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In safety-critical engineering applications, such as robust prediction against adversarial noise, it is necessary to quantify neural networks' uncertainty. Interval neural networks (INNs) are effective models for uncertainty quantification, giving an interval of predictions instead of a single value for a corresponding input. This article formulates the problem of training an INN as a chance-constrained optimization problem. The optimal solution of the formulated chance-constrained optimization naturally forms an INN that gives the tightest interval of predictions with a required confidence level. Since the chance-constrained optimization problem is intractable, a sample-based continuous approximate method is used to obtain approximate solutions to the chance-constrained optimization problem. We prove the uniform convergence of the approximation, showing that it gives the optimal INN consistently with the original ones. Additionally, we investigate the reliability of the approximation with finite samples, giving the probability bound for violation with finite samples. Through a numerical example and an application case study of anomaly detection in wind power data, we evaluate the effectiveness of the proposed INN against existing approaches, including Bayesian neural networks, highlighting its capability to significantly improve the performance of applying INNs for regression and unsupervised anomaly detection.
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BACKGROUND: Abnormal expression of protein tyrosine kinase 6 (PTK6) has been proven to be involved in the development of gynecological tumors. However, its immune-related carcinogenic mechanism in other tumors remains unclear. OBJECTIVE: The aim of this study was to identify PTK6 as a novel prognostic biomarker in pan-cancer, especially in lung adenocarcinoma (LUAD), which is correlated with immune infiltration, and to clarify its clinicopathological and prognostic significance. METHODS: The prognostic value and immune relevance of PTK6 were investigated by using bio-informatics in this study. PTK6 expression was validated in vitro experiments (lung cancer cell lines PC9, NCI-H1975, and HCC827; human normal lung epithelial cells BEAS-2B). Western blot (WB) revealed the PTK6 protein expression in lung cancer cell lines. PTK6 expression was inhibited by Tilfrinib. Colony formation and the Cell Counting Kit-8 (CCK-8) assay were used to detect cell proliferation. The wound healing and trans-well were performed to analyze the cell migration capacity. Then flow cytometry was conducted to evaluate the cell apoptosis. Eventually, the relationship between PTK6 and immune checkpoints was examined. WB was used to estimate the PD-L1 expression at different Tilfrinib doses. RESULTS: PTK6 was an independent predictive factor for LUAD and was substantially expressed in LUAD. Pathological stage was significantly correlated with increased PTK6 expression. In accordance with survival analysis, poor survival rate in LUAD was associated with a high expression level of PTK6. Functional enrichment of the cell cycle and TGF-ß signaling pathway was demonstrated by KEGG and GSEA analysis. Moreover, PTK6 expression considerably associated with immune infiltration in LUAD, as determined by immune analysis. Thus, the result of vitro experiments indicated that cell proliferation and migration were inhibited by the elimination of PTK6. Additionally, PTK6 suppression induced cell apoptosis. Obviously, PD-L1 protein expression level up-regulated while PTK6 was suppressed. CONCLUSION: PTK6 has predictive value for LUAD prognosis, and could up regulated PD-L1.
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Osteoarthritis (OA) is an extremely common type of chronic progressive disease in clinical practice. lncRNA TUC339 has a close association with bone marrow mesenchymal stem cell (BMSC) and an important impact on organismal inflammation. However, the mechanism of BMSC-derived lncRNA TUC339 on OA was poorly understood. In this study, we found that TUC339 was lower in the research group than in the control group and it was negatively correlated with IL-6, IL-8 and TNF-α. Prognosis TUC339 was lower in patients with recurrent OA than in those without recurrence, and ROC analysis manifested that TUC339 had a better predictive value for recurrence of OA. Phenotypic identification revealed elevated expression of CD29 and CD44 in BMSCs and TSG101, CD63 and CD81 in BMSCs-exosome (BMSCs-exo), with a stem cell versus exosome phenotype. Finally, animal experiments improved significantly in joint injury in the BMSCs-exo and TUC339-overexpression vector groups compared with control groups. Similarly, the activity of chondrocytes was enhanced, and apoptosis was reduced in the BMSCs-exo group versus the TUC339-overexpression vector group of rats. Study demonstrated that BMSCs-exo improves OA by elevating the expression of TUC339 to promote M1-type mø to M2-type polarization, suppressing inflammation and promoting chondrocyte activity, which provides a reliable basis for future transplantation therapy of MSCs for OA.
