Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential outcomes after sirolimus-eluting stent implantation: comparing on-label versus off-label patients in the ‘real world’

BackgroundRandomized controlled trials indicate that sirolimus-eluting stents (SES) reduce the rates of restenosis and need for subsequent revascularization procedures, but patients enrolled in randomized trials represent a highly selected population. This study examined the performance of SES in a ‘real world’ setting by comparing the outcomes of trial-eligible versus ineligible patients undergoing percutaneous coronary intervention. MethodsFrom the US commercial introduction of SES in April 2003 until December 2003, all patients that received an SES at our institution were followed in a prospective registry (n=838). For the purpose of this analysis, the registry population was divided into two groups based on the inclusion and exclusion criteria of the stenosis in a native coronary artery (SIRIUS) trial. The primary endpoint of the study was the rate of target lesion revascularization (TLR) at follow-up. Secondary endpoints included major adverse cardiac events (MACE) such as cardiac death, myocardial infarction, and target vessel revascularization. Clinical follow-up was complete for 92% of patients with a median duration of 14.2 months. ResultsOverall, 296 patients (35.3%) met entry criteria for the SIRIUS trial and thus comprised the SIRIUS eligible group. Patients in the SIRIUS ineligible group (n=542) were more likely to have chronic kidney disease and earlier bypass surgery and had longer mean stent length. At 1 year, TLR occurred in 3.0% of the SIRIUS eligible population and in 9.2% of the SIRIUS ineligible group (P=0.001). The secondary endpoint of cumulative MACE occurred in 6.6% of the SIRIUS eligible versus in 17.7% of the SIRIUS ineligible population (P<0.001). Two patients (0.4%) in the SIRIUS ineligible group had a late stent thrombosis on days 39 and 99, respectively, versus none in the SIRIUS eligible group. ConclusionAmong ‘real world’ patients treated with SES, the incidence of TLR and MACE at 1 year was substantially greater among SIRIUS ineligible patients compared with SIRIUS eligible patients. These findings confirm that pivotal clinical trials of drug-eluting stents tend to enroll low-risk patients and that the estimated rates of TLR and MACE derived from such trials may not reflect subsequent outcomes with unrestricted clinical use.
Non‐steroidal anti‐inflammatory drugs and upper gastrointestinal bleeding, a post‐marketing surveillance case‐control study

A post‐marketing surveillance case‐control study was set up and applied in an Italian hospital network to quantify the risk of upper gastrointestinal bleeding (UGB) and exposure to non‐steroidal anti‐inflammatory drugs (NSAIDs). During the period of study 441 cases of UGB and 1323 controls were recruited. The odds ratios associated with NSAIDs use were estimated for intake occurring over two different periods of time prior to hospital admission (i.e. during the preceding week and month). A strong association emerged for aspirin intake, both in the week (ORMLR = 11.2; 95% CI 7.8–16.9) and in the month (ORMLR = 6.9; 95% CI 4.6–10.2) preceding hospital admission. A significant increase in the risk of UGB and use of diclofenac, naproxen and ibuprofen, and indomethacin was also found in the two exposure periods considered, while for piroxicam a significant association was only apparent in the analysis of 1‐month exposure. As expected, paracetamol and pyrazolone derivatives were not associated with UGB. This pilot experience has shown the feasibility of setting up a multicentre post‐marketing surveillance programme and of establishing a network for drug monitoring within the Italian National Health Service, capable of providing a thorough evaluation of the benefit/risk profile of drugs.
Overlapping expression patterns and redundant roles for AP‐2 transcription factors in the developing mammalian retina

