tbuckley/cabot-search huggingface dataset:
Molecular and epidemiological characteristics of human Puumala and Dobrava-Belgrade hantavirus infections, Germany, 2001 to 2017
Authors: Mirko Faber, Detlev H Krüger, Brita Auste, Klaus Stark, Jörg Hofmann, Sabrina Weiss
Journal: Eurosurveillance (2019)

IntroductionTwo hantavirus species, Puumala (PUUV) and Dobrava-Belgrade (DOBV) virus (genotype Kurkino), are endemic in Germany. Recent PUUV outbreaks raised questions concerning increasing frequency of outbreaks and expansion of PUUV endemic areas.AimsTo describe the epidemiology of human PUUV and DOBV infections in Germany.MethodsWe conducted an observational retrospective study analysing national hantavirus surveillance data notified to the national public health institute and hantavirus nucleotide sequences from patients collected at the national consultation laboratory between 2001 and 2017. Matching molecular sequences with surveillance data, we conducted epidemiological, phylogenetic and phylogeographic analyses.ResultsIn total, 12,148 cases of symptomatic hantavirus infection were notified 2001-17 (mean annual incidence: 0.87/100,000; range: 0.09-3.51). PUUV infections showed a highly variable space-time disease incidence pattern, causing large outbreaks every 2-3 years with peaks in early summer and up to 3,000 annually reported cases. Sex-specific differences in disease presentation were observed. Of 202 PUUV nucleotide sequences obtained from cases, 189 (93.6%) fall into well-supported phylogenetic clusters corresponding to different endemic areas in Germany. DOBV infections caused few, mostly sporadic cases in autumn and winter in the north and east of Germany.ConclusionsThe frequency of PUUV outbreaks increased between 2001 and 2017 but our data does not support the suggested expansion of endemic areas. The epidemiology of PUUV and DOBV-Kurkino infections differs in several aspects. Moreover, the latter are relatively rare and combining efforts and data of several countries to identify risk factors and develop specific recommendations for prevention could be worthwhile.
Targeting Interleukin(IL)-30/IL-27p28 signaling in cancer stem-like cells and host environment synergistically inhibits prostate cancer growth and improves survival
Authors: Carlo Sorrentino, Zhinan Yin, Stefania Ciummo, Paola Lanuti, Li-Fan Lu, Marco Marchisio, Matteo Bellone, Emma Di Carlo
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Interleukin(IL)-30/IL-27p28 production by Prostate Cancer (PC) Stem-Like Cells (SLCs) has proven, in murine models, to be critical to tumor onset and progression. In PC patients, IL-30 expression by leukocytes infiltrating PC and draining lymph nodes correlates with advanced disease grade and stage. Here, we set out to dissect the role of host immune cell-derived IL-30 in PC growth and patient outcome. <h3>Methods</h3> PC-SLCs were implanted in wild type (WT) and IL-30 conditional knockout (IL-30KO) mice. Histopathological and cytofluorimetric analyses of murine tumors and lymphoid tissues prompted analyses of patients' PC samples and follow-ups. <h3>Results</h3> Implantation of PC-SLCs in IL-30KO mice, gave rise to slow growing tumors characterized by apoptotic events associated with CD4<sup>+</sup>T lymphocyte infiltrates and lack of CD4<sup>+</sup>Foxp3<sup>+</sup> T regulatory cells (Tregs). IL-30 knockdown in PC-SLCs reduced cancer cell proliferation, vascularization and intra-tumoral Indoleamine 2,3-Dioxygenase (IDO)<sup>+</sup>CD11b<sup>+</sup>Gr-1<sup>+</sup> myeloid-derived cells (MDCs) and led to a significant delay in tumor growth and increase in survival. IL-30-silenced tumors developed in IL-30KO mice, IL-30<sup>−/−</sup>tumors, lacked vascular supply and displayed frequent apoptotic cancer cells entrapped by perforin<sup>+</sup>TRAIL<sup>+</sup>CD3<sup>+</sup>Tlymphocytes, most of which had a CD4<sup>+</sup>T phenotype, whereas IL-10<sup>+</sup>TGFβ<sup>+</sup>Foxp3<sup>+</sup>Tregs were lacking. IL-30 silencing in PC-SLCs prevented lung metastasis in 73% of tumor-bearing WT mice and up to 80% in tumor-bearing IL-30KO mice. In patients with high-grade and locally advanced PC, those with IL-30<sup>−/−</sup>tumors, showed distinct intra-tumoral cytotoxic granule-associated RNA binding protein (TIA-1)<sup>+</sup>CD4<sup>+</sup>Tlymphocyte infiltrate, rare Foxp3<sup>+</sup>Tregs and a lower biochemical recurrence rate compared to patients with IL-30<sup>+/+</sup>tumors in which IL-30 is expressed in both tumor cells and infiltrating leukocytes. <h3>Conclusion</h3> The lack of host leukocyte-derived IL-30 inhibits Tregs expansion, promotes intra-tumoral infiltration of CD4<sup>+</sup>T lymphocytes and cancer cell apoptosis. Concomitant lack of MDC influx, obtained by IL-30 silencing in PC-SLCs, boosts cytotoxic T lymphocyte activation and cancer cell apoptosis resulting in a synergistic tumor suppression with the prospective benefit of better survival for patients with advanced disease.
Treatment of patients with chemotherapy-induced PPE using a prevention ointment containing high concentrations of antioxidants.
Authors: Juergen Lademann, Anja Martschick, Maxim E. Darvin, Franziska Kluschke, Leonhard Zastrow, Radoslav Chekerov, Jalid Sehouli
Journal: Journal of Clinical Oncology (2012)

