tbuckley/cabot-search huggingface dataset:
The impact of image-guided radiotherapy (IGRT) for prostate cancer (PC) on radiotherapy (RT)-related acute toxicities and prostate-specific antigen (PSA) kinetics.
Authors: Darren M. C. Poon, CM Leung, CM Chu, WY Lee, Louis Lee, Michael K. Kam, Sing Fai Leung, Kwok Hung Yu, Anthony T. C. Chan
Journal: Journal of Clinical Oncology (2012)

e15110 Background: IGRT for PC could potentially improve the therapeutic ratio by enhancing accuracy of delivery of radiation to the prostate gland. Our aim is to compare the treatment outcomes in terms of RT-related acute toxicities and PSA kinetics of PC patients (pts) undergoing radical intensity-modulated radiotherapy (IMRT) with or without image-guidance. Methods: A cohort of 21 consecutive pts treated by IGRT (I) from January 2010, when the IGRT system was introduced in our institution, was compared with an immediately precedent cohort of 21 pts receiving IMRT without image-guidance (Non-I). The prescription dose (76Gy in 38 fractions) and the treatment margins were the same between the 2 groups (gps). In the I gp, daily online verification and correction of treatment position was performed with reference to image registration of the daily pre-treatment on-board imaging with the corresponding digitally reconstructed radiographs, based on three-dimensional matching of three intra-prostatic fiducial markers. Androgen deprivation therapy was not used in both gps. Acute toxicities were scored weekly during the course of RT according to the Common Terminology Criteria for Adverse Events Version 4.02. The pre- and the post-RT PSA within 6 months after completion of RT were obtained. The PSA halving time (PSAHT) was calculated by first order kinetics. Results: There was no statistically significant difference regarding the baseline clinical characteristics (age, PSA at diagnosis, Gleason score, T staging) between the gps. No grade 3 or 4 acute genitourinary (GU) or gastrointestinal (GI) toxicities was encountered in either gps. Acute grade 1 or 2 GI toxicities were significantly less frequent in the I gp (23.8% vs 81.0%, p=0.001), and their median duration of such toxicity were also significantly shorter (0.33 week vs 1.38 week, p=0.004).The frequencies of acute grade 1 or 2 GU toxicities were comparable between both gps (66.6% vs 81.0%, p=0.45).The I gp had a shorter median PSAHT than the non-I gp (3.36 week vs 5.49 week, p=0.09). Conclusions: IGRT is effective in reducing acute GI toxicities in treatment of PC, and may have more favorable PSA kinetics.
Azithromycin and metronidazole versus metronidazole-based therapy for the induction of remission in mild to moderate paediatric Crohn’s disease : a randomised controlled trial
Authors: Arie Levine, Michal Kori, Jarek Kierkus, Rotem Sigall Boneh, Malgorzata Sladek, Johanna C Escher, Eytan Wine, Baruch Yerushalmi, Jorge Amil Dias, Ron Shaoul, Gigi Veereman Wauters, Mona Boaz, Guila Abitbol, Athos Bousvaros, Dan Turner
Journal: Gut (2018)

