bluuebunny/crossref_metadata_2025_split huggingface dataset:
The diagnosis of intramural esophageal squamous cell carcinoma without mucosal invasion using endoscopic ultrasound-guided fine needle aspiration biopsy
Authors: Pan Hanghai , Zhou XinXin , Zhao Fei , Lou Guochun 
Published: June 2020

Abstract

Rationale:
Intramural esophageal squamous cell carcinoma (ESCC) without mucosal invasion is extremely rare. Endoscopic mucosal biopsy results are often negative, making diagnosis difficult. In these cases, endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) biopsy is a useful diagnostic method.

Patient concerns:
A 78-year-old female was admitted to hospital due to dysphagia, and gastroscopy showed a concentric narrowing of the esophageal lumen with a smooth and undamaged esophageal mucosa.

Diagnoses:
Endoscopic ultrasound (EUS) revealed that the esophageal mucosa was thickened with a low echo, and the layers of the esophageal wall could not be clearly distinguished. Cytologic and pathologic diagnoses were obtained through EUS-FNA, which suggested ESCC.

Interventions:
According to the pathologic diagnosis obtained by EUS-FNA, surgery or radiotherapy were recommended for this patient. Eventually, this patient elected to seek treatment at another medical institution.

Outcomes:
This type of disease cannot be diagnosed according to gastroscopic biopsy alone, and the diagnosis was eventually confirmed through EUS-FNA.

Lessons:
When an imaging examination suggests a possible malignant lesion of the oesophagus, EUS-FNA may be considered if the surface mucosa contains no endoscopic damage. EUS-FNA has high diagnostic value with high sensitivity, minimal invasiveness, and high safety.
BRAIN MR SPECTROSCOPIC FINDINGS IN THREE CONSECUTIVE COVID-19 PATIENTS: PRELIMINARY OBSERVATIONS
Authors: Rapalino Otto , Weerasekera Akila , Moum Sarah J. , Eikermann-Haerter Katharina , Edlow Brian L. , Fischer David , Mukerji Shibani , Schaefer Pamela W. , Gonzalez R. Gilberto , Lev Michael , Ratai Eva-Maria 
Published: June 2020

ABSTRACTBrain magnetic resonance spectroscopic imaging (MRSI) was performed in three consecutive COVID-19 patients, as part of a pilot investigation of the pathophysiological processes underlying the brain involvement by the SARS-CoV-2 infection. These included one with necrotizing leukoencephalopathy, one after recent PEA cardiac arrest without leukoencephalopathy, and one without frank encephalopathy or recent severe hypoxic episode. The MRSI findings were compared to those of two patients with white matter pathology not SARS-CoV2 infection related, and a control patient without clinical encephalopathy. The N-acetylaspartate reduction, choline elevation, and glutamate/glutamine elevation found in the COVID necrotizing leukoencephalopathy patient and, to a lesser degree, the COVID post-cardiac arrest patient, follow a similar pattern as seen with the delayed post-hypoxic leukoencephalopathy patient. Lactate elevation was most pronounced in the patient with COVID necrotizing leukoencephalopathy.
Amplitude modulations of sensory responses, and deviations from Weber’s Law in pulsatile evidence accumulation
Authors: Koay Sue Ann , Thiberge Stephan Y. , Brody Carlos D. , Tank David W. 
Published: June 2020

AbstractHow do animals make behavioral decisions based on noisy sensory signals, which are moreover a tiny fraction of ongoing activity in the brain? Some theories suggest that sensory responses should be accumulated through time to reduce noise. Others suggest that feedback-based gain control of sensory responses allow small signals to be selectively amplified to drive behavior. We recorded from neuronal populations across posterior cortex as mice performed a decision-making task based on accumulating randomly timed pulses of visual evidence. Here we focus on a subset of neurons, with putative sensory responses that were time-locked to each pulse. These neurons exhibited a variety of amplitude (gain-like) modulations, notably by choice and accumulated evidence. These neural data inspired a hypothetical accumulation circuit with a multiplicative feedback-loop architecture, which parsimoniously explains deviations in perceptual discrimination from Weber-Fechner Law. Our neural observations thus led to a model that synthesizes both accumulation and feedback hypotheses.
Performance in even a simple perceptual task depends on mouse secondary visual areas
Authors: Goldbach Hannah C , Akitake Bradley , Leedy Caitlin E , Histed Mark H 
Published: June 2020

