Hydatid cyst disease of the lung as an unusual cause of massive hemoptysis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Echinococcosis and/or hydatidosis is one of the most important zoonotic diseases in the world. In Turkey, echinococcosis is an endemic disease, however, hydatid disease of the lung is uncommon and usually caused by <it>Echinococcus granulosus</it>.</p> <p>Case presentation</p> <p>In this report we describe a 17-year-old male patient who presented with massive hemoptysis due to hydatid disease of the lung.</p> <p>Conclusion</p> <p>Although it is one of the less common causes of massive hemoptysis, hydatid disease of the lung requires greater attention in countries, such as Turkey, in which hydatid cyst disease is common.</p

Longitudinal profiling of hormone receptor positive, HER2 negative metastatic breast cancer through droplet digital PCR-based circulating tumor DNA fragmentomics

Background: In the context of hormone receptor positive, HER2 negative Metastatic breast cancer (MBC), CDK 4/6 inhibitors (CDK4/6i) combined with endocrine therapy represent the standard first-line treatment, improving Progression-Free Survival (PFS) and Overall Survival (OS). Despite these benefits, resistance to treatment develops, necessitating early risk classification to guide clinical management. This study explores the potential of cell-free DNA (cfDNA) fragmentomics, specifically ACTB fragments, in predicting tumor dynamics and treatment outcomes in luminal MBC, based on the principle that shorter DNA fragments are generally indicative of circulating tumor DNA (ctDNA) from tumor cells, while longer fragments are associated with leukocyte lysis. Methods: In the MAGNETIC.1 study, 141 women with luminal-like MBC were enrolled between January 2018 and January 2023. Blood samples were collected at baseline (BL), and after 3 (T3) and 6 (T6) months of treatment. cfDNA was extracted and analyzed using droplet digital PCR (ddPCR) to quantify ACTB fragments (136 bp, 420 bp, and 2,000 bp). Continuous variables were compared using the Mann–Whitney test and Kruskall Wallis test depending on data distribution and number of groups. Categorical variables were compared using the Chi-square test or Fischer's exact test whenever appropriate. Differences in survival were tested by log-rank test and uni- and multivariable Cox regression. Results: By categorizing the values of actinic fragments into interquartiles (Q1, Q2, and Q3), ACTBshort Q3 at baseline was significantly associated with negative PR expression (RRR 0.27, P = 0.012) and a higher frequency of liver metastasis (RRR = 3.75, P = 0.009). In terms of clinical outcomes, regarding PFS a significant role was observed for baseline ACTBshort Q3 (HR 1.92, P = 0.041) and ACTBmedium Q3 (HR 0.47, P = 0.043), the latter maintaining significance in multivariable analysis (HR 0.33, 95 %, P = 0.012). For OS, ACTBshort Q3 demonstrated a significant impact in both univariable (HR 3.94, P = 0.003) and multivariable analyses (HR 3.25, P = 0.023). Conclusions: This study demonstrates the feasibility of employing a fragmentomics mutation agnostic approach in luminal MBC. Baseline and longitudinal changes in ACTB fragments were significantly associated with clinical outcomes, suggesting their potential as non-invasive biomarkers for early risk classification and monitoring tumor dynamics

Progression independent of relapse activity in relapsing multiple sclerosis: impact and relationship with secondary progression

Objectives: We investigated the occurrence and relative contribution of relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA) to confirmed disability accrual (CDA) and transition to secondary progression (SP) in relapsing multiple sclerosis (MS). Methods: Relapsing-onset MS patients with follow-up &gt; / = 5&nbsp;years (16,130) were extracted from the Italian MS Registry. CDA was a 6-month confirmed increase in Expanded Disability Status Scale (EDSS) score. Sustained disability accumulation (SDA) was a CDA with no EDSS improvement in all subsequent visits. Predictors of PIRA and RAW and the association between final EDSS score and type of CDA were assessed using logistic multivariable regression and multivariable ordinal regression models, respectively. Results: Over 11.8 ± 5.4&nbsp;years, 16,731 CDA events occurred in 8998 (55.8%) patients. PIRA (12,175) accounted for 72.3% of CDA. SDA occurred in 8912 (73.2%) PIRA and 2583 (56.7%) RAW (p &lt; 0.001). 4453 (27.6%) patients transitioned to SPMS, 4010 (73.2%) out of 5476 patients with sustained PIRA and 443 (24.8%) out of 1790 patients with non-sustained PIRA. In the multivariable ordinal regression analysis, higher final EDSS score was associated with PIRA (estimated coefficient 0.349, 95% CI 0.120–0.577, p = 0.003). Discussion: In this real-world relapsing-onset MS cohort, PIRA was the main driver of disability accumulation and was associated with higher disability in the long term. Sustained PIRA was linked to transition to SP and could represent a more accurate PIRA definition and a criterion to mark the putative onset of the progressive phase

