tbuckley/cabot-search huggingface dataset:
ACC/AHA/SCAI Practice Guidelines, February 21, 2006
Authors: Sidney C Smith, Ted E Feldman, John W Hirshfeld, Alice K Jacobs, Morton J Kern, Spencer B King, Douglass A Morrison, William W O'Neil, Hartzell V Schaff, Patrick L Whitlow, David O Williams, Elliott M Antman, Cynthia D Adams, Jeffrey L Anderson, David P Faxon, Valentin Fuster, Jonathan L Halperin, Loren F Hiratzka, Sharon Ann Hunt, Rick Nishimura, Joseph P Ornato, Richard L Page, Barbara Riegel
Journal: Circulation (2006)

Class I: Conditions for which there is evidence for and/or general agreement that a given procedure or treatment is beneficial, useful, and effective.Class II: Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment.Class IIa: Weight of evidence/opinion is in favor of usefulness/efficacy.Class IIb: Usefulness/efficacy is less well established by evidence/opinion.Class III: Conditions for which there is evidence and/or general agreement that a procedure/treatment is not useful/effective and in some cases may be harmful.In addition, the weight of evidence in support of the recommendation is listed as follows:• Level of Evidence A: Data derived from multiple random- ized clinical trials or meta-analyses.• Level of Evidence B: Data derived from a single random- ized trial or nonrandomized studies.• Level of Evidence C: Only consensus opinion of experts, case studies, or standard-of-care.A recommendation with level of evidence B or C does not imply that the recommendation is weak.Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials.Even though randomized trials e169
BLOOD CHOLESTEROL STUDIES IN MENTAL DISEASE II
Authors: Purcell G. Schube
Journal: American Journal of Psychiatry (1933)

1. A study of the blood cholesterol in schizophrenia is presented. 2. Many of the factors which might alter the blood cholesterol other than that induced by the mental disorder itself are investigated. 3. There is a definite tendency to a lowered blood cholesterol in schizophrenia as a group. 4. There are cases of schizophrenia in which the blood cholesterol is normal or increased, but the majority of cases show values below the lower limit of normal or in the lower limits of the normal range.
Does it matter what a hospital is “high volume” for? Specificity of hospital volume-outcome associations for surgical procedures: analysis of administrative data
Authors: David R Urbach, Nancy N Baxter
Journal: BMJ (2004)

To determine whether the improved outcome of a surgical procedure in high volume hospitals is specific to the volume of the same procedure.Analysis of secondary data in Ontario, Canada.Patients having an oesophagectomy, colorectal resection for cancer, pancreaticoduodenectomy, major lung resection for cancer, or repair of an unruptured abdominal aortic aneurysm between 1994 and 1999.Odds ratio for death within 30 days of surgery in relation to the hospital volume of the same surgical procedure and the hospital volume of the other four procedures. Estimates were adjusted for age, sex, and comorbidity and accounted for hospital level clustering.With the exception of colorectal resection, 30 day mortality seemed to be inversely related not only to the hospital volume of the same procedure but also to the hospital volume of most of the other procedures. In some cases the effect of the volume of a different procedure was stronger than the effect of the volume of the same procedure. For example, the association of mortality from pancreaticoduodenectomy with hospital volume of lung resection (odds ratio for death in hospitals with a high volume of lung resection compared with low volume 0.36, 95% confidence interval 0.23 to 0.57) was much stronger than the association of mortality from pancreaticoduodenectomy with hospital volume of pancreaticoduodenectomy (0.76, 0.44 to 1.32).The inverse association between high volume of procedure and risk of operative death is not specific to the volume of the procedure being studied.
Beneficial Effect of Maintaining Hepatic Reserve during Chemotherapy on the Outcomes of Patients with Hepatocellular Carcinoma
Authors: Takeshi Terashima, Tatsuya Yamashita, Kuniaki Arai, Kazunori Kawaguchi, Kazuya Kitamura, Taro Yamashita, Yoshio Sakai, Eishiro Mizukoshi, Masao Honda, Shuichi Kaneko
Journal: Liver Cancer (2017)

