bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early onset of glutamatergic and GABAergic synaptic activity in the visual layers of the rodent superior colliculus
Authors: Jüttner René , Henneberger Christian , Grantyn Rosemarie , Rothe Thomas 
Published: July 2002

AbstractDuring postnatal development, the retinocollicular pathway undergoes activity‐dependent refinement, resulting in the precise retinotopic map seen in adults. Previous studies established that retinal efferents reach the mouse superior colliculus (SC) by embryonic day 16. Morphologically, synapses were found in the rat SC before birth. As part of an extended project aimed at understanding the development of synaptic transmission in the visual layers of the SC, we report here the presence of functionally active synapses immediately after birth. Circuit activity in mouse SC neurons was detected in horizontal slices of the visual layers using cell‐attached voltage clamp. The spontaneous discharge of action potentials was abolished by glutamatergic blockers and facilitated by bicuculline, showing that circuit activity is based on synaptic transmission and that the action of γ‐aminobutyric acid is inhibitory. Using whole‐cell voltage clamp, spontaneous glutamatergic postsynaptic currents as well as miniature GABAergic postsynaptic currents were recorded on postnatal day 1. Excitatory and inhibitory postsynaptic currents could also be evoked by electrical stimulation. Glutamatergic postsynaptic currents comprised both (S)‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid and N‐methyl‐d‐aspartate receptor‐mediated components. The early function of glutamatergic and GABAergic synaptic transmission in the visual layers of SC suggests that SC neurons are able to process information originating from retinal axons immediately after birth.
Comparing the onset of action of antidepressants: Comparison of different criteria applied to the same data set
Authors: Niklson IA , Reimitz P-E 
Published: July 2002

SummaryThe issue of early onset of action (EOA) of an antidepressant was addressed by several authors. Unfortunately so far there is neither consensus nor convention on the definitions of EOA, or on measures and methods of assessments. There are several quite different approaches to the statistical analysis of the data. Our objective was to compare the results concerning EOA obtained by different statistical techniques applied on a data set which was generated by several independent conclusive double-blind, placebo controlled randomised trials with two antidepressants. The following statistical techniques were used: 1) statistically significant difference for the first time; 2) statistically significant and clinically relevant difference for the first time; 3) pattern analysis; 4) classical survival analysis without ‘sustained response’; 5) survival analysis with sustained response. The advantages and drawbacks of different methods are discussed.
Microeconomic foundations of an optimal currency area
Authors: Swofford James L 
Published: July 2002

AbstractThe concept of an optimum currency area has previously been developed using macroeconomic policy results and factor mobility as the criteria for the optimum extent of a common currency area. In this paper, microeconomic foundations for an optimum currency area are set forth. These microeconomic foundations are requirements for a common currency area to exist. One can test for consistency with these microeconomic foundations. Procedures for such tests are discussed. Some preliminary results are presented from tests of whether or not the Euro Area economies constitute a common currency area. The test results tentatively suggest that the Euro Area countries may encounter problems in their attempt to establish a common currency.
Comparisons of sensors to predict spring wheat grain yield and protein content
Authors: Veverka Donald , Chatterjee Amitava , Carlson Melissa 
Published: February 2021

AbstractCanopy vegetation indices can predict the spatial variability in grain yield before harvest across large spatial scale. Spring wheat (Triticum aestivum L.) canopy reflectance data using a hand‐held active sensor (RapidScan CS‐45) and a small unmanned aerial vehicle (sUAV)‐based passive light optical sensor (Micasense RedEdge) were collected three times during flag leaf to heading stages (in the month of June and July) from 16 site‐years across the Red River Valley of Minnesota and North Dakota. Potential of vegetation indices (VIs), red normalized vegetation (RNDVI) and red edge normalized vegetation (RENDVI), were compared to predict grain yield and protein content. Linear regression between two sensors showed a significant (p < .05) relationship based on RNDVI (R2 = .69) and RENDVI (R2 = .55) values (n = 48). Only for the 2nd year, RENDVI from both sensors could predict the grain yield; but only the RENDVI from sUAV‐based passive sensor could predict the protein content at Haun stages between five and eight (R2 = .60, RMSE = 14.8, p = .02). Use of sUAV based passive sensor has potential to predict protein content but selecting optimal growth stage and validation of developed regression models in neighboring fields are critical for the accurate prediction.
Organic‐Inorganic Dual Catalytic System for the Regioselective Construction of Diverse Quinone Derivatives via Benzannulation
Authors: Akhtar Muhammad Saeed , Yang Won‐Guen , Kim Sung Hong , Lee Yong Rok 
Published: February 2021

