bluuebunny/crossref_metadata_2025_split huggingface dataset:
Across Species “Natural Ablation” Reveals the Brainstem Source of a Noninvasive Biomarker of Binaural Hearing
Authors: Benichoux Victor , Ferber Alexander , Hunt Samuel , Hughes Ethan , Tollin Daniel 
Published: August 2018

The binaural interaction component (BIC) of the auditory brainstem response is a noninvasive electroencephalographic signature of neural processing of binaural sounds. Despite its potential as a clinical biomarker, the neural structures and mechanism that generate the BIC are not known. We explore here the hypothesis that the BIC emerges from excitatory–inhibitory interactions in auditory brainstem neurons. We measured the BIC in response to click stimuli while varying interaural time differences (ITDs) in subjects of either sex from five animal species. Species had head sizes spanning a 3.5-fold range and correspondingly large variations in the sizes of the auditory brainstem nuclei known to process binaural sounds [the medial superior olive (MSO) and the lateral superior olive (LSO)]. The BIC was reliably elicited in all species, including those that have small or inexistent MSOs. In addition, the range of ITDs where BIC was elicited was independent of animal species, suggesting that the BIC is not a reflection of the processing of ITDs per se. Finally, we provide a model of the amplitude and latency of the BIC peak, which is based on excitatory–inhibitory synaptic interactions, without assuming any specific arrangement of delay lines. Our results show that the BIC is preserved across species ranging from mice to humans. We argue that this is the result of generic excitatory–inhibitory synaptic interactions at the level of the LSO, and thus best seen as reflecting the integration of binaural inputs as opposed to their spatial properties.SIGNIFICANCE STATEMENTNoninvasive electrophysiological measures of sensory system activity are critical for the objective clinical diagnosis of human sensory processing deficits. The binaural component of sound-evoked auditory brainstem responses is one such measure of binaural auditory coding fidelity in the early stages of the auditory system. Yet, the precise neurons that lead to this evoked potential are not fully understood. This paper provides a comparative study of this potential in different mammals and shows that it is preserved across species, from mice to men, despite large variations in morphology and neuroanatomy. Our results confirm its relevance to the assessment of binaural hearing integrity in humans and demonstrates how it can be used to bridge the gap between rodent models and humans.
Retrospective Cues Mitigate Information Loss in Human Cortex during Working Memory Storage
Authors: Ester Edward F. , Nouri Asal , Rodriguez Laura 
Published: August 2018

Working memory (WM) enables the flexible representation of information over short intervals. It is well established that WM performance can be enhanced by a retrospective cue presented during storage, yet the neural mechanisms responsible for this benefit are unclear. Here, we tested several explanations for retrospective cue benefits by quantifying changes in spatial WM representations reconstructed from alpha-band (8–12 Hz) EEG activity recorded from human participants (both sexes) before and after the presentation of a retrospective cue. This allowed us to track cue-related changes in WM representations with high temporal resolution (tens of milliseconds). Participants encoded the locations of two colored discs for subsequent report. During neutral trials, an uninformative cue instructed participants to remember the locations of both discs across a blank delay, and we observed a monotonic decrease in the fidelity of reconstructed spatial WM representations with time. During valid trials, a 100% reliable cue indicated that the color of the disc participants would be probed to report. Critically, valid cues were presented immediately after the termination of the encoding display [“valid early” (VE) trials] or midway through the delay period [“valid late” (VL) trials]. During VE trials, the gradual loss of location-specific information observed during neutral trials was eliminated, while during VL trials it was partially reversed. Our findings suggest that retrospective cues engage several different mechanisms that together serve to mitigate information loss during WM storage.SIGNIFICANCE STATEMENTWorking memory (WM) performance can be improved by a cue presented during storage. This effect, termed a retrospective cue benefit, has been used to explore the limitations of attentional prioritization in WM. However, the mechanisms responsible for retrospective cue benefits are unclear. Here we tested several explanations for retrospective cue benefits by examining how they influence WM representations reconstructed from human EEG activity. This approach allowed us to visualize, quantify, and track the effects of retrospective cues with high temporal resolution (on the order of tens of milliseconds). We show that under different circumstances retrospective cues can both eliminate and even partially reverse information loss during WM storage, suggesting that retrospective cue benefits have manifold origins.
Hypertonic Saline in Bronchiolitis and Type I Error: A Trial Sequential Analysis
Authors: Harrison Wade , Angoulvant Francois , House Samantha , Gajdos Vincent , Ralston Shawn L. 
Published: August 2018

BACKGROUND AND OBJECTIVES:
Meta-analyses of nebulized hypertonic saline (HS) for acute viral bronchiolitis have yielded disparate conclusions. Trial sequential analysis (TSA) is a novel method designed to account for potential sources of error in conventional meta-analysis. We sought to use TSA to determine if the existing literature base is sufficient to draw firm conclusions about the effectiveness of HS in bronchiolitis.

