Miracle-dz/UniFAR-FTUs huggingface dataset:
Validation and psychometric properties of the Spanish Mood Rhythm Instrument

ABSTRACT Mood-related behavioral display a daily rhythmic pattern. However, most clinical instruments do not assess mood rhythm aspects. The Mood Rhythm Instrument (MRhI) intends to contribute to filling this gap. We evaluated the psychometric properties and validated the MRhI in a Spanish sample (N = 457), exploring the relationship with chronotype and social jetlag through the reduced version of the Morningness-Eveningness Questionnaire (rMEQ) and the Munich Chronotype Questionnaire (MCTQ), respectively. The MRhI proved to have adequate internal reliability. Somatic and cognitive variables displayed a higher self-reported frequency of rhythmic pattern than affective variables. Sex differences were only observed for sexual arousal, with females reporting higher rates of rhythmicity. The frequency of self-reported rhythmicity was similar between chronotypes. Chronotype and social jetlag scores correlated with most MRhI variables, though rhythmicity depended primarily on age. This study underlines the importance of assessing mood variability through a reliable and user-friendly instrument that could be useful in cross-cultural studies to further our knowledge on the association among mood symptoms, circadian rhythms, and mental illness.
ER transmembrane protein TMTC3 contributes to O-mannosylation of E-cadherin, Cellular Adherence and Embryonic Gastrulation

Protein glycosylation plays essential roles in protein structure, stability and activity such as cell adhesion. The cadherin superfamily of adhesion molecules carry O-linked mannose glycans at conserved sites and it was recently demonstrated that the TMTC1-4 genes contribute to the addition of these O-linked mannoses. Here, biochemical, cell biological and organismal analysis was used to determine that TMTC3 supports the O-mannosylation of E-cadherin, cellular adhesion and embryonic gastrulation. Using genetically engineered cells lacking all four TMTC genes, overexpression of TMTC3 rescued O-linked glycosylation of E-cadherin and cell adherence. The knockdown of the Tmtcs in Xenopus laevis embryos caused a delay in gastrulation that was rescued by the addition of human TMTC3. Mutations in TMTC3 have been linked to neuronal cell migration diseases including Cobblestone lissencephaly. Analysis of TMTC3 mutations associated with Cobblestone lissencephaly found that three of the variants exhibit reduced stability and missence mutations were unable to complement TMTC3 rescue of gastrulation in Xenopus embryo development. Our study demonstrates that TMTC3 regulates O-linked glycosylation and cadherin-mediated adherence, providing insight into its effect on cellular adherence and migration, as well the basis of TMTC3-associated Cobblestone lissencephaly.
Pan-transcriptome-based candidate therapeutic discovery for idiopathic pulmonary fibrosis

Background: There are two US Food and Drug Administration (FDA)-approved drugs, pirfenidone and nintedanib, for treatment of patients with idiopathic pulmonary fibrosis (IPF). However, neither of these drugs provide a cure. In addition, both are associated with several drug-related adverse events. Hence, the pursuit for newer IPF therapeutics continues. Recent studies show that joint analysis of systems-biology-level information with drug–disease connectivity are effective in discovery of biologically relevant candidate therapeutics. Methods: Publicly available gene expression signatures from patients with IPF were used to query a large-scale perturbagen signature library to discover compounds that can potentially reverse dysregulated gene expression in IPF. Two methods were used to calculate IPF–compound connectivity: gene expression-based connectivity and feature-based connectivity. Identified compounds were further prioritized if their shared mechanism(s) of action were IPF-related. Results: We found 77 compounds as potential candidate therapeutics for IPF. Of these, 39 compounds are either FDA-approved for other diseases or are currently in phase II/III clinical trials suggesting their repurposing potential for IPF. Among these compounds are multiple receptor kinase inhibitors (e.g. nintedanib, currently approved for IPF, and sunitinib), aurora kinase inhibitor (barasertib), epidermal growth factor receptor inhibitors (erlotinib, gefitinib), calcium channel blocker (verapamil), phosphodiesterase inhibitors (roflumilast, sildenafil), PPAR agonists (pioglitazone), histone deacetylase inhibitors (entinostat), and opioid receptor antagonists (nalbuphine). As a proof of concept, we performed in vitro validations with verapamil using lung fibroblasts from IPF and show its potential benefits in pulmonary fibrosis. Conclusions: As about half of the candidates discovered in this study are either FDA-approved or are currently in clinical trials for other diseases, rapid translation of these compounds as potential IPF therapeutics is possible. Further, the integrative connectivity analysis framework in this study can be adapted in early phase drug discovery for other common and rare diseases with transcriptomic profiles. The reviews of this paper are available via the supplemental material section.
Oceanic and coastal populations of a harvested macroinvertebrate Rochia nilotica in north-western Australia are isolated and may be locally adapted

