tbuckley/cabot-search huggingface dataset:
Radioimmunoassay Methodology: Application to Problems of Heterogeneity of Peptide Hormones
Authors: Rosalyn S. Yalow
Journal: Pharmacological Reviews (1973)

Competitive radioimmunoassay (RIA) is a general method for the determination of the concentration of virtually any substance which is or can be rendered immunogenic. The principle is simple. The concentration of an unknown unlabeled antigen is obtained by comparing its inhibitory effect on the binding of radioactively-labeled antigen to specific antibody with the inhibitory effect of known standards. Although up to now, the principal impact of RIA has been in the field of endocrinology, recent developments have demonstrated its applicability to fields as diverse as toxicology, virology, and cancer detection.

Problems encountered in RIA relate to the presence of non-hormonal factors which interfere in a non-specific fashion with the reaction of antigen with antibody and to the presence of cross reacting prohormones, molecular fragments, and related hormonal antigens which may alter the specificity of the immune reaction. However, the latter problem has been turned to an advantage in that the method has been instrumental in broadening our understanding of the mechanisms involved in the synthesis and degradation of peptide hormones. It would appear that many, if not all, peptide hormones are synthesized in a big precursor form of low or no biological activity, followed by the enzymatic conversion to the smaller, better known biologically active form and then rapid degradation to peptide fragments or constituent amino acids or both. For none of these systems has there been developed a complete picture of the complex interrelationships among precursor, active form(s), and degradation products. Especially desirable is a model which correlates immunoreactivity and biological activity as measured in the intact animal and in receptor site assay. One can only be certain that radioimmunoassay will continue to be involved in both the questions and the answers which will be necessary for the solution of this problem, as it has been for so many others in medicine.
O054 TM6SF2-T and PNPLA3-G genetic variants co-modulate the risk of hepatocellular carcinoma in caucasian patients with alcoholic cirrhosis. Inter-cohort validation in 1068 patients
Authors: P. Nahon, Q. Cao, E. Guyot, P. Rufat, A. Sutton, N. Ganne-Carrié, M. Ziol, T. Gustot, E. Quertinmont, J. Devière, D. Degré, J. Schreiber, A. Labkriman, N. Charnaux, C. Moreno, J.-C. Trinchet, D. Franchimont, J. Zucman-Rossi, E. Trepo
Journal: Journal of Hepatology (2015)
Restrictive chronic lung function decline after haematopoietic stem cell transplantation
Authors: Ji-Young Yang, Sang Young Oh, Jin Woo Song, Tae Sun Shim, Sei Won Lee, Jae Seung Lee, Dae-Young Kim, Je-Hwan Lee, Jung-Hee Lee, Kyoo-Hyung Lee, Kyung-Wook Jo
Journal: European Respiratory Journal (2015)

Until recently, it was generally thought that bronchiolitis obliterans syndrome (BOS), which is a type of obstructive lung disease with a dismal outcome, was the sole form of chronic lung allograft dysfunction (CLAD) occurring after lung transplantation. However, recent publications reported that some patients experience a restrictive form of chronic lung complication that has been termed restrictive allograft syndrome (RAS) [1]. Approximately one-third of patients with CLAD after lung transplantation can be classified as having RAS [2, 3]. This distinct form of CLAD is considered to be an important entity and has features that are distinct from those of BOS. First and foremost, the mortality of RAS is even greater than that from BOS: a previous study reported that the survival of patients with RAS was significantly poorer than that of patients with BOS [3]. Secondly, imaging of BOS on computed tomography (CT) has revealed air trapping, tree-in-bud opacities and peribronchial infiltrates, whereas RAS presented mainly with alveolar or interstitial changes such as septal thickening or reticulation [4]. Additionally, RAS has been histologically characterised by diffuse alveolar damage and extensive fibrosis in the alveolar interstitium and interlobular septa [2]. Some patients present with restrictive chronic lung function decline after haematopoietic stem cell transplantation <http://ow.ly/RpsAx>
JC polyomavirus mutants escape antibody-mediated neutralization
Authors: Upasana Ray, Paola Cinque, Simonetta Gerevini, Valeria Longo, Adriano Lazzarin, Sven Schippling, Roland Martin, Christopher B. Buck, Diana V. Pastrana
Journal: Science Translational Medicine (2015)

