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Tropical-tropopause-layer cirrus clouds and their radiative effects represent a major uncertainty in the evaluation of Earth’s energy budget. High-altitude aircraft offer an opportunity to provide observations at cirrus cloud altitudes, most commonly using in situ measurements of ice particle optical properties and composition. In particular, remote sensing of scattering properties and near-IR ice water absorption in the limb can provide unique insights into thin and sub-visible cirrus clouds. Here we present novel spectroscopic observations of path-averaged ice water absorptions on board NASA’s Global Hawk aircraft during the Airborne Tropical TRopopause Experiment (ATTREX), which took place in 2011, 2013, and 2014. The University of California Los Angeles and University of Heidelberg mini-differential optical absorption spectroscopy (mini-DOAS) instrument provided multi-angle limb-scanning observations of scattered solar radiation in the near-IR (900–1726 nm), allowing the identification of ice and liquid water, O2, CO2, and H2O. The VLIDORT-QS radiative transfer (RT) code was specifically developed for this study and used to simulate high-altitude limb observations for varied cloud scenarios. We performed a comprehensive sensitivity study, developing a fundamental understanding of airborne near-IR limb observations of cirrus clouds. We identified two general distinct cases: a linear regime for optically thin clouds, where the ice absorption is proportional to ice water content (IWC), and a regime for optically thick cirrus clouds, where ice absorption is in saturation and independent of IWC. Results also demonstrate how molecular oxygen absorption can be used to infer information on optical properties of ice particles in the second regime only, with minimal information for thin cirrus clouds. We also explored the feasibility of retrieving IWC from mini-DOAS path-averaged ice water absorption (SIWP) measurements. This innovative interpolation-based approach requires a small number of RT calculations per observation to determine the sensitivity of SIWP to IWC. Spectral retrievals were applied for a particularly interesting case during Science Flight 2 over Guam in February 2014, during which the aircraft flew in circles in the same general area for an extended period of time. Retrieved IWC results are consistent with independent in situ measurements from other instruments on board. The measurements of ice particle scattering and absorption at different azimuths relative to the sun and at different altitudes represent a unique opportunity to test our approach and to infer properties of the ice particles, together with information on cirrus cloud radiative transfer.

BackgroundIn the landscape of metastatic soft tissue sarcoma (mSTS) treatment, anthracyclines have shown efficacy; however, their associated toxicity imposes significant limitations, especially in frail elderly patients with mSTS who are highly susceptible to severe adverse effects. In this context, trabectedin, due to its distinct pharmacological profile and safety profile, may represent an interesting alternative being demonstrated to be active in treating mSTS. These features hold particular significance for elderly and unfit patients with mSTS, where balancing treatment benefits with potential adverse effects represents the pivotal objective.MethodsThe investigation was focused on a specific group of 11 elderly patients with mSTS aged ≥70, all undergoing first-line treatment with trabectedin, and it was supported by comprehensive pharmacokinetic and pharmacodynamic studies. Among these patients, 9 out of 11 started the treatment at a dose of 1.5 mg/m2.ResultsThe primary objective of this investigation is to highlight trabectedin as a valuable first-line treatment option for elderly and unfit patients with mSTS. Additionally, this investigation seeks to explore whether higher administered doses of trabectedin can enhance clinical outcomes while maintaining the same toxicity profiles. The median progression-free survival (PFS) was 77 days (95% CI, 53–89), the median overall survival (OS) was 397 days (95% CI, 66–2,102), while the overall toxicity of grade 3–4 severity amounted to 43%.ConclusionThese findings provide new insights into the clinical outcomes and toxicity associated with trabectedin in an elderly patient population, enhancing our understanding of better treatment approaches for a specific population of patients with mSTS.

