bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective Transformations of a Diprotected 2‐Oxobutanedial
Authors: Leiren Marit K. , Valdersnes Stig , Sydnes Leiv K. 
Published: October 2013

AbstractThe reactivity of 1,1‐diethoxy‐3‐(1,3‐dithian‐2‐yl)propan‐2‐one, a diacetal of oxobutanedial, and some of its derivatives toward selected reagents has been studied. As expected, hydride and Grignard‐type additions take place at the oxo moiety only and give the corresponding alcohols in good‐to‐excellent yields. Standard reductive amination occurs at the oxo moiety as well, but the reaction was in most cases not selective and furnished the expected amine mixed with 3‐(1,3‐dithian‐2‐yl)‐1,1‐diethoxypropan‐2‐ol. The conversion of the diethyl acetal moiety to an aldehyde group is generally an efficient transformation, but some aldehydes are unstable, making the deprotection useless. If the acetal contains a tertiary alcohol or a benzyloxy moiety, however, stable products are formed in good yields. Attempts to convert the 1,3‐dithiane substituent into an aldehyde group without concomitant decomposition of the product were totally unsuccessful. The chemical potential of this moiety, therefore, has to be utilized at an earlier stage and under different conditions.
Synthesis of 2‐Aryl‐5‐oxo‐4‐[2‐(phenylmethylidene)hydrazino]‐2,5‐dihydro‐1H‐pyrrole‐3‐carboxylates by the Reaction between Hydrazones, Acetylenedicarboxylates, and 1‐Aryl‐N,N′‐bis(arylmethylidene)methanediamines
Authors: Alizadeh Abdolali , Saberi Vahid , Mokhtari Javad 
Published: October 2013

AbstractAn efficient approach for the preparation of functionalized 2‐aryl‐2,5‐dihydro‐5‐oxo‐4‐[2‐(phenylmethylidene)hydrazino]‐1H‐pyrroles is described. The four‐component reaction between aldehydes, NH2NH2⋅H2O, dialkyl acetylenedicarboxylates, and 1‐aryl‐N,N′‐bis(arylmethylidene)methanediamines proceeds in EtOH under reflux in good‐to‐excellent yields (Scheme 1). The structures of 4 were corroborated spectroscopically (IR, 1H‐ and 13C‐NMR, and EI‐MS, and, in the case of 4f, by X‐ray crystallography). A plausible mechanism for this type of reaction is proposed (Scheme 2).
Cytokine and chemokine responses in the blood and cerebrospinal fluid of patients with human herpesvirus 6B‐associated acute encephalopathy with biphasic seizures and late reduced diffusion
Authors: Kawamura Yoshiki , Yamazaki Yumie , Ohashi Masahiro , Ihira Masaru , Yoshikawa Tetsushi 
Published: October 2013

AbstractAcute encephalopathy with biphasic seizures and late reduced diffusion has become increasingly common among various types of human herpesvirus 6B (HHV‐6B) encephalitis at the time of primary viral infection. The aim of the present study is to explore the pathophysiology of HHV‐6B‐associated acute encephalopathy with biphasic seizures and late reduced diffusion. Five cytokines and five chemokines were measured in serum and cerebrospinal fluid (CSF) obtained from 12 HHV‐6B‐associated acute encephalopathy with biphasic seizures and late reduced diffusion patients and 19 control exanthem subitum (without complications) patients. Serum interleukin (IL)‐10 (P = 0.007) and IL‐8 (P = 0.025) were significantly higher in the patients with the disease than controls. Serum IL‐1β (P = 0.034) and monocyte chemoattractant protein (MCP)‐1 (P = 0.002) were significantly higher in the controls than patients with the disease. In patients with the disease, IL‐10 (P = 0.012), regulated on activation normal T cell expressed and secreted (RANTES; P = 0.001), and monokine induced by interferon γ (MIG; P = 0.001) were significantly higher in serum than CSF, meanwhile IL‐6 (P = 0.034), IL‐8 (P = 0.034), and MCP‐1 (P = 0.001) were significantly higher in CSF than serum. Additionally, serum IL‐10 was significantly higher in the disease patients with sequelae than those without sequelae (P = 0.016). Several cytokines and chemokines may be associated with the pathogenesis of acute encephalopathy with biphasic seizures and late reduced diffusion. Moreover, the regulation of cytokine networks appears to be different between peripheral blood (systemic) and central nervous system. J. Med. Virol. 86:512–518, 2014. © 2013 Wiley Periodicals, Inc.
Late Neanderthal occupation in North‐West Europe: rediscovery, investigation and dating of a last glacial sediment sequence at the site of La Cotte de Saint Brelade, Jersey
Authors: BATES MARTIN , POPE MATTHEW , SHAW ANDREW , SCOTT BECCY , SCHWENNINGER JEAN‐LUC 
Published: October 2013

