Miracle-dz/UniFAR-FTUs huggingface dataset:
Methods for Handling Missing Data in the Behavioral Neurosciences: Don’t Throw the Baby Rat out with the Bath Water

Missing data are a major problem in the behavioral neurosciences, particularly when data collection is costly. Often researchers exclude cases with missing data, which can result in biased estimates and reduced power. Trying to avoid the deletion of a case because of a missing data point can be conducted, but implementing a naïve missing data method can result in distorted estimates and incorrect conclusions. New approaches for handling missing data have been developed but these techniques are not typically included in undergraduate research methods texts. The topic of missing data techniques would be useful for teaching research methods and for helping students with their research projects. This paper aimed to illustrate that estimating missing data is often more efficacious than complete case analysis, otherwise known as listwise deletion. Longitudinal data was obtained from an experiment examining the effects of an anorectic drug on food consumption in a small sample (n=17) of rats. The complete dataset was degraded by removing a percentage of datapoints (1–5%, 10%). Four missing data techniques: listwise deletion, mean substitution, regression, and expectation-maximization (EM) were applied to all six datasets to ensure that each approach was applied to the same missing data points. P-values, effect sizes, and Bayes factors were computed. Results demonstrated listwise deletion was the least effective method. EM and regression imputation were the preferred methods when more than 5% of the data were missing. Based on these findings it is recommended that researchers avoid using listwise deletion and consider alternative missing data techniques.
Alcohol-induced alterations on host defense after traumatic injury.

Alcohol abuse is a well-established risk factor for injuries of all types. Despite the impact of recent public health initiatives alcohol-related traumatic and burn injury remains a considerable health and economic burden to society, with the incidence of alcohol abuse estimated to be nearly 50% of burn and trauma admissions and as high as 70% in some populations. The prevalence of both acute and chronic alcohol abuse has been shown to be high among injured patients. However, a binge-like pattern of alcohol abuse has been particularly shown to confer the highest risk factor for injury. Overall, the evidence suggests that alcohol abuse has a detrimental impact on outcome from traumatic injury. Although a greater detrimental impact on survival has been reported for chronic alcohol users than for patients who are occasional alcohol users, the combination of chronic with acute alcohol abuse results in a significantly higher number of complications including infection, sepsis, pneumonia, and prolonged hospital stays for multiple injuries. Similar findings have been reported for pedestrian injuries and after smoke inhalation. Retrospective and prospective studies on burn victims indicate that chronic alcoholics have increased mortality, increased incidence of infectious complications, and longer length of hospital stays when compared with nonalcoholic, burn injured patients even when controlling for injury severity. Thus, although dissecting the contribution of acute versus chronic alcohol abuse to the consequences of traumatic injury in patients is not always feasible, the reports indicate that impaired outcome is not solely a function of injury severity, but rather that it may also be influenced by the victim’s preinjury alcohol consumption. Several preclinical studies have provided insight into the effects of alcohol that could impair outcome from traumatic injury in the clinical setting. Impaired sensorium, coordination, and reflexes in the acutely intoxicated patient can also contribute to the severity of injury. Hemodynamic, neuroendocrine, and metabolic counter-regulatory responses have all been shown to be impaired to various degrees after chronic or acute alcohol abuse and these, in turn, have been demonstrated to affect host recovery after a traumatic insult. Moreover, because preclinical and clinical studies have provided evidence indicating that the host defense response is central to recovery from traumatic injury, alcohol-mediated alterations in the immune response could be considered central to the deleterious outcome from traumatic injury. Hence, the increase in patient morbidity is thought to result partly from alcohol-induced dysregulation of host defense mechanisms. This review will provide an overview of the experimental and clinical evidence expounding the impact of alcohol abuse on outcome from traumatic injury, with special emphasis on its contribution to immune dysfunction and consequent morbidity and mortality.
Effect of antioxidant therapy on hospital stay and complications in patients with early acute pancreatitis: a randomised controlled trial.

