tbuckley/cabot-search huggingface dataset:
2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension - web addenda
Authors: Nazzareno Galiè, Marc Humbert, Jean-Luc Vachiery, Simon Gibbs, Irene Lang, Adam Torbicki, Gérald Simonneau, Andrew Peacock, Anton Vonk Noordegraaf, Maurice Beghetti, Ardeschir Ghofrani, Miguel Angel Gomez Sanchez, Georg Hansmann, Walter Klepetko, Patrizio Lancellotti, Marco Matucci, Theresa McDonagh, Luc A. Pierard, Pedro T. Trindade, Maurizio Zompatori, Marius Hoeper
Journal: European Respiratory Journal (2015)

Nazzareno Galie (ESC Chairperson), Marc Humbert (ERS Chairperson), Jean-Luc Vachiery, Simon Gibbs, Irene Lang, Adam Torbicki, Gerald Simonneau, Andrew Peacock, Anton Vonk Noordegraaf, Maurice Beghetti, Ardeschir Ghofrani, Miguel Angel Gomez Sanchez, Georg Hansmann, Walter Klepetko, Patrizio Lancellotti, Marco Matucci, Theresa McDonagh, Luc A. Pierard, Pedro T. Trindade, Maurizio Zompatori and Marius Hoeper The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and of the European Respiratory Society (ERS)
Tenofovir disoproxil fumarate (TDF) vs. emtricitabine (FTC)/TDF in lamivudine resistant hepatitis B: A 5-year randomised study
Authors: Scott Fung, Peter Kwan, Milotka Fabri, Andrzej Horban, Mijomir Pelemis, Hie-Won Hann, Selim Gurel, Florin A. Caruntu, John F. Flaherty, Benedetta Massetto, Kyungpil Kim, Kathryn M. Kitrinos, G. Mani Subramanian, John G. McHutchison, Leland J. Yee, Magdy Elkhashab, Thomas Berg, Ioan Sporea, Cihan Yurdaydin, Petr Husa, Maciej S. Jablkowski, Edward Gane
Journal: Journal of Hepatology (2016)
Correction: Corrigendum: Blocking c-Met–mediated PARP1 phosphorylation enhances anti-tumor effects of PARP inhibitors
Authors: Yi Du, Hirohito Yamaguchi, Yongkun Wei, Jennifer L Hsu, Hung-Ling Wang, Yi-Hsin Hsu, Wan-Chi Lin, Wen-Hsuan Yu, Paul G Leonard, Gilbert R Lee, Mei-Kuang Chen, Katsuya Nakai, Ming-Chuan Hsu, Chun-Te Chen, Ye Sun, Yun Wu, Wei-Chao Chang, Wen-Chien Huang, Chien-Liang Liu, Yuan-Ching Chang, Chung-Hsuan Chen, Morag Park, Philip Jones, Gabriel N Hortobagyi, Mien-Chie Hung
Journal: Nature Medicine (2016)
Reconstruction of Haplotype-Blocks Selected during Experimental Evolution
Authors: Susanne U. Franssen, Nicholas H. Barton, Christian Schlötterer
Journal: Molecular Biology and Evolution (2016)

The genetic analysis of experimentally evolving populations typically relies on short reads from pooled individuals (Pool-Seq). While this method provides reliable allele frequency estimates, the underlying haplotype structure remains poorly characterized. With small population sizes and adaptive variants that start from low frequencies, the interpretation of selection signatures in most Evolve and Resequencing studies remains challenging. To facilitate the characterization of selection targets, we propose a new approach that reconstructs selected haplotypes from replicated time series, using Pool-Seq data. We identify selected haplotypes through the correlated frequencies of alleles carried by them. Computer simulations indicate that selected haplotype-blocks of several Mb can be reconstructed with high confidence and low error rates, even when allele frequencies change only by 20% across three replicates. Applying this method to real data from D. melanogaster populations adapting to a hot environment, we identify a selected haplotype-block of 6.93 Mb. We confirm the presence of this haplotype-block in evolved populations by experimental haplotyping, demonstrating the power and accuracy of our haplotype reconstruction from Pool-Seq data. We propose that the combination of allele frequency estimates with haplotype information will provide the key to understanding the dynamics of adaptive alleles.
Variation in Medicare Expenditures for Treating Perioperative Complications
Authors: Jason C. Pradarelli, Mark A. Healy, Nicholas H. Osborne, Amir A. Ghaferi, Justin B. Dimick, Hari Nathan
Journal: JAMA Surgery (2016)