e19558 Background: The palmar-plantar erythrodysesthesia syndrome (PPE) is a cutaneous side effect often observed in patients under chemotherapy, e.g., with pegylated liposomal doxorubicin. This side effect entails a reduction in the antioxidative potential of the skin due to intensive radical formation. Recently, it was demonstrated that topical treatment of patients with an ointment containing high concentrations of antioxidants is an efficient prevention strategy against PPE when applied before the beginning of chemotherapy. In a 5-year observation period at the Department of Dermatology of the Charité we selected patients, who had developed a PPE during treatment with a variety of chemotherapeutics. The aim of the present study was to investigate whether the antioxidant containing ointment is also suited to treat PPE, which occurred during treatment of 13 types of cancer with chemotherapeutics besides doxorubicin. Methods: In 5 years, 68 patients having developed PPE during treatment with 12 different chemotherapeutics, including pegylated liposomal doxorubicin, capecitabin and sorafenib applied an ointment containing antioxidants with a high radical protection factor (RPF). 46 patients exhibited PPE grade III and 22 patients PPE grade II. All patients were treated with the antioxidant-containing ointment, which was applied at least twice daily in the palmar and plantar regions. Results: Treatment with the antioxidant-containing ointment resulted in a distinct regression or disappearance of PPE. After 4 weeks of treatment the PPE grade III originally diagnosed in 46 patients had reduced to grade II in 6 and to grade I in 33 patients. In 7 patients the PPE had completely disappeared. The PPE grade II diagnosed in 22 patients had alleviated to grade I in 7, and completely disappeared in 15 patients. Conclusions: Obviously, cutaneous side effects entailing radical formation processes are also induced by other types of chemotherapeutics. An antioxidant containing ointment with high RPF is not only suited to prevent PPE in patients under doxorubicin therapy, but is also effective in treating PPE caused by other chemotherapeutics.
Abstract 17356: Gender Differences in Clinical Presentation and Outcomes of Patients With Acute Myocardial Infarction and Spontaneous Coronary Artery Dissection: A Nationwide Inpatient Sample Matched Analysis
Authors: Setri Fugar, Juliet A Yirerong, Alfred Solomon, Ahmed A Kolkailah, Tauseef Akthar, Sisir Siddamsetti, Abraham Walusimbi, Jorge Gomez, Obafemi Sanni, Dominic Amakye, Alexis Okoh
Journal: Circulation (2018)

