tbuckley/cabot-search huggingface dataset:
The type 1 interferon signature: facts, fads and fallacies
Authors: T. Haupl, R. Biesen, B. Smiljanovic, J. R. Grun, J. Weix, B. Stuhlmuller, P. M. Villiger, G.-R. Burmester, A. Radbruch, A. Grutzkau
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> The type 1 interferon signature (IFN1) has been reported in systemic lupus erythematosus (SLE) and subsequently in many other diseases. It is deduced from the expression of a group of genes known as downstream events after IFN1 stimulation. Involving certain toll-like receptors and being related especially to an antiviral immune response, interpretation of these findings is difficult, in particular if such signatures are reported in bacterial infections as well. Therefore, the authors aimed for a better interpretation by comparing qualities and quantities of the IFN1 signature after stimulation and in various diseases. <h3>Materials and methods</h3> Transcriptomes of chronic inflammatory diseases, infections and defined stimulation experiments with IFN1 and other cytokines, which were generated by the authors or retrieved from the Gene Expression Omnibus were systematically investigated using the BioRetis analysis platform for primary analysis and Genesis for comparative visualisation. <h3>Results</h3> A typical IFN1 signature was identified by screening for differentially expressed genes before and after IFN1 treatment in patients or in vitro stimulation of immune cells with IFN1 compared to other cytokines. The pattern of these genes was compared with the pattern in transcriptomes from patients with different rheumatic diseases including rheumatoid arthritis (RA), spondyloarthritis, SLE, Sjögren9s Syndrome, Myositis, Scleroderma and juvenile rheumatic diseases as well as with infectious diseases. Leading candidates related to IFN1 were IFIT3, IFI44L, IFI35, IFI44, MX1, MX2, OAS1, OAS2, OAS3 or SIGLEC1 already known from previous studies. These genes were characteristic for viral infections, SLE and other connective tissue diseases. Bacterial infections were positive only in few exceptions, suggesting co-infection with viruses. When observed in arthritic conditions, the diagnosis of RA was challenged. When comparing signatures induced in vitro, a much broader range of immune reactions was observed in early stages with substantial overlap between different cytokines. However, magnitude of change was still an indicator for specificity, suggesting that specific triggers and responses are always associated with additional more or less unspecific activation patterns. This may be a general rule to enable subsequently the development of a higher complexity of the immune response whenever necessary. <h3>Conclusions</h3> In summary, the IFN1 signature is certainly a prominent observation in the current literature. However, definitions for the IFN1 response have to be applied carefully in order to avoid misinterpretations by overestimation of minor or negligible amounts. Therefore, analysis should include comparisons with typical positive IFN1 signatures as reference and if possible with changes in other pathways relevant for differential diagnosis.
The Key to the Door: Medicaid's Role in Improving Health Care for Women and Children
Authors: Diane Rowland, Alina Salganicoff, Patricia Seliger Keenan
Journal: Annual Review of Public Health (1999)

▪ Abstract Medicaid is the nation's major public financing program for providing health insurance coverage and long-term care services to the poor. This article assesses Medicaid's contributions over the last three decades to improving the coverage, access to care, and health of low-income children and women. The article reviews Medicaid's impact on the low-income population covered by this program, demonstrating both the role insurance plays and its limitations as a strategy for improving the health of vulnerable populations. Medicaid has shown over the last three decades that it is an important lever to help open the door to better health care, and ultimately to improved health for America's poor women and children, by substantially expanding coverage of the low-income population and helping to reduce differentials in access to care between the poor and the privately insured. Gaps in coverage and limitations in access persist, but overall the program has resulted in better coverage, access, and health care for millions of poor children and their parents.
Reflection in the systemic arterial system: effects of aortic and carotid occlusion
Authors: G. C. V. D. BOS, N. WESTERHOF, G. ELZINGA, P. SIPKEMA
Journal: Cardiovascular Research (1976)

