Miracle-dz/UniFAR-FTUs huggingface dataset:
Fluorinated benzenesulfonamide anticancer inhibitors of carbonic anhydrase IX exhibit lower toxic effects on zebrafish embryonic development than ethoxzolamide

Abstract The toxic effects of two recently discovered inhibitors (VD12-09 and VD11-4-2) that selectively and with extraordinary strong, picomolar binding affinity to human carbonic anhydrase (CA) isoform IX were investigated on zebrafish embryonic development. CA IX has been recently introduced as an anticancer target since it is highly overexpressed in numerous human cancers but nearly absent in normal tissues. Morphological changes in zebrafish treated by the compounds were studied by light-field microscopy and histological analysis. Homology models of zebrafish CA II and CA IX were built to identify the conserved amino acid residues in the active site of zebrafish CAs. The toxicity studies here showed that the LC50 values at 120 hours post-fertilization (hpf) were 13 μM for VD12-09, 120 μM for VD11-4-2, and 9 μM for ethoxzolamide (EZA), a non-selective CA inhibitor commonly used as a drug in clinics. Thus, EZA was the most toxic of the three compounds. The zebrafish embryos exposed to LC50 doses of VD12-09 and VD11-4-2 showed fewer phenotypic abnormalities compared with the embryos exposed to the corresponding dose of EZA. Histochemical studies did not show any gross morphological changes in the embryos treated with VD12-09 and VD11-4-2 unlike EZA. The results of our study indicate that the compounds exhibited 10-fold lower toxicity and induced fewer side effects in zebrafish than EZA. Therefore, the exposure to VD11-4-2 and VD12-09 at concentrations below LC50 did not lead to deleterious effects on the zebrafish embryonic development and thus both inhibitors may be further developed as drugs.
Why Do U.S. Securities Laws Matter to Non-U.S. Firms? Evidence from Private Class-Action Lawsuits

A continuing controversy is whether U.S. securities laws are enforced against foreign firms, since public enforcement actions by the SEC are infrequent and often result in insignificant penalties. We examine private enforcement actions of U.S. securities laws and find that 269 securities class-action lawsuits were filed against foreign firms from 1996 to 2008. We document the severity of the penalties imposed on foreign firms and show that while firms paid a total of $9 billion to settle lawsuits brought against them, the monetary penalties levied by the market are even larger. During the three-day period surrounding the lawsuit filing date, there is a significant negative stock price reaction of -6.16%, which translates to an average loss of $392 million dollars. Aggregating over all firms, the total dollar loss is $73 billion. Even foreign firms without significant U.S. assets experience significant valuation losses. Moreover, insiders of the firm bear direct financial losses through their shareholdings. Our results provide evidence that enforcement actions of U.S. securities laws against foreign firms are neither uncommon nor economically insignificant events.
Assessment of change in glucose metabolism in white matter of amyloid-positive patients with Alzheimer disease using F-18 FDG PET

Abstract In Alzheimer disease (AD), neuroinflammation is an important process related to the deposition of beta-amyloid plaques and the activation of microglia. The inflammatory process can occur in both the gray matter and the white matter. We evaluated glucose metabolism of the white matter in AD patients and compared the value with cognitive parameters of the patients. Eighteen AD patients and 18 healthy subjects underwent F-18 fluorodeoxyglucose (FDG) and F-18 florbetaben positron emission tomography (PET). After segmentation of the white matter in both PET images, the specific binding ratio (SBR) of the global and regional cerebral white matter was checked. We evaluated the differences in SBR of the global and regional white matter between AD patients and healthy subjects. Then, we assessed the correlation between SBR and cognitive parameters in AD patients. In F-18 FDG PET images, the global white matter SBR was significantly higher in AD patients than in healthy subjects. In the regional analysis, the white matter SBR was significantly higher for the frontal, temporal, and parietal areas in AD patients. In the correlation analysis with F-18 FDG PET, SBR was significantly correlated with the Global Deterioration Scale, Mini-Mental State Examination scores, and amyloid deposition. Glucose metabolism of the white matter was significantly higher in AD patients than in healthy subjects and it was related to the scores of cognitive parameters. We suggest that F-18 FDG PET, like 18-kDa translocator protein PET, could be used as an indicator of neuroinflammation; however, further research is needed for a direct comparison between the 2 tests.
Effects of structural analogues of apelin-12 in acute myocardial infarction in rats

