tbuckley/cabot-search huggingface dataset:
How to Keep Up with the Medical Literature: III. Expanding the Number of Journals You Read Regularly
Authors: R. BRIAN HAYNES
Journal: Annals of Internal Medicine (1986)

Clinicians can derive immense satisfaction from keeping abreast of new developments in patient care by regularly scanning the medical journal literature. Combined with good reading habits and self-discipline, this scanning generally can be accomplished within the time that most practitioners allot to attempting to keep up to date. We describe tactics for formulating a personalized journal-reading list and ensuring access to the key articles in one's field at a reasonable cost. These tactics begin with deleting low-yield journals from regular reading and adding journals more relevant to one's interests. The cost of multiple journal subscriptions can be reduced by circulating different journals among colleagues or by regular visits to the library. These tactics can be supplemented or replaced by using Current Contents or the Selective Dissemination of Information service of the National Library of Medicine and other database vendors.
The relationship between gut and adipose hormones, and reproduction
Authors: Alexander N. Comninos, Channa N. Jayasena, Waljit S. Dhillo
Journal: Human Reproduction Update (2013)

Reproductive function is tightly regulated by nutritional status. Indeed, it has been well described that undernutrition or obesity can lead to subfertility or infertility in humans. The common regulatory pathways which control energy homeostasis and reproductive function have, to date, been poorly understood due to limited studies or inconclusive data. However, gut hormones and adipose tissue hormones have recently emerged as potential regulators of both energy homeostasis and reproductive function. A PubMed search was performed using keywords related to gut and adipose hormones and associated with keywords related to reproduction. Currently available evidence that gut (ghrelin, obestatin, insulin, peptide YY, glucagon-like peptide-1, glucose-dependent insulinotropic peptide, oxyntomodulin, cholecystokinin) and adipose hormones (leptin, adiponectin, resistin, omentin, chemerin) interact with the reproductive axis is presented. The extent, site and direction of their effects on the reproductive axis are variable and also vary depending on species, sex and pubertal stage. Gut and adipose hormones interact with the reproductive axis as well as with each other. While leptin and insulin have stimulatory effects and ghrelin has inhibitory effects on hypothalamic GnRH secretion, there is increasing evidence for their roles in other sites of the reproductive axis as well as evidence for the roles of other gut and adipose hormones in the complex interplay between nutrition and reproduction. As our understanding improves, so will our ability to identify and design novel therapeutic options for reproductive disorders and accompanying metabolic disorders.
Gut-derived lipopolysaccharide augments adipose macrophage accumulation but is not essential for impaired glucose or insulin tolerance in mice
Authors: Robert Caesar, Christopher S Reigstad, Helene Kling Bäckhed, Christoph Reinhardt, Maria Ketonen, Gunnel Östergren Lundén, Patrice D Cani, Fredrik Bäckhed
Journal: Gut (2012)

<h3>Background</h3> Obesity is associated with accumulation of macrophages in white adipose tissue (WAT), which contribute to the development of insulin resistance. Germ-free (GF) mice have reduced adiposity and are protected against diet-induced obesity, <h3>Objective</h3> To investigate whether the gut microbiota and, specifically, gut-derived lipopolysaccharide (LPS) promote WAT inflammation and contribute to impaired glucose metabolism. <h3>Method</h3> Macrophage composition and expression of proinflammatory and anti-inflammatory markers were compared in WAT of GF, conventionally raised and <i>Escherichia coli</i>-monocolonised mice. Additionally, glucose and insulin tolerance in these mice was determined. <h3>Results</h3> The presence of a gut microbiota resulted in impaired glucose metabolism and increased macrophage accumulation and polarisation towards the proinflammatory M1 phenotype in WAT. Monocolonisation of GF mice for 4 weeks with <i>E.coli</i> W3110 or the isogenic strain MLK1067 (which expresses LPS with reduced immunogenicity) resulted in impaired glucose and insulin tolerance and promoted M1 polarisation of CD11b cells in WAT. However, colonisation with <i>E.coli</i> W3110 but not MLK1067 promoted macrophage accumulation and upregulation of proinflammatory and anti-inflammatory gene expression as well as JNK phosphorylation. <h3>Conclusion</h3> Gut microbiota induced LPS-dependent macrophage accumulation in WAT, whereas impairment of systemic glucose metabolism was not dependent on LPS. These results indicate that macrophage accumulation in WAT does not always correlate with impaired glucose metabolism.
Mucosal CXCR4<sup>+</sup>IgG plasma cells contribute to the pathogenesis of human ulcerative colitis through FcγR-mediated CD14 macrophage activation
Authors: Michihide Uo, Tadakazu Hisamatsu, Jun Miyoshi, Daiki Kaito, Kazuaki Yoneno, Mina T Kitazume, Maiko Mori, Akira Sugita, Kazutaka Koganei, Katsuyoshi Matsuoka, Takanori Kanai, Toshifumi Hibi
Journal: Gut (2012)

