Spatial metabolomics reveals glycogen as an actionable target for pulmonary fibrosis.

Matrix assisted laser desorption/ionization imaging has greatly improved our understanding of spatial biology, however a robust bioinformatic pipeline for data analysis is lacking. Here, we demonstrate the application of high-dimensionality reduction/spatial clustering and histopathological annotation of matrix assisted laser desorption/ionization imaging datasets to assess tissue metabolic heterogeneity in human lung diseases. Using metabolic features identified from this pipeline, we hypothesize that metabolic channeling between glycogen and N-linked glycans is a critical metabolic process favoring pulmonary fibrosis progression. To test our hypothesis, we induced pulmonary fibrosis in two different mouse models with lysosomal glycogen utilization deficiency. Both mouse models displayed blunted N-linked glycan levels and nearly 90% reduction in endpoint fibrosis when compared to WT animals. Collectively, we provide conclusive evidence that lysosomal utilization of glycogen is required for pulmonary fibrosis progression. In summary, our study provides a roadmap to leverage spatial metabolomics to understand foundational biology in pulmonary diseases.

Targetable IDH1 mutation identified in a rare case of pancreatic serous cystadenocarcinoma but not a series of serous cystadenomas.

Serous cystadenocarcinoma (SCAC) of the pancreas is rare, with only 35 cases reported in the literature. We present a case of SCAC, comparing the clinical presentation, management and molecular features of this case to a series of serous cystadenoma (SCA), which may be a precursor. Compared with SCAs (n = 5), SCAC was larger (11.5 vs median 3.6 cm). The case of SCAC invaded the spleen and exhibited distant metastasis, a requirement for diagnosis since pathologic features are otherwise indistinguishable from SCA. VHL mutations have been reported in about half of SCA in the literature. Accordingly, we identified either somatic or germline VHL mutations in 3 of 5 SCAs (60%), yet no pathogenic mutation was identified in the SCAC. A somatic mutation in IDH1 was found in SCAC only. This has been associated with multiple malignancies, is targetable with the drug ivosidenib and should be studied as a progression factor in SCAC.

Acute lower extremity running kinematics after a hamstring stretch.

CONTEXT: Limited passive hamstring flexibility might affect kinematics, performance, and injury risk during running. Preactivity static straight-leg raise stretching often is used to gain passive hamstring flexibility. OBJECTIVE: To investigate the acute effects of a single session of passive hamstring stretching on pelvic, hip, and knee kinematics during the swing phase of running. DESIGN: Randomized controlled clinical trial. SETTING: Biomechanics research laboratory. PATIENTS OR OTHER PARTICIPANTS: Thirty-four male (age = 21.2 ± 1.4 years) and female (age = 21.3 ± 2.0 years) recreational athletes. INTERVENTION(S): Participants performed treadmill running pretests and posttests at 70% of their age-predicted maximum heart rate. Pelvis, hip, and knee joint angles during the swing phase of 5 consecutive gait cycles were collected using a motion analysis system. Right and left hamstrings of the intervention group participants were passively stretched 3 times for 30 seconds in random order immediately after the pretest. Control group participants performed no stretching or movement between running sessions. MAIN OUTCOME MEASURE(S): Six 2-way analyses of variance to determine joint angle differences between groups at maximum hip flexion and maximum knee extension with an α level of .008. RESULTS: Flexibility increased between pretest and posttest in all participants (F(1,30) = 80.61, P < .001). Anterior pelvic tilt (F(1,30) = 0.73, P = .40), hip flexion (F(1,30) = 2.44, P = .13), and knee extension (F(1,30) = 0.06, P = .80) at maximum hip flexion were similar between groups throughout testing. Anterior pelvic tilt (F(1,30) = 0.69, P = .41), hip flexion (F(1,30) = 0.23, P = .64), and knee extension (F(1,30) = 3.38, P = .62) at maximum knee extension were similar between groups throughout testing. Men demonstrated greater anterior pelvic tilt than women at maximum knee extension (F(1,30) = 13.62, P = .001). CONCLUSIONS: A single session of 3 straight-leg raise hamstring stretches did not change pelvis, hip, or knee running kinematics.