ABSTRACTIn 2011, a programme of field research was undertaken to effect the stabilization of an unstable section in the West Ravine at the key Neanderthal occupation site of La Cotte de St Brelade on the Channel Island of Jersey. As part of this essential remedial work the threatened section was analysed to characterize its archaeological and palaeoenvironmental potential as well provide optically stimulated luminescence (OSL) dates. The work determined, through two concordant OSL dating programmes, that the section formed part of an extensive sequence of sedimentation spanning >105 to <48 ka. Furthermore, reanalysis of the archive determined that the sediment sequence examined contained the stratigraphic equivalent of deposits lying below those that have previously produced Neanderthal fossils. Through our work, we can now constrain these younger sediments to being younger than 48 ka. The combined results suggest that this sequence now represents the recovery of an extensive dataset, thought lost to science through complete excavation, which holds the potential to throw light on the disappearance of Neanderthal populations from the Atlantic‐edge outpost on the north‐west frontier of their world.
Outcomes in patients with mucosal melanomas
Authors: Keller Deborah S. , Thomay Alan A. , Gaughan John , Olszanski Anthony , Wu Hong , Berger Adam C. , Farma Jeffrey M. 
Published: October 2013

AbstractBackground and ObjectiveOur goal was to evaluate the different subtypes of mucosal melanoma and describe specific variables that predict outcomes.MethodsProspective review of two tertiary care center databases identified 76 mucosal melanoma patients; 73 with complete records were included. Demographic and clinical data were analyzed. Cox regression determined variables impacting recurrence and survival.ResultsIn the 73 patients, the mean age was 64 years, and 74% were female. Sixty‐seven percent presented with lymph node involvement, and 73% had ulcerated tumors. Major sites affected were nasal/palate/oral (36%), vulvar/vaginal/cervical (48%), and anorectal (15%). Mean overall and disease‐free survival were 56.9 and 27.2 months. Variables associated with decreased survival included: lymphovascular invasion (HR17.70, P = 0.0093), Caucasian race (HR3.02, P = 0.0362), nasal/palate/oral sub‐group (HR1.85, P = 0.026), Breslow thickness (HR1.23, P = 0.00004), T stage (HR1.34, P = 0.0075), M stage (HR3.03, P = 0.0039), and chemotherapy (HR3.13, P = 0.0002). The worst prognosis was seen in the nasal/palate/oral sub‐group, with a median overall survival of 9.7 months and recurrence‐free time of 4.5 months. This subtype also demonstrated high lymph node positivity, ulceration, and larger tumor size.ConclusionThe nasal, palate, oral subtype has the worst prognosis compared to other mucosal melanoma locations. Studies are ongoing to evaluate pathologic and genomic variables that may predict outcomes. J. Surg. Oncol. 2013; 108:516–520. © 2013 Wiley Periodicals, Inc.
A matched case‐control study of IBD‐associated colorectal cancer: IBD portends worse outcome
Authors: Hrabe Jennifer E. , Byrn John C. , Button Anna M. , Zamba Gideon K. , Kapadia Muneera R. , Mezhir James J. 
Published: October 2013

AbstractBackground and ObjectivesThe effect of inflammatory bowel disease (IBD) on outcome in patients with colorectal cancer (CRC) remains unclear. Our objective is to evaluate oncologic outcomes of patients with IBD‐associated CRC.MethodsWe retrospectively reviewed a prospectively maintained database to identify patients with IBD‐associated CRC. Clinicopathologic variables and overall survival were compared to patients with sporadic CRC using a 2:1 matched‐controlled analysis.ResultsFifty‐five patients with IBD and CRC were identified. On univariate analysis, CRC patients with IBD had a significantly shorter median overall survival (68.2 months vs. 204.3 months, P = 0.01) compared to patients with sporadic CRC. On multivariate analysis, after adjusting for N and M stage, IBD was associated with an increased risk of death compared to sporadic CRC (HR = 2.011, 95% CI 1.24–3.23, P = 0.004). Stage 3 CRC patients with IBD in particular showed significantly decreased survival (23.0 vs. 133.9 months, P = 0.008).ConclusionsIn this study, patients with node‐positive IBD‐associated CRC had a significant increased risk of death and a shorter overall survival than those with sporadic disease and may require tailored adjuvant therapy and surveillance protocols. Continued investigation to elucidate the mechanisms that contribute to these observations is justified. J. Surg. Oncol. 2014 109:117–121. © 2013 Wiley Periodicals, Inc.
Can patient reported outcomes help identify the optimal outcome in palliative surgery?
Authors: Badgwell Brian , Bruera Eduardo , Klimberg Suzanne V. 
Published: October 2013