Subject(s)
Exosomes , Mesenchymal Stem Cells , Osteoarthritis , RNA, Long Noncoding , Humans , Rats , Animals , Chondrocytes/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Exosomes/genetics , Exosomes/metabolism , Osteoarthritis/genetics , Osteoarthritis/therapy , Osteoarthritis/metabolism , Inflammation/metabolism , Mesenchymal Stem Cells/metabolism , Macrophages/metabolism , Apoptosis/geneticsABSTRACT
RATIONALE: Hypoglycemia may cause diverse neurological manifestations, ranging from focal neurological deficits to irreversible coma. Severe and persistent hypoglycemia can lead to hypoglycemic encephalopathy (HE). Imaging findings of HE at different stages of 18F-FDG positron emission tomography/computed tomography (PET/CT) have rarely been reported. Herein, we describe a case of HE occurring in the medial frontal cortex, cerebellar cortex, and dentate nucleus using 18F-FDG PET/CT images from different periods. 18F-FDG PET/CT has a high value in displaying the lesion range and indicating the prognosis. PATIENT CONCERNS: A 57-year-old male patient with type 2 diabetes (T2D) was transferred to the hospital with a history of unconsciousness for 1 night. The patient showed a significant decrease in blood glucose levels. DIAGNOSES: The patient was initially diagnosed with a hypoglycemic coma. INTERVENTIONS: The patient subsequently underwent a comprehensive treatment. The 18F-FDG PET/CT examination on the fifth day after admission revealed a significant symmetrical fluorodeoxyglucose (FDG)-positive accumulation in the bilateral medial frontal gyrus, cerebellar cortex, and dentate nucleus. A follow-up PET/CT examination 6 months later revealed hypometabolism in the bilateral medial frontal gyrus and no abnormalities in FDG uptake in the bilateral cerebellar cortex and dentate nucleus. OUTCOMES: The patient condition was stable 6 months later, with a slow response, memory deterioration, occasional dizziness, and episodes of hypoglycemia. LESSONS: HE lesions with a high metabolic status may be related to a metabolic compensation mechanism in response to gray matter loss. Some of the more severely damaged cells eventually die even after the blood sugar levels return to normal. Less damaged nerve cells can be recovered. 18F-FDG PET/CT has high value in indicating the lesion range and prognosis of HE.
Subject(s)
Diabetes Mellitus, Type 2 , Hypoglycemia , Male , Humans , Middle Aged , Fluorodeoxyglucose F18 , Positron Emission Tomography Computed Tomography/methods , Diabetes Mellitus, Type 2/complications , Hypoglycemia/diagnostic imaging , Hypoglycemia/etiology , RadiopharmaceuticalsABSTRACT
OBJECTIVE: To examine the early outcomes, associated factors and predictive values of clinical outcomes of different tandospirone doses in patients with a generalized anxiety disorder (GAD). METHODS: This was a posthoc analysis of "a randomized, controlled multicenter clinical trial of the efficacy and safety of different doses of tandospirone on GAD". A total of 274 patients with GAD were included and randomized into the high-dose (tandospirone 60 mg/d) and low-dose (tandospirone 30 mg/d) groups for a 6-week treatment. The Hamilton Anxiety (HAMA), Clinical Global Impression-Severity (CGI-S), Short-Form-12 (SF-12) scales were used for assessment. The trial was registered at clinical trail.gov (NCT01614041). RESULTS: (1) In the first week of treatment, 35.8% of patients in the high-dose group fulfilled the early onset criteria, which was significantly higher than 19.0% found in the low-dose group (p = 0.002). In the second week of treatment, 22.6% of patients in the high-dose group achieved an early response, versus 12.4% in the low-dose group, indicating a significant difference (p = .026). (2) Factors associated with early onset at week 1 included baseline HAMA total score (OR = 0.916, 95%CI 0.882-0.952), age (OR = 0.974, 95%CI 0.950-0.998), drug dose (30 mg vs. 60 mg; OR = 0.298, 95%CI 0.156-0.568) and SF-12 physiological total score (OR = 1.030, 95%CI 1.010-1.050). (3) Early onset was significantly associated with response rate (OR = 18.34, 95%CI 12.10-27.81), remarkable response rate (OR = 27.56, 95%CI 11.65-65.17) and recovery rate (OR = 11.85, 95%CI 4.98-28.18). Group (high dose group vs. low dose group) (χ2 = 8.535, p = .003) and baseline HAMA total score (χ2 = 70.840, p < .001) were independent predictors of onset time. CONCLUSIONS: The early outcomes of high-dose tandospirone in the treatment of GAD are better than those of the low-dose group. Patients with younger age at onset, milder anxiety symptoms and better physiological functions administered high-dose tandospirone showed rapid onset, great early outcomes, high recovery rate and good prognosis. Drug onset time had a good predictive effect on treatment outcome.
