Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of CSF-tau and CSF-Abeta42 as diagnostic markers for Alzheimer disease in clinical practice.

OBJECTIVE To evaluate the diagnostic potential of cerebrospinal fluid (CSF) levels of tau and beta-amyloid protein ending at amino acid 42 (Abeta42) as biomarkers for Alzheimer disease (AD) in clinical practice. DESIGN A 1-year prospective study. SETTING Community population-based sample of all consecutive patients admitted for investigation of cognitive symptoms to the Piteå River Valley Hospital, Piteå, Sweden. PATIENTS A total of 241 patients with probable AD (n = 105), possible AD (n = 58), vascular dementia (n = 23), mild cognitive impairment (n = 20), Lewy body dementia (n = 9), other neurological disorders (n = 3), and psychiatric disorders (n = 5) and nondemented individuals (n = 18). MAIN OUTCOME MEASURES Cerebrospinal fluid tau and CSF-Abeta42 were assayed each week as routine clinical neurochemical analyses. Sensitivity and specificity were defined using the regression line from 100 control subjects from a multicenter study. Positive and negative predictive values were calculated for different prevalence rates of AD. RESULTS We found increased CSF-tau and decreased CSF-Abeta42 levels in probable and possible AD. Sensitivity was 94% for probable AD, 88% for possible AD, and 75% for mild cognitive impairment, whereas specificity was 100% for psychiatric disorders and 89% for nondemented. Specificity was lower in Lewy body dementia (67%) mainly because of low CSF-Abeta42 levels and in vascular dementia (48%) mainly because of high CSF-tau levels. Sensitivity for CSF-tau and CSF-Abeta42 increased in patients with AD possessing the ApoE epsilon4 allele, approaching 100%. At a prevalence of AD of 45%, the positive predictive value was 90% and the negative predictive value was 95%. CONCLUSIONS Cerebrospinal fluid tau and CSF-Abeta42 have so far been studied in research settings, under conditions providing data on the optimal performance. We examined a prospective patient sample, with assays run in clinical routine, giving figures closer to the true performance of CSF-tau and CSF-Abeta42. The predictive value for AD was greater than 90%. Therefore, these biomarkers may have a role in the clinical workup of patients with cognitive impairment, especially to differentiate early AD from normal aging and psychiatric disorders.
Effects of basic fibroblast growth factor on the expression of extracellular matrix and matrix metalloproteinase‐1 in wound healing

Background. Basic fibroblast growth factor (bFGF) has shown potential in clinical practice to accelerate wound healing, but the underlying biomolecular mechanism remains largely unknown. Fibroblasts are the most important cells involved in producing and remodelling the extracellular matrix (ECM) in wound healing, and are one of the major target cells of bFGF in wound repair. To date, however, we have little idea of whether there is any specific relationship between bFGF and ECM metabolism. This study aimed to investigate whether bFGF improves wound repair by regulating the balance of ECM synthesis and degradation.
Variable Effects of Humor Styles on Organizational Outcomes

The relationship between individual humor styles and several organizational variables was investigated: stress, satisfaction with coworkers, team cooperation, and organizational commitment. Four humor styles from the Humor Styles Questionnaire were measured. Survey results of 349 participants indicated different humor styles (affiliative, self-enhancing, aggressive, and self-defeating) can have either a positive or negative effect on organizational outcomes. Results suggested that both researchers and practitioners can benefit from having a better understanding of how different humor styles affect people and outcomes in organizations.
Simultaneous Optimization of Low-pass Filter and Controller in Robust Repetitive Control Systems

One problem with existing methods of designing repetitive control systems is that they cannot simultaneously optimize the parameters of a low-pass filter and a repetitive controller. This paper presents a method of doing that for a repetitive control system containing a class of uncertain plants. First, linear matrix inequalities for calculating the parameter of a low-pass filter are derived under the condition that the robust stability of the system is guaranteed. Next, the problem of designing a state-feedback repetitive controller that guarantees the robust stability of the closed-loop system is converted into an Hinfin state-feedback design problem. Then, iterative algorithms for calculating the largest cut-off angular frequency of a low-pass filter and the gain of an Hinfin state-feedback controller are presented. The algorithms produce a combination of parameters that yields the highest control precision under the condition that the robust stability of the system is guaranteed. Finally, the validity of the method is verified by a numerical example.
Extended Pancreatectomy and Liver Perfusion Chemotherapy for Resectable Adenocarcinoma of the Pancreas

