Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss of GluN2A‐containing NMDA receptors impairs extra‐dimensional set‐shifting

Glutamate neurotransmission via the N‐methyl‐d‐aspartate receptor (NMDAR) is thought to mediate the synaptic plasticity underlying learning and memory formation. There is increasing evidence that deficits in NMDAR function are involved in the pathophysiology of cognitive dysfunction seen in neuropsychiatric disorders and addiction. NMDAR subunits confer different physiological properties to the receptor, interact with distinct intracellular postsynaptic scaffolding and signaling molecules, and are differentially expressed during development. Despite these known differences, the relative contribution of individual subunit composition to synaptic plasticity and learning is not fully elucidated. We have previously shown that constitutive deletion of GluN2A subunit in the mouse impairs discrimination and re‐learning phase of reversal when exemplars are complex picture stimuli, but spares acquisition and extinction of non‐discriminative visually cued instrumental response. To investigate the role of GluN2A containing NMDARs in executive control, we tested GluN2A knockout (GluN2AKO), heterozygous (GluN2AHET) and wild‐type (WT) littermates on an attentional set‐shifting task using species‐specific stimulus dimensions. To further explore the nature of deficits in this model, mice were tested on a visual discrimination reversal paradigm using simplified rotational stimuli. GluN2AKO were not impaired on discrimination or reversal problems when tactile or olfactory stimuli were used, or when visual stimuli were sufficiently easy to discriminate. GluN2AKO showed a specific and significant impairment in ventromedial prefrontal cortex‐mediated set‐shifting. Together these results support a role for GluN2A containing NMDAR in modulating executive control that can be masked by overlapping deficits in attentional processes during high task demands.
Associations between initial water pipe tobacco smoking and snus use and subsequent cigarette smoking: results from a longitudinal study of US adolescents and young adults.

IMPORTANCE Many adolescents and young adults use alternative tobacco products, such as water pipes and snus, instead of cigarettes. OBJECTIVE To assess whether prior water pipe tobacco smoking and snus use among never smokers are risk factors for subsequent cigarette smoking. DESIGN, SETTING, AND PARTICIPANTS We conducted a 2-wave national longitudinal study in the United States among 2541 individuals aged 15 to 23 years old. At baseline (October 25, 2010, through June 11, 2011), we ascertained whether respondents had smoked cigarettes, smoked water pipe tobacco, or used snus. At the 2-year follow-up (October 27, 2012, through March 31, 2013), we determined whether baseline non-cigarette smokers had subsequently tried cigarette smoking, were current (past 30 days) cigarette smokers, or were high-intensity cigarette smokers. We fit multivariable logistic regression models among baseline non-cigarette smokers to assess whether baseline water pipe tobacco smoking and baseline snus use were associated with subsequent cigarette smoking initiation and current cigarette smoking, accounting for established sociodemographic and behavioral risk factors. We fit similarly specified multivariable ordinal logistic regression models to assess whether baseline water pipe tobacco smoking and baseline snus use were associated with high-intensity cigarette smoking at follow-up. EXPOSURES Water pipe tobacco smoking and the use of snus at baseline. MAIN OUTCOMES AND MEASURES Among baseline non-cigarette smokers, cigarette smoking initiation, current (past 30 days) cigarette smoking at follow-up, and the intensity of cigarette smoking at follow-up. RESULTS Among 1596 respondents, 1048 had never smoked cigarettes at baseline, of whom 71 had smoked water pipe tobacco and 20 had used snus at baseline. At follow-up, accounting for behavioral and sociodemographic risk factors, baseline water pipe tobacco smoking and snus use were independently associated with cigarette smoking initiation (adjusted odds ratios: 2.56; 95% CI, 1.46-4.47 and 3.73; 95% CI, 1.43-9.76, respectively), current cigarette smoking (adjusted odds ratios: 2.48; 95% CI, 1.01-6.06 and 6.19; 95% CI, 1.86-20.56, respectively), and higher intensity of cigarette smoking (adjusted proportional odds ratios: 2.55; 95% CI, 1.48-4.38 and 4.45; 95% CI, 1.75-11.27, respectively). CONCLUSIONS AND RELEVANCE Water pipe tobacco smoking and the use of snus independently predicted the onset of cigarette smoking and current cigarette smoking at follow-up. Comprehensive Food and Drug Administration regulation of these tobacco products may limit their appeal to youth and curb the onset of cigarette smoking.
A case‐control study of brain structure and behavioral characteristics in 47,XXX syndrome