<h3>Background</h3> Chronic inflammation characterised by IgG-producing plasma cell infiltration of colonic mucosa is a histological hallmark of ulcerative colitis (UC); however, whether its function is pathogenic or protective remains unclear. <h3>Objective</h3> To explore the contribution of intestinal IgG plasma cells to UC pathogenesis. <h3>Methods</h3> We isolated lamina propria mononuclear cells (LPMCs) from intestinal mucosa of UC patients and analysed the characteristics of intestinal plasma cells (expression profiles of differentiation molecules and chemokine receptors). We investigated the involvement of IgG-immune complex (IC)-Fc gamma receptor (FcγR) signalling in intestinal inflammation by examining the cytokine production by LPMCs in response to IgG-IC stimulation. <h3>Results</h3> IgG plasma cells that were markedly increased in number in the inflamed mucosa of UC patients showed a distinct expression profile (CD19<sup>+</sup>CD27<sup>low</sup>, CCR10<sup>low</sup>CXCR4<sup>high</sup>) compared with IgA plasma cells (CD19<sup>+/−</sup>CD27<sup>high</sup>, CCR10<sup>high</sup>CXCR4<sup>−/low</sup>). In vitro IgG-IC stimulation activated intestinal CD14 macrophages that were increased in number in the inflamed mucosa of UC patients via FcγRI and FcγRII, and induced the extensive production of pro-inflammatory cytokines such as tumour necrosis factor (TNF) and interleukin-1β (IL-1β), comparable to the effect of commensal bacteria stimulation. Co-stimulation with IgG-IC and commensal bacteria increased TNF and IL-1β production more than stimulation with the latter alone. Furthermore, IgG-IC notably up-regulated the expression of TL1A, whereas commensal bacteria specifically induced IL-23. <h3>Conclusions</h3> Collectively, these results demonstrate a novel aspect of UC pathogenesis in which unique IgG plasma cells infiltrate the inflamed mucosa via CXCR4, and critically influence UC pathogenesis by exacerbating mucosal inflammation through the activation of 'pathogenic' intestinal CD14 macrophages via IgG-IC-FcγR signalling.
Adipose Tissue, Muscle, and Function: Potential Mediators of Associations Between Body Weight and Mortality in Older Adults With Type 2 Diabetes
Authors: Rachel A. Murphy, Ilse Reinders, Melissa E. Garcia, Gudny Eiriksdottir, Lenore J. Launer, Rafn Benediktsson, Vilmundur Gudnason, Palmi V. Jonsson, Tamara B. Harris
Journal: Diabetes Care (2014)

Studies in type 2 diabetes report both increased mortality for normal weight and no evidence of an obesity paradox. We aimed to examine whether adipose tissue, muscle size, and physical function, which are known to vary by weight, mediate associations between BMI and mortality.The AGES-Reykjavik cohort comprised participants aged 66-96 years with diabetes defined by fasting glucose, medications, or self-report. BMI was determined from measured height and weight and classified as normal (18.5-24.9 kg/m(2), n = 117), overweight (25.0-29.9 kg/m(2), n = 293, referent group) or obese (≥30.0 kg/m(2), n = 227). Thigh muscle area and intermuscular, visceral, and subcutaneous adipose tissues were assessed with computed tomography. Function was assessed from gait speed and knee extensor strength. Hazard ratios (HRs) and 95% CIs were estimated by Cox proportional hazards regression adjusted for demographics and diabetes-related risk factors.The median follow-up was 6.66 years, and there were 85, 59, and 44 deaths among normal weight, overweight, and obese participants, respectively. There was no mortality risk for obese participants and an increased risk among normal weight compared with overweight participants (HR 1.72 [95% CI 1.12-2.64]). Associations remained with adjustment for adipose tissues and knee extensor strength; however, mortality risk for normal weight was attenuated following adjustment for thigh muscle (HR 1.36 [95% CI 0.87-2.11]) and gait speed (HR 1.44 [95% CI 0.91-2.27]). Linear regression confirmed with bootstrapping indicated that thigh muscle size mediated 46% of the relationship between normal weight and mortality.Normal weight participants had elevated mortality risk compared with overweight participants. This paradoxical association was mediated in part by muscle size.
Relation of urinary cotinine concentrations to cigarette smoking and to exposure to other people's smoke.
Authors: S G Thompson, R Stone, K Nanchahal, N J Wald
Journal: Thorax (1990)