Treating surgical complications presents a major challenge for hospitals striving to deliver high-quality care while reducing costs. Costs associated with rescuing patients from perioperative complications are poorly characterized.To evaluate differences across hospitals in the costs of care for patients surviving perioperative complications after major inpatient surgery.Retrospective cohort study using claims data from the Medicare Provider Analysis and Review files. We compared payments for patients who died vs patients who survived after perioperative complications occurred. Hospitals were stratified using average payments for patients who survived following complications, and payment components were analyzed across hospitals. Administrative claims database of surgical patients was analyzed at hospitals treating Medicare patients nationwide. This study included Medicare patients aged 65 to 100 years who underwent abdominal aortic aneurysm repair (n = 69 207), colectomy for cancer (n = 107 647), pulmonary resection (n = 91 758), and total hip replacement (n = 307 399) between 2009 and 2012. Data analysis took place between November 2015 and March 2016.Clinical outcome of surgery (eg, no complication, complication and death, or complication and survival) and the individual hospital where a patient received an operation.Risk-adjusted, price-standardized Medicare payments for an episode of surgery. Risk-adjusted perioperative outcomes were also assessed.The mean age for Medicare beneficiaries in this study ranged from 74.1 years (pulmonary resection) to 78.2 years (colectomy). The proportion of male patients ranged from 37% (total hip replacement) to 77% (abdominal aortic aneurysm repair), and most patients were white. Among patients who experienced complications, those who were rescued had higher price-standardized Medicare payments than did those who died for all 4 operations. Assessing variation across hospitals, payments for patients who were rescued at the highest cost-of-rescue hospitals were 2- to 3-fold higher than at the lowest cost-of-rescue hospitals for abdominal aortic aneurysm repair ($60 456 vs $23 261; P < .001), colectomy ($56 787 vs $22 853; P < .001), pulmonary resection ($63 117 vs $21 325; P < .001), and total hip replacement ($41 354 vs $19 028; P < .001). Compared with lowest cost-of-rescue hospitals, highest cost-of-rescue hospitals had higher risk-adjusted rates of serious complications with similar rates of failure to rescue and overall 30-day mortality.After 4 selected inpatient operations, substantial variation was observed across hospitals regarding Medicare episode payments for patients rescued from perioperative complications. Notably, higher Medicare payments were not associated with improved clinical performance. These findings highlight the potential for hospitals to target efficient treatment of perioperative complications in cost-reduction efforts.
Chronic granulomatous disease: Clinical, functional, molecular, and genetic studies. The Israeli experience with 84 patients
Authors: Baruch Wolach, Ronit Gavrieli, Martin de Boer, Karin van Leeuwen, Sivan Berger‐Achituv, Tal Stauber, Josef Ben Ari, Menachem Rottem, Yechiel Schlesinger, Galia Grisaru‐Soen, Omar Abuzaitoun, Nufar Marcus, Ben Zion Garty, Arnon Broides, Jakov Levy, Polina Stepansky, Amos Etzioni, Raz Somech, Dirk Roos
Journal: American Journal of Hematology (2016)

Chronic granulomatous disease (CGD) is an innate immunodeficiency with a genetic defect of the nicotinamide adenosine dinucleotide phosphate, reduced, oxidase components. This leads to decreased reactive oxygen species (ROS) production, which renders patients susceptible to life-threatening infections. Over the course of 30 years, we diagnosed CGD in 84 patients from 61 families using functional, molecular, and genetic studies. The incidence of CGD in Israel is 1.05 per 100,000 live-births in the Jewish population and 1.49 in the Israeli Arab population. We diagnosed 52 patients (62%) with autosomal recessive inheritance (AR-CGD) and 32 (38%) with X-linked recessive inheritance (XLR-CGD). Consanguinity was detected in 64% of AR-CGD families (14% in Jews and 50% in Israeli Arabs). We found 36 different mutations (23 in XLR-CGD and 13 in AR-CGD patients), 15 of which were new. The clinical spectrum of CGD varied from mild to severe disease in both XLR and AR forms, although the AR subtype is generally milder. Further, residual ROS production correlated with milder clinical expression, better prognosis and improved overall survival. Patients with recurrent pyogenic infections developed fibrosis and hyperinflammatory states with granuloma formation. The management of CGD has progressed substantially in recent years, evolving from a fatal disease of early childhood to one of long-term survival. Our present cohort displays an encouraging 81% overall long term survival. Early hematopoietic stem cell transplantation is advisable before tissue damage is irreversible. Successful transplantation was performed in 18/21 patients. Therapeutic gene modification could become an alternative cure for CGD. Am. J. Hematol. 92:28-36, 2017. © 2016 Wiley Periodicals, Inc.
Bortezomib and high-dose melphalan as conditioning regimen before transplantation for de novo multiple myeloma patients: Updated data of the IFM phase II study.
Authors: M. Roussel, P. Moreau, A. Huynh, J. Mary, D. Caillot, C. Hullin, C. Mathiot, H. Avet-Loiseau, J. Harousseau, M. Attal
Journal: Journal of Clinical Oncology (2010)

