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952 in the training cohort, which was well validated in the internal validation cohort and external cohort with the AUCs of 0.856 and 0.817, respectively. Furthermore, the predictive score was identified as the only independent predictor for pCR. Patients with high discriminant score showed a significantly longer overall and relapse-free survival (P<.05).
We developed the first and applicable three-lncRNA signature of pCR and outcome prediction, which is robust and reproducible in multicenter cohorts for ESCCs with nCRT.
We developed the first and applicable three-lncRNA signature of pCR and outcome prediction, which is robust and reproducible in multicenter cohorts for ESCCs with nCRT.
Sickle cell anemia (SCA) is a clinically heterogeneous, monogenic disorder. Medical care has less-than-optimal impact on clinical outcomes in SCA in Africa due to several factors, including patient accessibility, poor access to resources, and non-availability of specific effective interventions for SCA.
Against this background, we investigated 192 African participants who underwent whole exome sequencing. Participants included 105 SCA patients spanning variable clinical expression a “long survivor” group (age over 40 years), a “stroke” group (at least one episode of overt stroke), and a “random” group (patients younger than 40 years without overt cerebrovascular disease). Fifty-eight ethnically matched homozygous hemoglobin A controls were also studied. Findings were validated in an independently recruited sample of 29 SCA patients. Statistical significance of the mutational burden of deleterious and loss-of-function variants per gene against a null model was estimated for each group, and gene-set associa in clinical expression of SCA. Identified genes and pathways suggest new avenues for other interventions.Cancer stem cells (CSCs) are important factors contributing to tumorigenesis. We examined whether CSCs isolated from colorectal cancer (CRC) cells possess metastatic properties that can be transferred to non-CSCs via the delivery of miR-200c enclosed in extracellular vesicles (EVs). The inhibitory effect of atractylenolide I (ATL-1), a traditional Chinese medicinal compound, on miR-200c activity and metastatic transfer was investigated. EVs were isolated from colorectal CSCs. The expression of miR-200c was evaluated in CSCs and CSC-derived EVs, and horizontal transfer of metastatic properties via EVs to non-CSCs was investigated in terms of cell behavior and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling. CSCs isolated from metastatic CRC cells exhibited higher levels of miR-200c than those in nonmetastatic CRC cells. Overexpression of miR-200c in CSCs enhanced metastatic potential by promoting proliferation and inhibiting apoptosis, in turn leading to the release of EVs carrying an excess of miR-200c. Non-CSCs co-cultured with miR-200c-containing EVs exhibited enhanced invasion and stemness maintenance associated with PI3K/Akt/mTOR activation, demonstrating successful metastatic transfer via EV delivery. Furthermore, ATL-1 impaired the EV-mediated transfer of metastatic properties by suppressing miR-200c activity and disrupting EV uptake by non-CSCs. click here EVs are critical signal transducers that facilitate intercellular communication and exchange of metastatic properties, which can be controlled by ATL-1. The findings are useful in the development of microRNA-based anticancer strategies by targeting EV-mediated activity, especially using natural compounds.Trillions of microorganisms inhabiting in the human gut play an essential role in maintaining physical and mental health. The connections between gut microbiome and neuropsychiatric diseases have been recently identified. The pathogenesis of bipolar disorder, a spectrum of diseases manifesting with mood and energy fluctuations, also seems to be involved in the bidirectional modulation of the microbiome-gut-brain (MGB) axis. In this review, we briefly introduce the concept of MGB axis, and then focus on the previous findings in human studies associated with bipolar disorder. These studies provided preliminary evidences on the gut microbial alterations in bipolar disorder. Limitations in these studies and future directions in this research field, such as fecal microbiome transplantation and microbiome-targeted therapy, were discussed. A research framework linking gut microbiome to determinants and health-related outcomes in BD was also proposed. Better characterizing and understanding of gut microbial biosignatures in bipolar patients contribute to clarify the etiology of this intractable disease and pave the new way for treatment innovation.Spontaneous pneumothorax presents a unique diagnostic and therapeutic challenge in veterinary medicine, specifically with regard to accurate identification of bullous lesions. Positioning of dogs with spontaneous pneumothorax during CT has not previously been evaluated. This retrospective, diagnostic accuracy study was performed to evaluate the sensitivity, positive predictive value (PPV), and interobserver variability for detection of pulmonary bullae with dogs positioned in multiple recumbencies. Dogs underwent CT in sternal and dorsal recumbency followed by thoracic exploration via median sternotomy. Three American College of Veterinary Radiology-certified veterinary radiologists blinded to surgical findings reviewed dorsal and sternal images simultaneously. Severity of pneumothorax, degree of atelectasis, lesion location and size, and view in which lesions were most confidently identified were compared to surgical and histologic findings. Sensitivities and PPVs for bulla detection ranged from 57.7% to 69.2% and 62.1% to 78.9%, respectively. For two of the 3 radiologists, the location of bullae in the thorax was significantly associated with the recumbency in which the lesion was best identified. Degree of atelectasis was found to be associated with the ability to identify lesions (P ≤ .02). The interobserver variability for identification was good (κ = 0.670). The sensitivity of CT when performed in both sternal and dorsal recumbency is similar to that previously reported. Because the distribution of bullae is unknown prior to advanced imaging and bulla location affects which recumbency is most useful for identification, acquisition of CT images in both sternal and dorsal recumbency may improve detection of bullous lesions and aid surgical planning.