bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fusion Kinases Identified by Genomic Analyses of Sporadic Microsatellite Instability–High Colorectal Cancers
Authors: Sato Kazuhito , Kawazu Masahito , Yamamoto Yoko , Ueno Toshihide , Kojima Shinya , Nagae Genta , Abe Hiroyuki , Soda Manabu , Oga Takafumi , Kohsaka Shinji , Sai Eirin , Yamashita Yoshihiro , Iinuma Hisae , Fukayama Masashi , Aburatani Hiroyuki , Watanabe Toshiaki , Mano Hiroyuki 
Published: October 2018

Abstract

Purpose:
Colorectal cancers with microsatellite instability–high (MSI-H) status, due to mismatch repair deficiency, are associated with poor patient outcomes after relapse. We aimed to identify novel therapeutic targets for them.

Experimental Design:
We performed MSI analyses of over 2,800 surgically resected colorectal tumors obtained from consecutive patients treated in Japan from 1998 through June 2016. Whole-exome sequencing, transcriptome sequencing, and methylation analyses were performed on 149 of 162 tumors showing MSI in BAT25 and BAT26 loci. We analyzed patient survival times using Bonferroni-adjusted log-rank tests.

Results:
Sporadic MSI-H colorectal cancers with promoter methylation of MLH1 (called MM) had a clinicopathological profile that was distinct from that of colorectal cancers of patients with germline mutations (Lynch syndrome, LS-associated) or somatic, Lynch-like mutations in mismatch repair genes. MM tumors had more insertions and deletions and more recurrent mutations in BRAF and RNF43 than LS-associated or Lynch-like MSI-H tumors. Eleven fusion kinases were exclusively detected in MM MSI-H colorectal cancers lacking oncogenic KRAS/BRAF missense mutations and were associated with worse post-relapse prognosis. We developed a simple method to identify MM tumors and applied it to a validation cohort of 28 MSI-H colorectal cancers, identifying 16 MM tumors and 2 fusion kinases.

Conclusions:
We discovered that fusion kinases are frequently observed among sporadic MM MSI-H colorectal cancers. The new method to identify MM tumors enables us to straightforwardly group MSI-H patients into candidates of LS or fusion kinase carriers.
Arming an Oncolytic Herpes Simplex Virus Type 1 with a Single-chain Fragment Variable Antibody against PD-1 for Experimental Glioblastoma Therapy
Authors: Passaro Carmela , Alayo Quazim , DeLaura Isabel , McNulty John , Grauwet Korneel , Ito Hirotaka , Bhaskaran Vivek , Mineo Marco , Lawler Sean E. , Shah Khalid , Speranza Maria C. , Goins William , McLaughlin Eric , Fernandez Soledad , Reardon David A. , Freeman Gordon J. , Chiocca E. Antonio , Nakashima Hiroshi 
Published: October 2018

Abstract

Purpose:
Glioblastoma (GBM) is resistant to standard of care. Immune checkpoints inhibitors (such as anti-PD-1 mAbs) efficiently restore antitumor T-cell activity. We engineered a new oncolytic herpes simplex virus (oHSV) expressing a single-chain antibody against PD-1 (scFvPD-1) to evaluate its efficacy in mouse models of GBM.

Experimental Design:
NG34scFvPD-1 expresses the human GADD34 gene transcriptionally controlled by the Nestin promoter to allow replication in GBM cells and a scFvPD-1 cDNA transcriptionally controlled by the CMV promoter. ELISA assays were performed to detect binding of scFvPD-1 to mouse and human PD-1. In vitro cytotoxicity and replication assays were performed to measure NG34scFvPD-1 oncolysis, and scFvPD-1 expression and secretion were determined. In vivo survival studies using orthotopic mouse GBM models were performed to evaluate the therapeutic potency of NG34scFvPD-1.

Results:
NG34scFvPD-1–infected GBM cells express and secrete scFvPD-1 that binds mouse PD-1. The introduction of the scFvPD-1 sequence in the viral backbone does not alter the oncolytic properties of NG34scFvPD-1. In situ NG34scFvPD-1 treatment improved the survival with a tail of durable survivorship in 2 syngeneic immunocompetent mouse models of GBM. Mice that survived the first GBM challenge rejected the second challenge of GBM when implanted in the contralateral hemisphere. However, this was not true when athymic mice were employed as the recipients of the second challenge, consistent with the need for an intact immune system to obtain a memory response.