Experiments were performed in seven closed-chest anaesthetized male dogs to determine the role of pulse wave reflection in the pattern of flow and pressure in the ascending aorta. Ten days after implantation of an electromagnetic flow transducer around the ascending aorta a balloon catheter was placed in the descending aorta via the femoral arteries. At the same time a tip manometer was introduced into the ascending aorta. Aortic occlusions at three different sites caused pressure pulses with secondary systolic rises and flow pulses with biphasic deceleration. Secondary rises occurred 45 ± 9.0 ms after the initial pressure rise for high aortic occlusion; this time was 75±8.5ms for occlusion at the level of the diaphragm and 114± 16.5 ms for occlusion near the level of the renal arteries. These times approximate the times in which the pulse travels from the tip manometer to the inflated balloons and back. Forward and reflected pressure and flow waves were calculated from reflection coefficients. Aortic occlusion caused larger reflected waves and the recorded wave forms were caused by the summation of forward and backward waves, the latter contributing the secondary pressure rise and the increased flow deceleration. Occlusion of both carotid arteries showed no specific reflection site but reflected waves were larger. This increased reflection can probably be explained as the result of greater total reflection from distributed sites under increased peripheral resistance.
Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial
Authors: Tadatoshi Takayama, Teruaki Sekine, Masatoshi Makuuchi, Susumu Yamasaki, Tomoo Kosuge, Junji Yamamoto, Kazuaki Shimada, Michiie Sakamoto, Setsuo Hirohashi, Yasuo Ohashi, Tadao Kakizoe
Journal: The Lancet (2000)
Exhaustion of bacteria-specific CD4 T cells and microbial translocation in common variable immunodeficiency disorders
Authors: Matthieu Perreau, Selena Vigano, Florence Bellanger, Céline Pellaton, Guillaume Buss, Denis Comte, Thierry Roger, Christine Lacabaratz, Pierre-Alexandre Bart, Yves Levy, Giuseppe Pantaleo
Journal: The Journal of Experimental Medicine (2014)

In the present study, we have investigated the functional profile of CD4 T cells from patients with common variable immunodeficiency (CVID), including production of cytokines and proliferation in response to bacteria and virus-derived antigens. We show that the functional impairment of CD4 T cells, including the reduced capacity to proliferate and to produce IFN-γ and IL-2, was restricted to bacteria-specific and not virus-specific CD4 T cells. High levels of endotoxins were found in the plasma of patients with CVID, suggesting that CD4 T cell dysfunction might be caused by bacterial translocation. Of note, endotoxemia was associated with significantly higher expression of programmed death 1 (PD-1) on CD4 T cells. The blockade of the PD-1-PD-L1/2 axis in vitro restored CD4 T cell proliferation capacity, thus indicating that PD-1 signaling negatively regulates CD4 T cell functions. Finally, we showed that intravenous immunoglobulin G (IVIG) treatment significantly reduced endotoxemia and the percentage of PD-1(+) CD4 T cells, and restored bacteria-specific CD4 T cell cytokine production and proliferation. In conclusion, the present study demonstrates that the CD4 T cell exhaustion and functional impairment observed in CVID patients is associated with bacterial translocation and that IVIG treatment resolves bacterial translocation and restores CD4 T cell functions.
Does This Coughing Adolescent or Adult Patient Have Pertussis?
Authors: Paul B. Cornia
Journal: JAMA (2010)

