tbuckley/cabot-search huggingface dataset:
Increasing risk over time of weather-related hazards to the European population: a data-driven prognostic study
Authors: Giovanni Forzieri, Alessandro Cescatti, Filipe Batista e Silva, Luc Feyen
Journal: The Lancet Planetary Health (2017)

The observed increase in the effects on human beings of weather-related disasters has been largely attributed to the rise in population exposed, with a possible influence of global warming. Yet, future risks of weather-related hazards on human lives in view of climate and demographic changes have not been comprehensively investigated.We assessed the risk of weather-related hazards to the European population in terms of annual numbers of deaths in 30 year intervals relative to the reference period (1981-2010) up to the year 2100 (2011-40, 2041-70, and 2071-100) by combining disaster records with high-resolution hazard and demographic projections in a prognostic modelling framework. We focused on the hazards with the greatest impacts-heatwaves and cold waves, wildfires, droughts, river and coastal floods, and windstorms-and evaluated their spatial and temporal variations in intensity and frequency under a business-as-usual scenario of greenhouse gas emissions. We modelled long-term demographic dynamics through a territorial modelling platform to represent the evolution of human exposure under a corresponding middle-of-the-road socioeconomic scenario. We appraised human vulnerability to weather extremes on the basis of more than 2300 records collected from disaster databases during the reference period and assumed it to be static under a scenario of no adaptation.We found that weather-related disasters could affect about two-thirds of the European population annually by the year 2100 (351 million people exposed per year [uncertainty range 126 million to 523 million] during the period 2071-100) compared with 5% during the reference period (1981-2010; 25 million people exposed per year). About 50 times the number of fatalities occurring annually during the reference period (3000 deaths) could occur by the year 2100 (152 000 deaths [80 500-239 800]). Future effects show a prominent latitudinal gradient, increasing towards southern Europe, where the premature mortality rate due to weather extremes (about 700 annual fatalities per million inhabitants [482-957] during the period 2071-100 vs 11 during the reference period) could become the greatest environmental risk factor. The projected changes are dominated by global warming (accounting for more than 90% of the rise in risk to human beings), mainly through a rise in the frequency of heatwaves (about 2700 heat-related fatalities per year during the reference period vs 151 500 [80 100-239 000] during the period 2071-100).Global warming could result in rapidly rising costs of weather-related hazards to human beings in Europe unless adequate adaptation measures are taken. Our results could aid in prioritisation of regional investments to address the unequal burden of effects on human beings of weather-related hazards and differences in adaptation capacities.European Commission.
THU0372 Effect of tnfi versus nsaid on spinal radiographic progression over 4 years in early ankylosing spondylitis: results from two observational cohorts in south korea
Authors: JW Park, MJ Kim, JK Park, YJ Lee, EB Lee, YW Song, EY Lee
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> It is uncertain whether early suppression of inflammation by tumor necrosis factor inhibitor (TNFi) leads to a decreased radiographic progression in axial spondyloarthritis (axSpA). <h3>Objectives</h3> To compare the radiographic progression over 4 years in patients with early ankylosing spondylitis (AS) using TNFi versus nonsteroidal antiinflammatory drug (NSAID) <h3>Methods</h3> A total of 215 patients with early AS (symptom duration&lt;10 years) were included based on the availability of radiographs at baseline and 2- and/or 4-years of follow up. Among them, 135 patients with TNFi were from SNUH-biologics cohort (TNFi group) and other 80 patients with NSAID were from control cohort in Seoul National University Bundang Hospital (NSAID group). Radiographic progression was assessed by two blinded readers using modified Stokes AS Spinal Score (mSASSS). Linear mixed model was applied to compare the radiographic progression between the two groups after adjustment for clinical factors. We also performed a sensitivity analysis after the propensity score matching in which age, smoking status, baseline CRP and baseline mSASSS were included as covariates. <h3>Results</h3> Patients in the TNFi group showed higher baseline BASDAI (6.7 vs. 3.1) and CRP (2.2 vs. 1.1mg/dL) as compared with those in the NSAID group. There were no differences between the two groups regarding age, gender, HLA-B27, smoking status and baseline radiographic damage. Overall, radiographic progression rate (95% CI) during the observation was 0.72 (0.57–0.87) unit/year. TNFi group showed significantly slower progression than NSAID group (β=-0.33 unit/year, p=0.042). This result was consistent after adjusting for age, smoking status, baseline CRP and presence of baseline syndesmophytes (β=-0.50 unit/year, p=0.001) (Table). In the subgroup analysis of patients without baseline syndesmophytes, TNFi group showed no radiographic progression over time whereas NSAID group did not (0.03 [-0.22–0.27] vs. 0.45 [0.20–0.71] unit/year). These results were not changed when the same analysis was performed in the post-matched population (78 TNFi group vs. 78 NSAID group). <h3>Conclusions</h3> In patients with early AS, TNFi led to a decreased radiographic progression as compared with NSAID treatment. This result suggests that early and durable suppression of inflammation using TNFi can have beneficial effect on the radiographic outcome of AS. <h3>Disclosure of Interest</h3> None declared
Oestrogen inhibition reverses pulmonary arterial hypertension and associated metabolic defects
Authors: Xinping Chen, Eric D. Austin, Megha Talati, Joshua P. Fessel, Eric H. Farber-Eger, Evan L. Brittain, Anna R. Hemnes, James E. Loyd, James West
Journal: European Respiratory Journal (2017)