Rhinophyma is characterized by chronic inflammation of the tissues of the nose, resulting in irregular exophytic growth and telangiectasias. The disease progresses with hyperplasia and hypertrophy of the nasal sebaceous glands, associated with fibrosis and dilation of local blood vessels and connective tissue. These changes can lead to complete nose deformity and compromise the patients' quality of life. There are different treatment methods, such as laser, microdermabrasion, chemical exfoliation, cryosurgery, surgery with skin graft, and electrosurgery, with varying results and costs. We report two cases of rhinophyma treated with electrosurgery with very satisfactory results.

Potent partnerships among researchers, policymakers, and community members have potential to produce positive changes in communities on a range of topics, including behavioral health. The paper provides a brief illustrative review of such partnerships and then describes the development and evolution of one partnership in particular in Virginia. The origin of the partnership is traced, along with its founding vision, mission, and values. Some of its several projects are described, including (a) needs assessment for implementation of evidence-based programs (EBPs) pursuant to the Family First Prevention Services Act; (b) statewide fidelity monitoring of key EBPs; and (c) projects to synergize state investments in specific EBPs, like multisystemic therapy, functional family therapy, and high fidelity wraparound. The paper concludes with some themes around which the center has evolved to serve the state and its citizens more effectively.

In recent years, many researchers have focused on designing hydrogels with specific functional groups that exhibit high affinity for various contaminants, such as heavy metals, organic pollutants, pathogens, or nutrients, or environmental parameters. Novel approaches, including cross-linking strategies and the use of nanomaterials, have been employed to enhance the structural integrity and performance of the desired hydrogels. The evolution of these hydrogels is further highlighted, with an emphasis on fine-tuning features, including water absorption capacity, environmental pollutant/factor sensing and selectivity, and recyclability. Furthermore, this review investigates the emerging topic of stimuli-responsive smart hydrogels, underscoring their potential in both sorption and detection of water pollutants. By critically assessing a wide range of studies, this review not only synthesizes existing knowledge, but also identifies advantages and limitations, and describes future research directions in the field of chemically engineered hydrogels for water purification and monitoring with a low environmental impact as an important resource for chemists and multidisciplinary researchers, leading to improvements in sustainable water management technology.

Ambrosia artemisiifolia is an invasive weed and primary cause of pollen-induced hayfever. Here, the authors report its chromosome-level phased genome assembly, examine genome-wide variation among modern and historic accessions, and identify large haploblocks underling rapid adaptation.

Heart failure (HF) is a growing issue in developed countries; it is often the result of underlying processes such as ischemia, hypertension, infiltrative diseases or even genetic abnormalities. The great majority of the affected patients present a reduced ejection fraction (≤40%), thereby falling under the name of “heart failure with reduced ejection fraction” (HFrEF). This condition represents a major threat for patients: it significantly affects life quality and carries an enormous burden on the whole healthcare system due to its high management costs. In the last decade, new medical treatments and devices have been developed in order to reduce HF hospitalizations and improve prognosis while reducing the overall mortality rate. Pharmacological therapy has significantly changed our perspective of this disease thanks to its ability of restoring ventricular function and reducing symptom severity, even in some dramatic contexts with an extensively diseased myocardium. Notably, medical therapy can sometimes be ineffective, and a tailored integration with device technologies is of pivotal importance. Not by chance, in recent years, cardiac implantable devices witnessed a significant improvement, thereby providing an irreplaceable resource for the management of HF. Some devices have the ability of assessing (CardioMEMS) or treating (ultrafiltration) fluid retention, while others recognize and treat life-threatening arrhythmias, even for a limited time frame (wearable cardioverter defibrillator). The present review article gives a comprehensive overview of the most recent and important findings that need to be considered in patients affected by HFrEF. Both novel medical treatments and devices are presented and discussed.

