Miracle-dz/UniFAR-FTUs huggingface dataset:
Wnt5a modulates dendritic spine dynamics through the regulation of Cofilin via small Rho GTPase activity in hippocampal neurons

Dendritic spines are small, actin‐rich protrusions that act as the receiving sites of most excitatory inputs in the central nervous system. The remodeling of the synapse architecture is mediated by actin cytoskeleton dynamics, a process precisely regulated by the small Rho GTPase family. Wnt ligands exert their presynaptic and postsynaptic effects during formation and consolidation of the synaptic structure. Specifically, Wnt5a has been identified as an indispensable synaptogenic factor for the regulation and organization of the postsynaptic side; however, the molecular mechanisms through which Wnt5a induces morphological changes resulting from actin cytoskeleton dynamics within dendritic spines remain unclear. In this work, we employ primary rat hippocampal cultures and HT22 murine hippocampal neuronal cell models, molecular and pharmacological tools, and fluorescence microscopy (laser confocal and epifluorescence) to define the Wnt5a‐induced molecular signaling involved in postsynaptic remodeling mediated via the regulation of the small Rho GTPase family. We report that Wnt5a differentially regulates the phosphorylation of Cofilin in neurons through both Ras‐related C3 botulinum toxin substrate 1 and cell division cycle 42 depending on the subcellular compartment and the extracellular calcium levels. Additionally, we demonstrate that Wnt5a increases the density of dendritic spines and promotes their maturation via Ras‐related C3 botulinum toxin substrate 1. Accordingly, we find that Wnt5a requires the combined activation of small Rho GTPases to increase the levels of filamentous actin, thus promoting the stability of actin filaments. Altogether, these results provide evidence for a new mechanism by which Wnt5a may target actin dynamics, thereby regulating the subsequent morphological changes in dendritic spine architecture.
Characterization of Psychotropic PRN Medications in a Canadian Psychiatric Intensive Care Unit

BACKGROUND: Pro re nata (PRN) antipsychotics and benzodiazepines are routinely used for the rapid stabilization of acutely agitated patients. Despite the popular use of PRN medications in mental health units, primary literature supporting efficacy and safety is poor, and there is no single universally accepted practice guideline. PRN psychotropic medications have the potential to cause adverse effects when used inappropriately. AIMS: Our objective was to characterize the prescribing, administration, and documentation practices of PRN psychotropic medications in a psychiatric intensive care unit. METHODS: We conducted a retrospective chart review of patients admitted to a 12-bed psychiatric intensive care unit between June and September 2018. All PRN antipsychotic and benzodiazepine orders, administrations, documentation practices, and attempted nonpharmacological strategies were assessed for each order and patient. Descriptive statistics were used to analyze data. RESULTS: Thirty-two patients with a total of 123 physicians’ orders and 1,179 PRN administrations of antipsychotics and benzodiazepines were reviewed. Of the total administrations, 720 (61%) were combinations with at least two psychotropic agents. Forty-one (33%) physicians’ orders had a prescribed indication, and 559 (47%) administrations had an attempted nonpharmacological method prior to PRN administration. Eight patients (25%) had antipsychotic PRN orders, which exceeded the total daily maximum dose. Three adverse drug effects were attributed to PRN administration. CONCLUSIONS: Areas of improvement that we identified included documentation practices of effectiveness of administered PRNs, prescriptions to include clear indications and dosage within the 24-hour maximum limits, and documentation of nonpharmacological methods utilized.
Computational modeling of tau pathology spread reveals patterns of regional vulnerability and the impact of a genetic risk factor

Spread of tau pathology follows brain connectivity, is modulated by selective vulnerability, and is predicted by network analysis. Neuropathological staging studies have suggested that tau pathology spreads through the brain in Alzheimer’s disease (AD) and other tauopathies, but it is unclear how neuroanatomical connections, spatial proximity, and regional vulnerability contribute. In this study, we seed tau pathology in the brains of nontransgenic mice with AD tau and quantify pathology development over 9 months in 134 brain regions. Network modeling of pathology progression shows that diffusion through the connectome is the best predictor of tau pathology patterns. Further, deviations from pure neuroanatomical spread are used to estimate regional vulnerability to tau pathology and identify related gene expression patterns. Last, we show that pathology spread is altered in mice harboring a mutation in leucine-rich repeat kinase 2. While tau pathology spread is still constrained by anatomical connectivity in these mice, it spreads preferentially in a retrograde direction. This study provides a framework for understanding neuropathological progression in tauopathies.
Second-Line Tests in the Diagnosis of Adrenocorticotropic Hormone-Dependent Hypercortisolism

