tbuckley/cabot-search huggingface dataset:
Sudden Gains in the Treatment of Obsessive-Compulsive Disorder
Authors: Idan M. Aderka, Gideon E. Anholt, Anton J.L.M. van Balkom, Johannes H. Smit, Haggai Hermesh, Patricia van Oppen
Journal: Psychotherapy and Psychosomatics (2011)

&lt;i&gt;Background:&lt;/i&gt; The present study examined sudden gains during treatment for obsessive-compulsive disorder (OCD) and their relationship to short- and long-term outcome. &lt;i&gt;Methods:&lt;/i&gt; Ninety-one individuals (age 19–64) completed either cognitive treatment, exposure treatment, or their combination with fluvoxamine for OCD. Participants’ obsessive-compulsive symptoms were assessed before each weekly treatment session. In addition, obsessive-compulsive and depressive symptoms were assessed pre treatment and post treatment as well as 12 months following treatment termination. &lt;i&gt;Results:&lt;/i&gt; Sudden gains were found among 34.1% of participants and constituted 65.5% of the total reduction in obsessive-compulsive symptoms. Compared to individuals who did not experience sudden gains, individuals who experienced sudden gains reported lower levels of OCD symptoms post treatment, and this was maintained during follow-up. &lt;i&gt;Conclusions:&lt;/i&gt; Sudden gains are common in treatments for OCD and are predictive of treatment outcome and follow-up. Sudden gains mark a distinct trajectory of response to treatment for OCD. Individuals with sudden gains greatly improve during treatment and maintain their gains during follow-up, whereas individuals without sudden gains improve to a significantly lesser extent. Thus, treatment planning and development can benefit from considering sudden gains and the intra-individual course of improvement.
The Evolutionary History of Archaeal MCM Helicases: A Case Study of Vertical Evolution Combined with Hitchhiking of Mobile Genetic Elements
Authors: M. Krupovic, S. Gribaldo, D. H. Bamford, P. Forterre
Journal: Molecular Biology and Evolution (2010)

Genes encoding DNA replication proteins have been frequently exchanged between cells and mobile elements, such as viruses or plasmids. This raises potential problems to reconstruct their history. Here, we combine phylogenetic and genomic context analyses to study the evolution of the replicative minichromosome maintenance (MCM) helicases in Archaea. Several archaeal genomes encode more than one copy of the mcm gene. Genome context analysis reveals that most of these additional copies are encoded within mobile elements. Exhaustive analysis of these elements reveals diverse groups of integrated archaeal plasmids or viruses, including several head-and-tail proviruses. Some MCMs encoded by mobile elements are structurally distinct from their cellular counterparts, with one case of novel domain organization. Both genome context and phylogenetic analysis indicate that MCM encoded by mobile elements were recruited from cellular genomes. An accelerated evolution and a dramatic expansion of methanococcal MCMs suggest a host-to-virus-to-host transfer loop, possibly triggered by the loss of the archaeal initiator protein Cdc6 in Methanococcales. Surprisingly, despite extensive transfer of mcm genes between viruses, plasmids, and cells, the topology of the MCM tree is strikingly congruent with the consensus archaeal phylogeny, indicating that mobile elements encoding mcm have coevolved with their hosts and that DNA replication proteins can be also useful to reconstruct the history of the archaeal domain.
Statins and Renal Diseases
Authors: Giuseppe D’Amico
Journal: Journal of the American Society of Nephrology (2006)