BACKGROUND Oxidative stress (OS) in acute pancreatitis (AP) has been pathologically linked with the systemic inflammatory response and antioxidant supplementation may have a clinical benefit. METHODS In this prospective, randomised open label, controlled pilot study, patients admitted within 72 hours of onset of pain were randomised to receive either placebo (only standard medical treatment; SMT) or antioxidants (vitamin C 500 mg, N-acetyl cysteine 200 mg 8 hourly and antoxyl forte 1 capsule hourly with standard medical treatment; SMT + AO) daily, following informed consent. Patients with co-morbid illness and pregnancy were excluded. Primary efficacy measures were length of hospital stay and complications whilst secondary measures were biochemical markers of oxidative stress (thiobarbituric acid reactive substances [TBARS] and superoxide dismutase [SOD] and total antioxidant capacity [TAC] and vitamin C) at Days 1, 3 and 7. RESULTS Of 53 patients, 30 patients were randomised to SMT and 23 patients to SMT + AO. The mean duration of hospital stay in the SMT group (10.3 +/- 7 days) was more compared to SMT + AOT (7.2 +/- 5 days), but was not statistically significant (p=0.07), complications were similar in the 2 groups. At Day 7, OS was significantly lower in the SMT + AO group when compared with the SMT group (TBARS, p=0.05; SOD, p=0.03) with a significant increase in FRAP and vitamin C (p=0.01). CONCLUSIONS Antioxidant supplementation may decrease the length of hospital stay and complication rate in patients with AP, but a larger clinical trial is needed to support this hypothesis. Further, it decreased the OS and improved the antioxidant status in patients with AP.
A NEW BIRTH-INTERVAL APPROACH TO ESTIMATING DEMOGRAPHIC PARAMETERS OF HUMPBACK WHALES

A demographic model is developed based on interbirth intervals and is applied to estimate the population growth rate of humpback whales (Megaptera novaeangliae) in the Gulf of Maine. Fecundity rates in this model are based on the probabilities of giving birth at time t after a previous birth and on the probabilities of giving birth first at age x. Maximum likelihood methods are used to estimate these probabilities using sighting data collected for individually identified whales. Female survival rates are estimated from these same sighting data using a modified Jolly–Seber method. The youngest age at first parturition is 5 yr, the estimated mean birth interval is 2.38 yr (se = 0.10 yr), the estimated noncalf survival rate is 0.960 (se = 0.008), and the estimated calf survival rate is 0.875 (se = 0.047). The population growth rate (λ) is estimated to be 1.065; its standard error is estimated as 0.012 using a Monte Carlo approach, which simulated sampling from a hypothetical population of whales. The simulat.
Cost-of-illness analysis reveals potential healthcare savings with reductions in type 2 diabetes and cardiovascular disease following recommended intakes of dietary fiber in Canada

Background: Type 2 diabetes (T2D) and cardiovascular disease (CVD) are leading causes of mortality and two of the most costly diet-related ailments worldwide. Consumption of fiber-rich diets has been repeatedly associated with favorable impacts on these co-epidemics, however, the healthcare cost-related economic value of altered dietary fiber intakes remains poorly understood. In this study, we estimated the annual cost savings accruing to the Canadian healthcare system in association with reductions in T2D and CVD rates, separately, following increased intakes of dietary fiber by adults. Methods: A three-step cost-of-illness analysis was conducted to identify the percentage of individuals expected to consume fiber-rich diets in Canada, estimate increased fiber intakes in relation to T2D and CVD reduction rates, and independently assess the potential annual savings in healthcare costs associated with the reductions in rates of these two epidemics. The economic model employed a sensitivity analysis of four scenarios (universal, optimistic, pessimistic, and very pessimistic) to cover a range of assumptions within each step. Results: Non-trivial healthcare and related savings of CAD$35.9-$718.8 million in T2D costs and CAD$64.8 million–$1.3 billion in CVD costs were calculated under a scenario where cereal fiber was used to increase current intakes of dietary fiber to the recommended levels of 38 g per day for men and 25 g per day for women. Each 1 g per day increase in fiber consumption resulted in annual CAD$2.6 to $51.1 million savings for T2D and $4.6 to $92.1 million savings for CVD. Conclusion: Findings of this analysis shed light on the economic value of optimal dietary fiber intakes. Strategies to increase consumers’ general knowledge of the recommended intakes of dietary fiber, as part of healthy diet, and to facilitate stakeholder synergy are warranted to enable better management of healthcare and related costs associated with T2D and CVD in Canada.
Desmopressin-induced improvement in bleeding times in chronic renal failure patients correlates with platelet serotonin uptake and ATP release.