<h3>Context</h3>Pertussis is often overlooked as a cause of chronic cough, especially in adolescents and adults. Several symptoms are classically thought to be suggestive of pertussis, but the diagnostic value of each of them is uncertain.<h3>Objective</h3>To systematically review the evidence regarding the diagnostic value of 3 classically described symptoms of pertussis: paroxysmal cough, posttussive emesis, and inspiratory whoop.<h3>Data Sources, Study Selection, and Data Extraction</h3>We searched MEDLINE (January 1966–April 2010), EMBASE (January 1969 to April 2010), and the bibliographies of pertinent articles to identify relevant English-language studies. Articles were selected that included children older than 5 years, adolescents, or adults and confirmed the diagnosis of pertussis among patients with cough illness (of any duration) with an a priori–defined accepted reference standard. Two authors independently extracted data from articles that met selection criteria and resolved any discrepancies by consensus.<h3>Data Synthesis</h3>Five prospective studies met inclusion criteria; 3 were used in the analysis. Presence of posttussive emesis (summary likelihood ratio [LR], 1.8; 95% confidence interval [CI], 1.4-2.2) or inspiratory whoop (summary LR, 1.9; 95% CI, 1.4-2.6) increases the likelihood of pertussis. Absence of paroxysmal cough (summary LR, 0.52; 95% CI, 0.27-1.0) or posttussive emesis (summary LR, 0.58; 95% CI, 0.44-0.77) reduced the likelihood. Absence of inspiratory whoop was less useful (summary LR, 0.78; 95% CI, 0.66-0.93). No studies evaluated combinations of findings.<h3>Conclusions</h3>In a nonoutbreak setting, data to determine the diagnostic usefulness of symptoms classically associated with pertussis are limited and of relatively weak quality. The presence or absence of posttussive emesis or inspiratory whoop modestly change the likelihood of pertussis; therefore, clinicians must use their overall clinical impression to decide about additional testing or empirical treatment.
Ritonavir-boosted darunavir combined with raltegravir or tenofovir–emtricitabine in antiretroviral-naive adults infected with HIV-1: 96 week results from the NEAT001/ANRS143 randomised non-inferiority trial
Authors: François Raffi, Abdel G Babiker, Laura Richert, Jean-Michel Molina, Elizabeth C George, Andrea Antinori, Jose R Arribas, Jesper Grarup, Fleur Hudson, Christine Schwimmer, Juliette Saillard, Cédrick Wallet, Per O Jansson, Clotilde Allavena, Remko Van Leeuwen, Jean-François Delfraissy, Stefano Vella, Geneviève Chêne, Anton Pozniak
Journal: The Lancet (2014)
Randomized, open-label, phase II trial of oral capecitabine (Xeloda®) vs. a reference arm of intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) as first-line therapy for advanced/metastatic breast cancer
Authors: J.A. O’Shaughnessy, J. Blum, V. Moiseyenko, S.E. Jones, D. Miles, D. Bell, R. Rosso, L. Mauriac, B. Osterwalder, H.-U. Burger, S. Laws
Journal: Annals of Oncology (2001)

Oral capecitabine was evaluated in terms of overall response rate, safety, and tolerability as first-line therapy in women aged > or = 55 years with advanced/metastatic breast cancer.Ninety-five patients were randomized (2:1) to either intermittent oral capecitabine 1,255 mg/m2 twice daily (two weeks' treatment followed by a one-week rest period) or intravenous CMF (cyclophosphamide. methotrexate, 5-fluorouracil [5-FU]) administered every three weeks.The overall response rate in the capecitabine group was 30% (95% confidence interval (95% CI): 19%-43%), including three complete responses (5%). The response rate observed in the CMF group was 16% (95% CI: 5%-33%), with no complete responses. Median time to disease progression was 4.1 months with capecitabine and 3.0 months with CME. Survival was similar in the two treatment groups (median 19.6 months with capecitabine. 17.2 months with CMF). The safety profiles were different for capecitabine and CMF. However, both regimens were generally well tolerated and treatment interruption and/or dose modification was effective in managing toxicities associated with capecitabine. Alopecia and myelosuppression were rare in patients receiving capecitabine while diarrhea and hand-foot syndrome were more common. Treatment interruption and/or individual dose adjustment of capecitabine was required in 34% of patients and was generally effective in managing adverse events. Treatment was stopped owing to toxicity in 16% of patients in the capecitabine arm. The incidence of deaths during or within 28 days of stopping study treatment was 8% and 6% in the capecitabine and CMF arms, respectively.An oral, twice-daily regimen of capecitabine is effective and well tolerated when used as first-line chemotherapy in older patients (> or = 55 years) with advanced/metastatic breast cancer, and is suitable for outpatient therapy.
Antiretroviral Therapy in Early HIV Infection
Authors: Bruce D. Walker, Martin S. Hirsch
Journal: New England Journal of Medicine (2013)

Antiretroviral therapy (ART) has transformed the course of human immunodeficiency virus (HIV) infection. More than two dozen HIV drugs are now available in resource-rich environments, and newer combination regimens have ever-increasing efficacy and decreasing toxicity. As a result, life expectancy and quality of life are close to normal for HIV-infected persons with access to these medications.1 As more is learned about the long-term adverse effects of persistent viremia and the benefits of ART, HIV treatment guidelines have recommended earlier and earlier initiation of therapy. In resource-rich environments, guidelines frequently recommend treatment for nearly all persons who receive a diagnosis of . . .
The kisspeptin-GnRH pathway in human reproductive health and disease
Authors: Karolina Skorupskaite, Jyothis T George, Richard A Anderson
Journal: Human Reproduction Update (2014)