Objective Crohn’s disease (CD) pathogenesis associated with dysbiosis and presence of pathobionts in the lumen, intracellular compartments and epithelial biofilms. Azithromycin is active in all three compartments. Our goal was to evaluate if azithromycin-based therapy can improve response and induce remission compared with metronidazole alone in paediatric CD. Design This blinded randomised controlled trial allocated children 5–18 years with 10&lt;Pediatric Crohn’s Disease Activity Index (PCDAI)≤40 to azithromycin 7.5 mg/kg, 5 days/week for 4 weeks and 3 days/week for another 4 weeks with metronidazole 20 mg/kg/day (group 1) or metronidazole alone (group 2), daily for 8 weeks. Failures from group 2 were offered azithromycin as open label. The primary end point was response defined by a decrease in PCDAI&gt;12.5 or remission using intention to treat analysis. Results 73 patients (mean age 13.8±3.1 years) were enrolled, 35 to group 1 and 38 to group 2. Response and remission rates at week 8 were identical 23/35 (66%) in group 1 and 17/38 (45%) and 15/38 (39%) in group 2 (P=0.07 and P=0.025, respectively). The needed to treat for remission was 3.7. Faecal calprotectin declined significantly in group 1 (P=0.003) but not in group 2 (p=0.33), and was lower at week 8 (P=0.052). Additional therapy was required in 6/35(17%) from group 1 versus 16/38(42%) in group 2 (P=0.027) by week 8. Among 12 failures in group 2, open-label azithromycin led to remission in 10/12 (83%). Conclusions The combination of azithromycin and metronidazole failed to improve response but was superior for induction of remission and reduction in calprotectin. Trial registration number NCT01596894 .
Increased GATA-3 and T-bet expression in eosinophilic esophagitis versus gastroesophageal reflux disease
Authors: Benjamin L. Wright, Nathalie Nguyen, Kelly P. Shim, Joanne C. Masterson, Elizabeth A. Jacobsen, Sergei I. Ochkur, James J. Lee, Glenn T. Furuta
Journal: Journal of Allergy and Clinical Immunology (2018)
Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria: an open-label, randomised controlled trial
Authors: Mical Paul, George L Daikos, Emanuele Durante-Mangoni, Dafna Yahav, Yehuda Carmeli, Yael Dishon Benattar, Anna Skiada, Roberto Andini, Noa Eliakim-Raz, Amir Nutman, Oren Zusman, Anastasia Antoniadou, Pia Clara Pafundi, Amos Adler, Yaakov Dickstein, Ioannis Pavleas, Rosa Zampino, Vered Daitch, Roni Bitterman, Hiba Zayyad, Fidi Koppel, Inbar Levi, Tanya Babich, Lena E Friberg, Johan W Mouton, Ursula Theuretzbacher, Leonard Leibovici
Journal: The Lancet Infectious Diseases (2018)
Hair loss is an important symptom of the menopause
Authors: Amr Salam, Christos Tziotzios, David A Fenton
Journal: BMJ (2018)

Hickey and colleagues provide a comprehensive overview of non-hormonal treatments for menopausal symptoms.1 But they do not discuss female pattern hair loss (FPHL), also referred to as androgenetic alopecia, which many women experience around menopause. 

FPHL is the most common cause of hair loss in women. It is a non-scarring alopecia that …
Brief Report: Pharmacodynamics, Safety, and Clinical Efficacy of AMG 811, a Human Anti–Interferon‐γ Antibody, in Patients With Discoid Lupus Erythematosus
Authors: Victoria P. Werth, David Fiorentino, Barbara A. Sullivan, Michael J. Boedigheimer, Kit Chiu, Christine Wang, Gregory E. Arnold, Michael A. Damore, Jeannette Bigler, Andrew A. Welcher, Chris B. Russell, David A. Martin, James B. Chung
Journal: Arthritis & Rheumatology (2017)

Interferon-γ (IFNγ) is implicated in the pathogenesis of discoid lupus erythematosus (DLE). This study sought to evaluate a single dose of AMG 811, an anti-IFNγ antibody, in patients with DLE.The study was designed as a phase I randomized, double-blind, placebo-controlled crossover study of the pharmacodynamics, safety, and clinical efficacy of AMG 811 in patients with DLE. Patients received a single subcutaneous dose of AMG 811 (180 mg) or placebo. The patients in sequence 1 received AMG 811 followed by placebo, while those in sequence 2 received placebo followed by AMG 811. Pharmacodynamic end points included global transcriptional analyses of lesional and nonlesional skin, IFNγ blockade signature (IGBS) transcriptional scores in the skin and blood, keratinocyte IFNγ RNA scores, and serum levels of CXCL10 protein. Additional end points were efficacy outcome measures, including the Cutaneous Lupus Erythematosus Disease Area and Severity Index, and safety outcome measures.Sixteen patients with DLE were enrolled in the study (9 in sequence 1 and 7 in sequence 2). AMG 811 treatment reduced the IGBS score (which was elevated in DLE patients at baseline) in both the blood and lesional skin. The keratinocyte IFNγ RNA score was not affected by administration of AMG 811. Serum CXCL10 protein levels (which were elevated in the blood of DLE patients) were reduced with AMG 811 treatment. The AMG 811 treatment was well tolerated but did not lead to statistically significant improvements in any of the efficacy outcome measures.AMG 811 treatment led to changes in IFNγ-associated biomarkers and was well tolerated, but no significant clinical benefit was observed in patients with DLE.
Chronic hip pain
Authors: Heather White, Michael Barrett, Christopher Gooding
Journal: BMJ (2018)