Hemostatic defects resulting in life-threatening hemorrhagic episodes are a common occurrence in the chronic renal failure patient. Hemorrhagic tendencies correlate best with laboratory tests of bleeding times. The identification of a specific hemostatic defect and its role in bleeding dyscrasias has yet to be elucidated. Our studies demonstrate that factor VIII coagulant activity and factor VIII related antigen (vWF:Ag) are normal or greatly elevated in uremic renal failure patients with greatly prolonged bleeding times. The multimeric state of the von Willebrand factor is also normal in these patients. The bleeding times were normalized in all 15 patients, 90 minutes post-infusion with desmopressin (DDAVP). No significant changes in factor VIII/vWF associated properties, blood cell counts, or coagulation factors were observed post-DDAVP treatment. However, a significant increase in platelet serotonin uptake (p less than .025) and ATP release (p less than .025) was detected after DDAVP treatment. These results indicate that DDAVP acts on the platelet membrane. This is further substantiated by the ability of DDAVP to block vasopressin-induced platelet aggregation in a dose- and time-dependent fashion. Perturbations in the movement and storage of serotonin and the release of adenosine 5'-triphosphate (ATP) in the platelets of uremic individuals are proposed to play a critical role in regulating bleeding times.
Problems of reproducibility – does geologically ancient DNA survive in amber–preserved insects?

Apparently ancient DNA has been reported from amber–preserved insects many millions of years old. Rigorous attempts to reproduce these DNA sequences from amber– and copal–preserved bees and flies have failed to detect any authentic ancient insect DNA. Lack of reproducibility suggests that DNA does not survive over millions of years even in amber, the most promising of fossil environments.
Elevated Carbon Monoxide in the Exhaled Breath of Mice during a Systemic Bacterial Infection

Blood is the specimen of choice for most laboratory tests for diagnosis and disease monitoring. Sampling exhaled breath is a noninvasive alternative to phlebotomy and has the potential for real-time monitoring at the bedside. Improved instrumentation has advanced breath analysis for several gaseous compounds from humans. However, application to small animal models of diseases and physiology has been limited. To extend breath analysis to mice, we crafted a means for collecting nose-only breath samples from groups and individual animals who were awake. Samples were subjected to gas chromatography and mass spectrometry procedures developed for highly sensitive analysis of trace volatile organic compounds (VOCs) in the atmosphere. We evaluated the system with experimental systemic infections of severe combined immunodeficiency Mus musculus with the bacterium Borrelia hermsii. Infected mice developed bacterial densities of ∼107 per ml of blood by day 4 or 5 and in comparison to uninfected controls had hepatosplenomegaly and elevations of both inflammatory and anti-inflammatory cytokines. While 12 samples from individual infected mice on days 4 and 5 and 6 samples from uninfected mice did not significantly differ for 72 different VOCs, carbon monoxide (CO) was elevated in samples from infected mice, with a mean (95% confidence limits) effect size of 4.2 (2.8–5.6), when differences in CO2 in the breath were taken into account. Normalized CO values declined to the uninfected range after one day of treatment with the antibiotic ceftriaxone. Strongly correlated with CO in the breath were levels of heme oxygenase-1 protein in serum and HMOX1 transcripts in whole blood. These results (i) provide further evidence of the informativeness of CO concentration in the exhaled breath during systemic infection and inflammation, and (ii) encourage evaluation of this noninvasive analytic approach in other various other rodent models of infection and for utility in clinical management.
Characterization and Functional Analysis of Calmodulin and Calmodulin-Like Genes in Fragaria vesca

Calcium is a universal messenger that is involved in the modulation of diverse developmental and adaptive processes in response to various stimuli. Calmodulin (CaM) and calmodulin-like (CML) proteins are major calcium sensors in all eukaryotes, and they have been extensively investigated for many years in plants and animals. However, little is known about CaMs and CMLs in woodland strawberry (Fragaria vesca). In this study, we performed a genome-wide analysis of the strawberry genome and identified 4 CaM and 36 CML genes. Bioinformatics analyses, including gene structure, phylogenetic tree, synteny and three-dimensional model assessments, revealed the conservation and divergence of FvCaMs and FvCMLs, thus providing insight regarding their functions. In addition, the transcript abundance of four FvCaM genes and the four most related FvCML genes were examined in different tissues and in response to multiple stress and hormone treatments. Moreover, we investigated the subcellular localization of several FvCaMs and FvCMLs, revealing their potential interactions based on the localizations and potential functions. Furthermore, overexpression of five FvCaM and FvCML genes could not induce a hypersensitive response, but four of the five genes could increase resistance to Agrobacterium tumefaciens in Nicotiana benthamiana leaves. This study provides evidence for the biological roles of FvCaM and CML genes, and the results lay the foundation for future functional studies of these genes.
Mechanismfrom Dendritic Cells Via an IL-10-Dependent Production 4 Expression and Leukotriene B 5-Lipoxygenase-Activating Protein Prostaglandins Inhibit

