bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct inhibition of CD40L expression can contribute to the clinical efficacy of daclizumab independently of its effects on cell division and Th1/Th2 cytokine production
Authors: Snyder James T. , Shen Jijia , Azmi Hooman , Hou Jeannie , Fowler Daniel H. , Ragheb Jack A. 
Published: March 2007

AbstractHumanized anti-CD25 antibodies (eg, daclizumab) have been successfully used to treat several autoimmune diseases. Paradoxically, IL-2 blockade in mice can induce autoimmunity. An interspecies difference in the relative contribution of IL-2 to CD25+ T regulatory cell (CD25+Treg) versus CD25+ effector cell function might explain this conundrum. Consistent with this are reports that daclizumab inhibits human CD25+ effector cell cytokine production by blocking the expression of CD40L. However, in mice, IL-4 and IL-12 regulate CD40L expression. As human Th1/Th2 cytokine production is also dependent on IL-2, daclizumab's inhibition of CD40L expression could be due to an indirect, rather than a direct, effect of IL-2. Here, we clarify the mechanisms underlying CD40L expression. In contrast to the mouse, human CD40L is regulated by CD28 signaling and IL-2, not the principal Th1/Th2-polarizing cytokines. We find that CD40L is expressed on naive and memory cells and inhibited by daclizumab independently of cell division. Collectively, our results indicate that daclizumab could inhibit CD25+ effector T-cell function in vivo by directly blocking CD40L expression. This difference between mice and human may help explain the paradoxical effects of IL-2R blockade in the 2 species.
A computational approach for detecting peptidases and their specific inhibitors at the genome level
Authors: Bartoli Lisa , Calabrese Remo , Fariselli Piero , Mita Damiano G , Casadio Rita 
Published: March 2007

Abstract

Background
Peptidases are proteolytic enzymes responsible for fundamental cellular activities in all organisms. Apparently about 2–5% of the genes encode for peptidases, irrespectively of the organism source. The basic peptidase function is "protein digestion" and this can be potentially dangerous in living organisms when it is not strictly controlled by specific inhibitors. In genome annotation a basic question is to predict gene function. Here we describe a computational approach that can filter peptidases and their inhibitors out of a given proteome. Furthermore and as an added value to MEROPS, a specific database for peptidases already available in the public domain, our method can predict whether a pair of peptidase/inhibitor can interact, eventually listing all possible predicted ligands (peptidases and/or inhibitors).

Results
We show that by adopting a decision-tree approach the accuracy of PROSITE and HMMER in detecting separately the four major peptidase types (Serine, Aspartic, Cysteine and Metallo- Peptidase) and their inhibitors among a non redundant set of globular proteins can be improved by some percentage points with respect to that obtained with each method separately. More importantly, our method can then predict pairs of peptidases and interacting inhibitors, scoring a joint global accuracy of 99% with coverage for the positive cases (peptidase/inhibitor) close to 100% and a correlation coefficient of 0.91%. In this task the decision-tree approach outperforms the single methods.

Conclusion
The decision-tree can reliably classify protein sequences as peptidases or inhibitors, belonging to a certain class, and can provide a comprehensive list of possible interacting pairs of peptidase/inhibitor. This information can help the design of experiments to detect interacting peptidase/inhibitor complexes and can speed up the selection of possible interacting candidates, without searching for them separately and manually combining the obtained results. A web server specifically developed for annotating peptidases and their inhibitors (HIPPIE) is available at http://gpcr.biocomp.unibo.it/cgi/predictors/hippie/pred_hippie.cgi
The BioPrompt-box: an ontology-based clustering tool for searching in biological databases
Authors: Corsi Claudio , Ferragina Paolo , Marangoni Roberto 
Published: March 2007

Abstract

Background
High-throughput molecular biology provides new data at an incredible rate, so that the increase in the size of biological databanks is enormous and very rapid. This scenario generates severe problems not only at indexing time, where suitable algorithmic techniques for data indexing and retrieval are required, but also at query time, since a user query may produce such a large set of results that their browsing and "understanding" becomes humanly impractical. This problem is well known to the Web community, where a new generation of Web search engines is being developed, like Vivisimo. These tools organize on-the-fly the results of a user query in a hierarchy of labeled folders that ease their browsing and knowledge extraction. We investigate this approach on biological data, and propose the so called The BioPrompt-boxsoftware system which deploys ontology-driven clustering strategies for making the searching process of biologists more efficient and effective.

