bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutant IDH1 inhibitor ivosidenib (IVO; AG-120) in combination with azacitidine (AZA) for newly diagnosed acute myeloid leukemia (ND AML).
Authors: Dinardo Courtney Denton , Stein Anthony Selwyn , Stein Eytan M. , Fathi Amir Tahmasb , Frankfurt Olga , Schuh Andre C. , Martinelli Giovanni , Patel Prapti Arvind , Raffoux Emmanuel , Tan Peter , Zeidan Amer Methqal , de Botton Stéphane , Kantarjian Hagop M. , Stone Richard M. , Lam Du Hung , Gong Jing , Zhang Vickie , Winkler Thomas , Wu Bin , Vyas Paresh 
Published: March 2020

7011 Background: IVO, a mutant IDH1 (mIDH1) inhibitor, is approved for the treatment of relapsed/refractory mIDH1 AML. We report results from an ongoing phase 1b study of patients (pts) with mIDH1 ND AML ineligible for intensive treatment who received combination IVO+AZA (NCT02677922). Methods: Pts received oral IVO 500 mg daily continuously and subcutaneous AZA 75 mg/m2 on D1–7 in 28-d cycles. ORR comprised CR + CRi/CRp + PR+ MLFS. CR with partial hematologic recovery (CRh) was defined as CR with ANC > 0.5×109/L and platelets > 50×109/L. Exploratory analysis included digital PCR assessment of m IDH1 allele frequency in bone marrow mononuclear cells (≤0.04% sensitivity). Results: As of 9Oct2018, 23 pts received IVO+AZA (11 male; median age 76 yrs [range 61–88]). Median duration of exposure was 11 mo (0.3–25.3); 12 pts remained on treatment at data cutoff. All-grade adverse events (AEs) regardless of cause in ≥30% pts were thrombocytopenia (65%), nausea (61%), diarrhea (57%), anemia (52%), constipation (52%), febrile neutropenia (39%), pyrexia (39%), vomiting (35%), fatigue (35%), hypokalemia (35%), dizziness (35%), insomnia (35%), and neutropenia (30%). AEs of special interest included ECG QT prolonged (26%), IDH differentiation syndrome (17%), and leukocytosis (13%). Grade 3/4 AEs in ≥10% pts were thrombocytopenia (61%), anemia (44%), febrile neutropenia (39%), neutropenia (26%), sepsis (22%), and ECG QT prolonged (13%). ORR was 78% (n = 18): CR 57%, CRi/CRp 13%, and MLFS 9%. CR+CRh rate was 70% (n = 16). Median time to response was 1.8 mo (0.7–3.8) and to CR 3.5 mo (0.8–6.0); median response duration not yet reached. m IDH1 clearance was seen in 10/16 pts (63%) with CR/CRh, including 9/13 (69%) with CR. Conclusions: IVO+AZA was well tolerated with a safety profile consistent with IVO or AZA monotherapy. All-grade cytopenia-related AEs were infrequent relative to other non-intensive therapies. CR and ORR rates exceeded those of AZA alone (Dombret et al., Blood 2015) and most responders achieved m IDH1 mutation clearance. Based on these findings, a phase 3 double-blind placebo-controlled study of IVO +AZA (AGILE, NCT03173248) is actively enrolling pts. Clinical trial information: NCT02677922.
Results of the PI3Kδ inhibitor ME-401 alone or with rituximab in relapsed/refractory (R/R) follicular lymphoma (FL).
Authors: Zelenetz Andrew David , Jagadeesh Deepa , Reddy Nishitha M. , Stathis Anastasios , Salman Huda S. , Asch Adam Steven , Kenkre Vaishalee Padgaonkar , Jhangiani Haresh S. , Iasonos Alexia , Soumerai Jacob D. , Llorin Judith , Pagel John M. 
Published: March 2020