Deficient humoral immunity is a common aspect of PML pathogenesis that may be overcome by vaccination.
Impact of antibody Fc carbohydrate fucosylation on antibody-dependent cellular cytotoxicity by HuMax-EGFr —A fully human epidermal growth factor receptor antibody
Authors: M. Dechant, J. Lammerts van Bueren, M. Peipp, W. Bleeker, T. Beyer, P. Van Berkel, P. W. Parren, J. G. Van de Winkel, T. Valerius
Journal: Journal of Clinical Oncology (2006)

2543 Background: HuMax-EGFr - a human IgG1 EGF-R antibody in phase II clinical trials - was demonstrated to block EGF binding, to interfere with cellular signaling and to efficiently recruit effector cells for ADCC. Triggering of ADCC requires antibody binding to cellular Fc receptors which can be modulated by antibody glycosylation. Here, we investigated whether the glycosylation profile of HuMax-EGFr altered effector functions, and compared the contribution of mononuclear (MNC) and polymorphonuclear (PMN) cells for ADCC in human blood. Methods: Varying concentrations of two HuMax-EGFr batches, differing in the level of fucosylation of the complex-type oligosaccharides present in the Fc fragment, were compared in their capacity to kill EGF-R expressing tumor cells. Antibody binding and inhibition of proliferation was analyzed by flow cytometry and measuring vital cell mass, respectively. ADCC by isolated PMN, MNC and human whole blood was analyzed by chromium release assays. Results: Both batches of HuMax-EGFr bound similarly to target cells, and inhibited their proliferation to a similar extent. Low-fucosylated HuMax-EGFr demonstrated higher affinity for recombinant FcγRIIIa than fully fucosylated antibody. As expected, low-fucosylated antibody was significantly better in mediating ADCC by MNC (EC50 obtained at 10-fold lower antibody concentrations, p&lt;0.05). In contrast, PMN-mediated ADCC was unaffected by the antibody fucosylation level. Importantly, whole blood ADCC assays also revealed little differences between both batches. ADCC was significantly enhanced by blood from G-CSF-primed patients, but again both high- and low-fucosylated antibody performed similarly. Conclusions: Both HuMax-EGFr batches were equally potent in inhibiting cell proliferation, and were highly active in triggering ADCC by MNC and PMN. Differences in fucosylation of Fc carbohydrate affected MNC-mediated lysis, whereas PMN- and whole blood-mediated cell killing were only minimally affected. Thus, fucosylation of antibody Fc may only prove critical for therapeutic antibodies which predominantly recruit NK cells for ADCC, while it may be less relevant for PMN-recruiting antibodies. [Table: see text]
Effects of whole body vibration in Japanese patients with chronic obstructive pulmonary disease. A randomized controlled trial
Authors: Mitsunobu Ito, Masao Yamada, Shinji Inamura, Yoshiya Tsunoda, Kenji Hayashihara, Takefumi Saito, Shimao Fukai
Journal: European Respiratory Journal (2013)

Background: Chronic obstructive pulmonary disease (COPD) is a respiratory condition symptomatically characterised by dyspnea. Exercise tolerance, functionally, is low in patients with COPD, leading to dyspnea and lower limb skeletal muscle dysfunction. Endurance and strength training are established in patients with COPD. There, however, is an unmet need for further research in new and complementary exercise modalities. Whole-body vibration (WBV) is a mode of physical activity known to improve muscular function of the lower limbs, though such a new approach has not yet been investigated in Japanese patients with COPD.

Methods: Ten male patients (74.4 ± 4.6 yrs, FEV(1) pred. 67.8 ± 27.2%) with COPD in GOLD stage I to IV assessed for a 12-week outpatient multidisciplinary rehabilitation program were on top randomly assigned to one of two intervention groups: (1) 2 × 3 min of bilateral dynamic squat exercises on a side-alternating vibration platform at 12-24 Hz twice per week (WBV) and (2) a control group (CON) with the same amount of exercise time without WBV.

Results: All the patients completed the study in each group. The improvement in 6-min walking distance was significantly higher in the WBV-group when compared to the CON-group (WBV: 69.0 ± 28.2 m, CON: 31.0 ± 20.7 m with a between-group difference of 38 m (p <0.05). Significant improvements in symptoms, activity and impact of the St. George's Respiratory Questionnaire were shown in the WBV-group, compared to the CON-group.

