Development and evaluation of a deep learning-based model for simultaneous detection and localization of rib and clavicle fractures in trauma patients' chest radiographs.

Purpose: To develop a rib and clavicle fracture detection model for chest radiographs in trauma patients using a deep learning (DL) algorithm. Materials and methods: We retrospectively collected 56 145 chest X-rays (CXRs) from trauma patients in a trauma center between August 2008 and December 2016. A rib/clavicle fracture detection DL algorithm was trained using this data set with 991 (1.8%) images labeled by experts with fracture site locations. The algorithm was tested on independently collected 300 CXRs in 2017. An external test set was also collected from hospitalized trauma patients in a regional hospital for evaluation. The receiver operating characteristic curve with area under the curve (AUC), accuracy, sensitivity, specificity, precision, and negative predictive value of the model on each test set was evaluated. The prediction probability on the images was visualized as heatmaps. Results: The trained DL model achieved an AUC of 0.912 (95% CI 87.8 to 94.7) on the independent test set. The accuracy, sensitivity, and specificity on the given cut-off value are 83.7, 86.8, and 80.4, respectively. On the external test set, the model had a sensitivity of 88.0 and an accuracy of 72.5. While the model exhibited a slight decrease in accuracy on the external test set, it maintained its sensitivity in detecting fractures. Conclusion: The algorithm detects rib and clavicle fractures concomitantly in the CXR of trauma patients with high accuracy in locating lesions through heatmap visualization.

Motion compensated cone-beam CT reconstruction using ana priorimotion model from CT simulation: a pilot study.

Objective. To combat the motion artifacts present in traditional 4D-CBCT reconstruction, an iterative technique known as the motion-compensated simultaneous algebraic reconstruction technique (MC-SART) was previously developed. MC-SART employs a 4D-CBCT reconstruction to obtain an initial model, which suffers from a lack of sufficient projections in each bin. The purpose of this study is to demonstrate the feasibility of introducing a motion model acquired during CT simulation to MC-SART, coined model-based CBCT (MB-CBCT).Approach. For each of 5 patients, we acquired 5DCTs during simulation and pre-treatment CBCTs with a simultaneous breathing surrogate. We cross-calibrated the 5DCT and CBCT breathing waveforms by matching the diaphragms and employed the 5DCT motion model parameters for MC-SART. We introduced the Amplitude Reassignment Motion Modeling technique, which measures the ability of the model to control diaphragm sharpness by reassigning projection amplitudes with varying resolution. We evaluated the sharpness of tumors and compared them between MB-CBCT and 4D-CBCT. We quantified sharpness by fitting an error function across anatomical boundaries. Furthermore, we compared our MB-CBCT approach to the traditional MC-SART approach. We evaluated MB-CBCT's robustness over time by reconstructing multiple fractions for each patient and measuring consistency in tumor centroid locations between 4D-CBCT and MB-CBCT.Main results. We found that the diaphragm sharpness rose consistently with increasing amplitude resolution for 4/5 patients. We observed consistently high image quality across multiple fractions, and observed stable tumor centroids with an average 0.74 ± 0.31 mm difference between the 4D-CBCT and MB-CBCT. Overall, vast improvements over 3D-CBCT and 4D-CBCT were demonstrated by our MB-CBCT technique in terms of both diaphragm sharpness and overall image quality.Significance. This work is an important extension of the MC-SART technique. We demonstrated the ability ofa priori5DCT models to provide motion compensation for CBCT reconstruction. We showed improvements in image quality over both 4D-CBCT and the traditional MC-SART approach.

Performance and Solution Structures of Side-Chain-Bridged Oligo (Ethylene Glycol) Polymer Photocatalysts for Enhanced Hydrogen Evolution under Natural Light Illumination.