AbstractEfficient and regioselective synthesis of highly functionalized naphthoquinone and anthraquinone derivatives was accomplished in good yields using an organic‐inorganic dual catalyst through [4+2] cycloaddition reaction between various 1,4‐benzenediols or 1,4‐naphthalenediols and α,β‐unsaturated aldehydes. These atom‐economic reactions rapidly provided useful cycloaddition adducts in a one‐pot reaction. The technique was successfully applied to synthesize tectoquinone, a natural compound found in red heartwood‐type Cryptomeria japonica, and 2‐(4‐methylpent‐3‐enyl)anthracene‐9,10‐dione, found in the roots of Sesamum indicum, and their analogs.
Palladium‐Catalyzed C—C Bond Activation/Suzuki Reaction of Methylenecyclobutanes
Authors: Chen Xiao‐Bing , Li Li , Yang Wan‐Chun , Song Kun‐Long , Wu Bin , Gan Wan‐Er , Cao Jian , Xu Li‐Wen 
Published: February 2021

Main observation and conclusionTransition‐metal catalyzed C—C bond activation is a formidable challenge owing to the high bond energy. We report here a novel palladium‐catalyzed C—C bond activation manner of methylenecyclobutanes followed by subsequent Suzuki cross‐coupling reaction affording multisubstituted indanes. The tandem reaction process involves intramolecular carbopalladation of double bond, β‐carbon elimination and intermolecular trapping of the transient σ‐alkylpalladium complex with boronic acids. A new TADDOL‐derived phosphoramidite ligand bearing fluorine and silicon‐based bulky groups is found to be efficient for C—C bond activation of methylenecyclobutanes.
The effect of physical activity interventions on cognition function in patients with diabetes: A systematic review and meta‐analysis
Authors: Wang Ruitong , Yan Wenxin , Du Min , Tao Liyuan , Liu Jue 
Published: February 2021

AbstractBackgroundIn recent years, studies have revealed that cognition may be impaired by glucose metabolism disorder. Meanwhile, physical activity has been demonstrated to maintain blood glucose. This meta‐analysis was conducted to assess the effect of physical activity on cognition in patients with diabetes and provide evidence for the treatment of cognition impairment among them.MethodsWe searched studies published in five databases from 1 January 1984 to 29 August 2020. A random‐effect or fixed‐effect meta‐analysis was used to estimate the pooled effect of physical activity on the change of cognition throughout intervention duration and post‐intervention cognition scores by standardized mean difference (SMD) and its 95% confidence interval (CI). We used funnel plots to evaluate the publication bias, I2 statistic to evaluate the heterogeneity and did subgroup analysis stratified by sample size and follow‐up time.ResultsFive eligible studies involving 2581 patients with diabetes were included. The pooled effect of physical activity on cognition improvement in patients with diabetes was significant (SMD = 0.98, 95% CI: 0.34–1.62), while the effect on post‐intervention cognition scores was not significant (SMD = 0.35, 95% CI: −0.04–0.73). In the subgroup analysis, the pooled effect was significantly higher in studies of follow‐up time less than 1 year (SMD = 2.14, 95% CI: 1.63–2.64), while observing no significant effect in studies of follow‐up time over 1 year (SMD = 0.10, 95% CI: −0.11–0.32).ConclusionsPhysical activity is beneficial to improving cognition in patients with diabetes. However, the long‐term effect needs to be explored in future studies.
GC‐MS metabolomics identifies novel biomarkers to distinguish tuberculosis pleural effusion from malignant pleural effusion
Authors: Liu Yongxia , Mei Bin , Chen Deying , Cai Long 
Published: February 2021