A 55 year old woman presented to her general practitioner with a six month history of pain over the lateral aspect of her left hip in the trochanteric region. She described the pain as “a niggling pain that seems to be progressively getting worse.” The pain was exacerbated on weight bearing and by activity, but did not prevent her from being active. The pain woke her at night. She had a medical history of gastro-oesophageal reflux disease, essential hypertension, and early stage breast cancer. Her breast cancer was diagnosed and treated eight years ago, and she had since been discharged from follow-up. Her only regular medication was omeprazole. She lived at home with her husband and worked as a teaching assistant. On examination, she had a marked antalgic gait. She had a good range of pain-free movement but had discomfort over the lateral aspect of the left hip during the extremes of rotation. A radiograph of the pelvis was performed (fig 1).



Fig 1 
Radiograph of the pelvis (anteroposterior view)





### 1. What are the differential diagnoses?

#### Short answer

Secondary malignancy, primary bone malignancy, such as multiple myeloma, osteomyelitis, benign neoplasm such as giant cell tumour, brown tumour.

#### Discussion

The pelvic radiograph showed at least two lytic lesions in the left proximal femur and greater trochanter. Secondary bone malignancy is the most …
Abstract P329: Educational Attainment and Lifetime Risk of Cardiovascular Disease: the Atherosclerosis Risk in Communities Study
Authors: Yasuhiko Kubota, Gerardo Heiss, Richard F MacLehose, Nicholas S Roetker, Aaron R Folsom
Journal: Circulation (2017)

Background: Estimates of lifetime risk may help raise awareness of the extent to which educational inequalities affect risk of cardiovascular disease (CVD). To date, no study has reported the lifetime risk of CVD according to categories of educational attainment. Objectives: To estimate the lifetime risk of CVD from 45 through 85 years according to educational attainment. Methods: We followed 13,948 whites and African Americans initially free of CVD from 1,987 through 2,013, and used a life table approach to estimate lifetime risks of life-threatening CVD events (coronary heart disease, heart failure and stroke) according to educational attainment (grade school, high school without graduation, high school graduation, vocational school, college with or without graduation, and graduate/professional school). We adjusted for competing risks of death from underlying causes other than CVD. Results: During the 269,210 person-years of follow-up, we documented 4,512 CVD events, and 2,401 non-CVD deaths. Educational attainment displayed an inverse dose-response relation with cumulative risk of CVD, which became evident in middle-age, with the most striking gap between those not completing versus completing high school. Lifetime risk estimates of CVD from age 45 years though 85 years were 55.0% (95% confidence interval, 51.4-58.6) for grade school, 50.5% (47.3-53.3) for high school education without graduation, 41.7% (39.5-43.8) for high school graduation, 39.7% (35.5-43.4) for vocational school, 39.2% (36.4-41.4) for college with or without graduation, and 36.1% (31.9-39.7) for graduate/professional school. For both men and women, and whites as well as African Americans, those who did not graduate from high school had a sizably higher lifetime CVD risk. There was a similar pattern for cumulative CVD risk to 65 years. Lower family income and parental educational attainment were also associated with greater lifetime CVD risk, but individuals with more than a high school education had a lower lifetime risk than those with less educational attainment, regardless of their income or parental educational attainment. Conclusions: Educational attainment was inversely associated with the lifetime risk of CVD, and cumulative risk differences were already evident during middle-age, suggesting that greater educational attainment might promote lower lifetime risk of CVD.
High-density lipoprotein-mimicking nanodiscs carrying peptide for enhanced therapeutic angiogenesis in diabetic hindlimb ischemia
Authors: Hyun-Ji Park, Rui Kuai, Eun Je Jeon, Yoojin Seo, Youngmee Jung, James J. Moon, Anna Schwendeman, Seung-Woo Cho
Journal: Biomaterials (2018)
The Fanconi Pathway in Pediatric T-Cell Acute Lymphoblastic Leukemia
Authors: Gayle P. Pouliot, Melissa A. Burns, James Degar, Chau Vo, Lisa Moreau, Justine E. Roderick, Bose Kochupurakkal, Sofie Peirs, Bjorn Menten, Mignon L. Loh, Stephen P. Hunger, Lewis B. Silverman, Stephen E. Sallan, Marian H. Harris, Kristen E. Stevenson, Donna S. Neuberg, David M. Weinstock, Andrew P. Weng, Michelle Kelliher, Pieter Van Vlierberghe, Alan D. D'Andrea, Alejandro Gutierrez
Journal: Blood (2017)
Abstract 11420: Long-Term Mortality, MACE, and Angina Among Patients With Diabetes and Myocardial Infarction
Authors: Suzanne V Arnold, John A Spertus, Darren K McGuire, Kasia J Lipska, Yan Li, Yaping Xu, Joshua M Stolker, Abhinav Goyal, Mikhail Kosiborod
Journal: Circulation (2014)

