tbuckley/cabot-search huggingface dataset:
The generation of chromosomal deletions to provide extensive coverage and subdivision of the Drosophila melanogaster genome
Authors: R Kimberley Cook, Stacey J Christensen, Jennifer A Deal, Rachel A Coburn, Megan E Deal, Jill M Gresens, Thomas C Kaufman, Kevin R Cook
Journal: Genome biology (2012)

Chromosomal deletions are used extensively in Drosophila melanogaster genetics research. Deletion mapping is the primary method used for fine-scale gene localization. Effective and efficient deletion mapping requires both extensive genomic coverage and a high density of molecularly defined breakpoints across the genome.A large-scale resource development project at the Bloomington Drosophila Stock Center has improved the choice of deletions beyond that provided by previous projects. FLP-mediated recombination between FRT-bearing transposon insertions was used to generate deletions, because it is efficient and provides single-nucleotide resolution in planning deletion screens. The 793 deletions generated pushed coverage of the euchromatic genome to 98.4%. Gaps in coverage contain haplolethal and haplosterile genes, but the sizes of these gaps were minimized by flanking these genes as closely as possible with deletions. In improving coverage, a complete inventory of haplolethal and haplosterile genes was generated and extensive information on other haploinsufficient genes was compiled. To aid mapping experiments, a subset of deletions was organized into a Deficiency Kit to provide maximal coverage efficiently. To improve the resolution of deletion mapping, screens were planned to distribute deletion breakpoints evenly across the genome. The median chromosomal interval between breakpoints now contains only nine genes and 377 intervals contain only single genes.Drosophila melanogaster now has the most extensive genomic deletion coverage and breakpoint subdivision as well as the most comprehensive inventory of haploinsufficient genes of any multicellular organism. The improved selection of chromosomal deletion strains will be useful to nearly all Drosophila researchers.
Killing in vitro of Trypanosoma cruzi by macrophages from mice immunized with T. cruzi or BCG, and absence of cross-immunity on challege in vivo.
Authors: R Hoff
Journal: The Journal of Experimental Medicine (1975)

Peritoneal macrophages from T. cruzi-immune mice were resistant to infection in vitro with culture forms of the parasite. Macrophage resistance appeared in infected mice about 21 days postinfection when parasitemia was still rising. Resistance in vitro was nonspecific since macrophages from BCG-immune mice were resistant to T. cruzi, and since macrophages from T. cruzi-immune mice were resistant to infection in vitro with Listeria were not resistant to challenge with T. cruzi even when the parasites were opsonized.
Early Detection of Superficial Squamous Cell Carcinoma in the Head and Neck Region and Esophagus by Narrow Band Imaging: A Multicenter Randomized Controlled Trial
Authors: Manabu Muto, Keiko Minashi, Tomonori Yano, Yutaka Saito, Ichiro Oda, Satoru Nonaka, Tai Omori, Hitoshi Sugiura, Kenichi Goda, Mitsuru Kaise, Haruhiro Inoue, Hideki Ishikawa, Atsushi Ochiai, Tadakazu Shimoda, Hidenobu Watanabe, Hisao Tajiri, Daizo Saito
Journal: Journal of Clinical Oncology (2010)

Most of the esophageal squamous cell carcinomas (ESCCs) and cancers of the head and neck (H&N) region are diagnosed at later stages. To achieve better survival, early detection is necessary. We compared the real-time diagnostic yield of superficial cancer in these regions between conventional white light imaging (WLI) and narrow band imaging (NBI) in high-risk patients.In a multicenter, prospective, randomized controlled trial, 320 patients with ESCC were randomly assigned to primary WLI followed by NBI (n = 162) or primary NBI followed by WLI (n = 158) in a back-to-back fashion. The primary aim was to compare the real-time detection rates of superficial cancer in the H&N region and the esophagus between WLI and NBI. The secondary aim was to evaluate the diagnostic accuracy of these techniques.NBI detected superficial cancer more frequently than did WLI in both the H&N region and the esophagus (100% v 8%, P < .001; 97% v 55%, P < .001, respectively). The sensitivity of NBI for diagnosis of superficial cancer was 100% and 97.2% in the H&N region and the esophagus, respectively. The accuracy of NBI for diagnosis of superficial cancer was 86.7% and 88.9% in these regions, respectively. The sensitivity and accuracy were significantly higher using NBI than WLI in both regions (P < .001 and P = .02 for the H&N region; P < .001 for both measures for the esophagus, respectively).NBI could be the standard examination for the early detection of superficial cancer in the H&N region and the esophagus.
Prognostic and aetiological factors in chronic thromboembolic pulmonary hypertension
Authors: R. Condliffe, D. G. Kiely, J. S. R. Gibbs, P. A. Corris, A. J. Peacock, D. P. Jenkins, K. Goldsmith, J. G. Coghlan, J. Pepke-Zaba
Journal: European Respiratory Journal (2008)

