Miracle-dz/UniFAR-FTUs huggingface dataset:
Altered Circadian Secretion of Salivary Cortisol during Night Shift.

Background: Rotating night shift disrupts the circadian rhythms and has been associated with physiological stress, general fatigue, sleep disturbances and cardiovascular diseases. Alterations in the sleep pattern leads to increased cortisol and decreased melatonin which might be associated physiological stress and cardiovascular diseases. Objectives: The objective of the present study was to investigate circadian secretion of salivary cortisol in rotating night shift nursing professionals. Methods: 62 healthy nursing professionals of both genders performing day and night shifts duties were recruited. Each study subject had a monthly scheduled of regular 9 night shifts (12 hours night shift, from 20:00 to 08:00) followed by remaining 17-18 day shifts (6 hours day shift, from 08:00 to 14:00) with a total of 4 days off in between. Saliva samples were collected at around 8 hours interval while they were performing night duties and repeated when they were assigned day duties. Salivary cortisol level was estimated by the ELISA (Competitive) method. Results: Significant difference was found in night cortisol among night (4.34 ± 3.37) vs day shift (2.70 ± 2.32), (p<0.001). Alteration in morning cortisol was also found between night (3.73 ± 2.47) vs day shift (5.00 ± 2.73). The circadian pattern of cortisol was altered by rotating night shift particularly at night and in the morning time. Conclusion: The present study concluded that the desynchronization was appeared during night shift and entrainment of circadian rhythm was occurred in day shift.
PLK1 Phosphorylates Mitotic Centromere-associated Kinesin and Promotes Its Depolymerase Activity*

During cell division, interaction between kinetochores and dynamic spindle microtubules governs chromosome movements. The microtubule depolymerase mitotic centromere-associated kinesin (MCAK) is a key regulator of mitotic spindle assembly and dynamics. However, the regulatory mechanisms underlying its depolymerase activity during the cell cycle remain elusive. Here, we showed that PLK1 is a novel regulator of MCAK in mammalian cells. MCAK interacts with PLK1 in vitro and in vivo. The neck and motor domain of MCAK associates with the kinase domain of PLK1. MCAK is a novel substrate of PLK1, and the phosphorylation stimulates its microtubule depolymerization activity of MCAK in vivo. Overexpression of a polo-like kinase 1 phosphomimetic mutant MCAK causes a dramatic increase in misaligned chromosomes and in multipolar spindles in mitotic cells, whereas overexpression of a nonphosphorylatable MCAK mutant results in aberrant anaphase with sister chromatid bridges, suggesting that precise regulation of the MCAK activity by PLK1 phosphorylation is critical for proper microtubule dynamics and essential for the faithful chromosome segregation. We reasoned that dynamic regulation of MCAK phosphorylation by PLK1 is required to orchestrate faithful cell division, whereas the high levels of PLK1 and MCAK activities seen in cancer cells may account for a mechanism underlying the pathogenesis of genomic instability.
1α,25‐dihydroxyvitamin D3 inhibits matrix metalloproteinases induced by Mycobacterium tuberculosis infection

