bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphorylated KIT as a predictor of outcome in canine mast cell tumours treated with toceranib phosphate or vinblastine
Authors: Thamm Douglas H. , Weishaar Kristen M. , Charles Joseph B. , Ehrhart E. J. 
Published: July 2019

AbstractCanine cutaneous mast cell tumour (MCT) is the most common malignant skin tumour in dogs and can exhibit variable biologic behaviour. Dysregulated signalling through the receptor tyrosine kinase (RTK) KIT can promote cell proliferation and survival, and assessment of its dysregulation via detection of activating c‐kit gene mutations or assessment of KIT protein localization is associated with multiple features of malignancy. The aim of the current study was to use a previously validated immunohistochemical (IHC) assay to directly measure phosphorylated KIT (pKIT) in order to investigate its association with other established prognostic markers, response to therapy, progression free interval (PFI) and overall survival time (OST) in dogs treated medically for measurable MCT. Tumour tissue from 74 dogs enrolled in a prospective study comparing toceranib and vinblastine for MCT treatment were evaluated for pKIT immunoreactivity. pKIT was variably expressed, with some degree of positivity observed in 49/74 cases (66%). pKIT immunoreactivity was significantly associated with aberrant KIT localization, high mitotic index and high histologic grade. On univariate analysis, pKIT immunoreactivity predicted shorter PFI and OST in the entire patient population as well as shorter PFI in the toceranib treated group, and was the sole predictive factor for OST upon multivariate analysis, while mitotic index was the sole independent predictive factor for PFI. These results demonstrate that IHC detection of pKIT correlates with several features of aggressive behaviour, and may confer information that is complementary to other prognostic factors. However, the role of pKIT in predicting outcome needs to be studied further before recommendations can be made for its routine use.
Triaging the triage: reducing waiting time to triage in the emergency department at a tertiary care hospital in New Delhi, India
Authors: Kumar Akshay , Lakshminarayanan Dheeneshbabu , Joshi Nitesh , Vaid Sonali , Bhoi Sanjeev , Deorari Ashok 
Published: July 2019

BackgroundProlonged wait times prior to triage outside the emergency department (ED) were a major problem at our institution, compromising patient safety. Patients often waited for hours outside the ED in hot weather leading to exhaustion and clinical deterioration. The aim was to decrease the median waiting time to triage from 50 min outside ED for patients to <30 min over a 4-month period.MethodsA quality improvement (QI) team was formed. Data on waiting time to triage were collected between 12 pm and 1 pm. Data were collected by hospital attendants and recorded manually. T1 was noted as a time of arrival outside the ED, and T2 was noted as the time of first medical contact. The QI team used plan–do–study–act cycles to test solutions. Change ideas to address these gaps were tested during May and June 2018. Change ideas were focused on improving the knowledge and skills of staff posted in triage and reducing turnover of triage staff. Data were analysed using run chart rules.ResultsWithin 6 weeks, the waiting time to triage reduced to <30 min (median, 12 min; IQR, 11 min) and this improvement was sustained for the next 8 weeks despite an increase in patient load.ConclusionThe authors demonstrated that people new to QI could use improvement methods to address a specific problem. It was the commitment of the frontline staff, with the active support of senior leadership in the department that helped this effort succeed.
Stroke mechanisms and outcomes of isolated symptomatic basilar artery stenosis
Authors: Samaniego Edgar A , Shaban Amir , Ortega-Gutierrez Santiago , Roa Jorge A , Hasan David M , Derdeyn Colin , Dai Biyue , Adams Harold , Leira Enrique 
Published: July 2019