AbstractPrimary visual cortex (V1) in the mouse projects to numerous brain areas, including several secondary visual areas, frontal cortex, and basal ganglia. While it has been demonstrated that optogenetic silencing of V1 strongly impairs visually-guided behavior, it is not known which downstream areas are required for visual behaviors. Here we trained mice to perform a contrast-increment change detection task, for which substantial stimulus information is present in V1. Optogenetic silencing of visual responses in secondary visual areas revealed that their activity is required for even this simple visual task.In vivoelectrophysiology showed that, although inhibiting secondary visual areas could produce some feedback effects in V1, the principal effect was profound suppression at the location of the optogenetic light. The results show that pathways through secondary visual areas are necessary for even simple visual behaviors.
Spatiotemporal coding in the macaque supplementary eye fields: landmark influence in the target-to-gaze transformation
Authors: Bharmauria Vishal , Sajad Amirsaman , Yan Xiaogang , Wang Hongying , Douglas Crawford John 
Published: June 2020

ABSTRACTEye-centered (egocentric) and landmark-centered (allocentric) visual signals influence spatial cognition, navigation and goal-directed action, but the neural mechanisms that integrate these signals for motor control are poorly understood. A likely candidate for ego / allocentric integration in the gaze control system is the supplementary eye fields (SEF), a mediofrontal structure with high-level ‘executive’ functions, spatially tuned visual / motor response fields, and reciprocal projections with the frontal eye fields (FEF). To test this hypothesis, we trained two head-unrestrained animals to saccade toward a remembered visual target in the presence of a visual landmark that shifted during the delay, causing gaze end points to shift partially in the same direction. 256 SEF neurons were recorded, including 68 with spatially tuned response fields. Model fits to the latter established that, like the FEF and superior colliculus, spatially tuned SEF responses primarily showed an egocentric (eye-centered) target-to-gaze position transformation. However, the landmark shift influenced this default egocentric transformation: during the delay, motor neurons (with no visual response) showed a transient but unintegrated shift (i.e., not correlated with the target-to-gaze transformation), whereas during the saccade-related burst visuomotor neurons showed an integrated shift (i.e., correlated with the target-to-gaze transformation). This differed from our simultaneous FEF recordings (Bharmauria et al., 2020), which showed a transient shift in visuomotor neurons, followed by an integrated response in all motor responses. Based on these findings and past literature, we propose that prefrontal cortex incorporates landmark-centered information into a distributed, eye-centered target-to-gaze transformation through a reciprocal prefrontal circuit.
Sex differences in the effect of acute fasting on excitatory and inhibitory synapses onto ventral tegmental area dopamine neurons
Authors: Godfrey Nathan , Borgland Stephanie L. 
Published: June 2020

AbstractDopamine neurons in the ventral tegmental area (VTA) are important for energizing goal directed behaviour towards food and are sensitive to changes in metabolic states. Fasting increases the incentive motivation for food, mobilization of energy stores and have sex-dependent effects. However, it is unknown how acute fasting alters excitatory or inhibitory synaptic transmission onto VTA dopamine neurons. An acute 16h overnight fast induced increased food seeking behaviour that was more predominant in male mice. Fasting increased miniature excitatory postsynaptic current (mEPSC) frequency and amplitude in male, but not female mice. This effect was not due to altered release probability as there was no change in the paired pulse ratio, nor was it due to an altered postsynaptic response as there was no change in the AMPAR/NMDA ratio or response to glutamate uncaging. However, this effect was consistent with an increase in the number of release sites. In addition, depolarization-induced-suppression of excitation (DSE), a measure of short-term endocannabinoid-mediated plasticity, was enhanced in female but not male fasted mice. There were no fasting-induced changes at inhibitory synapses onto dopamine neurons of male or female mice. Taken together, these results demonstrate that fasting influences excitatory synapses differentially in male and female mice, but preserves inhibitory synapses onto dopamine neurons, indicating that the mesolimbic circuit of male and female mice respond differently to acute energy deprivation.Key PointsFasting can increase motivation for food and can energize reward-seeking.Ventral tegmental area (VTA) dopamine neurons respond to motivationally relevant information and fasting can influence mesolimbic dopamine concentration.An acute overnight fast differentially alters food approach behaviours and excitatory synaptic transmission onto VTA dopamine neurons of male or female mice.While inhibitory synapses onto VTA dopamine neurons are not altered by fasting in male or female mice, male mice had strengthened excitatory synapses whereas female mice had increased endocannabinoid-mediated short term plasticity at excitatory synapses.These results help us understand how fasting differentially influences excitatory synaptic transmission onto dopamine neurons and may inform different strategies for fasting-induced food seeking by male and female mice.
Age-related losses in cardiac autonomic activity during a daytime nap
Authors: Chen Pin-Chun , Sattari Negin , Whitehurst Lauren N. , Mednick Sara C. 
Published: June 2020

