bluuebunny/crossref_metadata_2025_split huggingface dataset:
NGS-based Molecular diagnosis of 105 eyeGENE® probands with Retinitis Pigmentosa
Authors: Ge Zhongqi , Bowles Kristen , Goetz Kerry , Scholl Hendrik P. N. , Wang Feng , Wang Xinjing , Xu Shan , Wang Keqing , Wang Hui , Chen Rui 
Published: December 2015

AbstractThe National Ophthalmic Disease Genotyping and Phenotyping Network (eyeGENE®) was established in an effort to facilitate basic and clinical research of human inherited eye disease. In order to provide high quality genetic testing to eyeGENE®’s enrolled patients which potentially aids clinical diagnosis and disease treatment, we carried out a pilot study and performed Next-generation sequencing (NGS) based molecular diagnosis for 105 Retinitis Pigmentosa (RP) patients randomly selected from the network. A custom capture panel was designed, which incorporated 195 known retinal disease genes, including 61 known RP genes. As a result, disease-causing mutations were identified in 52 out of 105 probands (solving rate of 49.5%). A total of 82 mutations were identified and 48 of them were novel. Interestingly, for three probands the molecular diagnosis was inconsistent with the initial clinical diagnosis, while for five probands the molecular information suggested a different inheritance model other than that assigned by the physician. In conclusion, our study demonstrated that NGS target sequencing is efficient and sufficiently precise for molecular diagnosis of a highly heterogeneous patient cohort from eyeGENE®.
DUF1220 copy number is associated with schizophrenia risk and severity: implications for understanding autism and schizophrenia as related diseases
Authors: Searles Quick V B , Davis J M , Olincy A , Sikela J M 
Published: December 2015

AbstractThe copy number of DUF1220, a protein domain implicated in human brain evolution, has been linearly associated with autism severity. Given the possibility that autism and schizophrenia are related disorders, the present study examined DUF1220 copy number variation in schizophrenia severity. There are notable similarities between autism symptoms and schizophrenia negative symptoms, and divergence between autism symptoms and schizophrenia positive symptoms. We therefore also examined DUF1220 copy number in schizophrenia subgroups defined by negative and positive symptom features, versus autistic individuals and controls. In the schizophrenic population (N=609), decreased DUF1220 copy number was linearly associated with increasing positive symptom severity (CON1 P=0.013, HLS1 P=0.0227), an association greatest in adult-onset schizophrenia (CON1 P=0.00155, HLS1 P=0.00361). In schizophrenic males, DUF1220 CON1 subtype copy number increase was associated with increased negative symptom severity (P=0.0327), a finding similar to that seen in autistic populations. Subgroup analyses demonstrated that schizophrenic individuals with predominantly positive symptoms exhibited reduced CON1 copy number compared with both controls (P=0.0237) and schizophrenic individuals with predominantly negative symptoms (P=0.0068). These findings support the view that (1) autism and schizophrenia exhibit both opposing and partially overlapping phenotypes and may represent a disease continuum, (2) variation in DUF1220 copy number contributes to schizophrenia disease risk and to the severity of both disorders, and (3) schizophrenia and autism may be, in part, a harmful by-product of the rapid and extreme evolutionary increase in DUF1220 copy number in the human species.
Mineralocorticoid Receptor Antagonists and Clinical Outcomes in
Primary Aldosteronism: As Good as Surgery?
Authors: Colussi G. L. , Novello M. , Uzzau A. , Catena C. , Sechi L. A. 
Published: December 2015

AbstractPrimary aldosteronism (PA) is detected with increasing frequency in hypertensive
patients and is associated with excess cardiovascular, renal, and metabolic
complications. For these reasons, appropriate choices for treatment of this
endocrine condition are mandatory. Adrenalectomy is safely performed in PA
patients when adrenal venous sampling (AVS) demonstrates lateralized aldosterone
secretion. AVS, however, is a complex procedure and even among worldwide
referral centers there are substantial discrepancies for interpretation of
results. Also, in the majority of PA patients with lateralized aldosterone
secretion, hypertension may persist after adrenalectomy requiring use of
additional antihypertensive agents. Treatment with mineralocorticoid receptor
antagonists (MRAs) is currently recommended for PA patients with bilateral
adrenal disease, but these agents effectively decrease blood pressure also in
patients with unilateral disease, although concern remains for possible
sex-related side effects. Prospective studies indicate that MRAs have
therapeutic values comparable to surgery in the long-term, inasmuch as they
effectively correct metabolic abnormalities and subclinical organ damage and
reduce the risk of cardiovascular events and renal disease progression. This
article overviews the clinical outcomes obtained in patients with PA with use of
MRAs.
Glucose Metabolism in Primary Aldosteronism
Authors: Remde H. , Hanslik G. , Rayes N. , Quinkler M. 
Published: December 2015