Converting solar energy into hydrogen energy using conjugated polymers (CP) is a promising solution to the energy crisis. Improving water solubility plays one of the critical factors in enhancing the hydrogen evolution rate (HER) of CP photocatalysts. In this study, a novel concept of incorporating hydrophilic side chains to connect the backbones of CPs to improve their HER is proposed. This concept is realized through the polymerization of carbazole units bridged with octane, ethylene glycol, and penta-(ethylene glycol) to form three new side-chain-braided (SCB) CPs: PCz2S-OCt, PCz2S-EG, and PCz2S-PEG. Verified through transient absorption spectra, the enhanced capability of PCz2S-PEG for ultrafast electron transfer and reduced recombination effects has been demonstrated. Small- and wide-angle X-ray scattering (SAXS/WAXS) analyses reveal that these three SCB-CPs form cross-linking networks with different mass fractal dimensions (f) in aqueous solution. With the lowest f value of 2.64 and improved water/polymer interfaces, PCz2S-PEG demonstrates the best HER, reaching up to 126.9 µmol h-1 in pure water-based photocatalytic solution. Moreover, PCz2S-PEG exhibits comparable performance in seawater-based photocatalytic solution under natural sunlight. In situ SAXS analysis further reveals nucleation-dominated generation of hydrogen nanoclusters with a size of ≈1.5 nm in the HER of PCz2S-PEG under light illumination.

SNAP29 mediates the assembly of histidine-induced CTP synthase filaments in proximity to the cytokeratin network.

Under metabolic stress, cellular components can assemble into distinct membraneless organelles for adaptation. One such example is cytidine 5'-triphosphate synthase (CTPS, for which there are CTPS1 and CTPS2 forms in mammals), which forms filamentous structures under glutamine deprivation. We have previously demonstrated that histidine (His)-mediated methylation regulates the formation of CTPS filaments to suppress enzymatic activity and preserve the CTPS protein under glutamine deprivation, which promotes cancer cell growth after stress alleviation. However, it remains unclear where and how these enigmatic structures are assembled. Using CTPS-APEX2-mediated in vivo proximity labeling, we found that synaptosome-associated protein 29 (SNAP29) regulates the spatiotemporal filament assembly of CTPS along the cytokeratin network in a keratin 8 (KRT8)-dependent manner. Knockdown of SNAP29 interfered with assembly and relaxed the filament-induced suppression of CTPS enzymatic activity. Furthermore, APEX2 proximity labeling of keratin 18 (KRT18) revealed a spatiotemporal association of SNAP29 with cytokeratin in response to stress. Super-resolution imaging suggests that during CTPS filament formation, SNAP29 interacts with CTPS along the cytokeratin network. This study links the cytokeratin network to the regulation of metabolism by compartmentalization of metabolic enzymes during nutrient deprivation.

Mechanical Thrombectomy and Stenting for Radiation-Induced Carotid Stenosis-Related Stroke: A Case Report.

Radiation-induced stenosis of the carotid artery is a significant risk factor for large-vessel ischemic stroke, which usually leads to significant impairment of neurological function. We performed intra-arterial thrombectomy on a 63-year-old male patient who had laryngeal cancer and postradiation carotid stenosis. He presented with acute-onset dysarthria and left hemiplegia. Brain computed tomography perfusion scan showed right middle cerebral artery ischemic change. Angiography confirmed total occlusion of the right internal carotid artery. Intra-arterial mechanical thrombectomy with carotid stenting was performed immediately, and recanalization was achieved. The patient fully recovered and was discharged after a 1-week hospitalization. Our experience suggests that early intervention for radiation-related carotid stenosis might be essential and beneficial for the outcome of large-vessel ischemic stroke.

Three-Dimensional Conformal Radiotherapy-Based or Intensity-Modulated Radiotherapy-Based Concurrent Chemoradiotherapy in Patients with Thoracic Esophageal Squamous Cell Carcinoma.

