Predicting likelihood of in vivo chemotherapy response in canine lymphoma using ex vivo drug sensitivity and immunophenotyping data in a machine learning model

We report a precision medicine platform that evaluates the probability of chemotherapy drug efficacy for canine lymphoma by combining ex vivo chemosensitivity and immunophenotyping assays with computational modelling. We isolated live cancer cells from fresh fine needle aspirates of affected lymph nodes and collected post‐treatment clinical responses in 261 canine lymphoma patients scheduled to receive at least 1 of 5 common chemotherapy agents (doxorubicin, vincristine, cyclophosphamide, lomustine and rabacfosadine). We used flow cytometry analysis for immunophenotyping and ex vivo chemosensitivity testing. For each drug, 70% of treated patients were randomly selected to train a random forest model to predict the probability of positive Veterinary Cooperative Oncology Group (VCOG) clinical response based on input variables including antigen expression profiles and treatment sensitivity readouts for each patient's cancer cells. The remaining 30% of patients were used to test model performance. Most models showed a test set ROC‐AUC > 0.65, and all models had overall ROC‐AUC > 0.95. Predicted response scores significantly distinguished (P < .001) positive responses from negative responses in B‐cell and T‐cell disease and newly diagnosed and relapsed patients. Patient groups with predicted response scores >50% showed a statistically significant reduction (log‐rank P < .05) in time to complete response when compared to the groups with scores <50%. The computational models developed in this study enabled the conversion of ex vivo cell‐based chemosensitivity assay results into a predicted probability of in vivo therapeutic efficacy, which may help improve treatment outcomes of individual canine lymphoma patients by providing predictive estimates of positive treatment response.     

Polyhydroxylated alkaloids isolated from mulberry trees (Morusalba L.) and silkworms (Bombyx mori L.)

New polyhydroxylated alkaloids, (2R,3R,4R)-2-hydroxymethyl-3,4-dihydroxypyrrolidine-N-propionamide from the root bark of Morus alba L., and 4-O-alpha-D-galactopyranosyl-calystegine B(2) and 3 beta,6 beta-dihydroxynortropane from the fruits, were isolated by column chromatography using a variety of ion-exchange resins. Fifteen other polyhydroxylated alkaloids were also isolated. 1-Deoxynojirimycin, a potent alpha-glucosidase inhibitor, was concentrated 2.7-fold by silkworms feeding on mulberry leaves. Some alkaloids contained in mulberry leaves were potent inhibitors of mammalian digestive glycosidases but not inhibitors of silkworm midgut glycosidases, suggesting that the silkworm has enzymes specially adapted to enable it to feed on mulberry leaves. The possibility of preventing the onset of diabetes and obesity using natural dietary supplements containing 1-deoxynojirimycin and other alpha-glucosidase inhibitors in high concentration is of great potential interest.     

Limb‐sparing in dogs using patient‐specific,three‐dimensional‐printed endoprosthesis for distal radial osteosarcoma: A pilot study

Limb‐sparing for distal radial osteosarcoma has a high rate of complications. Using personalized three‐dimensional (3D)‐printed implants might improve outcome. The goals of this study were to optimize use of patient‐specific, 3D‐printed endoprostheses for limb‐sparing in dogs in the clinical environment and to report the outcome. This was a pilot study where five client‐owned dogs were enrolled. Computed tomography (CT) of the thoracic limbs was performed, which was used to create patient‐specific endoprostheses and cutting guides, and repeated on the day of surgery. Intra‐arterial (IA) carboplatin was introduced in the clinical management. Limb‐sparing was performed. Outcome measures were time required to produce the endoprosthesis and cutting guide, fit between cutting guide and endoprosthesis with host bones, gait analysis, size of the tumour, percent tumour necrosis, complications, disease‐free interval (DFI) and survival time (ST). Four dogs received IA carboplatin. Excessive tumour growth between planning CT and surgery did not occur in any dog. The interval between the CT and surgery ranged from 14 to 70 days. Fit between the cutting‐guide and endoprosthesis with the host bones was good to excellent. At least one complication occurred in all dogs. Two dogs were euthanized with STs of 192 and 531 days. The other dogs were alive with a follow up of 534 to 575 days. IA chemotherapy is a promising strategy to minimize the risk of excessive tumour growth while waiting for the endoprosthesis and cutting‐guide to be made. The design of the cutting‐guide was critical for best fit of the endoprosthesis with host bones.     

