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Abstract Background This study aims to develop a machine learning-based application in a real-world medical domain to assist anesthesiologists in assessing the risk of complications in patients after a hip surgery. Methods Data from adult patients who underwent hip repair surgery at Chi-Mei Medical Center and its 2 branch hospitals from January 1, 2013, to March 31, 2020, were analyzed. Patients with incomplete data were excluded. A total of 22 features were included in the algorithms, including demographics, comorbidities, and major preoperative laboratory data from the database. The primary outcome was a composite of adverse events (in-hospital mortality, acute myocardial infarction, stroke, respiratory, hepatic and renal failure, and sepsis). Secondary outcomes were intensive care unit (ICU) admission and prolonged length of stay (PLOS). The data obtained were imported into 7 machine learning algorithms to predict the risk of adverse outcomes. Seventy percent of the data were randomly selected for training, leaving 30% for testing. The performances of the models were evaluated by the area under the receiver operating characteristic curve (AUROC). The optimal algorithm with the highest AUROC was used to build a web-based application, then integrated into the hospital information system (HIS) for clinical use. Results Data from 4,448 patients were analyzed; 102 (2.3%), 160 (3.6%), and 401 (9.0%) patients had primary composite adverse outcomes, ICU admission, and PLOS, respectively. Our optimal model had a superior performance (AUROC by DeLong test) than that of ASA-PS in predicting the primary composite outcomes (0.810 vs. 0.629, p

μ-glucosidases [GBA1 (glucocerebrosidase) and GBA2] are ubiquitous essential enzymes. Lysosomal GBA1 and cytosol-facing GBA2 degrade glucosylceramide (GlcCer); GBA1 deficiency causes Gaucher disease, a lysosomal storage disorder characterized by lysosomal accumulation of GlcCer, which is partly converted to glucosylsphingosine (GlcSph). GBA1 and GBA2 also may transfer glucose from GlcCer to cholesterol, yielding glucosylated cholesterol (GlcChol). Here, we aimed to clarify the role of zebrafish Gba2 in glycosphingolipid metabolism during Gba1 deficiency in zebrafish (Danio rerio), which are able to survive total Gba1 deficiency. We developed Gba1 (gba1−/−), Gba2 (gba2−/−), and double (gba1−/−:gba2−/−) zebrafish knockouts using CRISPR/Cas9 and explored the effects of both genetic and pharmacological interventions on GlcCer metabolism in individual larvae. Activity-based probes and quantification of relevant glycolipid metabolites confirmed enzyme deficiency. GlcSph increased in gba1−/− larvae (0.09 pmol/fish) but did not increase more in gba1−/−:gba2−/− larvae. GlcCer was comparable in gba1−/− and WT larvae but increased in gba2−/− and gba1−/−:gba2−/− larvae. Independent of Gba1 status, GlcChol was low in all gba2−/− larvae (0.05 vs. 0.18 pmol/fish in WT). Pharmacologic inactivation of zebrafish Gba1 comparably increased GlcSph. Inhibition of GlcCer synthase (GCS) in Gba1-deficient larvae reduced GlcCer and GlcSph, and concomitant inhibition of GCS and Gba2 with iminosugars also reduced excessive GlcChol. Finally, overexpression of human GBA1 and injection of recombinant GBA1 both decreased GlcSph. We determined that zebrafish larvae offer an attractive model to study glucosidase actions in glycosphingolipid metabolism in vivo, and we identified distinguishing characteristics of zebrafish Gba2 deficiency.

Abstract Background Cervical spondylotic myelopathy (CSM) is a degenerative cervical disease in which the spinal cord is compressed. Patients with CSM experience balance disturbance because of impaired proprioception. The weighting of the sensory inputs for postural control in patients with CSM is unclear. Therefore, this study investigated the weighting of sensory systems in patients with CSM. Method Twenty-four individuals with CSM (CSM group) and 24 age-matched healthy adults (healthy control group) were analyzed in this observational study. The functional outcomes (modified Japanese Orthopaedic Association Scale [mJOA], Japanese Orthopaedic Association Cervical Myelopathy Questionnaire [JOACMEQ], Nurick scale) and static balance (eyes-open and eyes-closed conditions) were assessed for individuals with CSM before surgery, 3 and 6 months after surgery. Time-domain and time–frequency-domain variables of the center of pressure (COP) were analyzed to examine the weighting of the sensory systems. Results In the CSM group, lower extremity function of mJOA and Nurick scale significantly improved 3 and 6 months after surgery. Before surgery, the COP mean velocity and total energy were significantly higher in the CSM group than in the control group for both vision conditions. Compared with the control group, the CSM group exhibited lower energy content in the moderate-frequency band (i.e., proprioception) and higher energy content in the low-frequency band (i.e., cerebellar, vestibular, and visual systems) under the eyes-open condition. The COP mean velocity of the CSM group significantly decreased 3 months after surgery. The energy content in the low-frequency band (i.e., visual and vestibular systems) of the CSM group was closed to that of the control group 6 months after surgery under the eyes-open condition. Conclusion Before surgery, the patients with CSM may have had compensatory sensory weighting for postural control, with decreased weighting on proprioception and increased weighting on the other three sensory inputs. After surgery, the postural control of the patients with CSM improved, with decreased compensation for the proprioceptive system from the visual and vestibular inputs. However, the improvement remained insufficient because the patients with CSM still had lower weighting on proprioception than the healthy adults did. Therefore, patients with CSM may require balance training and posture education after surgery. Trial registration Trial Registration number: NCT03396055 Name of the registry: ClinicalTrials.gov Date of registration: January 10, 2018 - Retrospectively registered Date of enrolment of the first participant to the trial: October 19, 2015