Objective: To examine cardioprotective effects of Ρ-terminal fragment of adipokine apelin-12 (A12), its novel structural analogue [MeArg1, NLe10]-A12 (I), and [d-Ala12]-A12 (II), a putative antagonist of APJ receptor, employing in vivo model of ischemia/reperfusion (I/R) injury. Materials and Methods: Peptides were synthesized by the automatic solid phase method using Fmoc technology. Anesthetized open-chest male Wistar rats were subjected to left anterior descending (LAD) coronary artery occlusion and coronary reperfusion. Hemodynamic variables and electrocardiogram (ECG) were monitored throughout the experiment. Myocardial injury was assessed by infarct size (IS), activity of necrosis markers in plasma, and metabolic state of the area at risk (AAR). Results: Intravenous injection of A12, I, or II at the onset of reperfusion led to a transient reduction of the mean arterial pressure. A12 or I administration decreased the percent ratio of IS/AAR by 40% and 30%, respectively, compared with control animals which received saline. Both peptides improved preservation of high-energy phosphates, reduced lactate accumulation in the AAR, and lowered CK-MB and LDH activities in plasma at the end of reperfusion compared with these indices in control. Treatment with II did not significantly affect either the IS/AAR, % ratio, or activities of both markers of necrosis compared with control. The overall metabolic protection of the AAR in the treated groups increased in the following rank: II < A12 < I. Conclusions: The structural analogue of apelin-12 [MeArg1, NLe10]-A12 may be a promising basis to create a new drug for the treatment of acute coronary syndrome.
Estimation of Marine Primary Productivity From Satellite-Derived Phytoplankton Absorption Data

The global ocean net primary production (NPP) was estimated from satellite-derived information using a phytoplankton pigment absorption (aph)-based model. Satellite-derived spectral-averaged aph was used as the key predictor of phytoplankton photosynthetic efficiency in the model. The aph-based model yields an annual integrated NPP of approximately 55 Pg C year-1 for the global oceans over the period 2003-2010. The accuracy of the model was validated by comparing it with in situ NPP at three sites, and the logarithmic root-mean-square error of the model was approximately 0.18. The model performance was also compared with two existing NPP models (chlorophyll-based model and carbon-based model) in terms of spatial distribution, seasonal cycles, and accuracy. The comparison results indicated that the aph-based model has improved accuracy in describing NPP variation for monthly timescales compared with the other two models. We were surprised to find that the spatial distribution of global ocean NPP provided by the aph-based model is more similar to the carbon-based model than the chlorophyll-based model. Although many additional studies need to be conducted, the performance of the aph-based model in this work may encourage us to estimate ocean NPP from satellite-derived phytoplankton pigment absorption.
Quantification of Posterior Capsule Tightness and Motion Loss in Patients with Shoulder Impingement

The relationship between posterior capsule tightness and dysfunction has long been recognized clinically but has not been biometrically quantified. The purpose of this study was to quantify changes in range of motion and posterior capsule tightness in patients with dominant or nondominant shoulder impingement. Measurements of posterior capsule tightness and external and internal rotation range of motion were made in 31 patients with shoulder impingement and in 33 controls without shoulder abnormality. Patients with impingement in the nondominant arm had increased posterior capsule tightness and decreased internal and external rotation range of motion compared with controls. Patients with impingement in their dominant arm had increased posterior capsule tightness and reduced internal rotation range of motion but no significant loss of external rotation range of motion compared with controls. Posterior capsule tightness in impingement patients showed a significant correlation with loss of internal rotation range of motion. Patients with shoulder impingement in their nondominant arm had a more global loss of range of motion compared with patients having impingement in their dominant arm. We believe we have described a valid clinical measurement for identifying posterior capsule tightness in patients with shoulder impingement.
Clinical Outcomes for Reconstruction of the Posterolateral Corner and Posterior Cruciate Ligament in Injuries With Mild Grade 2 or Less Posterior Translation