Subject(s)
Anxiety Disorders , Isoindoles , Humans , Isoindoles/adverse effects , Piperazines/therapeutic use , Pyrimidines/therapeutic useABSTRACT
This article introduces a neural approximation-based method for solving continuous optimization problems with probabilistic constraints. After reformulating the probabilistic constraints as the quantile function, a sample-based neural network model is used to approximate the quantile function. The statistical guarantees of the neural approximation are discussed by showing the convergence and feasibility analysis. Then, by introducing the neural approximation, a simulated annealing-based algorithm is revised to solve the probabilistic constrained programs. An interval predictor model (IPM) of wind power is investigated to validate the proposed method.
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This paper proposes an innovative framework of modeling the statistical properties of the near-accident event and pedestrian behavior at non-signalized intersections based on Poisson process and logistic regression. The first contribution of this study is that the predictive intensity model of the near-accident event is established by regarding the near-accident event as a Poisson process on space of the vehicle velocity, distance to the intersection and lateral distance to the pedestrian at the time when pedestrian appears. Besides, logistic regression is used to build the model which can predict the probability of pedestrian behavior. The two proposed models are validated in a generative simulation. The simulated pedestrian behavior data is generated by the proposed models and compared with the real data. The real data set is from the drive recorder data base of Smart Mobility Research Center (SMRC) at Tokyo University of Agriculture and Technology. Accident and near-accident data has been collected in the city streets with an image-captured drive recorder mounted on a taxi since 2006. The findings in this study are expected to be useful for constructions of traffic simulators or safety control design which considers the pedestrian-vehicle interaction.
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BACKGROUND: The National Violent Death Reporting System (NVDRS) collects data on the circumstances of violent deaths, and all firearm-related deaths, across states and territories in the USA. This surveillance system is critical to understanding patterns and risk factors for these fatalities, thereby informing targets for prevention. NVDRS variables include behavioral health conditions among decedents, but the validity of the reported behavioral health data is unknown. Using Department of Veterans Affairs (VA) healthcare records as a criterion standard, we examined the accuracy of NVDRS-reported behavioral health variables for veteran decedents in a sample state (Oregon) between 2003 and 2017. METHODS: We linked Oregon NVDRS data to VA healthcare data to identify veteran decedents who used VA services within two years of death. Veterans' VA diagnoses within this time frame, including depression, post-traumatic stress disorder (PTSD), anxiety, and substance use disorders, were compared to behavioral health variables identified in the Oregon NVDRS. Concordance, sensitivity, and correlates of sensitivity were examined over time and by decedent characteristics. RESULTS: We identified 791 VA-using veterans with violent and/or firearm-related fatal injuries documented in the Oregon NVDRS between 2003 and 2017. In this cohort, the Oregon NVDRS accurately identified only 49% of decedents who were diagnosed with depression, 45% of those diagnosed with PTSD, and 17% of those diagnosed with anxiety by the VA. Among 211 veterans diagnosed by the VA with a substance use disorder, the Oregon NVDRS coded only 56% as having a substance use problem. In general, the sensitivity of behavioral health variables in the Oregon NVDRS remained the same or decreased over the study period; however, the sensitivity of PTSD diagnoses increased from 21% in 2003-2005 to 54% in 2015-2017. Sensitivity varied by some decedent characteristics, but not consistently across behavioral health variables. CONCLUSIONS: NVDRS data from one state missed more than half of behavioral health diagnoses among VA-using veterans who died from violence or from firearm injuries. This suggests that reports of behavioral health conditions among decedents nationally may be severely undercounted. Efforts to improve validity of these variables in state NVDRS data are needed.