In glomerular diseases with nephrotic syndrome or protracted severe proteinuria, alterations of the lipid metabolism occur and are characterized mainly by increase of LDL cholesterol and frequently also of triglycerides and by qualitative abnormalities of HDL cholesterol and LDL cholesterol. In all renal diseases, when renal insufficiency develops, hyperlipidemia also occurs, with a near-elective increase in VLDL and intermediate-density lipoprotein cholesterol and a decrease of mature HDL cholesterol. There is clear evidence that these abnormalities may induce cardiovascular complications and, probably, also an accelerated progression of the renal damage. The inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase, the so-called statins, are effective in controlling hypercholesterolemia, even in the more advanced stages of renal failure and in patients who are on maintenance dialysis. This antilipidemic effect of statins combines with other effects—antioxidant, anti-inflammatory, immunomodulatory, and antithrombotic (called "pleiotropic" effects)—as a result of the inhibition of the mevalonate pathway induced by these agents. Also because of these non–lipid-dependent effects, statins could have an antiatherosclerotic and renoprotective effect, which has been demonstrated clearly <i>in vivo</i> on renal cells and in experimental models of nephropathy but is still less evident in human renal diseases. Ongoing large trials will establish more clearly whether such effects are present in renal patients.
Bone-Related Complications and Quality of Life in Advanced Breast Cancer: Results from a Randomized Phase III Trial of Denosumab versus Zoledronic Acid
Authors: Miguel Martin, Richard Bell, Hugues Bourgeois, Adam Brufsky, Ingo Diel, Alexandru Eniu, Lesley Fallowfield, Yasuhiro Fujiwara, Jacek Jassem, Alexander H.G. Paterson, Diana Ritchie, Günther G. Steger, Alison Stopeck, Charles Vogel, Michelle Fan, Qi Jiang, Karen Chung, Roger Dansey, Ada Braun
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Denosumab was shown to be superior to zoledronic acid in preventing skeletal related events (SRE) in patients with breast cancer and bone metastases in a randomized, double-blind phase III study. We evaluated further results from this study related to skeletal complications and health-related quality of life (HRQoL). Experimental Design: Patients were randomized 1:1 to receive subcutaneous denosumab 120 mg (n = 1,026) and intravenous placebo, or intravenous zoledronic acid 4 mg (n = 1,020) and subcutaneous placebo every 4 weeks. Analyses reported here include the proportion of patients with one or multiple on-study SREs, time to first radiation to bone, time to first SRE or hypercalcemia of malignancy, and change in HRQoL (functional assessment of cancer therapy–general). Results: Fewer patients receiving denosumab than zoledronic acid had an on-study SRE (31% vs. 36%, P = 0.006). The incidence of first radiation to bone was 12% (n = 123) with denosumab versus 16% (n = 162) with zoledronic acid. Denosumab prolonged the time to first radiation to bone by 26% versus zoledronic acid (HR, 0.74; 95% confidence interval [CI], 0.59–0.94, P = 0.012) and prolonged the time to first SRE or hypercalcemia of malignancy by 18% (HR, 0.82; 95% CI, 0.70–0.95; P = 0.007). Ten percent more patients had a clinically meaningful improvement in HRQoL with denosumab relative to zoledronic acid, regardless of baseline pain levels. Conclusions: Denosumab was superior to zoledronic acid in reducing bone-related complications of metastatic breast cancer and maintained HRQoL, providing an efficacious, well-tolerated treatment option for patients with bone metastases from breast cancer. Clin Cancer Res; 18(17); 4841–9. ©2012 AACR.
A Review of Study Designs and Outcomes of Phase I Clinical Studies of Nanoparticle Agents Compared with Small-Molecule Anticancer Agents
Authors: Whitney P. Caron, Katherine P. Morgan, Beth A. Zamboni, William C. Zamboni
Journal: Clinical Cancer Research (2013)

Nanoparticles or carrier-mediated agents have been designed to prolong drug circulation time, increase tumor delivery, and improve therapeutic index compared to their small-molecule counterparts. The starting dose for phase I studies of small molecules and nanoparticles anticancer agents is based on the toxicity profile of the most sensitive species (e.g., rat or canine), but the optimal animal model for these studies of nanoparticles is unclear. The objective of this study was to evaluate the design, progression, and outcomes of phase I studies of nanoparticles compared with small-molecule anticancer agents.In preclinical studies, the maximum tolerated dose (MTD) in rats and dogs was evaluated for nanoparticles and their respective small molecules. In phase I clinical trials in patients with advanced solid tumors, the basis for starting dose, the number of dose escalations, number of patients enrolled, and the ratio of MTD to starting dose was determined for nanoparticles and small molecules.The mean ratio of MTD to starting dose in clinical phase I studies was significantly greater for nanoparticles (13.9 ± 10.8) compared with small molecules (2.1 ± 1.1; P = 0.005). The number of dose levels in a clinical phase I study was also significantly greater for nanoparticles (7.3 ± 2.9) compared with small molecules (4.1 ± 1.5; P = 0.008).The degree of dose escalation from starting dose to MTD was significantly greater for nanoparticles as compared with small-molecule anticancer drugs. These findings necessitate the need to identify the most appropriate preclinical animal model to use when evaluating nanoparticles toxicity.
Sleep {middle dot} 8: Paediatric obstructive sleep apnoea
Authors: G M Nixon
Journal: Thorax (2005)

