Miracle-dz/UniFAR-FTUs huggingface dataset:
Human prostate‐infiltrating CD8+ T lymphocytes are oligoclonal and PD‐1+

Prostate‐infiltrating CD8+ T lymphocytes (CD8+ PIL) are prevalent in men with prostate cancer (PCa), however, it is unclear whether the presence of such cells reflects a non‐specific immune infiltrate or an oligoclonal, antigen‐driven adaptive immune response.
Regulated Clearance of Histone Deacetylase 3 Protects Independent Formation of Nuclear Receptor Corepressor Complexes*

Background: Nuclear receptor corepressors form complexes with histone deacetylase 3 (HDAC3). Results: Interplay of HDAC3 degradation and its complex formation with corepressors maintains free HDAC3 levels, allowing independent formation of nuclear receptor corepressor complexes. Conclusion: By controlling HDAC3 expression, N-CoR and SMRT corepressors do not interfere with their independent complex formation with HDAC3. Significance: Independent formation of nuclear receptor corepressor complexes ensures their independent biological functions. An important step in transcriptional regulation by corepressors N-CoR and SMRT is the formation of a stable and active histone deacetylase 3 (HDAC3)-containing complex. Although N-CoR and SMRT are thought to bind HDAC3 competitively, multiple studies have shown that they do not interfere with the function of each other. How this functional independence is sustained under the competitive interaction is unclear. Here, we show that the coupling of corepressor expression with HDAC3 degradation allows cells to maintain a stable level of uncomplexed HDAC3, thereby preventing mutual interference in the assembly of N-CoR and SMRT complexes. The free uncomplexed HDAC3 is highly unstable. Unexpectedly, the rate of HDAC3 degradation is inversely correlated with the expression level of corepressors. Our results indicate that reducing one corepressor accelerates HDAC3 clearance, thus preventing an increase in complex formation between HDAC3 and the other corepressor. In addition, this study also indicates that the formation of a stable and active HDAC3-corepressor complex is a stepwise process in which the C terminus of HDAC3 plays a critical role at late steps of the assembly process.
Electronic medical record systems in Saudi Arabia: Knowledge and preferences of healthcare professionals

Background: The use of Electronic Medical Record (EMR) systems is increasing internationally, though developing countries, such as Saudi Arabia, have tended to lag behind in the adoption and implementation of EMR systems due to several barriers. The literature shows that the main barriers to EMR in Saudi Arabia are lack of knowledge or experience using EMR systems and staff resistance to using the implemented EMR system. Methods: A quantitative methodology was used to examine health personnel knowledge and acceptance of and preference for EMR systems in seven Saudi public hospitals in Jeddah, Makkah and Taif cities. Results: Both English literacy and education levels were significantly correlated with computer literacy and EMR literacy. Participants whose first language was not Arabic were more likely to prefer using an EMR system compared to those whose first language was Arabic. Conclusion: This study suggests that as computer literacy levels increase, so too do staff preferences for using EMR systems. Thus, it would be beneficial for hospitals to assess English language proficiency and computer literacy levels of staff prior to implementing an EMR system. It is recommended that hospitals need to offer training and targeted educational programs to the potential users of the EMR system. This would help to increase English language proficiency and computer literacy levels of staff as well as staff acceptance of the system.
Inflammatory Factor Profiles One Hour following Vocal Fold Injury

