Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of the cerebellum in drug‐cue associative memory: functional interactions with the medial prefrontal cortex

Drug‐induced Pavlovian memories are thought to be crucial for drug addiction because they guide behaviour towards environments with drug availability. Drug‐related memory depends on persistent changes in dopamine‐glutamate interactions in the medial prefrontal cortex (mPFC), basolateral amygdala, nucleus accumbens core and hippocampus. Recent evidence from our laboratory indicated that the cerebellum is also a relevant node for drug‐cue associations. In the present study, we tested the role that specific regions of the cerebellum and mPFC play in the acquisition of cocaine‐induced preference conditioning. Quinolinic acid was used to manage a permanent deactivation of lobule VIII in the vermis prior to conditioning. Additionally, lidocaine was infused into the prelimbic and infralimbic (IL) cortices for reversible deactivation before every training session. The present findings show, for the first time, that the cerebellum and mPFC might act together in order to acquire drug‐cue Pavlovian associations. Either a dorsal lesion in lobule VIII or an IL deactivation encouraged cocaine‐induced preference conditioning. Moreover, simultaneous IL‐cerebellar deactivation prevented the effect of either of the separate deactivations. Therefore, similar to the IL cortex, neural activity in the cerebellum may be crucial for ensuring inhibitory control of the expression of cocaine‐related memories.
Exocytosis of neurosecretory granules from the crustacean sinus gland in freeze‐fracture

Exocytosis is clearly shown in freeze‐fracture preparations to be the mechanism for neurosecretion granule release from axon endings in the crayfish sinus gland. The cytoplasmic leaflet (A‐face) of axon ending membrane is characterized by randomly situated depressions representing invaginations of the axolemma, which are in contact with limiting membranes of neurohormone granules in the subjacent cytoplasm. The extracellular leaflet (B‐face) of the axolemma at release sites exhibits complementary volcano‐shaped protrusions which are cross‐fractures through necks of channels formed by invaginating plasma membrane in contact with underlying neurosecretion granules. Structural variation in B‐face protrusions is consistent with a spectrum of exocytotic profiles in various stages of formation, and with granules at different stages of passage out of the endings. Evidence in this study suggests that formation of exocytotic structures may begin by alteration of axon membrane structure at the neurosecretory ending‐hemolymph interface prior to contact of the neurohormone granules with the axolemma. Limiting membranes of neurosecretory granules exhibit protrusions which appear to interconnect granules adjacent to release sites and to attach granules to the axolemma. Freeze‐fracture is clearly shown to be an invaluable tool for monitoring the degree of exocytosis exhibited by sinus glands under normal conditions and under experimental acceleration of hormone release. This technique is capable therefore, of detecting slight increases in numbers of exocytotic profiles much more quickly and accurately than the examination of random thin sections.
Nonlinear optics on nano/micro-hierarchical structures on metals: focus on symmetric and plasmonic effects

ABSTRACT In this review, the authors study their creation of nano/micro-hierarchical structures on Ag and Ni substrates by femtosecond laser treatment and their investigation of their optical second-harmonic generation (SHG) signal intensities by SHG spectroscopy. The authors obtained the nanostructure-covered microgroove and microcube structures. These hierarchical surface structures were found to modify significantly the optical nonlinearity of the metal surfaces. The macroscopic symmetry of the surface’s shapes influenced SHG, and the excitation of surface plasmons enhanced SHG. On the other hand, the nanostructures on the microstructures had an additional effect on the generated SHG. For the microcube structures, the additional SHG emission was suppressed by removing a large amount of nanostructures. Left SHG was discussed by the effect of the propagating delay.
Pathophysiological aspects of nephropathy caused by non-steroidal anti-inflammatory drugs

