A survival prediction model via interpretable machine learning for patients with oropharyngeal cancer following radiotherapy.

PURPOSE: To explore interpretable machine learning (ML) methods, with the hope of adding more prognosis value, for predicting survival for patients with Oropharyngeal-Cancer (OPC). METHODS: A cohort of 427 OPC patients (Training 341, Test 86) from TCIA database was analyzed. Radiomic features of gross-tumor-volume (GTV) extracted from planning CT using Pyradiomics, and HPV p16 status, etc. patient characteristics were considered as potential predictors. A multi-level dimension reduction algorithm consisting of Least-Absolute-Selection-Operator (Lasso) and Sequential-Floating-Backward-Selection (SFBS) was proposed to effectively remove redundant/irrelevant features. The interpretable model was constructed by quantifying the contribution of each feature to the Extreme-Gradient-Boosting (XGBoost) decision by Shapley-Additive-exPlanations (SHAP) algorithm. RESULTS: The Lasso-SFBS algorithm proposed in this study finally selected 14 features, and our prediction model achieved an area-under-ROC-curve (AUC) of 0.85 on the test dataset based on this feature set. The ranking of the contribution values calculated by SHAP shows that the top predictors that were most correlated with survival were ECOG performance status, wavelet-LLH_firstorder_Mean, chemotherapy, wavelet-LHL_glcm_InverseVariance, tumor size. Those patients who had chemotherapy, with positive HPV p16 status, and lower ECOG performance status, tended to have higher SHAP scores and longer survival; who had an older age at diagnosis, heavy drinking and smoking pack year history, tended to lower SHAP scores and shorter survival. CONCLUSION: We demonstrated predictive values of combined patient characteristics and imaging features for the overall survival of OPC patients. The multi-level dimension reduction algorithm can reliably identify the most plausible predictors that are mostly associated with overall survival. The interpretable patient-specific survival prediction model, capturing correlations of each predictor and clinical outcome, was developed to facilitate clinical decision-making for personalized treatment.

A multi-objective based radiomics feature selection method for response prediction following radiotherapy.

Objective.Radiomics contains a large amount of mineable information extracted from medical images, which has important significance in treatment response prediction for personalized treatment. Radiomics analyses generally involve high dimensions and redundant features, feature selection is essential for construction of prediction models.Approach.We proposed a novel multi-objective based radiomics feature selection method (MRMOPSO), where the number of features, sensitivity, and specificity are jointly considered as optimization objectives in feature selection. The MRMOPSO innovated in the following three aspects: (1) Fisher score to initialize the population to speed up the convergence; (2) Min-redundancy particle generation operations to reduce the redundancy between radiomics features, a truncation strategy was introduced to further reduce the number of features effectively; (3) Particle selection operations guided by elitism strategies to improve local search ability of the algorithm. We evaluated the effectiveness of the MRMOPSO by using a multi-institution oropharyngeal cancer dataset from The Cancer Imaging Archive. 357 patients were used for model training and cross validation, an additional 64 patients were used for evaluation.Main results.The area under the curve (AUC) of our method achieved AUCs of 0.82 and 0.84 for cross validation and independent dataset, respectively. Compared with classical feature selection methods, the AUC of MRMOPSO is significantly higher than the Lasso (AUC = 0.74,p-value = 0.02), minimal-redundancy-maximal-relevance criterion (mRMR) (AUC = 0.73,p-value = 0.05), F-score (AUC = 0.48,p-value < 0.01), and mutual information (AUC = 0.69,p-value < 0.01) methods. Compared to single-objective methods, the AUC of MRMOPSO is 12% higher than those of the genetic algorithm (GA) (AUC = 0.68,p-value = 0.02) and particle swarm optimization algorithm (AUC = 0.72,p-value = 0.05) methods. Compared to other multi-objective feature selection methods, the AUC of MRMOPSO is 14% higher than those of multiple objective particle swarm optimization (MOPSO) (AUC = 0.68,p-value = 0.02) and nondominated sorting genetic algorithm II (NSGA2) (AUC = 0.70,p-value = 0.03).Significance.We proposed a multi-objective based radiomics feature selection method. Compared to conventional feature reduction algorithms, the proposed algorithm effectively reduced feature dimension, and achieved superior performance, with improved sensitivity and specificity, for response prediction in radiotherapy.

Midline Lumbar Fusion Versus Posterior Lumbar Interbody Fusion Involving L5-S1 For Degenerative Lumbar Diseases: A Comparative Study.