8129 Background: Autologous stem cell transplantation (ASCT) is a gold standard for untreated myeloma patients (pts). Achievement of at least very good partial response (≥ VGPR) is a main prognostic factor for survival after ASCT (Harousseau et al, JCO 2009). We previously reported that bortezomib (Bor) and high-dose melphalan (HDM) conditioning regimen was safe and highly effective in frontline pts with 70% achieving ≥VGPR (Roussel et al, Blood 2010). At time of publication of this phase 2 study, follow-up (FU) was too short to state on PFS. We present here updated data. Methods: From July to December 2007, 54 de novo pts were enrolled to receive Bor (1 mg/m2 × 4) and HDM (200 mg/m2) (Bor- HDM) before ASCT. Patients' characteristics were: median age = 58 y; ISS 1/2/3 = 29/13/12 pts; high-risk cytogenetics in 9 pts [del 17p and/or t(4;14)], induction therapy with VAD (54%), Bor-Dex (33%) or other (13%). Response rates (RR) were analyzed according to IMWG criteria at 3 months (mo) after ASCT. Pts were then off-study and 45 (85%) received consolidation therapy with either lenalidomide (n = 42), thalidomide (n = 2) or a second ASCT (n = 1). Consolidation therapy was well balanced in the 3 inductions groups of pts. Results: Fifty-three pts received Bor-HDM before ASCT. 37 pts (70%) achieved ≥ VGPR at 3 mo regardless of induction therapy. Consolidation therapy improved RR in 35% of pts with overall 83% achieving ≥ VGPR. In December 2009, median FU was 31 mo. 25 pts relapsed with a median PFS not reached (NR) and a 2-year PFS of 76% (SE, 6%). PFS was longer in pts achieving ≥ VGPR after ASCT (median NR vs 27 mo, p = 0.03) and after consolidation therapy (median NR vs 22 mo, p = 0.01). Predictive factors for longer PFS in Cox proportional-hazards regression were: no high-risk cytogenetics (p = 0.001), post consolidation response ≥ VGPR (p = 0.02) and consolidation therapy (p>0.001). There was no difference among the 3 induction groups (VAD = 27.5 mo, SE 9%, Bor-Dex = NR vs other = NR). Nevertheless, in pts who received Bor-Dex induction therapy followed by Bor-HDM plus ASCT and consolidation therapy, 2-year PFS is 100%. Conclusions: These data support to introduce new drugs at each phase of frontline treatment in MM pts. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene, Celldex Therapeutics, Janssen-Ortho
A Phase 1 Trial of the Hematopoietic Growth Factor CDX-301 (rhuFlt3L) in Healthy Volunteers
Authors: Niroshana Anandasabapathy, Arlene Hurley, Marina Caskey, Christine Trumpfheller, Popi Sarma, James Pring, Maggie Pack, Renee Riggs, Jennifer Green, Michael Yellin, Thomas A. Davis, Tibor Keler, Sarah Schlesinger
Journal: Blood (2012)
Which intervention reduces the risk of preterm birth in women with risk factors?
Authors: Sarah J Stock, Khaled M K Ismail
Journal: BMJ (2016)

#### What you need to know

The aim of preventing preterm birth is to improve the health of babies by prolonging pregnancy. Preterm birth, or delivery before 37 weeks’ gestation, affects 7.3% of pregnancies in the UK.1 Around 75% of these births result from spontaneous preterm labour. The remaining 25% are delivered for medical reasons and are not considered further in this article.

Box 1 lists clinical risk factors and ultrasound scan findings that are associated with an increased risk of spontaneous preterm birth. However, these factors have poor predictive value. Women with multiple pregnancy are also at high risk of preterm birth, and their management is discussed in the supplementary online material.

