Miracle-dz/UniFAR-FTUs huggingface dataset:
Tpbpa-Cre-mediated deletion of TFAP2C leads to deregulation of Cdkn1a, Akt1 and the ERK pathway, causing placental growth arrest

Loss of TFAP2C in mouse leads to developmental defects in the extra-embryonic compartment with lethality at embryonic day (E)7.5. To investigate the requirement of TFAP2C in later placental development, deletion of TFAP2C was induced throughout extra-embryonic ectoderm at E6.5, leading to severe placental abnormalities caused by reduced trophoblast population and resulting in embryonic retardation by E8.5. Deletion of TFAP2C in TPBPA+ progenitors at E8.5 results in growth arrest of the junctional zone. TFAP2C regulates its target genes Cdkn1a (previously p21) and Dusp6, which are involved in repression of MAPK signaling. Loss of TFAP2C reduces activation of ERK1/2 in the placenta. Downregulation of Akt1 and reduced activation of phosphorylated AKT in the mutant placenta are accompanied by impaired glycogen synthesis. Loss of TFAP2C led to upregulation of imprinted gene H19 and downregulation of Slc38a4 and Ascl2. The placental insufficiency post E16.5 causes fetal growth restriction, with 19% lighter mutant pups. Knockdown of TFAP2C in human trophoblast choriocarcinoma JAr cells inhibited MAPK and AKT signaling. Thus, we present a model where TFAP2C in trophoblasts controls proliferation by repressing Cdkn1a and activating the MAPK pathway, further supporting differentiation of glycogen cells by activating the AKT pathway. Highlighted article: In trophoblast progenitor cells, the transcription factor TFAP2C regulates proliferation and differentiation. Tfap2c mutant mice provide a model of intrauterine growth retardation.
Have the risks of rosiglitazone been exaggerated?

Nissen and Wolski recently reported a meta-analysis of 42 clinical trials of 27,847 subjectsthat ignited a firestorm of controversy by claim-ing that treatment with rosiglitazone (Avandia,GlaxoSmithKline [GSK]), a widely prescribedPPAR-γ agonist, was associated with a “…worri-some…” 43% greater risk of myocardial infarc-tion (MI; p = 0.03) and a 64% greater risk ofcardiovascular death (CVD; p = 0.06)
Predicting G-Protein-Coupled Receptor classes based on adaptive K-nearest neighbor algorithm

G-Protein-Coupled Receptor (GPCRs) play a key role in cellular signaling networks that regulate various physiological processes. The functions of many of GPCRs are unknown, because they are difficult to crystallize and most of them will not dissolve in normal solvents. This difficulty has motivated and challenged the development of a computational method which can predict the classification of the families and subfamilies of GPCRs based on their primary sequence so as to help us classify drugs. In this paper the adaptive K-nearest neighbor algorithm and protein cellular automata image (CAI) is introduced. Based on the CAI, the complexity measure factors derived from each of the protein sequences concerned are adopted for its Pseudo amino acid composition. GPCRs were categorized into nine subtypes. The overall success rate in identifying GPCRs among their nine family classes was about 83.5%. The high success rate suggests that the adaptive k-nearest neighbor algorithm and protein CAI holds very high potential to become a useful tool for understanding the actions of drugs that target GPCRs and designing new medications with fewer side effects and greater efficacy.
Neuropsychological test performance in social anxiety disorder

Abstract Background: The effect of state factors on neuropsychological performance in social anxiety disorder (SAD) has not been thoroughly investigated and the overall neuropsychological profile remains poorly understood. Aims: The primary objective of the study was to investigate the effect of state anxiety and state emotion suppression on neuropsychological performance in SAD. Methods: A neuropsychological test battery was administered before and after an anxiety manipulation (instruction to give a video-recorded speech) to 42 patients with SAD and to a gender and education matched group of 42 healthy controls (HCs). Results: Overall, participants with SAD performed worse than HCs on processing speed, visuospatial construction, visuospatial memory, verbal learning and word fluency, of which only the decreased visuospatial construction performance was considered clinically significant. State anxiety was not associated with neuropsychological performance at baseline, whereas state emotion suppression predicted decreased visuospatial memory in HCs and decreased verbal learning in the SAD group. Both groups performed better on working memory, processing speed and spatial anticipation, and worse on verbal learning and memory following the anxiety manipulation. The increase in state anxiety was associated with the decrease in verbal learning in both groups. Conclusions: Participants with SAD showed clinically significant difficulties with visuospatial construction and may experience verbal learning difficulties when suppressing emotions and experiencing an increase in anxiety.
Life‐Threatening Bradyarrhythmia After Massive Azithromycin Overdose

