Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinically important changes in health-related quality of life for patients with chronic obstructive pulmonary disease

BOJECTIVE: Without clinical input on what constitutes a significant change, health-related quality of life (HRQoL) measures are less likely to be adopted by clinicians for use in daily practice. Although standards can be determined empirically by within-person change studies based on patient self-reports, these anchor-based methods incorporate only the patients’ perspectives of important HRQoL change, and do not reflect an informed clinical evaluation. The objective of this study was to establish clinically important difference standards from the physician’s perspective for use of 2 HRQoL measures among patients with chronic obstructive pulmonary disease (COPD). DESIGN: We assembled a 9-person expert panel of North American physicians familiar with the use of the Chronic Respiratory Questionnaire (CRQ), a disease-specific HRQoL measure, or the generic Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36, Version 2.0) among patients with COPD.RESULTS: Using 2 rounds of the Delphi process, 1 in-person meeting, and an iterative improvement process for circulating and correcting the final report, the expert panel established small, moderate, and large clinically important change levels for the CRQ and SF-36.CONCLUSIONS: For this expert physician panel, levels for detecting clinically important differences on the CRQ were equal to or slightly higher than previous studies based on patient-reported differences. Clinically important differences on the SF-36, Version 2.0, were noticeably larger than previous estimates based on cross-sectional differences between clinically defined patient groups.
IAD: Interaction-Aware Diffusion Framework in Social Networks

In networks, multiple contagions, such as information and purchasing behaviors, may interact with each other as they spread simultaneously. However, most of the existing information diffusion models are built on the assumption that each individual contagion spreads independently, regardless of their interactions. Gaining insights into such interaction is crucial to understand the contagion adoption behaviors, and thus can make better predictions. In this paper, we study the contagion adoption behavior under a set of interactions, specifically, the interactions among users, contagions’ contents, and sentiments, which are learned from social network structures and texts. We develop an effective and efficient interaction-aware diffusion (IAD) framework, incorporating these interactions into a unified model. We also present a generative process to distinguish user roles, a co-training method to determine contagions’ categories and a new topic model to obtain topic-specific sentiments. Evaluation on the large-scale Weibo dataset demonstrates that our proposal can learn how different users, contagion categories, and sentiments interact with each other efficiently. With these interactions, we can make a more accurate prediction than the state-of-art baselines. Moreover, we can better understand how the interactions influence the propagation process and thus can suggest useful directions for information promotion or suppression in viral marketing.
Markers of bone metabolism in postmenopausal women with rheumatoid arthritis. Effects of corticosteroids and hormone replacement therapy.

OBJECTIVE To investigate bone metabolism in postmenopausal women with rheumatoid arthritis (RA) treated with or not treated with corticosteroids, and the response to hormone replacement therapy (HRT). METHODS One hundred six RA patients were divided into those taking low-dose steroids (RA+; n = 35) and those not (RA-; n = 71) and randomly allocated to receive HRT or calcium for 2 years. Bone formation markers included serum osteocalcin (OC) and bone-specific alkaline phosphatase, and resorption markers included urinary deoxypyridinoline (DPyr) and CrossLaps (XL). Bone mineral density (BMD) was measured annually using dual x-ray absorptiometry. RESULTS OC levels were significantly lower in both the RA+ and RA- groups compared with 112 healthy control subjects (P < 0.01 and P < 0.05, respectively), but were similar in the 2 RA groups. DPyr and XL levels were elevated in the RA+ group compared with the RA- group (P < 0.05) but were similar between the RA- group and controls. OC was negatively correlated with parameters of disease activity (P < 0.05). After HRT, XL excretion decreased significantly in the overall RA group. Three-month changes in XL correlated with 2-year changes in spinal BMD (P < 0.01). CONCLUSION Bone metabolism may be uncoupled in chronic RA. Bone formation appears to be reduced, partly reflecting disease activity, whereas resorption is increased only in steroid users. HRT reduces resorption in RA irrespective of steroid usage, emphasizing its value in the treatment of postmenopausal women with RA.
A role for the adenovirus inducible E2F transcription factor in a proliferation dependent signal transduction pathway.