PGs produced from arachidonic acid by the action of cyclooxygenase enzymes play a pivotal role in the regulation of both inﬂammatory and immune responses. Because leukotriene B 4 (LTB 4 ), a product of 5-lipoxygenase (5-LO) pathway, can exert numerous immunoregulatory and proinﬂammatory activities, we examined the effects of PGs on LTB 4 release from dendritic cells (DC) and from peritoneal macrophages. In concentration-dependent manner, PGE 1 and PGE 2 inhibited the production of LTB 4 from DC, but not from peritoneal macrophage, with an IC 50 of 0.04 (cid:1) M. The same effect was observed with MK-886, a 5-LO-activating protein (FLAP)-speciﬁc inhibitor. The decreased release of LTB 4 was associated with an enhanced level of IL-10. Furthermore, the inhibition of LTB 4 synthesis by PGs was signiﬁcantly reversed by anti-IL-10, suggesting the involvement of an IL-10-dependent mechanism. Hence, we examined the effects of exogenous IL-10 on the 5-LO pathway. We demonstrate that IL-10 suppresses the production of LTB 4 from DC by inhibiting FLAP protein expression without any effect on 5-LO and cytosolic phospholipase A 2 . Taken together, our results suggest links between DC cyclooxygenase and 5-LO pathways during the inﬂammatory response, and FLAP is a key target for the PG-induced IL-10-suppressive effects. The Journal of Immunology, 2002, 169: 139–146. PGE 2 . The effects of PGE 2 on LT production from exogenous substrate were analyzed in DC stimulated with calcium ionophore in the presence of 1 (cid:1) M of exogenous PGE 2 . Exogenous AA was added to cell culture for 30 min after 18 h of incubation. We also examined the concentration-depen-dent effect of MK-886, a FLAP-speciﬁc inhibitor (Biomol Research Lab- oratories, Plymouth Meeting, PA), and nor-dihydroguaiaretic acid (NDGA), a 5-LO inhibitor (Sigma-Aldrich), on the production of PGE 2 and LTB 4 from endogenous AA. The various prostanoids and drugs used did not affect the number of viable cells quantiﬁed by MTT essay. Cell-free supernatants were harvested, and commercial ELISA kits (Cayman) mea- sured eicosanoid production. The detection limits for PGE 2 and LTB 4 are 15 and 4 pg/ml, respectively.
The x-ray spectrum of the rapid burster using the Chandra HETGS

We present observations of the Rapid Burster (RB, also known as MXB 1730-335) using the Chandra High Energy Transmission Grating Spectrometer. The average interval between type II (accretion) bursts was about 40 s. There was one type I (thermonuclear flash) burst and about 20 "mini-bursts" which are probably type II bursts whose peak flux is 10-40% of the average peak flux of the other type II bursts. The time averaged spectra of the type II bursts are well fit by a blackbody with a temperature of kT = 1.6 keV, a radius of 8.9 km for a distance of 8.6 kpc, and an interstellar column density of 1.7e22 per sq. cm. No narrow emission or absorption lines were clearly detected. The 3 sigma upper limits to the equivalent widths of any features are < 10 eV in the 1.1-7.0 keV band and as small as 1.5 eV near 1.7 keV. We suggest that Comptonization destroys absorption features such as the resonance line of Fe XXVI.
Metronomic chemotherapy: changing the paradigm that more is better