Results
The BioPrompt-box (Bpb) defines a document as a biological sequence plus its associated meta-data taken from the underneath databank – like references to ontologies or to external databanks, and plain texts as comments of researchers and (title, abstracts or even body of) papers. Bpboffers several tools to customize the search and the clustering process over its indexed documents. The user can search a set of keywords within a specific field of the document schema, or can execute Blastto find documents relative to homologue sequences. In both cases the search task returns a set of documents (hits) which constitute the answer to the user query. Since the number of hits may be large, Bpbclusters them into groups of homogenous content, organized as a hierarchy of labeled clusters. The user can actually choose among several ontology-based hierarchical clustering strategies, each offering a different "view" of the returned hits. Bpbcomputes these views by exploiting the meta-data present within the retrieved documents such as the references to Gene Ontology, the taxonomy lineage, the organism and the keywords. Of course, the approach is flexible enough to leave room for future additions of other meta-information. The ultimate goal of the clustering process is to provide the user with several different readings of the (maybe numerous) query results and show possible hidden correlations among them, thus improving their browsing and understanding.

Conclusion
Bpb is a powerful search engine that makes it very easy to perform complex queries over the indexed databanks (currently only UNIPROT is considered). The ontology-based clustering approach is efficient and effective, and could thus be applied successfully to larger databanks, like GenBank or EMBL.
Soluble RAGE but not endogenous secretory RAGE is associated with albuminuria in patients with type 2 diabetes
Authors: Humpert Per M , Djuric Zdenka , Kopf Stefan , Rudofsky Gottfried , Morcos Michael , Nawroth Peter P , Bierhaus Angelika 
Published: March 2007

Abstract

Background
Total circulating soluble receptor for advanced glycation endproducts (sRAGE) and a more defined endogenous secretory splice variant of the receptor (esRAGE) were shown to be associated with different markers of cardiovascular risk in patients with diabetes. Since previous data were partly divergent, the aim of this study was to compare sRAGE and esRAGE in a head-to-head analysis in patients with type 2 diabetes (T2DM) with albuminuria.

Methods
sRAGE and esRAGE were studied in plasma of 110 T2DM patients using enzyme-linked immunosorbant assays (ELISA) detecting either sRAGE or esRAGE only. Both sRAGE and esRAGE were compared with regard to applicability as markers for vascular disease and glucose control in T2DM.

Results
In bivariate analysis, sRAGE correlated with age (R = 0.22, p = 0.02) and the 24 hour albumin excretion rate (R = 0.18, p = 0.05), while esRAGE correlated positively with age only (R = 0.23, p = 0.02). In contrast to previous reports, neither sRAGE nor esRAGE correlated with glucose control or intima-media-thickness (IMT) as a predictor of macrovascular disease. In multivariate regression models, the associations between sRAGE and albuminuria as well as esRAGE and age were shown to be independent of glucose control, diabetes duration, body-mass index, glomerular filtration rate, blood pressure and gender.

Conclusion
This is the first study comparing sRAGE and esRAGE as markers of vascular complications in patients with T2DM. sRAGE but not esRAGE is independently associated with albuminuria in these patients while neither sRAGE nor esRAGE are associated with markers of glucose control or macrovascular disease.
Irreversibility of cellular senescence: dual roles of p16INK4a/Rb-pathway in cell cycle control
Authors: Takahashi Akiko , Ohtani Naoko , Hara Eiji 
Published: March 2007

Abstract
The retinoblastoma (Rb) tumor suppressor gene product, pRb, has an established role in the implementation of cellular senescence, the state of irreversible G1 cell cycle arrest provoked by diverse oncogenic stresses. In murine cells, senescence cell cycle arrest can be reversed by subsequent inactivation of pRb, indicating that pRb is required not only for the onset of cellular senescence, but also for the maintenance of senescence program in murine cells. However, in human cells, once pRb is fully activated by p16INK4a, senescence cell cycle arrest becomes irreversible and is no longer revoked by subsequent inactivation of pRb, suggesting that p16INK4a/Rb-pathway activates an alternative mechanism to irreversibly block the cell cycle in human senescent cells. Here, we discuss the molecular mechanism underlying the irreversibility of senescence cell cycle arrest and its potential towards tumor suppression.
It's just the worry about not being able to control it! A qualitative study of living with overactive bladder
Authors: Nicolson Paula , Kopp Zoe , Chapple C. R. , Kelleher C. 
Published: March 2007