AbstractIn healthy, young individuals, a reduction in cardiovascular output and a shift from sympathetic to parasympathetic (vagal) dominance is observed from wake into stages of nocturnal and daytime sleep. This cardiac autonomic profile, measured by heart rate variability (HRV), has been associated with significant benefits for cardiovascular health. Aging is associated with decreased nighttime sleep quality and lower parasympathetic activity during both sleep and resting. However, it is not known whether age-related dampening of HRV extends to daytime sleep, diminishing the cardiovascular benefits of naps in the elderly. Here, we investigated this question by comparing the autonomic activity profile between young and older healthy adults during a daytime nap and a similar period of wakefulness (quiet wake; QW). For each condition, from the electrocardiogram (ECG), we obtained beat-to-beat HRV intervals (RR), root mean square of successive differences between adjacent heart-beat-intervals (RMSSD), high frequency (HF), low frequency (LF) power and total power (TP), HF normalized units (HFnu), and the LF/HF ratio. As previously reported, young subjects showed a parasympathetic dominance during NREM, compared with REM, pre-nap rest, and WASO. On the other hand, older, compared to younger, adults showed significantly lower vagally-mediated HRV (measured by RMSSD, HF, HFnu) during NREM. Interestingly, however, no age-related differences were detected during pre-nap rest or QW. Altogether, our findings suggest a sleep-specific reduction in parasympathetic modulation that is unique to NREM sleep in older adults.Impact StatementSleep is naturally modulated by the autonomic nervous system (ANS), with greater dominance of parasympathetic over sympathetic activity during non-rapid-eye-movement (NREM) sleep. As such, sleep has been termed a “cardiovascular holiday” and has been associated with positive health outcomes. Aging, however, is linked to decreases in cardiac autonomic activity and sympathovagal imbalance. While the impact of aging on ANS activity during nocturnal sleep has received some attention, the cardiac profiles during a daytime nap, to our knowledge, have not yet been studied under the context of aging. Herein, young adults demonstrated increased parasympathetic activity during deep sleep. Older adults, however, showed less parasympathetic modulation during NREM sleep, suggesting loss of the cardiovascular holiday. Importantly, no age-related declines in parasympathetic activity were detected during wake, suggesting a sleep-specific reduction in parasympathetic modulation that is unique to NREM sleep in older adults.
Obesity impairs cognitive function via metabolic syndrome and cerebrovascular disease: an SEM analysis in 15,000 adults from the UK Biobank
Authors: Morys Filip , Dadar Mahsa , Dagher Alain 
Published: June 2020

AbstractChronic obesity is associated with several complications, including cognitive impairment and dementia. However, we have piecemeal knowledge of the mechanisms linking obesity to central nervous system damage. Adiposity leads to the metabolic syndrome, consisting of inflammation, hypertension, dyslipidemia and insulin resistance. In turn, these metabolic abnormalities cause cerebrovascular dysfunction, which may cause white and grey matter tissue loss and consequent cognitive impairment. While there have been several neuroimaging studies linking adiposity to changes in brain morphometry, a comprehensive investigation of the relationship has so far not been done. Here we use structural equation modelling applied to over 15,000 individuals from the UK Biobank to identify the causal chain that links adiposity to cognitive dysfunction. We found that body mass index and waist-to-hip ratio were positively related to higher plasma C-reactive protein, dyslipidemia, occurrence of hypertension and diabetes, all of which were in turn related to cerebrovascular disease as measured by volume of white matter hyperintensities on magnetic resonance imaging. White mater hyperintensities were associated with lower cortical thickness and volume and higher subcortical volumes, which were associated with cognitive deficits on tests of visuospatial memory, fluid intelligence, and working memory among others. In follow-up analyses we found that inflammation, hypertension and diabetes mediated 20% of the relationship between obesity and cerebrovascular disease and that cerebrovascular disease mediated a significant proportion of the relationship between obesity and cortical thickness and volume. We also showed that volume of white matter hyperintensities was related to decreased fractional anisotropy and increased mean diffusivity in the majority of white matter tracts, pointing to white matter dysconnectivity as a major cause of impaired cognition. Our results have clinical implications, supporting a role for the management of adiposity in the prevention of late-life dementia and cognitive decline.
Higher clinical acuity and 7-day hospital mortality in non-COVID-19 acute medical admissions: prospective observational study
Authors: Lyall Marcus J , Lone Nazir I 
Published: June 2020