Hepatocellular carcinoma (HCC) usually develops in chronically damaged liver. We investigated hepatic reserves during chemotherapy of patients with advanced HCC and compensated liver function to evaluate the effect on patients' outcomes of maintaining hepatic reserve after chemotherapy. We retrospectively reviewed the medical records of 190 patients with Child-Pugh A with advanced HCC who were treated with sorafenib or hepatic arterial infusion chemotherapy (HAIC). We investigated the Child-Pugh score and albumin-bilirubin grade for hepatic reserve, and evaluated the effect of the change in Child-Pugh scores on patients' outcomes. Subjects were treated with sorafenib (&lt;i&gt;n&lt;/i&gt; = 59) or HAIC (&lt;i&gt;n&lt;/i&gt; = 131). Of patients with Child-Pugh data, 66.7% maintained or improved their Child-Pugh score after 4 weeks. Treatment with HAIC was the only factor that significantly contributed to maintaining Child-Pugh scores after 4 weeks. The overall survival of patients with a higher Child-Pugh score after 4 weeks was shorter than that of patients whose Child-Pugh classification was unchanged. Multivariate analysis demonstrated that an increased Child-Pugh score after 4 weeks was one of the independent unfavorable prognostic factors. The change of hepatic reserve as a function of albumin-bilirubin grade did not significantly correlate with patients' outcomes. Maintaining the Child-Pugh score during chemotherapy benefits the outcomes of patients with advanced HCC, even those with sufficient hepatic reserve.
Ability of a Genomic Classifier to Predict Metastasis and Prostate Cancer-specific Mortality after Radiation or Surgery based on Needle Biopsy Specimens
Authors: Paul L. Nguyen, Zaid Haddad, Ashley E. Ross, Neil E. Martin, Samineh Deheshi, Lucia L.C. Lam, Jijumon Chelliserry, Jeffrey J. Tosoian, Tamara L. Lotan, Daniel E. Spratt, Radka S. Stoyanova, Sanoj Punnen, Kaye Ong, Christine Buerki, Maria Aranes, Tyler Kolisnik, Jennifer Margrave, Kasra Yousefi, Voleak Choeurng, Elai Davicioni, Bruce J. Trock, Christopher J. Kane, Alan Pollack, John W. Davis, Felix Y. Feng, Eric A. Klein
Journal: European Urology (2017)

Decipher is a validated genomic classifier developed to determine the biological potential for metastasis after radical prostatectomy (RP).To evaluate the ability of biopsy Decipher to predict metastasis and Prostate cancer-specific mortality (PCSM) in primarily intermediate- to high-risk patients treated with RP or radiation therapy (RT).Two hundred and thirty-five patients treated with either RP (n=105) or RT±androgen deprivation therapy (n=130) with available genomic expression profiles generated from diagnostic biopsy specimens from seven tertiary referral centers. The highest-grade core was sampled and Decipher was calculated based on a locked random forest model.Metastasis and PCSM were the primary and secondary outcomes of the study, respectively. Cox analysis and c-index were used to evaluate the performance of Decipher.With a median follow-up of 6 yr among censored patients, 34 patients developed metastases and 11 died of prostate cancer. On multivariable analysis, biopsy Decipher remained a significant predictor of metastasis (hazard ratio: 1.37 per 10% increase in score, 95% confidence interval [CI]: 1.06-1.78, p=0.018) after adjusting for clinical variables. For predicting metastasis 5-yr post-biopsy, Cancer of the Prostate Risk Assessment score had a c-index of 0.60 (95% CI: 0.50-0.69), while Cancer of the Prostate Risk Assessment plus biopsy Decipher had a c-index of 0.71 (95% CI: 0.60-0.82). National Comprehensive Cancer Network risk group had a c-index of 0.66 (95% CI: 0.53-0.77), while National Comprehensive Cancer Network plus biopsy Decipher had a c-index of 0.74 (95% CI: 0.66-0.82). Biopsy Decipher was a significant predictor of PCSM (hazard ratio: 1.57 per 10% increase in score, 95% CI: 1.03-2.48, p=0.037), with a 5-yr PCSM rate of 0%, 0%, and 9.4% for Decipher low, intermediate, and high, respectively.Biopsy Decipher predicted metastasis and PCSM from diagnostic biopsy specimens of primarily intermediate- and high-risk men treated with first-line RT or RP.Biopsy Decipher predicted metastasis and prostate cancer-specific mortality risk from diagnostic biopsy specimens.
Association of Increased F4/80<sup>high</sup> Macrophages With Suppression of Serum‐Transfer Arthritis in Mice With Reduced FLIP in Myeloid Cells
Authors: Qi‐Quan Huang, Robert Birkett, Renee E. Doyle, G. Kenneth Haines, Harris Perlman, Bo Shi, Philip Homan, Lianping Xing, Richard M. Pope
Journal: Arthritis & Rheumatology (2017)