Trisomy X, the presence of an extra X chromosome in females (47,XXX), is a relatively common but under‐recognized chromosomal disorder associated with characteristic cognitive and behavioral features of varying severity. The objective of this study was to determine whether there were neuroanatomical differences in girls with Trisomy X that could relate to cognitive and behavioral differences characteristic of the disorder during childhood and adolescence. MRI scans were obtained on 35 girls with Trisomy X (mean age 11.4, SD 5.5) and 70 age‐ and sex‐matched healthy controls. Cognitive and behavioral testing was also performed. Trisomy X girls underwent a semi‐structured psychiatric interview. Regional brain volumes and cortical thickness were compared between the two groups. Total brain volume was significantly decreased in subjects with Trisomy X, as were all regional volumes with the exception of parietal gray matter. Differences in cortical thickness had a mixed pattern. The subjects with Trisomy X had thicker cortex in bilateral medial prefrontal cortex and right medial temporal lobe, but decreased cortical thickness in both lateral temporal lobes. The most common psychiatric disorders present in this sample of Trisomy X girls included anxiety disorders (40%), attention‐deficit disorder (17%) and depressive disorders (11%). The most strongly affected brain regions are consistent with phenotypic characteristics such as language delay, poor executive function and heightened anxiety previously described in population‐based studies of Trisomy X and also found in our sample.
Preliminary evidence of an effect of cerebellar volume on postural sway in FMR1 premutation males

Recent evidence suggests that early changes in postural control may be discernible among females with premutation expansions (55–200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene at risk of developing fragile X‐associated tremor ataxia syndrome (FXTAS). Cerebellar dysfunction is well described in males and females with FXTAS, yet the interrelationships between cerebellar volume, CGG repeat length, FMR1 messenger RNA (mRNA) levels and changes in postural control remain unknown. This study examined postural sway during standing in a cohort of 22 males with the FMR1 premutation (ages 26–80) and 24 matched controls (ages 26–77). The influence of cerebellar volume, CGG repeat length and FMR1 mRNA levels on postural sway was explored using multiple linear regression. The results provide preliminary evidence that increasing CGG repeat length and decreasing cerebellar volume were associated with greater postural sway among premutation males. The relationship between CGG repeat length and postural sway was mediated by a negative association between CGG repeat size and cerebellar volume. While FMR1 mRNA levels were significantly elevated in the premutation group and correlated with CGG repeat length, FMR1 mRNA levels were not significantly associated with postural sway scores. These findings show for the first time that greater postural sway among males with the FMR1 premutation may reflect CGG repeat‐mediated disruption in vulnerable cerebellar circuits implicated in postural control. However, longitudinal studies in larger samples are required to confirm whether the relationships between cerebellar volume, CGG repeat length and postural sway indicate greater risk for neurological decline.
Labor Scheduling, Part 1

This paper focuses on forecasting demand for services, the first of a four-part series on developing effective workforce schedules. Serving customers well, at a reasonable cost, requires the proper number and mix of employees. Scheduling too many employees means high labor costs, while scheduling too few workers can mean poor service that drives away business. Forecasting customer demand involves eight steps: determine the nature of the work, identify those factors that generate the work (i.e., the labor drivers), determine whether the labor drivers are time variant or time invariant, determine the time interval for tracking the time-variant labor drivers, forecast the time-variant labor drivers, smooth those forecasts, track the error in those forecasts, and define the allowable window for controllable work. Balancing employees' skills and availability, plus governmental regulations, company policies, and contractual obligations regarding work schedules, can be a manager's nightmare.
Associative and sensorimotor cortico‐basal ganglia circuit roles in effects of abused drugs

