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Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are considered mutually exclusive in non-small cell lung cancer (NSCLC), especially in lung adenocarcinoma (LUAC). However, sporadic cases harboring concomitant EGFR and ALK alterations have been increasingly reported. There is no consensus opinion regarding the treatment of patients positive for both molecular alterations. Linderalactone inhibitor NSCLC with EGFR/ALK coalterations should be separated into two subtypes unifocal and multifocal LUAC. Here, we present an overview of the available literature regarding this rare group of patients to provide useful suggestions for therapeutic strategies.Severe coronavirus disease 2019 (COVID-19) is associated with increased risk of venous thromboembolism events (VTE). This study performed a systematic review in PubMed/EMBASE of studies reporting the prevalence of VTE in patients with COVID-19 who were totally screened/assessed for deep vein thrombosis (DVT) and/or for pulmonary embolism (PE). Among 47 candidate studies (n = 6459; 33 in Europe), 17 studies (n = 3973; weighted age 63.0 years, males 60%, intensive care unit (ICU) 16%) reported the prevalence of PE with a pooled estimate of 32% (95% CI 25, 40%), and 32 studies (n = 2552; weighted age 62.6 years, males 57%, ICU 49%) reported the prevalence of DVT with a pooled estimate of 27% (95% CI 21, 34%). A total of 36 studies reported the use of at least prophylactic antithrombotic treatment in the majority of their patients. Meta-regression analysis showed that the prevalence of VTE was higher across studies with a higher percentage of ICU patients and higher study population mean D-dimer values, and lower in studies with mixed dosing of anticoagulation in ⩾ 50% of the population compared to studies with standard prophylactic dosing of anticoagulation in less then 50% of the population. The pooled odds ratio for death in patients with COVID-19 and VTE versus those without VTE (17 studies, n = 2882) was 2.1 (95% CI 1.2, 3.6). Hospitalized patients with severe COVID-19 are at high VTE risk despite prophylactic anticoagulation. Further research should investigate the individualized VTE risk of patients with COVID-19 and the optimal preventive antithrombotic therapy. PROSPERO Registration No. CRD42020185543.
To evaluate the chemopreventive efficacy of hesperidin (Hsd) in 1,2-dimethylhydrazine (DMH)-induced colorectal cancer (CRC) and demonstrate its role in mothers against decapentaplegic homolog 4(Smad4) and activin A signaling pathways.

A CRC rat model was established by DMH exposure, and the animals were randomly divided into five groups Control group, Hsd, DMH, DMH + Hsd, and DMH followed by Hsd. The resected colon was subjected to macroscopic, microscopic, molecular, histopathological, and immunohistochemical examination. Activin A, Smad4, malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), and superoxide dismutase (SOD) levels in tissues were also measured. The DMH group exhibited a significant increase in the gene and protein expression of activin A as well as MDA and NO levels in tissues. There was a significant reduction in the gene and protein expression of Smad4 as well as GSH and SOD levels in tissues. Administration of Hsd significantly upregulated Smad4 and activin A gene expressions in both the DMH + Hsd and DMH followed by Hsd groups. Moreover, Hsd improved the antioxidant status of the former two groups.

This study demonstrated the chemopreventive effect of Hsd against CRC by modulating Smad4 and activin A signaling in vivo. Further studies are needed to demonstrate its clinical value and explore its possible role in advanced malignancy.
This study demonstrated the chemopreventive effect of Hsd against CRC by modulating Smad4 and activin A signaling in vivo. Further studies are needed to demonstrate its clinical value and explore its possible role in advanced malignancy.C9orf72 mutation (C9+) is a common genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis. C9+ clinical phenotype is heterogeneous and epilepsy has been recently described in few cases. We report a 47-year-old patient who developed reflex reading epilepsy (RRE) at the age of 19. After the first years with exclusive reflex seizures, afterwards the patients developed drug-resistant, unprovoked seizures and progressive cognitive deterioration. In the last years, a progressive motor impairment with spastic tetraparesis also occurred. During the hospitalization, the patient underwent an extensive workup identifying C9+ expansion and a family history suggestive for an autosomal dominant inheritance. This report, together with the few cases already described, raises the possibility that epileptic manifestations are part of the clinical phenotype of C9ORF72 mutation and reflect hyperexcitability of cortical networks involved in neurodegeneration.Objective/Background Illness severity and resultant dysfunction are often linearly related and tightly coupled (concordant). Some percentage of individuals, however, exhibit discordant associations (high illness severity and low dysfunction [HL] or low illness severity and high dysfunction [LH]). In the present study, a sample of subjects with insomnia complaints were evaluated to determine what percentage of subjects exhibited discordant associations. Participants Archival data were drawn from a community-based sample (n = 4,680; 61.8% female; Ages 18-105). Methods Median splits were calculated for illness severity and daytime dysfunction and each individual was typed as High (H) or Low (L) for the concordant (HH and LL) and discordant domains (HL and LH). Results Given this typology, 61% were classified as concordant and 39% were classified as discordant. Of these, 38% were sub-typed as HH, 23% as LL, 26% as LH, and 13% as HL. Conclusions We propose that some of the discordance may be ascribable to a mismatch between sleep need and sleep ability. Those "who need a lot, may suffer a lot, in the face of only a little (LH)", whereas those "who need a little, may suffer only a little, in the face of a lot (HL)".
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