Objectives. This study reports the perceptions of patients with a diagnosis of OAB and people with undiagnosed OAB symptoms about their health‐related quality of life (HRQL) and psychological consequences.Design. A qualitative study which employed a series of in‐depth, semi‐structured individual and group interviews using thematic and interpretive techniques of data analysis.Methods. A mixture of previously diagnosed patients and people bothered by OAB symptoms were recruited from three British cities. The interviews explored issues around HRQL. Data were transcribed verbatim and analysed thematically to draw out the context in which people experience OAB. The study design was reviewed by a Multi‐Centre Research Ethics Committee and subjected to local research governance.Results. OAB has devastating consequences for sufferers of both sexes which impact upon their HRQL, self‐esteem and relationships. OAB without incontinence causes anxiety, fear of incontinence, a sense of depression and hopelessness all of which are worse for those with incontinence. Many sufferers feel too embarrassed to seek medical care.Conclusions. The psychological and HRQL consequences for OAB sufferers overlap with trajectories associated with chronic illness. However, because many sufferers avoid admitting to the condition and/or seeking treatment the psychological costs to them are even greater than with a diagnosed illness because the disruption remains unacknowledged and therefore unresolved.
Thermochemical properties of the Fe-analogue of cryolite, Na3FeF6
Authors: Nerád Ivan , Mikšíková Eva 
Published: March 2007

Abstract
Relative enthalpies for low-and high-temperature modifications of Na3FeF6 and for the Na3FeF6 melt have been measured by drop calorimetry in the temperature range 723–1318 K. Enthalpy of modification transition at 920 K, δtransH(Na3FeF6, 920 K) = (19 ± 3) kJ mol−1 and enthalpy of fusion at the temperature of fusion 1255 K, δfusH(Na3FeF6, 1255 K) = (89 ± 3) kJ mol−1 have been determined from the experimental data. Following heat capacities were obtained for the crystalline phases and for the melt, respectively: C p(Na3FeF6, cr, α) = (294 ± 14) J (mol K)−1, for 723 = T/K ≤ 920, C p(Na3FeF6, cr, β) = (300 ± 11) J (mol K)−1 for 920 ≤ T/K = 1233 and C p(Na3FeF6, melt) = (275 ± 22) J (mol K)−1 for 1258 ≤ T/K ≤ 1318. The obtained enthalpies indicate that melting of Na3FeF6 proceeds through a continuous series of temperature dependent equilibrium states, likely associated with the production of a solid solution.
Synthesis and proton conductivity of anhydrous dendritic electrolytes
Authors: Şenel Mehmet , Tülü Metin , Bozkurt Ayhan 
Published: March 2007

Abstract
Water soluble PEG cored dendritic hexa-acid which comprises peripheral carboxylic acidic groups were prepared via nucleophilic substitution reactions. Novel anhydrous proton conducting electrolytes were prepared by incorporation of the heterocyclic protogenic solvent imidazole (Im) into PEG cored dendritic hexa acid, (PEG-HA), at several molar ratios of Im to-COOH units of PEG-HA. The complexation of PEG-HA and Im was illustrated by infrared spectroscopy (FT-IR). The materials are thermally stable up to 150 °C as evidenced by thermogravimetry analysis (TGA). Differential scanning calorimetry (DSC) results verified that the organic electrolytes are homogeneous and amorphous. The proton conductivities were characterized by means of AC impedance spectroscopy and a maximum conductivity of 1 × 10−3 S/cm was measured at 120 °C in the anhydrous state.
HIV and the Skin
Authors: Bunker Christopher B. , Piguet Vincent 
Published: March 2024