Background: We have previously shown that the transcription factor AP‐2α (Tcfap2a) is expressed in postmitotic developing amacrine cells in the mouse retina. Although retina‐specific deletion of Tcfap2a did not affect retinogenesis, two other family members, AP‐2β and AP‐2γ, showed expression patterns similar to AP‐2α. Results: Here we show that, in addition to their highly overlapping expression patterns in amacrine cells, AP‐2α and AP‐2β are also co‐expressed in developing horizontal cells. AP‐2γ expression is restricted to amacrine cells, in a subset that is partially distinct from the AP‐2α/β‐immunopositive population. To address possible redundant roles for AP‐2α and AP‐2β during retinogenesis, Tcfap2a/b‐deficient retinas were examined. These double mutants showed a striking loss of horizontal cells and an altered staining pattern in amacrine cells that were not detected upon deletion of either family member alone. Conclusions: These studies have uncovered critical roles for AP‐2 activity in retinogenesis, delineating the overlapping expression patterns of Tcfap2a, Tcfap2b, and Tcfap2c in the neural retina, and revealing a redundant requirement for Tcfap2a and Tcfap2b in horizontal and amacrine cell development. Developmental Dynamics 241:814–829, 2012. © 2012 Wiley Periodicals, Inc.
Local bias and local-to-global interference without global deficit: A robust finding in autism under various conditions of attention, exposure time, and visual angle

A wide variety of paradigms have shown that autistic individuals present with superior performance on visual tasks. Here, the impact of task constraints on visual hierarchical processing in autism was investigated. By employing free- and forced-choice procedures, global and local processing of Navon-type hierarchical numerals was examined in 15 autistic persons (13 males, 2 females) and a comparison group. In the free-choice condition, autistics chose global and local targets randomly, though they were faster responding to local than to global targets, regardless of visual angle and exposure duration. In contrast, the comparison group exhibited a global advantage in naming time, which was evident only for shorter exposures, as well as effects of visual angle. In the forced-choice condition, autistics presented with a more important local-to-global interference than global-to-local interference, whereas the comparison group exhibited global advantage and bidirectional interference. Overall, the autistic participants presented with atypical local-to-global interference and local advantage in incongruent conditions (where global and local targets differ), in naming time as well as accuracy. The relative insensitivity of local bias to task constraints in autistics, in comparison to nonautistic participants, indicates that local bias, with local-to-global interference, is a key and characteristic feature of autistic visual cognition and a strong candidate for the “endophenotype” of autism.
Identification of novel transcription‐regulating genes expressed during murine molar development

Background: The mechanism of tooth development is a complex process regulated by numerous genes including transcription factors, growth factors, and other intra‐ and extracellular molecules. Especially, transcription factors play a central role in gene expression, regulating a wide spectrum of biological processes including organogenesis. Substantial evidence has been demonstrated by a number of studies using genetically engineered animal models. However, detailed molecular mechanisms of tooth development have not been completely elucidated, partially because numerous genes that play essential roles in tooth development remain unidentified. Results: In this study, we conducted an expression‐based screening using gene expression database and in situ hybridization assays. Based on the gene expression database “EMBRYS,” 207 out of 1,520 genes were expressed in the maxillary and/or mandibular processes and thus were selected for further analysis by section in situ hybridization. Among these candidates, 28 genes were newly identified as potential factors associated with tooth development by in situ hybridization assays with frontal sections of embryonic day 13.5 and 14.5 mouse embryos. The expression patterns were also examined at embryonic day 16.5 and 18.5. Conclusions: These results will contribute to elucidating the mechanisms of tooth development and to improving the technology for regeneration of tooth. Developmental Dynamics 241:1217–1226, 2012. © 2012 Wiley Periodicals, Inc.
Cognitive functions in euthymic state of bipolar disorder: An Indian study