The introduction of the “maximum tolerated dose” in usual treatment protocols (and its concomitant overt toxicity) made necessary the imposition of rest periods between cycles of therapy—a practice that not only involves re-growth of tumour cells, but also growth of selected clones resistant to the therapy. To avoid the problems caused by traditional chemotherapeutic regimens, a new modality of drug administration called “metronomic chemotherapy” has been proposed. This name makes reference to the chronic, equally spaced administration of (generally) low doses of various chemotherapeutic drugs without extended rest periods. The novelty of this treatment modality lies not only in its antitumour efficacy with very low toxicity, but also in a cell target switch, now aiming at tumour endothelial cells. The knowledge acquired in the experimental field of metronomic chemotherapy, plus the increasing experience that is being obtained in the clinical setting, will help to lead a change in the design of therapeutic protocols against cancer.
Leading Edge Review Molecular Mechanisms Underlying Bacterial Persisters

All bacteria form persisters, cells that are multidrug tolerant and therefore able to survive antibiotic treatment. Due to the low frequencies of persisters in growing bacterial cultures and the complex underlying molecular mechanisms, the phenomenon has been challenging to study. However, recent technological advances in microfluidics and reporter genes have improved this scenario. Here, we summarize recent progress in the field, revealing the ubiquitous bacterial stress alarmone ppGpp as an emerging central regulator of multidrug tolerance and persistence, both in stochastically and environmentally induced persistence. In several different organisms, toxin-antitoxin modules function as effectors of ppGpp-induced persistence.
Leptin Enhances the Calcification of Vascular Cells: Artery Wall as a Target of Leptin

Abstract— Leptin, the product of the ob gene, regulates food intake, energy expenditure, and other physiological functions of the peripheral tissues. Leptin receptors have been identified in the hypothalamus and in extrahypothalamic tissues. Increased circulating leptin levels have been correlated with cardiovascular disease, obesity, aging, infection with bacterial lipopolysaccharide, and high-fat diets. All these conditions have also been correlated with increased vascular calcification, a hallmark of atherosclerotic and age-related vascular disease. In addition, the differentiation of marrow osteoprogenitor cells is regulated by leptin. Thus, we hypothesized that leptin may regulate the calcification of vascular cells. In this report, we tested the effects of leptin on a previously characterized subpopulation of vascular cells that undergo osteoblastic differentiation and calcification in vitro. When treated with leptin, these calcifying vascular cells had a significant 5- to 10-fold increase in alkaline phosphatase activity, a marker of osteogenic differentiation of osteoblastic cells. Prolonged treatment with leptin enhanced the calcification of these cells, further supporting the pro-osteogenic differentiation effects of leptin. Furthermore, the presence of the leptin receptor on calcifying vascular cells was demonstrated using reverse transcriptase polymerase chain reaction, immunocytochemistry, and Western blot analysis. We also identified the presence of leptin receptor in the mouse artery wall, localized to subpopulations of medial and adventitial cells, and the expression of leptin by artery wall cells and atherosclerotic lesions in mice. Taken together, these results suggest that leptin regulates the osteoblastic differentiation and calcification of vascular cells and that the artery wall may be an important peripheral tissue target of leptin action.
Cellular and humoral immune response in progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a fatal, demyelinating disease caused by JC virus (JCV) in patients with severe immunosuppression. We studied the JCV‐specific cellular and humoral immune response in 7 healthy donors (HD), 6 human immunodeficiency virus‐1 (HIV‐1)‐infected patients without PML (HIV), 4 HIV‐1‐negative patients with PML (PML), and 8 HIV‐1‐positive patients with PML (HIV/PML). As antigens, recombinant virus‐like particles of the major structural protein VP1 (VP1‐VLP) of JCV, tetanus toxoid (TT), or the mitogen phytohemagglutinin (PHA) were used. Proliferation of peripheral blood mononuclear cells (PBMC) after stimulation with the VP1‐VLP was significantly suppressed in PML and HIV/PML patients compared to HD. After antigen stimulation the production of interferon‐γ (IFN‐γ) was reduced in PML, in HIV/PML, and in HIV patients. The production of interleukin‐10 (IL‐10), however, was elevated in HIV/PML patients. Neither proliferation nor cytokine production correlated with the presence of JCV DNA in PBMC. The immunoglobulin G serum antibody titer to the VP1‐VLP was slightly elevated in HIV, elevated in PML, and highly elevated in HIV/PML patients compared to HD. The development of PML appears to coincide with a general impairment of the Th1‐type T‐helper cell function of cell‐mediated immunity.