AbstractBackgroundTuberculous pleural effusions (TBPEs) and malignant pleural effusions (MPEs) are two of the most common and severe forms of exudative effusions. Clinical differentiation is challenging; however, metabolomics is a collection of powerful tools currently being used to screen for disease‐specific biomarkers.Methods17 TBPE and 17 MPE patients were enrolled according to the inclusion criteria. The normalization gas chromatography‐mass spectrometry (GC‐MS) data were imported into the SIMCA‐P + 14.1 software for multivariate analysis. The principal component analysis (PCA) and orthogonal partial least‐squares discriminant analysis (OPLS‐DA) were used to analyze the data, and the top 50 metabolites of variable importance projection (VIP) were obtained. Metabolites were qualitatively analyzed using the National Institute of Standards and Technology (NIST) databases. Pathway analysis was performed by MetaboAnalyst 4.0. The detection of biochemical indexes such as urea and free fatty acids in these pleural effusions was also verified, and significant differences were found between these two groups.Results1319 metabolites were screened by non‐targeted metabonomics of GC‐MS. 9 small molecules (urea, L‐5‐oxoproline, L‐valine, DL‐ornithine, glycine, L‐cystine, citric acid, stearic acid, and oleamide) were found to be significantly different (p < 0.05 for all). In OPLS‐DA, 9 variables were considered significant for biological interpretation (VIP≥1). However, after the ROC curve was performed, it was found that the metabolites with better diagnostic value were stearic acid, L‐cystine, citric acid, free fatty acid, and creatinine (AUC > 0.8), with good sensitivity and specificity.ConclusionStearic acid, L‐cystine, and citric acid may be potential biomarkers, which can be used to distinguish between the TBPE and the MPE.
Obesity and Critical Illness in COVID‐19: Respiratory Pathophysiology
Authors: Wolf Molly , Alladina Jehan , Navarrete-Welton Allison , Shoults Benjamin , Brait Kelsey , Ziehr David , Malhotra Atul , Hardin C. Corey , Hibbert Kathryn A. 
Published: February 2021

ObjectiveRecent cohort studies have identified obesity as a risk factor for poor outcomes in coronavirus disease 2019 (COVID‐19). To further explore the relationship between obesity and critical illness in COVID‐19, the association of BMI with baseline demographic and intensive care unit (ICU) parameters, laboratory values, and outcomes in a critically ill patient cohort was examined.MethodsIn this retrospective study, the first 277 consecutive patients admitted to Massachusetts General Hospital ICUs with laboratory‐confirmed COVID‐19 were examined. BMI class, initial ICU laboratory values, physiologic characteristics including gas exchange and ventilatory mechanics, and ICU interventions as clinically available were measured. Mortality, length of ICU admission, and duration of mechanical ventilation were also measured.ResultsThere was no difference found in respiratory system compliance or oxygenation between patients with and without obesity. Patients without obesity had higher initial ferritin and D‐dimer levels than patients with obesity. Standard acute respiratory distress syndrome management, including prone ventilation, was equally distributed between BMI groups. There was no difference found in outcomes between BMI groups, including 30‐ and 60‐day mortality and duration of mechanical ventilation.ConclusionsIn this cohort of critically ill patients with COVID‐19, obesity was not associated with meaningful differences in respiratory physiology, inflammatory profile, or clinical outcomes.
KRAS-Mutated, Estrogen Receptor-Positive Low-Grade Serous Ovarian Cancer: Unraveling an Exceptional Response Mystery
Authors: Kato Shumei , McFall Thomas , Takahashi Kenta , Bamel Kasey , Ikeda Sadakatsu , Eskander Ramez N. , Plaxe Steven , Parker Barbara , Stites Edward , Kurzrock Razelle 
Published: February 2021

Abstract

We report on a woman with aggressive estrogen receptor-positive, KRAS-mutated ovarian cancer who achieved a remarkable response to combination therapy with the MEK inhibitor (trametinib) and the aromatase inhibitor (letrozole), even though the disease had failed to respond to a combination of a PI3K inhibitor and different MEK inhibitor, as well as to trametinib and the estrogen modulator, tamoxifen, and to letrozole by itself. The mechanism of action for exceptional response was elucidated by in vitro experiments that demonstrated that the fact that tamoxifen can have an agonistic effect in addition to antagonist activity, whereas letrozole results only in estrogen depletion was crucial to the response achieved when letrozole was combined with an MEK inhibitor. Our current observations indicate that subtle variations in mechanisms of action of outwardly similar regimens may have a major impact on outcome and that such translational knowledge is critical for optimizing a precision medicine strategy.