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The etching of gold nanorods/nanobipyramid, or silver-coated nanorods/nanobipyramid inducing plasmon changes represents an efficient strategy to improve the performance of enzyme-linked immunosorbent assay (ELISA). However, the effect of shape on the sensitivity was negligible, especially the thickness of coated silver shell. Here, we propose a plasmonic ELISA for multi-colorimetric detection of CRP based on the etching of Ag-coated Au nanobipyramid (Au NBP@Ag). The effect of silver shell thickness on the sensitivity of plasmon peak shifting was investigated by experiments and DDA calculations. The relationship between the Ag shell thickness and the sensitivity of plasmon peak shifting was obtained. Our results reveal that the thickness of coated Ag shell acts as a key factor in the multi-color change of Au NBP@Ag etching. It is found that Au NBP@Ag with medium Ag shell thickness and rod-like shape has the higher sensitivity and is suitable for sensing. At the optimized most sensitive Ag shell, the detection limit of proposed plasmonic ELISA for CRP was determined to be 0.09 ng/mL with a spectrometer in the range from 0.09 ng/mL to 25 ng/mL. Importantly, the visual detection limit was 0.78 ng/mL, which allows the differential diagnosis with the naked eye. Compared with traditional ELISA with the monochromatic intensity variations, the multi-color ELISA proposed in this study has a large linear range and rich color variation for high-sensitivity and naked-eye semi-quantitative detection.
Subject(s)
Colorimetry , Metal Nanoparticles , C-Reactive Protein , Colorimetry/methods , Enzyme-Linked Immunosorbent Assay , Gold , SilverABSTRACT
THIS STUDY AIMED: to investigate the efficacy and long-term outcomes of endovascular embolization and surgical clipping for patients with posterior communicating artery unruptured aneurysms (PcomAs) concomitant with oculomotor nerve palsy (ONP). No significant (Pâ >â .05) difference existed in the age, gender, proportion of complete ONP, and size of eye fissure and pupil before treatment between 2 groups. After compared with before treatment, the eye fissure was widened significantly (Pâ <â .05) and the pupil narrowed significantly (Pâ <â .05), but no significant (Pâ >â .05) differences existed between the 2 groups. Complete ONP recovery was observed in 32 (80%) patients in the embolization group and 31 (77.5%) in the microsurgical group, partial ONP recovery occurred in 6 (15%) in the embolization group and 8 (20%) in the microsurgical group. The recovery rate was 95% in the embolization group and 97.5% in the microsurgical group, with no significant (Pâ >â .05) difference between 2 groups. The recovery rate of the ONP was significantly (Pâ <â .01) greater in the microsurgical group than that in the embolization group at follow-up of 1 month, 3 months, six and 12 months, respectively. At 18 months, the ONP recovery rate was not significantly different between 2 groups (95% vs 97.5%) Surgical clipping may have a faster effect on the recovery of oculomotor nerve palsy than endovascular embolization for patients with posterior communicating artery unruptured aneurysms complicated with oculomotor nerve palsy, but both approaches may result in a similar effect on the nerve recovery in the long run.Eighty patients treated with endovascular embolization or surgical clipping were retrospectively enrolled into the endovascular embolization group or surgical clipping and analyzed.
