bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive genomic profiling of parathyroid carcinoma.
Authors: Kang Hyunseok , Schubert Adrian Daniel , Ladenson Paul , Ball Douglas Wilmot , Chung Jon , Schrock Alexa Betzig , Ross Jeffrey S. , Miller Vincent A. , Stephens Philip J. , Ali Siraj Mahamed 
Published: July 2017

6088 Background: Parathyroid carcinoma (PC) is a rare endocrine malignancy, which can cause life-threatening hypercalcemia. Initial surgery is often noncurative, and adjunctive radiotherapy and previous chemotherapies have not been shown to be effective. Previous studies identified recurring mutations in CDC73 and PRUNE2in a limited number of patients. We queried whether comprehensive genomic profiling (CGP) would have potential to discover novel targets of therapy. Methods: DNA was extracted from 40 microns of FFPE sections from 13 consecutive cases of relapsed/metastatic PC. CGP was performed on hybridization-captured, adaptor ligation based libraries to a mean coverage depth of 672x for up to 315 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer. Genomic alterations (GA) included base substitutions (SUB), INDELs, copy number alterations (CNA) and fusions/rearrangements. Clinically relevant GA (CRGA) were defined as GA linked to drugs on the market or under evaluation in mechanism driven clinical trials. Results: Total of 13 specimens were identified from 7 male and 6 female patients. The mean age of the patients in this study was 54 years (range 38 to 76 years). All (100%) cases were Stage IV at the time of CGP. Tumor mutation burden was generally low - median mutation load per mega base was 1.8. There were 58 total GA (4.5 GA/sample) and 10 CRGA (0.8 CRGA/sample). The most frequent GA were non-CRGA mutations in TP53 (31%) and CDC73 (31%). MEN1 mutations were identified in 23% of cases. Frequent alterations in genes controlling cell cycle progression at G1 including CDKN1B, CDKN2A, CDKN2B and CDKN2C were identified (30%). The most frequent CRGA involved PTEN (23%), NF1 (23%) and KDR (15%). No alterations in BRAF or RETwere identified. A patient with KDR mutation treated with cabozantinib experienced > 50% drop in PTH level and radiographic partial response in 3 months. Conclusions: CGP identified previously unreported TP53 mutations in PCs and potentially actionable genomic alterations including PTEN, NF1 and KDR. Clinical benefit and response observed in a patient treated with VEGFR targeted therapy suggest that patients with this rare tumor may be candidates for targeted therapies.
Accelerating clinical trial enrollment with comprehensive genomic profiling (CGP) and just-in-time clinical trial sites: An index case of a paradigm shift.
Authors: Singal Gaurav , Madduri Deepu , Yuan Lara , Luo David , Upadhyay Aparna , Wiener Matthew B. , Wander Seth Andrew , Lynam Eric B. , Bourque David , Parker Alex , Manor Rob , McCarthy Will , Maneval Edna Chow , Ali Siraj Mahamed , Miller Vincent A. 
Published: July 2017

6539 Background: In many instances, trials may offer the best or only therapeutic option for patients with rare findings. However, conducting clinical trials of novel therapeutics targeting rare molecular variants is challenging. Patient populations are small, distributed, and predominantly in community settings where trial access remains limited by awareness and site availability. These challenges increase costs of drug development and approval, delaying widespread patient access. Methods: Foundation Medicine deployed a trial education and access program, “Precision Enrollment,” with Ignyta (a trial sponsor) and Pharmatech (a site management organization, or SMO, enabling “Just-In-Time” clinical trials) (Wiener, JCO 2007). Infrastructure and algorithms developed at Foundation Medicine (“SmartTrials Engine”) matched sequenced patients (avg n = 800/wk) with activating NTRK, ROS1, or ALK fusions to the phase II study of Entrectinib (NCT02568267). Oncologists at Foundation Medicine, through peer-to-peer outreach, facilitated trial access by providing trial and nearest site information to treating providers of matched patients. Results: 107 treatment-eligible patients with NTRK, ROS1, or ALK fusions were matched by the SmartTrials Engine; 36 (33%) expressed interest in trial participation. One such patient with NSCLC and a CD74-ROS1 fusion was unable to participate at an open trial site due to inability to travel. The patient’s site was part of the “Just-In-Time” network, with IRB and contract pre-approval, and was activated in only 3 days. Total time from patient identification to initiation of therapy was 7 days. Conclusions: We demonstrate a novel methodology for patient matching to trials targeting rare genomic findings, including in community settings. If extended, such innovative partnerships combined with computational matching infrastructure, could improve drug development and therapeutic access.
Loss of heterozygosity in multiple myeloma: A role for PARP inhibition?
Authors: Pawlyn Charlotte , Loehr Andrea , Tytarenko Ruslana , Deshpande Shayu , Sun James , Fedorchak Kyle , Mughal Tariq I. , Davies Faith , Walker Brian , Raponi Mitch , Morgan Gareth John 
Published: July 2017