The discovery of kisspeptin as key central regulator of GnRH secretion has led to a new level of understanding of the neuroendocrine regulation of human reproduction. The related discovery of the kisspeptin-neurokinin B-dynorphin (KNDy) pathway in the last decade has further strengthened our understanding of the modulation of GnRH secretion by endocrine, metabolic and environmental inputs. In this review, we summarize current understanding of the physiological roles of these novel neuropeptides, and discuss the clinical relevance of these discoveries and their potential translational applications. A systematic literature search was performed using PUBMED for all English language articles up to January 2014. In addition, the reference lists of all relevant original research articles and reviews were examined. This review focuses mainly on published human studies but also draws on relevant animal data. Kisspeptin is a principal regulator of the secretion of gonadotrophins, and through this key role it is critical for the onset of puberty, the regulation of sex steroid-mediated feedback and the control of adult fertility. Although there is some sexual dimorphism, both neuroanatomically and functionally, these functions are apparent in both men and women. Kisspeptin acts upstream of GnRH and, following paracrine stimulatory and inhibitory inputs from neurokinin B and dynorphin (KNDy neuropeptides), signals directly to GnRH neurones to control pulsatile GnRH release. When administered to humans in different isoforms, routes and doses, kisspeptin robustly stimulates LH secretion and LH pulse frequency. Manipulation of the KNDy system is currently the focus of translational research with the possibility of future clinical application to regulate LH pulsatility, increasing gonadal sex steroid secretion in reproductive disorders characterized by decreased LH pulsatility, including hypothalamic amenorrhoea and hypogonadotropic hypogonadism. Conversely there may be scope to reduce the activity of the KNDy system to reduce LH secretion where hypersecretion of LH adds to the phenotype, such as in polycystic ovary syndrome. Kisspeptin is a recently discovered neuromodulator that controls GnRH secretion mediating endocrine and metabolic inputs to the regulation of human reproduction. Manipulation of kisspeptin signalling has the potential for novel therapies in patients with pathologically low or high LH pulsatility.
Efficacy of Hepatitis B Immune Globulin for Prevention of Perinatal Transmission of the Hepatitis B Virus Carrier State: Final Report of a Randomized Double-Blind, Placebo-Controlled Trial
Authors: Palmer R. Beasley, Lu-Yu Hwang, Cladd E. Stevens, Chia-Chin Lin, Fon-Jou Hsieh, Kwei-Yu Wang, Tsu-Shen Sun, Wolf Szmuness
Journal: Hepatology (1983)

A randomized double-blind, placebo-controlled efficacy trial of hepatitis B immune globulin (HBIG) for prevention of the mother-to-infant transmitted HBsAg carrier state was conducted in Taiwan where the carrier rate in the general population is 15 to 20%. HBIG was given immediately after birth to infants of e antigen positive HBsAg carrier mothers, and all infants were followed for at least 15 months. Among 61 placebo recipients, the carrier rate was 92%; compared with 26% among 57 infants who received 0.5 ml HBIG at birth, 3 months, and 6 months, and 54% among 67 infants who received a single 1.0 ml dose of HBIG at birth only. Efficacy was 71 and 42%, respectively, for the two treatment schedules. The most common response of HBIG-treated infants was passive-active immunization which was 27% in the single-dose group and 61% in the three-dose group. Some of the infants who became carriers were probably infected as HBIG protection waned, and we expect that higher efficacy can be achieved by hepatitis B vaccine in conjunction with HBIG.
Effects of ambasilide, quinidine, flecainide and verapamil on ultra-rapid delayed rectifier potassium currents in canine atrial myocytes
Authors: Lixia Yue, Jian Lin Feng, Zhiguo Wang, Stanley Nattel
Journal: Cardiovascular Research (2000)