Several prognostic variables have previously been identified in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Specific medical conditions have also been associated with the development and prognosis of CTEPH. Using a national registry, the current authors have assessed the prognostic value of a larger number of variables and have also attempted to validate the clinical importance of previously identified aetiological factors. Baseline information for all 469 CTEPH patients diagnosed in the UK pulmonary hypertension service between January 2001 and June 2006 was collected from hospital records. Although univariate analysis confirmed the prognostic importance of pulmonary resistance, in multivariate analysis gas transfer and exercise capacity predicted pulmonary endarterectomy perioperative mortality. Cardiac index and exercise capacity independently predicted outcome in patients with nonoperable disease. Previous splenectomy was noted in 6.7% of patients, being significantly more common in patients with nonoperable than operable disease (13.7 versus 3.6%). Medical risk factors were not found to predict mortality. In a large national cohort, predictors of outcome in patients with both operable and nonoperable chronic thromboembolic pulmonary hypertension have been identified. These may be useful in planning treatment. The aetiological importance of previously identified medical risk factors has been confirmed, although the current authors were unable to validate their prognostic strength.
A Placebo-Controlled Study of Fluoxetine in Continued Treatment of Bulimia Nervosa After Successful Acute Fluoxetine Treatment
Authors: Steven J. Romano, Katherine A. Halmi, Neena P. Sarkar, Stephanie C. Koke, Julia S. Lee
Journal: American Journal of Psychiatry (2002)

The efficacy of fluoxetine in the acute management of bulimia nervosa is well established; however, few controlled studies have examined whether continuation of pharmacotherapy provides protection from relapse. This study compared the efficacy and safety of treatment with fluoxetine versus placebo in preventing relapse of bulimia nervosa during a 52-week period after successful acute fluoxetine therapy.Patients who met DSM-IV criteria for bulimia nervosa, purging type, were assigned to single-blind treatment with 60 mg/day of fluoxetine. After 8 weeks of treatment, patients were considered responders if they experienced a decrease > or =50% from baseline in the frequency of vomiting episodes during 1 of the 2 preceding weeks. Responders were randomly assigned to receive 60 mg/day of fluoxetine or placebo and were monitored for relapse for up to 52 weeks. Patients met relapse criteria if they experienced a return to the baseline vomiting frequency that persisted for 2 consecutive weeks.Of the 232 patients who entered the acute phase, 150 patients (65%) met response criteria and were randomly assigned to receive fluoxetine (N=76) or placebo (N=74). Fluoxetine-treated patients exhibited a longer time to relapse than placebo-treated patients. Quantitative analysis of other efficacy measures, including frequency of vomiting episodes, frequency of binge eating episodes, Clinical Global Impression severity and improvement scores, the patient's global impression score, and Yale-Brown-Cornell Eating Disorder Scale score, indicated that the efficacy of fluoxetine treatment was statistically superior, compared to placebo. There were no clinically relevant differences in safety between groups. Attrition in this study was high, especially in the first 3 months after random assignment to treatment groups.Continued treatment with fluoxetine in patients with bulimia nervosa who responded to acute treatment with fluoxetine improved outcome and decreased the likelihood of relapse.
Idiotype profile of an immune response. II. Reversal of the relative dominance of major and minor cross-reactive idiotypes in arsonate-specific T-independent responses.
Authors: J D Conger, E Lamoyi, G K Lewis, A Nisonoff, J W Goodman
Journal: The Journal of Experimental Medicine (1983)