Abstract Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used medications associated with nephrotoxicity, especially when used chronically. Factors such as advanced age and comorbidities, which in themselves already lead to a decrease in glomerular filtration rate, increase the risk of NSAID-related nephrotoxicity. The main mechanism of NSAID action is cyclooxygenase (COX) enzyme inhibition, interfering on arachidonic acid conversion into E2 prostaglandins E2, prostacyclins and thromboxanes. Within the kidneys, prostaglandins act as vasodilators, increasing renal perfusion. This vasodilatation is a counter regulation of mechanisms, such as the renin-angiotensin-aldosterone system works and that of the sympathetic nervous system, culminating with compensation to ensure adequate flow to the organ. NSAIDs inhibit this mechanism and can lead to acute kidney injury (AKI). High doses of NSAIDs have been implicated as causes of AKI, especially in the elderly. The main form of AKI by NSAIDs is hemodynamically mediated. The second form of NSAID-induced AKI is acute interstitial nephritis, which may manifest as nephrotic proteinuria. Long-term NSAID use can lead to chronic kidney disease (CKD). In patients without renal diseases, young and without comorbidities, NSAIDs are not greatly harmful. However, because of its dose-dependent effect, caution should be exercised in chronic use, since it increases the risk of developing nephrotoxicity.
To transfuse or not transfuse: an intensive appraisal of red blood cell transfusions in the ICU

Purpose of review This review is a critical appraisal of the current data comparing restrictive vs. liberal transfusion strategies for patients who are critically ill in ICUs. We focus on four subsets of critically ill patients: pediatric patients, patients with gastrointestinal bleeds, septic patients and patients undergoing cardiac surgery. Recent findings Almost a decade after the TRICC trial, a randomized trial showing the safety of a restrictive transfusion threshold in critically ill patients, four large randomized controlled trials have shown that a restrictive transfusion strategy is safe in pediatric critically ill patients, patients with acute upper gastrointestinal bleeds, patients with septic shock and patients undergoing cardiac surgery. A large multicenter randomized trial is underway to determine the safety of a restrictive strategy in myocardial infarction. Summary A restrictive transfusion threshold is recommended in nearly all critically ill patients. This is at least noninferior to more liberal transfusion practice; in addition, a restrictive threshold has shown improved outcomes in some patients and decreased chances of adverse events in patients. Judicious use of red cells improves patient outcome and protects the blood supply, a limited resource. More data are needed to determine appropriate transfusion threshold recommendations for patients with traumatic brain injury and acute coronary syndrome.
Estimating development and temperature thresholds of Ephestia kuehniella: toward improving a mass production system

Abstract The development of the Mediterranean flour moth, Ephestia kuehniella (Zeller), was evaluated at 10, 15, 17.5, 20, 22.5, 25, 27.5, 30 and 32.5°C with no lighting. None successfully completed development at 10 and 32.5°C. The total development time from egg to adult emergence was 164, 140, 98, 76, 61, 62 and 50 days, respectively, at the remaining temperatures. The developmental rate of E. kuehniella was described by the common linear model and six non-linear models. The lower temperature threshold for the immature stages and the thermal constant for E. kuehniella were 9°C and 1111 degree-days (DD) to complete development from egg to newly emerged adult. Non-linear models estimated the lower and upper thermal thresholds (Tmin and Tmax) and optimal temperature (Topt). The values of Tmax calculated by three nonlinear models ranged from 34°C to 46°C; Topt for each stage of development varied from 24 and 31°C, consistent with the temperature (30°C) at which the most rapid development occurred. Information on the threshold temperatures for development and thermal requirements can be utilized to predict E. kuehniella population dynamics and phenology and to evaluate optimal temperature conditions for mass rearing in stored products.
County-Level Socioeconomic Disparities in Use of Medical Services for Management of Infections by Medicare Beneficiaries With Diabetes-United States, 2012.

