tbuckley/cabot-search huggingface dataset:
Features of Structural Brain Abnormality Detected in First-Episode Psychosis
Authors: Dominic Fannon, Xavier Chitnis, Victor Doku, Lakshika Tennakoon, Séamus Ó’Ceallaigh, William Soni, Alex Sumich, Jennifer Lowe, Mar Santamaria, Tonmoy Sharma
Journal: American Journal of Psychiatry (2000)

Structural magnetic resonance imaging (MRI) studies that focus on first-episode psychosis avoid some common confounds, such as chronicity of illness, treatment effects, and long-term substance abuse. However, such studies may select subjects with poor short-term treatment response or outcome. In this study, the authors focus on structural brain abnormalities in never or minimally treated patients who underwent MRI scanning early in their first episode of psychosis.The authors examined 37 patients (13 medication naive, 24 previously treated) who were experiencing their first episode of psychosis; the mean duration of symptoms was short (31 weeks). These patients were comparable in age, gender, handedness, ethnicity, and parental socioeconomic status to a group of 25 healthy comparison subjects. A three-dimensional, inversion recovery prepared, fast spoiled gradient/recall in the steady state scan of the whole brain that used 1.5-mm contiguous sections was performed to acquire a T(1)-weighted data set. Human ratings of volumetric measurement of brain structures were performed with stereological techniques on three-dimensional reconstructed MRIs.The patient group had significant deficits in cortical gray matter, temporal lobe gray matter, and whole brain volume as well as significant enlargement of the lateral and third ventricles. Structural deviations were found in both treatment-naive and minimally treated subjects. No relationships were found between any brain matter volumes and positive or negative symptoms.Structural brain abnormalities were distributed throughout the cortex with particular decrement evident in gray matter. This feature is consistent with altered cell structure and disturbed neuronal connectivity, which accounts for the functional abnormality of psychosis.
Gene expression profiling of human prostate cancer stem cells reveals a pro-inflammatory phenotype and the importance of extracellular matrix interactions
Authors: Richard Birnie, Steven D Bryce, Claire Roome, Vincent Dussupt, Alastair Droop, Shona H Lang, Paul A Berry, Catherine F Hyde, John L Lewis, Michael J Stower, Norman J Maitland, Anne T Collins
Journal: Genome biology (2008)

Abstract Background The tumor-initiating capacity of many cancers is considered to reside in a small subpopulation of cells (cancer stem cells). We have previously shown that rare prostate epithelial cells with a CD133 + /α 2 β 1 hi phenotype have the properties of prostate cancer stem cells. We have compared gene expression in these cells relative to their normal and differentiated (CD133 - /α 2 β 1 low ) counterparts, resulting in an informative cancer stem cell gene-expression signature. Results Cell cultures were generated from specimens of human prostate cancers (n = 12) and non-malignant control tissues (n = 7). Affymetrix gene-expression arrays were used to analyze total cell RNA from sorted cell populations, and expression changes were selectively validated by quantitative RT-PCR, flow cytometry and immunocytochemistry. Differential expression of multiple genes associated with inflammation, cellular adhesion, and metastasis was observed. Functional studies, using an inhibitor of nuclear factor κB (NF-κB), revealed preferential targeting of the cancer stem cell and progenitor population for apoptosis whilst sparing normal stem cells. NF-κB is a major factor controlling the ability of tumor cells to resist apoptosis and provides an attractive target for new chemopreventative and chemotherapeutic approaches. Conclusion We describe an expression signature of 581 genes whose levels are significantly different in prostate cancer stem cells. Functional annotation of this signature identified the JAK-STAT pathway and focal adhesion signaling as key processes in the biology of cancer stem cells.
Different pathways with distinct properties conduct dilations in the microcirculation in vivo
Authors: Cor de Wit
Journal: Cardiovascular Research (2009)

AimsConduction of vasomotor signals along the vessel coordinates the behaviour of vascular cells and is attributed to the spread of hyperpolarizations through gap junctions. Intriguingly, conducted dilations encompass larger distances than can be expected by passive electrotonic spread. Because distances are quite distinct for different dilators, we hypothesized that separate pathways with distinct properties are involved.
Delayed Administration of a Single Dose of Lithium Promotes Recovery from AKI
Authors: Hui Bao, Yan Ge, Zhen Wang, Shougang Zhuang, Lance Dworkin, Ai Peng, Rujun Gong
Journal: Journal of the American Society of Nephrology (2014)