Introduction. It has recently been observed that some cognitive deficits in bipolar disorders persist even after the subsidence of active symptoms. The authors aim to study the cognitive functioning of patients with bipolar disorder, currently in euthymia and compare them with normal healthy controls. Methods. Fifteen patients having bipolar-I disorder and currently in euthymia were compared with fifteen age- and education-matched controlled subjects. Cognitive assessments were done using three computer-based tests, i.e., Wisconsin's Card Sorting Test (WCST), Spatial Working Memory Test (SWMT), and Continuous Performance Test (CPT). Results. Euthymic bipolar patients showed significant deficits in executive functions. Subtle deficits were present in attention and working memory that were not statistically significant. Conclusions. Executive deficits may be trait markers in bipolar disorder and may have clinical implications in patient rehabilitation.
Confabulation and delusion: A common monitoring framework

Confabulations and delusions both involve the production of false claims. Although they may have different types of content, they share several characteristics. For example, they are often held with considerable conviction and are resistant to counter evidence, they may be acted upon, and they may be accompanied by a lack of concern about the false claim or its implications. Confabulations and delusions may initially arise from failures in different systems (e.g., mnemonic vs. perceptual or affective). However, their shared characteristics raise the possibility that the monitoring deficits involved might be the same, resulting in failure to reject the confabulatory or delusional ideas. In this paper we will focus on the nature of these common monitoring deficits. Critically, we argue that monitoring in confabulation and delusion involves both unconscious and conscious processes. We propose that an unconscious process is responsible for tagging suspect content which needs to be checked for veracity by a separate set of conscious evaluative processes. Failure of these monitoring processes would allow ideas which ought to be checked and rejected to instead be uncritically accepted: This would result in the production of confabulations or delusions. Importantly, inclusion of both unconscious and conscious monitoring stages allows the model to account for both “endorsement” and “explanation” delusions, and both “primary” and “secondary” confabulations. Our hope is that this model may provide a theoretical framework to guide empirical investigation of the commonalities and differences between the conditions.
Moral reasoning in schizophrenia: An explorative study into economic decision making

Introduction. Previous research has suggested that patients with schizophrenia are impaired in appreciating moral values and social norms. Here, we tested the hypothesis—using economic games—that patients with schizophrenia are similar to normals in their ability to recognise unfairness, but perhaps more tolerant towards the acceptance of unfair offers depending on the severity of negative symptoms. Methods. Twenty-five patients with schizophrenia played an Ultimatum Game and a Dictator Game with punishment option to examine their ability to appreciate fairness rules and to reinforce equity in comparison to a healthy control group. Results. As hypothesised, patients accepted significantly more unfair offers than controls. However, rejection rates increased in relation to the unfairness of proposals in both groups. Patients did not differ significantly from controls in the likelihood of punishing unfairness in the Dictator Game or in punishment investment itself. Conclusions. Patients with schizophrenia seem to be less sensitive towards unfairness to their own disadvantage, but punish unfairness at a comparable level to controls, which opposes the common view of a general lack of moral value appreciation in schizophrenia.
Clinical Experience with Linezolid at a Large Academic Medical Center: A Case Series and Review of the Literature

Purpose The objectives of this study were to evaluate current patterns of use, microbiologic cure rates, and hematologic toxicities, including identification of risk factors, associated with linezolid utilization at our institution. Methods Utilization, clinical, microbiological, and toxicity data were collected prospectively over an 8-month period (August 1, 2006 to March 31, 2007). Binary logistic and multivariate stepwise regression analyses were performed to identify potential risk factors for linezolid-associated thrombocytopenia and anemia. Results A total of 116 linezolid courses (102 patients) were identified with a mean duration of therapy of 12.3 days. Appropriate infectious disease service approval and consults were found in 87.9% and 62.1% of the cases, respectively. Bloodstream, urinary tract, and respiratory tract infections accounted for 29%, 21%, and 16% of clinical indications, respectively. Vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), and coagulase-negative staphylococci accounted for 43%, 24%, and 7% of clinical isolates, respectively. Overall, the microbiologic cure rate among evaluable patients was 83.8%. Development of thrombocytopenia was found in approximately 30% of linezolid-treated patients. Risk factors for linezolid-associated thrombocytopenia included female gender (OR 5.66, P = .002), serum creatinine (SCr) ≥ 2 mg/dL (OR 4.48, P = .009), intensive care unit admission (OR 3.06, P = .038), and duration of therapy ≥ 28 days (OR 3.76, P = .049). Conclusion Utilization patterns may suggest strategies for conserving linezolid, including improved compliance with current approval policies and clinical pathway development. Linezolid microbiological cure rates were similar to those found in the primary literature. Linezolid-associated thrombocytopenia was common and risk factors were identified. Further well-designed prospective studies are needed to confirm these findings. Hosp Pharm-2010;45(12):916-926
Serum adiponectin and leptin as predictors of the presence and degree of coronary atherosclerosis.