Marine macroinvertebrates support important fisheries throughout the Indo-Pacific, but stocks of species such as trochus (Rochia nilotica) are easily overharvested. In north-western Australia, trochus are taken from inshore reefs by Indigenous Australians and oceanic reefs by artisanal Indonesian fishers. The management of these environmentally distinct regions relies on understanding their spatial interdependencies, yet connectivity between them has not been evaluated empirically. Here, we used genotype-by-sequencing analysis of 514 trochus samples collected from 17 locations (15 in the inshore Kimberley, 2 offshore oceanic sites). Analysis of 5428 polymorphic single nucleotide polymorphism loci revealed significant genetic subdivision between the oceanic and coastal sites, and a subset of loci exhibited significantly higher subdivision, suggesting they are subject to directional selection. Population differentiation was also evident between the two oceanic sites, but not between coastal sites. Trochus populations from the coastal Kimberley and oceanic reefs represent two genetically and demographically independent units, with preliminary evidence for local adaptation to these distinctive environments. Management strategies for R. nilotica reflect these divisions, but the limited connectivity among oceanic populations indicates that they are vulnerable to overexploitation. Furthermore, their potential adaptive distinctiveness indicates that coastal stocks may be unsuitable for replenishing oceanic stocks.
Interactions between calmodulin and neurogranin govern the dynamics of CaMKII as a leaky integrator

Calmodulin-dependent kinase II (CaMKII) has long been known to play an important role in learning and memory as well as long term potentiation (LTP). More recently it has been suggested that it might be involved in the time averaging of synaptic signals, which can then lead to the high precision of information stored at a single synapse. However, the role of the scaffolding molecule, neurogranin (Ng), in governing the dynamics of CaMKII is not yet fully understood. In this work, we adopt a rule-based modeling approach through the Monte Carlo method to study the effect of Ca2+ signals on the dynamics of CaMKII phosphorylation in the postsynaptic density (PSD). Calcium surges are observed in synaptic spines during an EPSP and back-propagating action potential due to the opening of NMDA receptors and voltage dependent calcium channels. We study the differences between the dynamics of phosphorylation of CaMKII monomers and dodecameric holoenzymes. The scaffolding molecule Ng, when present in significant concentration, limits the availability of free calmodulin (CaM), the protein which activates CaMKII in the presence of calcium. We show that it plays an important modulatory role in CaMKII phosphorylation following a surge of high calcium concentration. We find a non-intuitive dependence of this effect on CaM concentration that results from the different affinities of CaM for CaMKII depending on the number of calcium ions bound to the former. It has been shown previously that in the absence of phosphatase CaMKII monomers integrate over Ca2+ signals of certain frequencies through autophosphorylation (Pepke et al, Plos Comp. Bio., 2010). We also study the effect of multiple calcium spikes on CaMKII holoenzyme autophosphorylation, and show that in the presence of phosphatase CaMKII behaves as a leaky integrator of calcium signals, a result that has been recently observed in vivo. Our models predict that the parameters of this leaky integrator are finely tuned through the interactions of Ng, CaM, CaMKII, and PP1. This is a possible mechanism to precisely control the sensitivity of synapses to calcium signals.
MODULATION OF INFLAMMATORY CYTOKINE, CHEMOKINE, AND TOLL-LIKE RECEPTOR GENES AND TRANSCRIPTOME ANALYSIS OF EQUINE ENDOTHELIAL CELLS FOLLOWING INFECTION WITH EQUID HERPESVIRUS-1, AND EQUINE ARTERITIS VIRUS.