In order to increase the long-term survival after resection of pancreatic adenocarcinoma, it is essential to eradicate both locoregional recurrence and hepatic metastasis. We have added a wide range of lymphatic and connective tissue clearance to conventional pancreatectomy (extended pancreatectomy) and succeeded in improving the 5-year survival rate from 8 to 25% via decreasing the incidence of local failure. Among many procedures which together compose an extended pancreatectomy, connective tissue clearance seems to have played a more important role on patients’ prognosis rather than wide range lymphadenectomy. Concomitant resection of the portal vein is recommended for selected patients, and it is important not to overlook a minute invasion even though it appears macroscopically intact. With regard to adjuvant therapy in combination with our extended pancreatectomy, the addition of preoperative irradiation failed to further improve the long-term survival rate because the cause of cancer deaths shifted from local recurrence to hepatic metastasis. When liver perfusion chemotherapy was added to this operation (without radiation), the 5-year survival rate was improved to 39% by decreasing the incidence of hepatic metastasis. In the future, a combination of extended pancreatectomy with chemoradiation plus liver perfusion chemotherapy is one of the promising approaches for this cancer.
Städte und Regionen im Standortwettbewerb

Empfohlene Zitierung / Suggested Citation: Rosenfeld, M. T. W. (2012). Wie wirkt der verschärfte Standortwettbewerb auf die Stadtund Regionalentwicklung? Einführung in die Thematik und Erläuterungen zum Aufbau des Sammelbandes. In A. Kauffmann, & M. T. W. Rosenfeld (Hrsg.), Städte und Regionen im Standortwettbewerb: neue Tendenzen, Auswirkungen und Folgerungen für die Politik (S. 2-11). Hannover: Verl. d. ARL. https://nbn-resolving.org/urn:nbn:de:0168-ssoar-337491
Kunitz Protease Inhibitor‐Containing Amyloid β Protein Precursor Immunoreactivity in Alzheimer's Disease

The amyloid β protein (β/A4) that is deposited in senile plaques and in cerebral vessels in Alzheimer's disease (AD) is derived from a larger membrane-associated glycoprotein, the amyloid β protein precursor (APP). The gene encoding APP produces at least four major transcripts. Three of the four transcripts contain an alternatively-spliced exon encoding a Kunitz protease inhibitor domain (KPI). We now report the results of a series of experiments using novel immunohistochemical reagents to anatomically localize β/A4, APP, and KPI-containing forms of APP (APP-KPI) in the hippocampal formation and temporal neocortex. A new monoclonal antibody against β/A4 recognized senile plaques and vascular amyloid, but no cellular elements. Anti-APP and anti-KPI monoclonal antibodies stained neurons, including proximal axons and dendrites. The neuritic component of some plaques in patients with AD and in elderly control individuals were also immunoreactive for both APP and APP-KPI. Quantitative assessment of senile plaques in temporal neocortex showed that, on average, about one-third of β/A4 immunoreactive plaques stained with either anti-APP or anti-KPI. Amyloid β protein precursor and APP-KPI immunoreactivity were also found in the white and grey matter vessels of both AD patients and control individuals. These results suggest that KPI-containing forms of APP are present in dystrophic neurites of senile plaques, and normally in neurons, neuronal processes, and in the vascular compartment in the brain. Thus, APP-KPI is in a position to be intimately associated with β/A4 deposition in the neuropil, in plaques and in amyloid angiopathy.
Depression in patients with mild cognitive impairment increases the risk of developing dementia of Alzheimer type: a prospective cohort study.

BACKGROUND Mild cognitive impairment has been regarded as a precursor to dementia of Alzheimer type, but not all patients with mild cognitive impairment develop dementia. OBJECTIVE To determine whether depression may increase the risk of developing dementia. SETTING The outpatient clinics of a community general hospital. DESIGN Prospective cohort study. METHODS A cohort of 114 patients with amnestic mild cognitive impairment was followed up for a mean period of 3 years. At baseline, the patients underwent memory tests, the Spanish version of the Mini-Mental State Examination, a verbal fluency test, the Geriatric Depression Scale, and the Clinical Dementia Rating Scale for staging purposes. Psychiatric examination for depression was based on structured interview and Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition criteria. We also carried out either computed tomography or magnetic resonance imaging of the brain. MAIN OUTCOME MEASURES We carried out periodic evaluations based on the Mini-Mental State Examination, verbal fluency test, Geriatric Depression Scale, Blessed Dementia Rating Scale, and Clinical Dementia Rating Scale. The end point was the development of probable Alzheimer disease according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association. RESULTS Depression was observed in 41 patients (36%) at baseline. After a mean period of 3 years, 59 patients (51.7%) developed dementia of Alzheimer type, and 6 died. Of the depressed patients, 35 (85%) developed dementia in comparison with 24 (32%) of the nondepressed patients (relative risk, 2.6; 95% confidence interval, 1.8-3.6). The survival analysis also showed that depressed patients developed dementia earlier than the nondepressed. Most patients with depression at baseline exhibited a poor response to antidepressants. CONCLUSIONS We conclude that patients with mild cognitive impairment and depression are at more than twice the risk of developing dementia of Alzheimer type as those without depression. Patients with a poor response to antidepressants are at an especially increased risk of developing dementia.
TSLP production by epithelial cells exposed to immunodeficiency virus triggers DC-mediated mucosal infection of CD4+ T cells