AbstractBackgroundThe purpose of this pilot study was to determine whether an open‐ended questionnaire captures severe symptoms in cancer patients undergoing palliative surgical consultation that a structured, validated quality‐of‐life assessment does not capture.MethodsWe prospectively used the Functional Assessment of Cancer Therapy–General (FACT‐G) and an open‐ended questionnaire to assess the symptoms of patients with incurable malignancies who underwent palliative surgical consultation at our institution between January 2011 and September 2012.ResultsOf the 69 patients enrolled, the most common indications for consultation were bowel obstruction (54%), jaundice (13%), wound problems (10%), and gastrointestinal bleeding (7%). Of the severe symptoms patients reported, 76% were identified with the FACT‐G alone, 22% were identified with the open‐ended questionnaire alone, and 2% were duplicate responses captured with both the FACT‐G and open‐ended questionnaire. The open‐ended questionnaire captured 68 instances of severe symptoms in 47 patients that the FACT‐G did not capture; of these symptoms, 52 were considered to be highly relevant to surgery and potential outcome measures.ConclusionsAn open‐ended questionnaire can identify severe symptoms that a global quality of life survey cannot capture and could be used in conjunction with a global survey to reassess symptoms after palliative surgical consultation. J. Surg. Oncol. 2014 109:145–150. © 2013 Wiley Periodicals, Inc.
Neurophysiology of gait: From the spinal cord to the frontal lobe
Authors: Takakusaki Kaoru 
Published: October 2013

ABSTRACTLocomotion is a purposeful, goal‐directed behavior initiated by signals arising from either volitional processing in the cerebral cortex or emotional processing in the limbic system. Regardless of whether the locomotion initiation is volitional or emotional, locomotion is accompanied by automatic controlled movement processes, such as the adjustment of postural muscle tone and rhythmic limb movements. Sensori‐motor integration in the brainstem and the spinal cord plays crucial roles in this process. The basic locomotor motor pattern is generated by spinal interneuronal networks, termed central pattern generators (CPGs). Responding to signals in proprioceptive and skin afferents, the spinal interneuronal networks modify the locomotor pattern in cooperation with descending signals from the brainstem structures and the cerebral cortex. Information processing between the basal ganglia, the cerebellum, and the brainstem may enable automatic regulation of muscle tone and rhythmic limb movements in the absence of conscious awareness. However, when a locomoting subject encounters obstacles, the subject has to intentionally adjust bodily alignment to guide limb movements. Such an intentional gait modification requires motor programming in the premotor cortices. The motor programs utilize one's bodily information, such as the body schema, which is preserved and updated in the temporoparietal cortex. The motor programs are transmitted to the brainstem by the corticoreticulospinal system, so that one's posture is anticipatorily controlled. These processes enable the corticospinal system to generate limb trajectory and achieve accurate foot placement. Loops from the motor cortical areas to the basal ganglia and the cerebellum can serve this purpose. © 2013 International Parkinson and Movement Disorder Society
Cognitive contributions to gait and falls: Evidence and implications
Authors: Amboni Marianna , Barone Paolo , Hausdorff Jeffrey M. 
Published: October 2013