BackgroundWhile diffuse atherosclerotic disease affecting the posterior circulation has been described extensively, the prevalence, natural history and angiographic characteristics ofisolatedsymptomatic basilar artery stenosis (ISBAS) remain unknown.MethodsWe reviewed our prospective institutional database to identify patients with ≥50% symptomatic basilar artery (BA) stenosis without significant atherosclerotic burden in the vertebral or posterior cerebral arteries. Stroke mechanism, collateral circulation, and degree and length of stenosis were analysed. The primary outcome was time from index event to new transient ischaemic attack (TIA), acute ischaemic stroke (AIS) or death. Other outcome variables included modified Rankin Scale (mRS) score on discharge and last follow-up.ResultsOf 6369 patients with AIS/TIA, 91 (1.43%) had ISBAS. Seventy-three (80.2%) patients presented with AIS and 18 (19.8%) with TIA. Twenty-nine (31.9%) were women and the median age was 66.8±13.6 years. The mean follow-up time was 2.7 years. The most common stroke mechanism was artery-to-artery thromboembolism (45.2%), followed by perforator occlusion (28.7%) and flow-dependent/hypoperfusion (15.1%). The percentage of stenosis was lower in patients who had favourable outcome compared with those with mRS 3–6 on discharge (78.3±14.3 vs 86.9±14.5, p=0.007). Kaplan-Meier curves showed higher recurrence/death rates in patients with ≥80% stenosis, mid-basilar location and poor collateral circulation. Approximately 13% of patients with ISBAS presented with complete BA occlusion.ConclusionISBAS is an uncommon (1.43%) cause of TIA and AIS. Men in their 60s are mostly affected, and artery-to-artery embolism is the most common stroke mechanism. Mid-basilar location, ≥80% stenosis and poor collateral circulation are important factors associated with worse prognosis.
Fusion of halo nucleus 6He on 238U : Evidence for tennis-ball (bubble) structure of the core of the halo (even the giant-halo) nucleus
Authors: Abbas Syed Afsar 
Published: July 2019

In a decade-and-a-half old experiment, Raabe et al. [Nature 431, 823 (2004)], had studied fusion of an incoming beam of halo nucleus 6He with the target nucleus [Formula: see text]. We extract a new interpretation of the experiment, different from the one that has been inferred so far. We show that their experiment is actually able to discriminate between the structures of the target nucleus (behaving as standard nucleus with density distribution described with canonical RMS radius [Formula: see text] with [Formula: see text] fm), and the “core” of the halo nucleus, which surprisingly, does not follow the standard density distribution with the above RMS radius. In fact, the core has the structure of a tennis-ball (bubble)-like nucleus, with a “hole” at the center of the density distribution. This novel interpretation of the fusion experiment provides an unambiguous support to an almost two decades old model [A. Abbas, Mod. Phys. Lett. A 16, 755 (2001)], of the halo nuclei. This Quantum Chromodynamics based model succeeds in identifying all known halo nuclei and makes clear-cut and unique predictions for new and heavier halo nuclei. This model supports the existence of tennis-ball (bubble)-like core, of even the giant-neutron halo nuclei. This should prove beneficial to the experimentalists, to go forward more confidently, in their study of exotic nuclei.
Single-motor-unit discharge characteristics in lumbar multifidus muscle of acute low back pain patients
Authors: Lothe Lise R. , Raven Tim J. L. , Sandbæk Gunnar , Eken Torsten 
Published: July 2019

Acute low back pain (ALBP) causes rapid deterioration of paraspinal muscle function. The underlying neurophysiology is poorly understood. We therefore carried out this observational study in patients with ALBP to characterize motor unit (MU) activity in deep lumbar multifidus (LM) muscle and compare with our previous findings from pain-free subjects. Nine subjects (1 woman; age 26–59 yr) with ALBP duration of 1–21 days were recruited from outpatient clinics. Fine wire electromyography (EMG) electrodes were implanted bilaterally at the painful spinal level under computer tomography guidance. EMG was recorded during spontaneous sitting and standing, and during voluntary force production. Linear mixed models were utilized to test or control for the effects of a number of predefined variables. Compared with sitting, standing increased total duration of EMG activity, median MU discharge rate, interspike interval variability, and common drive measured as common drive coefficients (CDC) derived from concurrently active MU pairs. Median discharge rate in 73 MUs was 5.5 and 6.6 pulses per second (pps) during spontaneous sitting and standing, and 7.2 pps during voluntary force production. Interspike interval variability was lower during voluntary tasks than during spontaneous force production. Common drive was less pronounced in bilateral vs. unilateral unit pairs, also in spontaneous standing. This difference was not seen in our previous pain-free subjects, suggesting altered bilateral control of the spine in ALBP. The distribution of CDC values was not a homogeneous continuum but could be seen as two partially overlapping populations of CDC distributions. NEW & NOTEWORTHY We implanted fine-wire electrodes in the deepest part of axial postural muscles in patients with acute low back pain and characterized their motor unit activity. We found less pronounced common drive to the two sides of the spine compared with pain-free subjects, suggesting a different postural control strategy in patients with acute low back pain. An unexpected finding was that common drive coefficient values appeared to consist of two partially overlapping populations of normal distributions.
Persons with essential tremor can adapt to new walking patterns
Authors: Roper Jaimie A. , Brinkerhoff Sarah A. , Harrison Benjamin R. , Schmitt Abigail C. , Roemmich Ryan T. , Hass Chris J. 
Published: July 2019