Increased oestrogen is a strong epidemiological risk factor for development of pulmonary arterial hypertension (PAH) in patients, associated with metabolic defects. In addition, oestrogens drive penetrance in mice carrying mutations in bone morphogenetic protein receptor type II (BMPR2), the cause of most heritable PAH. The goal of the present study was to determine whether inhibition of oestrogens was effective in the treatment of PAH in these mice. The oestrogen inhibitors fulvestrant and anastrozole were used in a prevention and treatment paradigm in BMPR2 mutant mice, and tamoxifen was used for treatment. In addition, BMPR2 mutant mice were crossed onto oestrogen receptor (ESR)1 and ESR2 knockout backgrounds to assess receptor specificity. Haemodynamic and metabolic outcomes were measured. Oestrogen inhibition both prevented and treated PAH in BMPR2 mutant mice. This was associated with reduction in metabolic defects including oxidised lipid formation, insulin resistance and rescue of peroxisome proliferator-activated receptor-γ and CD36. The effect was mediated primarily through ESR2, but partially through ESR1. Our data suggest that trials of oestrogen inhibition in human PAH are warranted, and may improve pulmonary vascular disease through amelioration of metabolic defects. Although fulvestrant and anastrozole were more effective than tamoxifen, tamoxifen may be useful in premenopausal females, because of a reduced risk of induction of menopause.
Preliminary results of a phase II study of liposomal cisplatin-vinorelbine combination as first-line treatment in HER2/neu negative metastatic breast cancer (MBC)
Authors: F. S. Farhat, K. Ibrahim, J. Kattan, N. Bitar, R. Jalloul, G. Nsouly, M. Ghosn, N. Haddad, M. Bou Karroum, S. Tamraz, A. Shamseddine
Journal: Journal of Clinical Oncology (2009)

1068 Background: The frequent use of anthracyclines and taxanes in breast cancer's adjuvant setting has lead to drug resistance and cardiac toxicity. This has raised the need for new agents in the metastatic setting. Cisplatin-vinorelbine combination recently showed interesting results with an overall response rate of 64%. Nevertheless, the use of cisplatin was limited by the frequently induced nausea, vomiting, and nephrotoxicity. Liposomal cisplatin (Lipoplatin) is a nontoxic alternative agent to cisplatin. The aim of this study is to evaluate the efficacy and safety of liposomal cisplatin-vinorelbine combination in first line MBC patients (pts). Methods: From August 2007 to October 2008, 30 of 35 programmed pts with MBC and no prior treatment for their metastatic disease, PS 0–2, HER2/neu negative, and at least one measurable lesion, were enrolled. Of these 30 recruited pts, 26 with available data were analyzed. Treatment included I.V. vinorelbine 30 mg/m 2 on days 1 and 8, and liposomal cisplatin 120 mg/m 2 on days 1, 8, and 15. Cycles were repeated every 3 weeks for a total of 6 cycles. Primary objectives: objective response rate, time to treatment failure (TTF), and time to progression (TTP). Secondary objectives: overall survival and treatment-related toxicity. Results: The median age was 49 years (29–74). 69% of pts had visceral metastases. 35% had one metastatic site, 46% had 2, 19% had 3 or more. A total of 120 cycles were administered with a median number of 6 per patient. At the time of the analysis 22 pts were evaluable for response. An objective tumor response was observed in 11 pts (50%) and complete response in 1 patient (4.5%). Ten (45.5%) pts had stable disease. The median TTF and TTP were 5 and 8 months respectively. All pts (26) were evaluable for toxicity. The majority of adverse events were mild to moderate. No WHO grade 3–4 nephrotoxicity or neuropathy was noted. Grade 3–4 nausea/vomiting was observed in 3 pts (11.5%). Three pts (11.5%) had grade 3 anemia and 18 pts (69.2%) had grade 3–4 neutropenia. Three pts (11.5%) developed febrile neutropenia with no secondary mortality. Conclusions: The new combination of liposomal cisplatin and vinorelbine shows promising activity and good tolerance as first line treatment for HER2/neu negative MBC. Pts’ enrollment is ongoing. Updated results will be presented at the meeting. [Table: see text]
Multicenter phase II clinic trial of tripeptide tyroserleutide (YSL) for the patients with hepatoma
Authors: Wang Huaqing
Journal: Cancer Research (2007)

