Miracle-dz/UniFAR-FTUs huggingface dataset:
Crystal structure of cleaved vaspin (serpinA12)

Abstract The adipokine vaspin (serpinA12) is mainly expressed in white adipose tissue and exhibits various beneficial effects on obesity-related processes. Kallikrein 7 is the only known target protease of vaspin and is inhibited by the classical serpin inhibitory mechanism involving a cleavage of the reactive center loop between P1 (M378) and P1′ (E379). Here, we present the X-ray structure of vaspin, cleaved between M378 and E379. We provide a comprehensive analysis of differences between the uncleaved and cleaved forms in the shutter, breach, and hinge regions with relation to common molecular features underlying the serpin inhibitory mode. Furthermore, we point out differences towards other serpins and provide novel data underlining the remarkable stability of vaspin. We speculate that the previously reported FKGx1Wx2x3 motif in the breach region may play a decisive role in determining the reactive center loop configuration in the native vaspin state and might contribute to the high thermostability of vaspin. Thus, this structure may provide a basis for future mutational studies.
Biomechanical and biochemical regulation of cathepsin K expression in endothelial cells converge at AP-1 and NF-κB

Abstract Cathepsins K and V are powerful elastases elevated in endothelial cells by tumor necrosis factor-α (TNFα) stimulation and disturbed blood flow both of which contribute to inflammation-mediated arterial remodeling. However, mechanisms behind endothelial cell integration of biochemical and biomechanical cues to regulate cathepsin production are not known. To distinguish these mechanisms, human aortic endothelial cells (HAECs) were stimulated with TNFα and exposed to pro-remodeling or vasoprotective shear stress profiles. TNFα upregulated cathepsin K via JNK/c-jun activation, but vasoprotective shear stress inhibited TNFα-stimulated cathepsin K expression. JNK/c-jun were still phosphorylated, but cathepsin K mRNA levels were significantly reduced to almost null indicating separate biomechanical regulation of cathepsin K by shear stress separate from biochemical stimulation. Treatment with Bay 11-7082, an inhibitor of IκBα phosphorylation, was sufficient to block induction of cathepsin K by both pro-remodeling shear stress and TNFα, implicating NF-κB as the biomechanical regulator, and its protein levels were reduced in HAECs by vasoprotective shear stress. In conclusion, NF-κB and AP-1 activation were necessary to activate cathepsin K expression in endothelial cells, highlighting integration of biochemical and biomechanical stimuli to control cathepsins K and V, powerful elastases implicated for arterial remodeling due to chronic inflammation and disturbed blood flow.
Asthma susceptibility variants are more strongly associated with clinically similar subgroups

Abstract Objective: Genome-wide association studies (GWAS) identified single nucleotide polymorphisms (SNPs) reproducibly associated with asthma. This study evaluated whether GWAS-nominated SNPs are more strongly associated with asthma patients sharing the same clinical characteristics in order to refine the role of recently identified genes. Methods: Analyses were performed in unrelated French Canadian subjects (566 cases and 416 controls) with data collected on lung function, blood cell counts, atopy, disease history and medication. Previously defined asthma subgroups were used for analysis: 1) older patients with low atopy and low lung function, 2) high atopy, 3) young non-smoking women and 4) high smoking history. Allele frequencies of 68 GWAS-nominated SNPs were compared between controls and cases or controls and subgroups of cases defined by cluster analysis. Results: Twelve GWAS-nominated SNPs demonstrated evidence of replication (p value < 0.05) for association with asthma. In phenotypically similar asthma patients, rs10197862, located in IL1RL1/IL18R1, was the most strongly associated SNP with the high atopy subgroup (p = 0.0009). SNPs located at the IL33 and the STARD3/PGAP3 loci were also associated with the high atopy subgroup. Two SNPs, rs1544791 (PDE4D) and rs3806932 (TSLP), were more strongly associated with the high smoking history subgroup than with asthma or any other subgroups. All 10 SNPs that replicated for asthma per se and within subgroups had lower p values in subgroups. Moreover, 12 SNPs were only replicated in a subgroup. Conclusion: This study shows that the majority of GWAS-nominated SNPs are more strongly associated with homogeneous subgroups of asthma than broadly defined asthma.
Troponins, intrinsic disorder, and cardiomyopathy