8026 Background: PARP inhibitors can induce synthetic lethality in tumors characterized by homologous recombination deficiency (HRD). Two PARP inhibitors are approved for the treatment of BRCA mutated ovarian cancer. HRD can be detected by evaluating genome-wide loss of heterozygosity (LOH), which is associated with response to PARP inhibition. Myeloma (MM) is a genetically unstable tumor and we hypothesized that LOH could be detected in patient samples, supporting a potential role for PARP inhibition in MM. Methods: We analyzed 406 cases at all disease stages: MGUS (n = 7), smoldering MM (SMM, n = 30) newly diagnosed MM (NDMM, n = 71), treated MM (TRMM, n = 64) and relapsed MM (RLMM, n = 234). CD138+ plasma cell DNA underwent targeted next generation sequencing (FoundationOne Heme) interrogating 405 cancer related genes and 3543 single nucleotide polymorphisms (SNPs) across the genome. An algorithm using the minor allele frequencies of the examined SNPs and copy number profile across the 22 autosomal chromosomes identified LOH segments. Events unlikely to be caused by HRD, e.g. whole chromosome or chromosome-arm loss, were excluded. The percentage of genomic LOH for each sample was calculated as the sum of the lengths of included LOH segments divided by the length of the interrogated genome. Results: We found evidence of HRD detected by LOH with higher LOH selecting for patients with poor outcome. LOH increases with advancing disease stage from a median of 0.3% in MGUS to 3.1% in RLMM. LOH was highest in the PR and MMSET molecular subgroups and correlated significantly with the gene expression defined risk score GEP70 (R = 0.4, p < 0.001) and proliferation index (R = 0.4, p < 0.001). Outcome of RLMM patients, the biggest clinical group, was analyzed and patients with LOH above the 3rdquartile (≥5%LOH) had significantly worse overall survival than those with lower levels (p < 0.001). LOH correlates and overlaps with other metrics of poor prognosis, suggesting it may be a prognostic marker itself. Conclusions: We demonstrated LOH in MM samples, increasing as disease progresses and associated with poor prognosis. These data support the further evaluation of PARP inhibitors in MM patients, particularly in the relapsed setting with a high unmet need for new treatments.
Association of ALK resistance mutations by EML4-ALK variant (v3 vs. non-v3) in ALK+ non-small cell lung cancer (NSCLC).
Authors: Ou Sai-Hong Ignatius , Schrock Alexa Betzig , Gowen Kyle , Stephens Philip J. , Ross Jeffrey S. , Johnson Melissa Lynne , Lovly Christine Marie , Ali Siraj Mahamed , Miller Vincent A. , Shaw Alice Tsang 
Published: July 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 < 0.0002). G1202R mutation in particular was significantly associated with EML4-ALK v3 versus v1 (P < 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]
Characteristics of advanced non-small cell lung cancer (aNSCLC) patients (pts) receiving molecular diagnostic (MD) testing in U.S. routine clinical practice.
Authors: Wang Lisa I , Shewade Ashwini , Lambert Peter , Arnieri Brandon , Capra William , Khorshid Mohsen , Mughal Tariq I , Gay Laurie M. , Page Damian R. , Foser Stefan 
Published: July 2017