In the past 25 years there has been increasing recognition of obstructive sleep apnoea (OSA) as a common condition of childhood. Morbidity includes impairment of growth, cardiovascular complications, learning impairment, and behavioural problems. Diagnosis and treatment of this condition in children differs in many respects from that in adults. We review here the key features of paediatric OSA, highlighting differences from adult OSA, and suggest future directions for research.
Tongue protrusion force and fatiguability in male and female subjects
Authors: I.L. Mortimore, P. Fiddes, S. Stephens, N.J. Douglas
Journal: European Respiratory Journal (1999)

Limb and respiratory muscle (diaphragm) strength and fatiguability have been extensively studied in man and are known to vary with age and sex. However, in contrast to limb muscles and the diaphragm, force and fatiguability characteristics have not been studied in upper airway muscles. This study examines the hypotheses that tongue protrusion strength or fatiguability, determined by the properties of the intrinsic muscles and genioglossus, may change with age and may be reduced in males compared to females. A force transducer was used to compare maximal tongue protrusion force (Fmax) and fatiguability in 81 males and 86 females matched for age (mean+/-SD, 43+/-19 yrs, 42+/-19 yrs, respectively). Fatiguability indices were based on the time that subjects could maintain 50% of Fmax. Fmax declined with age in both males (r=-0.57, p&lt;0.001) and females (r=-0.56, p&lt;0.001). Fmax in males was greater than in females (males 26+/-8 N; females 20+/-7 N; p&lt;0.001). However, after correction of Fmax for sex differences in total body muscle (fat-free mass) there was no significant difference between males and females (p=0.3). There was also no difference in fatiguability between males and females (p=0.5). In conclusion, tongue protrusion strength is greater in males compared to females, and decreases with age. If these differences also apply to patients with sleep apnoea, the reduction in maximal tongue protrusion force with age could be of relevance to the observed increase in prevalence and severity of sleep apnoea-hypopnoea syndrome in middle age, but would not explain the gender difference in prevalence.
The Butler Did It: Search for Killer(s) of Kaposi's Sarcoma Cells in Preparations of Human Chorionic Gonadotropin
Authors: Z. Darzynkiewicz
Journal: JNCI Journal of the National Cancer Institute (1999)

Since its original description more than a century ago, Kaposi’s sarcoma (KS) was considered to be a rare dermatologic condition, and it attracted only limited attention. The association with immune deficiency, first noticed in patients who had undergone renal transplantation, started to generate more interest in this disease. The turning point, however, was the finding of a relationship between KS and acquired immunodeficiency syndrome (AIDS). KS is now recognized as the most prominent tumor of patients with AIDS, particularly common (>30%) among homosexual men. It is not surprising, therefore, that the interest in its etiology, pathogenesis, and therapy is widespread. Unfortunately, the treatment options for KS are limited. Radiotherapy or chemotherapy as well as the administration of interferon alfa have little impact on the disease. Furthermore, these treatments are toxic, especially when used in combination with antiviral therapies. It is not surprising, therefore, that the finding that sera from pregnant women, as well as commercial preparations of human chorionic gonadotropin (hCG), exhibit in vitro and in vivo activity against KS (1,2) stirred wide interest and raised hope for more efficient treatment. Phase I clinical trials of hCG demonstrated that partial remissions and stabilization of the disease could be achieved in more than half of the patients, with no evidence of toxicity (3). In a study reported in this issue of the Journal, Samaniego et al. (4) show that hCG preparations affect the expression of the apoptosis-modulating proteins c-Myc and c-Rel and induce apoptosis in KS cells in vitro and in vivo. It is interesting that hCG preparations were also shown to induce apoptosis in leukemia cells, as detected in vivo in patients with acute myelogenous leukemia, and to suppress proliferation of HL-60 leukemia cells (5). Reduced expression of the anti-apoptotic protein Bcl-2 was also observed in hCG-treated leukemia cells (5). The mechanism of hCG’s anti-KS activity is clouded in mystery. Since highly purified or recombinant hCG is inactive, it is presumed that the activity is not associated with hCG itself but with one or more factors that are co-purified with the hormone. These anti-KS factors are present in the urine of pregnant women and mice and are found in different proportions in hCG preparations from different vendors (6‐8).
Blood Rheology: Effect of Fibrinogen Deduced by Addition
Authors: Edward W. Merrill, Edwin R. Gilliland, T. S. Lee, Edwin W. Salzman
Journal: Circulation Research (1966)