Abstract Cardiac troponin is a dynamic complex of troponin C, troponin I, and troponin T (TnC, TnI, and TnT, respectively) found in the myocyte thin filament where it plays an essential role in cardiac muscle contraction. Mutations in troponin subunits are found in inherited cardiomyopathies, such as hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). The highly dynamic nature of human cardiac troponin and presence of numerous flexible linkers in its subunits suggest that understanding of structural and functional properties of this important complex can benefit from the consideration of the protein intrinsic disorder phenomenon. We show here that mutations causing decrease in the disorder score in TnI and TnT are significantly more abundant in HCM and DCM than mutations leading to the increase in the disorder score. Identification and annotation of intrinsically disordered regions in each of the troponin subunits conducted in this study can help in better understanding of the roles of intrinsic disorder in regulation of interactomes and posttranslational modifications of these proteins. These observations suggest that disease-causing mutations leading to a decrease in the local flexibility of troponins can trigger a whole plethora of functional changes in the heart.
Microalbuminuria and low hemoglobin as risk factors for the occurrence and increasing severity of diabetic retinopathy

Aim: To assess the influence of urinary microalbuminuria and hemoglobin concentration on the occurrence and severity of diabetic retinopathy (DR), clinically significant macular edema (CSME) and hard exudate formation. Materials and Methods: In this prospective cross-sectional study carried out over a period of 2 years, type 2 diabetic patients seeking ocular evaluation for DR were assessed for presence and severity of DR, presence of hard exudates and CSME. Retinal findings were correlated to severity of microalbuminuria, hemoglobin concentration and other systemic risk factors using linear regression analysis. Results: Three hundred and six patients were included in the study. DR of any grade was seen in 132 (43%) patients, hard exudate formation in 93/306 (30.4%) patients, CSME in 50/306 (16.3%) patients and proliferative DR in 26/306 (8.5%) patients. Duration of diabetes (P <0.001), microalbuminuria (P <0.001) and low hemoglobin (P = 0.001) were found to be highly significant risk factors for the development and increasing severity of DR as well as for CSME and hard exudate formation. Conclusion: Microalbuminuria and low hemoglobin are strong predictors for DR, CSME and hard exudate formation in type 2 diabetics even after correcting for duration of diabetes and other systemic risk factors. Although not directly involved in the pathogenesis, microalbuminuria can help in identifying patients at risk for more severe diabetic eye disease. Microalbuminuria warrants intensive monitoring of both retinal and renal status. The hemoglobin levels should be monitored regularly in diabetic patients to detect and treat anemia, thereby reducing one risk factor for DR.
Considerations made by the general practitioner when dealing with sick-listing of patients suffering from subjective and composite health complaints

Abstract Objectives. To explore GPs’ considerations in decision-making regarding sick-listing of patients suffering from SHC. Design. Qualitative analysis of data from nine focus-group interviews. Setting. Three cities in different regions of Norway. Participants. A total of 48 GPs (31 men, 17 women; aged 32–65) participated. The GPs were recruited when invited to a course dealing with diagnostic practice and assessment of sickness certificates related to patients with composite SHCs. Results. Decisions on sick-listing patients with SHCs were regarded as a very challenging task. Trust in the patient's own story and self-judgement was deemed crucial, but many GPs missed hard evidence of illness and loss of function. Several factors that might influence decision-making were identified: the patients’ ability to present their story to evoke sympathy, the GP's prior knowledge of the patient, and the GPs’ own experience as a patient and their tendency to avoid conflicts. The approach to the task of sick-listing differed from patient-led cooperation to resistant confrontation. Conclusion and implications. Issuing sickness certification in patients with composite health complaints is considered challenging and burdensome. It is seen as mainly patient-driven, and the decisions vary according to GPs’ attitudes, beliefs, and personalities. Guiding the GPs to a more focused awareness of the decision process should be considered.
Characterizing breast cancer xenograft epidermal growth factor receptor expression by using near-infrared optical imaging