Conclusions: WBV training seems to be a promising new exercise modality for Japanese outpatients with COPD.
Phase I/II clinical trial of a genetically modified and oncolytic vaccinia virus GL-ONC1 in patients with unresactable, chemotherapy-resistant peritoneal carcinomatosis.
Authors: Ulrich Lauer, Martina Zimmermann, Julia Sturm, Ursula Koppenhoefer, Michael Bitzer, Nisar P Malek, Joerg Glatzle, Alfred Koenigsrainer, Robert Moehle, Falko Fend, Christina Pfannenberg, Tanja Auth, Tony Yu, Aladar A Szalay
Journal: Journal of Clinical Oncology (2013)

3098 Background: For therapy-resistant peritoneal carcinomatosis (PC) viruses exhibiting oncolytic properties open up new perspectives. Our phase I/II study in patients with refractory PC (NCT01443260) is designed to assess the safety, MTD, and anti-tumor activity of GL-ONC1, a recombinant vaccinia virus (VACV) genetically engineered to selectively replicate in and destroy cancer cells. Methods: GL-ONC1 was administered intraperitoneally up to 4 times every 28 days under a standard 3+3 dose escalation design. Safety was assessed using CTCAEv4.0. Anti-tumor activity was determined by “fluid biopsies” obtained via repetitive paracenteses and by serial PET-CT scans. Patient samples were collected for pharmacokinetics, pharmacodynamics and viral shedding analysis. Results: Up to now, 4 patients have received 10 doses of GL-ONC1 ranging from 10 7 to 10 8 infectious viral particles per application.Adverse events have generally been limited to grade 1/2, being mostly transient flu-like symptoms as well as increased abdominal pain resulting from treatment-induced peritonitis. No DLT was reported. No viral shedding was observed. In one gastric cancer patient, effective intraperitoneal replication of GL-ONC1 was demonstrated for more than 3 weeks. Using either anti-EpCAM or anti-VACV specific antibodies, around 5% of all ascitic cells were found to be EpCAM-positive 3 days after treatment in this patient, and only around 5-10% of these cancer cells were VACV positive at the same time point. In contrast, 4 days later (i.e. 7 days after virotherapeutic treatment), less than 2% of all ascitic cells were still EpCAM-positive, and more than 90% of these cancer cells were VACV positive. Of note, VACV-positive cancer cells morphologically showed significant degenerative changes. Conclusions: Preliminary data demonstrate that GL-ONC1 is well tolerated when infused intraperitoneally. Importantly, a single intraperitoneal delivery of GL-ONC1 was found to be sufficient to cause a dramatic decline in the number of malignant cells in the ascitic fluid, suggesting that GL-ONC1 effectively removes tumor cells in the ascites of patients with PC. Clinical trial information: NCT01443260.
ACOSOG Z0011: A randomized trial of axillary node dissection in women with clinical T1-2 N0 M0 breast cancer who have a positive sentinel node.
Authors: A. E. Giuliano, L. M. McCall, P. D. Beitsch, P. W. Whitworth, M. Morrow, P. W. Blumencranz, A. M. Leitch, S. Saha, K. Hunt, K. V. Ballman
Journal: Journal of Clinical Oncology (2010)

CRA506 Background: Sentinel node biopsy (SNB) eliminates the need for axillary dissection (ALND) in patients whose sentinel node (SN) is tumor-free. However, completion ALND remains the gold standard for patients with a tumor-involved sentinel node. ALND achieves regional control, but its effect on survival remains controversial. The main objective of ACOSOG Z0011 was to compare outcomes of patients with hematoxylin and eosin (H&amp;E) detected metastasis in SN managed with or without ALND and no axillary irradiation. Methods: Clinically node-negative patients who underwent SN biopsy and had 1 or 2 SN with metastases detected by H&amp;E were randomized to ALND or no further axillary specific treatment. All patients were treated with lumpectomy and opposing tangential field irradiation. Adjuvant systemic therapy was at the discretion of their physicians. Overall survival (OS), disease-free survival (DFS), and locoregional control were evaluated. Results: 446 patients were randomized to SNB alone and 445 to SNB plus ALND. Patients treated with SNB alone were similar to those treated with SNB + ALND with respect to age, tumor size, Bloom-Richardson score, estrogen receptor status, adjuvant systemic therapy, tumor type, and T stage. Patients randomized to SNB alone had a median of two lymph nodes removed whereas patients randomized to ALND had a median of 17 lymph nodes removed. 17.6% of ALND patients had 3 or more involved nodes compared to 5.0% of SNB patients (p &lt; 0.001). Median follow-up is 6.2 years. 5-year in breast recurrence after ALND was 3.7% compared to 2.1% for SNB (p = 0.16) while 5-year nodal recurrence was 0.6% compared to 1.3% (p = 0.44) respectively. The five-year OS for patients undergoing SNB + ALND is 91.9% compared to 92.5% for SNB alone (p = 0.24), and DFS is 82.2% compared to 83.8% respectively (p = 0.13). Conclusions: Despite the widely held belief that ALND improves survival, no significant difference was recognized by this study of SN node-positive women. Although the study closed early because of low accrual/event rate, it is the largest phase III study of ALND for node-positive women, and it demonstrates no trend toward clinical benefit of ALND for patients with limited nodal disease. [Table: see text]
Anatomy of a swallow
Authors: Stephen L Ball, Puveendran Arullendran
Journal: BMJ (2015)