Subject(s)
Embolization, Therapeutic , Endovascular Procedures , Intracranial Aneurysm , Oculomotor Nerve Diseases , Arteries , Embolization, Therapeutic/methods , Endovascular Procedures/methods , Humans , Intracranial Aneurysm/complications , Intracranial Aneurysm/surgery , Oculomotor Nerve Diseases/complications , Oculomotor Nerve Diseases/surgery , Recovery of Function/physiology , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Osteoarthritis (OA) is a prevalent degenerative joint disease that not only significantly impairs the quality of life of middle-aged and elderly individuals but also imposes a significant financial burden on patients and society. Due to their significant biological properties, extracellular vesicles (EVs) have steadily received great attention in OA treatment. This study aimed to investigate the influence of EVs on chondrocyte proliferation, migration, and apoptosis and their protective efficacy against OA in mice. METHODS: The protective impact of EVs derived from human umbilical cord mesenchymal stem cells (hucMSCs-EVs) on OA in mice was investigated by establishing a mouse OA model by surgically destabilizing the medial meniscus (DMM). Human chondrocytes were isolated from the cartilage of patients undergoing total knee arthroplasty (TKA) and cultured with THP-1 cells to mimic the in vivo inflammatory environment. Levels of inflammatory factors were then determined in different groups, and the impacts of EVs on chondrocyte proliferation, migration, apoptosis, and cartilage extracellular matrix (ECM) metabolism were explored. N6-methyladenosine (m6A) level of mRNA and methyltransferase-like 3 (METTL3) protein expression in the cells was also measured in addition to microRNA analysis to elucidate the molecular mechanism of exosomal therapy. RESULTS: The results indicated that hucMSCs-EVs slowed OA progression, decreased osteophyte production, increased COL2A1 and Aggrecan expression, and inhibited ADAMTS5 and MMP13 overexpression in the knee joint of mice via decreasing pro-inflammatory factor secretion. The in vitro cell line analysis revealed that EVs enhanced chondrocyte proliferation and migration while inhibiting apoptosis. METTL3 is responsible for these protective effects. Further investigations revealed that EVs decreased the m6A level of NLRP3 mRNA following miR-1208 targeted binding to METTL3, resulting in decreased inflammatory factor release and preventing OA progression. CONCLUSION: This study concluded that hucMSCs-EVs inhibited the secretion of pro-inflammatory factors and the degradation of cartilage ECM after lowering the m6A level of NLRP3 mRNA with miR-1208 targeting combined with METTL3, thereby alleviating OA progression in mice and providing a novel therapy for clinical OA treatment.
Subject(s)
Extracellular Vesicles , Mesenchymal Stem Cells , MicroRNAs , Osteoarthritis, Knee , Aged , Animals , Chondrocytes/metabolism , Disease Models, Animal , Extracellular Vesicles/metabolism , Humans , Knee Joint/metabolism , Macrophages/metabolism , Menisci, Tibial , Mesenchymal Stem Cells/metabolism , Methyltransferases/metabolism , Mice , MicroRNAs/genetics , MicroRNAs/metabolism , Middle Aged , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Osteoarthritis, Knee/genetics , Osteoarthritis, Knee/metabolism , Osteoarthritis, Knee/therapy , Quality of Life , RNA, Messenger/metabolism , Umbilical Cord/metabolismABSTRACT
RATIONALE: Mucinous cystadenoma is a benign tumor that is commonly found in the pancreas, ovaries, or appendix, but is rarely encountered in the lungs. Worldwide, only a few reported cases of these tumors originate in the lungs. Herein, we analyzed the imaging features of a case of pulmonary mucinous cystadenoma (PMCA). To the best of our knowledge, this is the first reported case of PMCA complicated by significant infection. PATIENT CONCERNS: A 57-year-old man was admitted to our hospital with blood in sputum for more than 2âmonths. Serum laboratory examination showed significantly elevated leukocyte and tumor marker, carcinoembryonic antigen. Enhanced thoracic computed tomography and whole-body positron emission tomography/computed tomography showed a cystic-solid ill-defined mass in the right upper lung. DIAGNOSIS: The tumor was considered malignant, both clinically and radiologically. INTERVENTIONS: The patient underwent right upper lobe tumor resection and mediastinal lymph node dissection. OUTCOMES: Postoperative specimen pathology was diagnosed as PMCA with infection. The patient was not administered any further treatment. The patient was alive without any recurrence or metastasis of the tumor after 2âyears of follow-up. LESSONS: Preoperative diagnosis of PMCA with atypical imaging and clinical manifestations is extremely difficult. This is the first reported case of PMCA complicated by a significant infection that was misdiagnosed preoperatively as a malignancy.
Subject(s)
Cystadenoma, Mucinous/diagnosis , Lung Neoplasms/diagnosis , Lung/diagnostic imaging , Pneumonia, Bacterial/diagnosis , Cystadenoma, Mucinous/complications , Female , Humans , Lung Neoplasms/complications , Male , Middle Aged , Pneumonia, Bacterial/complications , Positron Emission Tomography Computed Tomography , Rare Diseases , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: Follicular lymphoma (FL) is more common in lymph nodes, while primary extranodal lymphomas are rare. Urinary tract lymphoid neoplasms are extremely rare, accounting for less than 5% of all extranodal lymphomas. Only one case of FL from the renal pelvis has previously been reported. CASE SUMMARY: A 70-year-old male patient with a history of esophageal cancer visited our hospital for follow-up examination. Abdominal computed tomography revealed a malignant mass in the right renal pelvis. The whole-body positron emission tomography/computed tomography showed a significant increase in fluorodeoxyglucose uptake of this soft tissue mass and no abnormal fluorodeoxyglucose uptake in the esophageal wall. The patient underwent radical resection of a malignant tumor in the right kidney, which was confirmed by postoperative pathology to be FL. The patient received no radiation or chemotherapy after surgery, and no recurrence of lymphoma or other malignant tumors was found at the 1-year follow-up. CONCLUSION: Extranodal FL is more common in the skin and gastrointestinal tract but rarely occurs in the urinary tract. This is the second report of primary renal FL. Localized extranodal FL is expected to have a favorable prognosis and can be cured by local resection.