A 9‐month‐old infant was inadvertently administered azithromycin 50 mg/kg, taken from floor stock, instead of the prescribed ceftriaxone. Shortly thereafter, she became unresponsive and pulseless. The initial heart rhythm observed when cardiopulmonary resuscitation was started was a wide‐complex bradycardia, with a prolonged rate‐corrected QT interval and complete heart block. The baby was resuscitated with epinephrine and atropine, but she suffered severe anoxic encephalopathy. Torsade de pointes and QT‐interval prolongation have been reported after administration of macrolide antibiotics, including azithromycin, both intravenously and orally. This has occurred especially in the context of coadministered drugs that inhibit the cytochrome P450 (CYP) 3A4 isoenzyme, such as ketoconazole and astemizole. However, bradycardia with complete heart block has not, to our knowledge, been reported specifically with intravenous administration of azithromycin alone, either with therapeutic doses or overdose. Clinicians should be alerted about the potential of azithromycin to cause life‐threatening bradycardia, and pharmacy systems should be implemented to ensure special care in the safe administration of this drug, especially when dispensed from a point‐of‐care source.
Utility of direct immunofluorescence and virus culture for detection of varicella-zoster virus in skin lesions

A direct immunofluorescence assay (DFA) with a monoclonal antibody from Ortho Diagnostic Systems was compared with conventional cell culture for the rapid detection of varicella-zoster virus (VZV) in 140 dermal lesions from 133 patients. A total of 79 (56%) specimens were positive for VZV: 40 (51%) by DFA alone, 2 (3%) by culture only, and 37 (47%) by both culture and DFA. After discordant analysis, the sensitivities and negative predictive values, respectively, were 97.5% (77 of 79) and 96.8% (61 of 63) for DFA and 49.4% (39 of 79) and 60.4% (61 of 101) for viral culture. Of the 39 positive viral cultures, VZV was isolated from 38 (97%) cultures in A549 cells, 23 (59%) in primary rhesus monkey kidney cells, and only 16 (41%) in MRC-5 cells. We conclude that DFA is the optimal method for rapid identification of VZV. In addition, better recovery of VZV in culture may be achieved by using A549 cells.
Spirituality and ethical behaviour in the workplace: wishful thinking or authentic reality

The link between religion and work is not new. For centuries, people have strived to interpret their work through religious lenses. Recently, however, a significant paradigm shift has occurred. The current view is that spirituality, as opposed to religion, is a better construct for understanding the relationship between the individual and modern pluralistic workplaces. This current perspective, sourced in various socio-cultural factors, views spirituality as positively influencing numerous organisational outcomes. Also implicit within this discourse is the notion that allowing and encouraging spirituality in the workplace leads to improved ethical behaviour at a personal level and an enhanced ethical climate/culture at an organisational level. What is unclear, however, is how an individual’s spirituality translates into ethical behaviour within an organisational context and the impact of this conversion. This paper develops a model explaining this process. A review of the relevant literature recognised several characteristics that permeate discussions on spirituality. This paper’s premise is that these characteristics inform an individual’s choice of values – they form a type of regulative ideal. The model developed explains the link between these values and virtue and therefore ethical behaviour in the workplace. The values frameworks developed recently in the spirituality literature specify those things a spiritual person perceives as worth having, getting or doing. This paper contends that these values, particular to spiritual persons, contribute to the flourishing of individuals and therefore lead to the acquisition of virtue. Spiritual persons are likely to be ethical persons. Such individuals are likely to be of significant benefit to their organisations.
Analysis of the characteristics and factors influencing lymph node metastasis in thoracic esophageal carcinoma and cancer of the gastric cardia.