Background: Epidermal growth factor receptor (EGFR) overexpression is associated with several key features of cancer development and growth. Therefore, EGFR is a very promising biological target for tumor diagnosis and anticancer therapy. Characterization of EGFR expression is important for clinicians to select patients for EGFR-targeted therapy and evaluate therapeutic effects. Purpose: To investigate whether near-infrared (NIR) fluorescent dye Cy5.5-labeled anti-EGFR monoclonal antibody Erbitux can characterize EGFR expression level in MDA-MB-231 and MCF-7 breast cancer xenografts using an in vivo NIR imaging method. Material and Methods: A fluorochrome probe was designed by coupling Cy5.5 to Erbitux through acidylation, and the fluorescence property of the Erbitux-Cy5.5 conjugate was characterized by fluorospectroscopy. Flow cytometry and laser confocal microscopy were used to test the EGFR specificity of the antibody probe in vitro. Erbitux-Cy5.5 was also injected intravenously into immune-deficient mice bearing MDA-MB-231 or MCF-7 tumors. Whole-body and region-of-interest fluorescence images were acquired and analyzed. The EGFR expression was also analyzed and confirmed by immunohistochemical assay. Results: The maximum excitation/emission wavelength for the Erbitux-Cy5.5 probe was 674/697 nm, similar to that of free Cy5.5 (674/712 nm). Confocal microscopy confirmed receptor-specific uptake in MDA-MB-231 and MCF-7 cells. In flow cytometry probe specificity assay, Erbitux-Cy5.5 showed a 9.32-fold higher affinity for MDA-MB-231 than MCF-7 cells. In vivo NIR imaging also indicated specific uptake in EGFR-positive tumors. Probe uptake rate and maximum intake dose in MDA-MB-231 were significantly higher than those in MCF-7 xenografts (P < 0.001). Immunohistochemical staining confirmed the in vivo imaging results, showing differentiated EGFR expression in MDA-MB-231 (+ + +) and MCF-7 (+) tumor tissues. Conclusion: Erbitux-Cy5.5 may be used as a specific NIR contrast agent for the noninvasive characterization of EGFR expression level in breast cancer xenografts.
Breast plasmacytoma

Background: Breast plasmacytoma (BP) is extremely rare. The published data on this manifestation include predominantly case reports and do not provide any statistical information. Purpose: To identify clinical signs and radiological features of BP. Material and Methods: Five patients with BP were retrospectively identified in the pathological and radiological databases of the years 1997–2009 at our institution. Additionally, 48 patients were collected from the literature in the period from 1988 to date. Therefore, our study involves 53 patients. Results: The prevalence of BP in our institution was 1.5% of all identified cases with plasmacytoma and 0.2% of the cases with breast cancer. In 8 of 53 patients (15%), primary BP was diagnosed, and in 45 patients (85%) involvement of the breast was a secondary event of the multiple myeloma (MM). Clinically, 83% of the patients presented with breast lumps. BP was diagnosed incidentally in 9%. In 8% of the cases clinical signs were not reported. On mammography, intramammary round or oval masses were most commonly found (89%). They were solitary in 66% of the cases and multiple in 34%. Median size was 21 mm, ranging from 8 to 90 mm. In 9% of the identified cases BP manifested as diffuse infiltration of the breast. In 2% no abnormalities were identified on mammography. On ultrasound, identified lesions were homogeneously echo-poor or hypoechoic, less frequently mixed hypo- to hyperechoic. Treatment of BP is the same as for other localizations of plasmacytoma and is based on chemotherapy and/or radiotherapy. Primary BP had a better prognosis than breast involvement as a secondary event in MM. Conclusion: In conclusion, BP does not have specific radiological or clinical features and can be misdiagnosed as primary breast carcinoma or even as a benign process. However, BP should be considered in the differential diagnosis of breast disorders, especially in patients with MM.
Meningitis and sepsis due to multidrug-resistant Elizabethkingia meningoseptica in a premature neonate