Cushing’s syndrome (CS) is a rare disease caused by chronic and excessive cortisol secretion. When adrenocorticotropin hormone (ACTH) is measurable, autonomous adrenal cortisol secretion could be reasonably ruled out in a differential diagnosis of CS. ACTH-dependent CS accounts for 80%–85% of cases and involves cortisol production stimulated by uncontrolled pituitary or ectopic ACTH secretion. Pituitary adenoma is not detected in up to one-third of cases with pituitary ACTH secretion, whereas cases of CS due to ectopic ACTH secretion may be associated with either malignant neoplasia (such as small cell lung carcinoma) or less aggressive neuroendocrine tumors, exhibiting only the typical symptoms and signs of CS. Since the differential diagnosis of ACTH-dependent CS may be a challenge, many strategies have been proposed. Since none of the available tests show 100% diagnostic accuracy, a step-by-step approach combining several diagnostic tools and a multidisciplinary evaluation in a referral center is suggested. In this review, we present a clinical case to demonstrate the diagnostic work-up of ACTH-dependent CS. We describe the most commonly used dynamic tests, as well as the applications of conventional or nuclear imaging and invasive procedures.
Environmental effects on soil NO concentrations and root N uptake in beech and spruce forests

This study aimed to investigate the shifts in net nitrogen (N) uptake and N compounds of fine roots over the vegetation period (i.e., spring, summer, autumn) and correlate this with NO concentration in the soil. Soil NO concentration was measured using gas lysimeters for collection and a chemiluminescence analyzer for quantification. Net N uptake by the roots was determined using the 15N enrichment technique. N pools were quantified using spectrophotometric techniques. Soil NO concentrations at beech and spruce forest sites were highest in spring (June), and lowest in winter (December). Total N of the roots was similar during the seasons and between the two years under study despite considerable variation of different N compounds. Net N uptake generally increased with higher N supply. Correlation analysis revealed a positive relationship between soil NO concentration and net N uptake only for spruce trees. This relationship seemed to be modulated by environmental factors and tree species.
Residue analysis of fungicide boscalid in cucumbers following applications of boscalid 50% water dispersible granule

This study determined the residue of fungicide boscalid in/on cucumbers following three applications of boscalid 50% water dispersible granule (WG). The fungicide was applied to cucumbers at two rates, 0.5 and 0.83 kg a.i./ha. Samples were collected at 0, 1, 2, 3, 4, 6, 7, 10, 12, 15, 18, and 21 d after the last application. The sample was extracted with methanol/H2O/2 N HCl (70:25:5, v/v) and n-hexane and subject to GC analysis. Residues of boscalid were determined by GC/μ-ECD with DB-5 capillary column. Recoveries of boscalid in/on cucumbers ranged from 86.0 to 103.6% and the relative standard deviation (RSD) ranged from 1.2 to 4.8%. The limit of quantification was 0.01 μg/mL (S/N＞10). This analytical method was applied to study the dissipation of boscalid in/on cucumbers. The results indicated that the residues of boscalid were declined in/on cucumbers with time. Only 5 and 17% of the initial deposits were found in/on the cucumbers 6 d after the last application at the low and high dose, respectively.
Alterations in arterial CO2 rather than pH affect the kinetics of neurovascular coupling in humans

We investigated the influence of arterial PCO2 ( PaCO2 ) with and without acute experimental metabolic alkalosis on neurovascular coupling (NVC). We assessed stepwise iso‐oxic alterations in PaCO2 prior to and following intravenous NaHCO3 to acutely elevate arterial pH and [HCO3–]. The NVC response was not altered following NaHCO3 between stepwise PaCO2 stages; therefore, NVC is acutely mediated by PaCO2 rather than the prevailing arterial [H+]/pH. The NVC response was attenuated by 27–38% with −10 mmHg PaCO2 and the absolute peak change was reduced by −19% with +10 mmHg PaCO2 irrespective of acutely elevated arterial pH/[HCO3–]. The NVC kinetics (i.e. time to peak) were markedly slower with hypercapnia versus hypocapnia (24 ± 5 vs. 7 ± 5 s, respectively) likely indicating an influence of resting cerebrovascular tone on NVC responsiveness.
When the Action to Be Performed at the Stage of Retrieval Enacts Memory of Action Verbs