Key Points
This report describes the remarkable response of a patient with KRAS-mutated, estrogen receptor-positive low-grade serous ovarian cancer treated with trametinib (MEK inhibitor) and letrozole (aromatase inhibitor), despite prior progression on similar agents including tamoxifen (estrogen modulator). In vitro investigation revealed that tamoxifen can have agonistic in addition to antagonistic effects, which could be the reason for the patient not responding to the combination of trametinib and tamoxifen. The current observations suggest that drugs with different mechanisms of action targeting the same receptor may have markedly different anticancer activity when used in combinations.
Preoperative Predictors of Futile Resection of Intraabdominal Extrahepatic Metastases from Hepatocellular Carcinoma
Authors: Le Linn Yun , Guo Yuxin , Koh Ye‐Xin , Chow Pierce K. H. , Chan Chung‐Yip , Chung Alexander Y. F. , Ooi London L. P. J. , Goh Brian K. P. 
Published: January 2021

AbstractBackgroundThe management of post‐liver resection recurrence is often the life‐limiting factor in HCC treatment. While much has been published on intrahepatic recurrence and lung metastasis, there is a relative lack of data on intraabdominal extrahepatic metastasis (EHM). We sought to evaluate the outcomes of patients post‐resection of intraabdominal EHM and assess preoperative factors predictive of early recurrence post‐metastasectomy.MethodsWe performed a retrospective review of 25 consecutive patients who underwent metastasectomy for intraabdominal EHM from 2003 to 2016 at our institution.ResultsOf the 25 cases of EHM, 16 were in the peritoneum, 3 in the adrenal glands, 3 in the large bowel, 1 in the spleen, 1 in the pancreas and 1 in the omentum. Median overall survival was 27 months (IQR 15–89 months). Twenty‐one patients (84%) developed recurrence post‐metastasectomy of EHM of which 12 patients experienced early recurrence within 12 months. The median time to recurrence post‐metastasectomy was 11(IQR 15.5) months. Multivariate analysis demonstrated both hepatitis B (11 (91.6%) versus 4 (44.4%), p = 0.00) status and high tumour grade (8 (66.6%) versus 3 (25%), p = 0.004) to be significant independent predictors of early recurrence. Patients who experienced early recurrence had a significantly shorter median overall survival (18 months (95% CI 12.9–23.0)) compared to those who did not (89 months (95% CI 24.8–153.1), p = 0.004).ConclusionPatients with EHM who underwent metastasectomy had a median overall survival of 27 months. Hepatitis B positivity and high primary tumour grade were preoperative predictors of futile surgery. All 7 patients who had both hepatitis B and high tumour grade experienced early recurrence post‐metastasectomy.
Expert Consensus of Data Elements for Collection for Enhanced Recovery After Cardiac Surgery
Authors: Hirji Sameer A. , Salenger Rawn , Boyle Edward M. , Williams Judson , Reddy V. Seenu , Grant Michael C. , Chatterjee Subhasis , Gregory Alexander J. , Arora Rakesh , Engelman Daniel T. 
Published: January 2021

AbstractBackgroundDespite the emergence of Enhanced Recovery Protocols (ERPs) in cardiac surgery, there is no consensus on the essential elements for data reporting for quality improvement efforts, as well as accountability and standardization of outcome reporting across institutions. The aim of this study was to establish a consensus on essential data elements for cardiac ERAS®.MethodsA 2‐round modified Delphi technique was utilized based on existing recommendations from the recently published ERAS® cardiac surgery consensus guidelines. Round 1 included a steering committee of 10 experts who oversaw formulation of a focused list of data elements into 3 main areas: Preoperative, intraoperative and postoperative. Round 2 consisted of a multidisciplinary, multinational, heterogenous group of 50 voting experts from across the United States and Europe. All participants evaluated their level of agreement with each data element using a 5‐point Likert scale with consensus threshold of 70%.ResultsIn round 1, 17 data elements were considered essential (consensus >  = 70%, either positive or negative) and 6 were considered marginal (consensus <  = 70%, either positive or negative). In round 2, positive consensus was achieved for 15/17 (88.2%) data elements in the essential category, and all six data elements (100%) in the marginal category, indicating a high level of overall agreement.ConclusionThis initial study, which identified 21 key data elements for collection in an ERAS® cardiac program, will aid clinicians in establishing a framework for evaluating the quality of their contemporary ERP processes and will allow acquisition of data to help benchmark performance metrics between hospitals.
Improving long-term health outcomes of preterm infants: how to implement the findings of nutritional intervention studies into daily clinical practice
Authors: Ruys Charlotte A. , van de Lagemaat Monique , Rotteveel Joost , Finken Martijn J. J. , Lafeber Harrie N. 
Published: January 2021