The relation of urinary cotinine measurements to tobacco consumption in smokers and to exposure to other people9s smoke in non-smokers was studied in 49 smokers and 184 reported non-smokers attending a health screening centre. The median urinary cotinine concentration was 1623 ng/ml in the smokers and 6.1 ng/ml in the non-smokers. In smokers the average urinary cotinine concentration increased with reported habitual cigarette consumption; in non-smokers it increased with the reported total seven day duration of exposure to other people9s tobacco smoke. Cotinine concentrations were approximately three times higher in non-smokers living with a spouse or partner who was a smoker than in those living with a non-smoker; their reported duration of exposure to tobacco smoke was also three times higher. Non-smoking subjects who were exposed to any tobacco smoke and who lived with a smoker reported 70% of their exposure to be at home (56% for men and 86% for women); the men reported more exposure at work than non-smoking men who lived with a non-smoker. This study confirms the relation of urinary cotinine to stated tobacco smoke exposure in both smokers and non-smokers and further validates the use of information on the smoking habits of the spouse or partner as a measure of tobacco smoke exposure in epidemiological studies of non-smokers.
THE BIOLOGICAL, IMMUNOLOGICAL, AND PHYSICOCHEMICAL CHARACTERIZATION OF A TRANSMISSIBLE AGENT CAPABLE OF INDUCING DNA AND THYMINE DEGRADATION IN CULTURED HUMAN CELLS
Authors: R. Shihman Chang, Maryellen Humes
Journal: The Journal of Experimental Medicine (1962)

EXPERIMENTS DESIGNED TO CHARACTERIZE AN UNIDENTIFIED TRANSMISSIBLE AGENT BROUGHT FORTH THE FOLLOWING FINDINGS: The cytopathology consisted of the formation of intranuclear globules, collapse of the involved nuclei, and the extrusion of nuclear materials. The relatively dormant primary human amnion cells were less susceptible than the rapidly growing cell lines. Similarly, the slowly multiplying ribose variants were less susceptible than their corresponding parent cell lines. Interferon-like activity was released from infected cells. Infectivity was readily demonstrated following storage at 0-4 degrees C for at least 8 months or at 37 degrees C for at least 2 weeks. Freeze-thawing, however, markedly reduced or completely destroyed its infectivity. Infectivity was destroyed completely by ether and chloroform; partially by desoxycholate, and not affected by trypsin, papain, RNAse, DNAse, hyaluronidase, lysozyme, lecithinase, or pancreatic lipase. The rate of inactivation by 0.025 per cent formalin was much slower than that of vaccinia and herpes viruses. Its synthesis was suppressed by 5-fluorodeoxyuridine. This suppression was not reversed by thymidine and/or uracil. Heat-stable neutralizing antibody could not be demonstrated in 379 human and animal serums, in human gamma globulins, or in serums from animals "immunized" with this agent. Heat-labile inhibitors (lipoprotein-like) capable of inhibiting the infectivity of this agent were demonstrated in 154 of the 157 serums tested. Experimental evidence indicated the non-identity of this ubiquitous inhibitor and the properdin system. The non-infectious complex between this agent and the ubiquitous serum inhibitor may be dissociated (hence, become infectious) by simple dilution. Repeated attempts to reisolate a similar agent have not been successful. We have hypothesized that this agent is a virus consisting of DNA wrapped in a surface coat rich in lipid, and suggest that this virus be referred to tentatively as a lipovirus.
Tumour necrosis factor superfamily cytokines and the pathogenesis of inflammatory osteolysis
Authors: J Lam, Y Abu-Amer, C A Nelson, D H Fremont, F P Ross, S L Teitelbaum
Journal: Annals of the Rheumatic Diseases (2002)