METHODS:
We used the cohort of studies identified in previously published conventional meta-analyses. Included studies were those in which authors compared treatment with HS versus normal saline (or supportive care) in children with bronchiolitis to reduce hospital length of stay (LOS) or hospitalizations. TSA results are used to provide a required information size and monitoring boundaries for statistical significance.

RESULTS:
For the LOS outcome, 17 studies including 1866 patients analyzed in which authors used conventional meta-analysis reveal a statistically significant benefit (mean difference = −0.41 days; 95% confidence interval = −0.07 to −0.75); however, TSA suggests that those conclusions are premature because of failure to reach the adequate information size of 2665 individuals. For the risk of hospitalization outcome, 8 studies including 1728 patients analyzed in which authors used conventional meta-analysis reveal a reduction in the relative risk of hospitalization (relative risk = 0.86; 95% confidence interval = 0.76 to 0.98); however, TSA suggests these conclusions are premature because of failure to reach the adequate information size of 4770. Both LOS and hospitalization results from conventional meta-analysis would be considered potentially false-positives by TSA.

CONCLUSIONS:
TSA reveals that concluding benefit from HS for children with bronchiolitis potentially represents type I error.
Monitoring Serum VEGF in Neoadjuvant Chemotherapy for Patients with Triple-Negative Breast Cancer: A New Strategy for Early Prediction of Treatment Response and Patient Survival
Authors: Wang Ruo-Xi , Chen Sheng , Huang Liang , Zhou Ying , Shao Zhi-Ming 
Published: August 2018

Abstract

Background
This study aimed to investigate the clinical utility of serum biomarker changes during neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC).

Methods
A total of 303 patients with TNBC were included in this study. Serum samples were taken at three time points during NAC: baseline, prior to the third cycle, and prior to surgery. Luminex multibiomarker panel for 29 serum biomarkers was used to detect their correlation with NAC response. The predictive and prognostic value of each selected biomarker was then studied.

Results
Vascular endothelial growth factor (VEGF) was the only biomarker that correlated with treatment response, with a decreasing trend in pCR patients relative to non-pCR patients (p &lt; .001). Univariable and multivariable analyses revealed that the relative change in VEGF prior to the third cycle of NAC had a remarkable predictive value for both pCR and pathological nonresponse with high sensitivity and specificity. VEGF was also independently correlated with disease-free survival.

Conclusion
Our findings indicate that monitoring serum VEGF could help identify patients with different responses at an early time point of NAC and at varying risk of disease relapse. Serum VEGF may also serve as an alternative to traditional response-evaluating methodologies in tailoring and modifying the NAC strategy for both operable and advanced TNBCs.
A Phase III Study to Compare the Efficacy and Safety of Paclitaxel Versus Irinotecan in Patients with Metastatic or Recurrent Gastric Cancer Who Failed in First-line Therapy (KCSG ST10-01)
Authors: Lee Keun-Wook , Maeng Chi Hoon , Kim Tae-You , Zang Dae Young , Kim Yeul Hong , Hwang In Gyu , Oh Sang Cheul , Chung Joo Seop , Song Hong Suk , Kim Jin Won , Jeong Su Jin , Cho Jae Yong 
Published: August 2018

Abstract

Lessons Learned
Irinotecan could not be proven noninferior to paclitaxel as a second-line treatment for patients with metastatic or recurrent gastric cancer. The failure to demonstrate noninferiority may have been a result of insufficient patient enrollment. Both agents were tolerable but showed different toxicity profiles.

Background
This phase III study compared the efficacy and safety of paclitaxel versus irinotecan in patients with metastatic or recurrent gastric cancer (MRGC) who had experienced disease progression following first-line chemotherapy.

Methods
Patients were randomized to receive either paclitaxel (70 mg/m2; days 1, 8, 15, every 4 weeks) or irinotecan (150 mg/m2 every other week). The primary endpoint was progression-free survival (PFS).