OF DISSERTATION MODULATION OF INFLAMMATORY CYTOKINE, CHEMOKINE, AND TOLLLIKE RECEPTOR GENES AND TRANSCRIPTOME ANALYSIS OF EQUINE ENDOTHELIAL CELLS FOLLOWING INFECTION WITH EQUID HERPESVIRUS1, AND EQUINE ARTERITIS VIRUS. EHV-1 is a double-stranded DNA virus whereas EAV is a positive sense, singlestranded RNA virus. Therefore, genetically, they are very different from one another. However, both these viruses are endotheliotropic and thus, infect and replicates in equine endothelial cells resulting in vasculitis. Vasculitis is central to the pathogenesis of these two viruses. Thus, the main objective of this thesis was to investigate the inflammatory and innate immune responses of EECs that contributes towards the development of vasculitis following infection with EHV-1 and EAV in-vitro. Since proinflammatory cytokines and chemokines produced by endothelial cells play a significant role in the development of vasculitis, we investigated their gene expression as well as secretion. Results from this study showed that the proinflammatory response of EECs induced by EAV is relatively less when compared with the corresponding results from EHV-1 infected EECs. Furthermore, EAV elicits a lower type I interferon response in EECs when compared with EHV-1. Further investigations revealed an active role played by TLR 3 in inducing the proinflammatory response in EHV-1 infected EECs during the first 6 hours of infection but not in EAV infected EECs. Analyzing the whole transcriptome of EHV-1 and EAV infected EECs revealed a complex pattern of gene regulation and cellular pathways related to cellular immune, inflammatory and apoptotic responses. Finally, we investigated host genetic factors associated with EHV-1 induced myeloencephalopathy but found no evidence for a recessive allele influencing the development of EHM following EHV-1 infection for any genetic locus was identified. However, more complex host-pathogen interactions are possible.
A study to assess the effectiveness of planned health teaching programme using child-to -child approach on knowledge of selected first aid measures among school children in selected schools at Dharapuram in Tamil Nadu, India

“All citizens – All health workers” Everyone, even the children also have responsible to involve in health services & act as change agents for health promotion. The study was to assess the effectiveness of teaching programme using child-to-child approach on knowledge of selected first aid measures in children. The aim of the study to assess effectiveness of planned health teaching programme on selected first aid measures among school children using child-to-child approach. Quasi experimental design was adopted. The present study was conducted at Dharapuram in Erode district, Tamil Nadu India. The samples were 200 selected by simple random sampling method. The results showed that (‘Z’ value =1.96) mean pre and post-tests value were 10.26 and 21.55. The study concluded that about 68.5percent of students gained adequate knowledge after teaching programme using child-to-child approach.
EPIDEMIOLOGICAL AND CLINICAL FEATURES OF LICHEN PLANUS IN JORDANIAN PATIENTS

Objectives: To study the epidemiological and clinical features of LP in Jordanian patients. Patients and Methods: A retrospective study was done. The files of 167 patients with LP, who attended the Dermatology Clinic, Queen Alia Military Hospital, Amman, Jordan, from January 2003 to December 2005, were analyzed. Results: The 167 patients with LP formed 0.73% of the total number of new dermatology outpatients. The male: female ratio was 1: 1.1. The patient ages ranged from 6 to 73 years, most being in the age range from 34 to 59 years (mean, 39.7 years). No familial cases were seen. No precipitating factors were detected. The majority of the patients (57.7%) showed classical lesions followed by hypertrophic type next in frequency. Most patients (83.6%) had pruritus. Limbs were the most common site to be involved at onset (61.3%). Mucous membranes were involved along with skin in 48.5%. Nail changes were observed in 9% of patients and hair affection in 1.2%. Conclusion: The epidemiological and clinical features of the disease in Jordan are similar to those mentioned in literature, with higher prevalence of actinic type which is the case in most countries of Middle East.
ATRIAL FIBRILLATION IN MITRAL STENOSIS AND ITS CORRELATION WITH LEFT ATRIAL SIZE, MITRAL VALVE AREA AND LEFT ATRIAL THROMBUS