ABSTRACTDementia and gait impairments often coexist in older adults and patients with neurodegenerative disease. Both conditions represent independent risk factors for falls. The relationship between cognitive function and gait has recently received increasing attention. Gait is no longer considered merely automated motor activity but rather an activity that requires executive function and attention as well as judgment of external and internal cues. In this review, we intend to: (1) summarize and synthesize the experimental, neuropsychological, and neuroimaging evidence that supports the role played by cognition in the control of gait; and (2) briefly discuss the implications deriving from the interplay between cognition and gait.In recent years, the dual task paradigm has been widely used as an experimental method to explore the interplay between gait and cognition. Several neuropsychological investigations have also demonstrated that walking relies on the use of several cognitive domains, including executive‐attentional function, visuospatial abilities, and even memory resources. A number of morphological and functional neuroimaging studies have offered additional evidence supporting the relationship between gait and cognitive resources. Based on the findings from 3 lines of studies, it appears that a growing body of evidence indicates a pivotal role of cognition in gait control and fall prevention. The interplay between higher‐order neural function and gait has a number of clinical implications, ranging from integrated assessment tools to possible innovative lines of interventions, including cognitive therapy for falls prevention on one hand and walking program for reducing dementia risk on the other. © 2013 International Parkinson and Movement Disorder Society
Objective biomarkers of balance and gait for Parkinson's disease using body‐worn sensors
Authors: Horak Fay B. , Mancini Martina 
Published: October 2013

ABSTRACTBalance and gait impairments characterize the progression of Parkinson's disease (PD), predict the risk of falling, and are important contributors to reduced quality of life. Advances in technology of small, body‐worn, inertial sensors have made it possible to develop quick, objective measures of balance and gait impairments in the clinic for research trials and clinical practice. Objective balance and gait metrics may eventually provide useful biomarkers for PD. In fact, objective balance and gait measures are already being used as surrogate endpoints for demonstrating clinical efficacy of new treatments, in place of counting falls from diaries, using stop‐watch measures of gait speed, or clinical balance rating scales. This review summarizes the types of objective measures available from body‐worn sensors. The metrics are organized based on the neural control system for mobility affected by PD: postural stability in stance, postural responses, gait initiation, gait (temporal‐spatial lower and upper body coordination and dynamic equilibrium), postural transitions, and freezing of gait. However, the explosion of metrics derived by wearable sensors during prescribed balance and gait tasks, which are abnormal in individuals with PD, do not yet qualify as behavioral biomarkers, because many balance and gait impairments observed in PD are not specific to the disease, nor have they been related to specific pathophysiologic biomarkers. In the future, the most useful balance and gait biomarkers for PD will be those that are sensitive and specific for early PD and are related to the underlying disease process. © 2013 International Parkinson and Movement Disorder Society
LIDAR‐based F‐factor for wind shear alerting: different smoothing algorithms and application to departing flights
Authors: Lee Y. F. , Chan P. W. 
Published: October 2013

ABSTRACTRapid fluctuations of wind shear hazard factor (or F‐factor) calculated from the headwind profile measured by Doppler Light Detection and Ranging (LIDAR) may make it difficult for use in wind shear alerting at an airport such as Hong Kong International Airport (HKIA). Preprocessing by flight simulator or post‐processing by averaging over a certain length are attempted in this study to smooth the F‐factor and enhance its skills on wind shear alerting. The F‐factor so obtained is used for alerting of wind shear (headwind change exceeding 15 knots) for departing flights. Through case studies and statistical studies, the LIDAR‐based F‐factors are found to have good correlation with the F‐factor determined from flight data (the Quick Access Recorder, or QAR, data from the commercial jets). Using the relative operating characteristics (ROC) curves, the LIDAR‐based F‐factor obtained by smoothing over a window size of 300–500 m is found to have good skills in wind shear alerting, and the performance is comparable with, or even better than, the LIDAR‐based F‐factor using the flight simulator approach. By choosing an optimal alerting threshold specific for each runway corridor, the F‐factor successfully alerts 86% of pilot wind shear reports with the percentage of time on alert of 12%, which is found to be satisfactory for real‐time use. The performance of the F‐factor on stronger wind shear (headwind change of 25 knots or more) is also studied.
Interactive Learning Online at Public Universities: Evidence from a Six‐Campus Randomized Trial
Authors: Bowen William G. , Chingos Matthew M. , Lack Kelly A. , Nygren Thomas I. 
Published: October 2013

AbstractOnline instruction is quickly gaining in importance in U.S. higher education, but little rigorous evidence exists as to its effect on student learning. We measure the effect on learning outcomes of a prototypical interactive learning online statistics course by randomly assigning students on six public university campuses to take the course in a hybrid format (with machine‐guided instruction accompanied by one hour of face‐to‐face instruction each week) or a traditional format (as it is usually offered by their campus, typically with about three hours of face‐to‐face instruction each week). We find that learning outcomes are essentially the same—that students in the hybrid format are not harmed by this mode of instruction in terms of pass rates, final exam scores, and performance on a standardized assessment of statistical literacy. We also conduct speculative cost simulations and find that adopting hybrid models of instruction in large introductory courses has the potential to significantly reduce instructor compensation costs in the long run.
Inhibition of constitutively active Stat3 reverses enzalutamide resistance in LNCaP derivative prostate cancer cells
Authors: Liu Chengfei , Zhu Yezi , Lou Wei , Cui Yuanyuan , Evans Christopher P. , Gao Allen C. 
Published: October 2013