Viscometric measurements near zero shear stress were made on human blood and on suspensions of red cells in saline solutions of dialysed and nondialysed fibrinogen at 37°C at an hematocrit of 40. The principal viscometric parameter studied was the yield shear stress. The higher the value of yield stress, the greater is the viscosity defined as the ratio of shear stress to shear rate, in the region near zero flow, and the greater is the variation of viscosity with shear rate. The yield stress, zero in suspensions containing no fibrinogen, was found to increase with the fibrinogen concentration. At a given concentration of clottable fibrinogen (up to 1.20 g/100 ml) the yield shear stress was substantially greater in suspensions of red cells in their original plasma than in saline solutions of fractionated fibrinogen. Dialysis of the fractionated fibrinogen had no significant effect on the viscosity characteristics. For a given concentration of fibrinogen added to saline solutions, a higher yield stress was produced in the presence of A + cells than in the presence of O + cells.
Comprehensive disease control (CDC): what does achieving CDC mean for patients with rheumatoid arthritis?
Authors: Paul Emery, Arthur Kavanaugh, Yanjun Bao, Arijit Ganguli, Parvez Mulani
Journal: Annals of the Rheumatic Diseases (2014)

Background This study assessed the impact of simultaneous achievement of clinical, functional and structural efficacy, herein referred to as comprehensive disease control (CDC), on short-term and long-term work-related outcomes, health-related quality of life (HRQoL), pain and fatigue. Methods Data were pooled from three randomised trials of adalimumab plus methotrexate for treatment of early-stage or late-stage rheumatoid arthritis (RA). CDC was defined as 28-joint Disease Activity Score using C reactive protein &lt;2.6, Health Assessment Questionnaire &lt;0.5 and change from baseline in modified Total Sharp Score ≤0.5. Changes in scores at weeks 26 and 52 for work-related outcomes, Short Form 36 (SF-36) physical (PCS) and mental component scores (MCS), a Visual Analogue Scale measuring pain (VAS-Pain) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were compared between patient groups defined by achievement of CDC at week 26 using linear regression with adjustment for baseline scores. Results Patients with RA who achieved CDC at week 26 (n=200) had significantly greater improvements in VAS-Pain (46.9 vs 26.9; p&lt;0.0001), FACIT-F (13.3 vs 7.5; p&lt;0.0001), SF-36 PCS (19.7 vs 8.9; p&lt;0.0001) and SF-36 MCS (8.1 vs 5.0; p=0.0004) than those who did not (n=1267). Results were consistent at week 52 and among methotrexate-naive patients with early RA, methotrexate-experienced patients with late-stage RA and patients with inadequate response to methotrexate. Conclusions Patients with RA who achieved CDC at week 26 had improved short-term and long-term HRQoL, pain, fatigue and work-related outcomes compared with patients who do not. These results demonstrate that the joint achievement of all CDC components provides meaningful benefits to patients. Trial registration numbers DE019: NCT00195702 , PREMIER: NCT00195702 , OPTIMA: NCT00195702 .
Misunderstanding the Female Athlete Triad: Refuting the IOC Consensus Statement on Relative Energy Deficiency in Sport (RED-S)
Authors: Mary Jane De Souza, Nancy I Williams, Aurelia Nattiv, Elizabeth Joy, Madhusmita Misra, Anne B Loucks, Gordon Matheson, Marion P Olmsted, Michelle Barrack, Rebecca J Mallinson, Jenna C Gibbs, Marci Goolsby, Jeanne F Nichols, Barbara Drinkwater, Charlotte (Barney) Sanborn, Rosemary Agostini, Carol L Otis, Mimi D Johnson, Anne Zeni Hoch, Julia M K Alleyne, L Tyler Wadsworth, Karsten Koehler, Jaci VanHeest, Paula Harvey, Amanda K Weiss Kelly, Michael Fredericson, George A Brooks, Emma O'Donnell, Lisa R Callahan, Margot Putukian, Lauren Costello, Suzanne Hecht, Mitchell J Rauh, Jacalyn McComb
Journal: British Journal of Sports Medicine (2014)