Objectives Inflammatory factors are key mediators of wound healing processes following injury, and their modulation may improve healing outcomes. The objective of this study was to characterize in vivo inflammatory factor and extracellular matrix (ECM) messenger RNA (mRNA) expression levels 1 hour after vocal fold injury. Methods Five Sprague-Dawley rats were subjected to bilateral vocal fold injury, 5 rats were reserved as uninjured controls, and 1 rat was subjected to unilateral vocal fold injury and reserved for histology. Tissue was harvested 1 hour after injury. Real-time reverse transcription–polymerase chain reaction was performed to examine the mRNA expression profiles of inflammatory factors nuclear factor kappa beta (NF-κ β), interferon gamma (IFN-γ), cyclooxygenase 2 (COX-2), transforming growth factor beta isoform 1 (TGF-β1), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β), as well as ECM genes hyaluronic acid synthase (HAS) 1, HAS-2, procollagen 1, procollagen 3, and elastin, in the injured samples compared with the uninjured controls. Results Injury resulted in subepithelial bleeding throughout the vocal fold. The COX-2, TNF-α, IL-1β, and HAS-1 mRNA expression levels were significantly up-regulated 1 hour after injury compared with the uninjured controls. Conclusions Inflammatory factor and ECM gene expression changes occur in vocal fold wound sites as early as 1 hour after injury. These results should inform future efforts to attenuate vocal fold scarring via the modulation of inflammatory factors.
Assessment of patient and caregiver needs in fragile X-associated tremor/ataxia syndrome by utilizing Q-sort methodology

Objectives: Psychosocial stressors faced by patients with fragile X-associated tremor/ataxia syndrome (FXTAS) and their caregivers have not been systematically explored. FXTAS is a neurodegenerative disease occurring in approximately 45% of elderly male carriers and 8–16% of female carriers of the fragile X mental retardation one premutation. This study investigated the subjective needs of patients with FXTAS and their family caregivers, by utilizing Q-sort methodology. Method: Patients with FXTAS and their caregivers seen during January 2005 to June 2007 participated. The Q-sort was composed of 17 (eight formal and nine informal) items, designed to explore emotional, informational, and instrumental needs of patients with FXTAS and their caregivers. Item scores were generated from 1 = least important to 7 = most important. Analysis included descriptive statistics for all the demographic and outcome variables. Generalized estimating equations were used to identify which of the need domains were perceived as most important by the participants. Results: A total of 24 patients (79% men, mean age 65.6 ± 6.4 years) with FXTAS and 18 caregivers (11% men, mean age 63.6 ± 6.2 years) completed the Q-sort. Both patients and caregivers rated informational needs as most important, followed by emotional and, finally, by instrumental needs. Participants lacked many important resources, in particular those addressing instrumental needs. Conclusion: Providers should be educated and able to provide timely information and referrals to formal services, as well as to informal resources, including the National Fragile X Foundation online support network (www.fragilex.org).
Language plus for international graduate students in nursing.

PURPOSE To provide information about an English-language support program that focuses on the needs of international graduate nursing students. The growing presence of these students coincides with the increasing numbers of universities committed to world health. Crucial social and language competence affect the success and progress of international students in graduate nursing programs. DESIGN Reviewed literature was 1980 to 1998, in nursing and applied linguistic research including second-language acquisition, phonology, discourse analysis, and language pragmatics to identify social and language phenomena. FINDINGS Investigators suggest essential elements such as conventions of academic writing, reading comprehension, vocabulary, and pronunciation skills be included in the supportive Language Plus program. CONCLUSIONS Ongoing development of the Language Plus program can promote collaboration between nurses and linguists and increase the success of international graduate nursing students.
Epithelial‐to‐mesenchymal transition in hpv‐33‐transfected cervical keratinocytes is associated with increased invasiveness and expression of gelatinase a

The invasive potential of a set of HPV‐33‐ and HPV‐33+ras‐transfected cervical keratinocytes was investigated. These cell lines were previously separated into 2 groups according to their behavior on collagen rafts. Cell lines from the first group reconstituted CINIII‐like lesions, whereas cell lines from the second group reconstituted epithelia comparable to microinvasive carcinomas. They were thus postulated to represent distinct stages of cervical carcinogenesis. The present results have shown that lines from group I, which have conserved an epithelial morphology in monolayer, (i) could not invade matrigel when tested in a modified Boyden chamber assay, (ii) produced solely gelatinase B and (iii) were unable to activate exogenous gelatinase A. On the other hand, lines from group II associated epithelial‐to‐mesenchymal transition (acquisition of elongated morphology, vimentin positivity) with high in vitro invasive potential and with the ability both to produce and to activate gelatinase A. These results strongly support the hypothesis that the epithelial‐to‐mesenchymal transition and the associated events might be implicated in the progression to the metastatic phenotype.
Histologic examination of bone development in juvenile chimpanzees.