#### Box 1: Risk factors for preterm birth234

##### Clinical history*

##### Imaging

Three treatment interventions are available to women at risk of spontaneous preterm birth (fig 1⇓). Considerable uncertainty exists over the effectiveness of these interventions, however, in part because clinical trials are hard to perform. Large numbers of trial participants are needed because most women at high risk of spontaneous preterm birth deliver at term, even without treatment. It is difficult and expensive to include neonatal and childhood …
Reflex Control of the Systemic Venous Bed
Authors: EUGENE BRAUNWALD, JOHN ROSS, RICHARD L. KAHLER, THOMAS E. GAFFNEY, ALLAN GOLDBLATT, DEAN T. MASON
Journal: Circulation Research (1963)

In a series of investigations on the control of venous tone, it was shown in anesthetized, open-chest dogs on cardiopulmonary bypass that venoconstriction occurs during the infusions of norepinephrine and epinephrine, while trimethaphan results in venodilatation. Lowering the pressure acting on the carotid baroreceptors and on the receptors within the left atrium and left ventricle results in reflex venoconstriction, while stimulation of these receptors relaxes the veins. Hypoxia produces venoconstriction as a result of stimulation of the carotid chemoreceptors, but the veno constriction which results from hypercapnia evidently is primarily central in origin. Reflex venoconstriction to carotid occlusion and central vagal stimulation can be blocked by the administration of guanethidine and reserpine. In intact, unanesthetized human subjects, to whom these drugs were administered orally in doses which are commonly utilized in clinical practice, reflex venoconstriction of the forearm veins was blocked. These investigations emphasize that the systemic venous bed reacts vigorously to neural and humoral stimuli, and that these reactions profoundly alter the cardiac output. In this manner, by exerting control of the rate at which the blood is delivered into the systemic arterial bed, the venous side of the circulation plays an important role in the control of the arterial pressure as well.
A multicenter randomized phase II trial on Kanglaite Injection (KLT) plus gemcitabine hydrochloride (GEM) versus GEM in patients with local advanced and metastatic pancreatic cancer.
Authors: Y. Sun, Y. Li, S. Qin, D. MA, S. C. Jiao, S. Y. Yu, J. Li, D. Liu, D. Song, D. Li
Journal: Journal of Clinical Oncology (2011)

e14510 Background: Pancreatic carcinoma is a malignant cancer with a 5-year survival rate of less than 5%. According to the meta-analysis on 2,422 advanced pancreatic patients reported in 2010 ASCO Annual Meeting, compared with GEM alone, GEM combined with DDP or oxaliplatin or capcitabine were less than 3% in absalute benefit of survival rate. KLT is a nature botanical medicine, which has been combined with GEM in treating pancreatic patients to prolong survival time based on report from China and Russia. Methods: Patients with advanced pancreatic cancer were randomized at 2:1 to KLT+GEM(KG)group and GEM (G) group. All were confirmed by histopathology, with assessable lesions, without previous chemotherapy. KG group: KLT, 200ml/d, i.v. within 80 minutes, d1-5, d8-12, d15-19, 28 days as a cycle. GEM 1000mg/m2, i.v. within 30 minutes, d1,8,15, 28 days as a cycle. G group: The same as KG group but without KLT. Primary endpoint: Median time to progress (mTTP, month). Secondary endpoints: response rate (RR %), disease control rate (DCR %); median overall survival (mOS, month); clinical benefit rate and quality of life (QOL). Results: 58 patients enrolled were randomized to KG group (40 cases) and G group (18 cases). In KG group, mTTP was 5.69 months, mOS was 8.59 months. Compared to G group, patients in KG group had their QOL obviously improved, with a more evident trend of survival benefit, but without significance. Conclusions: KLT+GEM has a trend to improve survival of patients with advanced pancreatic cancer, a large phase III randomized controlled trial is needed. mTTP: KG group versus G group (months, 95%CI). ITT (n=58) PP (n=50) KG G KG G 5.69 (1.97,7.60) 4.38 (2.76,6.35) 6.58 (1.97,8.49) 4.38 (2.76,6.35) P 0.66 0.33
Fludarabine and cytarabine versus high‐dose cytarabine in consolidation treatment of <i>t</i>(8; 21) acute myeloid leukemia: A prospective, randomized study
Authors: Ruiqi Li, Xiaoxia Hu, Libing Wang, Hui Cheng, Shuqing Lv, Weiping Zhang, Jianmin Wang, Jianmin Yang, Xianmin Song
Journal: American Journal of Hematology (2016)