Chronic rheumatic heart disease is the commonest cause of mitral stenosis. Incidence of rheumatic MS parallels that of acute rheumatic fever. Atrial fibrillation usually develops in the presence of pre-existing ECG evidence of left atrial enlargement and is related to the size of the chamber, the extent of fibrosis of the left atrial myocardium, the duration of the atriomegaly and the age of the patient. The tendency for development of systemic embolization correlates directly with the patient’s age and the size of the left atrial appendages and inversely with the cardiac output. Eighty percent of the patients of MS in whom systemic emboli develop are in atrial fibrillation. A descriptive study was designed in the Department of Medicine, K E Medical College / Mayo Hospital and Punjab Institute of Cardiology, Lahore. A total of 129 conservative cases of mitral stenosis were included in this study, based upon convenient patient sampling. A total of 112 patients were followed up properly, the remaining 17 were lost to follow. The results showed left atrial size and MVA have an inverse correlation (p = 0.017). LAT has a strong association with AF in cases of MS (p = 0.002). The severity of MS does not influence the frequency of AF (p = 0.24). It was thus concluded that left atrial size and MVA have an inverse correlation (p = 0.017). LAT has a strong association with AF in cases of MS (p = 0.002). The severity of MS does not influence the frequency of AF (p = 0.24).
Co-infection with Angiostrongylus chabaudi and Dirofilaria immitis in a wildcat, Felis silvestris from Romania – a case report

Dirofilaria immitis is a worldwide spread nematode affecting the pulmonary artery and the heart of dogs (rarely reported in cats), especially in areas where the dogs show a high prevalence of infection. Angiostrongylus chabaudi is, in turn, a cardiopulmonary nematode of felids identified in several southern European countries and Germany. Co-infections of Dirofilaria immitis and Angiostrongylus spp. are known only in canids. We report a case of D. immitis and A. chabaudi co-infection in a road-killed wildcat originating from Southeastern Romania. Overall, 17 nematodes were collected from the pulmonary arteries of the wildcat and were morphologically identified as A. chabaudi (2 males and 15 females). Another nematode was collected from the right ventricle and identified as adult male D. immitis. Genomic DNA was extracted from one nematode of each of the two species and a fragment of the cox1 gene was amplified and sequenced. The sequences obtained from the nematodes showed 100% similarity to a sequence of A. chabaudi isolated from Romania (Accession number KU521521) and to various D. immitis sequences from Europe, Asia and Australia (e.g. KT716014, EU159111, AJ537512). This is the first report of A. chabaudi and D. immitis co-infection in a felid, revealing the possibility of similar situations in domestic cats. This requires a more in-depth clinical and laboratory examination of animals with respiratory and cardiac symptoms.
Pharmaceutical Care Education and Practice in Jordan in the New Millennium

Objectives: Pharmacy practice in Jordan is still developing. Modernization and advancement in pharmacy practice are being slowly adapted by pharmacy professionals and faculties of pharmacy. This study aim was to look into current status of pharmaceutical care in pharmacy education and practice in Jordan. Possible problems that would face Pharmaceutical Care application were explored. Methods: This study consisted of a quantitative part in which the pharmacy curricula from the two governmental universities and four private universities were compared as to how many credit hours are allocated for Pharmaceutical Care education. In the qualitative part, a structured interview was conducted with leaders in the Pharmacy profession. The main theme in the interview was the development and implementation of Pharmaceutical Care education and practice in Jordan. The selected fourteen recognized leaders of pharmacy profession in Jordan were asked to express their views on issues related to status of education, practice, and pharmacy curricula. Results: Current B.Sc. pharmacy curricula in Jordan have a weak emphasis on Pharmaceutical Care education and training. One governmental university (Jordan university of Science and Technology) and two private universities (Philadelphia University and Al-Isra’a Private University) had the highest percentage of their curricular hours allocated to Pharmaceutical- care- related courses. But this was only 20% of total hours required in the pharmacy curriculum. None of the six universities included had a structured patient - oriented training for pharmacy students. In the qualitative part, leaders of pharmacy believe that both the practice and education should be directed towards Pharmaceutical Care. Recognized problems facing this new direction could be: the influence that comes from pharmacy professionals as well as other professions, lack of a proper job description for pharmacists, and the slow change in educational programs. Conclusions: The leadership of pharmacy is in support of changes towards Pharmaceutical Care education and practice, coming from within the profession.
Recovery Effects from Oxidative Cell Damage by So-Hap-Hyang-Won on Bovine Aortic Endothelial Cells (BAEC)