OBJECTIVE To assess county-level socioeconomic disparities in medical service usage for infections among Medicare beneficiaries with diabetes (MBWDs) who had fee-for-service health insurance claims during 2012. DESIGN We used Medicare claims data to calculate percentage of MBWDs with infections. SETTING Medicare beneficiaries. PARTICIPANTS We estimated the percentage of MBWDs who used medical services for each of 3 groups of infections by sex and quintiles of the prevalence of social factors in the person's county of residence: anatomic site-specific infections; pathogen-specific infections; and HHST infections (human immunodeficiency virus/acquired immunodeficiency syndrome, viral hepatitis, sexually transmitted diseases, and tuberculosis). MAIN OUTCOME MEASURES Using quintiles of county-specific socioeconomic determinants, we calculated absolute and relative disparities in each group of infections for male and female MBWDs. We also used regression-based summary measures to estimate the overall average absolute and relative disparities for each infection group. RESULTS Of the 4.5 million male MBWDs, 15.8%, 25.3%, and 2.7% had 1 or more site-specific, pathogen-specific, and HHST infections, respectively. Results were similar for females (n = 5.2 million). The percentage of MBWDs with 1 or more infections in each group increased as social disadvantage in the MBWDs' county of residence increased. Absolute and relative county-level socioeconomic disparities in receipt of medical services for 1 or more infections (site- or pathogen-specific) were 12.9 or less percentage points and 65.5% or less, respectively. For HHST infections, percentage of MBWDs having 1 or more HHST infections for persons residing in the highest quintile (Q5) was 3- to 4-fold higher (P < .001) than persons residing in the lowest quintile (Q1). CONCLUSIONS Infection burden among MBWDs is generally associated with county-level contextual socioeconomic disadvantage, and the extent of health disparities varies by infection category, socioeconomic factor, and quintiles of socioeconomic disadvantage. The findings imply ongoing need for efforts to identify effective interventions for reducing county-level social disparities in infections among patients with diabetes.
Impaired Motion Processing in Schizophrenia and the Attenuated Psychosis Syndrome: Etiological and Clinical Implications.

OBJECTIVE: The ability to perceive the motion of biological objects, such as faces, is a critical component of daily function and correlates with the ability to successfully navigate social situations (social cognition). Deficits in motion perception in schizophrenia were first demonstrated about 20 years ago but remain understudied, especially in the early, potentially prodromal, stages of the illness. The authors examined the neural bases of visual sensory processing impairments, including motion, in patients with schizophrenia (N=63) and attenuated psychosis (clinical high risk) (N=32) compared with age-matched healthy control subjects (N=67). METHOD: Electrophysiological recordings during stimulus and motion processing were analyzed using oscillatory (time frequency) approaches that differentiated motion-onset-evoked activity from stimulus-onset sensory-evoked responses. These were compared with functional MRI (fMRI) measures of motion processing. RESULTS: Significant deficits in motion processing were observed across the two patient groups, and these deficits predicted impairments in both face-emotion recognition and cognitive function. In contrast to motion processing, sensory-evoked stimulus-onset responses were intact in patients with attenuated psychosis, and, further, the relative deficit in motion-onset responses compared with stimulus-onset responses predicted transition to schizophrenia. In patients with schizophrenia, motion detection deficits mapped to impaired activation in motion-sensitive visual cortex during fMRI. Additional visual impairments in patients with schizophrenia, not present in patients with attenuated psychosis, implicated other visual regions, including the middle occipital gyrus and pulvinar thalamic nucleus. CONCLUSIONS: The study findings emphasize the importance of sensory-level visual dysfunction in the etiology of schizophrenia and in the personal experience of individuals with the disorder and demonstrate that motion-processing deficits may predate illness onset and contribute to impaired function even in patients with attenuated psychosis.
Exploring Cross-Sectional Predictors of Suicide Ideation, Attempt, and Risk in a Large Online Sample of Transgender and Gender Nonconforming Youth and Young Adults.