Essential tremor (ET) is a common movement disorder that causes motor deficits similar to those seen in cerebellar disorders. These include kinetic tremor, gait ataxia, and impaired motor adaptation. Previous studies of motor adaptation in ET have focused on reaching while the effects of ET on gait adaptation are currently unknown. The purpose of this study was to contrast locomotor adaptation in persons with and without ET. We hypothesized that persons with ET would show impaired gait adaptation. In a cross-sectional study, persons with ET ( n = 14) and healthy matched controls ( n = 12) walked on a split-belt treadmill. Participants walked with the belts moving at a 2:1 ratio, followed by overground walking to test transfer, followed by a readaptation period and finally a deadaptation period. Step length asymmetry was measured to assess the rate of adaptation, amount of transfer, and rates of readaptation and deadaptation. Spatial, temporal, and velocity contributions to step length asymmetry were analyzed during adaptation. There were no group by condition interactions in step length asymmetry or contributions to step length asymmetry. Regardless of condition, persons with ET walked slower and exhibited lower temporal ( P < 0.001) and velocity ( P = 0.001) contributions to step length asymmetry than controls. Persons with ET demonstrated a preserved ability to adapt to, store, and transfer a new walking pattern. Despite probable cerebellar involvement in ET, locomotor adaptation is an available mechanism to teach persons with ET new gait patterns. NEW & NOTEWORTHY This study is the first to investigate walking adaptation abilities of people with essential tremor. Despite evidence of cerebellar impairment in this population, people with essential tremor can adapt their walking patterns. However, people with essential tremor do not modulate the timing of their footsteps to meet walking demands. Therefore, this study is the first to report impairments in the temporal aspects of walking in people with essential tremor during both typical and locomotor learning.
A Tumor-Localized Approach to Bypass Anti-4-1BB Immuno-Toxicity
Authors: Su Tina Tianjiao , Gao Xiaobin , Wang Jun 
Published: July 2019

Abstract
4-1BB (CD137) is an important costimulatory molecule upregulated on antigen-experienced T cells, however, clinical development of 4-1BB agonists has stalled because of significant liver immuno-toxicity. Using rational protein engineering, a next-generation anticalin-antibody–based therapy achieved localized 4-1BB activation triggered by tumor-expressed antigen, helping to revitalize this pathway in immuno-oncology.
See related article by Hinner et al., p. 5878
Mystus prabini, a new species of catfish (Siluriformes: Bagridae) from Arunachal Pradesh, north-eastern, India
Authors: DARSHAN ACHOM , ABUJAM SANTOSHKUMAR , KUMAR RAM , PARHI JANMEJAY , SINGH YAMBEM SURESH , VISHWANATH WAIKHOM , DAS DEBANGSHU NARAYAN , PANDEY PRAMOD KUMAR 
Published: July 2019

Mystus prabini, new species, is described from the Sinkin and the Dibang River in the Lower Dibang Valley District of Arunachal Pradesh, India. The new species differs from all South-Asian congeners except M. bleekeri, M. cavasius, M. zeylanicus, M. falcarius, M. seengtee, M. cineraceus, M. ngasep, M. rufescens and M. ankutta in having a long adipose fin that reaches anteriorly (vs. distinctly does not reach) the base of the last dorsal-fin ray. The new species can be distinguished from the named nine species in having (vs. lacking) a narrow black mid-lateral stripe extending from the anterior region of tympanic spot to the rounded black spot at the caudal-fin base. The analysis of mitochondrial cytochrome c oxidase subunit I (COI) gene sequence shows that the K2P value between Mystus prabini and all other Mystus species ranges from 8.6–22.1%. Mystus prabini is closest genetically to M. bleekeri and M. albolineatus, from which species it has a genetic distance of 8.6% and 13.9%, respectively. The genetic distance (K2P) between the new species and M. dibrugarensis is 21.1%.
Clinical Approach After Complicated Ear Mold Fitting: A Case Series of Six Patients and Evaluation of Literature
Authors: van den Boer Cindy , van Spronsen Erik , Holland Carlijn T. Q. , Ebbens Fenna A. , Waterval Jérôme J. 
Published: July 2019