Background: Patients with diabetes mellitus (DM) are at higher risk for adverse events after MI, including death and recurrent ischemia. As such, we sought to develop prediction models to identify DM patients at highest risk for these outcomes. Methods: We examined 3 adverse outcomes (3-year mortality, 1-year angina, 1-year MACE [mortality, MI, stroke, urgent revascularization]) among patients with DM discharged alive after MI from 24 US hospitals. Using Harrell’s backward selection, we developed hierarchical multivariable models with a parsimonious set of covariates for each outcome. The mortality and angina models were validated in a separate 19-site US MI registry. Results: Among 1626 DM patients, event rates were 19% for 3-year mortality, 11% for 1-year MACE, and 27% for 1-year angina. The models had good discrimination, with c-indices of 0.80, 0.72, and 0.73, respectively, and excellent calibration. The strongest predictors (in terms of F-value) were age, hemoglobin, and creatinine for mortality; depression, hemoglobin, and history of heart failure for MACE; and angina prior to MI, age, and prior CABG for angina (Table). The observed rates of outcomes in the lowest to highest decile of predicted risk ranged broadly for all 3 outcomes, with ranges of 1-58% for mortality, 1-38% for MACE, and 8-62% for angina. The mortality and angina models performed well in the validation cohort, although they tended to over-predict mortality at higher levels of risk and under-predict angina at lower levels of risk. Conclusion: Patients with DM and MI represent a particularly high-risk cohort, with increased mortality, MACE, and angina. However, patients with DM are not a homogenous group, as there is a broad range of risk levels for adverse outcomes within the DM population. We have developed and validated models so as to identify the highest-risk DM patients for whom closer follow-up and secondary prevention strategies can be targeted most aggressively.
Abstract 13077: Impact of Age on the Morphology of Left Atrial Appendage in Atrial Fibrillation
Authors: Yukia Hirata, Hirotsugu Yamada, Kenya Kusunose, Rikuto Shimizu, Yuta Torii, Susumu Nishio, Hiromitsu Seno, Yoshihito Saijo, Shuji Hayashi, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata
Journal: Circulation (2016)