The purpose of this study is to determine whether histologic skeletal development in chimpanzees (Pan troglodytes) differs from that in humans. Currently, minimal quantitative data are available on the bone histology of great apes. In addition to providing baseline data on juvenile chimpanzee bone histology, the data generated by this study have potential applications for studying the comparative development between chimpanzees and humans and other primates, as well as investigating the evolution of human bone development, differences in development among limb elements, and differences in histology related to locomotor function. The study sample includes thin sections from the femoral, tibial, and fibular midshafts of 13 chimpanzees originally prepared by Kerley ([1966] Tulane Stud. Zool. 13:71-82) as part of a study on skeletal age changes in the chimpanzee. Twelve juveniles, ranging in known age from 2-15.3 years, and one adult, with a known age of 35 years, are represented. For each specimen, numbers of osteons, osteon fragments, and non-Haversian canals were counted, and percent lamellar bone was estimated. Results were compared with data extracted from Kerley ([1965] Am. J. Phys. Anthropol. 23:149-164) on a juvenile human sample. Results indicate that juvenile chimpanzees and humans exhibit similar age-related changes in histologic variables. However, age is not as strong a predictor of variation in microstructural variables in chimpanzees as it is in humans.
WHY EMPLOYEES DO BAD THINGS: MORAL DISENGAGEMENT AND UNETHICAL ORGANIZATIONAL BEHAVIOR

We examine the influence of individuals’ propensity to morally disengage on a broad range of unethical organizational behaviors. First, we develop a parsimonious, adult-oriented, valid and reliable measure of an individual’s propensity to morally disengage, and demonstrate the relationship between it and a number of theoretically relevant constructs in its nomological network. Then, in four additional studies spanning laboratory and field settings, we demonstrate the power of the propensity to moral disengage to predict multiple types of unethical organizational behavior. In these studies we demonstrate that the propensity to morally disengage predicts several outcomes (self-reported unethical behavior, a decision to commit fraud, a self-serving decision in the workplace, and co-worker- and supervisor-reported unethical work behaviors) beyond other established individual difference antecedents of unethical organizational behavior, as well as the most closely related extant measure of the construct. We conclude that scholars and practitioners seeking to understand a broad range of undesirable workplace behaviors can benefit from taking an individual’s propensity to morally disengage into account. Implications for theory, research, and practice are discussed.
Implicit-Explicit Linear Multistep Methods for Stiff Kinetic Equations

We consider the development of high order asymptotic-preserving linear multistep methods for kinetic equations and related problems. The methods are first developed for BGK-like kinetic models and then extended to the case of the full Boltzmann equation. The behavior of the schemes in the Navier-Stokes regime is also studied and compatibility conditions derived. We show that, compared to IMEX Runge-Kutta methods, the IMEX multistep schemes have several advantages due to the absence of coupling conditions and to the greater computational efficiency. The latter is of paramount importance when dealing with the time discretization of multidimensional kinetic equations.
Object-oriented Ease-based parallel primitives in C++

The paper presents our language C++-with-Ease, a superset of C++ with primitives for process creation and communication. The work adopts the semantics of the Ease parallel primitives, as defined by S.E. Zenith (1990), within the object oriented paradigm. The result is a general purpose, high level, imperative parallel programming language that allows the simple expression of parallel algorithms within a type-safe implementation. Our language implementation is best suited to homogeneous parallel MIMD machines, independent of architecture, but also runs under threads packages. C++-with-Ease addresses efficiency for message copying and provides extensions to allow the passing of arbitrary messages in a natural fashion within the paradigm. The implementation and associated message protocols are discussed.
Voices from the past: Comparing the rapid prompting method and facilitated communication