Adenovirus E1A dependent trans‐activation of transcription involves the utilization of cellular promoter specific transcription factors. One such factor termed E2F is important for the transcription of the viral E2 gene and appears to be a rate limiting component targeted during the trans‐activation event. Since E2F is of cellular origin and likely to be involved in cellular gene control, we have identified E2F binding sites in cellular genes. Examples include the c‐myc, c‐myb and N‐myc protoncogenes, the DHFR gene and the EGF receptor gene. The transcription of these genes is regulated by cell proliferation signals and each falls into the so‐called immediate early class: genes that are activated independent of new protein synthesis. Because of these common properties of regulation, we have addressed the possible role of E2F in growth factor dependent activation of transcription. Expression of a c‐myc promoter driven CAT gene, transfected into quiescent 3T3 cells, is stimulated by serum addition whereas an identical gene containing mutations in the E2F binding sites is not responsive. The DNA binding activity of E2F is increased 4‐fold upon serum stimulation and the kinetics of activation parallel activation of c‐myc transcription. Furthermore, this increase in E2F activity is independent of new protein synthesis indicating that serum stimulation results in an activation of a pre‐existing factor. These results thus provide strong evidence linking E2F and proliferation dependent control of transcription. We also believe that the E2F transcription factor is the first example of a regulator of the class of immediate early genes that is slowly activated by stimulation of cell proliferation.
Developmental changes in the inhibition of cultured rat uterine cell proliferation by opioid peptides

Abstract. Opioid peptides are negative regulators of cell proliferation in several organs including the uterus. In the present study, the ontogeny of the direct inhibitory action of opioid peptides on the proliferation of cultured rat uterine cells was investigated. Uteri of 7, 14, 21, 28, 35 and 60‐day‐old rats were removed in a sterile way. Tissue blocks were dispersed by limited digestions with trypsin and collagenase. Cells were cultured in enriched Dulbecco's modified Eagle's medium (DMEM). Treatments were present during the entire culture period. Cell densities of the monolayers were determined by counting the cells following trypsinization and trypan blue exclusion. Rat uterine mixed cell cultures grew to confluence within 10 days. The average population doubling time gradually increased with the age of animals. Epidermal growth factor (EGF) increased cell densities of cultures from all age groups. The oestradiol (E2)‐responsiveness appeared at 21 days of age. The effect of [D‐Met2‐Pro5]‐enkephalinamide (ENK) was biphasic. ENK and [Met5]‐enkephalin (OGF) decreased cell densities of both unstimulated and EGF‐stimulated cultures from 7‐day‐old rats to the same extent. ENK failed to act in 14‐day‐old animals. From 21 days of age on, the E2‐ or EGF‐stimulated proliferation was inhibited only by ENK and DAMGO, while 30 nm DPDPE, Dynorhin‐A, OGF, [Leu5]‐enkephalin, beta‐endorphin, and morphiceptin were ineffective. The half‐inhibitory concentration of ENK was 0.3 nm. The effects of ENK were prevented by concomitant treatment with naloxone. Our novel data demonstrate two different phases of the inhibitory action of opioid peptides on rat uterine cell proliferation during ontogeny with an insensitive interval in between.
Lack of host SPARC enhances vascular function and tumor spread in an orthotopic murine model of pancreatic carcinoma