7512 Background: ME-401, a potent and selective oral PI3kδ inhibitor, is being evaluated in a Phase 1b study in patients (pts) with R/R B-cell malignancies (NCT02914938). 70 pts were treated; we report here results in FL. Methods: Pts with ECOG ≤2, no prior PI3K therapy and progression of disease (POD) after ≥1 prior therapy were initially enrolled in a dose escalation phase (60-180 mg) then in 60 mg expansion cohorts as monotherapy or in combination with rituximab. ME-401 was given initially on a daily continuous schedule (CS) until POD or unacceptable toxicity. An intermittent schedule (IS) on days 1-7 of a 28-day cycle was then evaluated after 2 cycles (n = 18) or ≥3 cycles (n = 9) of CS. Toxicity on CS managed by switch to IS. POD on IS managed by switch to CS. Results: 48 FL pts received ME-401 alone (n = 39) or with rituximab (n = 9). Median age 64.5 yrs. (range 38-81), median prior therapies 2 (range 1-10), 30 had ≥3 prior therapies and 25 were POD24. 28 pts remain on therapy with median follow-up of 9.3 months (range 0.5-22.5) and 20 discontinued: 9 POD, 4 adverse events (AEs), 4 withdrew consent, and 3 for stem cell transplant. Delayed (> Cycle 2) grade 3 immune related AEs (irAEs), primarily diarrhea/colitis and rash, reported in 9/30 (30%) on CS and 2/18 (11%) switched to IS after 2 cycles, with irAEs noted 15 and 18 days after switch. 4 pts with grade 3 irAEs had a drug holiday and corticosteroids then resumed ME-401 on IS without AE recurrence. Objective responses in 34/43 pts (79%) with follow-up disease assessment: 79% with ME-401 alone (including 26% morphologic/metabolic CR), 78% with ME-401 plus rituximab, 91% in POD24, and 75% in ≥3rd line therapy. 24/27 (89%) IS pts continue therapy, 20 on IS and 4 who switched to CS due to POD on IS, and 3 pts discontinued due to persistent POD after switch to CS. Conclusions: ME-401 achieves a high rate of durable responses in R/R FL. IS appears to reduce the incidence of irAEs and maintains responses. POD on IS can be salvaged by reverting to CS. A randomized study to evaluate ME-401 given by IS or CS is enrolling pts with R/R FL, with switch to IS for irAEs and switch to CS if POD on IS. Clinical trial information: NCT02914938. [Table: see text]
Randomized phase II study of adjuvant afatinib for three months versus two years in patients with resected stage I-III EGFR mutant NSCLC.
Authors: Chaft Jamie E. , Costa Daniel Botelho , Muzikansky Alona , Shrager Joseph B , Lanuti Michael , Huang James , Ramchandran Kavitha , Rangachari Deepa , Huberman Mark , Piotrowska Zofia , Kris Mark G. , Azzoli Christopher G. , Sequist Lecia V. , Neal Joel W. 
Published: March 2020

8507 Background: EGFR tyrosine kinase inhibitors are superior to chemotherapy in patients with advanced EGFR+ lung cancers. In the adjuvant setting, erlotinib for two years improves recurrence free survival (RFS) compared to historical controls. The optimal duration of adjuvant TKI is unknown. Methods: Patients with completely resected Stage I-III NSCLC with a sensitizing EGFR mutation were enrolled after standard adjuvant therapy. Pts were randomly assigned to 3 months (3m) or 2 years (2y) of adjuvant afatinib. Afatinib was started at 30 mg by mouth daily. Patients without toxicity after 28 days were allowed to escalate to 40 mg daily. Patients were imaged with CT every 6 months for 3 years and then annually or as clinically indicated. RFS was measured from the date of randomization. The primary study endpoint was recurrence rate at 2 years. 60 randomized patients would provide 82.5% power to detect a 26% difference in 2y-recurrence rate. Results: Patient characteristics are in the Table. The study was terminated for slow accrual after 46 of the planned 60 patients. Planned treatment was completed by 92% (22/24) pts in the 3m arm and 41% (9/22) of pt in the 2y arm. 22 patients required ≥1 dose modification due to toxicity including expected GI, mucosal, and skin AEs. With a median follow-up of ≥38 months there were 10 recurrences and 3 deaths in the 3m arm and there were 5 recurrences (2 on treatment) and 2 deaths in the 2y arm. Median RFS has not been reached in either arm, but recurrence was more common in the 3m arm at every landmark. 2y-recurrence rates were 29% for 3m and 15% for 2y. Conclusions: Recurrences at 2 years were 14% less common with 2y versus 3m of adjuvant afatinib. This difference did not meet the primary study endpoint. The RFS curves show a durable and clinically meaningful separation with substantial follow-up. Failure to meet significance was likely influenced by under-accrual and early drug discontinuation on the 2y arm. In the era of TKIs with improved tolerance, duration of adjuvant therapy remains an important question. Clinical trial information: NCT01746251. [Table: see text]
ml-RECIST: Machine learning to estimate RECIST in patients with NSCLC treated with PD-(L)1 blockade.
Authors: Arbour Kathryn Cecilia , Anh Tuan Luu , Rizvi Hira , Yala Adam , Hellmann Matthew David , Barzilay Regina 
Published: March 2020

