduced progression in BCVY cell lines and also in all triple negative subtypes when cell lines were treated with LMK-235. Conclusions: In BCVY, we found higher expression of HDAC5. Overexpression of HDAC5 in BCVY correlates with lower survival rates. LMK-235 could be a potential treatment in BCVY. [ABSTRACT FROM AUTHOR]