<h3>ABSTRACT</h3> Chest computed tomography (CT) is widely used for the management of Coronavirus disease 2019 (COVID-19) 49 pneumonia because of its availability and rapidity<sup>1–3</sup>. The standard of reference for confirming COVID-19 relies on microbiological tests but these tests might not be available in an emergency setting and their results are not immediately available, contrary to CT. In addition to its role for early diagnosis, CT has a prognostic role by allowing visually evaluating the extent of COVID-19 lung abnormalities<sup>4, 5</sup>. The objective of this study is to address prediction of short-term outcomes, especially need for mechanical ventilation. In this multi-centric study, we propose an end-to-end artificial intelligence solution for automatic quantification and prognosis assessment by combining automatic CT delineation of lung disease meeting expert’s performance and data-driven identification of biomarkers for its prognosis. AI-driven combination of variables with CT-based biomarkers offers perspectives for optimal patient management given the shortage of intensive care beds and ventilators<sup>6, 7</sup>.
Novel retinoic acid, 9-cis retinoic acid, in combination with all-trans retinoic acid is an effective inducer of differentiation of retinoic acid-resistant HL-60 cells
Authors: M Kizaki, H Nakajima, S Mori, T Koike, M Morikawa, M Ohta, M Saito, HP Koeffler, Y Ikeda
Journal: Blood (1994)
Phase I study of alpha-tocopherlyoxyacetic acid in patients with advanced cancer
Authors: Brendan D Curti, Emmanuel Akporiaye, Kim Sutcliffe, Keith S Bahjat, Yoshinobu Koguchi, Julie Cramer, Walter Urba
Journal: Journal for ImmunoTherapy of Cancer (2015)

A drug-induced change in the fine morphology of the plasma membrane of heart muscle cells is described. Thus, in rabbits the chronic administration of oxyfedrine caused a marked proliferation of the plasma membrane. At the same time the mitochondria became swollen and vacuolated, and there was evidence of lysis of myofibrils. These changes are not accounted for in terms of the release of endogenous stores of catecholamines.
Manchester expands seven day general practice to three million people
Authors: G. Iacobucci
Journal: BMJ (2015)

Greater Manchester will become the first area in England to roll out full, seven day general practice services by the end of 2015, after an evaluation of pilot schemes showed a 3% reduction in emergency department activity.

The move, which will offer more than three million people access to full primary care and diagnostic services seven days a week, marks the first phase of the government’s plan to devolve Greater Manchester’s entire £6bn (€8.2bn; $9.3bn) health and social care budget to a new regional authority.1

Announcing the plans on 10 June, officials said that the evaluation of several pilots covering 500 000 people had found reductions in hospital emergency …
The effect of doxycycline on bone turnover and tumor markers in breast cancer (BC) patients with skeletal metastases
Authors: S. K. Dhesy-Thind, J. Julian, R. Tozer, P. Ellis, A. Arnold, G. Singh, M. Levine
Journal: Journal of Clinical Oncology (2005)