Conclusions:
NG34scFvPD-1 treatment induces a durable antitumor response in 2 preclinical mouse models of GBM with evidence for antitumor memory.
Predictive Biomarkers for Checkpoint Immunotherapy: Current Status and Challenges for Clinical Application
Authors: Tray Nancy , Weber Jeffrey S. , Adams Sylvia 
Published: October 2018

Abstract
Immune-checkpoint blockade (ICB), in particular PD-1 inhibition, has rapidly changed the treatment landscape and altered therapeutic paradigms across many tumor types, with unprecedented rates of durable clinical responses in a number of cancers. Despite this success, only a subset of patients responds to ICB and, as a result, predictive biomarkers would be useful to guide the selection of patients for these therapies. This article highlights currently used biomarkers, as well as several promising novel candidates, and also discusses the challenges involved in establishing their analytic validity and clinical utility. Progress is being evaluated in melanoma and non–small cell lung cancer, for which PD-1 ± CTLA-4 inhibitors have become standard therapy, to other malignancies for which PD-L1 inhibitors remain investigational. Although single biomarkers have substantial limitations, a combination of biomarkers that reflect the interaction of host and tumor will likely be needed to provide a reproducible surrogate for the benefit of checkpoint modulation. Cancer Immunol Res; 6(10); 1122–8. ©2018 AACR.
A new approach to concept basicness and stability as a window to the robustness of concept list rankings
Authors: Dellert Johannes , Buch Armin 
Published: October 2018

Abstract
Based on a recently published large-scale lexicostatistical database, we rank 1,016 concepts by their suitability for inclusion in Swadesh-style lists of basic stable concepts. For this, we define separate measures of basicness and stability. Basicness in the sense of morphological simplicity is measured based on information content, a generalization of word length which corrects for distorting effects of phoneme inventory sizes, phonotactics and non-stem morphemes in dictionary forms. Stability against replacement by semantic shift or borrowing is measured by sampling independent language pairs, and correlating the distances between the forms for the concept with the overall language distances. In order to determine the relative importance of basicness and stability, we optimize our combination of the two partial measures towards similarity with existing lists. A comparison with and among existing rankings suggests that concept rankings are highly data-dependent and therefore less well-grounded than previously assumed. To explore this issue, we evaluate the robustness of our ranking against language pair resampling, allowing us to assess how much volatility can be expected, and showing that only about half of the concepts on a list based on our ranking can safely be assumed to belong on the list independently of the data.
Linguistic diversification as a long-term effect of asymmetric priming
Authors: Baumann Andreas , Sommerer Lotte 
Published: October 2018

Abstract
This paper tries to narrow the gap between diachronic linguistics and research on population dynamics by presenting a mathematical model corroborating the notion that the cognitive mechanism of asymmetric priming can account for observable tendencies in language change. The asymmetric-priming hypothesis asserts that items with more substance are more likely to prime items with less substance than the reverse. Although these effects operate on a very short time scale (e.g. within an utterance) it has been argued that their long-term effect might be reductionist, unidirectional processes in language change. In this paper, we study a mathematical model of the interaction of linguistic items that differ in their formal substance, showing that, in addition to reductionist effects, asymmetric priming also results in diversification and stable coexistence of two formally related variants. The model will be applied to phenomena in the sublexical as well as the lexical domain.
Three tree priors and five datasets
Authors: Rama Taraka 
Published: October 2018