BACKGROUND/AIMS To analyze the metastatic characteristics of lymph nodes in thoracic esophageal carcinoma and cancer of the gastric cardia, and to explore the factors influencing lymph node metastasis. METHODOLOGY A retrospective analysis of the treatment of 37 patients who received surgical treatment for thoracic esophageal and gastric cardia cancers from January 2010 to January 2012 was carried out, RESULTS Lymph node metastasis in patients with thoracic esophageal carcinoma was frequently found on the superior mediastinum, hilum of the lung, and inferior extremity of the carina. Metastasis in patients with cancer of the gastric cardia occurred mainly in the abdominal cavity and peripheral gastric cardia. A single factor analysis showed that a tumor infiltrating full-thickness, > 5 cm in length, and with a low degree of cell differentiation affected lymph node metastasis (P < 0.05). The degree of differentiation, length, and infiltrating depth of the tumor were independent factors affecting lymph node metastasis (P < 0.05). CONCLUSIONS Lymph node metastasis in patients with cancers of the esophagus and gastric cardia exhibits special characteristics. The cleaning scope should be assessed according to the actual situation, including the degree of tumor differentiation, lesion length, and infiltration depth.
Randomized, double‐blind trial of mazindol in Duchenne dystrophy

There is evidence that growth hormone may be related to the progression of weakness in Duchenne dystrophy. We conducted a 12‐month controlled trial of mazindol, a putative growth hormone secretion inhibitor, in 83 boys with Duchenne dystrophy. Muscle strength, contractures, functional ability and pulmonary function were tested at baseline, and 6 and 12 months after treatment with mazindol (3 mg/d) or placebo. The study was designed to have a power of >0.90 to detect a slowing to 25% of the expected rate of progression of weakness at P < 0.05. Mazindol did not benefit strength at any point in the study. Side effects attributable to mazindol included decreased appetite (36%), dry mouth (10%), behavioral change (22%), and gastrointestinal symptoms (18%); mazindol dosage was reduced in 43% of patients. The effect of mazindol on GH secretion was estimated indirectly by comparing the postabsorptive IGF‐I levels obtained following 3, 6, 9, and 12 months in the mazindol treated to those in the placebo groups. Although mazindol‐treated patients gained less weight and height than placebotreated patients, no significant effect on IGF‐I levels was observed. Mazindol does not slow the progression of weakness in Duchenne dystrophy.
A new time‐space accounting scheme to predict stream water residence time and hydrograph source components at the watershed scale

Hydrograph source components and stream water residence time are fundamental behavioral descriptors of watersheds but, as yet, are poorly represented in most rainfall‐runoff models. We present a new time‐space accounting scheme (T‐SAS) to simulate the pre‐event and event water fractions, mean residence time, and spatial source of streamflow at the watershed scale. We use a physically based hydrologic model together with field data from the well‐studied Maimai M8 watershed and HJ Andrews WS10 watershed to explore how catchment properties, particularly soil depth, controls the age and source of streamflow. Our model simulates unsaturated, saturated subsurface, and surface rainfall‐runoff processes. We first demonstrate the ability of the model to capture hydrograph dynamics and compare the model flow component and age simulations against measured values at the two sites. We show that the T‐SAS approach can capture flow and transport dynamics for the right dominant process reasons. We then conduct a series of virtual experiments by switching soil depths between the two watersheds to understand how soil depth and its distribution control water age and source. Results suggest that thicker soils increase mean residence time and damp its temporal dynamics in response to rainfall inputs. Soil depth influenced the geographic source of streamflow, whereas pre‐event water sources became more concentrated to near stream zones as soil depth increased. Our T‐SAS approach provides a learning tool for linking the dynamics of residence time and time‐space sources of flow at the watershed scale and may be a useful framework for other distributed rainfall‐runoff models.
Difference in Blood Pressure between Arms of Normotensive Female Farmers in the Semi-arid Midlands of Kenya