SUMMARY Utilizing subcutaneous tumor models, we previously validated SPARC (secreted protein acidic and rich in cysteine) as a key component of the stromal response, where it regulated tumor size, angiogenesis and extracellular matrix deposition. In the present study, we demonstrate that pancreatic tumors grown orthotopically in Sparc-null (Sparc−/−) mice are more metastatic than tumors grown in wild-type (Sparc+/+) littermates. Tumors grown in Sparc−/− mice display reduced deposition of fibrillar collagens I and III, basement membrane collagen IV and the collagen-associated proteoglycan decorin. In addition, microvessel density and pericyte recruitment are reduced in tumors grown in the absence of host SPARC. However, tumors from Sparc−/− mice display increased permeability and perfusion, and a subsequent decrease in hypoxia. Finally, we found that tumors grown in the absence of host SPARC exhibit an increase in alternatively activated macrophages. These results suggest that increased tumor burden in the absence of host SPARC is a consequence of reduced collagen deposition, a disrupted vascular basement membrane, enhanced vascular function and an immune-tolerant, pro-metastatic microenvironment.
Effect of bacterial endotoxin and interleukin-1 beta on hippocampal serotonergic neurotransmission, behavioral activity, and free corticosterone levels: an in vivo microdialysis study

In this study the effect of immune system stimulation and intracerebroventricular (i.c.v.) administration of interleukin-1 beta (IL-1 beta) on hippocampal serotonergic neurotransmission, behavioral activity, and the hypothalamic-pituitary-adrenocortical (HPA) axis is described. An in vivo microdialysis method was used to measure hippocampal extracellular concentrations of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in conscious, freely moving rats. In addition, we established a method to continuously monitor free corticosterone levels in dialysates. Behavioral activity was scored by measuring the time during which rats were active (locomotion, grooming, eating, drinking). We found a significant, positive relationship between behavioral activity and hippocampal extracellular concentrations of 5-HT. Intraperitoneal (i.p.) administration of the bacterial endotoxin lipopolysaccharide (LPS; 30, 100, and 300 micrograms/kg body weight) produced an increase in the extracellular concentrations of 5-HT and 5-HIAA in the hippocampus, which was paralleled by a significant decline in behavioral activity and a marked increase in extracellular corticosterone levels. Thus, the close correlation between hippocampal extracellular 5-HT levels and behavioral activity observed in control rats was disrupted in the LPS- treated animals. The effects of i.p. LPS could be mimicked by i.c. v. application of recombinant human IL-1 beta (hIL-1 beta; 100 ng). i.c. v. pretreatment with the IL-1 receptor antagonist (IL-1ra; 10 micrograms) antagonized the hIL-1 beta-induced effects. IL-1ra showed no intrinsic effects. Furthermore, it was found that i.c. v. pretreatment with IL-1ra (10 micrograms) significantly attenuated the i.p. LPS-induced (100 micrograms/kg body weight) rise in hippocampal extracellular 5-HT levels.
Penetration of antibiotics into the surgical wound in a canine model

The dose and timing of antimicrobial agents given for surgical wound prophylaxis should be based on the concentration-time profile of the drug in tissue at the site of contamination. However, concentrations of antimicrobial agents in surgical wounds are difficult to determine accurately. Since a surgical wound is a unique extravascular compartment with increased vascular permeability and a high surface area/volume ratio, antibiotic concentrations in sera and surgical wounds should be similar. To test this hypothesis, the pharmacokinetics of single intravenous doses of cefazolin (40 mg/kg) and gentamicin (4 mg/kg) in sera and surgical wounds in a clinically relevant surgical model using dogs were compared. Drug concentrations were determined in interstitial fluid in muscle biopsies taken randomly from wound surfaces and serial wound fluid samples collected after the incisions were closed. Protein binding of cefazolin and gentamicin in sera and wound fluids was low (less than or equal to 29 +/- 9%) in this canine model. Cefazolin and gentamicin equilibrated rapidly (less than or equal to 30 min) between serum and the surgical wound, and concentrations in the two sites declined in parallel. Values for the area under the concentration-time curve, mean residence time, and terminal half-life in serum and the surgical site for each drug were similar. Cefazolin concentrations in serum underestimated the time during which concentrations in surgical wounds exceeded the susceptibility breakpoint MIC for important pathogens by an average of 58 min (range, 26 to 109 min; P = 0.036); for gentamicin, the underestimation averaged 30 min (range, 10 to 60 min; P = 0.036). These data support the concept that the concentration-time profiles of antimicrobial agents in serum may prove valuable clinically as guides to determining the and timing of antibiotic administration necessary for effective antimicrobial prophylaxis in surgery. Further studies are needed to determine the surgical wound pharmacokinetics of highly protein-bound antibodies.
Galectin-1 is a novel functional receptor for tissue plasminogen activator in pancreatic cancer.