AbstractIn recent years, an increasing number of studies have revealed deleterious effects of aldosterone via the mineralocorticoid receptor (MR). Especially in patients with primary aldosteronism (PA) a significant higher estimated risk of developing cardiovascular comorbidities and comortalities compared to essential hypertensives was reported. As diabetes mellitus and the metabolic syndrome are one of the major contributors to cardiovascular morbidity and mortality their connection to aldosterone excess became a focus of research in PA patients. Several studies assessed the effect of PA on glucose metabolism, the prevalence of diabetes mellitus, and the effect of PA treatment on both revealing different results. Therefore, we performed an extensive literature research. This review focuses on the current knowledge of the connection between aldosterone excess, glucose homeostasis, and diabetes mellitus in patients with PA. We have highlighted this topic from a pro and contra perspective followed by a summarizing concluding remark. Additionally, we have briefly reviewed the data on possible underlying mechanisms and indicated future considerations on the possible impact of cortisol co-secretion in PA.
Parathyroid Gland Function in Primary Aldosteronism
Authors: Bekeran M. , Reincke M. , Asbach E. 
Published: December 2015

AbstractPrimary aldosteronism (PA) is the most frequent cause of secondary arterial
hypertension. Beyond its effects on intravascular volume and blood pressure,
PA causes metabolic alterations and a higher cardiovascular morbidity, which
is reduced by PA-directed therapy. Experimental studies demonstrated that
mineralocorticoid excess may also influence mineral homeostasis. A role in
cardiovascular disease has also been attributed to parathyroid hormone
(PTH). Increasing evidence supports a bidirectional interaction between
aldosterone and PTH.Primary hyperparathyroidism is associated with arterial hypertension and an
increased cardiovascular morbidity and mortality, which might be associated
to higher aldosterone values; parathyreoidectomy results in lowered
aldosterone and blood pressure levels. PA leads to secondary
hyperparathyroidism, which is reversible by PA-directed therapy. A lower
bone mineral density and a higher fracture rate were also shown to be
reversible by PA-directed therapy. There is a suspicion of a bidirectional
interaction between aldosterone and PTH, which might lead to a higher
cardiovascular risk. There are more and more reports about coincident PA and
primary hyperparathyroidism. From a pathophysiologic point of view this
constellation is best characterized as tertiary hyperparathyroidism. Future
aspects should further clarify the extent of these endocrine interactions
and analyze the influence of this interplay on cardiovascular morbidity and
mortality and bone health.
Steroid Hormone Production in Patients with Aldosterone Producing
Adenomas
Authors: Moors M. , Williams T. A. , Deinum J. , Eisenhofer G. , Reincke M. , Lenders J. W. M. 
Published: December 2015

AbstractPrimary aldosteronism encompasses 2 major underlying causes: (1) aldosterone
producing adenoma and (2) bilateral adrenal hyperplasia. In addition to the
aldosterone excess, increased production of other compounds of the steroidogenic
pathways may be involved. Until recently, most studies examined the production
of steroids other than aldosterone in tumor tissue, urine, or peripheral plasma
samples, but several new studies have also addressed steroid levels in adrenal
venous blood samples using liquid chromatography tandem mass spectrometry.
Plasma and tissue levels of several precursors of aldosterone with
mineralocorticoid activity are higher in patients with aldosterone producing
adenomas than in those with bilateral hyperplasia. These include corticosterone,
deoxycorticosterone, and their 18-hydroxylated metabolites. Similarly, urinary,
peripheral, and adrenal venous concentrations of the hybrid steroids
18-oxocortisol and 18-hydroxycortisol are higher in patients with aldosterone
producing adenomas than in bilateral hyperplasia. Differences in the
pathophysiology and in clinical and biochemical phenotypes caused by aldosterone
producing adenomas and bilateral adrenal hyperplasia may be related to the
differential expression of steroidogenic enzymes, and associated to specific
underlying somatic mutations. Correct appreciation of differences in steroid
profiling between aldosterone producing adenomas and bilateral adrenal
hyperplasia may not only contribute to a better understanding of the
pathogenesis of primary aldosteronism but may also be helpful for future
subtyping of primary aldosteronism.
Retrograde Endovascular Approach for Treating Unruptured Basilar Apex Aneurysms: Two Case Reports and Review of Literature
Authors: Rotta Marcus , Dias Guilherme , Rezende André , Pahl Felix , Oliveira Matheus , Rotta José 
Published: December 2015