Results
This study was stopped early due to low accrual rate. A total of 112 patients were enrolled; 54 were allocated to paclitaxel and 58 to irinotecan. Median PFS for the paclitaxel and irinotecan groups was 3.5 and 2.1 months, respectively (hazard ratio [HR], 1.27; 95% confidence interval [CI], 0.86–1.88; p = .234). Noninferiority of irinotecan to paclitaxel was not proved because the upper boundary of the 95% CI (1.88) exceeded the predefined upper margin of noninferiority (1.32). Median overall survival (OS) was 8.6 months in the paclitaxel group and 7.0 months in the irinotecan group (HR, 1.39; 95% CI, 0.91–2.11; p = .126). Among toxicities greater than or equal to grade 3, neutropenia (11.5%) was the most common, followed by peripheral neuropathy (7.7%) in the paclitaxel group, and neutropenia (34.5%) followed by nausea, vomiting, and anemia (8.6%, respectively) in the irinotecan group.

Conclusion
Although paclitaxel showed numerically longer PFS and OS compared with irinotecan, this was statistically insignificant. Both irinotecan and paclitaxel are valid second-line treatment options in MRGC.
A Phase II Trial of Sorafenib and Dacarbazine for Leiomyosarcoma, Synovial Sarcoma, and Malignant Peripheral Nerve Sheath Tumors
Authors: D'Adamo David R. , Dickson Mark A. , Keohan Mary L. , Carvajal Richard D. , Hensley Martee L. , Hirst Catherine M. , Ezeoke Marietta O. , Ahn Linda , Qin Li-Xuan , Antonescu Cristina R. , Lefkowitz Robert A. , Maki Robert G. , Schwartz Gary K. , Tap William D. 
Published: August 2018

Abstract

Background
Sorafenib and dacarbazine have low single-agent response rates in metastatic sarcomas. As angiogenesis inhibitors can enhance the efficacy of chemotherapy, we investigated the combination of sorafenib and dacarbazine in select sarcoma subtypes.

Materials and Methods
Patients with leiomyosarcoma (LMS), synovial sarcoma (SS), or malignant peripheral nerve sheath tumors (MPNST) with up to two previous lines of therapy and adequate hepatic, renal, and marrow function received 3-week cycles of sorafenib at 400 mg oral twice daily and dacarbazine 1,000 mg/m2 intravenously (later reduced to 850 mg/m2). Patients were evaluated for response every 6 weeks. The primary objective was to determine the disease control rate (DCR) of sorafenib plus dacarbazine in the selected sarcoma subtypes.

Results
The study included 37 patients (19 female); median age was 55 years (range 26–87); and histologies included LMS (22), SS (11), and MPNST (4). The DCR was 46% (17/37). Median progression-free survival was 13.4 weeks. The RECIST response rate was 14% (5/37). The Choi response rate was 51% (19/37). Median overall survival was 13.2 months. Of the first 25 patients, 15 (60%) required dacarbazine dose reductions for hematologic toxicity, with one episode of grade 5 neutropenic fever. After reducing the starting dose of dacarbazine to 850 mg/m2, only 3 of the final 12 (25%) patients required dose reduction.

Conclusion
This phase II study met its primary endpoint with an 18-week DCR of 46%. The clinical activity of dacarbazine plus sorafenib in patients with these diagnoses is modest.
FDA Approval Summary: Midostaurin for the Treatment of Advanced Systemic Mastocytosis
Authors: Kasamon Yvette L. , Ko Chia-Wen , Subramaniam Sriram , Ma Lian , Yang Yuching , Nie Lei , Shord Stacy , Przepiorka Donna , Farrell Ann T. , McKee Amy E. , Pazdur Richard 
Published: August 2018

Abstract

In April 2017, the U.S. Food and Drug Administration granted regular approval to midostaurin for the treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL). Approval was based on results from CPKC412D2201, a single-arm trial of midostaurin (100 mg orally twice daily) in previously treated or untreated patients. For the patients with ASM and SM-AHN, efficacy was established on the basis of confirmed complete remission (CR) plus incomplete remission (ICR) by modified Valent criteria with six cycles of midostaurin. There were no CRs reported; ICR was achieved by 6 of 16 patients (38%; 95% confidence interval [CI]: 15%–65%) with ASM and by 9 of 57 patients (16%; 95% CI: 7%–28%) with SM-AHN. Within the follow-up period, the median duration of response was not reached for the patients with ASM (range, 12.1+ to 36.8+ months) or with SM-AHN (range, 6.6+ to 52.1+ months). For the patients with MCL, efficacy was established on the basis of confirmed CR using modified 2013 International Working Group-Myeloproliferative Neoplasms Research and Treatment-European Competence Network on Mastocytosis criteria. Of 21 patients with MCL, 1 (5%) achieved a CR. Of 142 patients with SM evaluated for safety, 56% had dose modifications for toxicity, and 21% discontinued treatment due to a toxicity. Over 50% reported nausea, vomiting, or diarrhea, and ≥30% reported edema, musculoskeletal pain, fatigue, abdominal pain, or upper respiratory tract infection. New or worsening grade ≥3 lymphopenia, anemia, thrombocytopenia, or neutropenia developed in ≥20%. Although midostaurin is an active drug for treatment of advanced SM, it is not clear that the optimal dose has been identified.