Objective: A dog atrial ultra-rapid delayed rectifier current (IKur.d) is involved in canine atrial repolarization and shares similarities with the human atrial ultra-rapid delayed rectifier (IKur). Almost no information is available about the actions of antiarrhythmic drugs on IKur.d. This study evaluated effects of ambasilide, quinidine, flecainide and verapamil on IKur.d in isolated canine atrial myocytes. Methods: Standard whole-cell patch clamp techniques were used to study the effects of multiple concentrations of each drug. Results: All drugs produced reversible concentration-, voltage- and time-dependent IKur.d inhibition. Significant effects of quinidine, flecainide and ambasilide were noted at atrial-effective antiarrhythmic concentrations in the dog. Upon the onset of a depolarizing pulse, block developed exponentially in relation to time, with the blocking rate-constant increasing with drug concentration, consistent with open-channel blockade and permitting the calculation of forward and reverse rate-constants. For all drugs, the 50% blocking concentration (EC50) showed significant voltage-dependence, decreasing at more positive potentials. The magnitude of voltage-dependent block was directly related to the degree of drug-induced shift in the voltage dependence of activation (r=0.97), pointing to open-channel block as a mechanism for voltage-dependent action. An additional component of voltage-dependence suggested that blocking sites were subjected to 17–21% of the transmembrane voltage field. Conclusions: Ambasilide, quinidine, flecainide and verapamil inhibit IKur.d, with preferential action on the open state. IKur.d inhibition may play a role in antiarrhythmic effects in canine atrial arrhythmia models. Comparisons between the effects of these drugs on IKur.d and previously studied effects on IKur suggest potential opportunities for investigating the molecular structural determinants of drug-blocking action on atrial-specific ultrarapid delayed rectifiers.
Attitudes and Long-term Adjustment of Patients Surviving Cardiac Arrest
Authors: M. Dobson, A. E. Tattersfield, M. W. Adler, M. W. McNicol
Journal: BMJ (1971)

Twenty patients surviving cardiac resuscitation following myocardial infarction were seen at least six months after the cardiac arrest. The patient and spouse were interviewed separately. Though they had not usually been informed by the medical staff, 16 of the 20 patients were aware that a cardiac arrest had occurred and had a good understanding of what this meant. Six patients remembered the start or end of the cardiac arrest and five specifically remembered external cardiac massage. Their feelings and their attitudes to the cardiac arrest are described.Initial anxiety was experienced by all the patients and their spouses, particularly after hospital discharge, but in the long term only five patients failed to make a reasonably satisfactory adjustment. Poor rehabilitation seemed to be mainly associated with persisting physical disability and personality factors and not with features associated with the cardiac arrest, such as the duration of external cardiac massage. The spouses often found it difficult to know exactly how to treat the patients after hospital discharge and most patients and spouses felt that more explanation and discussion with the medical staff would have helped to alleviate anxiety.
Tenascin is overexpressed in vitiligo lesional skin and inhibits melanocyte adhesion
Authors: I.C. LE POOLE, R.M.G.J. VAN DEN WIJNGAARD, W. WESTERHOF, P.K. DAS
Journal: British Journal of Dermatology (1997)

The aetiology of vitiligo remains obscure. In this study, the role of integrins in the observed inability of melanocytes to repopulate lesional skin was investigated. Antibodies directed to α2, α3, α5, αv, α6, β1 and β3 integrin subunits were used. Immunohistology revealed no marked differences in the overall levels of expression of integrins between control, non‐lesional, perilesional or lesional skin. Moreover, no differences were noted in the level of expression of integrins or the adhesive capacity between cultured control cells derived from three separate donors and vitiligo‐derived melanocytes from two donors. Rather, it was clearly observed that towards the lesion, vitiligo skin contains increasing amounts of tenascin in the basal membrane and papillary dermis in five patients employing T2H5 antihuman tenascin antibody. The anti‐adhesive effect observed in vitro for this extracellular matrix molecule using normal melanocytes may contribute to loss of pigment cells in vitiligo or to ineffective repopulation of the lesions.
Acute Respiratory Distress Syndrome: Physiology and New Management Strategies
Authors: Ann B. Weinacker, Laszlo T. Vaszar
Journal: Annual Review of Medicine (2001)

▪ Abstract The acute respiratory distress syndrome (ARDS) has been recognized for more than three decades as a cause of respiratory failure in patients with a variety of illnesses. Clinically, it is characterized by pulmonary edema, refractory hypoxemia, diffuse pulmonary infiltrates, and altered lung compliance. Pathologically, it is distinguished by infiltration of the lungs with inflammatory cells, interstitial and alveolar edema, hyaline membrane formation, and ultimately fibrosis. Although we have learned much about the pathophysiology of this inflammatory syndrome since its earliest descriptions, ARDS continues to claim the lives of 40%–70% of its victims. Many treatment strategies have been used to prevent or treat ARDS, but thus far the most encouraging strategy to prevent lung injury and improve survival is mechanical ventilation with low tidal volumes and high levels of positive end-expiratory pressure.