Background Treatment of target lesions when parent vessels are injured or diseased may be quite difficult. Moret et al have proposed an endovascular technique based on retrograde transcirculation approach through communicating vessels.
Methods We report on the first Brazilian experience with retrograde endovascular approach, to the best of our knowledge.
Results The two cases illustrate difficult anterograde approach techniques to treat basilar apex aneurysms. In the first case, tortuosity and angulation of both vertebral arteries associated to stenosis did not allow an anterograde approach. In the second case, after a SAH of a basilar apex aneurysm treated more than a decade ago with bilateral vertebral artery trapping, the patient underwent a retrograde approach.
Conclusion For this approach, follow-up data are still lacking and complications are usually more common than in anterograde approach. Nevertheless, in select cases, it may be applied by experienced hands with acceptable risks when no other treatment option (surgical or endovascular) is available.
Patientenzufriedenheit als Maßeinheit im Qualitätsmanagement – ein Vergleich zwischen einem Universitätsklinikum und einem Krankenhaus der Regelversorgung
Authors: Eichhorn L. , Murday A.-K. , Kohnen B. , Guttenthaler V. , Türler A. , Baumgarten G. , Wittmann M. 
Published: December 2015

Zusammenfassung
Ziel der Studie: Ziel der Studie war der Vergleich der Zufriedenheit von Patienten eines Regelversorgers mit der eines Universitätsklinikums. Aus Wichtigkeit des Parameters und ermittelter Zufriedenheit wurde ein Patientenzufriedenheits-Index berechnet. Mittel- bis langfristig soll so die Wettbewerbsfähigkeit und Auslastung des Krankenhauses optimiert werden sowie vorhandene Ressourcen kosteneffizient zur Steigerung der Attraktivität eingesetzt werden.
Methode: Die Autoren führten eine fragebogengestützte Erhebung in einem Universitätsklinikum (Universitätsklinikum Bonn, UKB, 1 224 Betten) und einem Krankenhaus der Regelversorgung (Johanniterkrankenhaus Bonn, JKH, 364 Betten) durch. Darin konnten Patienten anonymisiert Fragen zu unterschiedlichen Gesichtspunkten ihres Krankenhausaufenthalts beantworten. Es wurde sowohl die Zufriedenheit der Patienten mit den einzelnen Aspekten als auch die Einschätzung der Wichtigkeit erfasst. Hieraus wurde ein Patientenzufriedenheitsindex (PZI) ermittelt und statistisch ausgewertet.
Ergebnis: Die Ansprüche und Wünsche der Patienten beider Krankenhäuser, deren Zufriedenheit und die Gewichtung der einzelnen Gesichtspunkte unterscheiden sich in allen abgefragten Bereichen (Informations-, Beteiligungs-, Kontakt- und Komfortaspekt während des Krankenhausaufenthaltes) nicht signifikant. Die Studie ergab, dass den Patienten die Kommunikation beziehungsweise der Kontakt mit Ärzten und Pflegern an beiden Kliniken signifikant wichtiger ist als der Komfort (jeweils p<0,001). Die höchsten PZI-Werte ergaben sich beim Unterhaltungsangebot (UKB 1,02; JKH 1,25) und dem Kontakt zum Pflegepersonal (UKB 0,94; JKH 0,96). Auch mit der medizinisch-technischen Versorgungsqualität (UKB 0,93; JKH 0,95) zeigen sich die Patienten in beiden Kliniken sehr zufrieden. Verbesserungsbedarf besteht vor allem in der Kommunikation von Fehlern (PZI UKB 0,33; PZI JKH 0,31).
Schlussfolgerung: Durch das Erfassen der Ansprüche und Kritikpunkte der Patienten wird die patientenorientierten Gestaltung des Klinikalltages verbessert. Dadurch können personelle und materielle Ressourcen effizienter genutzt und durch konsequente Hinterfragung der eingesetzten Mittel die Attraktivität der Klinik gesteigert werden.
Mapping bilateral information interests using the activity of Wikipedia editors
Authors: Karimi Fariba , Bohlin Ludvig , Samoilenko Anna , Rosvall Martin , Lancichinetti Andrea 
Published: December 2015