Two different cross-reactive idiotype (CRI) groups are distinguishable in the Ab response of A/J mice to the p-azobenzenearsonate (ABA) hapten: CRIA and CRIm. These two groups showed distinct patterns of relative dominance in the ensuing response depending on whether the inducing Ag was a T cell-dependent (TD) form of ABA, such as ABA-KLH or ABA-CGG, or a T-independent type 1 (TI-1) form, such as ABA-Brucella abortus or ABA-lipopolysaccharide (LPS), and on whether the response was elicited in vivo or in vitro. The CRI+ component of primary in vivo plaque-forming cell (PFC) responses to TD ABA Ags was largely (greater than 90%) CRIA+ as was, to a slightly lesser extent (greater than 75%) the CRI+ portion of secondary or hyperimmune serum Ab or PFC responses to the same Ags. In contrast, in vivo primary and hyperimmune PFC responses to ABA-Bru or ABA-LPS showed a significantly lower CRIA/CRI ratio, averaging 0.5-0.6, with some individual mice giving figures as low as 0.2, indicating predominance of CRIm over CRIA. Serological analysis of hyperimmune anti-ABA Abs from a group of 5 A/J mice immunized with ABA-Bru gave a figure of less than 0.5 for the CRIA/CRI ratio. The most striking disparity from the TD pattern was seen in primary in vitro PFC responses to the TI ABA Ags; here ratios of less than 0.2 were generally seen. Since T cell removal did not alter the Id pattern in the TI responses, CRIA-specific Ts cells do not account for the weak expression of CRIA in such responses. We propose a model that explains these results on the basis of differential expression of IdX dominance by two distinct B cell subpopulations--equatable to the Lyb-5+ and Lyb-5- B cell subsets--along with differential relative activation of these subsets in different types of responses. Examination of anti-ABA PFC responses of F1 progeny of CBA/N and A/J mice to ABA-Bru lends support to this hypothesis since CRIA expression was significantly lower in mice with the xid defect.
British Guideline on the Management of Asthma
Authors: Graham Douglas, Bernard Higgins, Neil Barnes, Anne Boyter, Sherwood Burge, Chris Cates, Gary Connett, Jon Couriel, Paul Cullinan, Sheila Edwards, Erica Evans, Monica Fletcher, Chris Griffiths, Liam Heaney, Michele Hilton Boon, Steve Holmes, Ruth McArthur, Cathy Nelson-Piercy, Martyn Partridge, James Paton, Ian Pavord, Elaine Carnegie, Hilary Pinnock, Safia Qureshi, Colin Robertson, Mike Shields, John Warner, John White
Journal: Thorax (2008)

<h3>Abstract</h3> <h3>Background</h3> Long Covid remains a relatively new phenomenon with emerging understanding. Estimated UK prevalence of Long Covid with three or more symptoms lasting for 12 weeks or more was 2.2% at the end of 2021. The population-based French SAPRIS-SERO cohort has novel information about the pattern of symptoms of Long Covid that has been obscured by controversy around the original paper. <h3>Methods</h3> Secondary analysis was used to describe and re-interpret the pattern of persistent symptoms by IgG seropositivity and self-reported Long Covid in the SAPRIS-SERO survey. Participants in the cross-sectional analysis were 26 823 individuals from the French population-based CONSTANCES cohort, included between 2012 and 2019, who took part in the nested SAPRIS and SAPRIS-SERO surveys. Between May and November 2020, the Euroimmun enzyme-linked immunosorbent assay was used to detect anti–SARS-CoV-2 antibodies. Surveyed online between December 2020 and January 2021, participants self-reported previous COVID-19 infection and physical symptoms during the previous four weeks that were new since March 2020, and had persisted for at least eight weeks. <h3>Results</h3> There was similarity of prevalence over the majority of symptoms in those self-reporting COVID-19 infection, regardless of blood test result. Persistent symptoms significantly associated with self-reported COVID-19 infection and common in both groups include respiratory tract symptoms and a group of symptoms that might be related to chronic fatigue, malaise or postural issues. Seropositivity for IgG antibodies did not predict symptoms independently of self-reported Long Covid, except for anosmia. <h3>Conclusions</h3> There may be three common sub-syndromes of Long Covid, one with persistent anosmia, another with other respiratory tract symptoms and a third, currently under researched, with symptoms relatable to chronic fatigue. Antibody tests are insufficient for case detection while Long Covid remains poorly understood. <h3>Key Messages</h3> IgG seropositivity is insufficient to identify potential cases of Long Covid Persistent anosmia is very strongly associated with IgG seropositivity and may define a subsyndrome of Long Covid Other potential subsyndromes are those with persistent respiratory symptoms and those with persistent symptoms relatable to fatigue, malaise or postural issues The Long Covid research effort should be rebalanced towards understanding the fatigue/tiredness subsyndrome.
Still's Disease: Juvenile Chronic Polyarthritis
Authors: M. E. Carter
Journal: Annals of the Rheumatic Diseases (1977)