e20627 Background: Hybrid capture (HC)-based next generation sequencing (NGS) combined with extensive molecular interpretation, such as Foundation Medicine (FMI) testing, is increasingly important for a comprehensive molecular diagnosis in the routine clinical management of lung cancer (LC) pts. FMI and other NGS platforms (including HC alone) support optimal treatment (trt) decisions by assessing multiple genetic alterations that drive LC progression. Our aim was to characterize aNSCLC pts receiving FMI or other types of MD tests using a real world oncology electronic health record (EHR) database. Methods: Flatiron aggregates pt-level EHR from a large network of cancer clinics in the US. Inclusion criteria were aNSCLC diagnosis and ≥2 clinic visits within the Flatiron network on or after January 1, 2011. Presence of MD testing was based on 5 LC biomarkers ( EGFR, ALK, KRAS, ROS1, PD-L1). Demographic and tumor characteristics at the time of aNSCLC diagnosis and trts received were summarized across 3 mutually exclusive testing groups (grps): FMI, other NGS and non-NGS. Results: As of Sept 30, 2016, the aNSCLC cohort included 30,489 pts across 4 groups: FMI (1,019 pts); other NGS (1,327 pts); non-NGS (15,205); no tests (12,938). As expected, the number of pts with FMI or NGS testing has increased in recent years. Pts in the FMI grp tended to be younger (66 vs. 68-69 years), non-smokers (25% vs. 17-19%) and have squamous cell histology (13% vs. 8-10%) compared to other MD test grps. 30% of FMI pts received testing prior to initiating first trt, compared with 38% of other NGS and 53% of non-NGS pts. For 565 pts (of 1,019) with available data on first trt after FMI testing, 24% (136 pts) initiated a NCCN recommended targeted trt for LC. In the FMI grp, 528 pts (52%) received at least one other MD test: EGFR (89%), ALK (83%), ROS1 (39%), KRAS (31%), PD-L1 (18%) and test types were 67% FISH, 55% PCR, 17% other NGS and 15% IHC. Conclusions: Differences in age, smoking and histology exist between pts receiving FMI vs. other MD tests. This analysis of a large real world pt cohort tested with FMI further supports the value of broad genomic profiling to identify rare driver mutations and ensure optimal trt.
Diphenyleneiodonium Mitigates Bupivacaine-Induced Sciatic Nerve Damage in a Diabetic Neuropathy Rat Model by Attenuating Oxidative Stress
Authors: Ji Zhong-Hua , Liu Zhong-Jie , Liu Zi-Ting , Zhao Wei , Williams Brian A. , Zhang Hong-Fei , Li Le , Xu Shi-Yuan 
Published: July 2017

BACKGROUND:
Increased oxidative stress has been linked to local anesthetic-induced nerve injury in a diabetic neuropathy (DN) rat model. The current study explores the effects of diphenyleneiodonium (DPI) chloride, an NADPH oxidase (NOX) inhibitor, on bupivacaine-induced sciatic nerve injury in DN rats.

METHODS:
A rat DN model was established through high-fat diet feeding and streptozotocin injection. The model was confirmed via testing (i) blood glucose, (ii) hindpaw allodynia responses to von Frey (VF) monofilaments, (iii) paw withdrawal thermal latency (PWTL), and (iv) nerve conduction velocity (NCV). Bupivacaine (Bup, 0.2 mL, 5 mg/mL) was used to block the right sciatic nerve. DPI (1 mg/kg) was injected subcutaneously 24 hours and 30 minutes before the sciatic block. At 24 hours after the block, NCV, various reactive oxygen species, and Caspase-3 were evaluated to determine the extent of sciatic nerve injury.

RESULTS:
The DN rat model was successfully established. Compared with the DN control group, the postblock values of VF responses (DN-Con, 16.5 ± 1.3 g; DN + Bup, 19.1 ± 1.5 g, P < .001) and PWTL significantly increased (DN-Con, 13.3 ± 1.1 seconds; DN + Bup, 14.6 ± 1.1 seconds, P = .028); the NCV of sciatic nerve was significantly reduced (DN-Con, 38.8 ± 2.4 m/s, DN + Bup, 30.5 ± 2.0 m/s, P = .003), and sciatic nerve injury (as indicated by axonal area) was more severe in the bupivacaine-treated DN group (DN-Con, 11.6 ± 0.3 μm2, DN + Bup, 7.5 ± 0.3 μm2, P < .001). In addition, DPI treatment significantly improved nerve function (VF responses, 17.3 ± 1.3 g; PWTL, 13.4 ± 1.1 seconds; NCV, 35.6 ± 3.1 m/s) and mitigated loss of axonal area (9.6 ± 0.3 μm2). Compared to the DN + Bup group (without DPI), the levels of lipid peroxides and hydroperoxides, as well as the protein expression of NOX2, NOX4, and Caspase-3, were significantly reduced in the DN + Bup + DPI group (P < .05).