The mammalian forebrain is characterized by the presence of several parallel cortico‐basal ganglia circuits that shape the learning and control of actions. Among these are the associative, limbic and sensorimotor circuits. The function of all of these circuits has now been implicated in responses to drugs of abuse, as well as drug seeking and drug taking. While the limbic circuit has been most widely examined, key roles for the other two circuits in control of goal‐directed and habitual instrumental actions related to drugs of abuse have been shown. In this review we describe the three circuits and effects of acute and chronic drug exposure on circuit physiology. Our main emphasis is on drug actions in dorsal striatal components of the associative and sensorimotor circuits. We then review key findings that have implicated these circuits in drug seeking and taking behaviors, as well as drug use disorders. Finally, we consider different models describing how the three cortico‐basal ganglia circuits become involved in drug‐related behaviors. This topic has implications for drug use disorders and addiction, as treatments that target the balance between the different circuits may be useful for reducing excessive substance use.
Sputum Microscopy With Fluorescein Diacetate Predicts Tuberculosis Infectiousness

Summary Fluorescein diacetate microscopy was used to assess Mycobacterium tuberculosis metabolic activity in pretreatment sputa. Lower results predicted greater infectiousness in transmitting tuberculosis to household contacts. Fluorescein diacetate microscopy–negative bacteria may be better adapted to airborne tuberculosis transmission and consequently more contagious.
Genomic Epidemiology of a Major Mycobacterium tuberculosis Outbreak: Retrospective Cohort Study in a Low-Incidence Setting Using Sparse Time-Series Sampling

Since 1992, Denmark has documented the largest outbreak of tuberculosis in Scandinavia ascribed to a single genotype, termed C2/1112-15. As of spring 2017, the International Reference Laboratory of Mycobacteriology in Copenhagen has collected and identified isolates from more than a thousand cases belonging to this outbreak via routine mycobacterial interspersed repetitive units-variable number of tandem repeats typing. Here, we present a retrospective analysis of the C2/1112-15 dataset, based on whole-genome data from a sparse time series consisting of 5 randomly selected isolates from 23 years of sampling. Even if these data are derived from only 12% of the collected isolates, we have been able to extract important key information, such as mutation rate and conserved single-nucleotide polymorphisms to identify discrete transmission chains, as well as the possible historical origins of the outbreak.
Deficiency of aminopeptidase P1 causes behavioral hyperactivity, cognitive deficits, and hippocampal neurodegeneration

Metabolic diseases affect various organs including the brain. Accumulation or depletion of substrates frequently leads to brain injury and dysfunction. Deficiency of aminopeptidase P1, a cytosolic proline‐specific peptidase encoded by the Xpnpep1 gene, causes an inborn error of metabolism (IEM) characterized by peptiduria in humans. We previously reported that knockout of aminopeptidase P1 in mice causes neurodevelopmental disorders and peptiduria. However, little is known about the pathophysiological role of aminopeptidase P1 in the brain. Here, we show that loss of aminopeptidase P1 causes behavioral and neurological deficits in mice. Mice deficient in aminopeptidase P1 (Xpnpep1−/−) display abnormally enhanced locomotor activities in both the home cage and open‐field box. The aminopeptidase P1 deficiency in mice also resulted in severe impairments in novel‐object recognition, the Morris water maze task, and contextual, but not cued, fear memory. These behavioral dysfunctions were accompanied by epileptiform electroencephalogram activity and neurodegeneration in the hippocampus. However, mice with a heterozygous mutation for aminopeptidase P1 (Xpnpep1+/−) exhibited normal behaviors and brain structure. These results suggest that loss of aminopeptidase P1 leads to behavioral, cognitive and neurological deficits. This study may provide insight into new pathogenic mechanisms for brain dysfunction related to IEMs.
The genetics of human personality

Personality traits are the relatively enduring patterns of thoughts, feelings and behaviors that reflect the tendency to respond in certain ways under certain circumstances. Twin and family studies have showed that personality traits are moderately heritable, and can predict various lifetime outcomes, including psychopathology. The Research Domain Criteria characterizes psychiatric diseases as extremes of normal tendencies, including specific personality traits. This implies that heritable variation in personality traits, such as neuroticism, would share a common genetic basis with psychiatric diseases, such as major depressive disorder. Despite considerable efforts over the past several decades, the genetic variants that influence personality are only beginning to be identified. We review these recent and increasingly rapid developments, which focus on the assessment of personality via several commonly used personality questionnaires in healthy human subjects. Study designs covered include twin, linkage, candidate gene association studies, genome‐wide association studies and polygenic analyses. Findings from genetic studies of personality have furthered our understanding about the genetic etiology of personality, which, like neuropsychiatric diseases themselves, is highly polygenic. Polygenic analyses have showed genetic correlations between personality and psychopathology, confirming that genetic studies of personality can help to elucidate the etiology of several neuropsychiatric diseases.
Domperidone upregulates dopamine receptor expression and stimulates locomotor activity in larval zebrafish (Danio rerio)