Matrix metalloproteinases (MMP) can degrade all components of pulmonary extracellular matrix. Mycobacterium tuberculosis induces production of a number of these enzymes by human macrophages, and these are implicated in the pathogenesis of pulmonary cavitation in tuberculosis. The active metabolite of vitamin D, 1α,25‐dihydroxyvitamin D3 [1α,25(OH)2D3], has previously been reported to inhibit secretion of MMP‐9 in human monocytes (MN), but its influence on the secretion and gene expression of MMP and tissue inhibitors of MMP (TIMP) in M. tuberculosis‐infected cells has not previously been investigated. We therefore determined the effects of 1α,25(OH)2D3 on expression, secretion and activity of a number of MMP and TIMP in M. tuberculosis‐infected human leucocytes; we also investigated the effect of 1α,25(OH)2D3 on the secretion of interleukin‐10 (IL‐10) and prostaglandin E2 (PGE2), both transcriptional regulators of MMP expression. We found that M. tuberculosis induced expression of MMP‐1, MMP‐7 and MMP‐10 in MN and MMP‐1 and MMP‐10 in peripheral blood mononuclear cells (PBMC). 1α,25(OH)2D3 significantly attenuated M. tuberculosis‐induced increases in expression of MMP‐7 and MMP‐10, and suppressed secretion of MMP‐7 by M. tuberculosis‐infected PBMC. MMP‐9 gene expression, secretion and activity were significantly inhibited by 1α,25(OH)2D3 irrespective of infection. In contrast, the effects of 1α,25(OH)2D3 on the expression of TIMP‐1, TIMP‐2 and TIMP‐3 and secretion of TIMP‐1 and TIMP‐2 were small and variable. 1α,25(OH)2D3 also induced secretion of IL‐10 and PGE2 from M. tuberculosis‐infected PBMC. These findings represent a novel immunomodulatory role for 1α,25(OH)2D3 in M. tuberculosis infection.
Both Transcriptional Regulation and Translational Control of ATF4 Are Central to the Integrated Stress Response*

In response to different environmental stresses, phosphorylation of eIF2 (eIF2∼P) represses global translation coincident with preferential translation of ATF4. ATF4 is a transcriptional activator of the integrated stress response, a program of gene expression involved in metabolism, nutrient uptake, anti-oxidation, and the activation of additional transcription factors, such as CHOP/GADD153, that can induce apoptosis. Although eIF2-P elicits translational control in response to many different stress arrangements, there are selected stresses, such as exposure to UV irradiation, that do not increase ATF4 expression despite robust eIF2∼P. In this study we addressed the underlying mechanism for variable expression of ATF4 in response to eIF2∼P during different stress conditions and the biological significance of omission of enhanced ATF4 function. We show that in addition to translational control, ATF4 expression is subject to transcriptional regulation. Stress conditions such as endoplasmic reticulum stress induce both transcription and translation of ATF4, which together enhance expression of ATF4 and its target genes in response to eIF2∼P. By contrast, UV irradiation represses ATF4 transcription, which diminishes ATF4 mRNA available for translation during eIF2∼P. eIF2∼P enhances cell survival in response to UV irradiation. However, forced expression of ATF4 and its target gene CHOP leads to increased sensitivity to UV irradiation. This combination of transcriptional regulation and translational control allows the eIF2 kinase pathway to selectively repress or activate key regulatory genes subject to preferential translation, providing the integrated stress response versatility to direct the transcriptome that is essential for maintaining the balance between stress remediation and apoptosis.
Causes of work-related injuries among young workers in British Columbia.

BACKGROUND We conducted a study to determine the types and causes of serious injuries to young workers (YW) (ages 14-24) in British Columbia. METHODS The WorkSafeBC database from 2000 to 2005 was searched for all claims, all non-health-care-only (NHCO) injuries and all serious injury claims involving workers aged 14-24. RESULTS Of 384,250 NHCO claims, 15.6% were for YW, not significantly different from the British Columbia workforce (P > 0.75). Of the 5217 serious injuries, 9.8% (including 40 fatalities) were to YW-455 males and 56 females, significantly different from the workforce (50% male) ((2) = 259.8; df = 1; P < 0.001). Ten percentage of YW injuries occurred in the first week, 20% in the first month, of employment. Education level of injured YWs was lower than average for the provincial workforce. Only 38% of YWs injured in vehicle crashes (the most common cause of fatalities) were wearing seatbelts. CONCLUSIONS Safety training should be provided before YWs start work and in media other than school. Seatbelt use should be addressed.
Ex vivo expanded cord blood CD4 T lymphocytes exhibit a distinct expression profile of cytokine‐related genes from those of peripheral blood origin

