tbuckley/cabot-search huggingface dataset:
A simplified nomogram to predict long-term survival after conversion chemotherapy followed by hepatectomy for initially unresectable colorectal liver metastases.
Authors: Katsunori Imai, Marc Antoine Allard, Carlos Castro Benitez, Eric Vibert, Antonio Sa Cunha, Daniel Cherqui, Denis Castaing, Hideo Baba, Rene Adam
Journal: Journal of Clinical Oncology (2015)

3551 Background: Although the recent advances in surgury and chemotherapy have enabled hepatectomy in patient with initially unresectable colorectal liver metastases (CRLM), limited number of patients could actually benefit from this strategy. The aim of this study was to develop a simplified nomogram to predict long-term survival for initially unresectable CRLM treated with conversion chemotherapy followed by hepatectomy. Methods: From a cohort of 1275 patients who underwent hepatectomy between 1990 and 2012, 439 patients (34.4%) with initially unresectable CRLM were enrolled in this study. A nomogram to predict overall survival was developed based on the result of multivariate cox model. The predictive performance of the model was assessed by C-index, Kaplan-Meier curve, and calibration plots. Results: The median number of liver metastases was 5 both at diagnosis and at hepatectomy, and median tumor size was 50 mm at diagnosis and 35 mm at hepatectomy, respectively. Median number of preoperative chemotherapy courses was 10 with 136 patients (31.0%) receiving more than 1 line. Concomitant extrahepatic disease was observed in 148 patients (33.7%). Liver curative and globally curative surgery were achieved in 380 (86.6%) and 335 patients (76.3%), respectively. The 5-year overall and disease-free survival was 39.9% and 10.0%, respectively. Based on the multivariate cox model, 5 independent prognostic factors were selected into the nomogram and assigned score for each factor as follows; primary N positive: 5, tumor number at hepatectomy > 6: 7, carbohydrate antigen 19-9 at hepatectomy > 37 ng/mL: 10, disease progression during first-line chemotherapy: 9, and presence of concomitant extrahepatic disease: 3. The model achieved good discrimination and calibration, with a C-index of 0.66. The overall survival for patients with total score > 15 was significantly worse than those with £ 15 (5-year survival rate: 4.1% vs 46.3%, P< 0.0001). Conclusions: The proposed nomogram could easily stratify individual patients with initially unresectable CRLM into prognostic groups. Patients with nomogram-predicted score > 15 should be contraindicated to surgery.
Is transhepatic chemoembolization with CPT-11 charged microbeads in combination with systemic fotemustine (f-TACE) effective in uveal melanoma liver metastases? A retrospective analysis of 127 consecutive patients.
Authors: Sara Valpione, Jacopo Pigozzo, Camillo Aliberti, Raffaele Parrozzani, Silvia Stragliotto, Edoardo Midena, Pierluigi Pilati, Luca Giovanni Campana, Vanna Chiarion-Sileni
Journal: Journal of Clinical Oncology (2014)