BACKGROUND: A retrospective cohort study to evaluate the efficacy and safety of midline lumbar fusion (MIDLF) for lumbosacral fusion compared to posterior lumbar interbody fusion (PLIF). METHODS: Patients who had undergone posterior lumbosacral fusion surgery were divided into a MIDLF group (n = 37) and a PLIF group (n = 42). The follow-up time was at least 12 months. The operation data, recovery condition, complications, clinical outcomes, and status of implants and fusion were compared between the 2 groups. RESULTS: The MIDLF group experienced significantly less blood loss, lower postoperative creatine kinase levels and total drainage volume, earlier time to ambulation, and less hospital stay times after surgery compared to the PLIF group (P < 0.05). The mean postoperative back pain visual analog scale scores in the MIDLF group were significantly lower than the PLIF group (P < 0.05). The improvement in Oswestry Disability Index scores during 3-month follow-up displayed a significant difference between the 2 groups (P < 0.05). The fusion rate tended to be higher in the MIDLF group; however, the difference was not significant (P > 0.05). There was no significant difference in respect to screw loosening and cage subsidence rate. There were 2 cases of complications both occurring in the PLIF group. CONCLUSIONS: MIDLF is safe and effective for lumbosacral fusion and in line with the concept of enhanced recovery after surgery.

PABPN1L assemble into "ring-like" aggregates in the cytoplasm of MII oocytes and is associated with female infertility†.

Infertility affects 10-15% of families worldwide. However, the pathogenesis of female infertility caused by abnormal early embryonic development is not clear. A recent study showed that poly(A)binding protein nuclear 1-like (PABPN1L) recruited BTG anti-proliferation factor 4 (BTG4) to mRNA 3'-poly(A) tails and was essential for maternal mRNA degradation. Here, we generated a PABPN1L-antibody and found "ring-like" PABPN1L aggregates in the cytoplasm of MII oocytes. PABPN1L-EGFP proteins spontaneously formed "ring-like" aggregates in vitro. This phenomenon is similar with CCR4-NOT catalytic subunit, CCR4-NOT transcription complex subunit 7 (CNOT7), when it starts deadenylation process in vitro. We constructed two mouse model (Pabpn1l-/- and Pabpn1l  tm1a/tm1a) simulating the intron 1-exon 2 abnormality of human PABPN1L and found that the female was sterile and the male was fertile. Using RNA-Seq, we observed a large-scale up-regulation of RNA in zygotes derived from Pabpn1l-/- MII oocytes. We found that 9222 genes were up-regulated instead of being degraded in the Pabpn1l-♀/+♂zygote. Both the Btg4 and CCR4-NOT transcription complex subunit 6 like (Cnot6l) genes are necessary for the deadenylation process and Pabpn1l-/- resembled both the Btg4 and Cnot6l knockouts, where 71.2% genes stabilized in the Btg4-♀/+♂ zygote and 84.2% genes stabilized in the Cnot6l-♀/+♂zygote were also stabilized in Pabpn1l-♀/+♂ zygote. BTG4/CNOT7/CNOT6L was partially co-located with PABPN1L in MII oocytes. The above results suggest that PABPN1L is widely associated with CCR4-NOT-mediated maternal mRNA degradation and PABPN1L variants on intron 1-exon 2 could be a genetic marker of female infertility.

Low-intensity extracorporeal shock wave therapy for midshaft clavicular delayed union: A case report and review of literature.

BACKGROUND: One of the most common complications following surgery for midshaft clavicle fracture is nonunion/delayed union. Extracorporeal shock wave therapy (ESWT) is an alternative to promote new bone formation without surgical complications. To date, no literature has reported low-intensity ESWT (LI-ESWT) in delayed union of midshaft clavicle fracture. CASE SUMMARY: We reported a 66-year-old Chinese amateur cyclist with clavicle delayed union treated with 10 sessions of LI-ESWT (radial, 0.057 mJ/mm2, 3 Hz, 3000 shocks). No anesthetics were applied, and no side effects occurred. At the 4 mo and 7 mo follow-ups, the patient achieved clinical and radiographical recovery, respectively. CONCLUSION: In conclusion, our findings indicated that LI-ESWT could be a good option for treating midshaft clavicular delayed union.

Eef2k is not required for fertility in male mice.

BACKGROUND: Eukaryotic elongation factor-2 kinase (Eef2k) is a protein kinase associated with the calmodulin-induced signaling pathway and an atypical alpha-kinase family member. Eef2k-mediated phosphorylation of eukaryotic translation elongation factor 2 (Eef2) can inhibit the functionality of this protein, altering protein translation. Prior work suggests Eef2k to be overexpressed in breast, pancreatic, brain, and lung cancers wherein it may control key processes associated with apoptosis, autophagy, and cell cycle progression. The functional importance of Eef2k in the testes of male mice, however, has yet to be clarified. METHODS: A CRISPR/Cas9 approach was used to generate male Eef2k-knockout mice, which were evaluated for phenotypic changes in epididymal or testicular tissues through histological and immunofluorescent staining assays. In addition, TUNEL staining was conducted to assess the apoptotic death of cells in the testis. Fertility, sperm counts, and sperm motility were further assessed. RESULTS: Male Eef2k-knockout mice were successfully generated, and exhibited normal fertility and development. No apparent differences were observed with respect to spermatogenesis, sperm counts, or germ cell apoptosis when comparing male Eef2k -/- and Eef2k +/+ mice. CONCLUSIONS: Male Eef2k-knockout mice remained fertile and were free of any evident developmental or spermatogenic abnormalities, suggesting Eef2k to be dispensable in the context of male fertility.