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RATIONALE: Melanotic schwannoma (MS) is an unusual variant of a nerve sheath neoplasm that accounts for less than 1% of all primary peripheral nerve sheath tumors. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has unique value in detecting malignant MS lesions. To date, only 4 cases of MS with hepatic metastasis have been reported. Herein, we report the fifth case, which is the first reported patient with MS of Asian ethnicity with hepatic metastasis. PATIENT CONCERNS: A 29-year-old woman with a 1-day history of backache was admitted to our hospital. PET/CT showed a paravertebral heterogeneous soft tissue mass along the spinal nerve at the L2-L3 level with strong FDG uptake, and a nodule with increased FDG uptake in the lateral lobe of the left liver. DIAGNOSIS: A puncture biopsy of the L3 bony destruction and surrounding soft tissue mass was performed. The final diagnosis was spinal MS with hepatic metastasis. INTERVENTIONS: The patient underwent 6 courses of systemic chemotherapy. OUTCOMES: The patient did not receive further treatment for half a year after the end of chemotherapy and recovered well. LESSONS: Unlike conventional schwannomas, which are completely benign, MS has an unpredictable prognosis. It is thought to have low malignant potential, and the malignant type tends to metastasize. FDG PET/CT has a unique and important value in the differential diagnosis of benign and malignant lesions, in detecting occult metastases, monitoring the treatment response, and assessing the prognosis of MS.
Subject(s)
Fluorodeoxyglucose F18/administration & dosage , Neurilemmoma/diagnosis , Positron Emission Tomography Computed Tomography/methods , Radiopharmaceuticals/administration & dosage , Spinal Neoplasms/diagnosis , Adult , Antineoplastic Agents/therapeutic use , Female , Humans , Liver Neoplasms/secondary , Lumbar Vertebrae/physiology , Neurilemmoma/diagnostic imaging , Neurilemmoma/drug therapy , Neurilemmoma/pathology , Spinal Neoplasms/diagnostic imaging , Spinal Neoplasms/drug therapy , Spinal Neoplasms/pathology , Spinal Nerve Roots/pathologyABSTRACT
RATIONALE: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of cutaneous lymphoma, which was first defined as a clinical entity in 1991 as a cytotoxic T-cell lymphoma preferentially infiltrating subcutaneous tissue. Herein, we report 2 patients of SPTCL who are a pair of twin brothers. PATIENT CONCERNS: The disease afflicted the monozygotic twin brothers at different time with an interval period of 5 years. The older twin brother had disease onset at 27 years of age. In June 2012, he developed prolonged fever accompanied by subcutaneous nodules in the left upper arm and left chest due to unknown origin. The younger twin brother had disease onset at 32 years of age. In June 2017, the younger brother presented with repeated high fever for more than 10 days, accompanied by head distension. DIAGNOSIS: On August 7, 2012, skin biopsy was performed on the lesion of left upper arm of the older twin brother, and then, a diagnosis of subcutaneous panniculitis-like T cell lymphoma (SPTCL) was made. On June 19, 2017, the younger twin brother underwent whole-body fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography for diagnosis. Soon afterwards, abdominal subcutaneous nodule resection and biopsy was performed on June 28, 2018, and the specimen was diagnosed as SPTCL. INTERVENTIONS: For the older brother, a total of 14 systemic chemotherapy sessions were performed from August 16, 2012, to September 21, 2014. For the younger brother, a total of 9 systemic chemotherapy sessions were performed from July 14, 2017, to March 8, 2018, then he was switched to oral chemotherapy with chidamide twice a week for 6 months. OUTCOMES: The older twin brother died in March 2015, the younger brother has recovered well and is no longer receiving any treatment LESSONS:: To the best of our knowledge, twin brothers both having this disease has never been previously reported. Moreover, some of the involved areas are also extremely rare detected by fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography at initial stage. It is beneficial to people to gain some new understanding for SPTCL by this special case and some extremely unusual involved sites in the younger twin brother.
Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols , Fluorodeoxyglucose F18 , Lymphoma, T-Cell/diagnostic imaging , Panniculitis/diagnostic imaging , Positron Emission Tomography Computed Tomography , Adult , Humans , Lymphoma, T-Cell/drug therapy , Male , Panniculitis/drug therapy , Twins, MonozygoticABSTRACT
Nitrogen removal with energy recovery through denitrification dependent N2O production is garnering recent attention due to its cost advantages. The most effective current method requires alternating COD and nitrite to achieve high N2O production making it incompatible with typical wastewaters and consequently difficult to use in most settings. The work described here introduces a robust and highly efficient N2O recovery approach which has the potential to work with wastewaters containing COD and nitrite simultaneously. This method relies on low pH incubation and inert gas sparging (IGS) to shift a community of mainly N2 producing nitrite denitrifiers to a community that accumulates N2O when incubated in the absence of IGS. Before experiencing IGS, samples from activated sludge incubated at a pH of 4.5 and 6.0 only achieved a maximum N2O production efficiency (PE_N2O) of â¼26%. After IGS the PE_N2O values increased to â¼97.5% and â¼80.2% for samples from these same pH 4.5 and pH 6.0 reactors, respectively. IGS did not lead to N2O production in a pH 7.5 bioreactor. Meta-omics analysis revealed that IGS resulted in an increase in bacteria utilizing the clade I nitrous oxide reductase (nosZI) relative to bacteria utilizing the clade II nitrous oxide reductase (nosZII). This likely results from IGS flushing out N2O leaving nitrite as the principal nitrogen oxide available for respiration, favoring nosZI utilizing bacteria which are more likely to be complete denitrifiers. Metatranscriptomic analysis suggested that the high PE_N2O values that occurred after stopping IGS result from the NO generated by chemodenitrification accumulating to levels that inactivate [4Fe:4S] clusters in the NosR protein essential for N2O reduction in the nosZI denitrifiers. This study provides an efficient and straightforward method for N2O recovery, widening the options for energy recovery from nitrogen-based wastes.
Subject(s)
Nitrites , Nitrous Oxide , Bioreactors , Denitrification , NitrogenABSTRACT
@#【Objective】To evaluate the efficacy of ziprasidone injection and the related influencing factors for treating agitation in schizophrenic patients based on published literature in English or Chinese. 【Methods】We searched PubMed, EMBASE, Web of Knowledge, Cochrane Library, Wanfang data, Chinese Journal Full- Text Database(CJFD),Chinese Biomedical Literature Database(CBMdisc)and VIP Chinese Technology Periodical Database(VIP). The Consolidated Standards of Reporting Trials(CONSORT)statement was used as a criterion for screening and assessing the literature. Meta-analysis and meta-regression were conducted by using STATA. With the effect size as the dependent variable and sex,age,baseline PANSS scale total score and oral antipsychotics as the covariates ,the meta- regression model was analyzed. 【Results】The Grades of Recommendation ,Assessment ,Development and Evaluation(GRADE) approach was employed to rate the overall quality of evidence. A total of 14 studies(5 in English and 9 in Chinese)were included in meta analysis and meta regression. The samples were ,respectively,1 197 and 1 149 at baseline and after treatment. Random effect Meta analysis showed that ziprasidone injection had significant efficacy in the treatment of agitation symptoms[SMD=2.04,95%CI(1.47,2.61),P = 0.000]. Meta regression revealed that the efficacy was related to baseline PANSS scores(t = 5.57 ,P = 0.011)and oral antipsychotics(t = 4.07 ,P = 0.027),but irrelevant to age(t = 0.74,P = 0.539)and language published(t = -0.57,P = 0.625). The efficacy was better in female patients than that in male patients (t = -2.95 ,P = 0.060). 【Conclusion】 Ziprasidone injection has significant efficacy in schizophrenia patients with agitation symptoms and the efficacy may be enhanced in those patients with higher baseline PANSS score and added with oral antipsychotics.