Abstract Elizabethkingia meningoseptica is known to cause meningitis in premature neonates and severe infections in immunocompromised adults. It may cause a therapeutic dilemma as it often shows discrepancies between various methods of antimicrobial susceptibility testing. Here, we present a case of multi drug resistant E. meningoseptica meningitis and sepsis in a premature baby, which caused a therapeutic challenge. The strain was susceptible to piperacillin, piperacillin-tazobactam and trimethoprim/sulfamethoxazole by disk diffusion method. On the other hand the minimum inhibitory concentration values for these antibiotics were much higher to be interpreted as resistant by VITEK 2C (bioMérieux). This case showed significant clinical improvement with combination therapy of piperacillin-tazobactam and amikacin, and the same drugs were continued. Relying on the clinical outcome in this case, we observe that VITEK 2C may be less accurate than disk diffusion method for detection of antimicrobial resistance in this organism.
Bewertung visueller Signalgestaltung in der Chirurgie mittels Eye-Tracking / Assessment of Visual Signals in Surgery

Zusammenfassung Ziel der Studie ist es, die optimale Präsentationsart visueller Hinweisreize für chirurgische Assistenzsysteme zu bestimmen. Diese Hinweise können dazu dienen, dem Chirurgen verschiedene Statusinformationen zu präsentieren oder ihn an Gefahrenstellen zu warnen. Dafür müssen die Hinweise die Aufmerksamkeit des Chirurgen erregen, ohne vom eigentlichen Operationsgeschehen abzulenken. Die Studie wurde im Demonstrator-Operationssaal des Innovation Center Computer Assisted Surgery Leipzig (ICCAS) durchgeführt. Die 30 Studienteilnehmer sahen Videoausschnitte einer realen Operation aus dem Sichtfeld des Operateurs, in denen Landoltringe als Hinweisreize präsentiert wurden. Die Landoltringe wurden entweder statisch, blinkend, an- und abschwellend oder hüpfend dargestellt. Die primäre Aufgabe bestand darin, die Elemente zu zählen, die dem Situs hinzugefügt wurden. Während der Durchführung wurden die Augenbewegungen mit einem Eye-Tracker erfasst. Außerdem wurden die subjektive Einschätzung der Sichtbarkeit und der Störung durch die Landoltringe mittels strukturierter Interviews erhoben. Die blinkende Variante zeigte sich sowohl in den subjektiven Einschätzungen als auch in der Blickbewegungsanalyse als beste Wahl für einen Hinweisreiz. Summary The aim of the current study is to find the optimal presentation design for visual cues during surgery. Therefore, cue stimuli have to attract the surgeon’s attention without distracting him from the surgery itself. The analysis of four different presentation designs included questionnaires and eyetracking. A flashing signal showed the best results in the eyetracking analysis and in the subjective rating results for visibility and distraction.
Is there a role for BLADE acquisition in T2-weighted breast MRI?

Background: Standard T2-weighted (T2W) magnetic resonance imaging (MRI) is a necessary component of routine breast MRI. However, breast MRI suffers from minor subject movements, which degrade the image quality. BLADE acquisition MRI is a promising motion degradation method currently used in brain imaging. Purpose: To compare T2W BLADE acquisition breast MR images with routine T2W images in the evaluation of motion artifacts and overall image quality. Material and Methods: MRI was performed with a 1.5 T system on 25 volunteers and 25 consecutive patients with identical imaging parameters for both MRI sequences (TR 5240 ms, TE 112–108 ms, acquisition 1, spatial resolution 0.9×0.9× 4 mm). Motion and flow artifacts and pectoral muscle and lesion contour delineations were assessed. Signal to noise ratios (SNRs) of images and contrast to noise ratios (CNRs) of the incidental lesions were calculated. The results were evaluated with the Wilcoxon signed-ranks test. Results: Of the 50 patients, 44 were included in the analysis (mean age 42.1 years). Motion artifacts were prominent in 48% cases on routine T2W and in only 2% of BLADE cases. The SNR values of BLADE images were significantly higher than routine T2W (P<0.05). Pectoral muscle contours were better assessed on BLADE in all cases. Sequence performances were similar in flow artifacts, CNR values, and contour delineation of incidental lesions. The readers chose BLADE sequence MRI in 25 cases and found the overall performance of sequences equal in 19 cases. None of the readers preferred routine T2W to BLADE. Conclusion: The performance of BLADE is superior to routine T2W images in eliminating motion artifacts, provides better SNRs, shows detailed pectoral muscle contours, and may be the sequence of choice.
Challenging barriers to employment, training and education for mental health service users: The service user's perspective