AbstractWe live in a global village where electronic communication has eliminated the geographical barriers of information exchange. The road is now open to worldwide convergence of information interests, shared values and understanding. Nevertheless, interests still vary between countries around the world. This raises important questions about what today’s world map of information interests actually looks like and what factors cause the barriers of information exchange between countries. To quantitatively construct a world map of information interests, we devise a scalable statistical model that identifies countries with similar information interests and measures the countries’ bilateral similarities. From the similarities we connect countries in a global network and find that countries can be mapped into 18 clusters with similar information interests. Through regression we find that language and religion best explain the strength of the bilateral ties and formation of clusters. Our findings provide a quantitative basis for further studies to better understand the complex interplay between shared interests and conflict on a global scale. The methodology can also be extended to track changes over time and capture important trends in global information exchange.
Site-specifically labeled CA19.9-targeted immunoconjugates for the PET, NIRF, and multimodal PET/NIRF imaging of pancreatic cancer
Authors: Houghton Jacob L. , Zeglis Brian M. , Abdel-Atti Dalya , Aggeler Robert , Sawada Ritsuko , Agnew Brian J. , Scholz Wolfgang W. , Lewis Jason S. 
Published: December 2015

Significance
Pancreatic cancer will soon be the second leading cause of cancer deaths annually, yet no adequate molecular imaging tools exist to aid in the staging, monitoring, and treatment of the disease. Here we describe the development and preclinical evaluation of three unique immunoconjugates for positron emission tomography, near-infrared fluorescent optical imaging, and multimodal imaging of pancreatic ductal adenocarcinoma (PDAC). The probes were developed using a site-specific, chemoenzymatic methodology that is robust, reproducible, and modular. By targeting CA19.9, the most abundant antigen in >90% of PDAC tumors, we were able to obtain high-quality images in multiple murine models of PDAC, suggesting these constructs could be the core of a molecular imaging toolkit aimed at improving outcomes for patients with PDAC.
Lung inflammation promotes metastasis through neutrophil protease-mediated degradation of Tsp-1
Authors: El Rayes Tina , Catena Raúl , Lee Sharrell , Stawowczyk Marcin , Joshi Natasha , Fischbach Claudia , Powell Charles A. , Dannenberg Andrew J. , Altorki Nasser K. , Gao Dingcheng , Mittal Vivek 
Published: December 2015

SignificanceLungs are highly susceptible to inflammation. However, molecular insights into how external inflammation enhances metastatic outgrowth in the lungs remain lacking. Clinically, approaches are required to block tumor outgrowth in secondary organs for effective treatment of metastatic cancers. We demonstrate a previously unidentified mechanism of thrombospondin-1 (Tsp-1) regulation by inflammatory neutrophil proteases in the metastatic organ. Our findings suggest the potential of using neutrophil protease inhibitors as antimetastatic therapies.
Lymphomagenic CARD11/BCL10/MALT1 signaling drives malignant B-cell proliferation via cooperative NF-κB and JNK activation
Authors: Knies Nathalie , Alankus Begüm , Weilemann Andre , Tzankov Alexandar , Brunner Kristina , Ruff Tanja , Kremer Marcus , Keller Ulrich B. , Lenz Georg , Ruland Jürgen 
Published: December 2015

Significance
The activated B cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) has a poor clinical outcome and is characterized by constitutive caspase recruitment domain-containing protein 11 (CARD11)/B-cell CLL/lymphoma 10 (BCL10)/mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1) signaling and nuclear factor kappa-B (NF-κB) activation, which is essential for tumor cell survival. However, NF-κB inhibitors have not reached the clinic due to high toxicity, and alternative strategies for targeted therapies are needed. Using mouse genetics, we demonstrate that forced CARD11/BCL10/MALT1 signaling drives lethal lymphoproliferation through simultaneous NF-κB and c-Jun N-terminal kinase (JNK) activation. Pharmacological inhibition of JNK was similar to NF-κB blockage and toxic to autonomously proliferating murine B cells, and constitutive JNK activity was observed in human ABC-DLBCL cells, which are also sensitive to JNK inhibitors. Our results identify the JNK pathway as a therapeutic target for DLBCL.
Rod disc renewal occurs by evagination of the ciliary plasma membrane that makes cadherin-based contacts with the inner segment
Authors: Burgoyne Thomas , Meschede Ingrid P. , Burden Jemima J. , Bailly Maryse , Seabra Miguel C. , Futter Clare E. 
Published: December 2015