Abstract
The age of the root of the Indo-European language family has received much attention since the application of Bayesian phylogenetic methods by Gray and Atkinson (2003). With the application of new models, the root age of the Indo-European family has tended to decrease from an age that supported the Anatolian origin hypothesis to an age that supports the Steppe origin hypothesis (Chang et al., 2015). However, none of the published work in Indo-European phylogenetics has studied the effect of tree priors on phylogenetic analyses of the Indo-European family. In this paper, I intend to fill this gap by exploring the effect of tree priors on different aspects of the Indo-European family’s phylogenetic inference. I apply three tree priors—Uniform, Fossilized Birth-Death (FBD), and Coalescent—to five publicly available datasets of the Indo-European language family. I evaluate the posterior distribution of the trees from the Bayesian analysis using Bayes Factor, and find that there is support for the Steppe origin hypothesis in the case of two tree priors. I report the median and 95 % highest posterior density (HPD) interval of the root ages for all three tree priors. A model comparison suggests that either the Uniform prior or the FBD prior is more suitable than the Coalescent prior to the datasets belonging to the Indo-European language family.
The Influence of Topography on the Stability of the Norwegian Atlantic Current off Northern Norway
Authors: Ghaffari Peygham , Isachsen Pål Erik , Nøst Ole Anders , Weber Jan Erik 
Published: October 2018

AbstractThe steep continental slope off the Lofoten–Vesterålen islands of northern Norway appears to be the source of the most intense mesoscale eddy field in all of the Nordic Seas. Here we use linearized two-layer shallow-water equations to study the stability of the Norwegian Atlantic Current in this region. The study extends previous works that used linearized quasigeostrophic vertical mode equations to examine the effects of bottom topography on baroclinic instability here. We find evidence of baroclinic instability in the stacked shallow-water model but also of barotropic instability that is associated with the upper-layer lateral shear. The calculations give an indication that growth rates of barotropic instability may be comparable to or larger than those of baroclinic instability over the steepest parts of the continental slope.
Evaluation of the Team Workload Questionnaire (TWLQ) in a Team-Choice Task
Authors: Greenlee Eric T. , Funke Gregory J. , Rice Lindsay 
Published: October 2018

Objective: The present study was designed to evaluate the team workload questionnaire (TWLQ) in a task that was distinct from the task used to create it. Background: The TWLQ was created from workload ratings generated by members of athletic sports teams. Given that such teams represent only a portion of the diversity of operational teams, we aimed to assess the generalizability of the TWLQ. Method: The present study applied the TWLQ in a collaborative choice task (hiring decision) to determine whether the factor structure reported in the initial publication of the scale would generalize from the execution tasks it was developed from to a disparate team task focused on consensus building. Results: Confirmatory factor analysis indicated that the present data ( N = 144) were a poor fit for the three-factor structure of the TWLQ. Subsequent exploratory factor analysis revealed a much more interrelated model of team workload with no clear division between the three conceptual factors described in the original validation of the TWLQ. Conclusion: The factor structure of the TWLQ did not generalize to the present team-choice task. Application: Given that the duties of operational teams vary, it is critical that future research examine how the conceptual structure of team workload may be altered by task type.
Treatment of Tonsillar Carcinoma following Nononcologic Tonsillectomy: Efficacy of Transoral Robotic Revision Tonsillectomy
Authors: Gobillot Theodore A. , Kaka Azeem S. , Patel Sapna A. , Rodriguez Cristina , Cannon Richard B. , Futran Neal D. , Houlton Jeffrey J. 
Published: October 2018

ObjectiveTo evaluate whether transoral robotic surgery (TORS) is a suitable treatment approach for patients diagnosed with tonsillar carcinoma after a standard palatine tonsillectomy.Study DesignRetrospective cohort study.SettingTertiary care medical center.Subjects and MethodsPatients who underwent TORS at the University of Washington from 2010 to 2017 (n = 150) were identified. All patients who were diagnosed with tonsillar carcinoma following a nononcologic tonsillectomy and subsequently underwent TORS radical tonsillectomy were included (n = 14). Tumor stage–matched subjects (n = 44) were included who did not undergo standard tonsillectomy prior to TORS. Our primary outcome was final margin status. Secondary outcomes were presence of residual tumor, receipt and dose of postoperative adjuvant therapy, disease‐free survival (DFS), and disease‐specific survival. Patients with <6 months of follow‐up following definitive treatment were excluded from survival analyses.ResultsFinal margin status was clear in all subjects. Residual tumor was not identified in 13 of 14 (92.9%) prior‐tonsillectomy subjects following TORS radical tonsillectomy. Seven of 14 (50%) prior‐tonsillectomy subjects and 12 of 44 (27.3%) TORS‐matched subjects did not require adjuvant therapy due to favorable pathology. Among subjects who received post‐TORS radiation therapy (RT) at our institution, RT dose reduction was achieved in 3 of 4 (75%) prior‐tonsillectomy subjects and 21 of 24 (87.5%) TORS‐matched subjects. Ten of 14 (71.4%) prior‐tonsillectomy subjects and 31 of 44 (70.5%) TORS‐matched subjects avoided post‐TORS chemotherapy. DFS was not significantly different (P =. 87) between prior‐tonsillectomy and TORS‐matched groups, and no subjects died of related disease.ConclusionsPatients diagnosed with tonsillar carcinoma following a prior nononcologic standard palatine tonsillectomy are suitable candidates for revision surgery with TORS radical tonsillectomy.
Effect of Postoperative Xylitol Nasal Irrigation on Patients with Sinonasal Diseases
Authors: Kim Do Hyun , Kim Yeonji , Lim Il Gye , Cho Jin Hee , Park Yong Jin , Kim Sung Won , Kim Soo Whan 
Published: October 2018

