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Case Presentation A 21-year-old man was admitted to our hospital with recurrent bilateral pneumothorax and hemoptysis. Three years earlier, he underwent coil embolization due to a subarachnoid hemorrhage caused by an intracerebral aneurysm rupture. Two months after the coil embolization, he underwent an emergent total colectomy due to a massive infarction of the colon. One year after the colectomy, he started to have recurrent hemoptysis, and a few months later, multiple episodes of bilateral pneumothorax that required a chest tube placement began to occur. Notably, he had a history of easy bruising. He was taking Depakote and aspirin to prevent seizure and thromboembolic complications, respectively, both of which he began taking after the coil embolization. He denied the use of any illicit drugs. The histories of his parents and sister were not remarkable.

Electrochemical oxidative radical sulfonylation/semipinacol rearrangement sequences of alkenylcyclobutanols have been developed. The reaction proceeds in an undivided electrochemical cell equipped with platinum plate electrodes employing sodium iodide as a redox catalyst and a supporting electrolyte. This approach is environmentally benign by using shelf-stable arylsulfonyl hydrazides as arylsulfonyl radical precursor and electrons as oxidizing reagents. The present protocol offers a facile way to prepare β-sulfonated cyclic ketone derivatives.

Electrochemical oxidative selenylation of imidazo[1,2–a]pyridines has been developed. The reaction proceeds in an undivided electrochemical cell equipped with glassy carbon electrodes employing LiClO4 as a supporting electrolyte. This approach is environmentally benign by using shelf-stable diselenides as selenium source and electrons as oxidizing reagents. The present protocol offers a facile way to prepare 3-selenylated imidazopyridine derivatives.

We evaluated the clinical outcome of patients with stage III to IV thymomas (Ts) or stage II to IV thymic carcinomas (TCs) treated with complete thymectomy and local radiation therapy (LRT, targeting the tumor bed and anterior mediastinal areas only) or elective nodal irradiation (ENI, targeting the entire mediastinal and supraclavicular regions).Data from 47 patients diagnosed with Ts or TCs and treated with surgery and adjuvant RT from May 2002 to May 2015 were analyzed. The standard RT dose was 50.4 Gy in 28 fractions; patients with a positive resection margin received a further 4 to 10 Gy. Survival outcomes determined at 5 years included local recurrence-free survival, regional recurrence-free survival, distant metastasis-free survival, and overall survival.Five-year local recurrence-free survival was similar in both groups (LRT, 94.7% vs. ENI, 96.2%; P = .849). Significant differences were seen in 5-year regional recurrence-free survival (LRT, 55.1% vs. ENI, 83.7%; P = .006); however, tumor size was seen to be a significant factor (7 cm, 95.2% vs. ≥ 7 cm, 48.9%; P .001), and the LRT group contained a greater proportion of patients with ≥ 7-cm tumors (70% vs. 33%). Multivariate analysis demonstrated that tumor size was the only significant prognostic factor (P .001). No differences in 5-year overall survival were seen (LRT, 91.7% vs. ENI, 100%; P = .106).ENI may not be indicated in all cases, as additional benefit in reducing recurrence or improving survival was not predominant. LRT seems to be a feasible option with favorable patient outcomes.

Potassium iodide-mediated radical sulfonylation/1,2-carbon migration sequences of alkenylcyclobutanols has been developed. The reaction was effectively accelerated using potassium iodide as a catalyst under mild reaction conditions without other metal oxidant. This approach is environmentally benign by use of shelf-stable arylsulfonyl hydrazides as arylsulfonyl radical precursor and water as solvent. This approach offers a facile way to prepare β-sulfonated cyclic ketone derivatives.

Objective To evaluate the efficacy and safety of involved-field radiation therapy (IFRT) in patients with locoregionally confined recurrent or persistent epithelial ovarian cancer. Methods This study included patients with recurrent epithelial ovarian cancer eligible for IFRT either during diagnosis of the recurrence or after salvage therapies. IFRT was performed at a dose of ≥45 Gy for all tumors with 10–15-mm margins as seen on standard imaging. The primary endpoint was progression-free survival (PFS); the secondary endpoints were safety, response rate, local control, and overall survival (OS). Results Thirty patients with a mean number of 5.7 metastatic lesions each were enrolled between 2014 and 2016. Seventeen were treated with 3-D conformal radiation therapy (RT) and 13 with intensity-modulated RT. IFRT was well tolerated in all patients, and acute toxicity ≥ grade 2 was not observed. One case of grade 3 abdominal pain was reported 10 months post-RT. The overall and complete response rates were 85.7% and 50%, respectively. After a median follow-up of 28 (range, 17–42) months, the median PFS was 7 months. The 2-year PFS rate was 39.3%. Six of the 16 patients who developed outfield disease progression after IFRT were successfully treated with repeat IFRT as salvage treatment. The 3-year local control and OS rates were 84.4% and 55.8%, respectively. Conclusions Although the primary endpoint was not met, IFRT might be safe and effective for in-field tumor control in patients with persistent epithelial ovarian cancer with a limited number of metastatic foci. We plan to conduct a larger scale multi-center phase II prospective study.