BACKGROUND: To date, intensity-modulated radiation therapy (IMRT) with concurrent chemoradiotherapy (CCRT) and CCRT with standard fractionation three-dimensional conformal radiation therapy (3D-CRT) have not been compared. In this study, the outcomes of IMRT-based concurrent CCRT and those of 3D-CRT-based CCRT were compared in patients with thoracic esophageal squamous cell carcinoma (TESCC). METHODS: We enrolled 2062 patients with TESCC who had received CCRT and categorized them into two groups on the basis of their treatment modality: Group 1 (3D-CRT-based CCRT) and Group 2 (IMRT-based CCRT). RESULTS: Multivariate Cox regression analysis indicated that the American Joint Committee on Cancer advanced stages (≥IIIA) and 3D-CRT were significant independent predictors of poor outcomes in patients with TESCC who received definitive CCRT. Moreover, receiving IMRT-based CCRT (adjusted hazard ratio [aHR]: 0.88, 95% confidence interval [CI]: 0.78-0.98) was a significant independent prognostic factor for overall survival (p = 0.0223). In Group 2, aHRs (95% CIs) for overall mortality at early (IA-IIB) and advanced clinical stages were 0.91 (0.67-1.25, p = 0.5746) and 0.88 (0.77-0.99, p = 0.0368), respectively. CONCLUSION: IMRT-based CCRT resulted in higher survival rates in patients with advanced clinical stages of TESCC (i.e., IIIA-IIIC), namely, clinical T3, clinical T4, or lymph node involvement.

Histidine-Dependent Protein Methylation Is Required for Compartmentalization of CTP Synthase.

CTP synthase (CTPS) forms compartmentalized filaments in response to substrate availability and environmental nutrient status. However, the physiological role of filaments and mechanisms for filament assembly are not well understood. Here, we provide evidence that CTPS forms filaments in response to histidine influx during glutamine starvation. Tetramer conformation-based filament formation restricts CTPS enzymatic activity during nutrient deprivation. CTPS protein levels remain stable in the presence of histidine during nutrient deprivation, followed by rapid cell growth after stress relief. We demonstrate that filament formation is controlled by methylation and that histidine promotes re-methylation of homocysteine by donating one-carbon intermediates to the cytosolic folate cycle. Furthermore, we find that starvation stress and glutamine deficiency activate the GCN2/ATF4/MTHFD2 axis, which coordinates CTPS filament formation. CTPS filament formation induced by histidine-mediated methylation may be a strategy used by cancer cells to maintain homeostasis and ensure a growth advantage in adverse environments.

Efficacy of thoracic radiotherapy in patients with stage IIIB-IV epidermal growth factor receptor-mutant lung adenocarcinomas who received and responded to tyrosine kinase inhibitor treatment.

PURPOSE: Large-scale, prospective, randomized studies of the efficacy of thoracic radiotherapy (RT) in patients with unresectable stage IIIB-IV epidermal growth factor receptor (EGFR)-mutant lung adenocarcinomas who received and responded to EGFR tyrosine kinase inhibitor (TKI) treatment are not currently available. Therefore, we designed a propensity score-matched, nationwide, population-based, cohort study for estimating the effects of thoracic RT on patients with EGFR-mutant lung adenocarcinomas. PATIENTS AND METHODS: We analyzed patients with unresectable stage IIIB-IV EGFR mutant lung adenocarcinomas and categorized them into two groups according to treatment modality and compared their outcomes; groups 1 and 2 consisted of patients who received EGFR TKI treatment alone until tumor progression and those who received and responded to EGFR TKI treatment and subsequently received thoracic RT for lung tumors, respectively. The patients in groups 2 and 1 were matched at a ratio of 1:4. RESULTS: The matching process yielded a final cohort of 1475 patients (1180 and 295 patients in groups 1 and 2, respectively) who were eligible for further analysis. According to both univariate and multivariate Cox regression analyses, the adjusted hazard ratios (aHRs) (95% confidence interval [CI]) derived for thoracic RT for lung tumor after EGFR TKI use and tumor response (group 2) compared with EGFR TKI treatment alone (group 1) was 0.72 (0.60-0.85). CONCLUSIONS: Thoracic RT might be associated with overall survival in patients with unresectable stage IIIB-IV EGFR-mutant lung adenocarcinomas who received and responded to EGFR TKI treatment.

Effects of Risperidone and Aripiprazole on Serum Levels of Prolactin, Testosterone and Estradiol in Female Patients with Schizophrenia.