9052 Background: Real-world evidence (RWE) is increasingly important for discovery and may be an opportunity for regulatory approval. Effective use of RWE relies on determining treatment-specific outcomes, such as overall response rate (ORR) and progression-free survival (PFS), which are challenging to accurately evaluate retrospectively and at scale. We hypothesized the use of machine learning of text radiology reports from patients with NSCLC treated with PD-1 blockade could be used to train a model that estimates RECIST-defined outcomes. Methods: 2753 imaging reports from 453 patients with advanced NSCLC treated with PD-1 blockade were collected and separated into independent training (80%, n = 362) and validation (20%, n = 92) cohorts. Reports were limited to interval of PD-1 blockade. RECIST reads performed by thoracic radiologists on all patients served as “gold standard” to determine ORR, occurrence of, and date of progression. Baseline reports were compared to all follow up reports to determine machine-learning RECIST (ml-RECIST). A four layers neural-network model for classification was proposed to solve the three above tasks. Results: In the training cohort, ml-RECIST best estimated ORR by RECIST (accuracy CR/PR 84%, SD 82%, POD 91%). ml-RECIST estimated PFS by RECIST accurately predicting progression occurred at any time (86%) and exact progression date (65%). Date of progression was closely correlated (Pearson’s r coefficient = 0.91, 95% CI:0.89-0.94, p < 0.001) in patients determined to have progressed by both methods. Similar accuracy of ml-RECIST was observed in the validation cohort (accuracy CR/PR 84%, SD 80%, POD 90%; progression occurred 86%, progression date 72%). Accuracy was consistent when RECIST reads were performed prospectively as part of clinical trials vs retrospectively for standard of care treatment (e.g. CR/PR 82% vs 88%, respectively). ml-RECIST-defined response similarly determined improvement in overall survival compared to RECIST (HR = 0.19, p < 0.001 vs HR = 0.26, p < 0.001 respectively). Conclusions: Machine learning-RECIST ("ml-RECIST") accurately estimates outcomes using imaging text reports. ml-RECIST may be tool to determine outcomes expeditiously and at scale for use in RWE studies, enabling more useful and reliable applications of large clinical databases.
Late cholecystectomy in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.
Authors: Dieffenbach Bryan V , Li Nan , Madenci Arin L , Barnea Dana , Murphy Andrew J , Tonorezos Emily S. , Gibson Todd M. , Liu Qi , Leisenring Wendy , Howell Rebecca M. , Diller Lisa , Armstrong Gregory T. , Yasui Yutaka , Oeffinger Kevin C. , Weldon Christopher Bertero , Weil Brent 
Published: March 2020

e21525 Background: Cholecystectomy (CCY) is among the most common operations performed in the developed world and is offered as a cure for symptomatic gallbladder disease. Whether survivors of childhood cancer undergo CCY at a higher rate than the general population is unknown. Methods: We identified 5-year survivors diagnosed between 1970 and 1999 who self-reported late (> 5 years after cancer diagnosis) CCY. Rates of CCY were determined among the entire cohort and in association with various risk factors and treatment exposures. Adjusted rate ratios (ARR) were estimated with multivariable piecewise exponential models. Results: Among 24,248 survivors (median follow-up 22.3, interquartile range [IQR] 16.2-30.1 years) and 5,038 siblings (median follow-up 26.4, IQR 19.3-33.7 years), the unadjusted cumulative incidence of CCY at age 50 was 7.2% (n = 757) in survivors and 6.5% (n = 168) in siblings. After adjusting for age, sex and race/ethnicity, survivors underwent CCY at higher rates compared to siblings (ARR = 1.3, 95% CI = 1.1-1.5). Relative to siblings, acute lymphoblastic leukemia survivors underwent CCY at a higher rate (ARR = 1.6, 95% CI = 1.3-2.0), all other diagnoses were not independently associated with higher rates of CCY. Among survivors, risk factors for late CCY included female sex, increasing body mass index (BMI) class, exposure to platinum agents and total body irradiation (TBI) (Table). Conclusions: CCY is performed more commonly among childhood cancer survivors relative to siblings. In addition to known risk factors for gallbladder disease, cancer treatment exposures may further enhance risk for CCY. Awareness and education regarding this observation may ensure timely diagnosis and treatment of symptomatic disease. [Table: see text]
References for Ultrasound Staging of Breast Maturation, Tanner Breast Staging, Pubic Hair, and Menarche in Norwegian Girls
Authors: Bruserud Ingvild Særvold , Roelants Mathieu , Oehme Ninnie Helén Bakken , Madsen Andre , Eide Geir Egil , Bjerknes Robert , Rosendahl Karen , Juliusson Petur B 
Published: March 2020

Abstract

Context
Discriminating adipose and glandular tissue is challenging when clinically assessing breast development. Ultrasound facilitates staging of pubertal breast maturation (US B), but has not been systematically compared to Tanner breast (Tanner B) staging, and no normative data have been reported.