With an increase in the importance of umbilical cord blood (CB) as an alternative source of haematopoietic progenitors for allogenic transplantation, donor lymphocyte infusion (DLI) with donor CB‐derived activated CD4+ T cells in the unrelated CB transplantation setting is expected to be of increased usefulness as a direct approach for improving post‐transplant immune function. To clarify the characteristics of activated CD4+ T cells derived from CB, we investigated their mRNA expression profiles and compared them with those of peripheral blood (PB)‐derived activated CD4+ T cells. Based on the results of a DNA microarray analysis and quantitative real‐time reverse transcriptase–polymerase chain reaction (RT‐PCR), a relatively high level of forkhead box protein 3 (Foxp3) gene expression and a relatively low level of interleukin (IL)‐17 gene expression were revealed to be significant features of the gene expression profile of CB‐derived activated CD4+ T cells. Flow cytometric analysis further revealed protein expression of Foxp3 in a portion of CB‐derived activated CD4+ T cells. The low level of retinoic acid receptor‐related orphan receptor γ isoform t (RORγt) gene expression in CB‐derived activated CD4+ T cells was speculated to be responsible for the low level of IL‐17 gene expression. Our data indicate a difference in gene expression between CD4+ T cells from CB and those from PB. The findings of Foxp3 expression, a characteristic of regulatory T cells, and a low level of IL‐17 gene expression suggest that CB‐derived CD4+ T cells may be a more appropriate source for DLI.
Pharmacotherapeutics for Nurse Practitioner Prescribers

Part 1 The foundation: the role of the nurse practitioner as prescriber review of basic principles of pharmacology rational drug selection legal and professional issues in prescribing adverse drug reactions factors that foster positive outcomes cultural and ethnic influences on pharmacotherapeutics nutrition and drug therapy pharmacology in complementary medicine information technology and pharmacology over-the-counter medications. Part 2 Pharmacotherapeutics with single drugs: drugs affecting the autonomic system drugs affecting the respiratory system drugs affecting the haematopoietic system drugs affecting the immune system drugs affecting the gastrointestinal system drugs affecting the endocrine system drugs affecting the reproductive system drugs affecting the integumentary system drugs used in treating infectious diseases drugs used in treating inflammatory processes drugs used in treating eye and ear disorders. Part 3 Pharmacotherapeutics with multiple drugs: anaemia chronic stable angina and low-risk unstable angina anxiety and depression asthma and chronic obstructive pulmonary disease contraception dermatologic conditions diabetes mellitus gastroesophageal reflux and peptic ulcer disease headaches heart failure human immunodeficiency virus disease and acquired immunodeficiency disease hormone replacement therapy and osteoporosis hyperlipidaemia hypertension hyperthyroidism pneumonia smoking cessation sexually transmitted diseases and vaginitis tuberculosis upper respiratory infections - viral upper respitatory infection, sinusitis, otitis media and otitis externa urinary tract infections. Part 4 Special drug treatment considerations: women as patients paediatric patients geriatric patients chronically ill and long-term care.
The value of rheumatoid factor and anti-citrullinated protein antibodies as predictors of response to infliximab in rheumatoid arthritis: an exploratory study.

OBJECTIVE It remains unclear whether autoantibodies are useful biomarkers to tailor the choice of biological treatment in RA. We investigated the relationship between the presence and levels of different RF and ACPA isotypes and the response to TNF blockade in an exploratory study. METHODS A total of 101 active RA patients were prospectively treated with infliximab (3 mg/kg). Changes in disease activity were monitored by the 28-joint DAS (DAS-28). Serum levels of different isotypes [immunoglobulins M, G and A (IgM, IgG and IgA)] of RF and anti-citrullinated peptide antibodies were measured by ELISA. RESULTS The mean DAS-28 decreased from 5.9 (1.1) at baseline to 4.0 (1.3) at Week 16 of infliximab treatment (P < 0.001). High baseline levels of different isotypes of RF (all P < 0.008), ACPA IgM (P = 0.008) and ACPA IgG (P = 0.07) were associated with an absolute decrease in DAS-28 after TNF blockade. This relationship persisted after adjusting for DAS-28 at baseline. However, the different isotypes of baseline RF and ACPA levels accounted for only a small proportion of variance in treatment response (RF: R² between 7 and 12% and ACPA: R² between 4 and 7%). The simultaneous presence of all three isotypes of RF or ACPA had no additive value. CONCLUSION Presence as well as the titres of RF and IgM ACPA at baseline are significantly correlated with better response to infliximab treatment. However, this correlation is not strong enough to allow a reliable prediction in individual patients. Trial Registration. ISRCTN Register, http://www.controlled-trials.com/isrctn/, ISRCTN36847425.
Reacciones adversas postransfusionales a componentes sanguíneos