OBJECTIVE: To evaluate the effects of treatment with risperidone and aripiprazole on serum prolactin, testosterone and estradiol levels in female patients with schizophrenia in China. METHODS: In the retrospective study, Data were collected and included prolactin, testosterone and estradiol levels of 30 female patients with risperidone monotherapy. In the prospective study, Another 30 female schizophrenic patients were randomized to receive risperidone or adjunctive aripiprazole for six weeks. Serum prolactin, testosterone and estradiol levels were measured. RESULTS: Serum prolactin, testosterone and estradiol levels in both studies were significantly decreased after risperidone treatment compared with baseline (P<0.05), and prolactin levels remained at a high level. Serum prolactin levels in the adjunctive aripiprazole group were significantly decreased after treatment compared with baseline in the prospective study (P<0.05). Doses of 5 mg and 10 mg of adjunctive aripiprazole achieved the same efficacy at the end of treatment. CONCLUSIONS: Risperidone treatment decreased serum testosterone and estradiol levels. Adjunctive aripiprazole relieved hyperprolactinemia, but had no effect on testosterone or estradiol levels. Adjunctive aripiprazole at a dose of 5 mg is recommended for clinical use.

Dose escalation intensity-modulated radiotherapy-based concurrent chemoradiotherapy is effective for advanced-stage thoracic esophageal squamous cell carcinoma.

PURPOSE: No studies have investigated the effects of irradiation-dose escalation intensity-modulated radiotherapy (IMRT)-based concurrent chemoradiotherapy (CCRT) in patients with thoracic esophageal squamous cell carcinoma (TESCC). PATIENTS AND METHODS: We analyzed data from patients with TESCC who were enrolled in the Taiwan Cancer Registry database. To compare treatment outcomes, the patients were categorized into two groups according to their radiotherapy doses: group 1, who received CCRT<60Gy with IMRT, and group 2, who received CCRT≥60Gy with IMRT. Group 1 was used as the control for investigating posttreatment mortality risk. RESULTS: We enrolled 2061 patients with TESCC without distant metastasis who received CCRT with IMRT. Multivariate Cox regression analysis indicated that advanced clinical American Joint Committee on Cancer (AJCC) stage (≥IIIA), alcohol consumption, and cigarette smoking were significant, poor independent predictors in patients with TESCC receiving IMRT-based CCRT. IMRT-based CCRT (≥60Gy; adjusted hazard ratio [aHR]: 0.75; 95% confidence interval [CI]: 0.63-0.83) was a significant independent prognostic factor for overall survival (P<0.0001). After adjustment for confounders, the aHRs (95% CIs) for overall mortality at all clinical stages were 0.75 (0.68-0.83, P<0.0001) in group 2. In group 2, the aHRs (95% CIs) for overall mortality at early (IA-IIB) and advanced (IIIA-IIIC) AJCC clinical stages were 0.89 (0.70-1.04, P=0.1905) and 0.75 (0.67-0.83, P<0.0001), respectively. CONCLUSION: Compared with standard-dose IMRT-based CCRT, high-dose IMRT-based CCRT yields more favorable survival outcomes in patients with advanced-stage TESCC.

Value and application of trimodality therapy or definitive concurrent chemoradiotherapy in thoracic esophageal squamous cell carcinoma.

BACKGROUND: Few large, prospective, randomized studies have investigated the value and optimal application of neoadjuvant chemoradiotherapy followed by surgery (trimodality therapy) or definitive concurrent chemoradiotherapy (CCRT) for patients with thoracic esophageal squamous cell carcinoma (TESCC). METHODS: The authors analyzed data from patients with TESCC in the Taiwan Cancer Registry database. To compare their outcomes, patients with TESCC were enrolled and categorized into the following groups according to treatment modality: group 1, those who underwent surgery alone; group 2, those who received trimodality therapy; and group 3, those who received definitive CCRT. Group 1 was used as the control arm for investigating the risk of mortality after treatment. RESULTS: In total, 3522 patients who had TESCC without distant metastasis were enrolled. Multivariate Cox regression analysis indicated that a Charlson comorbidity index score ≥3, American Joint Committee on Cancer stage ≥IIA, earlier year of diagnosis, alcohol consumption, cigarette smoking, and definitive CCRT were significant, independent predictors of a poor prognosis. After adjustment for confounders, adjusted hazard ratios and 95% confidence intervals (CIs) for overall mortality in patients with clinical stage I, IIA, IIB, IIIA, IIIB, and IIIC TESCC were 2.01 (95% CI, 0.44-6.18), 1.65 (95% CI, 0.99-2.70), 1.48 (95% CI, 0.91-2.42), 0.66 (95% CI, 1.08-1.14), 0.39 (95% CI, 0.26-0.57), and 0.44 (95% CI, 0.24-0.83), respectively, in group 2; and 2.06 (95% CI, 1.18-3.59), 2.65 (95% CI, 1.76-4.00), 2.25 (95% CI, 1.49-3.39), 1.34 (95% CI, 0.79-2.28), 0.82 (95% CI, 0.57-1.17), and 0.93 (95% CI, 0.51-1.71), respectively, in group 3. CONCLUSIONS: Trimodality therapy may be beneficial for the survival of patients with advanced-stage (IIIA-IIIC) TESCC, and CCRT might be an alternative to surgery alone in these patients. Cancer 2017;123:3904-15. © 2017 American Cancer Society.