AbstractPreterm-born children are at risk for later neurodevelopmental problems and cardiometabolic diseases; early-life growth restriction and suboptimal neonatal nutrition have been recognized as risk factors. Prevention of these long-term sequelae has been the focus of intervention studies. High supplies of protein and energy during the first weeks of life (i.e., energy > 100 kcal kg−1 day−1 and a protein-to-energy ratio > 3 g/100 kcal) were found to improve both early growth and later neurodevelopmental outcome. Discontinuation of this high-energy diet is advised beyond 32–34 weeks postconceptional age to prevent excess fat mass and possible later cardiometabolic diseases. After discharge, nutrition with a higher protein-to-energy ratio (i.e., > 2.5–3.0 g/100 kcal) may improve growth and body composition in the short term.Conclusion: Preterm infants in their first weeks of life require a high-protein high-energy diet, starting shortly after birth. Subsequent adjustments in nutritional composition, aimed at achieving optimal body composition and minimizing the long-term cardiometabolic risks without jeopardizing the developing brain, should be guided by the growth pattern. The long-term impact of this strategy needs to be studied.

What is Known:• Preterm infants are at risk for nutritional deficiencies and extrauterine growth restriction.• Extrauterine growth restriction and suboptimal nutrition are risk factors for neurodevelopmental problems and cardiometabolic disease in later life.

What is New:• Postnatally, a shorter duration of high-energy nutrition may prevent excess fat mass accretion and its associated cardiometabolic risks and an early switch to a protein-enriched diet should be considered from 32-34 weeks postconceptional age.• In case of formula feeding, re-evaluate the need for the continuation of a protein-enriched diet, based on the infant’s growth pattern.
Systemic therapy for recurrent and/or metastatic head and neck cancer: a population-based healthcare research study in Thuringia, Germany
Authors: Morkramer Lisa , Geitner Maren , Boeger Daniel , Buentzel Jens , Kaftan Holger , Mueller Andreas H. , Ernst Thomas , Guntinas-Lichius Orlando 
Published: January 2021

Abstract
Purpose
Systemic therapy choice for patients with recurrent and/or metastatic head and neck cancer (R/M HNC) is a challenge. Not much is known about systemic therapies used in daily clinical routine and their outcome.

Methods
Data of all 283 patients with R/M HNC (89.4% male, median age: 60 years) registered for first-line systemic therapy between 2015 and 2018 in the cancer registries of Thuringia, a federal state in Germany, were included. Patient characteristics and treatment patterns were summarized. Exploratory univariate and multivariate analyses were conducted on select of systemic therapy and prognostic factors for overall survival.

Results
The most frequent first-line regimens were platinum-based combinations (71.4%), mainly cetuximab + platinum + 5-fluorouracil (32.5%). 32.5, 13.1, 4.9, and 1.1%, respectively, received, a second, third, fourth, and fifth line of systemic therapy. Median follow-up was 5.5 months. Median real-world overall survival was 16.8 months [95% confidence interval (CI) 11.1–22.6]. Alcohol drinking [hazard ratio (HR) 2.375, CI 1.471–3.831; p < 0.001], no second-line therapy (HR 3.425, CI 2.082–5.635, p < 0.001), and application of three agents compared to one agent in first-line therapy (HR 2.798, CI 1.374–5.697; p = 0.005) were associated to decreased overall survival after start of first-line systemic therapy. Termination of second-line treatment because of deterioration of the general condition was the only independent negative prognostic factor (HR 4.202, CI 1.091–16.129; p = 0.037) after start of second-line systemic therapy.

Conclusions
This study offers useful information, mainly prior to the availability of immunotherapy, on patient characteristics, treatment patterns, and survival in a German real-world population.