Abstract
Within 2 years of defining acquired immune deficiency syndrome (AIDS) as a distinctive syndrome in 1981, human immunodeficiency virus (HIV) was identified as the causative agent. Dermatological involvement in AIDS has been appreciated since the disease was first recognised. Mucocutaneous involvement establishes criteria for diagnosis and staging; the prognostic significance of some complications, for example pruritic papular eruption/eosinophilic folliculitis, hairy leukoplakia and Kaposi sarcoma (KS), was well recognised before specific treatments were introduced. The proportion of patients with skin complications and the number of these manifestations in any one patient increase as HIV infection progresses and AIDS develops. The incidence and severity of several common cutaneous diseases (such as mollusca, herpes simplex and seborrhoeic dermatitis) are increased in patients with HIV and this correlates in many instances with the absolute numbers of CD4+ T cells. The effect HIV infection may have on some dermatological conditions such as psoriasis and leprosy is less clear‐cut. The advent of highly active combined antiretroviral therapy (ART) has been incalculably beneficial to patients with HIV, but novel side effects of these drugs (such as lipodystrophy) have emerged, and the skin can be affected by manifestations of the immune reconstitution inflammatory syndrome/immune reconstitution associated disease. The dermatological complications of HIV and AIDS may be distressing to patients and difficult for dermatologists to diagnose and manage. Also, many dermatoses presenting in the population at large need to be regarded as ‘indicator conditions’ to prompt advice about, and initiation of, HIV testing.
Recurrent Angio‐Oedema without Weals
Authors: Grattan Clive E. H. , Maurer Marcus 
Published: March 2024

Abstract

Angio‐oedema without weals may be hereditary or acquired. Nearly all types and cases of hereditary angio‐oedema (HAE) are mediated by bradykinin and require completely different assessment and treatment to acquired mast cell mediator‐induced angio‐oedema. It is inherited as an autosomal dominant disorder. Types 1 and 2 are due to mutations in
SERPING1
resulting in deficient or non‐functional C1 esterase inhibitor (CI‐INH) respectively. Hereditary angio‐oedema with normal C1‐INH is associated with several different mutations including gain‐of‐function mutations in
F12
. Bradykinin also causes angio‐oedema linked to treatment with angiotensin converting enzyme inhibitors or acquired C1‐INH deficiency resulting from its consumption or its inactivation by autoantibodies. About 10% of patients with chronic spontaneous urticaria present with mast cell mediator‐induced angio‐oedema without weals, thus it is much commoner than HAE. The assessment and treatment are similar to that in urticaria patients with weals. Acquired idiopathic angio‐oedema does not appear to be bradykinin or mast cell mediator induced. The entity is poorly defined as there are no diagnostic tests.
Mastocytosis
Authors: Grattan Clive E. H. , Radia Deepti H. 
Published: March 2024

Abstract

Mastocytosis is caused by a clonal expansion of neoplastic mast cells. It usually presents in the skin, bone marrow or both but may affect other tissues. Children with cutaneous mastocytosis present with urticaria pigmentosa, mastocytomas or diffuse cutaneous mastocytosis. Around 50% will remit spontaneously before adulthood. Most adults have indolent systemic mastocytosis and carry the D816V
KIT
mutation. A few will progress to advanced disease. Risks include anaphylaxis, reduction in bone density and the development of associated haematological disorders. Cutaneous symptoms include itching, hiving and flushing. Bowel symptoms include dyspepsia, pain and diarrhoea. Neuropsychiatric symptoms of fatigue, depression and ‘brain fog’ may occur. Diagnosis is confirmed on biopsy of skin, bone marrow or other tissues. Baseline blood tryptase is a useful marker of mast cell load. Management is primarily symptomatic and supportive although cytoreductive treatments may be necessary for advanced presentations causing organ damage. Targeted novel tyrosinase kinase inhibitors are under development.
Immunobullous Diseases
Authors: Schmidt Enno , Groves Richard 
Published: March 2024

Abstract
The immunobullous disorders represent a group of conditions characterised by antibody‐mediated autoimmune responses against structural elements of the skin resulting in blistering of the skin and/or mucosae. Antibody targets include proteins in the hemidesmosomes basement membrane zone and superficial dermis (pemphigoid group), desmosomes (pemphigus group) and epidermal and tissue‐type transglutaminase (dermatitis herpetiformis). If left untreated, immunobullous disorders are associated with significant morbidity and mortality and thus prompt, accurate diagnosis and treatment are mandatory. Therapeutic options include corticosteroids, steroid‐sparing immunosuppressants such as azathioprine, mycophenolate mofetil and anti‐inflammatory agents such as dapsone and tetracyclines. In severe and/or refractory patients, intravenous immunoglobulin, immunoadsorption and anti‐B‐cell agents such as rituximab may be of benefit. Indeed, recently international and European guidelines have recommended the use of rituximab as first line treatment in moderate and severe pemphigus vulgaris and foliaceous.
Lupus Erythematosus and Antiphospholipid Syndrome
Authors: Dutz Jan , Khosravi‐Hafshejani Touraj 
Published: March 2024