Significance
Photoreceptors of the vertebrate retina contain specialized outer segments (OSs) where phototransduction begins. Rod OSs contain stacks of ordered membranous discs that undergo a daily renewal process essential for vision. Mechanisms underlying disc renewal are unclear. The biosynthetic machinery resides in the inner segment (IS), which is connected to the OS via a connecting cilium. Here, we use electron microscopy and tomography to show that the visual pigment, rhodopsin, traffics to the OS via the ciliary plasma membrane, which evaginates to form discs that are initially extracellularly exposed and that make novel contacts with the IS. Leading edges of adjacent evaginations then fuse to form discrete discs. Tomographic analysis leads us to propose a potential mechanism underlying the evagination process.
Data contradict common perceptions about a controversial provision of the US Endangered Species Act
Authors: Malcom Jacob W. , Li Ya-Wei 
Published: December 2015

Significance
The US Endangered Species Act is the most comprehensive law any nation has enacted to protect imperiled species. Many of its protections come from section 7 of the Act, but how government regulators use this tool is poorly understood. Our analysis is the first to systematically evaluate how the US Fish and Wildlife Service has implemented section 7 over an extend timeframe and across all listed species. The results inform current efforts to improve the conservation effectiveness of section 7 and rebut certain claims about the regulatory burdens of complying with section 7.
Oscillatory phase shapes syllable perception
Authors: ten Oever Sanne , Sack Alexander T. 
Published: December 2015

Significance
The environment is full of temporal information that links specific auditory and visual representations to each other. Especially in speech, this is used to guide perception. The current paper shows that syllables with varying visual-to-auditory delays get preferably processed at different oscillatory phases. This mechanism facilitates the separation of different representations based on consistent temporal patterns in the environment and provides a way to categorize and memorize information, thereby optimizing a wide variety of perceptual processes.
Ezh2 regulates differentiation and function of natural killer cells through histone methyltransferase activity
Authors: Yin Jie , Leavenworth Jianmei W. , Li Yang , Luo Qi , Xie Huafeng , Liu Xinhua , Huang Shan , Yan Han , Fu Zheng , Zhang Liyun Y. , Zhang Litao , Hao Junwei , Wu Xudong , Deng Xianming , Roberts Charles W. M. , Orkin Stuart H. , Cantor Harvey , Wang Xi 
Published: December 2015

Significance
How NK cell development diverges from T/B cell commitment at the common lymphoid progenitor stage is poorly understood. Histone modification near critical gene loci often influences lineage determination. Ezh2 is a histone methyltransferase frequently associated with gene repression. Here we observed that Ezh2-null hematopoietic stem and progenitor cells (HSPCs) or HSPCs treated with Ezh2 inhibitors gave rise to increased NK precursors and mature progeny that display enhanced cytotoxicity against tumor cells. The latter effects were associated with up-regulation of IL-15R (CD122) and the NKG2D-activating receptor. These findings may provide insight into the contribution of epigenetic regulation to the genesis of NK cells and suggest that Ezh2 inhibitors may inhibit tumor growth directly and indirectly through mobilization of NK cells.
The courage of conviction
Authors: Paul Sarah K. 
Published: December 2015

AbstractIs there a sense in which we exercise direct volitional control over our beliefs? Most agree that there is not, but discussions tend to focus on control in forming a belief. The focus here is on sustaining a belief over time in the face of ‘epistemic temptation’ to abandon it. It is argued that we do have a capacity for ‘doxastic self-control’ over time that is partly volitional in nature, and that its exercise is rationally permissible.
Every coprime linear group admits a base of size two
Authors: Halasi Zoltán , Podoski Károly 
Published: December 2015

Let

G
G

be a linear group acting faithfully on a finite vector space

V
V

and assume that

(

|

G

|

,

|

V

|

)
=
1

(|G|,|V|) =1

. In this paper we prove that

G
G

admits a base of size two and that this estimate is sharp. This generalizes and strengthens several former results concerning base sizes of coprime linear groups. As a direct consequence, we answer a question of I. M. Isaacs in the affirmative.