Abstract. According to the embodied approach of language, concepts are grounded in sensorimotor mental states, and when we process language, the brain simulates some of the perceptions and actions that are involved when interacting with real objects. Moreover, several studies have highlighted that cognitive performances are dependent on the overlap between the motor action simulated and the motor action required by the task. On the other hand, in the field of memory, the role of action is under debate. The aim of this work was to show that performing an action at the stage of retrieval influences memory performance in a recognition task (experiment 1) and a cued recall task (experiment 2), even if the participants were never instructed to consider the implied action. The results highlighted an action-based memory effect at the retrieval stage. These findings contribute to the debate about the implication of motor system in action verb processing and its role for memory.
Advances in Myocardial Perfusion MR Imaging: Physiological Implications, the Importance of Quantitative Analysis, and Impact on Patient Care in Coronary Artery Disease

Stress myocardial perfusion imaging (MPI) is the preferred test in patients with intermediate-to-high clinical likelihood of coronary artery disease (CAD) and can be used as a gatekeeper to avoid unnecessary revascularization. Cardiac magnetic resonance (CMR) has a number of favorable characteristics, including: (1) high spatial resolution that can delineate subendocardial ischemia; (2) comprehensive assessment of morphology, global and regional cardiac functions, tissue characterization, and coronary artery stenosis; and (3) no radiation exposure to patients. According to meta-analysis studies, the diagnostic accuracy of perfusion CMR is comparable to positron emission tomography (PET) and perfusion CT, and is better than single-photon emission CT (SPECT) when fractional flow reserve (FFR) is used as a reference standard. In addition, stress CMR has an excellent prognostic value. One meta-analysis study demonstrated the annual event rate of cardiovascular death or non-fatal myocardial infarction was 4.9% and 0.8%, respectively, in patients with positive and negative stress CMR. Quantitative assessment of perfusion CMR not only allows the objective evaluation of regional ischemia but also provides insights into the pathophysiology of microvascular disease and diffuse subclinical atherosclerosis. For accurate quantification of myocardial perfusion, saturation correction of arterial input function is important. There are two major approaches for saturation correction, one is a dual-bolus method and the other is a dual-sequence method. Absolute quantitative mapping with myocardial perfusion CMR has good accuracy in detecting coronary microvascular dysfunction. Flow measurement in the coronary sinus (CS) with phase contrast cine CMR is an alternative approach to quantify global coronary flow reserve (CFR). The measurement of global CFR by quantitative analysis of perfusion CMR or flow measurement in the CS permits assessment of microvascular disease and diffuse subclinical atherosclerosis, which may provide improved prediction of future event risk in patients with suspected or known CAD. Multi-institutional studies to validate the diagnostic and prognostic values of quantitative perfusion CMR approaches are required.
Clinical Features of de novo Pure 16q21q24.1 Chromosome Duplication

Pure partial duplications of the long arm of chromosome 16 are rare and few cases are described with delineation by chromosomal microarray. Data about clinical abnormalities of pure partial 16q duplications are incomplete because many individuals die during the perinatal period. We describe the clinical features of a 47-month-old Brazilian girl with 16q21q24.1 duplication. To the best of our knowledge, she is the first person with this specific chromosome segment duplication, and we compare her phenotype with the only reported individual alive with intermediate–distal pure 16q duplication.
Is SF-12 a valid and reliable measurement of health-related quality of life among adults with Marfan syndrome? A confirmatory study