2651    Objectives  :  To study the efficacy and safety for different dosage of YSL for the treatment of patients with  PHC, and the curative dose.   Methods  :  324 patients were randomized in a 1:1:1 ratio to receive YSL 2ug(0.0012mg/m 2 /d),YSL2mg (1.2mg/m 2 /d)or YSL4mg (2.4mg/m 2 /d) (overall diluted in 250 ml normal saline) once daily by intravenous drip in the velocity of 40-50 dpm for 6 months. We observed the following items within 7 days before or after the end of each course: 1) physical examination 2) vital sign 3) adverse event assessment 4) concomitant drug assessment 5) ECOG and QOL score 6) blood routine,urine routine,OB,blood chemistry (glucose, lipids, liver function, renal function, serum calcium, serum magnesium, serum phosphorus), AFP 7) ECG 8) CT/MRI, and assessed the survival time, TTP, clinic benefit rate, change of the summation of the longest diameter of focus and QOL of 6 months, and compare the different between low dose group and middle/high dose group.     Results:  At the end of the study, the median survival time of low_dose group is 88.5 days and that of middle and high_dose group is 167 days. The difference between two groups are assessed using Log-rank test and the result shows that the median survival time of middle and high_dose group are significantly different from that of low_dose group (p=0.004). According to Cox model, the relative risk of middle and high_dose group to low_dose group is 0.61, which means the risk of death in the former is about 60% of that in the latter. The median TTP in low, middle and high dose groups were 49d, 72d and 60d, respectively. The median TTP of middle/high dose group was longer (23 days and 11 days respectively) than that of the low dose group. But compared TTP between every groups, there was no difference statistically (p>0.05). Compared 6-months Clinical benefit rate between each group, there was no difference statistically. Compared base line, in the last observation, the change of the summation of longest diameter of target focus in each dose group increased. There was no difference statistically between three groups. QOL changes of every group decreased , especially in the middle dose group. Compared three groups, there was no difference statistically.   Conclusions:  The 6-months median survival time of patients with PHC after treated by YSL prolonged obviously, especially in the dose of  1.2 mg/m 2 /d. There wasn’t markedly toxicity and side effect during the treatment, and the tolerance was well.   Keywords : Tripeptide tyroserleutide (YSL), Primary hepatic carcinoma, Clinic trial
成熟雄マウスにおける生殖器系上のCdTe量子ドットの毒性効果の評価【Powered by NICT】
Authors: Li Xiaohui, Yang Xiangrong, Yuwen Lihui, Yang Wenjing, Weng Lixing, Teng Zhaogang, Wang Lianhui
Journal: Biomaterials (2016)
Carcinogenic Action of Two Azo Compounds in Mice
Authors: Andervont, Howard B., Edwards, Jesse E.
Journal: JNCI Journal of the National Cancer Institute (1943)

Journal Article Carcinogenic Action of Two Azo Compounds in Mice Get access Howard B. Andervont, Howard B. Andervont principal biologist Search for other works by this author on: Oxford Academic PubMed Google Scholar Jesse E. Edwards Jesse E. Edwards research fellow National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 3, Issue 4, February 1943, Pages 349–354, https://doi.org/10.1093/jnci/3.4.349 Published: 01 February 1943
A Survey on Biofeedback and Actuation in Wireless Body Area Networks (WBANs)
Authors: Rui Li, Daniel T. H. Lai, WeeSit Lee
Journal: IEEE Reviews in Biomedical Engineering (2017)