Epidemiological studies into the rheumatic diseases started in the United Kingdom with the Glover reports to the Ministry of Health in the 1920s, showing that these disorders accounted for one-sixth of total industrial disability, a yearly expenditure of £2 000 000 in sickness benefits, and a loss of 21 million working days every year.
Glycosylation of a VH residue of a monoclonal antibody against alpha (1----6) dextran increases its affinity for antigen.
Authors: S C Wallick, E A Kabat, S L Morrison
Journal: The Journal of Experimental Medicine (1988)

We have observed that antidextran hybridomas with potential N-linked glycosylation sites in VH have higher affinity for polymeric dextran and for isomaltoheptaose than those lacking potential glycosylation sites. In these studies we have used gene transfection and expression techniques to verify that the carbohydrate addition sites in VH were used. The carbohydrate of the VH region was accessible for binding by the lectin Con A. By ELISA analysis it was demonstrated that the aKa of the antibody for dextran was influenced by the presence of carbohydrate in VH, with the aglycosylated antibody having an aKa 15-fold lower than its untreated counterpart. The aKa for antigen of antibodies that contain carbohydrate only in their constant region was unaffected by lack of carbohydrate. Thus, not only the amino acid sequence of the variable region but also its carbohydrate moieties can determine the magnitude of the antigen-antibody interaction.
Comparison of the Informed Consent Process for Randomized Clinical Trials in Pediatric and Adult Oncology
Authors: Christian M. Simon, Laura A. Siminoff, Eric D. Kodish, Christopher Burant
Journal: Journal of Clinical Oncology (2004)

To compare the informed consent processes for phase III pediatric and adult oncology clinical trials in view of the critical importance of human subjects protection in both pediatric and adult cancer care. Findings are discussed in terms of the opportunities for improving pediatric and adult oncology informed consent.A total of 219 subjects are reported on. Adult oncology patients made up 36.1% (n = 79) of the sample. Pediatric surrogates made up the remaining 63.9% (n = 140). Subjects in both studies were observed and audiotaped in conversation with their oncologists, and interviewed afterwards. Comparisons between the adult and pediatric subjects were done using chi(2) statistics and t tests.Differences between the pediatric and adult informed consent processes were found. Adult oncology decision makers were, on average, more fully informed and more actively engaged by their oncologists. Pediatric decision makers were, however, given more information about survival/cure, randomization, and voluntariness. Comprehension difficulties were more frequent among pediatric decision makers. Suggestions for improvement are made in view of the differences between adult and pediatric oncology research environments.Ongoing efforts to improve the ethical framework of clinical cancer research need to take into account the key differences between pediatric and adult oncology informed consent. More research needs to be done to explore the differences between adult and pediatric informed consent processes in oncology.
Reply: Palliative Care: A Core Competency for Intensive Care Unit Doctors
Authors: May Hua, Guohua Li, Craig Blinderman, Hannah Wunsch
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

We thank Dr. Lamas and colleagues for their comments related to our article on estimating palliative care needs in critically ill patients (1).We agree that integrative models of palliative care in intensive care units (ICUs) certainly deserve further study and attention.This method of delivering palliative care is essential not only because there is a shortage of fellowship-trained palliative care specialists to meet these needs but also as a matter of professional integrity for critical care providers to be able to have the competencies to treat pain and symptoms common in this population, facilitate goals-of-care conversations, and provide high-quality end-of-life care for patients who die in the ICU.An ongoing challenge is how to best allocate specialized palliative care.The role of specialized palliative care is likely to change depending on the practice setting.For example, in ICUs with an open staffing model, patients may not have a primary critical care provider who is concerned with the provision of adequate palliative care, and palliative care consultants may be needed to perform a needs assessment; in closed units with adequate training, palliative care consultation may be reserved for only the most challenging cases: difficult-to-manage symptoms, complex decision making, or conflict resolution.As with any other consultation service, the amount of specialist involvement that is required inherently depends on the services that can be provided by the primary team.Adequate delivery of palliative care to critically ill patients should be a high priority, and figuring out how to best meet these needs will require buy-in and cooperation from ICU clinicians, palliative care specialists, patients' primary physicians, and hospital administrators.It is imperative that we collaborate together, and, as Dr. Lamas and colleagues point out, study interventions, to create best practices and models that allow us to reach this common goal.
Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis
Authors: C H Seow, A Newman, S P Irwin, A H Steinhart, M S Silverberg, G R Greenberg
Journal: Gut (2009)