Introduction The structural validity and reliability of the Short-Form Health Survey 12 (SF-12) has not yet been tested in adults with the Marfan syndrome (MFS). This gap could undermine an evidence-grounded practice and research, especially considering that the need to assess health-related quality of life in patients with MFS has increased due to the improved life expectancy of these patients and the need to identify their determinants of quality of life. For this reason, this study aimed to confirm the dimensionality (structural validity) of the SF-12, its concurrent validity, and its reliability (internal consistency). Methods We performed a cross-sectional study in a convenience sample of 111 Italian adults with MFS, collecting anamnestic and socio-demographic information, the SF-12, and short-form Health Survey 36 (SF-36). A confirmatory factor analysis was performed to verify whether the items of SF-12 related to physical restrictions, physical functioning, and bodily pain were retained by the physical summary component of the SF-12. The items referred to the role limitations due to emotional issues, social functioning, and mental health were retained by the mental summary component (MCS12). SF-36 was used to assess the concurrent validity of SF-12, hypothesizing positive correlations among the equivalent summary scores. Results The two-factor structural solution resulted in fitting the sample statistics adequately. The internal consistency was adequate for the two factors. Furthermore, the physical and mental summary scores of the SF-36 were positively correlated with their equivalent summary scores derived from the SF-12. Conclusions This study confirmed the factor structure of the SF-12. Therefore, the use of SF-12 in clinical practice and research for assessing the health-related quality of life among adults with MFS is evidence-grounded. Future research is recommended to determine whether the SF-12 shows measurement invariance in different national contexts and determine eventual demographic variation in the SF-12 scores among patients with MFS.
The Effect of Perioperative Blood Transfusion on Long-Term Survival Outcomes After Surgery for Pancreatic Ductal Adenocarcinoma

Supplemental digital content is available in the text. Objective To evaluate survival outcomes associated with perioperative allogeneic red blood cell transfusion (RBCT) in patients with pancreatic ductal adenocarcinoma undergoing surgery. Methods PubMed, Embase, Cochrane, and Web of Science Core Collection were queried for English-language articles until May 28, 2020. Studies evaluating long-term outcomes of RBCT compared with no transfusion in adults with pancreatic ductal adenocarcinoma undergoing pancreatectomy were included. E-value sensitivity analysis assessed the potential for unmeasured confounders to overcome these findings. Results Of 4379 citations, 5 retrospective cohort studies were included. Three studies reported shorter recurrence-free survival by 1 to 5 months with RBCT. Two studies found shorter disease-specific survival by 5 to 13 months with RBCT. Overall survival was reduced by 5 to 7 months with RBCT in 3 studies. All multivariable findings associated with RBCT could be readily overcome unmeasured confounding on sensitivity analysis. Confounding in baseline characteristics resulted in high risk of bias. Conclusions Imprecision, unmeasured confounding, small effect sizes, and overall low quality of the available literature result in uncertainty regarding the effect of transfusion on recurrence-free survival, disease-specific survival, and overall survival in patients undergoing surgery for pancreatic cancer. Randomized trials are needed to determine if there is a causal relationship between transfusion and survival after pancreatic resection.
L-asparaginase from Aspergillus oryzae spp.: effects of production process and biochemical parameters

Abstract L-asparaginases prevent the formation of acrylamide, a substance commonly found in foods subjected to heat and that also contains reducing sugars and L-asparagine. This work aimed to select a strain of Aspergillus spp. able to produce L-asparaginase and to optimize the fermentation parameters, the partial purification and biochemical characterization were also performed. The Aspergillus oryzae IOC 3999 was selected due to its greater enzymatic activity: 1443.57 U/mL of L-asparaginase after 48 h of fermentation. The optimized conditions allowed for an increase of 223% on the L-asparaginase production: 2.9% lactose, 2.9% L-asparagine and 0.7% hydrolyzed casein, 0.152% KH2PO4, 0.052% KCl and MgSO4, 0.001% of CuNO3.3H2O, ZnSO4.7H2O and FeSO4.7H2O adjusted to pH 7.0; added a concentration of 5.05x106 spores/mL at 30 °C for 100 rpm. A purification factor of 2.11 was found and the molecular mass was estimated at 20.8 kDa. The enzyme showed optimum activity at 60 °C and pH 5 and stability at 50 °C for 1 h. The enzyme presented desirable biochemical characteristics, mainly the acid pH stability, indicating that the enzyme would work well in food matrices due to the closeness of pH, meaning that it could be a potential option for use in the food industry.
One-Time Spinners and Spin-Thrill Seekers in Sex Offenses against Minors: Is Situational Prevention Possible?