Background: Left atrial appendage (LAA) is the main location of thrombus formation in patients with atrial fibrillation (AF), which has a variety of structure. Recent studies reported that “non-chicken wing” LAA morphology had a significantly higher risk of stroke compared with “chicken wing” morphology. However, LAA morphology might be affected by aging or AF. Thus, we evaluated the relationship between age and frequency of LAA morphology in patients with AF and sinus rhythm (SR). Methods: We enrolled 145 AF patients and 199 SR patients without any cardiovascular disease. LAA volume and morphology were assessed by contrast-enhanced multi-detector computed tomography. The morphology was visually classified “chicken wing” or “non-chicken wing” according to the previous report. Results: LAA volume index was significantly higher in the AF group than in the SR group (6.8±2.8 ml/m 2 vs. 4.4±1.8 ml/m 2 , p&lt;0.001).There was no significant trend in frequency of non-chicken wing among ages in SR group (p=0.36 for trend), whereas it was negatively related to age in AF group (p=0.002 for trend). In multivariable logistic regression analysis, age (OR 0.95, p=0.021) and duration of AF (OR 0.97, p=0.002) were independent factors of non-chicken wing LAA morphology. Conclusions: LAA morphology is affected by age, especially in patients with AF. When we utilize LAA morphology (non-chicken wing type) as a stroke risk factor in patients with AF, we may have to pay attention to their age.
Germline gain-of-function myeloid differentiation primary response gene–88 (MYD88) mutation in a child with severe arthritis
Authors: Keith A. Sikora, Joshua R. Bennett, Laurens Vyncke, Zuoming Deng, Wanxia Li Tsai, Ewald Pauwels, Gerlinde Layh-Schmitt, April Brundidge, Fatemeh Navid, Kristien J.M. Zaal, Eric Hanson, Massimo Gadina, Louis M. Staudt, Thomas A. Griffin, Jan Tavernier, Frank Peelman, Robert A. Colbert
Journal: Journal of Allergy and Clinical Immunology (2018)
Atypical chemokine receptor 4 shapes activated B cell fate
Authors: Ervin E. Kara, Cameron R. Bastow, Duncan R. McKenzie, Carly E. Gregor, Kevin A. Fenix, Rachelle Babb, Todd S. Norton, Dimitra Zotos, Lauren B. Rodda, Jana R. Hermes, Katherine Bourne, Derek S. Gilchrist, Robert J. Nibbs, Mohammed Alsharifi, Carola G. Vinuesa, David M. Tarlinton, Robert Brink, Geoffrey R. Hill, Jason G. Cyster, Iain Comerford, Shaun R. McColl
Journal: The Journal of Experimental Medicine (2018)

Activated B cells can initially differentiate into three functionally distinct fates—early plasmablasts (PBs), germinal center (GC) B cells, or early memory B cells—by mechanisms that remain poorly understood. Here, we identify atypical chemokine receptor 4 (ACKR4), a decoy receptor that binds and degrades CCR7 ligands CCL19/CCL21, as a regulator of early activated B cell differentiation. By restricting initial access to splenic interfollicular zones (IFZs), ACKR4 limits the early proliferation of activated B cells, reducing the numbers available for subsequent differentiation. Consequently, ACKR4 deficiency enhanced early PB and GC B cell responses in a CCL19/CCL21-dependent and B cell–intrinsic manner. Conversely, aberrant localization of ACKR4-deficient activated B cells to the IFZ was associated with their preferential commitment to the early PB linage. Our results reveal a regulatory mechanism of B cell trafficking via an atypical chemokine receptor that shapes activated B cell fate.
Abstract P175: Hypertension Burden in Luxembourg: Geographic Variations and Individual Risk Factors From the 2013-15 European Health Examination Survey
Authors: Maria Ruiz-Castell, Ngianga-Bakwin Kandala, Andrea Kuemmerle, Jessica Barré, Anna Schritz, Charles Delagardelle, Jean-Claude Schmit, Saverio Stranges
Journal: Circulation (2016)