Objectives: Insertion of mold material into the middle ear is a complication of molding procedure for ear impression. These cases are referred to an ENT specialist. There is no standardized approach to this problem. Literature shows different clinical strategies. The aim of this study is to share our experience and to analyze the adverse outcome of different clinical approaches. Methods: A case series of six patients with molding material inside the middle ear after complicated molding procedure for swimming earplugs are described. Additionally, available literature was reviewed to analyze results of the clinical approach after iatrogenic molding procedures. Forty-nine ears were included. Results: In-office removal of the material is associated with a significant risk of adverse outcome if the eardrum cannot be examined. This also accounts for ossicular involvement. Conclusions: Temporal bone CT is advised in patients after complicated ear mold fitting if the tympanic membrane cannot be examined completely or the middle ear is involved. Blind removal should be avoided. Retroauricular transcanal tympanotomy or transmastoidal tympanotomy with facial recess approach is best practice in case the mold material has entered the middle ear. A clinical treatment algorithm is presented.
Changes in prevalence of faecal occult blood positivity over time
Authors: Goulding Anna , Clark Gavin RC , Anderson Annie S , Strachan Judith A , Fraser Callum G , Steele Robert JC 
Published: July 2019

Objectives Changes in the prevalence of faecal occult blood test positivity over time have not been previously reported, but could have important implications. This study examined the positivity of the initial guaiac faecal occult blood test, a surrogate marker for colorectal bleeding, in participants aged 50 in a national bowel screening programme. Methods Data from the Scottish Bowel Screening Programme were used to study the initial positivity of the guaiac faecal occult blood test between 2007 and 2017. Positive predictive values of the testing process for colorectal cancer and adenoma were assessed over the same time period. Results Across Scotland, the initial guaiac faecal occult blood test positivity increased from 4.1 to 10.8%. In NHS Grampian and NHS Fife, two of the three NHS Boards which began roll-out of screening in 2007, it increased from 4.0 to 10.9%. In the Scottish Bowel Screening Programme, the positive predictive value declined from 11.0 to 6.6% for colorectal cancer and increased from 31.6 to 39.8% for adenoma. Conclusions In the Scottish programme over a decade, initial guaiac faecal occult blood test positivity increased in participants aged 50. This may be associated with changes in lifestyle and might have implications for screening clinical outcomes, including positive predictive value.
Incidence and risk factors of transfusion reactions in postpartum blood transfusions
Authors: Thurn Lars , Wikman Agneta , Westgren Magnus , Lindqvist Pelle G. 
Published: July 2019

AbstractPostpartum hemorrhages with blood transfusions are increasing in many high-resource countries. Currently, up to 3% of all women receive blood transfusion postpartum. Most blood transfusions are safe and, in many cases, are lifesaving, but there are significant concerns about adverse reactions. Pregnancy is associated with higher levels of leukocyte antibodies and has a modulating effect on the immune system. Our objective was to investigate whether blood transfusions postpartum are accompanied by an increased risk for transfusion reactions (TRs) compared with transfusions given to nonpregnant women. We included all women who gave birth in Stockholm County, Sweden between 1990 and 2011. Data from the Swedish National Birth Registry were linked to the Stockholm Transfusion Database and included information on blood components administered and whether a TR occurred in women who received blood transfusions postpartum. Background controls were nonpregnant women who received blood transfusions during the study period. The study cohort consisted of 517 854 women. Of these, 12 183 (2.4%) received a blood transfusion. We identified 96 events involving a TR postpartum, giving a prevalence of 79 per 10 000 compared with 40 per 10 000 among nonpregnant women (odds ratio, 2.0; 95% confidence interval, 1.6-2.5). Preeclampsia was the single most important risk factor for TRs (odds ratio, 2.1; 95% confidence interval, 1.7-2.6). We conclude that special care should be taken when women with preeclampsia are considered for blood transfusion postpartum, because our findings indicate that pregnancy is associated with an increased risk for TRs.
Correlation Between MYCN Gene Status and MYCN Protein Expression in Neuroblastoma: A Pilot Study To Propose the Use of MYCN Immunohistochemistry in Limited-Resource Areas
Authors: Santiago Teresa , Tarek Nidale , Boulos Fouad , Hayes Caleb , Jeha Sima , Raimondi Susana , Rodriguez-Galindo Carlos 
Published: July 2019