Objective: This article briefly reviews the history and damage caused by facilitated communication (FC) and highlights the parallels between FC and the Rapid Prompting Method (RPM). Background: FC involves a therapist (or facilitator) supporting the hand of a person with autism while a message is typed on a letter board. FC is widely acknowledged to be a pseudoscientific, unsafe, and unethical treatment for people with autism. RPM is a more recent intervention for people with autism that involves the facilitator holding and moving the letter board while the individual with autism moves their own hand. Those who espouse the perceived benefits of FC and RPM make strikingly similar claims of hidden intelligence and extraordinary communication abilities in people with autism following treatment. Conclusion: Clients, proponents, and practitioners of RPM should demand scientific validation of RPM in order to ensure the safety of people with disabilities that are involved with RPM.
Variations in circulating inflammatory factors are related to changes in calorie and carbohydrate intakes early in the course of surgery-induced weight reduction.

BACKGROUND Obesity is considered a low-grade inflammatory state that improves with weight loss. In addition to acute-phase proteins, other cytokines might contribute to systemic inflammation. OBJECTIVE Our objective was to compare serum concentrations of a large panel of inflammation-related factors in obese and normal-weight subjects and to determine kinetic changes induced by caloric restriction. DESIGN The cohort comprised 14 normal-weight women and 51 obese women who were followed over 2 y after Roux-en-Y gastric bypass. Multiplexed proteomics were used to simultaneously assay 27 cytokines and growth factors in serum. RESULTS Concentrations of interleukin (IL)-9, IL-1-receptor antagonist, IL-10, interferon-γ-inducible protein 10, macrophage inflammatory protein 1β, monocyte chemoattractant protein 1, IL-8, RANTES (regulated upon activation, normal T cell expressed and secreted), monokine induced by interferon-γ, and vascular endothelial growth factor were found to be elevated in obesity. IL-10 was further elevated in diabetic obese patients, whereas eotaxin was found to be higher only in diabetic subjects. After surgery, many factors showed a biphasic pattern of variation, decreasing sharply at month 3 before rising back to presurgical values at month 6; these changes closely tracked similar kinetic changes in calorie and carbohydrate intake. After 1 y, an overall reduction in cytokines accompanied the reduction in body mass index and an amelioration in metabolic status. CONCLUSIONS Obesity is associated with elevated circulating concentrations of a large panel of cytokines. Coordinated kinetic changes during weight loss suggest an early influence of calorie and carbohydrate intakes, whereas a longer-term reduction in corpulence might prevail in regulating circulating cytokine concentrations. This trial is registered at clincaltrials.gov as NCT00476658.
Quantitation of circulating peripheral blood plasma cells and their relationship to disease activity in patients with multiple myeloma

Background. The analysis of peripheral blood mononuclear cells for plasma cells and B‐cell surface light chain ratios may provide additional insight on the pathogenesis of multiple myeloma and predict disease activity. The goals of this study were to correlate these parameters with clinically determined disease activity and establish a cutoff value of circulating plasma cells that could be used in future clinical trials.
Overexpression of LAMC2 predicts poor prognosis in colorectal cancer patients and promotes cancer cell proliferation, migration, and invasion

Laminin γ2 (LAMC2) has been reported to be involved in the development and progression of a variety of tumors. However, its function in human colorectal cancer is unclear. Our study aimed to investigate the role of laminin γ2 in colorectal cancer. We first performed the multiple Kaplan–Meier survival analysis of laminin γ2 in a cohort of Gene Expression Omnibus datasets and evaluated its relationship with clinical outcomes of colorectal cancer patients. Then, we established stable colorectal cancer cell lines with laminin γ2 overexpression and examined the functional assays in vitro. Finally the expression pattern of laminin γ2 in colorectal cancer clinical samples was analyzed by immunohistochemistry and quantitative real-time polymerase chain reaction. We found that laminin γ2 was significantly correlated with poor clinical outcomes such as disease-specific, recurrence-free, disease-free, and overall survival in colorectal cancer. Moreover, stably overexpressing laminin γ2 promoted proliferation, migration, and invasion of colorectal cancer cells. In addition, overexpressed laminin γ2 was identified in tumor tissues compared with paired adjacent normal tissues and was related to tumor–node–metastasis stage (p = 0.001) and lymph node metastasis (p < 0.001). In summary, our results strongly suggest that laminin γ2 may be a potential prognostic biomarker and therapeutic target in colorectal cancer.
An ex vivo evaluation of efficacy of refrigerated canine plasma.