Macrophages are critical in the pathogenesis of rheumatoid arthritis (RA). We recently demonstrated that FLIP is necessary for the differentiation and/or survival of macrophages. We also showed that FLIP is highly expressed in RA synovial macrophages. This study was undertaken to determine if a reduction in FLIP in mouse macrophages reduces synovial tissue macrophages and ameliorates serum-transfer arthritis.Mice with Flip deleted in myeloid cells (Flipf/f LysMc/+ mice) and littermate controls were used. Arthritis was induced by intraperitoneal injection of K/BxN serum. Disease severity was evaluated by clinical score and change in ankle thickness, and joints were examined by histology and immunohistochemistry. Cells were isolated from the ankles and bone marrow of the mice and examined by flow cytometry, real-time quantitative reverse transcriptase-polymerase chain reaction, or Western blotting.In contrast to expectations, Flipf/f LysMc/+ mice developed more severe arthritis early in the clinical course, but peak arthritis was attenuated and the resolution phase more complete than in control mice. Prior to the induction of serum-transfer arthritis, the number of tissue-resident macrophages was reduced. On day 9 after arthritis induction, the number of F4/80high macrophages in the joints of the Flipf/f LysMc/+ mice was not decreased, but increased. FLIP was reduced in the F4/80high macrophages in the ankles of the Flipf/f LysMc/+ mice, while F4/80high macrophages expressed an antiinflammatory phenotype in both the Flipf/f LysMc/+ and control mice.Our observations suggest that reducing FLIP in macrophages by increasing the number of antiinflammatory macrophages may be an effective therapeutic approach to suppress inflammation, depending on the disease stage.
Assessing the validity of genetic association studies.
Authors: A E Hegab, T Sakamoto, K Sekizawa
Journal: Thorax (2005)

We read with interest your approved guidance on the key issues which should be considered in preparing a genetic association study to be acceptable for publication in Thorax .1,2 While we agree with several points in this guidance, other points we consider to be exaggerated or, at best, controversial. We note that, in the eight genetic association studies published in Thorax since 2004, some of them do not conform to this guidance with regard to population size, number of polymorphisms studied, and their functionality. This is seen clearly in the latest published association study by Yarden and colleagues3 who examined four polymorphisms in the TNFα gene in patients with cystic fibrosis. Three of the studied polymorphisms were without functional information; no assessment of linkage disequilibrium, haplotype analysis or correction for multiple comparisons had been performed; and the population size—even after pooling the two different ethnic groups—showed that the study was underpowered.

With regard to the population size required in your guidance, the numbers in table 1 are too high (regardless of the typing error that caused the cases required for minor allele frequencies of 0.2 and 0.4 to be reversed). The reason for this is the unusual use of 90% power instead of the widely applied 80%. In fact, 80% power is the default for the online genetic power calculator you yourself provided in your editorial. Using this default of 80%, much smaller numbers of cases could be obtained and considered as having enough power. For example, with the relative risk set at 2, only 130 or 170 cases are required when the “minor allele frequency” is 0.4 and 0.2, respectively. We therefore think …
Surgery of the Hand
Authors: Robert A. Chase
Journal: New England Journal of Medicine (1972)

Vascular Trauma110 Conservative treatment of arterial injuries advocated in the past can no longer be justified.111 When the injury is associated with sensory or motor loss, pallor or coolness, lack of pulses, the extremity must be considered for exploration with arteriography in the operating room as indicated. Some authorities recommend exploration of any wound near vascular bundles.Technical failure of vascular reconstruction in the past has been attributed to inadequate arterial debridement and attempts to repair arteries under tension rather than to interpose a vein graft. Venous reconstruction, thrombectomy and fasciotomy done at the time of arterial repair may aid . . .
STUDIES ON MENINGOCOCCUS INFECTION
Authors: H. E. Alexander, Geoffrey Rake
Journal: The Journal of Experimental Medicine (1937)

Precipitin tests have been carried out on spinal fluid from cases of meningococcal and other forms of meningitis, with monovalent anti-meningococcus horse serum of high titer. Using such a test it has been possible within 2 hours to diagnose and type cases of Type I and Type II meningococcal meningitis. In a certain number of cases fluids which were negative when first drawn became positive after standing for 1 or 2 days at 37 degrees C. or room temperature. In 9.5 per cent of all Type I cases the fluids did not become positive. Fluids from cases due to atypical meningococci may react with the type serum of the group to which they belong (i.e., Types II* and VII, which belong to group II, with Type II serum) but do not in every case. Fluids from forms of meningitis other than meningococcal give no reaction. The use of concentrated sera is not advantageous at present, owing to the heterologous reactions which occur.
Monoclonal antibody against the common beta subunit (beta c) of the human interleukin-3 (IL-3), IL-5, and granulocyte-macrophage colony- stimulating factor receptors shows upregulation of beta c by IL-1 and tumor necrosis factor-alpha
Authors: Y Watanabe, T Kitamura, K Hayashida, A Miyajima
Journal: Blood (1992)
Changes in the Bronchial Epithelium in Relation to Smoking and Cancer of the Lung
Authors: Oscar Auerbach, J. Brewster Gere, Jerome B. Forman, Thomas G. Petrick, Harold J. Smolin, Gerald E. Muehsam, Dicran Y. Kassouny, Arthur Purdy Stout
Journal: New England Journal of Medicine (1957)