Evidence suggests that glycogen synthase kinase 3β (GSK3β) contributes to AKI; however, its role in post-AKI kidney repair remains uncertain. Here, delayed treatment with a single dose of lithium, a selective inhibitor of GSK3β and a US Food and Drug Administration-approved mood stabilizer, accelerated recovery of renal function, promoted repopulation of renal tubular epithelia, and improved kidney repair in murine models of cisplatin- and ischemia/reperfusion-induced AKI. These effects associated with reduced GSK3β activity and elevated expression of proproliferative molecules, including cyclin D1, c-Myc, and hypoxia-inducible factor 1α (HIF-1α), in renal tubular epithelia. In cultured renal tubular cells, cisplatin exposure led to transient repression of GSK3β activity followed by a prolonged upregulation of activity. Rescue treatment with lithium inhibited GSK3β activity, enhanced nuclear expression of cyclin D1, c-Myc, and HIF-1α, and boosted cellular proliferation. Similarly, ectopic expression of a kinase-dead mutant of GSK3β enhanced the expression of cyclin D1, c-Myc, and HIF-1α and amplified cellular proliferation after cisplatin injury, whereas forced expression of a constitutively active mutant of GSK3β abrogated the effects of lithium. Mechanistically, GSK3β colocalized and physically interacted with cyclin D1, c-Myc, and HIF-1α in tubular cells. In silico analysis revealed that cyclin D1, c-Myc, and HIF-1α harbor putative GSK3β consensus phosphorylation motifs, implying GSK3β-directed phosphorylation and subsequent degradation of these molecules. Notably, cotreatment with lithium enhanced the proapoptotic effects of cisplatin in cultured colon cancer cells. Collectively, our findings suggest that pharmacologic targeting of GSK3β by lithium may be a novel therapeutic strategy to improve renal salvage after AKI.
Defense Mechanism Changes in Successfully Treated Patients With Obsessive-Compulsive Disorder
Authors: Ronald C. Albucher, James L. Abelson, Randolph M. Nesse
Journal: American Journal of Psychiatry (1998)

Changes in defense mechanisms after treatment of patients with obsessive-compulsive disorder (OCD) were measured by using an established rating scale.Before and after 7-week group behavior therapy, 17 patients with DSM-III-R OCD were assessed with the Defense Style Questionnaire, Yale-Brown Obsessive Compulsive Scale, and Beck Depression Inventory.After behavior therapy the patients evidenced significant decreases in Yale-Brown Obsessive Compulsive Scale scores and significant increases in the use of more adaptive defense mechanisms. There were no significant changes in three maladaptive defense mechanism categories. The improvement in adaptive defenses was independently linked to improvement both in OCD and in depression.Personality as defined by defense mechanisms may be more amenable to brief behavioral treatment than previously thought. The permanence of these changes must be further assessed.
Incidence of peptic ulcer disease in Gothenburg, 1985.
Authors: I. M. Schoon, D. Mellstrom, A. Oden, B. O. Ytterberg
Journal: BMJ (1989)

To determine the incidence and age distribution of peptic ulcer disease in adults in Gothenburg.Retrospective study of patients with symptoms over one year.All gastroenterology and x ray departments.Any patient found to have an active ulcer crater during 1985.Sex, age, past history of gastrointestinal ulcers, and smoking habit.In 1985, 1402 peptic ulcers were diagnosed in 1137 adults. Over half (403; 54%) of the ulcers in men and 393 (60%) ulcers in women were in patients aged over 60. All types of ulcer showed increasing incidence with age. The sex ratio of patients aged 40-50 with peptic ulcers was 1:1. Nearly half (109; 48%) of ulcers diagnosed for the first time in men and 129 (57%) of such ulcers in women were in patients aged over 60. Elderly men and women were also more likely to develop haemorrhage.In Gothenburg there is a surprisingly high incidence of peptic ulcer disease, which increases considerably with age, possibly explained by the availability of modern diagnostic techniques as 1121 (80%) ulcers had been diagnosed by gastroscopy. Compared with earlier studies there was no difference in the incidence between men and women aged 40-50.
Rates and patterns of mitochondrial DNA sequence evolution in fringilline finches (fringilla spp.) and the greenfinch (Carduelis chloris)
Authors: H. D. Marshall, A. J. Baker
Journal: Molecular Biology and Evolution (1998)