PURPOSE The most significant adverse risk factor for neuroblastoma (NB) is MYCN gene amplification, which strongly associates with high-risk disease. Fluorescent in situ hybridization (FISH) is considered the best method to evaluate MYCN gene status. However, it requires a laboratory that can perform highly complex testing, specialized personnel, and costly reagents. Herein, we aimed to investigate the feasibility of using immunohistochemistry (IHC) to detect MYCN protein expression in lieu of FISH, a strategy potentially useful in areas with limited resources. METHODS A pilot cohort of 78 patients with NB, including 34 of Middle Eastern descent (MED) who had a higher prevalence of MYCN gene amplification (44.11%) and 44 of North American descent (NAD), nine (20.45%) of whom had MYCN amplification, was evaluated with IHC for MYCN protein. Correlations of FISH results and protein expression are presented. RESULTS A positive correlation between MYCN gene amplification and protein expression by IHC was seen in 22 (91.66%) of the 24 MYCN-amplified NB cases—14 (93.33%) of 15 patients of MED and eight (88.88%) of nine patients of NAD. Agreement between negative FISH and negative IHC results was noted in 18 (94.73%) patients of MED and 34 (97.14%) patients of NAD. Two cases had weak protein expression but no gene amplification (MED: n = 1; 5.0%; NAD: n = 1; 2.9%). CONCLUSION An excellent overall correlation between MYCN gene status by FISH and MYCN protein expression by IHC was confirmed. MYCN IHC in NB with reflexing to FISH in equivocal cases is potentially useful in a limited-resource setting. Evaluation of effectiveness using a larger cohort and optimization to perform MYCN IHC manually is needed.
Cancer-Specific Thresholds Adjust for Whole Exome Sequencing–Based Tumor Mutational Burden Distribution
Authors: Fernandez Evan M. , Eng Kenneth , Beg Shaham , Beltran Himisha , Faltas Bishoy M. , Mosquera Juan Miguel , Nanus David M. , Pisapia David J. , Rao Rema A. , Robinson Brian D. , Rubin Mark A. , Elemento Olivier , Sboner Andrea , Shah Manish A. , Song Wei 
Published: July 2019

PURPOSE To understand the clinical context of tumor mutational burden (TMB) when comparing a pan-cancer threshold and a cancer-specific threshold. MATERIALS AND METHODS Using whole exome sequencing data from primary tumors in The Cancer Genome Atlas (n = 3,534) and advanced and/or metastatic tumors from Weill Cornell Medicine Advanced (n = 696), TMB status was determined using a pan-cancer and cancer-specific threshold. Survival curves, number of samples classified as TMB high, and predicted neoantigens were used to evaluate the differences between thresholds. RESULTS The distribution of TMB varied dramatically among cancer types. A cancer-specific threshold was able to adjust for the different TMB distributions, whereas the pan-cancer threshold was often too stringent. The dynamic nature of the cancer-specific threshold resulted in more tumors being classified as TMB high compared with the static pan-cancer threshold. In addition, no significant difference in survival outcomes was found with the cancer-specific threshold compared with the pan-cancer threshold. Furthermore, the cancer-specific threshold maintained higher predicted neoantigen load for the TMB-high samples compared with the TMB-low samples, even when the threshold was lower than the pan-cancer threshold. CONCLUSION TMB is determined within the context of cancer type, metastatic state, and disease stage. Compared with a pan-cancer threshold, a cancer-specific threshold classifies more patients as TMB high while maintaining clinical outcomes that are not significantly different. Furthermore, the cancer-specific threshold identifies patients with a high number of predicted neoantigens. Because of the potential impact in the care of patients with cancer, TMB status should be determined in a cancer-specific manner.