9060 Background: Uveal melanoma is a rare cancer, it represents 5% to 6% of all melanoma diagnoses (annual incidence approximately 0.5-0.7:100000). Up to 50% of patients with UM will develop metastatic disease within 15 years from the treatment of primary tumor. The preferred spread is hematogenous and the liver is the first or prevalent site of metastatic disease in up to 95% of the recurring patients. The median survival time of metastatic uveal melanoma is generally poor, with reported median life expectancy from 3.6 to 15 months and no standard therapy established so far. Methods: We retrospectively reviewed our database of patients treated at Veneto Region Oncology Research Institute for metastatic uveal melanoma, grouped by liver replacement percentage, to evaluate the benefit of treatment with transarterial chemoembolization with CPT-11 charged microbeads combined with systemic fotemustine (f-TACE) in this set of patients. From 1990 to 2013, 156 patients were treated for metastatic uveal melanoma in our Centre. Among them, 147 patients had liver metastases and 127 had enough information recorded to perform the study and were analyzed. Results: Among 127 patients with liver metastases, 49 were treated with f-TACE as first line-therapy. The cohort of patients treated with f-TACE and the cohort that did not receive f-TACE were not significantly different for prognostic factors. The treatment with f-TACE conferred a survival advantage (20.6 vs 14.7 months, respectively; p=.050); the advantage was maintained when analysis was performed with stratification for liver metastatic substitution (HR= 0.58, p=.002). The treatment was not affected by severe toxicities. Conclusions: F-TACE seems a tolerable regimen that confers an improvement in survival of uveal melanoma patients with liver metastases. Our data prompt for the conduction of perspective comparative studies confirming the efficacy of f-TACE and, in the future, we advise combination treatments with targeted drugs.
Retrograde Synaptic Inhibition Is Mediated by α-Neurexin Binding to the α2δ Subunits of N-Type Calcium Channels
Authors: Xia-Jing Tong, Eduardo Javier López-Soto, Lei Li, Haowen Liu, Daniel Nedelcu, Diane Lipscombe, Zhitao Hu, Joshua M. Kaplan
Journal: Neuron (2017)
Molecular Epidemiology of Norovirus Strains Circulating in Ireland between 2003 and 2005
Authors: A Waters, S Coughlan, WW Hall
Journal: Endoscopy (2006)

Aims: Norovirus-associated gastroenteritis, or 'winter vomiting disease', is increasing in Ireland and the objectives of this study were to characterise, using phylogenetics, the genetic diversity within Irish norovirus strains. The study was designed to analyse representative samples from both healthcare and community-based outbreaks, thereby including strains originating from all infection settings, over a period of two years.
A phase I trial of oral 5-azacitidine in combination with romidepsin in advanced solid tumors with an expansion cohort in virally mediated cancers and liposarcoma.
Authors: Kim Anna Reiss, Michelle A. Rudek, Susan Sartorius-Mergenthaler, Melinda Downs, David Cosgrove, Stephanie Gaillard, Stephen Baylin, Nita Ahuja, Nilofer Saba Azad
Journal: Journal of Clinical Oncology (2015)

TPS2619 Background: Epigenetic alterations leading to silencing of tumor-suppressor genes play a key role in carcinogenesis and are reversible, therefore representing an appealing anti-cancer target. Hypermethylation of promoter regions by DNA methyltransferases (DNMTs) and deacetylation of histones by histone deacetylases (HDACs) are two mechanisms by which tumor suppressors are silenced. DNMT and HDAC inhibitors have been shown to reverse this process in multiple tumor types. Preclinically, combination DNMT and HDAC inhibition can synergistically re-express tumor suppressor genes and inhibit tumor growth in xenograft models. Emerging work shows that epigenetic agents modulate genes involved in viral response. We designed a phase I dose-escalation trial of oral 5-azacitidine (CC-486) and romidepsin in advanced solid tumors with an expansion cohort in virally mediated cancers and liposarcoma. Methods: We have enrolled 11 patients to date. Patients must have a metastatic or unresectable solid tumor or, for the expansion cohort, a known virally mediated cancer (e.g. EBV+ nasopharyngeal cancer, HPV+ head and neck, cervical, or anal cancer) or liposarcoma and must have failed at least one prior line of chemotherapy. Patients are enrolled in a standard 3+3 design. Toxicity is followed using the NCI CTCAE version 4.0 and disease response is followed using RECIST 1.1 criteria with serial imaging q8weeks. In the expansion cohort, patients will have paired biopsies as well as blood work for PK and PD analysis. Correlative work includes global and candidate gene methylation analysis of plasma samples and biopsy specimens. Potential candidate genes include: p16, SFRP1, TFP1, IGFBP3, EVL, CD109 and SOX17. Clinical trial information: NCT01537744.
Axon Death Pathways Converge on Axundead to Promote Functional and Structural Axon Disassembly
Authors: Lukas J. Neukomm, Thomas C. Burdett, Andrew M. Seeds, Stefanie Hampel, Jaeda C. Coutinho-Budd, Jonathan E. Farley, Jack Wong, Yonca B. Karadeniz, Jeannette M. Osterloh, Amy E. Sheehan, Marc R. Freeman
Journal: Neuron (2017)
Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma
Authors: M. Dreyling, F. Morschhauser, K. Bouabdallah, D. Bron, D. Cunningham, S.E. Assouline, G. Verhoef, K. Linton, C. Thieblemont, U. Vitolo, F. Hiemeyer, M. Giurescu, J. Garcia-Vargas, I. Gorbatchevsky, L. Liu, K. Koechert, C. Peña, M. Neves, B.H. Childs, P.L. Zinzani
Journal: Annals of Oncology (2017)