Introduction: Spontaneous Coronary Artery Dissection (SCAD) is reported to occur predominantly in young women. Gender differences in the clinical presentation and outcomes of patients with SCAD have not been studied on a population level. We sought to compare the in-hospital outcomes of men and women presenting with acute myocardial infarction (AMI) and SCAD. Methods: We identified patients from the National Inpatient Sample (NIS) between 2005 and 2015 who presented with primary diagnoses of AMI and SCAD. We identified SCAD with ICD-9 code 414.12. A 1:1 propensity-matched cohort was created to examine the outcomes between men and women. Primary endpoint was in-hospital mortality. Secondary endpoints included in-hospital cardiac and non-cardiac complications. Results: Of the 6617 (32017 weighted national estimates) patients with SCAD over the study period, majority were males 3667 (55.4%). Males were younger than females (60.32 yr vs. 61.59 yr) and presented more often with ST-elevation myocardial infarction (STEMI) (53.0% vs. 45.9% P=&lt;0.001). Propensity matching yielded 2366 males and 2366 females. In the matched group, there was no significant difference in in-hospital mortality between males and females (OR 1.20 95% CI -0.93-1.54). With regards to in-hospital complications, ventricular tachycardia (V-Tach) was significantly less frequent in females as compared to males (8.0% vs. 10.1% OR 0.76 p-value 0.003). There was no significant difference between females and males in the frequency of other complications, including intracranial hemorrhage (0.2% vs 0.2% OR 1.45 p-value 0.50), GI bleed (1.8% vs 1.3% OR 1.35 p-value 0.13), cardiogenic shock (9.8% vs 9.7% OR 1.01 p-value 0.86), acute heart failure (3% vs 2.6% OR 1.18 p-value 0.26), ventricular fibrillation(vfib) (5.6% vs 6.0% OR 0.928 p-value 0.48) or stroke ( 1.5% vs 1.0% OR 1.535 p-value 0.06) Conclusion: In our large population-based analysis, compared to females, males were more likely to present with STEMI as compared to females. With the except of V-Tach, which was higher in males, there were no significant gender differences in hospital outcomes namely inpatient mortality, cardiogenic, Vfib or acute heart failure.
Phase II California Cancer Consortium Trial of Gemcitabine-Eribulin Combination in Cisplatin-Ineligible Patients With Metastatic Urothelial Carcinoma: Final Report (NCI-9653)
Authors: Sarmad Sadeghi, Susan G. Groshen, Denice D. Tsao-Wei, Rahul Parikh, Amir Mortazavi, Tanya B. Dorff, Cheryl Kefauver, Christopher Hoimes, Laurence Doyle, David I. Quinn, Edward Newman, Primo N. Lara Jr
Journal: Journal of Clinical Oncology (2019)

Patients with metastatic urothelial carcinoma are often ineligible for cisplatin-based treatments. A National Cancer Institute Cancer Therapy Evaluation Program-sponsored trial assessed the tolerability and efficacy of a gemcitabine-eribulin combination in this population.
Association between angiotensin-converting enzyme I gene I/d polymorphism and bevacizumab activity in advanced colorectal neoplasm.
Authors: Aranda E, Juan de la Haba-Rodriguez, Martinez A, M.Auxiliadora Gomez, Pulido G, Serrano R, Rodriguez B, Rodriguez R, Cantizani P, Rodriguez Antonio
Journal: Journal of Clinical Oncology (2013)

e14559 Background: Previous studies have found relation between the secondary hypertension to bevacizumab treatment and response in colorectal cancer. Some authors have suggested a critical role of the angiotensin converting enzyme (ACE) in blood pressure regulation. Furthermore, up-regulation of ACE gene expression has been observed in patients with hypertension. Over the past decade, the insertion/deletion (I/D) polymorphism of a 287-bp Alu element in intron 16 of the ACE gene has been extensively investigated and a positive association between the DD genotype and an increased risk of in hypertension has been demonstrated. We have studied the association between the ACE I/D polymorphism and the response and time to progression to bevacizumab treatment in advanced colorectal cancer. Methods: Sixty-four patients treated with the combination of fluoropirimidins oxaliplatin and bevacizumab were included in this study. The median of time to progression was 37 weeks(CI95%:9528.7-45.23) with a global rate response of 73.4%(CR:9.4%, PR:35.9%, SD:28.1%). Genomic DNA is purified from peripheral blood using the MagNaPure LC DNA isolation kit I. The ACE insertion / deletion (I / D) polymorphisms (rs1799752) was analyzed by real time PCR. We will perform SNP genotyping with SimpleProbe probes in a LightCycler 480 Real-Time PCR System (Roche Applied Science), in a 96 multiwell-plated format. We analyzed the serum levels of ECA and VEGF-A by ELISA. Results: We found a higher rate global response in the genotype D/D (In/In:57.2%, In/Del: 93.1% and Del/Del: 100%) X 2 :16.887 p:0.031. The worst time to progression was observed in the genotype In/In.(In/In:14w, In/Del:37w and Del/Del: 36w) p:n.s. There was a significant correlation between the ACE and VEGF-A serum levels (Pearson test:0.201, p:0.03). Conclusions: There is an association between angiotensin-converting enzyme I gene I/D polymorphism and the activity of bevacizumab plus chemotherapy in advanced colorectal neoplasm. These results strongly support the hypothesis for a relationship between response to antiangiogenic therapy and hypertension.
Assessment of Parent-Based Interventions for Adolescent Sexual Health
Authors: Laura Widman, Reina Evans, Hannah Javidi, Sophia Choukas-Bradley
Journal: JAMA Pediatrics (2019)