Introduction: Hypertension is a modifiable risk factor for cardiovascular disease, the latter still representing the main cause of death in Luxembourg. The aim of this study was to estimate the current prevalence of hypertension, associated risk factors, and its geographic variations in the Grand Duchy of Luxembourg. Methods: Cross-sectional, population-based data on 1,508 randomly selected residents of Luxembourg, aged 25 to 64, were collected as part of the European Health Examination Survey (EHES-LUX) between 2013 and 2015. Hypertension was defined as systolic/diastolic blood pressure of ≥140/90 mmHg, self-report of a physician diagnosis or on anti-hypertensive medication. Standard and Bayesian regressions were used to examine associations between hypertension and covariates. We mapped hypertension‘s geographic distribution by using a Bayesian geo-additive mixed model adjusted by health-related behaviours, socioeconomic characteristics, body mass index, depressive symptoms and general health status. Results: 31% (471 of 1508) of Luxembourg residents were hypertensive, and half of them were unaware of their condition. Among those who were aware of their condition, nearly 50% (121 of 261) were not adequately controlled. In men, the likelihood of being hypertensive was: lower in those being more physically active (&gt;3h/week) (odds ratio [OR] and 95% credible region [CR]: 0.60[0.37, 0.92]) and consuming alcohol daily (0.33 [0.10, 0.83]), and higher in those with a low health perception (1.63 [1.01, 2.69]). In women, the likelihood of being hypertensive was higher in those experiencing depressive symptoms (1.83[1.27, 2.68]). There was a clear variation in hypertension prevalence across cantons and municipalities, with a North to South gradient: the highest odds ratio was observed in the South-West region of the country (1.21 [0.94, 1.57]), one of the most industrialized regions in Luxembourg. We observed a significant positive spatial effect in this region at 90% nominal level. Conclusions: In Luxembourg, the vast majority of people with hypertension are either unaware of their condition or not adequately controlled, which constitutes a major public health issue. There are geographic differences in hypertension prevalence in Luxembourg, which is remarkable given the size of the country. It is therefore necessary to consider the role of individual and regional (canton and commune level) risk factors in hypertension prevalence, as well as public health initiatives to control and promote awareness about this condition in order to reduce its burden in Luxembourg.
Modifier variant of METTL13 suppresses human GAB1–associated profound deafness
Authors: Rizwan Yousaf, Zubair M. Ahmed, Arnaud P.J. Giese, Robert J. Morell, Ayala Lagziel, Alain Dabdoub, Edward R. Wilcox, Sheikh Riazuddin, Thomas B. Friedman, Saima Riazuddin
Journal: Journal of Clinical Investigation (2018)

A modifier variant can abrogate the risk of a monogenic disorder. DFNM1 is a locus on chromosome 1 encoding a dominant suppressor of human DFNB26 recessive, profound deafness. Here, we report that DFNB26 is associated with a substitution (p.Gly116Glu) in the pleckstrin homology domain of GRB2-associated binding protein 1 (GAB1), an essential scaffold in the MET proto-oncogene, receptor tyrosine kinase/HGF (MET/HGF) pathway. A dominant substitution (p.Arg544Gln) of METTL13, encoding a predicted methyltransferase, is the DFNM1 suppressor of GAB1-associated deafness. In zebrafish, human METTL13 mRNA harboring the modifier allele rescued the GAB1-associated morphant phenotype. In mice, GAB1 and METTL13 colocalized in auditory sensory neurons, and METTL13 coimmunoprecipitated with GAB1 and SPRY2, indicating at least a tripartite complex. Expression of MET-signaling genes in human lymphoblastoid cells of individuals homozygous for p.Gly116Glu GAB1 revealed dysregulation of HGF, MET, SHP2, and SPRY2, all of which have reported variants associated with deafness. However, SPRY2 was not dysregulated in normal-hearing humans homozygous for both the GAB1 DFNB26 deafness variant and the dominant METTL13 deafness suppressor, indicating a plausible mechanism of suppression. Identification of METTL13-based modification of MET signaling offers a potential therapeutic strategy for a wide range of associated hearing disorders. Furthermore, MET signaling is essential for diverse functions in many tissues including the inner ear. Therefore, identification of the modifier of MET signaling is likely to have broad clinical implications.