Miracle-dz/UniFAR-FTUs huggingface dataset:
A Test of Lindesmith's Theory of Addiction: The Frequency of Euphoria Among Long-Term Addicts

Lindesmith and others claim that once physical dependence is established addicts do not experience euphoria. Consequently, euphoria cannot explain chronic addiction. Data are presented to show that, contrary to this view, long-term addicts experience euphoria frequently, crave it, and act to obtain it. "Lack of money" is the most important reason addicts give for not experiencing euphoria more often. Based on success in achieving euphoria, two classes of addicts are identified. The sources of income of addicts who experience euphoria most often correspond to those of types described by others as highest in prestige. Analysis suggests an addict stratification system founded on the two major psychopharmacological phenomena of opiates: withdrawal and euphoria. Addicts who barely succeed at tending to their daily need to avoid withdrawal are lowest in prestige. In the higher prestige ranges, addicts are stratified by their success in achieving euphoria. Thus, the social as well as the value system of addicts owes much to success at achieving what are universally considered, at the individual level, to be the most fundamental reinforcers. Since these reinforcers operate at the individual level, our analysis reveals the addict social system as a microcosm of broader theoretical interest, with transitions between physiological, psychological, cultural, economic, and sociological phenomena in plain view.
Evaluation of Health-Related Quality of Life among Tuberculosis Patients in Two Cities in Yemen

Background The health-related quality of life (HRQoL) of Tuberculosis (TB) patients is important because it directly influences the outcome of TB patients in several aspects. The current study aims to evaluate and to find the factors influencing the HRQoL of TB patients in two major TB-prevalent cities (Taiz and Alhodidah) in Yemen. Methods A prospective study was conducted, and all TB patients meeting the HRQoL criteria were asked to complete the HRQoL SF-36 survey. The records of TB patients were examined for disease confirmation, and a follow-up was consequently performed for patients during treatment between March 2013 and February 2014 in Taiz and Alhodidah Cities. HRQol scores were calculated by using QM scoring software version 4.5, in which the physical component score (PCS) and mental component score (MCS) were obtained. The scores obtained between 47–53 normal based score (NBS) were considered equivalent to the US normal score. Low scores indicate the poor health situation of TB patients Results A total of 243 TB patients enrolled in the study at the beginning of the treatment. A total of 235 and 197 TB patients completed the questionnaire at the end of the intensive phase (I.P.) and continuation phase (C.P.), respectively. The final dropout rate was 16.2%. The mean PCS and MCS scores at the beginning of treatment were low, thus showing the poor health situation of TB patients. The mean PCS scores at the beginning of treatment, end of I.P., and end of treatment were (36.1), (44.9), and (48), respectively. Moreover, the mean MCS score at the beginning of treatment, end of I.P., and end of treatment were (35.1), (42.2), and (44.3), respectively. The result shows that significant increases are observed at the end of I.P. for PCS and MCS because of the treatment and slight changes at the end of C.P. Despite this finding, the MCS score remains below the normal range (47), thus indicating a significant risk of depression among TB patients. Furthermore, general linear repeated measure ANOVA was performed for selected variables, to examine the changes of PCS and MCS over time. It was found that Alhodiah city, chewing khat habit, stigmatization, and duration of treatment more than six months were greatly associated with low mean MCS score of TB patient, indicating great risk of depression which may result in poor treatment outcome. Conclusion TB patients in Yemen were found to have poor QoL, with a significant likelihood of depression. Highly risk depression was found among TB patients in Alhodiah city, khat chewers, stigmatization and having a duration of treatment more than 6 months. Therefore, additional efforts should be made to improve their QoL because it may affect the final clinical outcome of patients.
Functional Differences between Human NKp44− and NKp44+ RORC+ Innate Lymphoid Cells