Implications for Practice
Midostaurin is the only U.S. Food and Drug Administration-approved therapy for patients with systemic mastocytosis with associated hematological neoplasm and mast cell leukemia and is the only therapy approved for patients with aggressive systemic mastocytosis regardless of KIT D816V mutation status. Based on response rate and duration, midostaurin has meaningful clinical activity in these rare, life-threatening diseases.
Experiencias significativas para la enseñabilidad de la oralidad dentro del proceso civil colombiano desde el aula de clase
Authors: Sánchez Novoa Pedro Alirio 
Published: August 2018

El presente artículo busca realizar un análisis sobre las herramientas pedagógicas y didácticas que sean las más adecuadas para la enseñanza de la Oralidad para afrontar el nuevo Proceso Civil Colombiano que se enmarca en la celebración de audiencias y en dejar a un lado el sistema procesal escritural para hace más expeditos y efectivos los procesos. Es importante que la Facultad de Derecho de la Universidad Libre Seccional Cúcuta, tome cartas en el asunto y prepare los microcurrículos en torno a un eje trasversal que propendan por la Oralidad en el proceso Civil.
ENRAIZAMENTO DE ESTACAS DE VARIEDADES DE FIGUEIRA COM O EMPREGO DE ÁCIDO INDOLBUTÍRICO
Authors: Ferraz Rafael Augusto , Leonel Sarita , Souza Jackson Mirellys Azevedo , Silva Marcelo de Souza , Gonçalves Bruno Henrique Leite 
Published: August 2018

O presente trabalho teve como objetivo avaliar o desempenho propagativo de estacas semilenhosas de variedades de figueira, com o uso de ácido indolbutírico. As variedades avaliadas foram Roxo de Valinhos, White Genova, PI – 189 e Troiano e a dosagem empregada do ácido indolbutírico foi 2000 mg L-1. O delineamento experimental utilizado foi o inteiramente ao acaso, em esquema fatorial 4 x 2 (variedades x com e sem aplicação do regulador vegetal), com cinco repetições e dez estacas por parcela experimental. Foram avaliadas a porcentagem de estacas vivas, de estacas enraizadas e de estacas brotadas, número de brotos, comprimento da maior raiz (cm), número de folhas, volume da raiz (cm3), peso seco da raiz (mg) e peso seco das folhas (mg). As estacas que não receberam a aplicação do regulador vegetal tiveram maior porcentagem de estacas vivas, enraizadas e brotadas, com exceção das variedades Roxo de Valinhos e Troiano, que não apresentaram diferença na aplicação. Mediante esses resultados, foi possível concluir que não é recomendado o uso do ácido indolbutírico para essas variedades, na época de coleta das estacas correspondente ao mês de agosto.PALAVRAS-CHAVE: Ficus carica L., propagação, regulador de crescimento FIG TREE VARIETIES CUTTINGS ROOTING USING INDOLEBUTYRIC ACID ABSTRACT: The present study aimed to evaluate the propagative performance of fig trees cuttings with application of indolebutyric acid (IBA). The evaluated varieties were “Roxo of Valinhos, White Genova, PI -189 and Troiano and the dosage of indolebutyric acid used was 2000 mg L-1. The experimental design used was entirely random, in factorial scheme 4 x 2 (varieties x with or without application of plant regulator), with five replications and ten cuttings per plot. It was evaluated the percentage of live cuttings, rooted cuttings and sprouted cuttings, number of shoots, length of the largest root (cm), number of leaves, root volume (cm3), root dry weight (mg) and leaves dry weight (mg). The cuttings that did not receive treatment with indolebutyric acid had higher percentage of live, rooted and sprouted cuttings, except for Roxo of Valinhos” and Troiano varieties, which showed no difference among treatments . Based on the results, it is possible to conclude that the use of indolebutyric acid for such varieties is not recommended in August, month of cuttings harvest in this study. KEYWORDS: Ficus carica L., propagation, growth regulator.
Um estudo na literatura da Shoah com Walter Benjamin e Gaston Bachelard
Authors: Senna Alecrides Jahne Raquel Castelo Branco de 
Published: August 2018