BACKGROUND & AIMS Tissue plasminogen activator (tPA) exerts many different functions in addition to its role in fibrinolysis. In pancreatic ductal adenocarcinoma (PDA), tPA is overexpressed and plays an important role in proliferation, invasion, and angiogenesis. tPA interaction with cell membrane receptors has been related to increased proteolytic activity and to signal transduction through nonenzymatic mechanisms. The aim was to analyze the role of galectin-1 (Gal-1), an endogenous lectin that also is overexpressed in PDA, as a new functional receptor for tPA. METHODS Gal-1/tPA interaction was analyzed using surface plasmon resonance and pull-down assays. Pancreatic cells and tumors were used to study Gal-1 expression and localization by Western blot and immunostaining. Down-regulation of Gal-1 by small interference RNA was used to analyze the involvement of Gal-1/tPA interaction in extracellular signal-regulated kinase 1/2 activation, cell proliferation, and invasion in pancreatic and fibroblastic cells. RESULTS Gal-1/tPA interaction is direct, specific, and of high affinity. Gal-1 moderately increases the catalytic activity of tPA. High Gal-1 levels were detected in PDA cells in culture, where it concentrates at the migration front, and in tissues, where it is expressed in epithelial cells and in the stroma. Down-regulation of Gal-1 abolished the effects of tPA on extracellular signal-regulated kinase 1/2 activation, cell proliferation, and invasion, both in pancreatic and in tumor-derived fibroblasts. CONCLUSIONS These findings support a new molecular mechanism by which Gal-1 interaction with tPA contributes to PDA progression involving both transformed epithelial cells and tumor fibroblasts.
Design and Evaluation of a Hand-held Trackball-based Touch-Haptic Interface for Providing Directional Feedback

In this article, we present a design and an evaluation of a hand-held, trackball-based, touchhaptic interface, named ‘Touchball’, for conveying directional cues. By the nature of the trackball mechanism, the device provides flexibility in terms of directional degrees of freedom compared with conventional vibro-tactile devices. It also has the advantage of a direct transfer of force feedback through frictional touch (leveraging on human’s high skin sensitivity), thus requiring only a relatively small amount of inertia by the actuator. This leads to a compact hand-held design appropriate for mobile and 3D interactive applications. We first conducted psychophysical experiments to discover the detection thresholds and measure the perceived amount of directional force feedback. In addition, we conducted a performance and usability test, comparing the Touchball to a vibro-tactile (another touch-based) and aural (another modality) feedback device for an actual application, namely a navigational guide. Experimental results have shown that while both the Touchball and vibro-tactile devices produced comparable task completion time to that with aural feedback, their accuracies were significantly lower. The usability, in most categories, was higher in the order of the sound feedback, Touchball, then vibro-tactile feedback with statistically significant differences. To convey more than just on–off information through tactility such as directions, the vibro-tactile device requires relatively many vibrators and contact points, whereas the Touchball is a more compact and equally effective but with higher usability (e.g. mental load, ease of use, naturalness, etc.). Thus, Touchball offers a viable or even better alternative to a single vibrator or grid-based tactile feedback device especially as a supplementary modality device (to the visual or aural centric interface).
Mycophenolate mofetil and cyclosporine as graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation.