ObjectiveTo examine the effect of xylitol nasal irrigation in a large sample size of patients who had undergone nasal surgery.Study DesignDouble‐blinded randomized controlled crossover study.SettingTertiary referral center.MethodsThe study included 100 patients with sinonasal disease who underwent endoscopic sinus surgery (ESS), septoplasty, or both concurrently. To identify patients with allergic sensitization, serum‐specific immunoglobulin E levels were measured. Nasal symptoms were evaluated with the NOSE (Nasal Obstruction Symptoms Evaluation) and SNOT‐20 (Sino‐Nasal Outcome Test–20) and via visual analog scale (VAS) scores.ResultsIn the ESS group (n = 34), the general nasal symptom score evaluated by the SNOT‐20 showed significantly greater improvement in the xylitol group versus the saline group (P =. 022). VAS symptom scores for sneezing (P =. 003), headache (P =. 02), and facial pain (P =. 037) were also more improved in the xylitol group. In the septoplasty group (n = 39), the VAS score for nasal stuffiness showed a significantly greater improvement in the xylitol group when compared with the saline irrigation group (P =. 001). Among the patients with allergic sensitization (n = 31), rhinorrhea symptoms improved significantly more in the xylitol group than in the saline group (P =. 024). The preference survey showed that more than half of the patients in each surgical group preferred xylitol irrigation.ConclusionWe found that xylitol nasal irrigation was useful in postoperative ESS and septoplasty care. For patients with allergic sensitization, rhinorrhea showed greater improvement in the xylitol group than in the saline group.
Effects of a self-management programme on patient participation in patients with chronic heart failure or chronic obstructive pulmonary disease: A randomized controlled trial
Authors: Luhr Kristina , Eldh Ann C , Theander Kersti , Holmefur Marie 
Published: October 2018

Background: Self-management strategies are crucial to patients with long-term conditions and can presumably promote patient participation, given that to patients, patient participation connotes opportunities for self-care (along with being engaged in an exchange of knowledge, a phrasing of joint goals and planning of care). So far, limited attention has been given to what components support self-management and what outcomes can be achieved. An exclusive self-management programme in primary healthcare entailed assessing its influence on patient participation. Aim: To describe the effects of a self-management programme on preferences for, and experiences of, patient participation in patients with chronic obstructive pulmonary disease or chronic heart failure. Methods: A randomized controlled trial with a six session intervention programme, including phrasing of individual action plans and group discussions on the patients’ issues. The intervention group ( n=59) received standard care and the self-management programme, and the control group ( n=59) received standard care only. Data was collected at baseline and at three months and 12 months after the intervention started, using the Patient Preferences for Patient Participation (the 4Ps) measure. Results: No significant differences were found within the groups, or between the groups, in preferences and experiences of patient participation, either in summary score or at an item level. Conclusion: A self-management group programme led by trained primary healthcare staff in primary care did not serve as means to influence patients’ experience of patient participation in the care of their long-term condition. Further studies are needed in regard to what facilitates patient participation in this setting and beyond.
The case for early post-vasectomy semen analysis combining small non-motile sperm and azoospermia
Authors: Hendry Jane , Small Robert , Zreik Abdullah , Smyth Niamh , Taylor Joby 
Published: October 2018