MANY investigators have reported an association between the occurrence of lung cancer and exposure to certain dusts and vapors such as uranium and chromate dusts, general air pollution and cigarette smoke.1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 When inhaled, presumably, these substances are widely distributed over the inner surface of the tracheobronchial tree.When a carcinogenic agent is applied to the tissue, a number of changes such as hyperplasia and metaplasia usually precede the appearance of cancer, and neoplastic changes are apt to occur at several different points. Therefore, if inhalants of one sort or another are a major factor in the causation of lung cancer, . . .
Correlation of prognosis with the gradually increased Golgi protein 73 expression in the progression of benign liver diseases to precancerous lesions and hepatocellular carcinoma.
Authors: Yijun Wang, Shigang Shan, Yingtang Gao, Qin Zhang, Fengmei Wang, Xiang Jing, Zhi Du
Journal: Journal of Clinical Oncology (2013)

e15050 Background: Serum golgi protein73 (sGP73) is a novel biomarker for hepatocellular carcinoma (HCC). However, there are few reports on the pattern of GP73 expression in the progression of benign liver diseases to precancerous lesions and HCC. This study aimed to investigate GP73 expression and it correlation with clinicopathologic parameters. Methods: Tissue GP73 (tGP73) levels were detected in specimens of group A (n=186) including HCC (n=62), peritumoral tissue (PTL) (n=43), high/low-grade hepatic atypical hyperplasia (AH) (n=32/2), chronic hepatitis B (CHB) (n=42) and normal controls (NC) (n=5) by immunohistochemistry, and GP73 expression in group B (n=159) and group C (n=16) were detected by RT-PCR and Western blot respectively. sGP73 levels were detected in subjects of group D (n=287) by ELISA. Results: GP73 expression increased gradually from NC, CHB, PTL to high-grade AH and HCC at both protein and mRNA levels (P&lt;0.05), while sGP73 in HCC group was lower than in liver cirrhosis (LC) group (P&lt;0.001). Both tGP73 and sGP73 levels were negatively associated with tumor size and TNM stage, and tGP73 levels were positively associated with tumor differentiation. The high-tGP73 group showed significantly better overall and disease-free survival than low-tGP73 group (P=0.008, P=0.018). Multivariate analysis revealed that the tGP73 level was an independent prognostic factor for HCC, but not sGP73. Conclusions: GP73 increases gradually in the progression ofbenign liver diseases to precancerous lesions and HCC. This expression pattern suggests the regulatory mechanism of GP73 is related to the progression of chronic liver diseases. Furthermore, a high level of tGP73 is a favorable prognostic factor for HCC.
Combined Impact of Smoking and Early-Life Exposures on Adult Lung Function Trajectories
Authors: James P. Allinson, Rebecca Hardy, Gavin C. Donaldson, Seif O. Shaheen, Diana Kuh, Jadwiga A. Wedzicha
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Both adverse early-life exposures and adult smoking can negatively influence adult lung function trajectory, but few studies consider how the impact of early-life exposures may be modified by subsequent smoking.The Medical Research Council National Survey of Health and Development is a nationally representative cohort, initially of 5,362 individuals, followed since enrollment at birth in March 1946. Using data collected prospectively across life and multilevel modeling, we investigated how the relationships between early-life exposures (infant lower respiratory infection, manual social class, home overcrowding, and pollution exposure) and FEV1 and FVC trajectories between ages 43 and 60-64 years were influenced by smoking behavior.Among 2,172 individuals, there were synergistic interactions of smoking with infant respiratory infection (P = 0.04) and early-life home overcrowding (P = 0.009), for FEV1 at 43 years. Within smoker-stratified models, there were FEV1 deficits among ever-smokers associated with infant lower respiratory infection (-108.2 ml; P = 0.001) and home overcrowding (-89.2 ml; P = 0.002), which were not evident among never-smokers (-15.9 ml; P = 0.69 and -13.7 ml; P = 0.70, respectively). FVC modeling, including 1,960 individuals, yielded similar results. FEV1 decline was greater in smokers (P < 0.001), but there was no effect of any early-life exposure on FEV1 decline. Neither smoking nor early-life exposures were associated with FVC decline.Besides accelerating adult FEV1 decline, cigarette smoking also modifies how early-life exposures impact on both midlife FEV1 and FVC. These findings are consistent with smoking impairing pulmonary development during adolescence or early adulthood, thereby preventing catch-up from earlier acquired deficits.
The chimeric monoclonal antibody MHCSZ-123 against human von Willebrand factor A3 domain inhibits high-shear arterial thrombosis in a Rhesus monkey model
Authors: Shundong Ji, Miao Jiang, Bin Yan, Fei Shen, Yang He, Aini Wan, Lijun Xia, Changgeng Ruan, Yiming Zhao
Journal: Journal of Hematology & Oncology (2017)