BACKGROUND Mycophenolate mofetil (MMF) is an inhibitor of purine nucleotide de novo synthesis leading to impaired proliferation of activated lymphocytes. Studies in animals show a synergistic effect of MMF and cyclosporine (CsA) in preventing acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation. We performed a pilot study evaluating the feasibility of the combined application of MMF and CsA as GVHD prophylaxis after allogeneic blood stem cell transplantation. Toxicity and the bioavailability of MMF in this setting were investigated. METHODS Fourteen patients who had received grafts from HLA-compatible siblings received 2 g of oral MMF from day 1 to 14 combined with intravenous CsA at 4 mg/kg starting at day-1. Plasma levels of mycophenolic acid (MPA) and its glucoronide were measured by high-performance liquid chromatography. Fifteen patients treated with a combination of CsA and methotrexate at the same institution were referred to as the control group. RESULTS Trilineage engraftment was achieved in all study and control patients. Acute GVHD > or = grade II was observed in 46.5% and 60% of the study and control patients, respectively. No major differences in the rate of acute toxicities were detectable. The mean trough blood level of MPA in 10 patients was 0.28 microg/ml, and 5.7 microg/ml for MPA glucoronide. Reduced peak levels of MPA indicate a reduced absorption rate of MMF in the early posttransplant phase. CONCLUSIONS The combined administration of MMF and CsA was shown to be feasible in patients after allogeneic blood stem cell transplantation. Because of the decreased bioavailability of MMF, dose-finding studies for an intravenous formulation are warranted.
Patient‐Centered Medical Homes and Physician Assistant Education: Preparing the PA Student for the Practice of the Future

Purpose: The patient‐centered medical home (PCMH) holds promise for improving primary health care delivery, but little is known about its impact on medical education. The purpose of this study was to examine the extent to which physician assistant (PA) students are exposed to elements of the PCMH during the didactic and clinical phases of their education. Methods: A survey was distributed to clinical coordinators at all accredited PA programs in the United States that met the study inclusion criteria. The survey inquired about curricula central to practice in the PCMH: team‐based care, electronic medical record utilization, and principles of care coordination. Results: Of the 211 clinical coordinators that were surveyed, we received responses from 87 (41%), of which 94% stated that they teach principles of interprofessional team‐based practice during the didactic phase. Sixty percent or more teach concepts related to physician‐directed teams, quality improvement, care coordination, and electronic medical records. Only 25% of respondents provide instruction in payment structures that reward care coordination and high quality care, and 22% stated that their students do not have exposure to the PCMH. Most importantly, less than 25% of respondents utilize designated PCMH clinical sites, and those that do have been doing so for less than two years. Conclusion: Many PA programs teach some of the core concepts of PCMH during the didactic phase, but exposure to PCMH during clinical clerkships remains limited. Concerted effort is needed to better prepare PA students to function in these emerging team‐based practices.
Social support and cognitive functioning as resources for elderly persons with chronic arthritis pain

Objective: Arthritis pain and depression are prevalent physical and psychological disorders in late life and co-occur frequently. We explored the stability and covariation of arthritis pain and depressive symptoms. We also addressed the influence of cognitive functioning and social support on the relationship between pain and depressive symptoms among community-dwelling older individuals. Method: This longitudinal study utilized a sample of 299 residents of Florida retirement communities who participated in a long-term panel study using yearly assessments across 4 years. Using multilevel modeling, we modeled the individual differences as well as stability in arthritis pain and depressive symptoms simultaneously. Further, we tested the role of cognitive functioning and social support in the association between arthritis pain and depressive symptoms. Results: We found substantial within-person variation in both pain and depressive symptoms (between 58% and 65%) across 4 years even after controlling for a time effect. After controlling for arthritis pain, persons with higher social support and higher cognitive functioning reported lower levels of depressive symptoms. Discussion: Findings suggest that fluctuations in pain and depressive symptoms are common for older adults. Furthermore, social support and intact cognitive functioning may serve as useful resources, as they buffer the negative impact of arthritis pain on depressive symptoms.