Human RORC+ lymphoid tissue inducer cells are part of a rapidly expanding family of innate lymphoid cells (ILC) that participate in innate and adaptive immune responses as well as in lymphoid tissue (re) modeling. The assessment of a potential role for innate lymphocyte-derived cytokines in human homeostasis and disease is hampered by a poor characterization of RORC+ innate cell subsets and a lack of knowledge on the distribution of these cells in adults. Here we show that functionally distinct subsets of human RORC+ innate lymphoid cells are enriched for secretion of IL-17a or IL-22. Both subsets have an activated phenotype and can be distinguished based on the presence or absence of the natural cytotoxicity receptor NKp44. NKp44+ IL-22 producing cells are present in tonsils while NKp44− IL-17a producing cells are present in fetal developing lymph nodes. Development of human intestinal NKp44+ ILC is a programmed event that is independent of bacterial colonization and these cells colonize the fetal intestine during the first trimester. In the adult intestine, NKp44+ ILC are the main ILC subset producing IL-22. NKp44− ILC remain present throughout adulthood in peripheral non-inflamed lymph nodes as resting, non-cytokine producing cells. However, upon stimulation lymph node ILC can swiftly initiate cytokine transcription suggesting that secondary human lymphoid organs may function as a reservoir for innate lymphoid cells capable of participating in inflammatory responses.
Ethnobotanical Study on Medicinal Plants Used by Local Communities in Debark Wereda, North Gondar Zone, Amhara Regional State, Ethiopia

An ethnobotanical study of the knowledge on use and management of medicinal plants by local people in Debark Wereda, North Gondar (Ethiopia), was conducted from October 2010 to May 2011. Semi-structured interviews, field observations and various ranking and comparison methods were employed and information was collected from a sample of 84 informants (36 females and 48 males). These included 24 key and 60 randomly selected informants. A total of 126 plant species, representing 114 genera and 57 families, were collected, and 122 of them were claimed to be traditional medicinal plants. The Asteraceae, which contributed 12 (9.52%) species, stood first followed by Fabaceae, Solanaceae and Euphorbiaceae with 11, 9 and 7 species respectively Most of the species (72) were collected from the wild while 50 were collected from homegardens. A total of 88 (76.03%) species were mentioned for the treatment of 62 human ailments while 10 species were used to treat 20 livestock health problems. Herbs were the most used plants, accounting for 60 (49.58%) species, followed by shrubs, trees and climbers. The most frequently used plant part was the leaves (50.27%) and fresh plant materials (54.39%). The common route medicine administration were oral (45.99%), followed by dermal and nasal. Some of the remedies are taken with additives and solvents including water (33.76), butter (16.88%) and honey (15.58%). The most widely used method of preparation was squeezing (33.33%) of the different plant parts followed by crushing (25%). The most commonly used application of medicinal plant was drinking (31.22%) followed by creamed (19.45%) and dropping (12.21%). Medicinal plants with higher informant consensus included Zehneria scabra, Verbascum sinaiticum and Rumex nepalensis while the disease category with the highest ICF value (0.870) was fibril illness. There was high preference for Plantogo lanceolata for treating wound while paired comparison showed Zehneria scabra to be the most preferred species for treatment of fibril illness by traditional healers. Cordia africana was shown to be the top multipurpose species while agricultural expansion, firewood collection and charcoal making were considered major threats to plants in general and medicinal plants in particular. Provisions for participation of the local people, awareness raising and establishment of protected forests need encouraging.
Predator-induced macroevolutionary trends in Mesozoic crinoids

Sea urchins are a major component of recent marine communities where they exert a key role as grazers and benthic predators. However, their impact on past marine organisms, such as crinoids, is hard to infer in the fossil record. Analysis of bite mark frequencies on crinoid columnals and comprehensive genus-level diversity data provide unique insights into the importance of sea urchin predation through geologic time. These data show that over the Mesozoic, predation intensity on crinoids, as measured by bite mark frequencies on columnals, changed in step with diversity of sea urchins. Moreover, Mesozoic diversity changes in the predatory sea urchins show a positive correlation with diversity of motile crinoids and a negative correlation with diversity of sessile crinoids, consistent with a crinoid motility representing an effective escape strategy. We contend that the Mesozoic diversity history of crinoids likely represents a macroevolutionary response to changes in sea urchin predation pressure and that it may have set the stage for the recent pattern of crinoid diversity in which motile forms greatly predominate and sessile forms are restricted to deep-water refugia.
Involvement of the insular cortex in regulating glucocorticoid effects on memory consolidation of inhibitory avoidance training