Objective
To present normative references for US B along with references for Tanner B, pubic hair (PH), and menarche.

Design, Setting, and Participants
A cross-sectional sample of 703 healthy girls aged 6 to 16 years were examined.

Main Outcome Measures
Breast development was determined with US B and Tanner B staging. Tanner PH and menarcheal status were recorded. The age distributions of entry in US B, Tanner B, and PH stages and menarche were estimated with generalized linear and generalized additive models with a probit link. Method agreement was tested with weighted Cohen’s kappa.

Results
The median (±2SD) ages for thelarche, US B2 and Tanner B2, were 10.2 (7.7, 12.8) and 10.4 (8.0, 12.7) years. The median (±2SD) ages at Tanner PH2 and menarche were 10.9 (8.5, 13.3) and 12.7 (11.0, 16.2) years. Cohen’s kappa of agreement (95% confidence interval) between US B and Tanner B was 0.87 (0.85–0.88). When the methods disagreed, US B was usually more advanced.

Conclusion
Thelarche occurred at a slightly younger age when assessed with ultrasound compared to clinical Tanner staging, although the 2 methods had a very good agreement when determining pubertal breast maturation. A significant decrease of 2.8 months in age at menarche was observed during the past decade in Norwegian girls.
Patients with metabolic syndrome have a greater rate of complications after arthroplasty
Authors: Guofeng Cui , Chen Yue , Rong Wei , Ruiyu Liu , Kunzheng Wang 
Published: March 2020

Aims Patients with metabolic syndrome (MetS) are known to be at increased risk of postoperative complications, but it is unclear whether MetS is also associated with complications after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Here, we perform a systematic review and meta-analysis linking MetS to postoperative complications in THA and TKA. Methods The PubMed, OVID, and ScienceDirect databases were comprehensively searched and studies were selected and analyzed according to the guidelines of the Meta-analysis of Observational Studies in Epidemiology (MOOSE). We assessed the methodological quality of each study using the Newcastle-Ottawa Scale (NOS), and we evaluated the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Data were extracted and meta-analyzed or qualitatively synthesized for several outcomes. Results Ten cohort studies involving 1,352,685 patients were included. Qualitative analysis suggested that MetS was associated with a higher incidence of cardiovascular events, and meta-analysis showed that MetS increased the risk of all-cause complications (risk ratio (RR) 1.55, 95% confidence interval (CI) 1.28 to 1.89), surgical site infection (SSI; RR 2.99, 95% CI 1.30 to 6.90), urinary tract infection (UTI; RR 2.58, 95% CI 1.03 to 6.43), and 30-day readmission (RR 1.45, 95% CI 1.33 to 1.59). There was insufficient evidence for assessing an association between MetS and venous thromboembolism events, pulmonary or gastrointestinal complications, or mortality. Conclusion Patients with MetS undergoing THA and TKA are at increased risk of all-cause complications, cardiovascular complications, SSI, UTI, and 30-day readmission. Surgeons should be aware of the increased risk of these complications in MetS, and presurgical protocols for these complications should give special consideration to MetS patients. Cite this article: Bone Joint Res. 2020;9(3):120–129.
Voces y silencios de la tierra en la composición polifónica de las geografías ético-poéticas sur-sur
Authors: Noguera De Echeverri Ana Patricia , Bernal Arias Diana Alexandra , Echeverri Noguera Sergio Manuel 
Published: March 2020

La composición polifónica musical nos permite hablar de la emergencia, en el sur y desde el sur que somos, de Voces de la Tierra, que han susurrado, cantado, llorado o gritado el dolor producido por las maneras de habitar humanas construidas en la modernidad cosificadora de la tierra y del mundo de la vida, modernidad mercantil, industrial y global cuya ética se ha reducido a valores absolutamente euro-antropo-racional-centristas, permeados por el valor supremo del capital. En este artículo, emergente de pensadores ambientales latinoamericanos y pensadores-otros que han sospechado radicalmente del edificio de la ética ambiental emergente de la conferencia del Club de Roma o del Informe Burndtland, intentamos desplegar lo ético, como ethos con e larga, que en griego significa casa, y desde este lugar de enunciación, intentamos salirnos del sujeto y del objeto en la variación ética ambiental eurocentrista, y proponer con las voces de la tierra sur, abya yala, diseños del ethos, ligado óntica-relacionalmente con el cuerpo-tierra. Diseñamos, inspirados en Husserl, Heidegger, Deleuze, Guattari, Ángel-Maya, Enrique Leff, Noguera, Echeverri, pensadores-otros y voces de montañas, animales, ríos, y plantas, la vida, territorios de libertad entendida ésta como expansión de los cuerpos en la naturaleza y de paz integral y completa, entendiendo que no puede haber paz, si no amamos ni respetamos la tierra que somos. Esto exige el giro óntico-etico- estético-político de la ética en clave de un Pensamiento Ambiental Sur.
Pentagamavunon-0 (PGV-0) Enhance Cytotoxic Effect of Doxorubicin through Increasing of Apoptosis, Senescence and ROS Level on Triple Negative Breast Cancer 4T1
Authors: Hadi Ismanurrahman , Jenie Riris Istighfari , Meiyanto Edy 
Published: March 2020