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With the aim of achieving high microwave absorption and electromagnetic shielding performance, reduced graphene oxide (rGO) and Fe3O4@SiO2 nanochains are successfully combined at various mass ratios. By selecting the right mass ratio, an rGO/Fe3O4@SiO2 composite with excellent microwave absorption properties is obtained, and, due to the addition of highly conductive rGO, the desired shielding effectiveness is also achieved. The reflection loss (RL) value of the composite can reach -48.34 dB with a mass ratio of 1:1, and the effective bandwidth (<-10 dB) can cover 4.88 GHz at a thickness of 2.0 mm. Moreover, the composite with a mass ratio of 4:1 exhibits outstanding electromagnetic shielding performance, which also broadens its fields of application. This outstanding microwave absorption and electromagnetic shielding performance indicate that the composite can potentially be employed as a multi-functional material.
ABSTRACT
BACKGROUND: Glioblastoma (GB) is one of the most common malignancies with limited standard therapies such as surgery, radiotherapy (RT) plus temozolomide (TMZ). Molecularly targeted drugs have been investigated among various clinical trials and are expected to develop in the field of tumor therapy, while the efficacy remains uncertain due to limited previous results. Thus, we focus on the evaluation of molecularly targeted drugs to clarify its overall effectiveness in terms of treating newly diagnosed GB. METHODS: Electronic databases were searched for eligible literatures updated to April 2018. Randomized-controlled trials were included to assess the efficacy and safety of molecularly targeted drugs in patients with newly diagnosed GB. The main outcomes were further calculated including the following parameters: PFS (progression-free survival), OS (overall survival) as well as AEs (adverse events). All data were pooled along with their 95% confidence interval using RevMan software. Sensitivity analyses and heterogeneity were evaluated quantitatively. RESULTS: The combination of molecularly targeted drugs with TMZâ+âRT had no significant effects on OS (ORâ=â0.96, 95%CIâ=â0.89-1.04, Pâ=â.36). Meanwhile, the combination regimen significantly improved the PFS of patients with newly diagnosed GB (ORâ=â0.86 ,95% CI 0.75-0.98, Pâ=â.02). The rate of AEs (ORâ=â1.68,95%CIâ=â1.44-1.97, Pâ<â.00001) was higher in patients receiving molecularly targeted drugs, which was comparable to the contemporary group. CONCLUSION: Longer PFS and a higher rate of AEs were observed with the addition of molecularly targeted drugs to standard chemoradiation in patients harboring newly diagnosed GB. Nevertheless, compared with the control arm, the regimen did not significantly prolong OS.
Subject(s)
Brain Neoplasms/drug therapy , Glioblastoma/drug therapy , Temozolomide/therapeutic use , Brain Neoplasms/radiotherapy , Chemoradiotherapy , Female , Glioblastoma/radiotherapy , Humans , Male , Molecular Targeted Therapy , Prognosis , Randomized Controlled Trials as Topic , Survival Analysis , Treatment OutcomeABSTRACT
Interactions between transmembrane receptors and their ligands play important roles in normal biological processes and pathological conditions. However, the binding partners for many transmembrane-like proteins remain elusive. To identify potential ligands of these orphan receptors, we developed a screening platform using a homogenous nonwash binding assay in live cells. A collection of ~1900 cDNA clones, encoding full-length membrane proteins, was assembled. As a proof of concept, cDNA clones were individually transfected into CHO-K1 cells in a high-throughput format, and soluble PD-L1-Fc fusion protein was used as bait. The interaction between the putative receptor and PD-L1-Fc was then detected by Alexa Fluor 647 conjugated anti-human immunoglobulin G Fc antibody and visualized using the Mirrorball fluorescence plate cytometer. As expected, PDCD1, the gene encoding programmed cell death protein 1 (PD-1), was revealed as the predominant hit. In addition, three genes that encode Fc receptors (FCGR1A, FCGR1B, and FCGR2A) were also identified as screen hits as the result of the Fc-tag fused to PD-L1, which has provided a reliable internal control for the screen. Furthermore, the potential of using a biotinylated ligand was explored and established to expand the versatility of the cDNA platform. This novel screening platform not only provides a powerful tool for the identification of ligands for orphan receptors but also has the potential for small-molecule target deconvolution.