Selective inhibition of HDAC6 regulates expression of the oncogenic driver EWSR1-FLI1 through the EWSR1 promoter in Ewing sarcoma

Ewing sarcoma (EWS) is an aggressive bone and soft tissue tumor of children and young adults in which the principal driver is a fusion gene, EWSR1-FLI1. Although the essential role of EWSR1-FLI1 protein in the regulation of oncogenesis, survival, and tumor progression processes has been described in-depth, little is known about the regulation of chimeric fusion-gene expression. Here, we demonstrate that the active nuclear HDAC6 in EWS modulates the acetylation status of specificity protein 1 (SP1), consequently regulating the SP1/P300 activator complex binding to EWSR1 and EWSR1-FLI1 promoters. Selective inhibition of HDAC6 impairs binding of the activator complex SP1/P300, thereby inducing EWSR1-FLI1 downregulation and significantly reducing its oncogenic functions. In addition, sensitivity of EWS cell lines to HDAC6 inhibition is higher than other tumor or non-tumor cell lines. High expression of HDAC6 in primary EWS tumor samples from patients correlates with a poor prognosis in two independent series accounting 279 patients. Notably, a combination treatment of a selective HDAC6 and doxorubicin (a DNA damage agent used as a standard therapy of EWS patients) dramatically inhibits tumor growth in two EWS murine xenograft models. These results could lead to suitable and promising therapeutic alternatives for patients with EWS.Research in the E.D.A. lab is supported by Asociación Española Contra el Cáncer (AECC), the Ministry of Science of Spain-FEDER (CIBERONC, PI1700464, PI2000003, RD06/0020/0059)S. D.G.D. and L.H.P. are supported by CIBERONC (CB16/12/00361). D.G.D., M.J.R. and L.H.P. are PhD researchers funded by the Consejería de Salud, Junta de Andalucía (PI-0197-2016, ECAI F2-0012-2018 and PI-0013-2018, respectively).Peer reviewe

Stability and Hydrolyzation of Metal Organic Frameworks with Paddle-Wheel SBUs upon Hydration

Instability of most prototypical metal organic frameworks (MOFs) in the presence of moisture is always a limita- tion for industrial scale development. In this work, we examine the dissociation mechanism of microporous paddle wheel frameworks M(bdc)(ted)0.5 [M=Cu, Zn, Ni, Co; bdc= 1,4-benzenedicarboxylate; ted= triethylenediamine] in controlled humidity environments. Combined in-situ IR spectroscopy, Raman, and Powder x-ray diffraction measurements show that the stability and modification of isostructual M(bdc)(ted)0.5 compounds upon exposure to water vapor critically depend on the central metal ion. A hydrolysis reaction of water molecules with Cu-O-C is observed in the case of Cu(bdc)(ted)0.5. Displacement reactions of ted linkers by water molecules are identified with Zn(bdc)(ted)0.5 and Co(bdc)(ted)0.5. In contrast,. Ni(bdc)(ted)0.5 is less suscept- ible to reaction with water vapors than the other three compounds. In addition, the condensation of water vapors into the framework is necessary to initiate the dissociation reaction. These findings, supported by supported by first principles theoretical van der Waals density functional (vdW-DF) calculations of overall reaction enthalpies, provide the necessary information for de- termining operation conditions of this class of MOFs with paddle wheel secondary building units and guidance for developing more robust units

Cancer stem cell metabolism

Cancer is now viewed as a stem cell disease. There is still no consensus on the metabolic characteristics of cancer stem cells, with several studies indicating that they are mainly glycolytic and others pointing instead to mitochondrial metabolism as their principal source of energy. Cancer stem cells also seem to adapt their metabolism to microenvironmental changes by conveniently shifting energy production from one pathway to another, or by acquiring intermediate metabolic phenotypes. Determining the role of cancer stem cell metabolism in carcinogenesis has become a major focus in cancer research, and substantial efforts are conducted towards discovering clinical targets