Effectiveness of esophagectomy in patients with thoracic esophageal squamous cell carcinoma receiving definitive radiotherapy or concurrent chemoradiotherapy through intensity-modulated radiation therapy techniques.

BACKGROUND: Few large, prospective, randomized studies have investigated the effectiveness of esophagectomy in patients with thoracic esophageal squamous cell carcinoma (TESCC) who receive definitive radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) through modern, intensity modulated-RT (IMRT) techniques. The therapeutic effects of esophagectomy in patients with TESCC were evaluated using modern clinical staging and RT techniques and suitable RT doses. METHODS: The authors analyzed data from patients with TESCC from the Taiwan Cancer Registry database. Patients were categorized into the following groups on the basis of treatment modality to compare their outcomes: group 1 received definitive CCRT, group 2 received neoadjuvant RT followed by esophagectomy (total IMRT dose, ≥50 grays [Gy]), and group 3 receiving neoadjuvant CCRT followed by esophagectomy (total IMRT dose, ≥ 50 Gy). The median total RT dose and fraction size were 50.4 Gy and 1.8 Gy per fraction, respectively. Group 1 was used as the control arm for investigating the risk of mortality after treatment. RESULTS: In total, 3123 patients who had TESCC without distant metastasis were enrolled. Patient ages 65 years and older, Charlson comorbidity index scores ≥3, advanced clinical stages (IIA-IIIC), alcohol consumption, and cigarette smoking were identified as significant, independent poor prognostic risk factors for overall survival in multivariate Cox regression analyses. In group 3, after adjustment for confounders, the adjusted hazard ratios (95% confidence intervals [CIs]) for overall mortality were 0.62 (95% CI, 0.41-0.93) for patients with clinical stage IIA disease, 0.61 (95% CI, 0.41-0.91) for those with clinical stage IIB disease, 0.47 (95% CI, 0.38-0.55) for those with clinical stage IIIA disease, 0.47 (95% CI, 0.39-0.56) for those with clinical stage IIIB disease, and 0.46 (95% CI, 0.37-0.57) for those with clinical stage IIIC disease. CONCLUSIONS: Esophagectomy can be beneficial in patients with TESCC after definitive CCRT, especially in those who have advanced-stage disease. Cancer 2017;123:2043-2053. © 2017 American Cancer Society.

Microwave-Assisted Synthesis of Nanoporous Aluminum-Based Coordination Polymers as Catalysts for Selective Sulfoxidation Reaction.

A series of aluminum-based coordination polymers or metal⁻organic frameworks (Al⁻MOFs), i.e., DUT-4, DUT-5, MIL-53, NH2-MIL-53, and MIL-100, have been facile prepared by microwave (MW)-assisted reactions and used as catalysts for selective sulfoxidation reactions. The MW-assisted synthesis drastically reduced the reaction time from few days to hours. The prepared MOFs have smaller and uniform particle sizes and better yield compared to conventional hydrothermal method. Furthermore, the Al⁻MOFs have been successfully demonstrated as catalysts in oxidation reaction of methyl phenyl sulfide with H2O2 as oxidant, even under mild conditions, with more than 95% conversion.

Efficacy of postoperative radiotherapy in patients with pathological stage N2 epidermal growth factor receptor wild type adenocarcinoma and squamous cell carcinoma lung cancer.