Mucosal dendritic cells have been implicated in the capture, storage, and transmission of HIV to CD4+ T cells as well as in the promotion of HIV replication in activated CD4+ T cells during the cognate T-cell and DC interaction. We report that HIV induces human genital mucosal epithelial cells to produce thymic stromal lymphopoietin (TSLP) via activation of the NFκB signaling pathway. The TSLP secreted by HIV exposed epithelial cells activated DC, which promoted proliferation and HIV-1 replication of co-cultured autologous CD4+ T cells. In rhesus macaques, we observed dramatic increases in TSLP expression concurrent with an increase in viral replication in the vaginal tissues within the first 2 weeks after vaginal SIV exposure. These data suggest that HIV-mediated TSLP production by mucosal epithelial cells is a critical trigger for DC-mediated amplification of HIV-infection in activated CD4+ T cells. The cross talk between mucosal epithelial cells and DC, mediated by HIV-induced TSLP, may be an important mechanism for the high rate of HIV infection in women through the vaginal mucosa.
An Assessment of the Expanded Classification of Congenital Cystic Adenomatoid Malformations and Their Relationship to Malignant Transformation

The purpose of this study was to review cases of congenital cystic adenomatoid malformations (CCAMs) arising in children and adults, in order to assess the recently expanded classification system for these lesions and their association with malignant transformation. Of 28 CCAMs, there were 16 type 1, 4 type 2, and 8 type 4 lesions, 12 of which presented in adults. Five of 16 type 1 CCAMs were accompanied by microscopic foci of bronchioloalveolar carcinoma; two others showed focal mucous cell hyperplasia. In two further cases, foci of nonmucinous atypical adenomatous hyperplasia were identified in the adjacent lung parenchyma. The bronchioloalveolar carcinomas showed less cytologic atypia, proliferative activity (Ki-67), and p53 expression than a comparative group of bronchioloalveolar carcinomas arising de novo, but this was not statistically significant (p = 0.15). Neither bronchioloalveolar carcinomas nor hyperplasia was identified in type 2 or type 4 CCAMs. Four of the eight type 4 CCAMs showed focal stromal hypercellularity, and one case subsequently developed a pleuropulmonary blastoma. We conclude that classification according to the current system is of clinical value. Bronchioloalveolar carcinomas arise in association with type 1 CCAMs, but recurrence following resection is exceptional. Type 4 CCAMs show histologic overlap with grade 1 pleuropulmonary blastomas, and distinction between these entities may not be possible on histology alone. However, stromal cellularity in a type 4 CCAM should raise the possibility of blastomatous transformation.
Adrenomedullin: a new and promising target for drug discovery

Adrenomedullin (AM) is a 52 amino acid peptide that plays a critical role in several diseases such as hypertension, cancer, diabetes, cardiovascular and renal disorders, among others. Interestingly, AM behaves as a protective agent against some pathologies, yet is a stimulating factor for other disorders. Thus, AM can be considered as a new and promising target for the design of non-peptidic modulators that could be useful for the treatment of those pathologies, by regulating AM levels or the activity of AM. A full decade on from its discovery, much more is known about AM molecular biology and pharmacology, but this knowledge still needs to be applied to the development of clinically useful drugs.
Intestinal dysbacteriosis contributes to decreased intestinal mucosal barrier function and increased bacterial translocation

The purpose of this study was to determine the effect of colistin‐induced intestinal dysbacteriosis on intestinal mucosal barrier function and bacterial translocation in a mouse model. Colistin or saline was administered orally for 7 days, and populations of viable organisms from the caecal mucosa and its content, the ileal segments, the mesenteric lymph nodes (MLNs) and the internal organs were prepared for examination. In the intestinal dysbacteriosis model, intestinal barrier dysfunction was observed and associated with increased bacterial translocation to extraintestinal sites. The extent of bacterial translocation to the MLNs and internal organs in the colistin group was significantly higher than in the saline group. Colistin‐induced intestinal dysbacteriosis was shown to injure the intestinal mucosa barrier function and increase bacterial dislocation.
A novel metric for quantification of homogeneous and heterogeneous tumors in PET for enhanced clinical outcome prediction