Background: There have been no previous studies showing clinical outcomes according to treatment options of posterior cruciate ligament (PCL) injury with mild grade 2 or less posterior translation (<7 mm) combined with posterolateral rotatory instability. Purpose: To compare the clinical outcomes of posterolateral corner (PLC) reconstruction with or without simultaneous PCL reconstruction in PCL injuries with mild posterior translation. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 46 patients with a PCL injury with mild posterior translation combined with posterolateral rotatory instability were retrospectively reviewed. Twenty-two patients had undergone isolated PLC reconstruction (group A), and 24 patients had undergone simultaneous reconstruction of the PCL and PLC (group B). Each patient was assessed for knee instability with the dial test at 30° and 90° as well as with varus and posterior stress radiography and were evaluated with the Lysholm knee score and International Knee Documentation Committee (IKDC) subjective and objective grading. Results: In all cases, the minimum follow-up period was 24 months. At the final follow-up evaluation, no significant side-to-side difference was found on varus stress radiography (group A, 1.55 ± 0.78 mm vs group B, 1.35 ± 1.00 mm; P = .458) or the dial test (at 30°: group A, 4.00° ± 1.83° vs group B, 4.04° ± 1.30°; P = .929; at 90°: group A, 3.64° ± 1.18° vs group B, 3.67° ± 1.37°; P = .937). However, group B showed a significant improvement compared with group A on posterior stress radiography (group A, 0.16 ± 0.44 mm vs group B, –1.44 ± 0.74 mm; P < .001), Lysholm knee score (group A, 18.36 ± 8.73 vs group B, 23.42 ± 7.44; P = .040), IKDC subjective score (group A, 25.51 ± 7.11 vs group B, 33.08 ± 5.89; P < .001), and IKDC objective score (group A preoperatively: grade C = 19 patients, grade D = 3; group B preoperatively: grade C = 20, grade D = 4; group A postoperatively: grade B = 11, grade C = 11; group B postoperatively: grade A = 12, grade B = 9, grade C = 3) (P < .001). Conclusion: Simultaneous reconstruction of the PCL and PLC is recommended when addressing PCL injuries with mild grade 2 or less posterior translation combined with posterolateral rotary instability.
Thoracic epidural spinal angiolipoma with coexisting lumbar spinal stenosis: Case report and review of the literature

Background Spinal angiolipomas (SALs) are uncommon benign lesions that may present insidiously with back pain or acutely with weakness due to tumor bleeding/thrombosis. Given their rarity, these lesions are often overlooked in the differential diagnosis of epidural masses. The purpose of this article is to report the case of an epidural SAL and to conduct a literature review on the topic. Methods A case report and review of the literature using the PubMed/Medline databases. All case reports and case series were reviewed up to June 2015. Results A 65-year old female presented with neurogenic claudication and magnetic resonance imaging (MRI) revealed lumbar spinal stenosis. Following decompressive surgery, she experienced symptom resolution, but three months postoperatively she presented to the emergency department with acute paraparesis. A thoracic MRI revealed a lesion located between T8 and T10 causing severe spinal cord compression. Following emergent laminectomy and en bloc resection, the patient regained function and the lesion was diagnosed as SAL. Our literature review revealed 178 reported cases, with a female and thoracic predominance. The majority of patients underwent surgical treatment, achieving a gross total resection in most cases. Similarly, complete symptom resolution was the most common outcome. Conclusion Spinal angiolipomas are uncommon spinal tumors. However, they may be treated as any other space-occupying lesion, and surgical resection allows for complete symptom recovery in most patients.
Loss of heterozygosity of chromosome 12p does not correlate with KRAS mutation in non‐small cell lung cancer