eriarticular osteolysis is a debilitating complication of inflammatory arthritis.While controversy exists as to whether pannus, itself, is capable of degrading bone, the osteoclast is clearly the principal, if not exclusive, bone resorptive cell in rheumatoid disease and other osteopenic disorders.Thus, the treatment of inflammatory osteolysis depends upon understanding the means by which the osteoclast resorbs bone, and the mechanisms that govern its differentiation from precursor cells.. . . . . . . .
The habenula is crucial for experience-dependent modification of fear responses in zebrafish
Authors: Masakazu Agetsuma, Hidenori Aizawa, Tazu Aoki, Ryoko Nakayama, Mikako Takahoko, Midori Goto, Takayuki Sassa, Ryunosuke Amo, Toshiyuki Shiraki, Koichi Kawakami, Toshihiko Hosoya, Shin-ichi Higashijima, Hitoshi Okamoto
Journal: Nature Neuroscience (2010)
Treatment Utilization by Patients With Personality Disorders
Authors: Donna S. Bender, Regina T. Dolan, Andrew E. Skodol, Charles A. Sanislow, Ingrid R. Dyck, Thomas H. McGlashan, M. Tracie Shea, Mary C. Zanarini, John M. Oldham, John G. Gunderson
Journal: American Journal of Psychiatry (2001)

Utilization of mental health treatment was compared in patients with personality disorders and patients with major depressive disorder without personality disorder. Semistructured interviews were used to assess diagnosis and treatment history of 664 patients in four representative personality disorder groups-schizotypal, borderline, avoidant, and obsessive-compulsive-and in a comparison group of patients with major depressive disorder. Patients with personality disorders had more extensive histories of psychiatric outpatient, inpatient, and psychopharmacologic treatment than patients with major depressive disorder. Compared to the depression group, patients with borderline personality disorder were significantly more likely to have received every type of psychosocial treatment except self-help groups, and patients with obsessive-compulsive personality disorder reported greater utilization of individual psychotherapy. Patients with borderline personality disorder were also more likely to have used antianxiety, antidepressant, and mood stabilizer medications, and those with borderline or schizotypal personality disorder had a greater likelihood of having received antipsychotic medications. Patients with borderline personality disorder had received greater amounts of treatment, except for family/couples therapy and self-help, than the depressed patients and patients with other personality disorders. These results underscore the importance of considering personality disorders in diagnosis and treatment of psychiatric patients. Borderline and schizotypal personality disorder are associated with extensive use of mental health resources, and other, less severe personality disorders may not be addressed sufficiently in treatment planning. More work is needed to determine whether patients with personality disorders are receiving adequate and appropriate mental health treatments.
Major Medical Outcomes With Spinal Augmentation vs Conservative Therapy
Authors: Brendan J. McCullough, Bryan A. Comstock, Richard A. Deyo, William Kreuter, Jeffrey G. Jarvik
Journal: JAMA Internal Medicine (2013)

The symptomatic benefits of spinal augmentation (vertebroplasty or kyphoplasty) for the treatment of osteoporotic vertebral compression fractures are controversial. Recent population-based studies using medical billing claims have reported significant reductions in mortality with spinal augmentation compared with conservative therapy, but in nonrandomized settings such as these, there is the potential for selection bias to influence results.To compare major medical outcomes following treatment of osteoporotic vertebral fractures with spinal augmentation or conservative therapy. Additionally, we evaluate the role of selection bias using preprocedure outcomes and propensity score analysis.Retrospective cohort analysis of Medicare claims for the 2002-2006 period. We compared 30-day and 1-year outcomes in patients with newly diagnosed vertebral fractures treated with spinal augmentation (n = 10,541) or conservative therapy (control group, n = 115,851). Outcomes were compared using traditional multivariate analyses adjusted for patient demographics and comorbid conditions. We also used propensity score matching to select 9017 pairs from the initial groups to compare the same outcomes.Spinal augmentation (vertebroplasty or kyphoplasty) or conservative therapy.Mortality, major complications, and health care utilization.Using traditional covariate adjustments, mortality was significantly lower in the augmented group than among controls (5.2% vs 6.7% at 1 year; hazard ratio, 0.83; 95% CI, 0.75-0.92). However, patients in the augmented group who had not yet undergone augmentation (preprocedure subgroup) had lower rates of medical complications 30 days post fracture than did controls (6.5% vs 9.5%; odds ratio, 0.66; 95% CI, 0.57-0.78), suggesting that the augmented group was less medically ill. After propensity score matching to better account for selection bias, 1-year mortality was not significantly different between the groups. Furthermore, 1-year major medical complications were also similar between the groups, and the augmented group had higher rates of health care utilization, including hospital and intensive care unit admissions and discharges to skilled nursing facilities.After accounting for selection bias, spinal augmentation did not improve mortality or major medical outcomes and was associated with greater health care utilization than conservative therapy. Our results also highlight how analyses of claims-based data that do not adequately account for unrecognized confounding can arrive at misleading conclusions.
<i>PIK3CA</i> Mutations Are Associated With Decreased Benefit to Neoadjuvant Human Epidermal Growth Factor Receptor 2–Targeted Therapies in Breast Cancer
Authors: Ian J. Majewski, Paolo Nuciforo, Lorenza Mittempergher, Astrid J. Bosma, Holger Eidtmann, Eileen Holmes, Christos Sotiriou, Debora Fumagalli, Jose Jimenez, Claudia Aura, Ludmila Prudkin, Maria Carmen Díaz-Delgado, Lorena de la Peña, Sherene Loi, Catherine Ellis, Nikolaus Schultz, Evandro de Azambuja, Nadia Harbeck, Martine Piccart-Gebhart, René Bernards, José Baselga
Journal: Journal of Clinical Oncology (2015)