Context 68Gallium prostate-specific membrane antigen positron emission tomography (68Ga-PSMA PET) is an emerging imaging modality for assessment of prostate cancer. Recent studies show promising results regarding its ability to detect recurrent or metastatic prostate cancer superior to that of conventional imaging modalities. However, the impact of 68Ga-PSMA PET on management of patients with prostate cancer has not been well established. Objective To perform a systematic review and meta-analysis to evaluate the impact of 68Ga-PSMA PET on management of patients with prostate cancer. Evidence acquisition Pubmed and EMBASE databases were searched up to January 20, 2018. We included studies that reported proportion of management change after 68Ga-PSMA PET in patients with prostate cancer. The quality of the studies was evaluated using the GRADE system. The proportion of management changes were pooled using random-effects model. Subgroup analyses and meta-regression analyses were performed to explore heterogeneity. Evidence synthesis Fifteen studies (1163 patients) were included. The pooled proportion of management changes was 54% (95% confidence interval 47–60%). At meta-regression analyses, PET positivity (%) was a significant factor of heterogeneity (p=0.0486). For patients with biochemical failure, the proportion of radiotherapy (from 56% to 61%), surgery (from 1% to 7%), focal therapy (from 1% to 2%), and multimodal treatment (from 2% to 6%) increased, whereas that of systemic treatment (from 26% to 12%) and no treatment (from 14% to 11%) decreased with 68Ga-PSMA PET. Conclusions 68Ga-PSMA PET had a large impact on the management of patients with prostate cancer. Greater PET positivity was associated with higher proportion of management changes. Patient summary We reviewed all previous studies assessing the impact of 68Gallium prostate-specific membrane antigen positron emission tomography (68Ga-PSMA PET) in patients with prostate cancer. We found that 68Ga-PSMA PET altered the management in approximately half of the patients.

A visible light photoredox-catalyzed difluoromethylation and ring expansion via 1,2-carbon migration of 1-(1-arylvinyl)cyclobutanol derivatives has been developed. This approach offers a facile way to prepare difluoromethyl-substituted cyclopentanone derivatives.

The organocatalytic enantioselective conjugate reaction of 2-fluoro-1,3-diketones to nitroalkenes promoted by chiral binaphthyl-modified squaramide has been achieved. Treatment of 2-fluoro-1,3-diketones with nitroalkenes under mild reaction conditions afforded the corresponding Michael products containing fluorinated quaternary carbon stereocenter with excellent enantioselectivity (up to 98% ee).

SUMMARY: We analyze the transcriptome of baseline and on-therapy tumor biopsies from 101 patients with advanced melanoma treated with nivolumab (anti-PD-1) alone or combined with ipilimumab (anti-CTLA-4). We find that T cell infiltration and interferon-γ (IFNγ) signaling signatures correspond most highly with clinical response to therapy, with a reciprocal decrease in cell cycle and WNT signaling pathways in responding biopsies. We model the interaction in 58 human cell lines, where IFNγ in vitro exposure leads to a conserved transcriptome response unless cells have IFNγ receptor alterations. This conserved IFNγ transcriptome response in melanoma cells serves to amplify the antitumor immune response. Therefore, the magnitude of the antitumor T cell response and the corresponding downstream IFNγ signaling are the main drivers of clinical response or resistance to immune checkpoint blockade therapy. ETOC BLURB: Analyzing the transcriptome of biopsies of patients during immune checkpoint blockade therapy, Grasso et al. show that the increase of T cell infiltration and the downstream IFNγ signaling drive clinical responses.

