The natural history of small cell lung cancer (SCLC) includes rapid evolution from chemosensitivity to chemoresistance, although mechanisms underlying this evolution remain obscure due to scarcity of post-relapse tissue samples. We generated circulating tumor cell (CTC)-derived xenografts (CDXs) from SCLC patients to study intratumoral heterogeneity (ITH) via single-cell RNAseq of chemo-sensitive and -resistant CDXs and patient CTCs. We found globally increased ITH including heterogeneous expression of therapeutic targets and potential resistance pathways, such as EMT, between cellular subpopulations following treatment-resistance. Similarly, serial profiling of patient CTCs directly from blood confirmed increased ITH post-relapse. These data suggest that treatment-resistance in SCLC is characterized by coexisting subpopulations of cells with heterogeneous gene expression leading to multiple, concurrent resistance mechanisms. These findings emphasize the need for clinical efforts to focus on rational combination therapies for treatment-naïve SCLC tumors to maximize initial responses and counteract the emergence of ITH and diverse resistance mechanisms.

Despite decreases in the overall US smoking rate, tobacco use remains more common in some areas and by some groups. Deeper understanding of group differences is needed in order to tailor public health campaigns to the interests, perceptions and experiences of targeted audiences. Although some differences have been identified across African American and Caucasian smokers in the United States, additional insight is needed regarding factors that differentiate these groups. This study examined tobacco-related perceptions and practices, with an emphasis on identifying differences across African American and Caucasian smokers. Toward this goal, we examined key demographic variables of race and age, and tobacco use characteristics.

The sample consisted of 284 people from the Jackson, Mississippi area who participated in focus groups and completed surveys addressing a variety of tobacco-related topics, including knowledge and perceptions of products as well as use and health information seeking behavior. The seleroups. Knowledge of such differences has the potential to improve strategic public health messaging, allowing health campaigns to more effectively prevent tobacco product uptake as well as promote interest in quitting tobacco.Polycystic kidney disease (PKD) is an inherited disorder characterized by renal cyst formation and enlargement of the kidney. PKD severity can be staged noninvasively by measuring total kidney volume (TKV), a promising biomarker that has recently received regulatory qualification. In preclinical mouse models, where the disease is studied and potential therapeutics are evaluated, the most popular noninvasive method of measuring TKV is magnetic resonance imaging (MRI). learn more Although MRI provides excellent 3D resolution and contrast, these systems are expensive to operate, have long acquisition times, and, consequently, are not heavily used in preclinical PKD research. In this study, a new imaging instrument, based on robotic ultrasound (US), was evaluated as a complementary approach for assessing PKD in rodent models. The objective was to determine the extent to which TKV measurements on the robotic US scanner correlated with both in vivo and ex vivo reference standards (MRI and Vernier calipers, respectively). A cross-sectional study design was implemented that included both PKD-affected mice and healthy wild types, spanning sex and age for a wide range of kidney volumes. It was found that US-derived TKV measurements and kidney lengths were strongly associated with both in vivo MRI and ex vivo Vernier caliper measurements (R2=0.94 and 0.90, respectively). In addition to measuring TKV, renal vascular density was assessed using acoustic angiography (AA), a novel contrast-enhanced US methodology. AA image intensity, indicative of volumetric vascularity, was seen to have a strong negative correlation with TKV (R2=0.82), suggesting impaired renal vascular function in mice with larger kidneys. These studies demonstrate that robotic US can provide a rapid and accurate approach for noninvasively evaluating PKD in rodent models.Purpose This study aimed to compare the risk of orthodontic mini-implant (OMI) failure between maxilla and mandible. A critical analysis of finite-element studies was used to explain the contradiction of the greatest clinical success for OMIs placed in the maxilla, despite the higher quality bone of mandible. Materials and Methods Four tridimensional FE models were built, simulating an OMI inserted in a low-dense maxilla, control maxilla, control mandible, and high-dense mandible. A horizontal force was applied to simulate an anterior retraction of 2 N (clinical scenario) and 10 N (overloading condition). The intra-bone OMI displacement and the major principal bone strains were used to evaluate the risk of failure due to insufficient primary stability or peri-implant bone resorption. Results The OMI displacement was far below the 50-100 µm threshold, suggesting that the primary stability would be sufficient in all models. However, the maxilla was more prone to lose its stability due to overload conditions, especially in the low-dense condition, in which major principal bone strains surpassed the pathologic bone resorption threshold of 3000 µstrain. Conclusions The differences in orthodontic mini-implant failures cannot be explained by maxilla and mandible bone quality in finite-element analysis that does not incorporate the residual stress due to OMI insertion.

Dysphagia is a common complication of critical illness, and many known risk factors are also present in critically ill coronavirus disease 2019 victims.

To investigate dysphagia in patients with severe coronavirus disease 2019.

In this case series, we report results of dedicated evaluation of swallowing function in six consecutive, tracheotomized coronavirus disease 2019 patients after they had survived acute respiratory distress syndrome and were weaned from the respirator.

Dysphagia was assessed with flexible endoscopic evaluation of swallowing.

Three patients suffered from severe dysphagia and airway compromise precluding decannulation, whereas in the other, three swallowing was less critically impaired, and the tracheal cannula could be removed. Four patients presented with additional laryngeal dysfunctions not typically seen in acute respiratory distress syndrome survivors.

Dysphagia with impaired airway protection is a key feature in coronavirus disease 2019 acute respiratory distress syndrome survivors.