Rates and patterns of evolution in partial sequences of five mitochondrial genes (cytochrome b, ATPase 6, NADH dehydrogenase subunit 5, tRNA(Glu), and the control region) were compared among taxa in the passerine bird genera Fringilla and Carduelis. Rates of divergence do not vary significantly among genes, even in comparisons with the control region. Rate variation among lineages is significant only for the control region and NADH dehydrogenase subunit 5, and patterns of variation are consistent with the expectations of neutral theory. Base composition is biased in all genes but is stationary among lineages, and there is evidence for directional mutation pressure only in the control region. Despite these similarities, patterns of substitution differ among genes, consistent with alternative regimes of selective constraint. Rates of nonsynonymous substitution are higher in NADH dehydrogenase subunit 5 than in other protein-coding genes, and transitions exist in elevated proportions relative to transversions. Transitions appear to accumulate linearly with time in tRNA(Glu), and despite exhibiting the highest overall rate of divergence among species, there are no transversional changes in this gene. Finally, for resolving phylogenetic relationships among Fringilla taxa, the combined protein-coding data are broadly similar to those of the control region in terms of phylogenetic informativeness and statistical support.
Renal Enlargement Precedes Renal Hyperfiltration in Early Experimental Diabetes in Rats
Authors: MARTIN BAK, KLAUS THOMSEN, THORA CHRISTIANSEN, ALLAN FLYVBJERG
Journal: Journal of the American Society of Nephrology (2000)

Abstract. The order of appearance between renal hypertrophy and hyperfunction in early experimental diabetes is still disputed. The reason for previous discrepant results is believed to be methodologic problems, as most previous studies of renal function have been performed in anesthetized animals. In the present study in nondiabetic and streptozotocin-diabetic animals, renal volume was measured by a noninvasive magnetic resonance imaging technique, while renal function parameters were measured in conscious, chronically catheterized animals. To avoid artifacts caused by the procedures associated with induction of streptozotocin-diabetes (fasting, brief anesthesia, and transient hypoglycemia) on renal growth and function, diabetic animals were injected with insulin to obtain euglycemia for 4 d before study start. At day 0, insulin administration was withdrawn and all animals developed hyperglycemia within 12 h. Renal volume and kidney function were measured on days 0, 1, 2, 3, 5, and 7. Renal enlargement was detectable at day 1 (20%) and reached an increase of 40% at day 7. No changes were seen in effective renal plasma flow or effective renal vascular resistance within the first 7 d after development of hyperglycemia. GFR tended to rise on day 5 and was increased by 16% at day 7. The absolute proximal reabsorption showed a pronounced rise (30%) at day 7, whereas no change was seen in the proximal tubular fluid output. It is concluded that renal enlargement precedes renal hyperfunction in the early phase after onset of experimental diabetes.
New antibody approaches to lymphoma therapy
Authors: Tejas Suresh, Lisa X Lee, Jitesh Joshi, Stefan K Barta
Journal: Journal of Hematology & Oncology (2014)

The CD20-directed monoclonal antibody rituximab established a new era in lymphoma therapy. Since then other epitopes on the lymphoma surface have been identified as potential targets for monoclonal antibodies (mAb). While most mAbs eliminate lymphoma cells mainly by antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity or direct cell death, others counter mechanisms utilized by malignant cells to evade immune surveillance. Expression of PD-L1 on malignant or stromal cells in the tumor environment for example leads to T-cell anergy. Targeting either PD-1 or PD-L1 via mAbs can indirectly eliminate cancer cells by unblocking the host intrinsic immune response. Yet another mechanism of targeted therapy with mAbs are bi-specific T-cell engagers (BiTE) such as blinatumomab, which directly engages the host immune cells. These examples highlight the broad spectrum of available therapies targeting the lymphoma surface with mAbs utilizing both passive and active immune pathways. Many of these agents have already demonstrated significant activity in clinical trials. In this review we will focus on novel CD20-directed antibodies as well as mAbs directed against newer targets like CD19, CD22, CD40, CD52 and CCR4. In addition we will review mAbs unblocking immune checkpoints and the BiTE blinatumomab. Given the success of mAbs and the expansion in active and passive immunotherapies, these agents will play an increasing role in the treatment of lymphomas.
Intestinal Transport of Cystine and Cysteine in Man: Evidence for Separate Mechanisms*
Authors: Leon E. Rosenberg, John C. Crawhall, Stanton Segal
Journal: Journal of Clinical Investigation (1967)