Introduction: Hypertension has been identified as the leading risk factor for mortality worldwide. The common clinical practice of one arm blood pressure measure and the presence of a difference between arm measurements is likely to lead to delayed diagnosis of hypertension and is associated with a higher prevalence of poor control of hypertension. Objective: To examine inter-arm differences that could give rise to undetected hypertension. Methods: A household cross-sectional survey was undertaken amongst 293 females who were participating in agricultural farm activities in lower Eastern Kenya. Six alternating arm blood pressure readings were taken, three on each arm with 3 minutes rest between each session. Results: Marginal but statistically significant inter-arm differences were observed in mean systolic blood pressure (right-arm 124.4 ± 12.5 mmHg; left-arm 123.3 ± 13.2 mmHg) and diastolic blood pressure (right-arm 75.4 ± 8.9 mmHg; left-arm 76.2 ± 9.1 mmHg). Right arm blood pressure readings indicated a higher prevalence of prehypertension and hypertension (51.2% and 12.3%) than left-arm (47.8 and 10.6%; p=0.001) readings. Statistically significant intra-arm differences (p=0.001) were observed between the 1st vs. 2nd and the 1st vs. 3rd right and left arm systolic blood pressure and diastolic blood pressure readings respectively. Conclusion and recommendation: Repeated blood pressure readings when measured on both arms can assist in more accurate identification of elevated blood pressure and timely diagnosis of hypertension. Population-wide studies are needed to examine the long term significance of blood pressure differences between arms.
Perioperative Sublingual Isosorbide Dinitrate for the Prevention of Cardiac Complications in Cardiac Patients Undergoing Noncardiac Surgery

One hundred fifty-two consecutive patients with a known or suspected diagnosis of atherosclerotic coronary artery disease were administered 5 mg sublingual isosorbide dinitrate 2 hours and/hour preoperatively and every 4 hours postoperatively for 3 days, for the prevention of cardiovascular morbidity and mortality, which could result from various noncardiac surgical procedures; 125 patients received general anesthesia. Cardiovascular complications occurred in 3 patients (1.9%). Two patients did not enter the study, owing to side effects of the medication (1.3%). The complications were 1 each (0.6%) of the following: atrial fibrillation, hypotension, and cardiac arrest. Mortality was 0%. These results are exceptionally favorable when compared to the average cardiovascular morbidity rate of 2.8% to 49% in patients assigned to various risk stratifications in the medical literature.
Altered coronary vasomotor function in young patients with systemic lupus erythematosus.

OBJECTIVE Accelerated atherosclerosis is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Altered coronary microvascular function may act as a marker of changes that predispose to the development of significant coronary vascular disease. The purpose of this study was to compare coronary flow reserve (CFR) in a group of premenopausal women with SLE and a group of age-, sex-, and race-matched healthy control subjects. METHODS Coronary flow velocity in 18 premenopausal women with SLE (mean +/- SD age 29.4 +/- 5.9 years) and 19 matched healthy controls (mean +/- SD age 28.2 +/- 4.3 years) was assessed by transthoracic Doppler echocardiography after an overnight fast. The CFR was calculated as the ratio of hyperemic to baseline coronary blood flow velocity in the left anterior descending coronary artery. Hyperemia was induced by intravenous administration of adenosine triphosphate. RESULTS The mean +/- SD duration of SLE was 8.2 +/- 7.2 years (range 0.25-25 years), and the mean +/- SD score on the Systemic Lupus Erythematosus Disease Activity Index was 11.0 +/- 5.3 (range 4.0-21.0). Adequate recordings of flow velocity in the left anterior descending artery under both conditions were obtained using an ultrasound procedure in all study subjects. CFR was significantly lower in SLE patients as compared with control subjects (mean +/- SD 3.4 +/- 0.8 versus 4.5 +/- 0.5; P < 0.0001). CONCLUSION These findings provide evidence that coronary vasomotor function is impaired in patients with SLE and support the notion that many of these young patients have subclinical coronary artery disease.
Pyrexia of undetermined origin, diarrhoea, and primary cerebral lymphoma associated with acquired immunodeficiency.