Activating mutations of RAS gene families have been found in a variety of human malignancies, including lung cancer, suggesting their dominant role in tumorigenesis. However, several studies have shown a frequent loss of the wild‐type KRAS allele in the tumors of murine models and an inhibition of oncogenic phenotype in tumor cell lines by transfection of wild‐type RAS, indicating that wild‐type RAS may have oncosuppressive properties. To determine whether loss of wild‐type KRAS is involved in the development of human lung cancer, we investigated the mutations of KRAS, NRAS and BRAF in 154 primary non‐small cell lung cancers (NSCLCs) as well as 10 NSCLC cell lines that have been shown to have KRAS mutations. We also determined the loss of heterozygosity status of KRAS alleles in these tumors. We detected point mutations of KRAS in 11 (7%) of 154 NSCLCs, with 10 cases at codon 12 and 1 at codon 61, but no mutations of NRAS or BRAF were found. Using the laser capture microdissection technique, we confirmed that 9 of the 11 tumors and 7 of the 10 NSCLC cell lines retained the wild‐type KRAS allele. Among the cell lines with heterozygosity of mutant and wild‐type KRAS, all of the cell lines tested for expression were shown to express more mutated KRAS than wild‐type mRNA, with higher amounts of KRAS protein also being expressed compared to the cell lines with a loss of wild‐type KRAS allele. In addition, among 148 specimens available for immunohistochemical analysis, 113 (76%) showed positive staining of KRAS, indicating that the vast majority of NSCLCs continue to express wild‐type KRAS. Our findings indicate that the wild‐type KRAS allele is occasionally lost in human lung cancer, and that the oncogenic activation of mutant KRAS is more frequently associated with an overexpression of the mutant allele than with a loss of the wild‐type allele in human NSCLC development. © 2003 Wiley‐Liss, Inc.
The Frankfurt Patient Safety Climate Questionnaire for General Practices (FraSiK): analysis of psychometric properties

Background Safety culture has been identified as having a major impact on how safety is managed in healthcare. However, it has not received much attention in general practices. Hence, no instrument yet exists to assess safety climate—the measurable artefact of safety culture—in this setting. This study aims to evaluate psychometric properties of a newly developed safety climate questionnaire for use in German general practices. Methods The existing Safety Attitudes Questionnaire, Ambulatory Version, was considerably modified and enhanced in order to be applicable in general practice. After pilot tests and its application in a random sample of 400 German practices, a first psychometric analysis led to modifications in several items. A further psychometric analysis was conducted with an additional sample of 60 practices and a response rate of 97.08%. Exploratory factor analysis with orthogonal varimax rotation was carried out and the internal consistency of the identified factors was calculated. Results Nine factors emerged, representing a wide range of dimensions associated with safety culture: teamwork climate, error management, safety of clinical processes, perception of causes of errors, job satisfaction, safety of office structure, receptiveness to healthcare assistants and patients, staff perception of management, and quality and safety of medical care. Internal consistency of factors is moderate to good. Conclusions This study demonstrates the development of a patient safety climate instrument. The questionnaire displays established features of safety climate and additionally contains features that might be specific to small-scale general practices.
Oxytocin release by infused prostaglandin.

There are few reports of acute cerebellar ataxia presenting in adults and it is of interest that Brumlik and Means3 describe two American cases showing "lightening eye movements, peculiar shuddering tremor and cerebellar ataxia. " It is tempting to postulate that encephalitis tremens, a benign epidemic form of acute cerebellar ataxia with R.I. M.E. L. limited geographically to a region of West Africa rain forest, might represent an abor virus encephalitis involving the brainstem. However, such an assumption awaits investigation. -I am, etc., HUGH COAKHAM Royal West Sussex Hospital, Chichester, Sussex
Altered control of skin blood flow during exercise at high internal temperatures.