Glucocorticoids are known to enhance the consolidation of memory of emotionally arousing experiences by acting upon a network of interconnected brain regions. Although animal studies typically do not consider the insular cortex (IC) to be part of this network, the present findings indicate that the IC is importantly involved in regulating glucocorticoid effects on memory consolidation of emotionally arousing inhibitory avoidance training. The specific glucocorticoid receptor (GR) agonist RU 28362 (3 or 10 ng in 0.5 μl) infused bilaterally into the IC of male Sprague–Dawley rats immediately after one-trial inhibitory avoidance training dose-dependently enhanced 48 h retention performance. Moreover, training on the inhibitory avoidance task increased neuronal activity of the IC, as assessed by an increased number of cells expressing immunoreactivity for phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2). However, systemic administration of a memory-enhancing dose of corticosterone (1 mg/kg) after inhibitory avoidance training rapidly reduced the number of pERK1/2-positive cells in the IC, suggesting that glucocorticoid administration reduces overall neuronal activity of the IC. To investigate which components of the inhibitory avoidance training experience were influenced by the intra-IC glucocorticoid administration, in the last experiment rats were trained on a modified inhibitory avoidance task in which context exposure and footshock training occur on two sequential days. RU 28362 administration into the IC enhanced later retention when infused immediately after either the context or footshock training. Thus, these findings indicate that the IC mediates glucocorticoid effects on the consolidation of memory of different components of inhibitory avoidance training and suggest that the IC might be an important element of the rodent brain network involved in emotional regulation of learning and memory.
The Polycomb Group Protein Pcgf1 Is Dispensable in Zebrafish but Involved in Early Growth and Aging

Polycomb Repressive Complex (PRC) 1 regulates the control of gene expression programs via chromatin structure reorganization. Through mutual exclusion, different PCGF members generate a variety of PRC1 complexes with potentially distinct cellular functions. In this context, the molecular function of each of the PCGF family members remains elusive. The study of PCGF family member expression in zebrafish development and during caudal fin regeneration reveals that the zebrafish pcgf genes are subjected to different regulations and that all PRC1 complexes in terms of Pcgf subunit composition are not always present in the same tissues. To unveil the function of Pcgf1 in zebrafish, a mutant line was generated using the TALEN technology. Mutant pcgf1-/- fish are viable and fertile, but the growth rate at early developmental stages is reduced in absence of pcgf1 gene function and a significant number of pcgf1-/- fish show signs of premature aging. This first vertebrate model lacking Pcgf1 function shows that this Polycomb Group protein is involved in cell proliferation during early embryogenesis and establishes a link between epigenetics and aging.
The Role of Cytokines and Molecular Pathways in Lung Fibrosis Following SARS-CoV-2 Infection: A Physiopathologic (Re)view

SARS-CoV-2 infection is a significant health concern that needs to be addressed not only during the initial phase of infection but also after hospitalization. This is the consequence of the various pathologies associated with long COVID-19, which are still being studied and researched. Lung fibrosis is an important complication after COVID-19, found in up to 71% of patients after discharge. Our research is based on scientific articles indexed in PubMed; in the selection process, we used the following keywords: “lung fibrosis”, “fibrosis mediators”, “fibrosis predictors”, “COVID-19”, “SARS-CoV-2 infection”, and “long COVID-19”. In this narrative review, we aimed to discuss the current understanding of the mechanisms of initiation and progression of post-COVID-19 lung fibrosis (PC-19-LF) and the risk factors for its occurrence. The pathogenesis of pulmonary fibrosis involves various mediators such as TGF-β, legumain, osteopontin, IL-4, IL-6, IL-13, IL-17, TNF-α, Gal-1, Gal-3, PDGF, and FGFR-1. The key cellular effectors involved in COVID-19 lung fibrosis are macrophages, epithelial alveolar cells, neutrophils, and fibroblasts. The main fibrosis pathways in SARS-CoV-2 infection include hypoxemia-induced fibrosis, macrophage-induced fibrosis, and viral-fibroblast interaction-induced fibrosis.
Long-Term Mortality After First-Ever and Recurrent Stroke in Young Adults