Oncologic PET images provide valuable information that can enable enhanced prognosis of disease. Nonetheless, such information is simplified significantly in routine clinical assessment to meet workflow constraints. Examples of typical FDG PET metrics include: (i) SUVmax, (2) total lesion glycolysis (TLG), and (3) metabolic tumor volume (MTV). We have derived and implemented a novel metric for tumor quantification, inspired in essence by a model of generalized equivalent uniform dose as used in radiation therapy. The proposed metric, denoted generalized effective total uptake (gETU), is attractive as it encompasses the abovementioned commonly invoked metrics, and generalizes them, for both homogeneous and heterogeneous tumors, using a single parameter a. We evaluated this new metric for improved overall survival (OS) prediction on two different baseline FDG PET/CT datasets: (a) 113 patients with squamous cell cancer of the oropharynx, and (b) 72 patients with locally advanced pancreatic adenocarcinoma. Kaplan-Meier survival analysis was performed, where the subjects were subdivided into two groups using the median threshold, from which the hazard ratios (HR) were computed in Cox proportional hazards regression. For the oropharyngeal cancer dataset, MTV, TLG, SUVmax, SUVmean and SUVpeak produced HR values of 1.86, 3.02, 1.34, 1.36 and 1.62, while the proposed gETU metric for a = 0.25 (greater emphasis on volume information) enabled significantly enhanced OS prediction with HR = 3.94. For the pancreatic cancer dataset, MTV, TLG, SUVmax, SUVmean and SUVpeak resulted in HR values of 1.05, 1.25, 1.42, 1.45 and 1.52, while gETU at a = 3.2 (greater emphasis on SUV information) arrived at an improved HR value of 1.61. Overall, the proposed methodology allows placement of differing degrees of emphasis on tumor volume versus uptake for different types of tumors to enable enhanced clinical outcome prediction.
Xerostomia: etiology, recognition and treatment.

BACKGROUND Clinicians may encounter symptoms of xerostomia, commonly called "dry mouth," among patients who take medications, have certain connective tissue or immunological disorders or have been treated with radiation therapy. When xerostomia is the result of a reduction in salivary flow, significant oral complications can occur. TYPES OF STUDIES REVIEWED The authors conducted an Index Medicus--generated review of clinical and scientific reports of xerostomia in the dental and medical literature during the past 20 years. The literature pertaining to xerostomia represented the disciplines of oral medicine, pathology, pharmacology, epidemiology, gerodontology, dental oncology, immunology and rheumatology. Additional topics included the physiology of salivary function and the management of xerostomia and its complications. RESULTS Xerostomia often develops when the amount of saliva that bathes the oral mucous membranes is reduced. However, symptoms may occur without a measurable reduction in salivary gland output. The most frequently reported cause of xerostomia is the use of xerostomic medications. A number of commonly prescribed drugs with a variety of pharmacological activities have been found to produce xerostomia as a side effect. Additionally, xerostomia often is associated with Sjögren's syndrome, a condition that involves dry mouth and dry eyes and that may be accompanied by rheumatoid arthritis or a related connective tissue disease. Xerostomia also is a frequent complication of radiation therapy. CONCLUSIONS AND CLINICAL IMPLICATIONS Xerostomia is an uncomfortable condition and a common oral complaint for which patients may seek relief from dental practitioners. Complications of xerostomia include dental caries, candidiasis or difficulty with the use of dentures. The clinician needs to identify the possible cause(s) and provide the patient with appropriate treatment. Remedies for xerostomia usually are palliative but may offer some protection from the condition's more significant complications.
Barriers to WIC Benefits Redemption among Participants in Washington State

Barriers to WIC Benefits Redemption among Participants in Washington State Shelly Katsuko Najjar Chair of the Supervisory Committee: Donna Johnson, PhD, RD Department of Health Services Objective: To generate knowledge about the experience of using Special Supplemental Nutrition Program for Women Infants and Children (WIC) checks to improve WIC check redemption rates. Design: Qualitative analysis of focus group discussions. Setting: Two WIC clinics in areas that have high redemption rates for WIC checks and one clinic in an area with low redemption rates in Washington State. Participants: Twenty three WIC participants in five focus groups. Phenomenon of interest: Barriers and enhancers of WIC check redemption, especially the cash value voucher (CVV) for fruits and vegetables. Analysis: Transcriptions were coded; coded statements were organized into major themes across a socioecologic framework. Coding structures and analysis were strengthened by iterative interactions between researchers. Results: Barriers to redemption arise from multiple sociological levels, but benefits and positive factors, as well as solutions participants use, may lessen the effects of barriers. Factors negatively impacting the WIC shopping experience included food package policies, grocery store experiences, and personal misunderstanding and embarrassment; positive factors included helpful vendors and both vendor and participant understandings about the use of CVV. Conclusions and Implications: WIC check redemption may be improved by state and local actions to educate participants and vendors and improve the shopping experience.