PURPOSE: Few large, prospective, randomized studies have compared the effects of postoperative radiotherapy (PORT) in pathological N2 (pN2) with those of surgical resection alone. in terms of long-term survival in lung adenocarcinoma (adenoCA; wild-type [WT] epidermal growth factor receptor [EGFR]) and squamous cell carcinoma (squCA) settings. This nationwide cohort study clarifies the role of PORT in the survival of pN2 lung adenoCA (WT EGFR) and squCA patientsPatients and Methods: We analyzed data of patients with adenoCA (WT EGFR) and squCA collected from the Taiwan Cancer Registry database. The patients were categorized into five groups according to the treatment modality: Group 1 (surgery alone), Group 2 (adjuvant chemotherapy [CT] alone), Group 3 (adjuvant radiotherapy [RT] alone), Group 4 (adjuvant concurrent chemoradiotherapy [CCRT]), and Group 5 (adjuvant sequential CT and intensity-modulated RT [IMRT]). RESULTS: We enrolled 588 lung adenoCA (WT EGFR) and squCA patients without distant metastasis. After adjustments for age at surgery, surgical years, and Charlson comorbidity index scores, the multivariate Cox regression analysis demonstrated that adjusted HRs (aHRs; 95% confidence intervals [CIs]) for the overall mortality of female lung adenoCA (WT EGFR) patients were 0.257 (0.111-0.594), 0.530 (0.226-1.243), 0.192 (0.069-0.534), and 0.399 (0.172-0.928) in Groups 2, 3, 4, and 5, respectively. For male lung squCA patients, the aHRs (95% CIs) for overall mortality were 0.269 (0.160-0.451), 0.802 (0.458-1.327), 0.597 (0.358-0.998), and 0.456 (0.265-0.783) in Groups 2, 3, 4, and 5, respectively. CONCLUSIONS: Adjuvant CCRT or sequential CT and IMRT at ≥5000 cGy significantly reduced the mortality rate of female lung adenoCA (WT EGFR) and male squCA pN2 patients.

Obatoclax, a Pan-BCL-2 Inhibitor, Targets Cyclin D1 for Degradation to Induce Antiproliferation in Human Colorectal Carcinoma Cells.

Colorectal cancer is the third most common cancer worldwide. Aberrant overexpression of antiapoptotic BCL-2 (B-cell lymphoma 2) family proteins is closely linked to tumorigenesis and poor prognosis in colorectal cancer. Obatoclax is an inhibitor targeting all antiapoptotic BCL-2 proteins. A previous study has described the antiproliferative action of obatoclax in one human colorectal cancer cell line without elucidating the underlying mechanisms. We herein reported that, in a panel of human colorectal cancer cell lines, obatoclax inhibits cell proliferation, suppresses clonogenicity, and induces G1-phase cell cycle arrest, along with cyclin D1 downregulation. Notably, ectopic cyclin D1 overexpression abrogated clonogenicity suppression but also G1-phase arrest elicited by obatoclax. Mechanistically, pre-treatment with the proteasome inhibitor MG-132 restored cyclin D1 levels in all obatoclax-treated cell lines. Cycloheximide chase analyses further revealed an evident reduction in the half-life of cyclin D1 protein by obatoclax, confirming that obatoclax downregulates cyclin D1 through induction of cyclin D1 proteasomal degradation. Lastly, threonine 286 phosphorylation of cyclin D1, which is essential for initiating cyclin D1 proteasomal degradation, was induced by obatoclax in one cell line but not others. Collectively, we reveal a novel anticancer mechanism of obatoclax by validating that obatoclax targets cyclin D1 for proteasomal degradation to downregulate cyclin D1 for inducing antiproliferation.

Thoracoscopic surgery via a single-incision subxiphoid approach is associated with less postoperative pain than single-incision transthoracic or three-incision transthoracic approaches for spontaneous pneumothorax.