SUMMARY The contribution of the different waves and sites of developmental hematopoiesis to fetal and adult blood production remains unclear. Here, we identify lymphatic vessel endothelial hyaluronan receptor-1 (LYVE1) as a marker of yolk sac (YS) endothelium and definitive hematopoietic stem and progenitor cells (HSPCs). Endothelium in mid-gestation YS and vitelline vessels, but not the dorsal aorta and placenta, were labeled by Lyve1-Cre. Most YSHSPCs and erythro-myeloid progenitors were Lyve1-Cre lineage traced, but primitive erythroid cells were not, suggesting that they represent distinct lineages. Fetal liver (FL) and adult HSPCs showed 35%–40% Lyve1-Cre marking. Analysis of circulation-deficient Ncx1−/− concepti identified the YS as a major source of Lyve1-Cre labeled HSPCs. FL proerythroblast marking was extensive at embryonic day (E) 11.5–13.5, but decreased to hematopoietic stem cell (HSC) levels by E16.5, suggesting that HSCs from multiple sources became responsible for erythropoiesis. Lyve1-Cre thus marks the divergence between YS primitive and definitive hematopoiesis and provides a tool for targeting YS definitive hematopoiesis and FL colonization., Graphical Abstract, In Brief Lee et al. identify LYVE1 as a marker that is highly enriched in yolk sac endothelium and definitive HSPCs during mid-gestation. Lyve1-Cre-labeled hematopoietic cells initiate fetal liver erythropoiesis and give rise to more than one-third of fetal and adult HSCs. The primitive erythroid lineage develops from LYVE1 negative precursors.

A visible light-mediated photocatalytic bis(alkoxycarbonyl)methylation/ring expansion of alkenyl cyclobutanols is described. This approach provides a mild and operationally simple access to the synthesis of bis(alkoxycarbonyl)methyl-substituted cyclic ketones from the coupling reaction of 1-(1-arylvinyl)cyclobutanols with aryl bromomalonates.

Hyperforin, a lipophilic constituent of medicinal herb St. John's Wort, has neurobiological effects including antidepressant activity, antibiotic potency, anti-inflammatory activity and anti-tumoral properties. Furthermore, hyperforin activates transient receptor potential conical channel-6 (TRPC6), a nonselective cation channel. To elucidate the roles of hyperforin and TRPC6 in neuroinflammation in vivo, we investigated the effect of hyperforin on neuroinflammatory responses and its related events in the rat piriform cortex (PC) following status epilepticus (SE). Hyperforin attenuated microglial activation, p65-serine 276 NFκB phosphorylation, and suppressed TNF-α expression in the PC following SE. Hyperforin also effectively alleviated SE-induced vasogenic edema formation, neuronal damage, microglial TRPC6 induction and blood-derived monocyte infiltration. Our findings suggest that hyperforin may effectively attenuate microglia-mediated neuroinflammation in the TRPC6-independent manner.

In the present study, we addressed the question of whether the distinct patterns of heat shock protein (HSP) 70 and HSP90 expressions in the brain region represents the regional specific responses to status epilepsticus (SE) in an effort to better understand the role of HSPs in epileptogenic insult. HSP70 immunoreactivity was increased in CA3 pyramidal cells as well as dentate granule cells at 12h-1week after SE. HSP70 immunoreactivity was transiently increased in neurons within the piriform cortex (PC) following SE. Linear regression analysis showed no correlation between the intensity of NeuN and that of HSP70. In contrast to HSP70, HSP90 immunoreactivity was decreased in CA1-3 pyramidal cells at 4days-4weeks after SE. In addition, HSP90 immunoreactivity was decreased in PC neurons at 12h-4weeks after SE. linear regression analysis showed a direct proportional relationship between the intensity of NeuN and that of HSP90. Therefore, these findings suggest that HSP90 degradation may be closely related to neuronal vulnerability to SE insult.

We investigate on the technological potential and issues of non-woven separator as an alternative to conventional separator in terms of various evaluation points. Thus, optimal evaluation systems for new nonwoven polyacrylonitrile (PAN) separator are proposed to compare with commercialized polyethylene (PE) separator, and corresponding stacking-type pouch batteries are used as an evaluation tool. Cell performance, electrochemical stability, and thermal stability for both separators are compared. Based on the comparison results, each separator’s effects are discussed in detail. In comparison to PE separator, the non-woven separator exhibits distinct advantage in microporous structure, leading to superior reliability of cell. Based on the understanding of non-woven separator, cell performances of the separator at different charge/discharge conditions are discussed in terms of ion transport of the separator and AC impedance of the cell. Moreover, the problems of nonwoven separator to be solved are clearly stated through the phenomenological analyses. The overall evaluation results indicate that the non-woven PAN separator has many advantages over the PE separator, which, in turn, contribute to superior cell performances. Therefore, the PAN nonwoven membrane can be the most promising candidate for separators of the next generation of lithium-ion battery if the problems to be stated will be solved.