Background: Post-vasectomy semen analysis timing and criteria guidelines have evolved over time. Through analysis of our unit’s practice of post-vasectomy semen analysis from earlier sampling protocols at 8 weeks to single sampling at 12 weeks then 16 weeks, the impact on success rates and patient compliance were assessed. In addition, the use of small numbers of non-motile sperm and azoospermia combined rates as a marker of sterility were examined. Methods: All patients who underwent vasectomy in 2011 (8 and 12-week samples), 2013 (12-week samples) and 2016 (16-week samples) were included. Patients were given written and verbal instructions explaining the sample delivery protocol and samples. χ2 Testing was used to compare patient compliance and the results of post-vasectomy semen analysis with significance set at P<0.05. Results: In total 1124 vasectomies were performed, with 21% ( N=232) of patients non-compliant with submitting samples at the requested time period. Azoospermia rates increased with a longer time to post-vasectomy semen analysis from 82% to 95%, P<0.001; however, declining compliance meant the proportion of patients given clearance remained the same (70% vs. 68%, P=0.32). Rates of small non-motile sperm declined over an increasing time to post-vasectomy semen analysis. Therefore combined azoospermia and small non-motile sperm rates remained stable over an increasing sampling time (95% vs. 99%, P=0.39). Conclusion: The use of earlier post-vasectomy semen analysis is recommended as patient compliance decreases with the time from vasectomy. When azoospermia and small non-motile sperm rates are combined the rates of success of the procedure remain the same over time therefore earlier testing at 8 weeks is feasible without compromising clearance rates. Level of evidence: Not applicable for this single centre audit.
Operative Treatment of Proximal Rectus Femoris Injuries in Professional Soccer Players: A Series of 19 Cases
Authors: Lempainen Lasse , Kosola Jussi , Pruna Ricard , Puigdellivol Jordi , Ranne Juha , Orava Sakari 
Published: October 2018

Background: Proximal rectus femoris (PRF) tears are relatively rare injuries among top-level athletes. PRF injuries can be avulsions of both tendon heads (direct and reflected heads) or of a single head, and some have a tendency to progress to recurrent injuries. Purpose: To describe a series of operatively treated PRF ruptures in professional soccer players. Study Design: Case series; Level of evidence, 4. Methods: Nineteen cases of PRF injuries (18 patients, 1 bilateral) in professional soccer players who were treated surgically were retrospectively reviewed. Perioperative findings with return-to-play data were recorded. Results: Of the PRF injuries, 10 total avulsions (both heads) and 9 single-head tears were seen on magnetic resonance imaging and were later confirmed during surgery. All 18 patients returned to their preinjury level of play (mean follow-up, 2.8 years [range, 1-11 years]). Conclusion: The repair of PRF tears in professional soccer players yielded good results and allowed all patients to return to their preinjury level of play.
Receiving Bad News: A Thematic Analysis of Stroke Survivor Experiences
Authors: Maddern Robyn , Kneebone Ian I 
Published: October 2018

Background: Breaking bad news to patients may be required in service provision to stroke survivors. While challenging, it may be critical to the retention of optimism and participation in rehabilitation. Objectives: To explore the experience of stroke survivors when receiving bad news (RBN) from medical practitioners. Methods: Data were obtained via 1:1 interviews conducted at stroke support groups with survivors at least 12 months into recovery and subsequently transcribed for thematic analysis and coded using NVivo. Results: Eight of 10 participants experienced RBN, and 2 participants did not. The themes of being “lucky to be alive” and waiting for “delayed information” were expressed by all participants early in the interviews. Three sub-themes emerged and were labelled alliance, dissent, and dissatisfaction, each with a further 3 contextual themes. The perception of RBN was marked amongst the dissent and dissatisfaction groups, with the latter reporting negative implications for their rehabilitation as well as negative emotions, such as anger and anxiety. The perception of a poor-quality relationship with medical practitioners was said to impede rehabilitation and recovery processes. The dissent group was characterized by initial disbelief after RBN and consequently poorer long-term outcomes, whilst the Alliance group experienced very good quality of care due to existing personal knowledge and therefore did not perceive RBN during their early medical meetings. Conclusions: In the period soon after their stroke, survivors required their medical practitioners to not only communicate knowledge and information, but also needed validation of their hopes and fears for the future from an empathically attuned clinician.