CONCLUSIONS:
Subcutaneous injection of DPI appears to protect against the functional and neurohistological damage of bupivacaine-blocked sciatic nerves in a high-fat diet/streptozotocin–induced DN model.
Review of Yannis Skalidakis', Η ελεύθερη Ελλάδα: Η εξουσία του ΕΑΜ στα χρόνια της κατοχής (1943-1944) [Free Greece: The power of EAM in the occupation years, 1943–44]
Authors: Haralabidis Menelaos 
Published: July 2017

Yannis Skalidakis. Η ελεύθερη Ελλάδα: Η εξουσία του ΕΑΜ στο χρόνια της κατοχής (1943-1944) [Free Greece: The power of EAM in the occupation years, 1943–44]. Athens: Asini, 2014. 416 pp.
Review of Kevin Featherstone et al., Οι τελευταίοι Οθωμανοί: Η μουσουλμανική μειονότητα της Δυτικής Θράκης 1940-1949 [The Last Ottomans: The Muslim Minority of Greece, 1940–1949]
Authors: Karakatsanis Leonidas 
Published: July 2017

Kevin Featherstone, Dimitris Papadimitriou, Argyris Mamarelis and Georgios Niarchos. Οι τελευταίοι Οθωμανοί: Η μουσουλμανική μειονότητα της Δυτικής Θράκης 1940-1949 [The Last Ottomans: The Muslim Minority of Greece, 1940–1949 (New York: Palgrave Macmillan, 2011)]. Athens: Alexandreia, 2013. 574 pp.
Inadequate pelvic radiographs: implications of not getting it right the first time
Authors: Parker S , Nagra NS , Kulkarni K , Pegrum J , Barry S , Hughes R , Ghani Y 
Published: July 2017

Introduction Pelvic radiography is a frequent investigation. European guidelines aim to ensure appropriate use and adequate quality. When initial images are inadequate, repeat radiographs are often required, which may have significant patient safety and economic implications. Objectives The study aimed to assess the adequacy of pelvic imaging across three orthopaedic centres, to identify causes for inadequate imaging and to establish the cost of inadequate imaging from financial and patient safety perspectives. Methods Pelvic radiographs were identified on Picture Archiving and Communication System software at three UK hospitals. Radiographs were assessed against European guidelines and indications for repeat imaging were analysed. Results A total of 1,531 sequential pelvic radiographs were reviewed. The mean age of patients was 60 years (range 5 months to 101 years). Of this total, 51.9% of images were suboptimal, with no significant difference across the three hospitals (P > 0.05). Hospital 3 repeated radiographs in 6.3% of cases, compare with 18.1% and 19.7% at hospitals 1 and 2, respectively (P > 0.05). Hospital 3 identified pathology missed on the initial radiograph in 1% of cases, compared with 5.4% and 5.5% at hospitals 1 and 2, respectively (P > 0.05). Out-of-hours imaging is associated with a higher rate of suboptimal quality (69.1%) compared with normal working hours (51.3%; P = 0.006). Adequacy rates vary with age (χ 2 = 43.62, P < 0.001). Risk of having a suboptimal radiograph increases above the age of 60-years (χ 2 = 4.45, P < 0.05). The annual cost of repeat radiographs was £56,200 per hospital. Discussion and conclusion High rates of pelvic radiograph inadequacy can lead to missed pathology and the requirement for repeat imaging, which has significant patient safety and financial implications. Risk factors for inadequate radiographs include older patients and those having out-of-hours imaging.
Contributing Factors in Increasing Health Care Associated Infection (Hai’s) in Phlebitis Cases
Authors: Theresia Siwi Ikaristi Maria , Wardani Yulia 
Published: July 2017