TNBC, one of the sub type of breast cancers was widely known with high tumorigenic and poor prognosis than others. The development of combination agent (co-chemotherapy) with doxorubicin for chemotherapy of TNBC were carried out to decrease doxorubicin side effect and resistance in cancer. This present study aims to explore the co-chemotherapeutic properties of PGV-0 and investigate induction of doxorubicin on apoptosis, senescence and ROS against TNBC. 4T1 Cell line were used as a TNBC in vitro model. Cytotoxic measurement was performed using MTT assay resulting in IC50 values of 52 μM. Meanwhile, the combination of doxorubicin and PGV-0 showed synergistic effect which decreased cell viability of 4T1 better than single treatment of doxorubicin. Apoptosis analysis was performed using annexin V/PI assay indicated that the combination treatment of PGV-0 and doxorubicin increased apoptosis evidence. Senescence detection was carried out using senescence-associated-β galactosidase (SA-β-gal) assay. The results showed that a single treatment of PGV-0 induced cellular senescence and increased senescence cells in combination treatment. Moreover, DCFDA staining showed that PGV-0 increased ROS level at single treatment, whereas combination treatment increased ROS intracellular compared to the positive control of doxorubicin. Based on these results, PGV-0 has potential as a co-chemotherapeutic candidate on TNBC.Keyword: 4T1, PGV-0, Co-chemotherapy, Cytotoxic, Senescence, Apoptosis, ROS
Trump’s Trade Revolution
Authors: Mastanduno Michael 
Published: March 2020

AbstractThe Trump administration has reversed a 70-year consensus and transformed both the substance of trade policy and the postwar role the US has played in its global management. It has also reconfigured the role of the president in the domestic trade policy process. Armed with the power and influence the US amassed during its long run as leader of the post-war liberal world economy, the Trump administration has used trade as its principle coercive weapon in foreign policy. It has achieved some success, albeit at high diplomatic cost and by putting at risk America’s long-standing structural advantages in the world economy. Given that domestic discontent with the liberal world economy has increased significantly, it is likely that the core aspects of Trump’s trade revolution will endure, even if subsequent administrations soften Trump’s provocative execution of it.
Effect of OPC on Fiber Nonlinearities for Dense Soliton Optical Communication Medium
Authors: Kumar Ghanendra , Kumar Chakresh 
Published: March 2020

Abstract
This review paper scrutinizes the staging of dense wavelength division multiplexing soliton system in return to zero and non-return to zero format. In-line optical phase conjugator (OPC) is used to depreciate the power of four wave mixing (FWM). Destructive interference between both the halves of in-line OPC plummets the FWM power sturdily. This paper concludes with the indication that return-to-zero with OPC gives out better performance with FWM suppression.
Should Liberal-Egalitarians Support a Basic Income? An Examination of the Effectiveness and Stability of Ideal Welfare Regimes
Authors: Sirsch Jürgen 
Published: March 2020

Abstract
The article deals with the question whether an unconditional basic income (UBI) is part of an ideal liberal-egalitarian welfare regime. Analyzing UBI from an ideal-theoretical perspective requires a comparison of the justice performance of ideal welfare regimes instead of comparing isolated institutional designs. This holistic perspective allows for a more systematic consideration of issues like institutional complementarity. I compare three potential ideal welfare regimes from a liberal-egalitarian perspective of justice: An ideal social democratic regime, a mixed regime containing a moderate UBI and a maximal UBI regime where UBI replaces most of the welfare state. These regimes are evaluated with respect to three aspects of justice performance: the scope and neutrality of opportunities provided, institutional complementarities with a dynamic, globalized economy and the policy feedback effects on the political stability of liberal-egalitarian political coalitions. I conclude that the overall performance of a mixed regime is superior to the other regimes.