Wireless body area networks (WBANs) have attained increasing popularity as the next generation framework of wearable technologies for human monitoring. Invasive or noninvasive wearable sensors designed in a WBAN are worn to gather vital information. Biofeedback is a recent concept where collected data are used to generate actuation signals in WBANs. Applications can be seen in various areas such as sports (e.g., locomotor velocity) or medicine (e.g., blood pressure measurement). However, since the body is closely regulated, the next generation WBAN technology must be smart enough to react to monitored data. The main aim of this paper is to review the current state of biofeedback and actuation technology on WBANs in terms of its structure, applications, benefits, and control approaches. The emphasis on the specific requirements when applying biofeedback to humans will be highlighted and discussed. Challenges and open research issues will be concluded at the end.
Osthole treatment ameliorates Th2-mediated allergic asthma and exerts immunomodulatory effects on dendritic cell maturation and function
Authors: Chen-Yuan Chiang, Chen-Chen Lee, Chia-Kwung Fan, Huei-Mei Huang, Bor-Luen Chiang, Yueh-Lun Lee
Journal: Cellular and Molecular Immunology (2017)
Abstract P329: The Thoracic and Abdominal Arterial Segments Are Genetically and Functionally Different
Authors: Ick-Mo Chung, David K Pritchard, Luis F Santana, Williams M Mahoney, Stephen M Schwartz
Journal: Circulation Research (2011)

Aims: Because arterial diseases are highly specific to different segments and because smooth muscle cells (SMCs) of different branches have distinct embryological origin, we undertook a systematic effort to determine the extent of differences in gene expression between the thoracic aorta (TA) and the abdominal aorta (AA). We also correlated these expression differences with physiologic function. Methods and Results: We utilized whole genome gene expression microarrays to compare expression patterns in the rat TA and AA. We identified 161 differentially expressed genes between these two segments. Functional analysis of differences in expression by Gene Set Enrichment Analysis identified different categories of genes enriched in each section of the aorta. For example, GPCR-related genes are overrepresented in the AA, while the TA showed dramatic enrichment of gene categories linked to mitochondria and energy generation. Because GPCR functions are implicated in many vascular diseases, we confirmed the differential expression of the arterial specific Regulator of G-protein signaling - 5 (RGS5), and extended the analysis to additional members of the RGS-R4 subfamily. RGS5 was the most abundant RGS-R4 mRNA in the AA, and it was the most differentially expressed family member across all vascular beds. To analyze functional correlates to the differential expression of RGS5, we performed aortic ring contraction assays from the TA and AA. Consistent with the hypothesis that RGS5 blocks angiotensin II (Ang II) type 1 receptor signaling via increased Gα-mediated GTPase activity, Ang II-induced force generation was significantly lower in AA relative to TA. Furthermore, whole-cell voltage-gated K + current (I Kv ) analysis revealed that I Kv was significantly greater in SMCs from the AA compared to cells from TA. Kv1.5 mRNA was more highly expressed in the AA relative to the TA. Conclusions: The differential gene expression pattern between TA and AA suggests distinct differentiation pathways may explain regional specificity of arterial diseases. Specifically, the enrichment of GPCR-related genes in the AA and mitochondrial genes in the TA may account for the diverse physiological function of these two distinct vascular segments.
FDA Approval Summary: Trabectedin for Unresectable or Metastatic Liposarcoma or Leiomyosarcoma Following an Anthracycline-Containing Regimen
Authors: Amy Barone, Dow-Chung Chi, Marc R. Theoret, Huanyu Chen, Kun He, Dubravka Kufrin, Whitney S. Helms, Sriram Subramaniam, Hong Zhao, Anuja Patel, Kirsten B. Goldberg, Patricia Keegan, Richard Pazdur
Journal: Clinical Cancer Research (2017)