Copanlisib is a pan-class I phosphatidylinositol 3-kinase inhibitor with predominant activity against the α- and δ-isoforms.This phase II study evaluated the response rate of copanlisib administered intravenously on days 1, 8, and 15 of a 28-day cycle, in patients with indolent or aggressive malignant lymphoma. Archival tumor tissues were used for immunohistochemistry, gene-expression profiling, and mutation analysis.Thirty-three patients with indolent lymphoma and 51 with aggressive lymphoma received copanlisib. Follicular lymphoma (48.5%) and peripheral T-cell lymphoma (33.3%) were the most common histologic subtypes. Most patients (78.6%) had received prior rituximab and 54.8% were rituximab-refractory. Median duration of treatment was 23 and 8 weeks in the indolent and aggressive cohorts, respectively (overall range 2-138). Eighty patients were evaluated for efficacy. The objective response rate was 43.7% (14/32) in the indolent cohort and 27.1% (13/48) in the aggressive cohort; median progression-free survival was 294 days (range 0-874) and 70 days (range 0-897), respectively; median duration of response was 390 days (range 0-825) and 166 days (range 0-786), respectively. Common adverse events included hyperglycemia (57.1%; grade ≥3, 23.8%), hypertension (54.8%; grade ≥3, 40.5%), and diarrhea (40.5%; grade ≥3, 4.8%), all generally manageable. Neutropenia occurred in 28.6% of patients (grade 4, 11.9%). Molecular analyses showed enhanced antitumor activity in tumors with upregulated phosphatidylinositol 3-kinase pathway gene expression.Intravenous copanlisib demonstrated promising efficacy and manageable toxicity in heavily pretreated patients with various subtypes of indolent and aggressive malignant lymphoma. Subtype-specific studies of copanlisib in patients with follicular, peripheral T-cell, and mantle cell lymphomas are ongoing. This trial is registered with ClinicalTrials.gov number NCT01660451 (Part A).
Development of new endoscopic irreversible electroporation ablation device: Animal experimental study
Authors: Woojung Kim, Geeho Min, Ji Choi Seong, Yup Lee Sang, Jai Chun Hoon, Min Lee Jung, kyung Yoo In, Min Lee Jae, Han Kim Seung, Soon Choi Hyuk, Sun Kim Eun, Bora Keum, Tae Jeen Yoon, Sik Lee Hong, Duck Kim Chang
Journal: Annals of Oncology (2017)
Viral Replication Complexes Are Targeted by LC3-Guided Interferon-Inducible GTPases
Authors: Scott B. Biering, Jayoung Choi, Rachel A. Halstrom, Hailey M. Brown, Wandy L. Beatty, Sanghyun Lee, Broc T. McCune, Erin Dominici, Lelia E. Williams, Robert C. Orchard, Craig B. Wilen, Masahiro Yamamoto, Jörn Coers, Gregory A. Taylor, Seungmin Hwang
Journal: Cell Host & Microbe (2017)
Association of <i>ALK</i> resistance mutations by <i>EML4-ALK</i> variant (v3 vs. non-v3) in <i>ALK</i>+ non-small cell lung cancer (NSCLC).
Authors: Sai-Hong Ignatius Ou, Alexa Betzig Schrock, Kyle Gowen, Philip J. Stephens, Jeffrey S. Ross, Melissa Lynne Johnson, Christine Marie Lovly, Siraj Mahamed Ali, Vincent A. Miller, Alice Tsang Shaw
Journal: Journal of Clinical Oncology (2017)