<h3>Background</h3> Smoking contributes to socioeconomic inequalities in mortality, but the extent to which this contribution has changed over time and driven widening or narrowing inequalities in total mortality remains unknown. We studied socioeconomic inequalities in smoking-attributable mortality and their contribution to inequalities in total mortality in 1990–1994 and 2000–2004 in 14 European countries. <h3>Methods</h3> We collected, harmonised and standardised population-wide data on all-cause and lung-cancer mortality by age, gender, educational and occupational level in 14 European populations in 1990–1994 and 2000–2004. Smoking-attributable mortality was indirectly estimated using the Preston-Glei-Wilmoth method. <h3>Results</h3> In 2000–2004, smoking-attributable mortality was higher in lower socioeconomic groups in all countries among men, and in all countries except Spain, Italy and Slovenia, among women, and the contribution of smoking to socioeconomic inequalities in mortality varied between 19% and 55% among men, and between −1% and 56% among women. Since 1990–1994, absolute inequalities in smoking-attributable mortality and the contribution of smoking to inequalities in total mortality have decreased in most countries among men, but increased among women. <h3>Conclusions</h3> In many European countries, smoking has become less important as a determinant of socioeconomic inequalities in mortality among men, but not among women. Inequalities in smoking remain one of the most important entry points for reducing inequalities in mortality.
Audit of enteral and parenteral management in post-operative intestinal failure in a district general hospital
Authors: P. Robinson, D. Pearl, L. Vokes, J. Pratt, C. Stapely, T. Trebble
Journal: Gut (2011)

<h3>Introduction</h3> Managing prolonged post-operative intestinal failure is complex and resource intense. Frequently, fluid, electrolyte and nutritional needs necessitate in-patient IV support or, if metabolically stable, home parenteral nutrition. Enteral nutrition is more physiological and less expensive than IV feeding but requires close clinical and biochemical monitoring in patients with metabolic instability usually only possible during in-patient stay. In 2006, PHT Nutrition Support Team introduced a ‘virtual ward’ outpatient model to facilitate home discharge of metabolically unstable IF patients requiring nutritional support until planned revision surgery or on a long term basis. <h3>Methods</h3> Twenty consecutive patients were identified and audited using a database of referrals to the nutrition team, from January 2009 to July 2010 for post-operative complications requiring nutritional support (excluding post-operative ileus). Information was collected on patient demographics, aetiology and anatomy of bowel dysfunction, and methods of nutritional support. Outcomes included re-admission days and time to definitive surgery. <h3>Results</h3> The audited population were 11 females, 9 males, aged 27-75yrs, with an aetiology of intestinal infarction (5), IBD (3), malignancy (7) and other (5); and resulting in high end stoma (1), jejunostomy with accessible distal bowel (8) and enterocutaneous fistulae (2), 15 had had intra-abdominal sepsis. All had reduced proximal small bowel length (23-230cm; mean 129cm), metabolic instability with fluid/electrolyte depletion on oral intake (despite medical management), and high stoma or fistula output (&gt;2l/d). 13/20 patients were for planned definitive surgery (6 completed). Mean inpatient time to discharge was 57 days. 14 patients were managed successfully as outpatients using enteral support (nasogastric (NG) or mucous fistula) with salt supplementation. 3 patients declined NG tubes but were maintained on oral rehydration solution (&gt;= 1l/d) (one with continued electrolyte depletion). 3 patients required TPN (multiple enterocutaneous fistulae (1) and failed mucous fistula feeding (2)). During the audit period 18 patients were discharged home for a total of 2731 days (mean 151 days). Re-admission days were 47 (excluding admissions for revision surgery) (2.1% of total days post-discharge). There were no recorded cases of MRSA. <h3>Conclusion</h3> Our audit suggests that post-operative intestinal failure was commonly associated with short bowel due to high small bowel stomas or enterocutaneous fistulas. This could be commonly managed through enteral support. A small number were maintained on oral rehydration fluids or required TPN.