Abstract On October 23, 2015, the FDA approved trabectedin, a new molecular entity for the treatment of patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-containing regimen. Approval was based on results of a single, randomized, active-controlled, 518-patient, multicenter study comparing the safety and efficacy of trabectedin 1.5 mg/m2 as a 24-hour continuous intravenous (i.v.) infusion once every 3 weeks with dacarbazine 1,000 mg/m2 i.v. once every 3 weeks. Treatment with trabectedin resulted in a statistically significant improvement in progression-free survival (PFS), with a PFS of 4.2 months and 1.5 months for trabectedin and dacarbazine, respectively (HR, 0.55; 95% confidence interval, 0.44–0.70; unstratified log-rank test, P &amp;lt; 0.001). The most common adverse reactions (≥20%) were nausea, fatigue, vomiting, constipation, decreased appetite, diarrhea, peripheral edema, dyspnea, and headache. Serious adverse reactions included anaphylaxis, neutropenic sepsis, rhabdomyolysis, hepatotoxicity, cardiomyopathy, and extravasation resulting in tissue necrosis. A postmarketing trial was required to evaluate the serious risk of cardiomyopathy. This approval provides another treatment option in a setting where no drug has been shown to improve overall survival. A key regulatory consideration during review of this application was the use of PFS as an endpoint to support regular approval of trabectedin. Clin Cancer Res; 23(24); 7448–53. ©2017 AACR.
迅速で効率的な交差血液脳関門プロピオニル化したアミロースヘリックスナノクラスタに基づく疎水性ドラッグデリバリーシステム【Powered by NICT】
Authors: Gao Wei, Liu Yongchun, Jing Guixia, Li Ke, Zhao Yuan, Sha Baoyong, Wang Qiang, Wu Daocheng
Journal: Biomaterials (2017)
A novel <i>IFIH1</i> mutation in the pincer domain underlies the clinical features of both Aicardi-Goutières and Singleton-Merten syndromes in a single patient
Authors: T. Takeichi, C. Katayama, T. Tanaka, Y. Okuno, N. Murakami, M. Kono, K. Sugiura, Y. Aoyama, M. Akiyama
Journal: British Journal of Dermatology (2017)
効果的な皮膚薬剤運搬の為の適合仕様の樹状コア‐多シェルナノキャリア:合成から前臨床試験までの体系的トップ‐ダウン法
Authors: Honzke Stefan, Gerecke Christian, Elpelt Anja, Zhang Nan, Unbehauen Michael, Kral Vivian, Fleige Emanuel, Paulus Florian, Haag Rainer, Schaefer-Korting Monika, Kleuser Burkhard, Hedtrich Sarah
Journal: Journal of Controlled Release (2016)
組織工学はヒト幹細胞を用いた伸張反射アークの機械感覚性回路:錘内筋線維の感覚ニューロンの神経支配【Powered by NICT】
Authors: Guo Xiufang, Colon Alisha, Akanda Nesar, Spradling Severo, Stancescu Maria, Martin Candace, J Hickman James
Journal: Biomaterials (2017)
Targeting RNA-Polymerase I in Both Chemosensitive and Chemoresistant Populations in Epithelial Ovarian Cancer
Authors: Robert Cornelison, Zachary C. Dobbin, Ashwini A. Katre, Dae Hoon Jeong, Yinfeng Zhang, Dongquan Chen, Yuliya Petrova, Danielle C. Llaneza, Adam D. Steg, Laura Parsons, David A. Schneider, Charles N. Landen
Journal: Clinical Cancer Research (2017)

Purpose: A hallmark of neoplasia is increased ribosome biogenesis, and targeting this process with RNA polymerase I (Pol I) inhibitors has shown some efficacy. We examined the contribution and potential targeting of ribosomal machinery in chemotherapy-resistant and -sensitive models of ovarian cancer.Experimental Design: Pol I machinery expression was examined, and subsequently targeted with the Pol I inhibitor CX-5461, in ovarian cancer cell lines, an immortalized surface epithelial line, and patient-derived xenograft (PDX) models with and without chemotherapy. Effects on viability, Pol I occupancy of rDNA, ribosomal content, and chemosensitivity were examined.Results: In PDX models, ribosomal machinery components were increased in chemotherapy-treated tumors compared with controls. Thirteen cell lines were sensitive to CX-5461, with IC50s 25 nmol/L-2 μmol/L. Interestingly, two chemoresistant lines were 10.5- and 5.5-fold more sensitive than parental lines. CX-5461 induced DNA damage checkpoint activation and G2-M arrest with increased γH2AX staining. Chemoresistant cells had 2- to 4-fold increased rDNA Pol I occupancy and increased rRNA synthesis, despite having slower proliferation rates, whereas ribosome abundance and translational efficiency were not impaired. In five PDX models treated with CX-5461, one showed a complete response, one a 55% reduction in tumor volume, and one maintained stable disease for 45 days.Conclusions: Pol I inhibition with CX-5461 shows high activity in ovarian cancer cell lines and PDX models, with an enhanced effect on chemoresistant cells. Effects occur independent of proliferation rates or dormancy. This represents a novel therapeutic approach that may have preferential activity in chemoresistant populations. Clin Cancer Res; 23(21); 6529-40. ©2017 AACR.