AbstractObjectivesTo understand the effect of COVID-19 lockdown measures on severity of illness and mortality in non-COVID-19 acute medical admissions.DesignA prospective observational studySetting3 large acute medical receiving units in NHS Lothian, Scotland. Participants: Non-covid-19 acute admissions (n = 1756) were examined over the first 31 days after the implementation of the COVID-19 lockdown policy in the United Kingdom on 23rd March 2019. Patients admitted over a matched interval in the previous 5 years were used as a comparator cohort (n = 14961).Main outcome measuresPatient demography, biochemical markers of clinical acuity and 7-day hospital inpatient mortality.ResultsNon-covid-19 acute medical admissions reduced by a mean 43.8% (95% CI 27.3, 59.4) across all 3 sites in comparison to the mean of the preceding 5 years P < 0.001. The reduction in admissions predominated in the over 75 age category and a greater proportion arrived by emergency ambulance transport. Non-covid-19 admissions during lockdown had a greater incidence of severe renal injury, hyperlactataemia and over twice the risk of hospital death within 7 days 5.01% vs 2.49% which persisted after adjustment for confounders (OR 2.17, 95% CI 1.70,2.73, P < 0.0001)ConclusionsThese data support current fears that patients are delaying seeking medical attention for acute illness which is associated with worsening clinical parameters and a higher risk of death following admission.
Mycobacterium tuberculosis-specific T cell activation identifies individuals at high risk of tuberculosis disease
Authors: Mpande Cheleka A.M. , Musvosvi Munyaradzi , Rozot Virginie , Mosito Boitumelo , Reid Timothy D. , Schreuder Constance , Lloyd Tessa , Bilek Nicole , Huang Huang , Obermoser Gerlinde , Davis Mark M. , Ruhwald Morten , Hatherill Mark , Scriba Thomas J. , Nemes Elisa ,   ACS Study Team
Published: June 2020

AbstractBackgroundProvision of tuberculosis preventive treatment (TPT) to individuals withMycobacterium tuberculosis(M.tb) infection (TBI) is a key strategy to reduce the global tuberculosis burden. Tuberculosis risk is significantly higher after recent compared to remote TBI. We aimed to define a blood-based biomarker, measured with a simple flow cytometry assay, to stratify different stages of TBI to infer risk of disease.MethodsHealthy adolescents were serially tested with QuantiFERON-TB Gold (QFT) to define recent (QFT conversion <6 months) and remote (persistent QFT+ for >1 year) TBI. M.tb-specific T cells were defined as IFN-g+TNF+CD3+ cells upon CFP-10/ESAT-6 or M.tb lysate stimulation. ΔHLA-DR median fluorescence intensity (MFI) was defined as the difference in HLA-DR expression between M.tb-specific and total T cells. Biomarker performance was assessed by blinded prediction in untouched test cohorts with recentversusremote TBI or tuberculosis disease, and unblinded analysis of asymptomatic adolescents with TBI who remained healthy (non-progressors) or who progressed to microbiologically-confirmed disease (progressors).FindingsIn the test cohorts, frequencies of M.tb-specific T cells differentiated between QFT- (n=25) and QFT+ (n=47) individuals [area under the ROC curve (AUCROC): 0.94; 95%CI: 0.87-1.00]. ΔHLA-DR MFI significantly discriminated between recent (n=20) and remote (n=22) TBI (AUCROC 0.91; 95%CI: 0.83-1.00); remote TBI and newly diagnosed tuberculosis (n=19; AUCROC 0.99; 95%CI: 0.96-1.00); and between tuberculosis progressors (n=22) and non-progressors (n=34; AUCROC 0.75, 95%CI: 0.63-0.87).InterpretationThe ΔHLA-DR MFI biomarker can identify individuals with recent TBI and those with disease progression, allowing targeted provision of TPT to those at highest risk of tuberculosis.
“The transcriptome-wide association search for genes and genetic variants which associate with BMI and gestational weight gain in women with type 1 diabetes”
Authors: Ludwig-Słomczyńska Agnieszka H. , Seweryn Michał T. , Kapusta Przemysław , Pitera Ewelina , Mantaj Urszula , Cyganek Katarzyna , Gutaj Paweł , Dobrucka Łucja , Wender-OŻegowska Ewa , Małecki Maciej T. , Wołkow Paweł P. 
Published: June 2020