Parent-based sexual health interventions have received considerable attention as one factor that can increase safer sexual behavior among youth; however, to our knowledge, the evidence linking parent-based interventions to youth sexual behaviors has not been empirically synthesized.To examine the association of parent-based sexual health interventions with 3 primary youth outcomes-delayed sexual activity, condom use, and parent-child sexual communication-as well as several secondary outcomes. We also explored potential moderators of intervention effectiveness.A systematic search was conducted of studies published through March 2018 using MEDLINE, PsycINFO, Communication Source, and CINAHL databases and relevant review articles.Studies were included if they: (1) sampled adolescents (mean age, ≤18 years), (2) included parents in a key intervention component, (3) evaluated program effects with experimental/quasi-experimental designs, (4) included an adolescent-reported behavioral outcome, (5) consisted of a US-based sample, and (6) were published in English.Standardized mean difference (d) and 95% confidence intervals were computed from studies and meta-analyzed using random-effects models. A secondary analysis evaluated potential moderating variables.The primary outcomes were delayed sexual activity, condom use, and sexual communication.Independent findings from 31 articles reporting on 12 464 adolescents (mean age = 12.3 years) were synthesized. Across studies, there was a significant association of parent-based interventions with improved condom use (d = 0.32; 95% CI, 0.13-0.51; P = .001) and parent-child sexual communication (d = 0.27; 95% CI, 0.19-0.35; P = .001). No significant differences between parent-based interventions and control programs were found for delaying sexual activity (d = -0.06; 95% CI, -0.14 to 0.02; P = .16). The associations for condom use were heterogeneous. Moderation analyses revealed larger associations for interventions that focused on younger, compared with older, adolescents; targeted black or Hispanic youth compared with mixed race/ethnicity samples; targeted parents and teens equally compared with emphasizing parents only; and included a program dose of 10 hours or more compared with a lower dose.Parent-based sexual health programs can promote safer sex behavior and cognitions in adolescents, although the findings in this analysis were generally modest. Moderation analyses indicated several areas where future programs could place additional attention to improve potential effectiveness.
BART-Seq: cost-effective massively parallelized targeted sequencing for genomics, transcriptomics, and single-cell analysis
Authors: Fatma Uzbas, Florian Opperer, Can Sönmezer, Dmitry Shaposhnikov, Steffen Sass, Christian Krendl, Philipp Angerer, Fabian J. Theis, Nikola S. Mueller, Micha Drukker
Journal: Genome biology (2019)

We describe a highly sensitive, quantitative, and inexpensive technique for targeted sequencing of transcript cohorts or genomic regions from thousands of bulk samples or single cells in parallel. Multiplexing is based on a simple method that produces extensive matrices of diverse DNA barcodes attached to invariant primer sets, which are all pre-selected and optimized in silico. By applying the matrices in a novel workflow named Barcode Assembly foR Targeted Sequencing (BART-Seq), we analyze developmental states of thousands of single human pluripotent stem cells, either in different maintenance media or upon Wnt/β-catenin pathway activation, which identifies the mechanisms of differentiation induction. Moreover, we apply BART-Seq to the genetic screening of breast cancer patients and identify BRCA mutations with very high precision. The processing of thousands of samples and dynamic range measurements that outperform global transcriptomics techniques makes BART-Seq first targeted sequencing technique suitable for numerous research applications.
Whole Exome Sequencing Reveals Acquisition of Mutations Leading to the Onset of Donor Cell Leukemia after Hematopoietic Transplantation. a Model of Leukemogenesis
Authors: Julia Suárez González, Carolina Martinez-Laperche, Nerea Martínez, Gabriela Rodriguez-Macías, Mi Kwon, Pascual Balsalobre, David Serrano, Miguel Angel A. Piris, Jorge Gayoso, Jose Luis Díez Martín, Ismael Buño
Journal: Blood (2016)
Clip-assisted endoscopic cyanoacrylate injection for gastric varices with a gastrorenal shunt: a multicenter study
Authors: Mingyan Zhang, Ping Li, Haijun Mou, Yongjun Shi, Biguang Tuo, Suyun Jin, Ruonan Sun, Guangchuan Wang, Jiali Ma, Chunqing Zhang
Journal: Endoscopy (2019)