9010 Background: ALK rearrangements are established targetable drivers in NSCLC. Recent reports indicate differential progression-free survival to ALK inhibitors according to specific EML4-ALK variant. Methods: We analyzed samples from 634 unique NSCLC patients (704 samples) with tumors harboring ALK rearrangements ( ALK+) detected using hybrid-capture based genomic profiling performed on DNA isolated from FFPE tissue specimens (676 samples) or ctDNA isolated from blood (28 samples) during the course of clinical care. Results: Of the 634 ALK+ cases, we identified 200 (32%) EML4- ALKv1 (E13; A20), 50 (8%) EML4-ALKv2 (E20; A20), 204 (32%) EML4- ALKv3 (E6; A20), 78 (12%) other EML4-ALK, and 102 (16%) non- EML4 ALK rearrangements. Despite relatively equal frequency of EML4-ALK v1 and v3 in this dataset, the presence of a known ALK resistance mutation (n = 40 cases) was significantly associated with v3 as compared to v1 (P &lt; 0.0002). G1202R mutation in particular was significantly associated with EML4-ALK v3 versus v1 (P &lt; 0.002), and as compared to all non-v3 (P = 0.02). The tumor mutation burden (TMB) was generally low (median v1: 1.8, v3: 2.5, non-v3: 1.8 mutations/Mb), and although significantly different between v1 and v3 (P = 0.0008) and v3 and non-v3 (P = 0.003), the difference is not expected to be clinically relevant. Available ALK+ cases with paired pre- and post-treatment samples tested for a single patient will also be evaluated by ALKfusion variant, as well as for novel non-ALK mechanisms of acquired resistance, including a case with MET kinase domain duplication acquired post-ALK targeted therapy. Conclusions: The use of tissue and blood-based next generation sequencing allows for detection of the specific ALK fusion partner, increases the understanding of the biology of ALK+ NSCLC, and may have value to foretell potential mechanisms of resistance and inform the selection of ALK inhibitor therapy. [Table: see text]
Sixty seconds on … snakebite
Authors: Anne Gulland
Journal: BMJ (2017)

No, you idiot. Not the drink but the injury caused by the long, slithery animal. The World Health Organization has just put snakebite envenoming on its list of the world’s top 20 neglected tropical diseases in what campaigners are hailing as a long overdue decision.

Exactly. Around five million people are thought to be bitten by snakes every …
New Molecular Diagnostic Approaches to Bacterial Infections and Antibacterial Resistance
Authors: Ephraim L. Tsalik, Robert A. Bonomo, Vance G. Fowler
Journal: Annual Review of Medicine (2018)

Recent advances in the field of infectious disease diagnostics have given rise to a number of host- and pathogen-centered diagnostic approaches. Most diagnostic approaches in contemporary infectious disease focus on pathogen detection and characterization. Host-focused diagnostics have recently emerged and are based on detecting the activation of biological pathways that are highly specific to the type of infecting pathogen (e.g., viral, bacterial, protozoan, fungal). Although this progress is encouraging, it is unlikely that any single diagnostic platform will fully address the clinician's need for actionable data with short turnaround times in all settings.
A clinical pathway for patients undergoing primary cytoreductive surgery with rectosigmoid colectomy for advanced ovarian or primary peritoneal cancer
Authors: M. A. Gerardi, A. Santillan, B. Meisner, T. P. Diaz-Montes, G. J. Gardner, R. L. Giuntoli, R. E. Bristow
Journal: Journal of Clinical Oncology (2007)