AbstractPURPOSEUse of enzalutamide has improved the treatment of advanced prostate cancer. However, resistance to enzalutamide can develop frequently in initial responders. This study aimed to test whether overexpression of IL‐6 and constitutive activation of Stat3 in prostate cancer cells increase resistance to enzalutamide.EXPERIMENTAL DESIGNSensitivity of prostate cancer cells to enzalutamide was tested using cell growth assays and clonogenic assays. Quantitative reverse transcription‐PCR, ELISA, and Western blotting were performed to detect expression levels of IL‐6, c‐Myc, survivin, and AR. Expression of Stat3 was downregulated using siRNA specific to Stat3. ChIP assay was performed to examine recruitment of AR to the PSA promoter.RESULTSProstate cancer cells expressing autocrine IL‐6 are resistant to enzalutamide and autocrine IL‐6 leads to constitutive activation of Stat3 and its target genes. Down regulation of Stat3 led to an increase in sensitivity of prostate cancer cells to enzalutamide. Overexpression of constitutively active Stat3 in prostate cancer cells induced resistance to enzalutamide treatment. Constitutively active Stat3 also enhanced the recruitment of AR to PSA promoter which could not be disrupted by enzalutamide. The Stat3 inhibitor AG490 reversed enzalutamide resistance in prostate cancer cells, while combination treatment with enzalutamide and AG490 significantly inhibited cell growth and induced cell apoptosis.CONCLUSIONSThis study demonstrates that the autocrine IL‐6 pathway induces enzalutamide resistance in prostate cancer cells via the constitutive activation of Stat3. Co‐targeting IL6‐Stat3 pathway with enzalutamide may be utilized for treatment of advanced prostate cancer. Prostate 74:201–209, 2014. © 2013 Wiley Periodicals, Inc.
Elevated insulin‐like growth factor binding protein‐1 (IGFBP‐1) in men with metastatic prostate cancer starting androgen deprivation therapy (ADT) is associated with shorter time to castration resistance and overall survival
Authors: Sharma Jaya , Gray Kathryn P. , Evan Carolyn , Nakabayashi Mari , Fichorova Raina , Rider Jennifer , Mucci Lorelei , Kantoff Philip W. , Sweeney Christopher J. 
Published: October 2013

AbstractBACKGROUNDInsulin‐like growth factor (IGF) and adipokines have been implicated in prostate cancer carcinogenesis.METHODData from 122 men with serum samples drawn within 3 months of starting ADT for metastatic prostate cancer was accessed retrospectively. IGF‐1, IGF binding protein (BP)‐1, leptin, and adiponectin levels were measured by multiplex electrochemiluminescence assays. A multivariable Cox model assessed the association of time to castration resistant prostate cancer (CRPC) and overall survival by the protein levels, adjusted for clinical variables, age and prostate specific antigen (PSA) levels at start of ADT, race, ECOG status, extent of metastases and were reported as hazard ratio (HR) with 95% confidence interval (CI).RESULTSMedian follow‐up and overall survival were 44 and 42.2 months, respectively. ECOG performance status (≥1 vs. 0) was negatively associated with overall survival [HR = 2.8 (1.1–7.0),P = 0.03], and PSA nadir <0.2 was predictive of longer time to CRPC [HR = 0.3 (0.2–0.5),P < 0.0001]. The median time to CRPC by low, middle, and top IGFBP‐1 tertile distribution was 20.7, 18.1, and 12.4 months, respectively, with HR for middle versus low tertile levels 3.1 (1.7–5),P = 0.0003, and for top versus low tertile levels was 2.4 (1.3–4.2),P = 0.003. The median overall survival by low, middle and top tertile IGFBP‐1 level was 48.5, 46.4, and 32.8 months, respectively, with HR for top versus low tertile 2.5 (1.2–5.1),P = 0.01. There was no association with IGF‐1, adiponectin and leptin.CONCLUSIONElevated IGFBP‐1 appears to be associated with shorter time to CRPC and lower overall survival in men with metastatic prostate cancer.Prostate 74:225–234, 2014. © 2013 Wiley Periodicals, Inc.