Antibodies to infliximab reduce serum infliximab with loss of clinical benefit, but undetectable trough serum concentrations of infliximab may occur without antibody formation. The relationship between trough serum infliximab and clinical outcomes was evaluated in acute ulcerative colitis.In a cohort of 115 patients with ulcerative colitis treated with three-dose induction followed by scheduled maintenance infliximab, rates of clinical remission, colectomy, antibodies to infliximab and trough serum infliximab were determined.Rates of remission were 32% at week 10 and 37% at week 54. Colectomy occurred in 40% of patients, at a median of 5.3 (IQR 1.9-12.1) months. Detectable trough serum infliximab was present in 39% of patients and, among patients with undetectable infliximab, 41% were antibody positive and 20% were antibody negative. For antibody-positive and antibody-negative patients, rates of remission (18% vs 14%), endoscopic improvement (25% vs 35%) and colectomy (52% vs 59%) were not different. A detectable serum infliximab was associated with higher rates of remission (69% vs 15%; p<0.001) and endoscopic improvement (76% vs 28%, p<0.001). An undetectable serum infliximab predicted an increased risk for colectomy (55% vs 7%, OR 9.3; 95% CI 2.9 to 29.9; p<0.001). Concurrent immunosuppression was not associated with clinical outcomes.For patients with ulcerative colitis treated with infliximab, a detectable trough serum infliximab predicts clinical remission, endoscopic improvement and a lower risk for colectomy. An undetectable trough serum infliximab, irrespective of antibody status, is associated with less favourable outcomes.
Bone marrow progenitors in inflammation and repair: new vistas in respiratory biology and pathophysiology
Authors: J. A. Denburg, S. F. van Eeden
Journal: European Respiratory Journal (2006)

### Bone marrow-derived stem cells

Respiratory and allergic/immune diseases such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, cystic fibrosis, and acute and chronic lung infections are leading causes of morbidity and mortality in Canada as well as globally. Inflammatory pathology is central to all of these diseases, recently recognised to include systemic processes involving the active recruitment and differentiation of bone marrow-derived haemopoietic and nonhaemopoietic “progenitors” (termed BMSC). These cells have the potential to differentiate into a diversity of cell types found in normal tissue 1–4, as well as to contribute to repair and remodelling following lung injury. Recently, it has been proposed that circulating BMSC can “sense” injured tissue, and undergo migration and recruitment to sites of tissue damage. Here they can differentiate into inflammatory effector cells (such as neutrophils, eosinophils, basophils, mast cells and monocytes), or nonhaemopoietic cells that can promote structural and functional tissue repair, revealing the plasticity of these pluripotent cell populations 5 and their participation in regenerative and/or inflammatory processes. Within tissues, the fate of haemopoietic progenitors is determined by locally elaborated growth factors that permit a process termed “ in situ haemopoiesis” 6–9. This leads to the accumulation of inflammatory effector cells, immunocompetent cells and tissue structural cells ( e.g. dendritic and endothelial cells).

### Markers of BMSC

A critically important marker of haemopoietic progenitors in the marrow, circulatory and tissue compartments 10–13 is the CD34 antigen. This is an integral membrane differentiation stage-speciﬁc glycoprotein that is expressed on the majority of immature haemopoietic cells 14, 15. It is also expressed on tissue structural cells, including fibroblasts and vascular endothelial cells 15, 16, functioning to regulate adhesion of these cells to haemopoietic inductive microenvironmental stroma and, presumably, to other elements in blood vessels and peripheral tissues 17. The CD34-knock …
BAP1tism of a Tumor Suppressor
Authors: Scott E. Woodman
Journal: Clinical Cancer Research (2011)

Driving cancer cells into a more differentiated state is a rational therapeutic approach. Primary uveal melanoma cells with a propensity to metastasize have less-differentiated features than their less aggressive counterparts. Treatment of uveal melanoma cells with histone deacetylase inhibitors induces a more differentiated phenotype with resultant lower growth capacity.