Em momentos históricos marcados pela violência infligida ao Outro, refletir sobre as marcas deixadas pelo sofrimento resultante de contextos sociais marcados pela violência, não é algo do qual a sociologia deve se eximir. Muito tem sido produzido sobre a Shoah (Catástrofe, em hebraico) e, igualmente, sobre a literatura resultante dos relatos escritos pelos sobreviventes. Esse estudo é uma tentativa de leitura desses relatos, dos campos de concentração nazistas, da segunda guerra mundial (1939-1945), e tem seu embasamento teórico em Walter Benjamin e Gaston Bachelard. Entendendo os relatos enquanto resgates de momentos históricos a partir da memória, faz-se uma discussão com os conceitos de Jeztzeit, Erfahrung e Erlebnis de Benjamin e, a concepção de instante de Gaston Bachelard. Na tentativa de colocar em constelação imagens do Lager, a leitura é feita numa perspectiva bachelardiana de repercussão e ressonância como instrumentos para uma atualização das imagens – que repercutem no pesquisador e produzem ressonâncias, que se associam às escolhas teóricas. Ao mesmo tempo em que incidem sobre uma preocupação específica, que foi o ponto de partida que é a substituição do nome pelo número no Lager, a leitura dos relatos fez luzir algumas questões que são discutidas ao longo do artigo.
Colorectal polyps and heterotrophic esophageal polyp of colon in a paediatric cohort in South India
Authors: R. Vishnu Abishek , Venkatakrishnan L. , S. Mukundan 
Published: August 2018

Background: Clinical profile of polyps in paediatric cases are less in South India. Juvenile Polyps were the most common polyps in paediatric cases described in literature, presenting as LGI bleed. The aim of the study is to describe the clinical profile of colorectal polyps in paediatric population in a single tertiary care centre in South India.Methods: Paediatric cases between 0 and 16 years of age who underwent colonoscopy in our department from January 2002 to July 2018 were included from database. These cases were retrospectively analysed for presence of polyps, clinical presentation, indication for colonoscopy, histopathology of the resected polyps and other demographic details. Incomplete procedures were excluded.Results: About 166 paediatric cases underwent colonoscopy in the study period. 21 cases (12.65%) had colorectal Polyps. 85.7% of the polyps were in recto sigmoid region. Most common histological type was Juvenile Polyp (51.6%). One infant had sessile polyp in descending colon which was reported as heterotrophic esophageal mucosa in histopathology. LGI bleed was the most common presentation in children with polyps (66.6%).Conclusions: The prevalence of polyps in our cohort was 12.65%. Solitary Juvenile Polyp was the most common polyp in children, with lower GI bleed as the most common presenting feature. Rare case of heterotrophic esophageal polyp was seen in descending colon.
Effect of intralesional platelet rich plasma in chronic localized vitiligo
Authors: Mahajan Rashmi , Ninama Kishan , Shah Hinal , Bilimoria Freny 
Published: August 2018

<p class="abstract"><strong>Background:</strong> Vitiligo is a disease caused by destruction of melanocytes in lesional skin. It occurs worldwide in occurance of 0.1 to 2.0 percent. It is a multifactorial polygenic disease with complex pathogenesis. Several treatments, old and new are advocated for such patients. The first line of treatment includes topical corticosteroids and calcineurin inhibitors, and phototherapy (NBUVB, PUVA). The second line of treatment includes systemic corticosteroids, topical calcipotriol 0.005%, lasers such as excimer laser (308 nm). The aim of the study was to evaluate the efficacy of platelet rich plasma in 40 cases of stable vitiligo with less than or equal to 1% body surface area involvement.</p><p class="abstract"><strong>Methods:</strong> 40 cases of stable vitiligo not responding to adequate topical therapy for more than 1 year were included in the study. They were subjected to intralesional injections of freshly prepared autologous platelet rich plasma (PRP) by double spin technique. Each patient was given injections every 2 weekly interwals for a total of 6 injections. Results were evaluated using the vitiligo area severity index (VASI) score.<strong></strong></p><p class="abstract"><strong>Results:</strong> Out of 40 patients15 Patients showed good response, 12 patients showed Average response and13 patients showed no response to treatment according to VASI score.</p><p class="abstract"><strong>Conclusions:</strong> PRP may be considered as an additional therapy in patients not responding adequately to traditional therapies. Our patients were not subjected to histopathology. It was also felt that patients might require more than 6 sittings for complete repigmentation.</p>