SZ-123, a murine monoclonal antibody that targets the human von Willebrand factor (VWF) A3 domain and blocks the binding of collagen, is a powerful antithrombotic. In a Rhesus monkey model of thrombosis, SZ-123 had no side effects, such as bleeding or thrombocytopenia. The mouse/human chimeric version of SZ-123, MHCSZ-123, was developed and maintained inhibitory capacities in vitro and ex vivo after injection into monkeys. CHO-S cells were selected for stable expression of MHCSZ-123. Cell clones with high levels of MHCSZ-123 expression were screened with G418 then adapted to serum-free suspension culture. The antithrombotic effect of MHCSZ-123 on acute platelet-mediated thrombosis was studied in monkeys where thrombus formation was induced by injury and stenosis of the femoral artery, which allowed for cyclic flow reductions (CFRs). CFRs were measured in the femoral artery of anesthetized Rhesus monkeys before and after intravenous administration of MHCSZ-123. Ex vivo VWF binding to collagen, platelet aggregation, platelet counts, and template bleeding time were used as measurements of antithrombotic activity. In addition, plasma VWF and VWF occupancy were measured by ELISA. Injection of 0.1, 0.3, and 0.6 mg/kg MHCSZ-123 significantly reduced CFRs by 29.4%, 57.9%, and 73.1%, respectively. When 0.3 and 0.6 mg/kg MHCSZ-123 were administered, 46.6%–65.8% inhibition of ristocetin-induced platelet aggregation was observed between 15 and 30 min after injection. We observed minimal effects on bleeding time, minimal blood loss, and no spontaneous bleeding or thrombocytopenia. The VWF-A3 inhibitor MHCSZ-123 significantly reduced thrombosis in Rhesus monkeys and appeared to be safe and well tolerated.
Do cancer patients present with subclinical peripheral neuropathy prior to initiating neurotoxic chemotherapy?
Authors: Sabrina Ramnarine, Linda J Williams, Marie T Fallon
Journal: Journal of Clinical Oncology (2015)

9631 Background: Chemotherapy-induced peripheral neuropathy (CIPN), is a common dose-limiting toxicity which may compromise patient survival, leaving many with chronic pain, disability and a negative impact on quality of life. The natural history and underlying pathophysiological mechanisms are unclear. Clinical management is challenging, therefore, early identification and prediction of patients who will develop CIPN is critical. Using a translational approach, this study aims to investigate and characterise the presence of subclinical peripheral neuropathy in gynaecological, colorectal and lung cancer patients. Methods: Quantitative Sensory Testing (QST) was conducted on 21 patients with the above cancers prior to starting neurotoxic chemotherapy and compared with 21 age and gender matched healthy controls, to characterise somatosensory profile. Skin temperature, thresholds for thermal, mechanical and sharpness detection along with sensorimotor function (grooved pegboard test) were assessed. Resting heart rate was measured as a marker of autonomic function. Results: Heart rate differed significantly between the two groups (healthy, mean 72.3 vs 87.9 in patients; p < 0.0001). Detection of painful thermal thresholds (lower limb) were also significantly different in the healthy group compared to patients (hot: 47.4°C vs 45.4°C; p = 0.005: cold: 9.7°C vs 16.2°C; p = 0.04) with evidence of variance in the upper limb for hot (42.0°C vs 39.4°C; p = 0.03). Although not statistically significant, large differences existed between the groups in the pegboard test: dominant hand 75.6secs vs 83.2secs (p = 0.15), non-dominant hand, 79.0secs vs 88.4secs (p = 0.06). Conclusions: This cohort of patients exhibited signs suggestive of subclinical autonomic and sensory nerve dysfunction prior to initiating chemotherapy manifested as: increased resting heart rate, hot and cold hyperalgesia and evidence of some sensorimotor impairment. This indicates a cancer-mediated process potentially contributing to CIPN and may provide insight into the complexities of the underlying pathophysiological mechanisms.