ABSTRACT This qualitative study examines (1) the circumstances under which “normative” individuals with no prior sexual attraction to children commit a sex offense against a minor with whom they had several times interacted during routine activities and (2) Their perception of situational deterrence exercised by adults present/nearby. The sample included eight of 14 offenders incarcerated in a prison rehabilitation unit (N = 20) for a sex offense against a minor. Content analysis of in-depth interviews indicated two types of offenders: The one-time spinners and the spin-thrill seekers both reported an unpremeditated sexual spin triggered by the victim. One-time spinners reported being caught in a one time sexual spin that took control of their conscious mind when interacting with the child in the presence of family members. The spin-thrill seekers reported several sexual spin-thrilling episodes during a sport/educational activity with an adolescent when adults were nearby. The first unpremeditated spin episode had motivated them to initiate additional thrilling episodes of increasing intensity that led to the offense. Out of the spin, one-time spinners expressed regret and concern for the victim; spin-thrill seekers expressed neither. Supervision and vigilance of adults usually present/nearby are recommended to prevent or stop many of these “accidental” sexual spinners from completing their crime.
Discursive Constructions of Domestic Violence Among Iranian Instagram Users

Domestic violence (DV) is a widespread social phenomenon, adversely impacting public mental and physical health. The abatement of such issue necessitates a priori social awareness and a posteriori social support. With that in mind, the present study aimed at disclosing dominant discursive constructions of DV among Iranian Instagram users. Driven by Fairclough’s (1992) notion of “moments of crisis,” critical discourse analysis was employed as the theoretical framework to elucidate the results obtained from 1,028 comments on nine DV-related posts. Our primary objective was to uncover Iranian Instagram commentators’ perception of the causes and consequences of DV as well as the perpetrator and victim’s roles through probing into the embedded social values and assumptions underpinning such discursive constructions represented within comments. Meticulous inspection of the data yielded six major themes, namely, (a) blaming the responsible, (b) offering solutions to the victims, (c) portraying the male perpetrators, (d) overgeneralizing the transgression, (e) disregarding men’s rights, and (f) portraying the female perpetrators. The results indicated that female and male commentators held dissimilar perspectives with regard to DV and that though the conceptualizations of DV were not destitute of prejudice, both perpetrators and victims were encouraged to take requisite steps to minimize the adverse impact of DV on their families and relations as well as on social and public health. The discursive themes identified in the current work may serve as the stepping stone toward the mitigation of DV within society.
Serum MMP‐3 and its association with central arterial stiffness among young adults is moderated by smoking and BMI

Central arterial stiffness is an independent predictor of cardiovascular disease. It is characterized by a marked reduction in the elastin‐collagen ratio of the arterial wall extracellular matrix (ECM), and is largely the result of degradation of various ECM components. Matrix metalloproteinase‐3 (MMP‐3) may contribute to central arterial stiffness via its involvement in ECM homeostasis and remodeling. This study examined the association between serum MMP‐3 concentrations and central arterial stiffness and potential interactions of MMP‐3 and traditional cardiovascular risk factors in a population of healthy young adults. A total of 206 participants (n = 109 females) aged 19–25 years were included in the current study. Central arterial stiffness was measured non‐invasively as carotid‐femoral pulse wave velocity (cfPWV) (m/s). MMP‐3 concentrations (ng/ml) were measured using ELISA techniques. Regression analyses were used to examine the association between cfPWV and MMP‐3, adjusting for age, sex, smoking status, body mass index (BMI), instantaneous mean arterial pressure (MAP) and heart rate, and serum C‐reactive protein. Interactions between MMP‐3 with smoking, BMI, sex, and MAP were analyzed in subsequent regression models. MMP‐3 was an independent predictor of cfPWV (β = 0.187, p = 0.007), and significant interactions between MMP‐3 and regular smoking (β = 0.291, p = 0.022), and MMP‐3 and BMI (β = 0.210, p = 0.013) were observed. Higher serum MMP‐3 concentrations were associated with a faster cfPWV and thus, greater central arterial stiffness. Interactions between MMP‐3 and smoking, and MMP‐3 and BMI may, in part, drive the association between MMP‐3 and central arterial stiffness.