Summary: Soft tissue sarcomas (STSs) are rare malignant tumors that are difficult to prognosticate using currently available instruments. Omics sciences could provide more accurate and individualized survival predictions for patients with metastatic STS. In this pilot, hypothesis-generating study, we integrated clinicopathological variables with proton nuclear magnetic resonance (1H NMR) plasma metabolomic and lipoproteomic profiles, capturing both tumor and host characteristics, to identify novel prognostic biomarkers of 2-year survival. Forty-five metastatic STS (mSTS) patients with prevalent leiomyosarcoma and liposarcoma histotypes receiving trabectedin treatment were enrolled. A score combining acetate, triglycerides low-density lipoprotein (LDL)-2, and red blood cell count was developed, and it predicts 2-year survival with optimal results in the present cohort (84.4% sensitivity, 84.6% specificity). This score is statistically significant and independent of other prognostic factors such as age, sex, tumor grading, tumor histotype, frailty status, and therapy administered. A nomogram based on these 3 biomarkers has been developed to inform the clinical use of the present findings.

Objective: Trabectedin is an anti-cancer drug commonly used for the treatment of patients with metastatic soft tissue sarcoma (mSTS). Despite its recognized efficacy, significant variability in pharmacological response has been observed among mSTS patients. To address this issue, this pharmacometabolomics study aimed to identify pre-dose plasma metabolomics signatures that can explain individual variations in trabectedin pharmacokinetics and overall clinical response to treatment.Methods: In this study, 40 mSTS patients treated with trabectedin administered by 24 h-intravenous infusion at a dose of 1.5 mg/m2 were enrolled. The patients' baseline plasma metabolomics profiles, which included derivatives of amino acids and bile acids, were analyzed using multiple reaction monitoring LC-MS/MS together with their pharmacokinetics profile of trabectedin. Multivariate Partial least squares regression and univariate statistical analyses were utilized to identify correlations between baseline metabolite concentrations and trabectedin pharmacokinetics, while Partial Least Squares-Discriminant Analysis was employed to evaluate associations with clinical response.Results: The multiple regression model, derived from the correlation between the AUC of trabectedin and pre-dose metabolomics, exhibited the best performance by incorporating cystathionine, hemoglobin, taurocholic acid, citrulline, and the phenylalanine/tyrosine ratio. This model demonstrated a bias of 4.6% and a precision of 17.4% in predicting drug AUC, effectively accounting for up to 70% of the inter-individual pharmacokinetic variability. Through the use of Partial least squares-Discriminant Analysis, cystathionine and hemoglobin were identified as specific metabolic signatures that effectively distinguish patients with stable disease from those with progressive disease.Conclusions: The findings from this study provide compelling evidence to support the utilization of pre-dose metabolomics in uncovering the underlying causes of pharmacokinetic variability of trabectedin, as well as facilitating the identification of patients who are most likely to benefit from this treatment.

Abstract Biological invasions offer a unique opportunity to investigate evolution over contemporary timescales. Rapid adaptation to local climates during range expansion can be a major determinant of invasion success, yet fundamental questions remain about its genetic basis. This study sought to investigate the genetic basis of climate adaptation in invasive common ragweed (Ambrosia artemisiifolia). Flowering time adaptation is key to this annual species' invasion success, so much so that it has evolved repeated latitudinal clines in size and phenology across its native and introduced ranges despite high gene flow among populations. Here, we produced a high‐density linkage map (4493 SNPs) and paired this with phenotypic data from an F2 mapping population (n = 336) to identify one major and two minor quantitative trait loci (QTL) underlying flowering time and height differentiation in this species. Within each QTL interval, several candidate flowering time genes were also identified. Notably, the major flowering time QTL detected in this study was found to overlap with a previously identified haploblock (putative inversion). Multiple genetic maps of this region identified evidence of suppressed recombination in specific genotypes, consistent with inversions. These discoveries support the expectation that a concentrated genetic architecture with fewer, larger, and more tightly linked alleles should underlie rapid local adaptation during invasion, particularly when divergently adapting populations experience high levels of gene flow.