Advances in aquaculture : T.V.R. Pillay and W.A. Dill (Editors), Fishing News (Books) Ltd., London, 1979. 651 pp., £52.00, ISBN 0-85238-092-5

Twenty-one isolates of saprolegniaceous fungi representing three genera, viz. Achlya, Aphanomyces and Saprolegnia, were isolated from 19 different species of fishes from Indian waters. The pathogenicity of these isolates has been tested by conducting artificial inoculation experiments under controlled laboratory conditions (proving Koch's postulates) using Anabas testudineus Bl. and Channa punctatus Bl. as test fishes.     

Length–weight relationships for 21 coastal fish species of the Azores, north-eastern Atlantic

Length–weight relationships were estimated for 21 coastal fish species of the Azores, namely Abudefduf luridus, Bothus podas, Chromis limbata, Coris julis, Diplodus sargus, Echiichthys vipera, Gaidropsarus guttatus, Labrus bergylta, Mullus surmuletus, Phycis phycis, Pomatomus saltator, Sarda sarda, Scorpaena maderensis, Scorpaena notata, Seriola rivoliana, Serranus atricauda, Sparisoma cretense, Sphyraena viridensis, Synodus saurus, Thalassoma pavo and Trachinotus ovatus. Significant length–weight relationships were found for all species. Sexual dimorphism did not affect the length–weight relationships, except in the cases of S. cretense and C. julis. Length–length equations for converting size measurements (standard length (SL) and fork length (FL) to total length (TL)) are also presented for all fish species.     

Swim bladder inflation and survival of Mugil cephalus to 50 days

Excessive inflation of the swim bladder causes immobility and mortality of 12-day old larvae of Mugil cephalus and other marine fish. Increased aeration or mechanical agitation of the water in rearing tanks maintained the larvae below the water surface, and the swim bladder formed and functioned normally. Survival was dramatically increased. Two experimental production tanks, stocked initially with 15 000 and 20 000 larvae, at a density of 5.25 and 7.0/l, respectively, yielded 33.5% and 16.9% juveniles on day 50. Only an outbreak of ciliated parasites prevented both tanks from having survival figures of over 30%.     

Comparison of long-term progestin-based protocols to synchronize estrus before fixed-time artificial insemination in beef heifers

Two experiments were conducted to compare pregnancy rates resulting from fixed-time AI (FTAI) after administration of 1 of 2 long-term controlled internal drug release (CIDR)-based protocols. Heifers were assigned to treatment by age, BW, and pubertal status. The CIDR Select-treated heifers (Exp. 1, n = 37; Exp. 2, n = 192) received a CIDR (1.38 g of progesterone) from d 0 to 14, followed by 100 μg of GnRH, intramuscularly (i.m.) 9 d after CIDR removal (d 23) and PGF(2α) (25 mg, i.m.) 7 d after GnRH treatment (d 30). Heifers assigned to the Show-Me-Synch protocol (Exp. 1, n = 40; Exp. 2, n = 200) received a CIDR from d 0 to 14, followed by PGF(2α) 16 d later (d 30). Artificial insemination was performed at 72 or 66 h after PGF(2α) treatment for the CIDR Select- and Show-Me-Synch-treated heifers, respectively, and each heifer was given GnRH (100 μg, i.m.) at the time of AI. In Exp. 1, ovaries of each heifer were examined by transrectal ultrasonography on d 23 and 30 to characterize follicular dynamics. Follicles ≥5 mm and the presence of corpora lutea were recorded. On d 25, ovaries of each heifer were examined to characterize the status of dominant follicles recorded on d 23. Heifers were fitted with HeatWatch (DDx Inc., Denver, CO) estrus-detection transmitters at PGF(2α) to characterize estrus distribution up to FTAI. The diameter of dominant follicles on d 23 at PGF(2α) and on d 30, and the estrous response after PGF(2α) treatment up to the point of FTAI did not differ between CIDR Select- and Show-Me-Synch-treated heifers. Concentrations of progesterone in serum at PGF(2α) were greater (P = 0.07) in Show-Me-Synch- than CIDR Select-treated heifers (6.0 vs. 4.8 ng/mL, respectively). Pregnancy rates of heifers resulting from FTAI did not differ (P = 0.33) between CIDR Select- and Show-Me-Synch-treated heifers (CIDR Select, 59%; Show-Me-Synch, 70%). In Exp. 2, FTAI pregnancy rates tended (P = 0.07) to be greater in Show-Me-Synch-treated (62%) than in CIDR Select-treated (51%) heifers. Pregnancy rates at the end of the breeding season did not differ (P = 0.72; CIDR Select, 85%; Show-Me-Synch, 83%) between treatments. In summary, pregnancy rates resulting from FTAI were comparable for heifers assigned to each of the 2 long-term progestin-based protocols. The reduced treatment cost and animal handling associated with administration of the Show-Me-Synch protocol offer distinct advantages over the CIDR Select protocol despite similarities in pregnancy rates resulting from FTAI.