PURPOSE Rates of suicide ideation and attempt appear to be particularly high in the transgender and gender nonconforming (TGNC) population, yet little is known about which factors are the most salient contributors for TGNC young people and how these contributors vary across suicide-related outcomes. METHODS Within the largest sample of TGNC young people to date (N = 1896; ages 14-30), we examined the contribution of demographics (age, assigned sex, gender identity, sexual orientation identity, race/ethnicity, and socioeconomic status), minority stress (gender-related affirmation, gender-related self-concept, victimization, and gender-affirming medical treatment desire/access), social support (from family and friends), and depressive symptoms in the cross-sectional prediction of three suicide-related outcomes: past-year attempt, past-year ideation, and a composite measure of suicide risk. RESULTS Each set of factors explained significant variance in each outcome; however, only several predictors remained significant in each of the full models. Gender-related victimization and depressive symptoms were independent predictors for all three outcomes. Additional predictors varied across outcome. Age, male identity, sexual orientation-based victimization, and friend support were associated with suicide attempt. Age, queer identity, gender-related self-concept negativity, and family support were associated with suicide ideation, and pansexual identity and gender-related self-concept negativity were associated with positive suicide risk screen. CONCLUSION Prevention and intervention efforts aimed at building support and positive self-concept, decreasing victimization, and treating depression are likely to partially reduce suicide ideation and attempt in TGNC adolescents and young adults. Comprehensive interventions with younger adolescents are particularly critical.
Time Reversal as Self-Supervision

A longstanding challenge in robot learning for manipulation tasks has been the ability to generalize to varying initial conditions, diverse objects, and changing objectives. Learning based approaches have shown promise in producing robust policies, but require heavy supervision to efficiently learn precise control, especially from visual inputs. We propose a novel self-supervision technique that uses time-reversal to learn goals and provide a high level plan to reach them. In particular, we introduce the time-reversal model (TRM), a self-supervised model which explores outward from a set of goal states and learns to predict these trajectories in reverse. This provides a high level plan towards goals, allowing us to learn complex manipulation tasks with no demonstrations or exploration at test time. We test our method on the domain of assembly, specifically the mating of tetris-style block pairs. Using our method operating atop visual model predictive control, we are able to assemble tetris blocks on a physical robot using only uncalibrated RGB camera input, and generalize to unseen block pairs. sites.google. com/view/time-reversal
WNT6 is a novel oncogenic prognostic biomarker in human glioblastoma

Glioblastoma (GBM) is a universally fatal brain cancer, for which novel therapies targeting specific underlying oncogenic events are urgently needed. While the WNT pathway has been shown to be frequently activated in GBM, constituting a potential therapeutic target, the relevance of WNT6, an activator of this pathway, remains unknown. Methods: WNT6 protein and mRNA levels were evaluated in GBM. WNT6 levels were silenced or overexpressed in GBM cells to assess functional effects in vitro and in vivo. Phospho-kinase arrays and TCF/LEF reporter assays were used to identify WNT6-signaling pathways, and significant associations with stem cell features and cancer-related pathways were validated in patients. Survival analyses were performed with Cox regression and Log-rank tests. Meta-analyses were used to calculate the estimated pooled effect. Results: We show that WNT6 is significantly overexpressed in GBMs, as compared to lower-grade gliomas and normal brain, at mRNA and protein levels. Functionally, WNT6 increases typical oncogenic activities in GBM cells, including viability, proliferation, glioma stem cell capacity, invasion, migration, and resistance to temozolomide chemotherapy. Concordantly, in in vivo orthotopic GBM mice models, using both overexpressing and silencing models, WNT6 expression was associated with shorter overall survival, and increased features of tumor aggressiveness. Mechanistically, WNT6 contributes to activate typical oncogenic pathways, including Src and STAT, which intertwined with the WNT pathway may be critical effectors of WNT6-associated aggressiveness in GBM. Clinically, we establish WNT6 as an independent prognostic biomarker of shorter survival in GBM patients from several independent cohorts. Conclusion: Our findings establish WNT6 as a novel oncogene in GBM, opening opportunities to develop more rational therapies to treat this highly aggressive tumor.
Effective Clinical Teaching Behaviors Views of Nursing Students and Nurse Educators at University of Gondar, Northwest Ethiopia: Cross-Sectional Institution Based Study