5569 Background: To evaluate the safety, feasibility, and economic impact of a clinical pathway including rapid diet advancement for patients undergoing rectosigmoid colectomy as part of cytoreductive surgery for advanced ovarian or primary peritoneal cancer. Methods: Post-operative management was dictated by surgeon preference in 45 consecutive patients (Group 1) and according to the prescribed clinical pathway in 19 consecutive patients (Group 2). Critical elements of the clinical pathway included: rapid diet advancement, early discontinuance of nasogastric suction, criteria-based utilization of parenteral nutrition, selective laboratory testing, and deferring initiation of chemotherapy until after discharge. Results: The median age was 58 years for Group 1 patients and 67 years for Group 2 patients. Median time to flatus was 6 days for both groups; however, the median time to tolerating diet was 6 days for Group 1, and 4 days for Group 2. Patients in Group 1 had a median length of hospital stay of 12 days (range=5–30 days), a median total 30-day post-operative hospital charge of $42,868 (range=$19,960-$130,252), and a 30-day readmission rate of 33%, compared to 8 days (range=4–28 days) (p=0.020), $32,840 (range=$18,353-$140,283) (p=0.016), and 21% (p=0.379) for Group 2, respectively. Clinical pathway-directed management was associated with a median reduction in hospital charges of $10,027 per patient. Conclusions: A critical pathway incorporating rapid diet advancement for patients undergoing primary cytoreductive surgery with rectosigmoid colectomy for ovarian or primary peritoneal cancer is feasible, safe, and associated with a significant reduction in length of hospital stay and hospital-related charges and did not increase morbidity. No significant financial relationships to disclose.
Laparoscopic versus Open Appendicectomy – A Retrospective Study
Authors: A Ghallab, H Ghous, S Mahmood, D McAvinchey
Journal: Endoscopy (2006)

Aims: Laparoscopy is the standard approach for many surgical diseases. However, its role in appendicitis is not well established yet. The aim of our study was to outline the advantages and disadvantages of laparoscopic versus open approach for patients with diagnosis of appendicitis.
Recurrent SPI1 (PU.1) fusions in high-risk pediatric T cell acute lymphoblastic leukemia
Authors: Masafumi Seki, Shunsuke Kimura, Tomoya Isobe, Kenichi Yoshida, Hiroo Ueno, Yaeko Nakajima-Takagi, Changshan Wang, Lin Lin, Ayana Kon, Hiromichi Suzuki, Yusuke Shiozawa, Keisuke Kataoka, Yoichi Fujii, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Teppei Shimamura, Kyoko Masuda, Hiroshi Kawamoto, Kentaro Ohki, Motohiro Kato, Yuki Arakawa, Katsuyoshi Koh, Ryoji Hanada, Hiroshi Moritake, Masaharu Akiyama, Ryoji Kobayashi, Takao Deguchi, Yoshiko Hashii, Toshihiko Imamura, Atsushi Sato, Nobutaka Kiyokawa, Akira Oka, Yasuhide Hayashi, Masatoshi Takagi, Atsushi Manabe, Akira Ohara, Keizo Horibe, Masashi Sanada, Atsushi Iwama, Hiroyuki Mano, Satoru Miyano, Seishi Ogawa, Junko Takita
Journal: Nature Genetics (2017)
A comparison of healthcare professional and school personnel perceptions and familiarity of academic adjustments for concussed adolescents
Authors: Cailee E Welch Bacon, Johna K Register-Mihalik, Tricia M Kasamatsu, Tamara C Valovich McLeod
Journal: British Journal of Sports Medicine (2017)