Con el objetivo de conocer las reacciones adversas postransfusionales, se realizo un estudio descriptivo transversal de tipo prospectivo mediante un metodo de vigilancia intensiva centrado en los componentes sanguineos transfundidos en un periodo de 6 meses. Se detectaron 12 reacciones adversas en 10 pacientes. Todas las reacciones fueron no hemoliticas inmediatas, para el 50 por ciento de estas de tipo febril y el 50 por ciento alergicas. Los globulos rojos produjeron el mayor numero de reacciones, lo que representa el 58 por ciento, con predominio de las de tipo febril. La edad, sexo, grupo sanguineo y factor Rh no influyeron en la aparicion de las reacciones adversas. El mayor numero de reacciones ocurrio en los pacientes transfundidos en 3 o mas ocasiones. La incidencia global de reacciones postransfusionales fue del 8 por ciento, con un predominio de las febriles de severidad moderada y las leves de tipo alergico
Calreticulin Is a Thermostable Protein with Distinct Structural Responses to Different Divalent Cation Environments*

Calreticulin is a soluble calcium-binding chaperone of the endoplasmic reticulum (ER) that is also detected on the cell surface and in the cytosol. Calreticulin contains a single high affinity calcium-binding site within a globular domain and multiple low affinity sites within a C-terminal acidic region. We show that the secondary structure of calreticulin is remarkably thermostable at a given calcium concentration. Rather than corresponding to complete unfolding events, heat-induced structural transitions observed for calreticulin relate to tertiary structural changes that expose hydrophobic residues and reduce protein rigidity. The thermostability and the overall secondary structure content of calreticulin are impacted by the divalent cation environment, with the ER range of calcium concentrations enhancing stability, and calcium-depleting or high calcium environments reducing stability. Furthermore, magnesium competes with calcium for binding to calreticulin and reduces thermostability. The acidic domain of calreticulin is an important mediator of calcium-dependent changes in secondary structure content and thermostability. Together, these studies indicate interactions between the globular and acidic domains of calreticulin that are impacted by divalent cations. These interactions influence the structure and stability of calreticulin, and are likely to determine the multiple functional activities of calreticulin in different subcellular environments.
Validación del Cuestionario de Actitudes ante las Intervenciones Asistidas por Perros (CAINTAP) en estudiantes universitarios del sur de España: beneficios y temores percibidos

Introduction: animal-assisted interventions (AAI) have a long tradition in some western countries, with many reviews and meta-analyses demonstrating their benefits, but little is known about expectations held by Spanish-speakers. This study develops an assessment tool, and provides empirical data on perceived opportunities and dangers. Methods: A total of 474 college students (aged X=22.7; SD=5.61 years), mostly women (80%), took part in the study. Researchers developed the Questionnaire on Attitudes Towards Dogs Assisted Interventions (CAINTAP), which was then validated. Results: Exploratory factor analysis revealed a two-factor structure which retained 20 items, scales being coined Positive Attitudes (N = 11) and Negative Attitudes (N = 9), both with alphas greater than 0.87. The students demonstrated good expectations for IAA, while the most frequent fears were related to easily modifiable behaviors. Discussion: This study provides psychometric data of the first questionnaire on IAA developed in Spanish, a useful tool that might help to anticipate difficulties regarding intervention with dogs.
MicroRNA-210 Regulates Cancer Cell Proliferation through Targeting Fibroblast Growth Factor Receptor-like 1 (FGFRL1)*