Introduction: Clinical teaching behavior is a critical determinant for quality of clinical learning. Nursing students’ and instructor’s perception of effective clinical teaching behavior (ECTB) is important to modify and facilitate clinical education. Thus, the main purpose of this study was to assess the effective clinical teaching behavior (ECTB) as perceived by students and nursing instructors. Methods: Facility based cross-sectional descriptive study design was conducted among 178 participants. Data were collected using pre-tested and self-administered questionnaire. Effective clinical teaching behaviors were measured by Nursing Clinical Teacher Effectiveness Inventory. Data were analyzed using descriptive and independent sample t-test. An adjusted odds ratio with 95% confidence interval computed to determine the level of significance. Results: The most important rated ECTB as perceived by students was teaching ability. For instructors, nursing competences was the most rated ECTB. The overall mean of ECTBs of the students and instructors were 4.26 (0.52) and 3.52 (0.74) respectively. There was statistically significant mean difference between them (t = 5.888). Conclusion: There was a statistically significant mean difference between the students' and instructors’ perception of ECTBs. Thus, authors suggest nursing instructors to consider the presence of students who prefers different teaching methods.
Early Responses to Severe Drought Stress in the Arabidopsis thaliana Cell Suspension Culture Proteome

Abiotic stresses are considered the most deleterious factor affecting growth and development of plants worldwide. Such stresses are largely unavoidable and trigger adaptive responses affecting different cellular processes and target different compartments. Shotgun proteomic and mass spectrometry-based approaches offer an opportunity to elucidate the response of the proteome to abiotic stresses. In this study, the severe drought or water-deficit response in Arabidopsis thaliana was mimicked by treating cell suspension callus with 40% polyethylene glycol for 10 and 30 min. Resulting data demonstrated that 310 proteins were differentially expressed in response to this treatment with a strict ±2.0-fold change. Over-representation was observed in the gene ontology categories of ‘ribosome’ and its related functions as well as ‘oxidative phosphorylation’, indicating both structural and functional drought responses at the cellular level. Proteins in the category ‘endocytosis’ also show significant enrichment and this is consistent with increased active transport and recycling of membrane proteins in response to abiotic stress. This is supported by the particularly pronounced enrichment in proteins of the endosomal sorting complexes that are required for membrane remodelling. Taken together, the findings point to rapid and complex physiological and structural changes essential for survival in response to sudden severe drought stress.
TP and/or EP3 receptors mediate the vasoconstrictor and pressor responses of prostaglandin F2α in mice and/or humans

The vasoconstrictor and/or pressor effects of prostaglandin (PG)F2α participate in the development of vascular pathologies and limit the clinical use of the agent. This study aimed to determine the receptor types responsible for the vasoconstrictor activity of PGF2α and whether they mediate the pressor response evoked by the prostanoid under in vivo conditions. Experiments were performed on genetically altered mice and/or on vessels from these mice or humans. Here we show that deletion of the thromboxane‐prostanoid receptor (TP−/−) abolished or drastically diminished the contraction to PGF2α in isolated mouse vessels (some of which were resistance arteries) and reduced the elevation in blood pressure evoked by the prostanoid under in vivo conditions. In accordance, TP antagonism abolished the contraction in small arteries of human omentum. Further deletion of E prostanoid receptor type 3 (EP3−/−) removed the PGF2α‐evoked contraction that remained in some TP−/− arteries and added to the effect of TP−/− on the elevation in blood pressure evoked by the prostanoid under in vivo conditions. In contrast, the uterine contraction to PGF2α mediated via the F prostanoid receptor (FP) was unaltered in TP−/−/EP3−/− mice. These results demonstrate that the non‐FP receptors TP and/or EP3 mediate the vasoconstrictor and pressor effects of PGF2α, which are still of concern under clinical conditions. —Liu, B. , Li, J., Yan, H. , Tian, D. , Li, H. , Zhang, Y. , Guo, T. , Wu, X. , Luo, W. , Zhou, Y. TP and/or EP3 receptors mediate the vasoconstrictor and pressor responses of prostaglandin F2α in mice and/or humans. FASEB J. 33, 2451–2459 (2019). www.fasebj. org