Until recently, effective therapies for advanced endometrial cancer progressing to a platinum-based combination were lacking. In this setting, immunotherapy with anti PD-1/PDL-1 monoclonal antibodies is rising as a new paradigm in particular for patients with microsatellites instability/mismatch repair deficiency. In this case report, we describe an exceptional and rapid response to dostarlimab in a platinum refractory endometrial cancer patient with high disease burden harboring a mismatch repair deficiency.

Metastatic soft-tissue sarcomas (mSTS) encompass a highly heterogeneous group of rare tumours characterized by different clinical behaviours and outcomes. Currently, prognostic factors for mSTS are very limited, posing significant challenges in predicting patient survival. Within a cohort of 39 mSTS patients undergoing trabectedin treatment, it was remarkable to find one patient who underwent 73 cycles of trabectedin achieving an unforeseen clinical outcome. To identify contributing factors to her exceptional long-term survival, we have explored circulation metabolomics and biohumoral biomarkers to uncover a potential distinct host biochemical phenotype. The long-term survival patient compared with the other mSTS patients exhibited a distinctive metabolic profile characterized by remarkably higher levels of ursodeoxycholic acid (UDCA) derivatives and vitamin D and lower levels of lithocholic acid (LCA) derivatives, as well as reduced levels of inflammatory C-Reactive Protein 4 (C-RP4) biomarker. Despite its exploratory nature, this study reveals a potential association between specific bile acid metabolic profiles and mSTS patients’ prognosis. Enhanced clinical understanding of the interplay between bile acid metabolism and disease progression could pave the way for new targeted therapeutic interventions which may improve the overall survival of mSTS patients.

We describe a rare case of a girl with an initial diagnostic hypothesis of chromosome 8 trisomy based on clinical findings and karyotyping, which identified a structural change in the short arm of chromosome 8 (46,XX,add(8)(p23)). At the age of 7, she developed type 1 diabetes mellitus and started insulin therapy with multiple daily doses, and then she started to use a continuous insulin infusion system (pump) at 10 years of age. At the age of 12, she underwent a molecular study that identified an unbalanced translocation between the short arms of chromosomes 6 and 8 – 46,XX,add(8)(p23).ish der(8) t(6;8)(GS-196I5+;RP-11338B22−).

In the framework of global and EU policies focused on stopping the loss of biodiversity process, deepening the genetic variability, especially of populations species identified as threatened, is crucial for defining conservation units and developing appropriate conservation strategies. This is more urgent for cetacean species in the Mediterranean because they assume a key ecological role in the marine food web and are severely affected by numerous and different anthropogenic pressures. This study aims to increase information on the genetic variability of striped dolphin in the Northern Ionian Sea by investigating the population structure, phylogenetic relationships and phylogeographic patterns using two mtDNA markers. From October 2020 to August 2021, a total of 88 skin tissue samples were collected from free-ranging dolphins in the Gulf of Taranto by applying the non-invasive technique of skin swabbing. An acceptable amount of DNA was extracted from 86 samples and used for subsequent genetic analysis conducted on the partial sequences of 421 and 704 bp in length of the cytb gene and D-loop control region, respectively. In addition, the sequences of the two mtDNA markers were joined together to compose a mtDNA concatenated sequence of 1125 bp for each sampled dolphin in order to investigate the genetic variability of the species population in the study area. Genetic analysis highlighted a low nucleotide diversity and high haplotypic diversity of the striped dolphin of the Gulf of Taranto, suggesting a population in rapid expansion after a period of reduction in size and diversity of the initial population. The phylogenetic analyses revealed the presence of at least two different lineages of Stenella coeruleoalba in the Mediterranean Sea, one specific to the Northern Ionian Sea and one shared with the Mediterranean population, confirming results already obtained for the local unit in the Gulf of Taranto. The results point out a potential problem of hybridization between striped and common dolphins which needs to be further investigated. Therefore, increasing the analysis of several markers may increase understanding of the genetic diversity of the population in the Ionian Sea and represent a useful tool to support the implementation of future effective conservation measures.