BACKGROUND The association of adipocyte-derived proteins, adiponectin and leptin, with the degree of coronary atherosclerosis has not been not been well elucidated. This study aimed to determine the relationship between serum adiponectin and leptin with the presence and degree of coronary atherosclerosis. METHODS Seventy patients and 20 matched controls were recruited. Angiographic evaluation of coronary atherosclerosis was carried out by assessing three atherosclerotic indices, severity (transverse disease), extent (longitudinal disease), and pattern (lesion complexity). RESULTS The independent predictors of atherosclerosis severity were larger waist/hip ratio, followed by higher low-density lipoprotein-cholesterol, low serum adiponectin level, older age, higher leptin level, current unstable angina, and finally previous myocardial infarction (MI). This model is a good one as indicated by the model-adjusted r (50%). For extent index, lower serum adiponectin level was by far the most important independent predictor, followed by higher low-density lipoprotein-cholesterol, older age, and previous MI, whereas higher serum leptin level was only a univariate predictor. The model-adjusted r was 65%. For pattern index, the independent predictors were previous MI, lower serum adiponectin level, larger waist/hip ratio, higher serum leptin level, older age, and higher fasting blood glucose level. The model-adjusted r was 62%. CONCLUSION Both serum adiponectin and leptin might play an important pathogenic role not only in the occurrence but also in the severity, extent, and lesion complexity in coronary artery disease patients.
Expression pattern of Nogo‐A, MAG, and NgR in regenerating urodele spinal cord

Background: The mammalian central nervous system is incapable of substantial axon regeneration after injury partially due to the presence of myelin‐associated inhibitory molecules including Nogo‐A and myelin associated glycoprotein (MAG). In contrast, axolotl salamanders are capable of considerable axon regrowth during spinal cord regeneration. Results: Here, we show that Nogo‐A and MAG, and their receptor, Nogo receptor (NgR), are present in the axolotl genome and are broadly expressed in the central nervous system (CNS) during development, adulthood, and importantly, during regeneration. Furthermore, we show that Nogo‐A and NgR are co‐expressed in Sox2 positive neural progenitor cells. Conclusions: These expression patterns suggest myelin‐associated proteins are permissive for neural development and regeneration in axolotls. Developmental Dynamics 242:847–860, 2013. © 2013 Wiley Periodicals, Inc.
Accessory limb induction on flank region and its muscle regulation in axolotl

Background: Urodele amphibians have high regeneration capability that has been studied for a long time. Recently, a new experimental system called the accessory limb model was developed and becomes alternative choice for amphibian limb regeneration study. Although the accessory limb model has many advantages, an improvement was needed for some specific analysis, such as studying muscle origin. For that purpose, an accessory limb induction on nonlimb regions was attempted. Results: Accessory limb induction on a nonlimb region (flank) was possible by nerve deviation and limb skin grafting. Retinoic acid injections improved the induction rate. The induced limb possessed the same tissue context as a normal limb. Muscle cells were also abundantly observed. It is speculated that the muscle cells are derived from flank muscle tissues, because limb muscle cells are a migratory cell population and the accessory limb was induced apart from the original limb. We also found that migration of the muscle cells was regulated by Hgf/cMet signaling as in other vertebrates. Conclusions: Accessory limb induction was possible even in the nonlimb flank region. The flank‐induced limb would be useful for further analysis of limb regeneration, especially for migratory cell populations such as muscle cells. Developmental Dynamics 242:932–940, 2013. © 2013 Wiley Periodicals, Inc.
Prevalence of menstrual dysfunction in Norwegian long‐distance runners participating in the Oslo Marathon games