Acute myeloid leukemia (AML) patients with t (8;21) aberration often have favorable outcomes, however, relapse still occurs in 30–40% patients, with only 50–60% of patients with t (8;21) AML cured with regimens containing high‐dose cytarabine (HD‐Ara‐C). To evaluate the effects of fludarabine and cytarabine (FA) consolidation therapy for t (8;21) AML patients, a prospective randomized study was performed. A total of 45 patients with t (8;21) AML after achieving complete remission (CR) were randomly assigned to receive four course consolidation with FA ( n = 23) or HD‐Ara‐C ( n = 22). Our study showed that at 36‐months, relapse‐free survival (RFS) was 81.73% in the FA arm and 50.73% in the HD‐Ara‐C arm ( P = 0.04), overall survival (OS) was 91.1% and 48.4% ( P = 0.01) in the FA arm and in the HD‐Ara‐C arm respectively; whereas cumulative incidence of relapse (CIR) was 18.27% and 47.39%, in the FA arm and in the HD‐Ara‐C arm respectively ( P = 0.05). In our study, treatment with FA, MRD2 status (reduction ≥ 3‐log) and absence of c‐kit mutations were identified as independent prognostic factors for lower risk of relapse, improved RFS and OS. We also found RFS for patients without c‐kit mutations was 100% in FA arm, and 57.8% in HD‐Ara‐C arm at 36 months ( P = 0.005); OS of both groups at 36 months was 100% and 51.4%, respectively ( P = 0.004), suggesting a benefit of consolidation therapy with FA for t(8;21) AML patients, especially, those without c‐kit mutations (Clinicaltrials.org ID NCT# 02024308). Am. J. Hematol. 92:12–17, 2017. © 2016 Wiley Periodicals, Inc.
Feasibility of achieving the 2025 WHO global tuberculosis targets in South Africa, China, and India: a combined analysis of 11 mathematical models
Authors: Rein M G J Houben, Nicolas A Menzies, Tom Sumner, Grace H Huynh, Nimalan Arinaminpathy, Jeremy D Goldhaber-Fiebert, Hsien-Ho Lin, Chieh-Yin Wu, Sandip Mandal, Surabhi Pandey, Sze-chuan Suen, Eran Bendavid, Andrew S Azman, David W Dowdy, Nicolas Bacaër, Allison S Rhines, Marcus W Feldman, Andreas Handel, Christopher C Whalen, Stewart T Chang, Bradley G Wagner, Philip A Eckhoff, James M Trauer, Justin T Denholm, Emma S McBryde, Ted Cohen, Joshua A Salomon, Carel Pretorius, Marek Lalli, Jeffrey W Eaton, Delia Boccia, Mehran Hosseini, Gabriela B Gomez, Suvanand Sahu, Colleen Daniels, Lucica Ditiu, Daniel P Chin, Lixia Wang, Vineet K Chadha, Kiran Rade, Puneet Dewan, Piotr Hippner, Salome Charalambous, Alison D Grant, Gavin Churchyard, Yogan Pillay, L David Mametja, Michael E Kimerling, Anna Vassall, Richard G White
Journal: The Lancet Global Health (2016)

BackgroundThe post-2015 End TB Strategy proposes targets of 50% reduction in tuberculosis incidence and 75% reduction in mortality from tuberculosis by 2025. We aimed to assess whether these targets are feasible in three high-burden countries with contrasting epidemiology and previous programmatic achievements.Methods11 independently developed mathematical models of tuberculosis transmission projected the epidemiological impact of currently available tuberculosis interventions for prevention, diagnosis, and treatment in China, India, and South Africa. Models were calibrated with data on tuberculosis incidence and mortality in 2012. Representatives from national tuberculosis programmes and the advocacy community provided distinct country-specific intervention scenarios, which included screening for symptoms, active case finding, and preventive therapy.FindingsAggressive scale-up of any single intervention scenario could not achieve the post-2015 End TB Strategy targets in any country. However, the models projected that, in the South Africa national tuberculosis programme scenario, a combination of continuous isoniazid preventive therapy for individuals on antiretroviral therapy, expanded facility-based screening for symptoms of tuberculosis at health centres, and improved tuberculosis care could achieve a 55% reduction in incidence (range 31–62%) and a 72% reduction in mortality (range 64–82%) compared with 2015 levels. For India, and particularly for China, full scale-up of all interventions in tuberculosis-programme performance fell short of the 2025 targets, despite preventing a cumulative 3·4 million cases. The advocacy scenarios illustrated the high impact of detecting and treating latent tuberculosis.InterpretationMajor reductions in tuberculosis burden seem possible with current interventions. However, additional interventions, adapted to country-specific tuberculosis epidemiology and health systems, are needed to reach the post-2015 End TB Strategy targets at country level.FundingBill and Melinda Gates Foundation
Targeting NF-κB with First in Class N-Quinoline Benzenesulfonamides (NQBS) Reveals Potent Activity in Models of Diffuse Large B-Cell Lymphoma (DLBCL)
Authors: Matko Kalac, Michael Mangone, Alison Rinderspacher, Shi-Xian Deng, Luigi Scotto, Jeremie Vendome, Mukesh Bansal, Andrea Califano, Donald Landry, Owen A. O'Connor
Journal: Blood (2015)