Abstract
Lupus erythematosus is an autoimmune disease that commonly affects the skin, and may present with cutaneous only disease. This chapter reviews the forms of cutaneous lupus‐specific skin disease (discoid lupus, subacute cutaneous lupus, lupus tumidus and acute cutaneous lupus), their clinical features, pathogenesis and treatment. A review of systemic lupus erythematosus is also provided with a discussion of diagnosis, clinical features, cutaneous aspects and treatment, germane for the dermatologist. Clinical features of neonatal lupus erythematosus and the antiphospholipid antibody syndrome, more commonly seen in systemic lupus erythematosus kindreds, are also discussed.
Cutaneous Amyloidoses
Authors: Schreml Stephan 
Published: March 2024

Abstract
Amyloids are common protein aggregates in nature. Some amyloids fulfill important biological tasks while others are known to cause diseases. Despite the fact that the ultrastructure of amyloid is highly conserved, the mechanism of amyloidogenesis remains a challenging research topic. In humans, amyloidoses can develop primarily in the skin, or systemic amyloidoses can lead to secondary cutaneous involvement. An accurate diagnostic procedure is crucial for planning therapy in this heterogeneous group of diseases. This chapter gives an overview on the different kinds of cutaneous amyloidoses as well as on diagnostic and therapeutic approaches. Furthermore, the contrast between functional and disease‐causing amyloid is discussed.
Cutaneous Mucinoses
Authors: Rongioletti Franco 
Published: March 2024

Abstract
Cutaneous mucinoses are a heterogeneous group of diseases whose main characteristic is the abnormal excessive deposition of mucin (glycosaminoglycans) in the skin. The aetiopathogenesis of cutaneous mucinoses is unknown, although a few cytokines such as tumour necrosis factor α and β, interleukin 1, interleukin 6, and transforming growth factor β and/or polyclonal immunoglobulins and monoclonal and other unidentified factors in patient serum, may induce pathological stimulation of glycosaminoglycan synthesis. Cutaneous mucinoses are divided into two groups: primary cutaneous mucinoses in which mucin deposition is the main histological feature leading to specific clinical lesions, and secondary mucinoses in which mucin deposition is only an additional histological epiphenomenon. Primary mucinoses can be divided into dermal and follicular mucinoses. The former includes lichen myxoedematosus (papular mucinosis), divided into diffuse/generalised lichen myxoedematosus (also called scleromyxoedema) and the localised form, reticular erythematous mucinosis (REM), scleroedema, mucinosis in thyroid disease, papular and nodular mucinosis in connective tissue diseases, self‐healing (juvenile) cutaneous mucinosis, cutaneous focal mucinosis and digital myxoid cyst. While the follicular mucinoses include Pinkus follicular mucinosis and urticaria‐like follicular mucinosis. Associated disorders include paraproteinaemia (scleromyxoedema, scleroedema), diabetes mellitus (scleroedema), hyperthyroidism (pretibial myxoedema), hypothyroidism (generalised myxoedema), and lupus erythematosus, dermatomyositis or scleroderma (papular and nodular mucinosis in patients with connective tissue). There are no evidence‐based therapies for the main conditions, although some positive results have been obtained with intravenous immunoglobulin in scleromixoedema, antimalarials in REM and phototherapy in scleroedema.
Skin Disorders in Diabetes Mellitus
Authors: Bourke Johnny , Murphy Matthew 
Published: March 2024

Abstract
Skin disease associated with diabetes is multifactorial and is often an indicator of systemic complications such as retinopathy, neuropathy or nephropathy. Vascular and neurological damage lead to leg and foot ulcers. Obesity and the metabolic syndrome lead to acanthosis nigricans, skin tags and eruptive xanthomas. Although controversial, there is some support from the literature for an increased risk of cutaneous infections. Treatment‐related skin disorders result from oral medication, insulin reactions and medical devices. Disease‐specific skin disorders include necrobiosis lipoidica, diabetic dermopathy, cheiroarthropathy and diabetic bullae.
Mucocutaneous Pain Syndromes
Authors: Goulding Jon , Bewley Anthony 
Published: March 2024

Abstract
The mucocutaneous pain syndromes typically involve the head, neck, genitalia and mouth. These are a heterogeneous group of disorders characterised by unpleasant dysaesthetic symptoms. Some have a clearly demonstrable neurological origin, while for many, no organic cause can be identified. Psychosocial co‐morbidities are frequently encountered in this patient group and outcomes may be optimised by offering holistic, patient‐centred, multidisciplinary management.