We have investigated further the behavior of skin blood flow (SkBF) as internal temperature (measured as esophageal temperature (Tes)) rises in a heated exercising man. A previous study showed that when skin temperature (Tsk) is driven up in exercising men, the increase in SkBF is less than that found for the same Tes and Tsk in a resting man. In this study, we extended our observations into the range of higher Tes to see if SkBF (measured plethysmographically as changes in forearm blood flow) could be driven to higher levels despite competition with skeletal muscle for cardiac output. After Tsk was elevated to 38 degrees C by means of water-perfused suits, subjects exercised at 525-900 kp.m/min (86-147 W) for 17-30 min while Tsk was held at 38 degrees C. We found that SkBF increase per unit increase in Tes is attenuated at higher Tes. In seven men, the average slope obtained from linear regression of FBF on Tes below 38 degrees C was 7.6 flow units/degrees C. Above 38 degrees C, the average was 2.12 flow units/degrees C. In some subjects, the FBF response appeared virtually saturated at a plateau despite a steady rate of increase in Tes with time. Clearly, SkBF does not increase in direct proportion to Tes without bound. Other stimuli (presumably related to blood pressure regulation) interact either to reduce the rate of SkBF increase or to prevent any further increase after Tes exceeds 38 degrees C.
Functional Association of Arabidopsis CAX1 and CAX3 Is Required for Normal Growth and Ion Homeostasis1

Cation levels within the cytosol are coordinated by a network of transporters. Here, we examine the functional roles of calcium exchanger 1 (CAX1), a vacuolar H+/Ca2+ transporter, and the closely related transporter CAX3. We demonstrate that like CAX1, CAX3 is also localized to the tonoplast. We show that CAX1 is predominately expressed in leaves, while CAX3 is highly expressed in roots. Previously, using a yeast assay, we demonstrated that an N-terminal truncation of CAX1 functions as an H+/Ca2+ transporter. Here, we use the same yeast assay to show that full-length CAX1 and full-length CAX3 can partially, but not fully, suppress the Ca2+ hypersensitive yeast phenotype and coexpression of full-length CAX1 and CAX3 conferred phenotypes not produced when either transporter was expressed individually. In planta, CAX3 null alleles were modestly sensitive to exogenous Ca2+ and also displayed a 22% reduction in vacuolar H+-ATPase activity. cax1/cax3 double mutants displayed a severe reduction in growth, including leaf tip and flower necrosis and pronounced sensitivity to exogenous Ca2+ and other ions. These growth defects were partially suppressed by addition of exogenous Mg2+. The double mutant displayed a 42% decrease in vacuolar H+/Ca2+ transport, and a 47% decrease in H+-ATPase activity. While the ionome of cax1 and cax3 lines were modestly perturbed, the cax1/cax3 lines displayed increased PO43−, Mn2+, and Zn2+ and decreased Ca2+ and Mg2+ in shoot tissue. These findings suggest synergistic function of CAX1 and CAX3 in plant growth and nutrient acquisition.
Comparative expression analysis of transcription factor genes in the endostyle of invertebrate chordates

The endostyle of invertebrate chordates is a pharyngeal organ that is thought to be homologous with the follicular thyroid of vertebrates. Although thyroid‐like features such as iodine‐concentrating and peroxidase activities are located in the dorsolateral part of both ascidian and amphioxus endostyles, the structural organization and numbers of functional units are different. To estimate phylogenetic relationships of each functional zone with special reference to the evolution of the thyroid, we have investigated, in ascidian and amphioxus, the expression patterns of thyroid‐related transcription factors such as TTF‐2/FoxE4 and Pax2/5/8, as well as the forkhead transcription factors FoxQ1 and FoxA. Comparative gene expression analyses depicted an overall similarity between ascidians and amphioxus endostyles, while differences in expression patterns of these genes might be specifically related to the addition or elimination of a pair of glandular zones. Expressions of Ci‐FoxE and BbFoxE4 suggest that the ancestral FoxE class might have been recruited for the formation of thyroid‐like region in a possible common ancestor of chordates. Furthermore, coexpression of FoxE4, Pax2/5/8, and TPO in the dorsolateral part of both ascidian and amphioxus endostyles suggests that genetic basis of the thyroid function was already in place before the vertebrate lineage. Developmental Dynamics 233:1031–1037, 2005. © 2005 Wiley‐Liss, Inc.
Comparing doctors' and nurses' accounts of how they provide emotional care for parents of children with acute lymphoblastic leukaemia

Despite the emphasis that communication skills training (CST) programmes place on attending to the emotional care of patients, evidence suggests that practitioners neglect this aspect of patient care. We describe and compare doctors' and nurses' accounts of managing the emotional care of parents of children with leukaemia, with the overall objective of examining how their accounts might inform training and policy.