Abstract Background The aim of this study was to evaluate the safety and efficacy of clip-assisted endoscopic cyanoacrylate injection for gastric varices with a gastrorenal shunt. Methods Records were reviewed of patients with gastric varices and concomitant gastrorenal shunts who underwent clip-assisted endoscopic cyanoacrylate injection at three tertiary centers between April 2016 and October 2018. The assessed outcomes were technical success rate, eradication of gastric varices, cyanoacrylate embolization, and all-cause rebleeding. Results A total of 61 patients were analyzed. The procedure was successful in all patients (100 %). Gastric varices were eradicated in 30 of 33 patients (90.9 %) according to contrast-enhanced computed tomography re-examination within 1 month after the procedure. No symptoms or signs of cyanoacrylate embolization related to the procedure were observed. Four patients (6.6 %) were lost to follow-up. All-cause rebleeding occurred in 13/57 patients (22.8 %) during a median follow-up period of 225 days (interquartile range 114 – 507 days). Conclusions Clip-assisted endoscopic cyanoacrylate injection appeared to be a safe procedure that was convenient and efficacious in the treatment of gastric varices with concomitant gastrorenal shunt.
Preliminary results of phase II study of irinotecan and capecitabine combination as first line chemotherapy for advanced and metastatic gastric cancer
Authors: F. Farhat, M. Bachour, M. El Seoudi, J. Kattan, M. Ghosn, F. Nasr, W. Moukadem, F. Younes, R. Mroueh, G. Chahine
Journal: Journal of Clinical Oncology (2006)

14030 Background: Chemotherapy has a proven palliative role in advanced gastric cancer. The most widely investigated single-agent chemotherapy is 5-fluorouracil with partial response rates up to 20%. Single-agent irinotecan achieved response rates of 18%-23%. We investigated the combination Irinotecan plus Capecitabine for previously untreated locally advanced or metastatic gastric cancer. Methods: We conducted a phase II study with the combination of Irinotecan 80 mg/m 2 on day 1, 8, and 15, and capecitabine 625 mg/m 2 twice daily on days 1 to 14 repeated every 4 weeks. Patients were evaluated every second cycle. Previous chemotherapy for metastatic disease was not allowed. Patients must have measurable disease, ECOG PS &lt; 2, life expectancy &gt; 2 months, adequate hematological, liver and renal functions. Response was evaluated according to RECIST and toxicities according to NCI common toxicity criteria 3.0. Results: Between February 2002 and December 2005 31 patients were enrolled (20 male and 11 female). The median age was 57 years [range 37–74 years]. 142 cycles were administered with a median of 4.6 cycles per patient [range 1–10 cycles]. 29 patients were evaluable for response, and two are on ongoing treatment. Partial response rate was 38.5% . 9 patients (29%) had stable disease. Overall tumor control rate was 67.5%. Median time to progression and overall survival were 5.8 months [range- 1–16] and 10.58 months [range- 1–21] respectively. There was no grade III-IV reported toxicity including no hand and foot syndrome. Conclusions: Irinotecan and capecitabine in combination show an interesting tumor control rate (67.5%) with extremely well tolerated toxicity in patients with extensive gastric cancer. No significant financial relationships to disclose.
Defining the “Metastasome”: Perspectives from the genome and molecular landscape in colorectal cancer for metastasis evolution and clinical consequences
Authors: Heike Allgayer, Jörg H. Leupold, Nitin Patil
Journal: Seminars in Cancer Biology (2019)

Metastasis still poses the highest challenge for personalized therapy in cancer, partly due to a still incomplete understanding of its molecular evolution. We recently presented the most comprehensive whole-genome study of colorectal metastasis vs. matched primary tumors and suggested novel components of disease progression and metastasis evolution, some of them potentially relevant for targeted therapy. In this review, we try to put these findings into perspective with latest discoveries of colleagues and recent literature, and propose a systematic international team effort to collectively define the "metastasome", a term we introduce to summarize all genomic, epigenomic, transcriptomic, further -omic, molecular and functional characteristics rendering metastases different from primary tumors. Based on recent discoveries, we propose a revised metastasis model for colorectal cancer which is based on a common ancestor clone, early dissemination but flexible early or late stage clonal separation paralleling stromal interactions. Furthermore, we discuss hypotheses on site-specific metastasis, colorectal cancer progression, metastasis-targeted diagnosis and therapy, and metastasis prevention based on latest metastasome data.