States. Analysis of 483 cases in man. N EnglJr Med 1965;273:857-64, 915-22. s Burke BJ, Searle JF, Mattingly D. Leptospirosis presenting with profuse haemoptysis. Br MedJ 1972;ii :982. 'Zlatzman M, Kallenbach JM, Goss GD, Lewis M, Zwi S, Gear JHS. Adult respiratory distress syndrome in Leptospira canicola infection. Br MedJ 1981 ;283:519-20. Jacobs JH. Spondylitis following Weil's disease. Ann Rheum Dis 1951; 10 :61-4.
Riboflavin uptake by the human‐derived liver cells Hep G2: Mechanism and regulation

The water‐soluble vitamin riboflavin (RF) plays a critical role in many metabolic reactions, and thus, is essential for normal cellular functions and growth. The liver plays a central role in normal RF metabolism and is the site of maximal utilization of the vitamin. The mechanism of liver uptake of RF has been studied in animals, but no information is available describing the mechanism of the vitamin uptake in the human situation and its cellular regulation. In this study, we used the human‐derived liver cells Hep G2 as an in vitro model system to address these issues. Uptake of RF by Hep G2 cells was found to be temperature‐ and energy‐dependent but Na+‐independent in nature. Uptake seemed to involve a carrier‐mediated process as indicated by the saturation as a function of substrate concentration (apparent Km 0.41 ± 0.08 μM), and by the ability of the structural analogs lumiflavin and lumichrome to inhibit the uptake process [inhibition constant (Ki) of 1.84 and 6.32 μM, respectively]. RF uptake was energy dependent, and was inhibited by the ‐SH group blocker p‐chloromercuriphenylsulfonate (p‐CMPS) (Ki of 0.10 mM). Specific modulators of intracellular protein kinase A (PKA)‐, protein kinase C (PKC)‐, and protein tyrosine kinase (PTK)‐mediated pathways did not affect RF uptake by Hep G2 cells. On the other hand, specific inhibitors of Ca2+/calmodulin‐mediated pathway significantly inhibited the uptake process; this effect seemed to be mediated through a decrease in the Vmax of the substrate uptake process. Maintaining Hep G2 cells in a RF‐deficient growth medium was associated with a significant up‐regulation in the substrate uptake; this effect was specific for RF and was mediated mainly by means of an increase in the Vmax of the uptake process. These results describe, for the first time, the mechanism and cellular regulation of RF uptake by a human‐derived liver cellular preparation, and shows the involvement of a carrier‐mediated system in the uptake process. Furthermore, the uptake process seems to be regulated by an intracellular Ca2+/calmodulin‐mediated pathway and by extracellular substrate levels. J. Cell. Physiol. 176:588–594, 1998. © 1998 Wiley‐Liss, Inc.
Longitudinal clinical and microbiological study on the relationship between infection with Streptococcus mutans and the development of caries in humans.

This 24 months prospective study was undertaken to test the principle that infection with S. mutans on human fissure and smooth tooth surfaces at risk for caries will lead to decalcification and/or cavitation lesions. Forty-eight elementary school students aged 7-8 years were recruited and enrolled in the study in an overlapping fashion. The children were examined annually for plaque, gingivitis and dental caries which was scored both clinically and radiographically. In addition, 4-6 microbiological samples were obtained every 3 months from each participant on predetermined sites of mesial aspects or fissures of first molars using sterile floss or hypodermic needles. The test sample represented 258 tooth surfaces at risk producing a total of 1528 microbiological samples. The samples were processed and identified on selective and non-selective media using anaerobic techniques. The total colony forming units (CFU/ml) and % of anaerobic and facultative organisms and S. mutans were enumerated. During the entire duration of the study 40 initial (DI) and 6 carious lesions with cavitation (DC) developed in 36 subjects. Eleven established initial lesions (EI) and 12 remineralized surfaces (R) were followed. The control sample consisted of three groups of sites which remained caries-free throughout the study: 34 sites in control group (CA) of caries-free children (DFS = 0), 35 sites in children with some filled teeth (CB) (DFS > 5) and 36 sites in children with only one initial lesion (CC) (DFS= 1 or 2) were followed microbiologically for 1-2 years. DI and DC showed significantly higher levels of S. mutans than controls 9 and 6 months prior to the clinical diagnosis, while R surfaces yielded significantly lower S. mutans levels 9, 6 and 3 months prior to the diagnosis of the reversal. However, in one single DC lesion, S. mutans could not be documented at any observation period prior to the diagnosis of the cavity. Thus, the results confirmed the role of S. mutans as an important, but not exclusive initiator of dental caries. Furthermore, a temporal relationship between infection with S. mutans and clinical diagnosis could be demonstrated.