Cystine and cysteine are transported by energy-dependent, mediated processes in human gut. When either of these amino acids is transported, only cysteine is recovered intracellularly, indicating that cystine is reduced to cysteine after achieving an intracellular location. In contrast to results with cystine, cysteine uptake is not defective in gut from cystinuric patients, nor do lysine and arginine compete with cysteine for transport. It is, therefore, concluded that cystine and cysteine are transported by different mechanisms, and that only the cystine transport mechanism is defective in cystinuria.
Psoriasis after treatment of juvenile idiopathic arthritis with etanercept
Authors: R Peek, R Scott-Jupp, H Strike, J Clinch, A V Ramanan
Journal: Annals of the Rheumatic Diseases (2006)

<h3>Abstract</h3> RNA sequencing offers unprecedented access to the transcriptome. Key to this is the identification and quantification of many different species of RNA from the same sample at the same time. In this study we describe a novel protocol for simultaneous detection of coding and non-coding transcripts using modifications to the Ion Total RNA-Seq kit v2 protocol, with integration of QIASeq FastSelect rRNA removal kit. We report highly consistent sequencing libraries can be produced from both frozen high integrity mouse hippocampal tissue and the more challenging post-mortem human tissue. Removal of rRNA using FastSelect was highly efficient, resulting in less than 1.5% rRNA content in the final library, significantly better than other reported rRNA removal techniques. We identified &gt;30,000 unique transcripts from all samples, including protein-coding genes and many unique species of non-coding RNA, in biologically-relevant proportions. Furthermore, normalized sequencing read count for select genes significantly negatively correlated with Ct values from RT-qPCR analysis from the same samples. These results indicate that this protocol accurately and consistently identifies and quantifies a wide variety of transcripts simultaneously. The highly efficient rRNA depletion, coupled with minimized sample handling and without complicated and high-loss size selection protocols, makes this protocol useful to researchers wishing to investigate whole transcriptomes.
Prevalence of Articles With Honorary Authors and Ghost Authors in Peer-Reviewed Medical Journals
Authors: Annette Flanagin
Journal: JAMA (1998)

Authorship in biomedical publications establishes accountability, responsibility, and credit. Misappropriation of authorship undermines the integrity of the authorship system, but accurate data on its prevalence are limited.To determine the prevalence of articles with honorary authors (named authors who have not met authorship criteria) and ghost authors (individuals not named as authors but who contributed substantially to the work) in peer-reviewed medical journals and to identify journal characteristics and article types associated with such authorship misappropriation.Mailed, self-administered, confidential survey.A total of 809 corresponding authors (1179 surveyed, 69% response rate) of articles published in 1996 in 3 peer-reviewed, large-circulation general medical journals (Annals of Internal Medicine, JAMA, and The New England Journal of Medicine) and 3 peer-reviewed, smaller-circulation journals that publish supplements (American Journal of Cardiology, American Journal of Medicine, and American Journal of Obstetrics and Gynecology).Prevalence of articles with honorary authors and ghost authors, as reported by corresponding authors.Of the 809 articles, 492 were original research reports, 240 were reviews and articles not reporting original data, and 77 were editorials. A total of 156 articles (1 9%) had evidence of honorary authors (range, 11%-25% among journals); 93 articles (11%) had evidence of ghost authors (range, 7%-16% among journals); and 13 articles (2%) had evidence of both. The prevalence of articles with honorary authors was greater among review articles than research articles (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2-2.6) but did not differ significantly between large-circulation and smaller-circulation journals (OR, 1.4; 95% CI, 0.96-2.03). Compared with similar-type articles in large-circulation journals, articles with ghost authors in smaller-circulation journals were more likely to be reviews (OR, 4.2; 95% CI, 1.5-13.5) and less likely to be research articles (OR, 0.49; 95% CI, 0.27-0.88).A substantial proportion of articles in peer-reviewed medical journals demonstrate evidence of honorary authors or ghost authors.
Treatment of multivessel coronary artery disease with sirolimus-eluting stent implantation: immediate and mid-term results
Authors: Dejan Orlic, Erminio Bonizzoni, Goran Stankovic, Flavio Airoldi, Alaide Chieffo, Nicola Corvaja, Giuseppe Sangiorgi, Massimo Ferraro, Carlo Briguori, Matteo Montorfano, Mauro Carlino, Antonio Colombo
Journal: Journal of the American College of Cardiology (2004)
Efficacy of Nordic walking in rehabilitation of patients with COPD: Preliminary data
Authors: Maria Aliani, Giuseppina Fumarulo, Silvano Dragonieri, Mauro D'Alessandro, Vincenzo Digilio, Mauro Carone
Journal: European Respiratory Journal (2012)