Dopamine (DA) plays a significant role in cognition, motor function and social behavior. The objectives of this study were to (1) quantify the temporal expression of transcripts (DA receptors, transporters and tyrosine hydroxylase) associated with DA signaling during early stages of zebrafish development and (2) determine their expression profiles following treatment with a D2 receptor antagonist domperidone (DMP). We also assessed locomotor behavior following treatment with DMP using alternating periods of light and dark (ie, dark photokinesis), as DA plays a key role in behavior. Relative expression levels of transcripts that were investigated and related to the DA system were detected after the first 24 hours postfertilization (hpf). Some DA receptor transcripts (eg, drd4c) increased in abundance earlier in the embryo compared with other receptors (eg, drd3), suggesting that DA receptor paralogs may have unique roles in development. Treatment of larvae with DMP resulted in the upregulation of DA receptor transcripts (ie, drd1, drd7, drd4b, drd4c) and DA transporter 1 (ie, slc6a3), and it is hypothesized that upregulation of genes related to the DA system is a compensatory neurophysiological response to DA receptor antagonism. Larval activity during dark photokinesis (measured by distance traveled) was also elevated by DMP. We hypothesize that behavioral responses observed with DMP may be related to the regulation of deep brain photoreception in zebrafish (Danio rerio) (ZF) larvae by DA.
Biogenicity of an Early Quaternary iron formation, Milos Island, Greece

A ~2.0‐million‐year‐old shallow‐submarine sedimentary deposit on Milos Island, Greece, harbours an unmetamorphosed fossiliferous iron formation (IF) comparable to Precambrian banded iron formations (BIFs). This Milos IF holds the potential to provide clues to the origin of Precambrian BIFs, relative to biotic and abiotic processes. Here, we combine field stratigraphic observations, stable isotopes of C, S and Si, rock petrography and microfossil evidence from a ~5‐m‐thick outcrop to track potential biogeochemical processes that may have contributed to the formation of the BIF‐type rocks and the abrupt transition to an overlying conglomerate‐hosted IF (CIF). Bulk δ13C isotopic compositions lower than ‐25‰ provide evidence for biological contribution by the Calvin and reductive acetyl–CoA carbon fixation cycles to the origin of both the BIF‐type and CIF strata. Low S levels of ~0.04 wt. % combined with δ34S estimates of up to ~18‰ point to a non‐sulphidic depository. Positive δ30Si records of up to +0.53‰ in the finely laminated BIF‐type rocks indicate chemical deposition on the seafloor during weak periods of arc magmatism. Negative δ30Si data are consistent with geological observations suggesting a sudden change to intense arc volcanism potentially terminated the deposition of the BIF‐type layer. The typical Precambrian rhythmic rocks of alternating Fe‐ and Si‐rich bands are associated with abundant and spatially distinct microbial fossil assemblages. Together with previously proposed anoxygenic photoferrotrophic iron cycling and low sedimentary N and C potentially connected to diagenetic denitrification, the Milos IF is a biogenic submarine volcano‐sedimentary IF showing depositional conditions analogous to Archaean Algoma‐type BIFs.
The role of advanced imaging in transcatheter aortic valve implantation