OBJECTIVES To determine thawing times of fresh frozen plasma (FFP), and to evaluate the activity of hemostatic proteins (coagulation factors V, VII, VIII, IX, X, and fibrinogen), clotting times (prothrombin time and activated partial thromboplastin time), and sterility of canine plasma stored refrigerated. DESIGN Prospective laboratory-based study. SETTING Veterinary teaching hospital blood bank. INTERVENTIONS Phase 1: Six units of canine FFP were retrieved from the blood bank and thawed individually in a warm water bath. Time for thaw was recorded in minutes and reported as mean ± SD. Phase 2: One unit of fresh whole blood was collected from 9 dogs and processed routinely. Resulting plasma was divided into 2 aliquots, 1 stored as refrigerated plasma (RP) and 1 as frozen plasma. Samples from the RP were taken at 0, 1, 5, 7, and 14 days and from the FFP at days 0 and 14 for determination of clotting factor activity (V, VII, VIII, IX, and X and fibrinogen) and clotting times. Coagulation factors and clotting times were analyzed using a mixed effects linear model for ANOVA, comparing changes over time as well as differences between groups. For all comparisons, a P value of <0.05 was considered significant. Batch bacterial aerobic and anaerobic cultures of the RP samples were submitted on days 7 and 14 and from the frozen plasma on day 14. MEASUREMENTS AND MAIN RESULTS Time to thaw for FFP units was 34.7 ± 1.38 minutes. Refrigerated storage resulted in significant decreases in the activity of all clotting factors and a subsequent prolongation in clotting times. However, no values were outside of the reference interval. All bacterial cultures yielded no growth. CONCLUSIONS Refrigerated storage results in only minor loss of coagulation factor activity in canine plasma. The use of RP, therefore, may be a viable option in high-volume veterinary hospitals for rapid correction of coagulopathy in critical care patients.
Evolutionary dynamics of bacteria in a human host environment

Laboratory evolution experiments have led to important findings relating organism adaptation and genomic evolution. However, continuous monitoring of long-term evolution has been lacking for natural systems, limiting our understanding of these processes in situ. Here we characterize the evolutionary dynamics of a lineage of a clinically important opportunistic bacterial pathogen, Pseudomonas aeruginosa, as it adapts to the airways of several individual cystic fibrosis patients over 200,000 bacterial generations, and provide estimates of mutation rates of bacteria in a natural environment. In contrast to predictions based on in vitro evolution experiments, we document limited diversification of the evolving lineage despite a highly structured and complex host environment. Notably, the lineage went through an initial period of rapid adaptation caused by a small number of mutations with pleiotropic effects, followed by a period of genetic drift with limited phenotypic change and a genomic signature of negative selection, suggesting that the evolving lineage has reached a major adaptive peak in the fitness landscape. This contrasts with previous findings of continued positive selection from long-term in vitro evolution experiments. The evolved phenotype of the infecting bacteria further suggests that the opportunistic pathogen has transitioned to become a primary pathogen for cystic fibrosis patients.
The CheZ Binding Interface of CheAS Is Located in α-Helix E

ABSTRACT Specific CheA-short (CheAS) residues, L123 and L126, were identified as critical for CheZ binding. In the CheAS ′P1-CheZ nuclear magnetic resonance structure, these residues form an interaction surface on α-helix E in the ′P1 domain. Both L123 and L126 are buried in CheA-long (CheAL), providing an explanation for why CheAL fails to bind CheZ.