So-Hap-Hyang-Won, a traditional oriental medicine used in the treatment of stroke patients, was examined for its ability to reverse the cell damage caused by lipid peroxidation products and oxidative stress in bovine aortic endothelial cells (BAEC). The effects of herbal medicine on cell proliferation and recovery of oxidative damaged situation were studied in BAEC, which was considered an appropriate in vitro model for stroke resulting from various vascular diseases prevalent in advanced age. In a clinical study of stroke patients, So-Hap-Hyang-Won appeared to improve considerably arm and leg movements as well as consciousness disturbance condition, compared with other traditional medicines used for stroke. When BAEC were treated with extracts of the lyophilized herbal medicines, only that of So-Hap-Hyang-Won stimulated cell proliferation and showed no toxicity even at high concentrations. In studies of BAEC treated with extracts of the lyophilized material of the 14 components of So-Hap-Hyang-Won, only the extract of Foeniculi Fructus stimulated cell growth at all concentrations tested. Moreover, when cells were treated with Foeniculi Fructus (10 and 100 mg/ml) extract after prior exposure to t-BHP (10 M) or HNE (0.2 M), lipid peroxidation products which are known to be involved in aging and vascular diseases, or after the exposure to SIN-1 (500 M), which generates nitric oxide (NO) and other reactive oxygen species, there was substantial recovery from the oxidative damage, presumably due to the radical-scavenging effect of Foeniculi Fructus extract. Foeniculi Fructus not only showed stimulatory effects on cell growth and cell damage repair in BAEC, but also appeared to show the most anti-aging activity among all the herbal components of So-Hap-Hyang-Won. (Korean J of Oriental Med 2003;24(4):71-81)
Their Contribution to Arthritis and the Differentiation of Th1 and Th17 Cells T Cell Priming Regulates + Location of CD4

Yoichiro Iwakua, Tibor T. Glant and Alison FinneganRachel Rodeghero, Yanxia Cao, Susan A. Olalekan,ol.1203045http://www.jimmunol.org/content/early/2013/04/28/jimmunJ Immunol€ published online 29 April 2013Subscriptionshttp://jimmunol.org/subscriptionsInformation about subscribing to The Journal of Immunology is online at: Permissionshttp://www.aai. org/ji/copyright.htmlSubmit copyright permission requests at: Email Alertshttp://jimmunol.org/cgi/alerts/etocReceive free email-alerts when new articles cite this article. Sign up at:
Deep brain stimulation modulates directional frontolimbic connectivity in obsessive‐compulsive disorder

Deep brain stimulation (DBS) is effective for patients with treatment‐refractory obsessive‐compulsive disorder. DBS of the ventral anterior limb of the internal capsule (vALIC) rapidly improves mood and anxiety with optimal stimulation parameters. To understand these rapid effects of vALIC‐DBS, we studied functional interactions within the affective amygdala circuit. We compared resting state functional magnetic resonance imaging data during chronic stimulation versus one week of stimulation discontinuation in patients, and obtained two resting state scans from matched healthy volunteers to account for test‐retest effects. Imaging data were analyzed using functional connectivity analysis and dynamic causal modelling. Improvement in mood and anxiety following DBS was associated with reduced amygdala‐insula functional connectivity. Directional connectivity analysis revealed that DBS increased the impact of the ventromedial prefrontal cortex on the amygdala, and decreased the impact of the amygdala on the insula. These results highlight the importance of the amygdala circuit in the pathophysiology of OCD, and suggest a neural systems model through which negative mood and anxiety are modulated by vALIC‐DBS for OCD and possibly other psychiatric disorders. One Sentence Summary Deep brain stimulation improves mood and anxiety in obsessive‐compulsive disorder by altering connectivity between the amygdala, insula and prefrontal cortex.