BACKGROUND: Comparison of the degree of postoperative pain associated with different thoracoscopic surgical techniques for spontaneous pneumothorax has never reported. In this study we compared perioperative outcomes and degrees of postoperative pain associated with single-incision subxiphoid thoracoscopic surgery, single-incision transthoracic thoracoscopic surgery and three-incision transthoracic thoracoscopic surgery for spontaneous pneumothorax. METHODS: During the period August 2013 to September 2015, fifty-seven consecutive patients with spontaneous pneumothorax were treated via single-incision subxiphoid thoracoscopic surgery, single-incision transthoracic thoracoscopic surgery or three-incision transthoracic thoracoscopic surgery. Demographic data, operative time, operative blood loss, length of hospital stay, duration of chest tube drainage, postoperative complications, and numeric pain rating scale scores were collected from the medical records for analysis. RESULTS: Among the 57 patients, 14 received single-incision subxiphoid thoracoscopic surgery, 26 underwent single-incision transthoracic surgery and 17 received three-incision thoracoscopic surgery. In all patients, surgeries were completed without the need for conversion to open surgery. Patients who underwent the single-incision subxiphoid procedure had significantly lower 1-, 8-, 24- and 32-hour postoperative pain scale scores than patients who underwent the other two procedures. The average and maximum pain scale scores during the first 24 hours were lowest in the single-incision subxiphoid group (P<0.0001). CONCLUSIONS: Single-incision subxiphoid thoracoscopic surgery is associated with significantly lower postoperative pain intensity than transthoracic approaches and therefore may provide an alternative surgical technique for patients with spontaneous pneumothorax.

The impact of RNA binding motif protein 4-regulated splicing cascade on the progression and metabolism of colorectal cancer cells.

Dysregulated splicing of pre-messenger (m)RNA is considered a molecular occasion of carcinogenesis. However, the underlying mechanism is complex and remains to be investigated. Herein, we report that the upregulated miR-92a reduced the RNA-binding motif 4 (RBM4) protein expression, leading to the imbalanced expression of the neuronal polypyrimidine tract-binding (nPTB) protein through alternative splicing-coupled nonsense mediated decay (NMD) mechanism. Increase in nPTB protein enhances the relative level of fibroblast growth factor receptor 2 IIIc (FGFR2) and pyruvate kinase M2 (PKM2) transcripts which contribute to the progression and metabolic signature of CRC cells. Expression profiles of RBM4 and downstream alternative splicing events are consistently observed in cancerous tissues compared to adjacent normal tissues. These results constitute a mechanistic understanding of RBM4 on repressing the carcinogenesis of colorectal cells.

Regulation of CTP Synthase Filament Formation During DNA Endoreplication in Drosophila.

CTP synthase (CTPsyn) plays an essential role in DNA, RNA, and lipid synthesis. Recent studies in bacteria, yeast, and Drosophila all reveal a polymeric CTPsyn structure, which dynamically regulates its enzymatic activity. However, the molecular mechanism underlying the formation of CTPsyn polymers is not completely understood. In this study, we found that reversible ubiquitination regulates the dynamic assembly of the filamentous structures of Drosophila CTPsyn. We further determined that the proto-oncogene Cbl, an E3 ubiquitin ligase, controls CTPsyn filament formation in endocycles. While the E3 ligase activity of Cbl is required for CTPsyn filament formation, Cbl does not affect the protein levels of CTPsyn. It remains unclear whether the regulation of CTPsyn filaments by Cbl is through direct ubiquitination of CTPsyn. In the absence of Cbl or with knockdown of CTPsyn, the progression of the endocycle-associated S phase was impaired. Furthermore, overexpression of wild-type, but not enzymatically inactive CTPsyn, rescued the endocycle defect in Cbl mutant cells. Together, these results suggest that Cbl influences the nucleotide pool balance and controls CTPsyn filament formation in endocycles. This study links Cbl-mediated ubiquitination to the polymerization of a metabolic enzyme and reveals a role for Cbl in endocycles during Drosophila development.

Subxyphoid single-incision thoracoscopic pulmonary metastasectomy.

Single-incision thoracoscopic surgery has increasingly attracted public interest and been applied in numerous thoracic procedures. However, single-incision thoracoscopic surgery is associated with requiring subsequent procedures, such as intercostal neuralgia. Herein, we extend the single-port technique of pulmonary metastasectomy through a single subxiphoid approach, and report the first two cases of this procedure to date.