The objective of this study was to estimate the prevalence of athletic amenorrhea in a wide range of long‐distance runners and the relation to possible risk factors. The study group consisted of 187 long‐distance runners between 16 and 46 years of age. Information was obtained through a mailed questionnaire consisting of 32 different entries, including questions on age, leanness, training history, menstrual history, performance level, stress, as well as some sociological and nutritional aspects. Seventy‐six per cent of the responding runners had normal menstrual function, 9.5% had minor irregularities (O), and 14.6% were amenorrheic (A), which is defined as absence of menstrual bleeding for more than 3 consecutive months the previous year. Half of the amenorrheic group had not had menstrual bleeding at all that year. The runners with menstrual disorders (O+A) had a significantly higher incidence of stress fractures. The most important factors associated with menstrual disorders were a feeling of conflict associated with food; age; and the age of menarche. There was no evidence that age of menarche was associated with an early training debut per se, the frequency and intensity of prepubertal training was not taken into account. All subgroups (E, O, and A) had low body mass index scores, and body composition did not seem to vary with menstrual status within the study group. Thus a high prevalence of menstrual disorders was observed in Norwegian long‐distance runners, a condition associated with increased training loads, but even more with age, menarchal age and a feeling of nutritional conflict.
Formation of the digestive tract in Ciona intestinalis includes two distinct morphogenic processes between its anterior and posterior parts

Background: In the ascidian Ciona intestinalis, the digestive tract, an essential system for animals, develops during metamorphosis from the two primordial tissues, the endoderm and endodermal strand, located in the larval trunk and tail, respectively. However, it has been largely unknown how the digestive tract develops from these primordial tissues. We examined the metamorphosing larvae for the tubular formation of the digestive tract, focusing on the epithelial organization of the endoderm, by combined confocal microscopy and computational rendering. Results: The tubular structure of the esophagus to the stomach was formed through the folding and closure of the endodermal epithelia in the central‐to‐right posterior trunk. By contrast, the intestine was formed in the left posterior trunk through the accumulation and rearrangement of the cells originated from the endodermal strand. This was confirmed by the cell‐tracing experiment using Kaede expression construct driven in the endodermal strand. Thus, the tubular formation of the digestive tract in C. intestinalis includes distinct morphogenetic processes and cell lineages between its anterior and posterior parts. Conclusion: This study provides the first detailed description of the digestive tract morphogenesis in C. intestinalis and serves as an important basis toward thorough understanding of its digestive tract development. Developmental Dynamics, 242:1172–1183, 2013. © 2013 Wiley Periodicals, Inc.
Psychological Changes Preceding Spontaneous Remission of Cancer

To develop hypotheses about psychological influences that may favorably affect tumor behavior, 11 patients were recruited who evinced spontaneous regression of histologically diagnosed and reviewed adenocarcinoma (n = 3), lymphoma (n =2), melanoma, chorion carcinoma, ovarian carcinoma, mesothelioma, liver carcinoma or sarcoma, and malignant giant cell tumor (a child). The authors studied retrospectively what had happened to these patients prior to the first signs of their clinical improvement. These patients seemed to have gained access to poignant activities and experiences, shortly prior to their tumor regression. Change involved an increased dystonic reaction to limited aspects of the personality and an increased syntonic reaction to a wider set of characteristics than normally accessed. These changes either followed other persons’ abusive behavior that “went beyond the pale” and elicited a different coping response than previously had been manifested by the patient, or were otherwise facilitated by particular events, independent of the patient’s behavior.