In 1999 the 'Care Programme to Work' project at the Institute for Applied Health and Social Policy undertook a survey of service users in Sheffield. The aim was to identify users' employment, education and training needs, as they perceived them. One hundred and fifty-six interviews were carried out across the city, followed by 11 focus groups to explore vocational issues in more detail and ensure that the views of groups under-represented in the interviews were included. Service users were employed as interviewers and focus group leaders. Open employment was the most frequently identified long-term goal. The study highlighted the need for an integrated approach to vocational guidance and support; for strong links with employment and educational agencies and with projects supporting diverse groups of users; for access to impartial benefits advice; and for mental health services themselves to take a lead in providing and promoting employment opportunities.
Anti-vascular endothelial growth factor antibody bevacizumab reduced the risk of anemia associated with chemotherapy–A meta-analysis

Abstract Introduction. Vascular endothelial growth factor (VEGF) may play a role in erythropoiesis. We performed a meta-analysis of randomized controlled trials (RCT) to determine the effect of the anti-VEGF antibody bevacizumab on anemia in cancer patients treated with chemotherapy. Methods. Databases from PUBMED, the Web of Science, Embase, the Cochrane Library, and abstracts presented at the American Society of Clinical Oncology (ASCO) conferences until May 2010 were searched to identify relevant studies. Eligible studies included prospective RCTs in which the combination of bevacizumab and chemotherapy was compared with chemotherapy alone. Summary incidence rate, relative risk (RR), and 95% confidence interval (CI) were calculated. Results. A total of 6439 patients with a variety of solid tumors were included for analysis from 11 RCTs. Among those patients receiving bevacizumab and chemotherapy, the incidences of all-grade and high-grade (grade 3 and above) anemia were 17.8% (95% CI: 11.1–27.1%) and 2.8% (95% CI: 1.6–5.0%) respectively. In comparison with chemotherapy alone, bevacizumab significantly reduced all-grade (RR, 0.79; 95% CI: 0.66–1.0, p = 0.007) and high-grade anemia (RR, 0.72; 95% CI: 0.57–0.90, p = 0.005). The effect did not vary significantly among bevacizumab doses (p = 0.88), tumor types (p = 0.75) or chemotherapy regimens (p = 0.98). Discussion. Bevacizumab may significantly reduce the risk of anemia with chemotherapy in cancer patients.
Validation of oesophageal cancer surgery data in the Swedish Patient Registry

Background. The Swedish Patient Registry provides data about diagnoses and surgical procedures for research purposes. There are, however, almost no validation studies of the data on surgical procedures, and none of oesophageal cancer surgery. Material and methods. This was a validation study of the accuracy of codes representing oesophageal cancer resection, surgical approach and oesophageal substitute in the Swedish Patient Registry during the period 1987–2005. The registered data were compared with a thorough review of the corresponding operation charts collected from medical records. Results. Among 1358 patients with a code representing oesophageal resection in the Patient Registry, the positive predictive value was 99.6%. The dominant surgical procedures in terms of surgical approach (transthoracic) and type of oesophageal substitute (gastric conduit) had positive predictive values of 99.8% and 99.4%, respectively. The more rare procedures with regards to approach (transhiatal) and substitute (bowel) had lower positive predictive values of 68.8% and 68.5%, respectively. Conclusion. The high accuracy of the data regarding oesophageal cancer resection in the Swedish Patient Registry stresses its appropriateness for research purposes.
Body size preferences among young women in five Arab countries: a cross-cultural study

Abstract Objective: The aim of this study was to highlight body size preferences among university females in five Arab countries. Methods: The sample comprised 1134 females between 17 and 32 years old from universities in five Arab countries: Bahrain, Egypt, Jordan, Oman and Syria. A silhouette figure scale was used to examine body size preferences. Results: There were significant differences between countries regarding female body size preferences (p<0.001) and for preferred body size for men (p<0.001). In general, the university females preferred a thinner body size for themselves than that perceived for men. Conclusion: There was a drastic change in body size preferences for women from plumpness to thinness. Sociocultural factors may play a role in the differences in the body size preferences between countries.