The importance of microRNAs (miRNAs) in human malignancies has been well recognized. Here, we report that the expression of microRNA-210 (miR-210) is down-regulated in human esophageal squamous cell carcinoma and derived cell lines. Marked decreases in the level of miR-210 were observed especially in poorly differentiated carcinomas. We found that miR-210 inhibits cancer cell survival and proliferation by inducing cell death and cell cycle arrest in G1/G0 and G2/M. Finally, we identified fibroblast growth factor receptor-like 1 (FGFRL1) as a target of miR-210 in esophageal squamous cell carcinoma and demonstrated that FGFRL1 accelerates cancer cell proliferation by preventing cell cycle arrest in G1/G0. Taken together, our findings show an important role for miR-210 as a tumor-suppressive microRNA with effects on cancer cell proliferation.
MHC Class II epitope predictive algorithms

Major histocompatibility complex class II (MHC‐II) molecules sample peptides from the extracellular space, allowing the immune system to detect the presence of foreign microbes from this compartment. To be able to predict the immune response to given pathogens, a number of methods have been developed to predict peptide–MHC binding. However, few methods other than the pioneering TEPITOPE/ProPred method have been developed for MHC‐II. Despite recent progress in method development, the predictive performance for MHC‐II remains significantly lower than what can be obtained for MHC‐I. One reason for this is that the MHC‐II molecule is open at both ends allowing binding of peptides extending out of the groove. The binding core of MHC‐II‐bound peptides is therefore not known a priori and the binding motif is hence not readily discernible. Recent progress has been obtained by including the flanking residues in the predictions. All attempts to make ab initio predictions based on protein structure have failed to reach predictive performances similar to those that can be obtained by data‐driven methods. Thousands of different MHC‐II alleles exist in humans. Recently developed pan‐specific methods have been able to make reasonably accurate predictions for alleles that were not included in the training data. These methods can be used to define supertypes (clusters) of MHC‐II alleles where alleles within each supertype have similar binding specificities. Furthermore, the pan‐specific methods have been used to make a graphical atlas such as the MHCMotifviewer, which allows for visual comparison of specificities of different alleles.
Unique Interaction Pattern for a Functionally Biased Ghrelin Receptor Agonist*

Based on the conformationally constrained d-Trp-Phe-d-Trp (wFw) core of the prototype inverse agonist [d-Arg1,d-Phe5,d-Trp7,9,Leu11]substance P, a series of novel, small, peptide-mimetic agonists for the ghrelin receptor were generated. By using various simple, ring-constrained spacers connecting the d-Trp-Phe-d-Trp motif with the important C-terminal carboxyamide group, 40 nm agonism potency was obtained and also in one case (wFw-Isn-NH2, where Isn is isonipecotic acid) ∼80% efficacy. However, in contrast to all previously reported ghrelin receptor agonists, the piperidine-constrained wFw-Isn-NH2 was found to be a functionally biased agonist. Thus, wFw-Isn-NH2 mediated potent and efficacious signaling through the Gαq and ERK1/2 signaling pathways, but in contrast to all previous ghrelin receptor agonists it did not signal through the serum response element, conceivably the Gα12/13 pathway. The recognition pattern of wFw-Isn-NH2 with the ghrelin receptor also differed significantly from that of all previously characterized unbiased agonists. Most importantly, wFw-Isn-NH2 was not dependent on GluIII:09 (Glu3.33), which otherwise is an obligatory TM III anchor point residue for ghrelin agonists. Molecular modeling and docking experiments indicated that wFw-Isn-NH2 binds in the classical agonist binding site between the extracellular segments of TMs III, VI, and VII, interacting closely with the aromatic cluster between TMs VI and VII, but that it does so in an opposite orientation as compared with, for example, the wFw peptide agonists. It is concluded that the novel peptide-mimetic ligand wFw-Isn-NH2 is a biased ghrelin receptor agonist and that the selective signaling pattern presumably is due to its unique receptor recognition pattern lacking interaction with key residues especially in TM III.