Background and Purpose— Mortality after first-ever stroke, and particularly after recurrent stroke, and predictors of long-term mortality among young and middle-aged stroke patients are not well-known. We assessed 17-year risk of mortality with focus on the effect of recurrence on the risk of death of young and middle-aged patients with stroke. Methods— Mortality and recurrent stroke rate of 970 consecutive 30-day survivors of first-ever ischemic stroke aged 15 to 49 years (1994–2007) were studied. Prospective follow-up data came from the Finnish Care Register for Health Care and Statistics Finland. Mean follow-up was 10.2±4.3 years. We compared survival between clinical subgroups and identified factors associated with mortality. Standardized mortality ratio was calculated for demographic and pathogenetic subgroups using mortality data of the general population matched with age, sex, calendar year, and geographical area. Results— At the end of follow-up, 152 (15.7%) patients had died (cumulative risk, 23.0%; 95% confidence interval, 19.1%–26.9%) and 132 (13.6%) had experienced a recurrent stroke. After adjusting for baseline characteristics, recurrent stroke was statistically the most important risk factor for mortality after first-ever ischemic stroke (hazard ratio, 16.68; 95% confidence interval, 2.33–119.56; P=0.005). Observed mortality was 7-fold higher than the expected mortality (standardized mortality ratio, 6.94; 95% confidence interval, 5.84–8.04) and particularly high among patients who experienced a recurrent stroke (standardized mortality ratio, 14.43; 95% confidence interval, 10.11–18.74). Conclusions— The high mortality rates and the striking impact of recurrent stroke on the risk of death should lead to development of more robust primary and secondary prevention strategies for young patients with stroke.
Online Learning in Markov Decision Processes with Adversarially Chosen Transition Probability Distributions

We study the problem of online learning Markov Decision Processes (MDPs) when both the transition distributions and loss functions are chosen by an adversary. We present an algorithm that, under a mixing assumption, achieves O(√T log |II| + log |II|) regret with respect to a comparison set of policies II. The regret is independent of the size of the state and action spaces. When expectations over sample paths can be computed efficiently and the comparison set II has polynomial size, this algorithm is efficient. We also consider the episodic adversarial online shortest path problem. Here, in each episode an adversary may choose a weighted directed acyclic graph with an identified start and finish node. The goal of the learning algorithm is to choose a path that minimizes the loss while traversing from the start to finish node. At the end of each episode the loss function (given by weights on the edges) is revealed to the learning algorithm. The goal is to minimize regret with respect to a fixed policy for selecting paths. This problem is a special case of the online MDP problem. It was shown that for randomly chosen graphs and adversarial losses, the problem can be efficiently solved. We show that it also can be efficiently solved for adversarial graphs and randomly chosen losses. When both graphs and losses are adversarially chosen, we show that designing efficient algorithms for the adversarial online shortest path problem (and hence for the adversarial MDP problem) is as hard as learning parity with noise, a notoriously difficult problem that has been used to design efficient cryptographic schemes. Finally, we present an efficient algorithm whose regret scales linearly with the number of distinct graphs.
Salvage therapy using FLT3 inhibitors may improve long‐term outcome of relapsed or refractory AML in patients with FLT3‐ITD

To determine the long‐term efficacy of FLT3 inhibitors (FLT3i) in the salvage setting for relapsed and refractory (rel/ref) acute myeloid leukemia (AML) with FLT3 internal tandem duplication (AML FLT3‐ITD), we conducted a retrospective study of 120 patients with rel/ref AML FLT3‐ITD who received salvage therapy with either FLT3i‐containing regimen (FLT3i group, N = 45) or conventional cytotoxic regimen (conventional group, N = 75). The median overall survival (OS) after the first salvage in the FLT3i group was 6·9 vs. 4·6 months in the conventional group (P = 0·17). The OS was better in the FLT3i group among patients with initial complete remission (CR) duration ≤12 months or with primary refractory disease (6·9 vs. 3·7 months; P < 0·01). The OS was better when FLT3i was combined with cytotoxic agents versus monotherapy (17 vs. 4·8 months; P = 0·017). Multivariate analysis revealed that the use of FLT3i was an independent predictor of OS (hazard ratio 0·58; 95% confidence interval, 0·38–0·88). Incorporating FLT3i into salvage strategies may improve long‐term outcome of patients with AML FLT3‐ITD. Prospective studies to validate this conclusion are warranted.
THE CLINICAL AND METABOLIC EFFECTS OF CALCITRIOL IN THE TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS

Osteoporosis is the most common metabolic disease of bone whose management is controversial. To evalu­ ate the efficacy and safety of calcitriol (1,25-dihydroxyvitamin DJ in postmenopausal osteoporosis, this pros­ pective, randomized, one-year clinical trial was planned. Seventy patients aged between 45-69 years were ran­ domly assigned to receive either calcitriol (0.25gr twice daily) or supplemental calcium (1gr/day) for one ye­ ar. Lumbar spine and femoral neck bone mineral density (BMD) values, pain intensity and disability measure scores and bone turnover markers J$erum osteocalcin and urinary hydoxyproline levels) were used as outco­ me parameters of treatment.
Development of a Semi-Mechanistic Modeling Framework for Wet Bead Milling of Pharmaceutical Nanosuspensions

This study aimed to develop a practical semi-mechanistic modeling framework to predict particle size evolution during wet bead milling of pharmaceutical nanosuspensions over a wide range of process conditions and milling scales. The model incorporates process parameters, formulation parameters, and equipment-specific parameters such as rotor speed, bead type, bead size, bead loading, active pharmaceutical ingredient (API) mass, temperature, API loading, maximum bead volume, blade diameter, distance between blade and wall, and an efficiency parameter. The characteristic particle size quantiles, i.e., x10, x50, and x90, were transformed to obtain a linear relationship with time, while the general functional form of the apparent breakage rate constant of this relationship was derived based on three models with different complexity levels. Model A, the most complex and general model, was derived directly from microhydrodynamics. Model B is a simpler model based on a power-law function of process parameters. Model C is the simplest model, which is the pre-calibrated version of Model B based on data collected from different mills across scales, formulations, and drug products. Being simple and computationally convenient, Model C is expected to reduce the amount of experimentation needed to develop and optimize the wet bead milling process and streamline scale-up and/or scale-out.
Endothelial Dysfunction and Low-Grade Inflammation Are Associated With Greater Arterial Stiffness Over a 6-Year Period

Endothelial dysfunction and low-grade inflammation are associated with cardiovascular disease. Arterial stiffening plays an important role in cardiovascular disease and, thus, may be a mechanism through which endothelial dysfunction and/or low-grade inflammation lead to cardiovascular disease. We investigated the associations between, on the one hand, biomarkers of endothelial dysfunction (soluble endothelial selectin, thrombomodulin, and both vascular and intercellular adhesion molecules 1 and von Willebrand factor) and of low-grade inflammation (C-reactive protein, serum amyloid A, interleukin 6, interleukin 8, tumor necrosis factor-&agr; and, soluble intercellular adhesion molecule 1) and, on the other hand, arterial stiffness over a 6-year period, in 293 healthy adults (155 women). Biomarkers were combined into mean z scores. Carotid, femoral, and brachial arterial stiffness and carotid-femoral pulse wave velocity were determined by ultrasonography. Measurements were obtained when individuals were 36 and 42 years of age. Associations were analyzed with generalized estimating equation and adjusted for sex, height, and mean arterial pressure. The endothelial dysfunction z score was inversely associated with femoral distensibility (&bgr;: −0.51 [95% CI: −0.95 to −0.06]) and compliance coefficients (&bgr;: −0.041 [95% CI: −0.076 to −0.006]) but not with carotid or brachial stiffness or carotid-femoral pulse wave velocity. The low-grade inflammation z score was inversely associated with femoral distensibility (&bgr;: −0.51 [95% CI: −0.95 to −0.07]) and compliance coefficients (&bgr;: −0.050 [95% CI: −0.084 to −0.016]) and with carotid distensibility coefficient (&bgr;: −0.910 [95% CI: −1.810 to −0.008]) but not with brachial stiffness or carotid-femoral pulse wave velocity. Biomarkers of endothelial dysfunction and low-grade inflammation are associated with greater arterial stiffness. This provides evidence that arterial stiffening may be a mechanism through which endothelial dysfunction and low-grade inflammation lead to cardiovascular disease.