Objective To compare healthcare professionals (HCPs) and school personnel (SP) perceptions of and familiarity with academic adjustments for adolescents following a concussion. Design Cross-sectional. Setting Self-reported online survey. Subjects 4,376 participants (1,095 males, 2,003 females, 1,278 missing sex; 2,209 HCPs, 2,156 SP; age=47.5 ± 14.8) from a convenience sample of 51,507 individuals (8.5% response rate) completed the Beliefs, Attitudes, and Knowledge of Paediatric Athletes with Concussions (BAKPAC) survey. Outcome measures The independent variable was role (2 levels: HCP, SP). The dependent variables were participants’ responses to the survey items. Mann Whitney U tests ( P &lt;0.05) were used to determine group differences. Results Both HCPs and SP agreed that concussions can affect school performance (3.7/4.0±0.9; P =0.08) and that concussed adolescents are eligible for consideration under the Americans with Disabilities Act (3.0/4.0±1.0; P =0.81). 57.3% of HCPs and 57.0% of SP reported that they have managed a concussed adolescent who experienced decreased school performance, while 61.0% of HCPs and 57.5% of SP noted concussed adolescents received academic adjustments. Familiarity with individualised education plans (IEPs; P ≤.001) and 504-plans ( P ≤.001) differed among groups. SP were moderately to extremely familiar with IEPs (3.5/4.0±0.71) and 504-plans (3.3/4.0±0.91), while HCPs were only minimally to moderately familiar (IEP: 2.8/4.0±1.2; 504-plans: 2.6/4.0±1.4). Conclusions HCPs and SP must collaborate to ensure proper concussion management for concussed adolescents. These results suggest the need for targeted education for HCPs and SP concerning academic adjustments to promote a safe return-to-learn. Competing interests None.
Clinical and Biological Features Associated with Engraftment of Acute Myeloid Leukemia Patient-Derived Xenografts
Authors: Giacomo Oliveira, Gabriele Bucci, Cristina Toffalori, Carolina Caserta, Lara Crucitti, Barbara Camisa, Raffaella Greco, Francesca Biavasco, Lucia Zanotti, Laura Zito, Jose Manuel Garcia-Manteiga, Dejan Lazarevic, Matteo Giovanni Carrabba, Massimo Bernardi, Attilio Bondanza, Chiara Bonini, Fabio Ciceri, Luca Vago
Journal: Blood (2016)
Achieving an Optimal Childhood Vaccine Policy
Authors: Douglas J. Opel, Jason L. Schwartz, Saad B. Omer, Ross Silverman, Jeff Duchin, Eric Kodish, Douglas S. Diekema, Edgar K. Marcuse, Walt Orenstein
Journal: JAMA Pediatrics (2017)

Policies to remove parents' ability to opt-out from school immunization requirements on the basis of religious or personal beliefs (ie, nonmedical exemptions) may be a useful strategy to increase immunization rates and prevent outbreaks of vaccine-preventable disease. However, there is uncertainty about the effectiveness of this strategy and the range of possible outcomes. We advocate for a more deliberative process through which a broad range of outcomes is scrutinized and the balance of values underlying the policy decision to eliminate nonmedical exemptions is clearly articulated. We identify 3 outcomes that require particular consideration before policies to eliminate nonmedical exemptions are implemented widely and outline a process for making the values underlying such policies more explicit.
Improved Sensitivity in Detection of FMS-like Tyrosine Kinase Internal Tandem Duplication of a Method Using Next-Generation Sequencing Data
Authors: Junghoon Shin, Daeyoon Kim, Yoojin Hong, Youngil Koh, Hongseok Yun, Dong-Yeop Shin, Sung-Soo Yoon, Inho Kim, Junglim Lee, Byung-Su Kim
Journal: Blood (2016)
Inhibitors of Bruton's Tyrosine Kinase Reduce Anti-Red Blood Cell Response in a Murine Model of Autoimmune Hemolytic Anemia
Authors: Kerry A. Rogers, Amy M. Lehman, Carolyn Cheney, Virginia M. Goettl, Rose Mantel, Lisa L. Smith, Minh Tran, Amy J. Johnson, John C. Byrd, Jennifer A. Woyach
Journal: Blood (2016)
Microneedles enhance topical delivery of 15-deoxy-Δ 12,14 -prostaglandin J 2 and reduce nociception in temporomandibular joint of rats
Authors: Cristina G. Macedo, Amit K. Jain, Michelle Franz-Montan, Marcelo H. Napimoga, Juliana T. Clemente-Napimoga, Harvinder Singh Gill
Journal: Journal of Controlled Release (2017)
Society must consider risks of sex robots, report warns
Authors: Ingrid Torjesen
Journal: BMJ (2017)

As robots designed for sex are now available, policy makers must start to consider how they are being used and whether regulation is needed, a report from the Foundation for Responsible Robotics warns, as use of these “sexbots” will inevitably grow as technology evolves and their price drops.1

Aimee van Wynsberghe, assistant professor in ethics and technology at the Technical University of Delft, Netherlands, and codirector of the Foundation for Responsible Robotics, told a UK press conference in London on 4 July that the report had been published to encourage policy makers, academics, the technology industry, and the public to think about the issues involved.

“Clearly there isn’t much of a conversation happening about what is acceptable or permissible and what should be promoted,” said van Wynsberghe. “There is a lot of talk about …