Backgrounds: One significant problem in hospital is Health Care Associated Infection (HAI’s) and it gives many effects on patients health status.Purpose: This study was aimed to examine the incidence rate of phlebitis, the procedures of IV insertion and the factors that influence the phlebitis case in-patient department at the hospital.Methods: The main method used in this study is descriptive explorative. Started by giving training education for 15 nursing staff , medical doctor and pharmacists. Then they were obseved in doing the procedures of IV incertion, care and documentation by Using Visual Infusion Phlebitis ( VIP) scale then followed by case studies to have clear results in describing the contribution factors which influence the phlebitis incidents.Result: 35 subjects in the experimental group and 35 subjects in the control group completed The result represents that 7 from 72 patients (9,7%) were suffer from phlebitis, 25 patients (34,7%) with IV insertion were not monitored well, 5% nurses did not do the hand washing, 78% did not use the skin perlak for preventing blood to the bed linen. The mode of desinfection direction were 44% circular, 55 % from distal to proximal part, and 11% did not do the desinfectant. 100% the nurses did not documentate the IV monitoring such as the swelling, redness, the size of IV canule and any other skin symptoms of phlebitis. Some medication, insertion side of IV canule on the metacarpal area and flushing procedures were also determinant factor that lead to phlebitis cases.Conclusion: This study conclude that the treatment, care and monitoring IV insertion is a significant and important procedures to prevent phlebitis and automatically becomes an important aspect in preventing Health Care Associated Infection (HAI’s) rate in hospital.
Structuraland antigenic analysis of a new Rhoptry Pseudokinase Gene (ROP54) in Toxoplasma gondii
Authors: Zhou Jian , Lu Gang , Wang Lin , Zhou Aihua H. , Han Yali L. , Guo Jingjing J. , Song Pengxia X. , Zhou Huaiyu Y. , Cong Hua , Hou Ming , He Shenyi Y. 
Published: July 2017

Abstractis defined as an obligate intracellular apicomplexan parasite and influences approximatelyone-third of the human all over the world. ROP54 protein is expressed in the rhoptry of
Diplectanids (Monogenea) parasitic on sciaenid fish from Peru with the proposal of Pseudorhamnocercoides n. gen., the description of Rhamnocercus dominguesi n. sp. and the redescription of Rhamnocercoides menticirrhi Luque and Iannacone, 1991
Authors: Chero Jhon D. , Cruces Celso L. , Sáez Gloria , Iannacone José , Luque José L. 
Published: July 2017

Abstract
The Prevalence of Cyclospora cayetanensis and Cryptosporidium spp. in Turkish patients infected with HIV-1
Authors: Uysal Hayriye Kirkoyun , Adas Gokhan Tolga , Atalik Kevser , Altiparmak Semih , Akgul Ozer , Saribas Suat , Gurcan Mert , Yuksel Pelin , Yildirmak Taner , Kocazeybek Bekir , Ziver Tevhide , Oner Yasar Ali 
Published: July 2017

AbstractOpportunistic infections such as cryptosporidiosis and cyclosporiasis are commonly encountered in patients with acquired immunodeficiency syndrome (AIDS). We investigated the existence of opportunistic protozoans that significantly affect the quality of life in HIV-1 infected patients using conventional and molecular methods. The study group comprised 115 HIV-1 positive patients. In the identification of
Intestinal coccidian parasites as an underestimated cause of travellers’ diarrhoea in Polish immunocompetent patients
Authors: Kłudkowska Matylda , Pielok Łukasz , Frąckowiak Krystyna , Paul Małgorzata 
Published: July 2017

AbstractIntestinal coccidian parasites are intracellular protozoa most frequently transmitted during food-borne and water-borne infections. This group of parasites is responsible for acute diarrhoeal illnesses especially among immunocompromised patients. However, they are more frequently detected in immunocompetent individuals including travellers, and they should also be considered as important etiologic factors of travellers’ diarrhoea. We examined 221 immunocompetent patients hospitalized due to acute or chronic diarrhoea and other gastrointestinal symptoms after returning from international journeys to hot climates. A basic microscopical examination and acid – fast staining of stool samples was performed. Each patient was also a part of the epidemiological investigation to define potential risk factors of tropical gastrointestinal infections. Intestinal coccidiosis was confirmed in 12 out of 221 successively hospitalized patients (5.4%). The most common coccidian parasite was
In vitro and in vivo studies of nematophagous fungi Arthrobotrys musiformis and Arthrobotrys robusta against the larvae of the trichostrongylides
Authors: Cai Kui Zheng , Wang Bo Bo , Xu Qiang , Liu Jun Lin , Wang Kang Ying , Xue Yu Jia , Zhang Hai Yan , Wang Hai Yu , Cao Xin , Ma Zhong Ren 
Published: July 2017

AbstractSix isolates of
New and previously described dactylogyrid species (Monogenoidea: Polyonchoinea) and a gastrocotylinean pre-adult (Heteronchoinea) from pomacentrid and caesionid (Perciformes) fishes from Lizard Island, Great Barrier Reef, Australia
Authors: Mendoza-Franco Edgar F. , Binning Sandra A. , Roche Dominique G. 
Published: July 2017

AbstractDuring a parasitological survey of perciform fishes from Lizard Island, Great Barrier Reef, Australia, we found the following gill monogenoidean species (Platyhelminthes):