Treatment of steroid-refractory chronic graft-versus-host disease (cGVHD) is a challenge. Here, we describe a retrospective analysis of 66 patients with steroid-refractory cGVHD treated with imatinib (starting dose of 100 mg in 70% of patients; maximum dose of 100-200 mg in 74%). Most patients had multi-organ involvement (≥2 organs, 83%), with the most affected being skin (85%), oral mucosa (55%), eyes (42%), and lungs (33%). The overall response rate was 41% (21 partial and three complete responses). The organ with the best response rate was the skin (46%), followed by gastrointestinal tract (43%), liver (41%), the oral mucosa (36%), eyes (29%), and lungs (18%). Imatinib led to steroid tapering in 17/38 patients. Twenty-five (38%) patients experienced imatinib-related adverse events, comprising extra-hematologic toxicity (n = 24, 36%) and hematologic toxicity (n = 6, 9%). No cases of grade 4-5 toxicity were reported. The main causes of imatinib discontinuation were treatment failure (52%) and toxicity (9%). After a median follow-up of 41 months, the 3-year overall survival was 81%, with no difference between imatinib responders and non-responders. These real-life results show that imatinib is safe and has moderate efficacy in patients with heavily pre-treated cutaneous sclerotic cGVHD; however, activity against lung cGVHD is very limited.This study aimed to determine the usefulness of colour and pulsed Doppler modes for the accurate diagnosis of donkeys suffering from subfertility to determine whether testicular vascularity assessment could be an indicator for sperm functionality. The study sample was composed of 10 male donkeys with normospermia (control group) and 10 donkeys with hypospermia. Animals underwent scrotal circumference measurement, testicular Doppler examination, seminal evaluation, blood sampling and hormonal assay. Semen volume and concentration were significantly (p ≤ .05) lower in the subfertile group (30.25 ± 1.22 ml and 89.44 ± 2.55 × 106 /ml) as compared with the control group (82.76 ± 1.65 ml and 452.78 ± 1.25 × 106 /ml), and total sperm/ejaculation was significantly (p ≤ .05) higher in the normal donkeys (28.30 ± 2.32 × 109 /total ejaculated) as compared with the subfertile group. Intratesticular coloured area showed a marked decline in the hypospermic males. There was no significant difference between the two groups in testosterone level, although the normal group showed an increase in nitric oxide metabolites. Both Doppler indices of the three branches of the testicular artery were elevated significantly (p ≤ .05) in abnormal donkeys, whereas Doppler peak systolic and end-diastolic velocities were increased in the normal group. Male donkeys with subfertility demonstrated lower arterial vascularity parameters in the form of intratesticular coloured area and blood flow rate; therefore, the most optimal parameters for differentiating subfertile hypospermic from normospermic donkeys were found to be the two Doppler indices, velocities parameters, testicular blood flow rate and nitric oxide levels.Squamous cell carcinoma (SCC) develops in more than 80% of individuals with the skin blistering disorder recessive dystrophic epidermolysis bullosa (RDEB). In contrast with UV-induced SCC, RDEB-SCC results from skin damage and has a high proliferative and metastatic rate with 5-year survival near zero. Our objective is to determine the mechanisms underlying the increased metastatic tendencies of RDEB-SCC. RDEB-SCC cultured cell lines were treated with RDEB and non-RDEB fibroblast conditioned media and assayed for migration and invasion with and without small molecule inhibitors for TGFβ and other downstream signal transduction pathways. TGFβ1 secreted by RDEB dermal fibroblasts has been found to induce migration and invasion and to increase expression of epithelial-to-mesenchymal transition markers in an RDEB-SCC line. These effects were reversed upon inhibition of TGFβ signalling and its downstream pathways MEK/ERK, P38 kinase and SMAD3. A number of small molecule inhibitors for these pathways are in different phases of various clinical trials and may be applicable to RDEB-SCC patients. Studying the mechanisms of the extreme form RDEB-SCC may inform studies of other types of SCC, as well as lead to better therapies for RDEB patients.
  Current standard practice for clinical radionuclide dosimetry utilizes reference phantoms, where defined organ dimensions represent population averages for a given sex and age. Greater phantom personalization would support more accurate dose estimations and personalized dosimetry. Tailoring phantoms is traditionally accomplished using operator-intensive organ-level segmentation of anatomic images. Modern mesh phantoms provide enhanced anatomical realism, which has motivated their integration within Monte Carlo codes. Here, we present an automatable strategy for generating patient-specific phantoms/dosimetry using intensity-based deformable image registration between mesh reference phantoms and patient CT images. This work demonstrates a proof-of-concept personalized dosimetry workflow, presented in comparison to the manual segmentation approach.
 
  A linear attenuation coefficient phantom was generated by resampling the PSRK-Man reference phantom onto a voxel grid and defining organ regions with correspondinmentation. Our study is limited to a proof-of-concept scope, but demonstrates that integration of personalized phantoms into clinical dosimetry workflows can reasonably be achieved when anatomical images (CT) are available.
 Deformable registration techniques can be used to create a personalized phantom and better support patient-specific dosimetry. This method is shown to be easier and faster than manual segmentation.  https://www.selleckchem.com/products/arv-110.html  Our study is limited to a proof-of-concept scope, but demonstrates that integration of personalized phantoms into clinical dosimetry workflows can reasonably be achieved when anatomical images (CT) are available.
  To assess cerebral oxygenation in premature infants who are transitioning from nasal continuous positive airway pressure (nCPAP) to heated humidified high-flow nasal cannula therapy (HFNC).
 
  A prospective observational study done in a single-centre neonatal intensive care unit (NICU). Regional cerebral oxygen saturations (RcSO
  ) were measured using frequency-domain near-infrared spectroscopy (FD-NIRS) in very low birthweight (VLBW) premature infants born at <32weeks transitioning from nCPAP to HFNC.
 
  Median gestational age was 27weeks and median birthweight was 924g. Recordings were performed at a median gestational age of 30weeks and a median postnatal age of 10days. Median weight at study entry was 1111g. Cerebral oxygenation was not significantly different in infants transitioning from nCPAP to HFNC (66% vs 66%).
 
  No difference in cerebral oxygenation in premature infants transitioning from nCPAP to HFNC was observed. This finding is reassuring and further supports the use of HFNC in preterm infants.