3198 Background: Doxycycline is a tetracycline analogue which is osteotropic with high affinity for mineralized bone. In experimental systems, it has anti-cancer effects including inhibition of matrix metallo proteinases, anti-angiogenic activity and a cytostatic effect on cancer cells. Methods: 17 patients with newly diagnosed bone metastases from BC, and no prior bisphosphonate therapy were treated with Doxycycline 100 mg po bid for 3 months. Treatment was discontinued for disease progression or unacceptable toxicity. Bone scans and serum bone markers [N-telopeptide (NTx - Osteomark NTx Serum) and bone specific alkaline phosphatase (BAP - Metra BAP)] were measured as markers of bone turnover and PTHrP as a marker of tumor progression at baseline and following 12 weeks of therapy. Patients subsequently received bisphosphonate therapy. The primary outcome was a 50% relative decrease in serum bone markers. Results: 12 patients were evaluable for response, 3 patients discontinued therapy due to toxicity and were non-evaluable, and results are pending for 2 others. Median age was 62.5 years and 4 patients had other metastatic sites. 3 patients received concurrent chemotherapy and 9 patients hormonal treatment. There were no cases of pathological fractures or hypercalcemia. Results of the bone markers studies are shown below. 11 of 12 patients had normal serum NTx values and 5/12 had normal BAP at baseline despite extensive bone metastases. PTHrP levels in 9 of 12 patients either declined or remained at the same level after 12 weeks. Conclusions: Although Doxycycline for 3 months was associated with a drop in serum bone markers in some patients, it failed to satisfy the pre-specified outcome measure of a 50% decrease. A possible explanation is the lack of responsiveness of the outcome measure. Our study demonstrated the feasibility of administration of long-term Doxycycline. Further studies evaluating this agent are warranted. No significant financial relationships to disclose.
PLK1shRNA and doxorubicin co-loaded thermosensitive PLGA–PEG–PLGA hydrogels for localized and combined treatment of human osteosarcoma
Authors: Chaoliang He, Hecheng Ma, Yilong Cheng, Dongsong Li, Yubao Gong, Jianguo Liu, Huayu Tian, Xuesi Chen
Journal: Journal of Controlled Release (2015)
A randomized comparative trial of carboplatin and iproplatin in advanced squamous carcinoma of the uterine cervix: a Gynecologic Oncology Group study.
Authors: W P McGuire, J Arseneau, J A Blessing, P J DiSaia, K D Hatch, F T Given, N N Teng, W T Creasman
Journal: Journal of Clinical Oncology (1989)

A total of 394 patients with advanced, measurable squamous carcinoma of the uterine cervix and no prior chemotherapy were randomized to therapy with either carboplatin or iproplatin. There were 23 patients ineligible for the study and 10 patients who were not evaluable; the remaining 361 patients were evaluable for response and adverse effects. Randomization was well balanced for age, performance status, and prior therapy. Both platinum analogs were given every 28 days with starting doses of 400 mg/m2 for carboplatin (340 mg/m2 if the patient underwent prior radiation) and 270 mg/m2 for iproplatin (230 mg/m2 if the patient underwent prior radiation). These doses are equivalent to cisplatin doses of 75 to 100 mg/m2. Hematologic toxicity was dose-limiting, among which thrombocytopenia was slightly more common than leukopenia. Gastrointestinal toxicity was also prominent with both agents; however, iproplatin was significantly more toxic than carboplatin (P less than .001). Renal, otic, and peripheral nervous system toxicities were absent or infrequent with both analogs. No electrolyte abnormalities were observed. The percentage of planned dosages that were actually administered was 100% of carboplatin doses and 85% of iproplatin doses (P less than .0001). The reduction in iproplatin dose was apparently due to gastrointestinal toxicity. Response rates were similar for both agents (15% for carboplatin, 11% for iproplatin) and appear to be inferior to those noted with the parent compound, cisplatin.
Pregnancy outcomes in patients with ankylosing spondylitis: a nationwide register study
Authors: Gustav L Jakobsson, Olof Stephansson, Johan Askling, Lennart T H Jacobsson
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Introduction</h3> Unlike other chronic inflammatory diseases, little is known about how ankylosing spondylitis (AS) affects outcomes of pregnancy and birth characteristics. <h3>Methods</h3> In a nationwide population-based case–control study, 388 deliveries among women with AS (identified in the Swedish National Patient Register and Medical Birth Register) and deliveries among matched controls (n=1082) from the general population were included. Information regarding pregnancies after AS diagnosis, birth outcomes and possible confounders were retrieved from the national Swedish registers. ORs with 95% CIs were calculated with generalised estimating equations. <h3>Results</h3> Emergency and elective Caesarean section (CS) were performed in 16.5% and 9.8% of deliveries among women with AS compared with 6.5% and 6.9%, respectively, in population controls, resulting in OR of 3.00 (95% CI 2.01 to 4.46) and 1.66 (95% CI 1.09 to 2.54), respectively. Offspring of women with AS were more often preterm (9.0% vs 4.9%) and small-for-gestational-age (SGA) (3.1% vs 1.5%), resulting in an OR of 1.92 (95% CI 1.17 to 3.15) and 2.12 (95% CI 1.00 to 4.50), respectively. Adjustment for smoking habits, age, educational level, parity and exclusion of women with comorbidities resulted in similar or only slightly lower point estimates of risk. Cases with a more extensive antirheumatic therapy exposures tended to have a higher risk for elective CS and being SGA. <h3>Conclusions</h3> Women with AS had a higher prevalence for several adverse birth outcomes, with results suggesting an influence by both disease severity and comorbidities.