We investigated whether mutations in the gene encoding the phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) correlates with response to neoadjuvant human epidermal growth factor receptor 2 (HER2) -targeted therapies in patients with breast cancer.Baseline tissue biopsies were available from patients with HER2-positive early breast cancer who were enrolled onto the Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial (NeoALTTO). Activating mutations in PIK3CA were identified using mass spectrometry-based genotyping.PIK3CA mutations were identified in 23% of HER2-positive breast tumors, and these mutations were associated with poorer outcome in all of the treatment arms. Patients treated with a combination of trastuzumab and lapatinib who had wild-type PIK3CA obtained a total pathologic complete response (pCR) rate of 53.1%, which decreased to 28.6% in patients with tumors that carried PIK3CA activating mutations (P = .012).Activating mutations in PIK3CA predicted poor pCR in patients with HER2-positive breast cancer treated with neoadjuvant therapies that target HER2. Consequently, the combination of anti-HER2 agents and PI3K inhibitors is being investigated.
New tests for tuberculosis: local immune responses have greater specificity
Authors: G. H Bothamley
Journal: Thorax (2007)

We all want a good test for tuberculosis. Sputum smears are negative in half of those with lung involvement.1 How can we detect tuberculosis if there are <105 bacilli per ml of sputum? We could use either a more sensitive test for something the tubercle bacillus produces or use the host’s response to amplify the signal. Mycobacterial culture, DNA-based amplification,2 breath tests for volatile organic chemicals3 and lipid profiles4 5 exhibit the first approach. Chest radiographs, non-specific inflammatory markers and tests based on the specific immune response (such as tuberculin testing) exploit the second option.

Local immune responses have previously been shown to have greater potential for diagnostic assays than systemic responses from peripheral blood.6 7 Studies using cells …
Differential expression of secretory granule proteases in mouse mast cells exposed to interleukin 3 and c-kit ligand.
Authors: M F Gurish, N Ghildyal, H P McNeil, K F Austen, S Gillis, R L Stevens
Journal: The Journal of Experimental Medicine (1992)

It is now established that the subclasses of mast cells (MC) that reside in mucosal and serosal environments can be distinguished from one another in terms of their expression of specific secretory granule-localized proteases and proteoglycans. Further, the hematopoietic- and connective tissue-derived cytokines that regulate expression of the genes that encode these constituents of the granule can now be identified using recently developed gene-specific probes and recombinant cytokines. When bone marrow-derived MC (BMMC) were developed with recombinant interleukin 3 (rIL-3) and maintained with this cytokine in the absence or presence of recombinant c-kit ligand (rKL), they remained safranin-, produced almost no 35S-labeled heparin proteoglycans, and contained greater levels of mouse MC protease (MMCP) -5 mRNA and mast cell carboxypeptidase A (MC-CPA) mRNA than MMCP-6 mRNA. They did not contain MMCP-4 or -2 mRNA, genes expressed late in the differentiation of progenitor cells into serosal and mucosal MCs, respectively. In contrast, BMMC developed with rKL alone or by sequential culture in medium containing rIL-3 followed by rKL expressed high levels of MMCP-4 and -6 mRNA, as well as the transcripts that encode MMCP-5 and MC-CPA. Although rKL-developed BMMC were safranin+ and produced substantial amounts of 35S-labeled heparin proteoglycans, they contained only minimal amounts of histamine and MC-CPA enzymatic activity relative to serosal MC. These are the first studies to characterize the transcriptional granule phenotype of a population of BMMC derived using any recombinant cytokine, to demonstrate a dissociation between histochemical staining and granule maturation, and to demonstrate antagonistic regulation of late expressed protease genes by a cytokine.