ABSTRACTBackgroundClinical data suggest that BMI and gestational weight gain (GWG) are strongly interconnected phenotypes, however the genetic basis of the latter is rather unclear. Here we aim to find genes and genetic variants which influence BMI and/or GWG.MethodsWe have genotyped 316 type 1 diabetics using Illumina Infinium Omni Express Exome-8 v1.4 arrays. The GIANT, ARIC and T2D-GENES summary statistics were used for TWAS (performed with PrediXcan) in adipose tissue. Next, the analysis of association of imputed expression with BMI in the general and diabetic cohorts (Analysis 1 and 2) or GWG (Analysis 3 and 4) was performed, followed by variant association analysis (1Mb around identified loci) with the mentioned phenotypes.ResultsIn Analysis 1 we have found 175 BMI associated genes and 19 variants (p<10−4) which influenced GWG, with the strongest association for rs11465293 in CCL24 (p=3.18E-06). Analysis 2, with diabetes included in the model, led to discovery of 1812 BMI associated loci and 207 variants (p<10−4) influencing GWG, with the strongest association for rs9690213 in PODXL (p=9.86E-07). In Analysis 3, among 648 GWG associated loci, 2091 variants were associated with BMI (FDR<0.05). In Analysis 4, 7 variants in GWG associated loci influenced BMI in the ARIC cohort.ConclusionsHere, we have shown that loci influencing BMI might have an impact on GWG and GWG associated loci might influence BMI, both in the general and T1DM cohorts. The results suggest that both phenotypes are related to insulin signaling, glucose homeostasis, mitochondrial metabolism, ubiquitinoylation and inflammatory responses.
Development and external validation of a diagnostic model for periprocedural bradycardia during primary percutaneous coronary intervention
Authors: Li Yong , Lyu Shuzheng 
Published: June 2020

AbstractBackgroundPeriprocedural bradycardia weaks the benefit of primary percutaneous coronary intervention (PPCI) and has deleterious effects on organ perfusion of patients with acute ST elevation myocardial infarction (STEMI).ObjectiveTo develop and externally validate a diagnostic model of periprocedural bradycardia..MethodsDesign: Multivariable logistic regression of a cohort of acute STEMI patients. Setting: Emergency department ward of a university hospital. Participants: Diagnostic model development: Totally 1820 acute STEMI patients who were consecutively treated with PPCI from November 2007 to December 2015 in Beijing Anzhen Hospital, Capital Medical University. External validation: Totally 716 acute STEMI patients who were treated with PPCI from January 2016 to June 2018 in Beijing Anzhen Hospital, Capital Medical University. Outcomes:Periprocedural bradycardia during PPCI. Periprocedural bradycardia was defined as preoperative heart rate ≥ 50 times / min, intraoperative heart rate <50 times / min persistent or transient.ResultsTotally 332 (18.2%)patients presented periprocedural bradycardia in the development dataset and 102 (14.2%) patients presented periprocedural bradycardia in the validation dataset. The strongest predictors of periprocedural bradycardia were intra-procedural hypotension, the culprit vessel was not left anterior descending (LAD), using thrombus aspiration devices during procedure, sex, history of coronary artery disease, total occlusion of culprit vessel, and no-reflow. We developed a diagnostic model of periprocedural bradycardia.The area under the receiver operating characteristic(ROC) curve(AUC) was 0.8384± 0.0122 in the development set. We constructed a nomogram based on predictors of periprocedural bradycardia using the development database. The AUC was 0.8437±0.0203 in the validation set. Discrimination, calibration, and decision curve analysis were satisfactory.ConclusionsWe developed and externally validated a diagnostic model of periprocedural bradycardia during PPCI.We registered this study with WHO International Clinical Trials Registry Platform(ICTRP). Registration number: ChiCTR1900023214.Registered Date :16 May 2019.http://www.chictr.org.cn/edit.aspx?pid=39087&htm=4