textabstractAortic stenosis, currently the most prevalent valvular heart disease in Europe, is an important public health problem, affecting thousands of patients every year. While surgical aortic valve replacement is still considered the “gold standard” treatment, recent innovations in transcatheter valve therapies have offered an attractive alternative: transcatheter aortic valve implantation (TAVI). In 2002, Cribier et al. announced the first human case description of a percutaneously implanted heart valve in a patient suffering from severe aortic stenosis. Since then, the number of patients that undergo TAVI has increased exponentially. Preliminary early and midterm results following TAVI have been promising. However, despite satisfactory hemodynamic results, TAVI procedures still face important safety issues such as paravalvular leaks, vascular complications, stroke, conduction disorders and the need for pacemaker implantation. Currently, TAVI is offered only to patients who are considered high risk candidates for surgical aortic valve replacement. A fundamental characteristic of percutaneous interventions is the lack of direct visualization of the target organ/tissue. Consequently, interventional cardiology is greatly related to and depending on imaging. Especially in TAVI, which is entering the field of traditional valve surgery, the role of multimodality cardiac imaging is mandatory. Contrast aortography, multi slice computed tomography (MSCT), magnetic resonance imaging and echocardiography can provide a detailed characterisation of vascular anatomy, aortic root dimensions, aortic valve calcifications and left ventricular (LV) function. The use of these imaging techniques is invaluable for patient selection and planning of the procedure. In addition, some techniques can be used during the operation to guide the implantation, as well as after the procedure to evaluate the positioning and function of the prosthesis. TAVI is a fascinating technology but it is still in its infancy. Further studies are needed in order to understand and modulate TAVI. The aim of the present thesis is to investigate the role of advanced cardiac imaging for TAVI.
Geochemically distinct carbon isotope distributions in Allochromatium vinosum DSM 180T grown photoautotrophically and photoheterotrophically

Anoxygenic, photosynthetic bacteria are common at redox boundaries. They are of interest in microbial ecology and geosciences through their role in linking the carbon, sulfur, and iron cycles, yet much remains unknown about how their flexible carbon metabolism—permitting either autotrophic or heterotrophic growth—is recorded in the bulk sedimentary and lipid biomarker records. Here, we investigated patterns of carbon isotope fractionation in a model photosynthetic sulfur‐oxidizing bacterium, Allochromatium vinosum DSM180T. In one treatment, A. vinosum was grown with CO2 as the sole carbon source, while in a second treatment, it was grown on acetate. Different intracellular isotope patterns were observed for fatty acids, phytol, individual amino acids, intact proteins, and total RNA between the two experiments. Photoautotrophic CO2 fixation yielded typical isotopic ordering for the lipid biomarkers: δ13C values of phytol > n‐alkyl lipids. In contrast, growth on acetate greatly suppressed intracellular isotopic heterogeneity across all molecular classes, except for a marked 13C‐depletion in phytol. This caused isotopic “inversion” in the lipids (δ13C values of phytol < n‐alkyl lipids). The finding suggests that inverse δ13C patterns of n‐alkanes and pristane/phytane in the geologic record may be at least in part a signal for photoheterotrophy. In both experimental scenarios, the relative isotope distributions could be predicted from an isotope flux‐balance model, demonstrating that microbial carbon metabolisms can be interrogated by combining compound‐specific stable isotope analysis with metabolic modeling. Isotopic differences among molecular classes may be a means of fingerprinting microbial carbon metabolism, both in the modern environment and the geologic record.
Essential anatomy and some clinical applications

PART ONE: GENERAL INTRODUCTION the Structure of the Body. The Vertebral Column PART TWO: THORAX the Thoracic Wall, Diaphragm and Breast. The Thoracic Cavity and Heart. Other Mediastinal Structures. The Pleura and Lungs. Lymph Drainage and the Autonomic Nervous System PART THREE: ABDOMEN and PELVIS the Abdomen and Peritoneum. The Abdominal Alimentary Tract. The Liver, Spleen and Pancreas. The Kidneys, Suprarenal Glands and Posterior Abdominal Wall. The Pelvis. The Perineum. The Blood Vessels, Lymph Drainage and Nerves PART FOUR: UPPER LIMB the Shoulder Region. The Axilla and Upper Arm. The Elbow and Forearm. The Wrist and Hand. The Fascia, Veins, Lymph Drainage and Nerves PART FIVE: LOWER LIMB the Hip and Thigh. The Knee, Leg and Dorsum of the Foot. The Foot. The Fascia, Veins, Lymph Drainage, Nerves and Posture PART SIX: HEAD and NECK the Skull, Scalp and Face. The Orbit, Nose and Mouth. The Temperomandibular Joint, Pharynx and Larynx. The Ear, Intracranial Region and Cranial Nerves. The Neck. The Vessels, Nerves and Lymph Drainage PART SEVEN: CENTRAL NERVOUS SYSTEM Introduction. The Forebrain. The Brain Stem and Cerebellum. The Spinal Cord and Reticular Formation. The Afferent and Efferent Pathways. The Meninges and Blood Supply PART EIGHT: CLINICAL EXAMINATION the Anatomy of Clinical Examination Index