BACKGROUND. Nordic walking is a well-known activity which combines sport and wellness. It was conceived in Scandinavian countries as summer training for Nordic ski athletes and it is extremely simple to perform. However, there are very few studies which evaluated the use of Nordic walking in the field of physical rehabilitation. The aim of the study is to assess the efficacy of Nordic walking in patients with COPD.

METHODS. We enrolled 11 patients with COPD (mean age 64,2±1,3) in a stable phase of their disease and randomized them into two groups. The study group was composed by 5 patients who performed a daily 30 minutes session of Nordic walking for 5 days a week for a total period of 3 weeks. The control group was composed by 6 patients who were treated with traditional rehabilitation (selective training of arms and legs) for the same period as study group. Both the groups performed educational intervention and exercises for respiratory coordination. The two groups of patients performed spirometry, blood gas analysis, 6 minutes walking test, MRC, BDI/TDI, EuroQoL and Saint George test before and after the rehabilitation period.

RESULTS.

Patients in the study group had a significant improvement in terms of post training 6 minutes walking test, MRC, EuroQoL and Saint George (p<0.05) whereas patients in the control group had only an improvement in MRC (p<0.05).

CONCLUSIONS.

This preliminary study shows the efficacy of nordic walking in reducing dyspnoea, improving physical performance and quality of life in a small group of patiens with COPD. If confirmed in larger studies nordic walking could become part of the training schedules for COPD rehabilitation.
A newly identified splice site mutation in<i>ZMPSTE24</i>causes restrictive dermopathy in the Middle East
Authors: C.S. Sander, N. Salman, M. van Geel, J.L.V. Broers, A. Al-Rahmani, F. Chedid, I. Hausser, V. Oji, K. Al Nuaimi, T.G. Berger, V.L.R.M. Verstraeten
Journal: British Journal of Dermatology (2008)

Restrictive dermopathy (RD) is a severe neonatal inherited skin syndrome of which children die shortly after birth. Clinical features include intrauterine growth retardation, taut translucent and easily eroded skin, multiple joint ankylosis and distinct facial features. RD is usually caused by homozygous or compound heterozygous mutations in ZMPSTE24, predicted to cause loss of function of the encoded zinc metalloproteinase STE24. ZMPSTE24 is essential for the processing of the nuclear intermediate filament protein prelamin A. We report two distantly related children from the United Arab Emirates with RD. Remarkably, they lived up to 2 months, suggesting some residual function of the mutant protein. We sought to confirm the diagnosis by thorough microscopic analysis of patient skin, to identify the causative mutation and to study its functional consequences. A skin biopsy was obtained and processed for light and electron microscopy. Peripheral blood leucocytes were used for DNA and RNA isolation, and detection of prelamin A by immunofluorescence. Analysis of the skin confirmed the earlier reported densely packed collagen bundles and lack of elastin fibres. In both patients a homozygous splice site mutation c.627+1G>C in ZMPSTE24 was identified. Analysis of the ZMPSTE24 mRNA revealed an in-frame exon 5 skipping. Accumulation of prelamin A could be detected at the nuclear envelope of patient blood lymphocytes. We thus report the first splice site mutation in ZMPSTE24, which is likely to be a founder mutation in the United Arab Emirates. The accumulation of prelamin A at the nuclear periphery is consistent with defective ZMPSTE24 function. Interestingly, a regular blood sample can be used to investigate prelamin A accumulation.