LiNi 0.5 Mn 1.5 O 4 , a cathode material for high potential applications, rapidly deteriorates at high temperatures. In this study, fluoride-containing additives are found to offer protection to the material in damaging temperature ranges. The results of investigations using a fluoride-rich pyrazole, fluoro-ethylene carbonate, trially cyanurate with multiple double bonds, and LiF explain the combined action of the protective layer and fluoride in promoting longer life cycles. Both fluoride in a protective film and free fluoride ions prevent LiF accumulation on the electrode, extending the life of the cathode material at high temperatures.

Summary The placenta provides the interface for gas and nutrient exchange between the mother and the fetus. Despite its critical function in sustaining pregnancy, the stem/progenitor cell hierarchy and molecular mechanisms responsible for the development of the placental exchange interface are poorly understood. We identified an Epcam hi labyrinth trophoblast progenitor (LaTP) in mouse placenta that at a clonal level generates all labyrinth trophoblast subtypes, syncytiotrophoblasts I and II, and sinusoidal trophoblast giant cells. Moreover, we discovered that hepatocyte growth factor/c-Met signaling is required for sustaining proliferation of LaTP during midgestation. Loss of trophoblast c-Met also disrupted terminal differentiation and polarization of syncytiotrophoblasts, leading to intrauterine fetal growth restriction, fetal liver hypocellularity, and demise. Identification of this c-Met-dependent multipotent LaTP provides a landmark in the poorly defined placental stem/progenitor cell hierarchy and may help us understand pregnancy complications caused by a defective placental exchange.

The self-discharge of Zn anode material is identified as a main factor that can limit the energy density of alkaline Zn–air batteries. Al 2 O 3 has most positive effect on controlling the hydrogen evolution reaction accompanied by corroding Zn anode among various additives. The overpotential for hydrogen evolution is measured by potentio-dynamic polarization analysis. Al-oxide with high overpotential for hydrogen evolution reaction is uniformly coated on the surface of Zn powders via chemical solution process. The morphology and composition of the surface-treated and pristine Zn powders are characterized by SEM, EDS, XRD and XPS analyses. Aluminum is distributed homogeneously over the surface of modified Zn powders, indicating uniform coating of Al-oxide, and O1s and Al2 p spectra further identified surface coating layer to be the Al-oxide. The Al-oxide coating layer can prevent Zn from exposing to the KOH electrolyte, resulting in minimizing the side reactions within batteries. The 0.25 wt.% aluminum oxide coated Zn anode material provides discharging time of more than 10 h, while the pristine Zn anode delivers only 7 h at 25 mA cm −2 . Consequently, a surface-treated Zn electrode can reduce self-discharge which is induced by side reaction such as H 2 evolution, resulting in increasing discharge capacity.

Purpose To evaluate the efficacy of stereotactic radiotherapy in patients with brain metastases by comparing two different treatment regimens, single-dose radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT). Methods and Materials Between November 2003 and December 2008, 98 patients with brain metastases were included. Fifty-eight patients were treated with SRS, and forty were treated with FSRT. Fractionated stereotactic radiotherapy was used for large lesions or lesions located near critical structures. The median doses were 20 Gy for the SRS group and 36 Gy in 6 fractions for the FSRT group. Results With a median follow-up period of 7 months, the median survival was 7 months for all patients, with a median of 6 months for the SRS group and 8 months for the FSRT group ( p = 0.89). Local progression–free survival (LPFS) rates at 6 months and 1 year were 81% and 71%, respectively, for the SRS group and 97% and 69%, respectively, for the FSRT group ( p = 0.31). Despite the fact that FSRT was used for large lesions and lesions in adverse locations, LPFS was not inferior to SRS. Toxicity was more frequently observed in the SRS group than in the FSRT group (17% vs. 5%, p = 0.05). Conclusions Because patients treated with FSRT exhibited similar survival times and LPFS rates with a lower risk of toxicity in comparison to those treated with SRS, despite the fact that FSRT was used for large lesions and lesions in adverse locations, we find that FSRT can particularly be beneficial for patients with large lesions or lesions located near critical structures. Further investigation is warranted to determine the optimal dose/fractionation.

Materials and Methods: We evaluated 335 consecutive patients with clinical stage II-III breast cancer with known hormone receptor (HR), HER2, and Ki-67 who received NAC plus BCT from 2002 to 2009. Patients were classified into six molecular subtypes: luminal A (HR+/HER2-/Ki-67