tbuckley/cabot-search huggingface dataset:
If at First You Don't Succeed
Authors: Jonathan M. Ross, Harold C. Sox
Journal: New England Journal of Medicine (1995)

A 22-year-old, non–English-speaking Laotian woman came to the clinic because she had abdominal pain. The history was obtained with her husband acting as interpreter. The pain was epigastric, described as a heartburn, and was somewhat relieved by eating and episodic use of antacids. She had had the pain intermittently for weeks or months during the previous two years. She reported no tobacco or alcohol use. She used antacids and occasionally used ibuprofen for headaches. She had immigrated to the United States five months earlier and had presented to a gynecology clinic requesting oral contraceptives. She was not taking any . . .
Outcomes in chronic lymphocytic leukemia (CLL) patients with NOTCH1 signaling pathway mutations.
Authors: Daniel R. Helbig, Ghaith F Abu Zeinah, Erica B. Bhavsar, John N. Allan
Journal: Journal of Clinical Oncology (2019)

7524 Background: NOTCH1 is one of the most frequently mutated genes in CLL and has emerged as a marker of poor prognosis. Additional mutations in the NOTCH1 signaling pathway, specifically MED12, FBXW7, and SPEN, have been identified in CLL but their clinical significance has yet to be fully determined. We evaluated the clinical outcome of time to first treatment (TTFT) to compare patients with mutations to those who are wild type for NOTCH1, MED12, FBXW7, and SPEN, hypothesizing that patients with these mutations will behave similarly to NOTCH1 mutated patients and have a shorter TTFT. Methods: We conducted a single center retrospective database review of 506 patients diagnosed with CLL from 1980 to 2018 who underwent whole exome profiling between 2015 to 2018 with a lymphoid specific 75-gene next generation sequencing (NGS) panel (Genoptix Inc). The TTFT was estimated using Kaplan-Meier methods, and the difference between groups was compared using the log-rank test. Multivariate analysis (MVA) was performed with Cox proportional hazards regression. Results: Of the 506 patients who underwent NGS testing, 121 (23.9%) had at least one mutation in the NOTCH1 signaling pathway. These patients were diagnosed at an older age (62.0 years vs. 60.0 years, p=0.04) and had higher rates of CD38 positivity (40.9% vs. 22.9%, p≤0.001), Trisomy 12 (36.0% vs. 15.8%, p≤0.001), and IGVH unmutated status (71.3% vs. 44.1%, p≤0.001). They also had a shorter TTFT with a median of 3.93 years compared to 5.02 years in patients without any mutation in the NOTCH1 signaling pathway (p=0.002). In MVA, IGVH unmutated status and CD38 positivity remained independently predictive for TTFT. Conclusions: We identified three mutations in genes associated with regulation of NOTCH1 signaling that appear to signify poor prognosis, predict for a shorter TTFT, and associate with similar baseline factors that NOTCH1 does such as Trisomy 12 and IGVH unmutated status. NOTCH1 mutated patients have poor response to chemoimmunotherapy and are associated with aggressive disease biology. Future research is needed to determine whether mutations in MED12, FBXW7, or SPEN may also predict for poor response to frontline chemoimmunotherapy or novel agents currently used in CLL.
Treatment of Congenital Deformities of the Hand and Forearm
Authors: Richard J. Smith, Robert W. Lipke
Journal: New England Journal of Medicine (1979)

(Second of Two Parts)Failure of Separation of PartsWebbing Webbing of the fingers is among the more common congenital anomalies of the hand.95 Webbing between fingers of disparate length causes rotation and angulation that may worsen unless the fingers are released early. If all fingers are webbed, as with Apert's syndrome96 or with patients who lack several digits, the border digits may be released as early as six months of age to allow the hand to be used for grasp. When simple syndactyly does not interfere with the growth or function of the hand, surgical release may be postponed . . .
Serial assessment of cell-free circulating tumor DNA (ctDNA) to assess treatment effect and minimal residual disease during neoadjuvant and adjuvant therapy in colorectal cancer
Authors: A. Parikh, E. Van Seventer, G. Boland, A. Hartwig, A. Jaimovich, V. Raymond, A. Talasaz, R. Corcoran
Journal: Annals of Oncology (2019)
Trends in Foster Care Entry Among Children Removed From Their Homes Because of Parental Drug Use, 2000 to 2017
Authors: Angélica Meinhofer, Yohanis Angleró-Díaz
Journal: JAMA Pediatrics (2019)

Correction: This article was corrected on August 19, 2019, to fix 2 labels switched in the Figure .The label "Entries owing to parental drug use" was positioned over the line that indicated the proportion of foster care entries owing to parental drug use, and the label "Proportion of entries owing to parental drug use" was positioned over the line indicating the total number of foster care entries owing to parental drug use.The labels have been moved to the correct positions.
Operative versus non-operative treatment for 2-part proximal humerus fracture: A multicenter randomized controlled trial
Authors: Antti P. Launonen, Bakir O. Sumrein, Aleksi Reito, Vesa Lepola, Juha Paloneva, Kenneth B. Jonsson, Olof Wolf, Peter Ström, Hans E. Berg, Li Felländer-Tsai, Karl-Åke Jansson, Daniel Fell, Inger Mechlenburg, Kaj Døssing, Helle Østergaard, Aare Märtson, Minna K. Laitinen, Ville M. Mattila
Journal: PLoS Medicine (2019)

Background Although increasingly used, the benefit of surgical treatment of displaced 2-part proximal humerus fractures has not been proven. This trial evaluates the clinical effectiveness of surgery with locking plate compared with non-operative treatment for these fractures. Methods and findings The NITEP group conducted a superiority, assessor-blinded, multicenter randomized trial in 6 hospitals in Finland, Estonia, Sweden, and Denmark. Eighty-eight patients aged 60 years or older with displaced (more than 1 cm or 45 degrees) 2-part surgical or anatomical neck proximal humerus fracture were randomly assigned in a 1:1 ratio to undergo either operative treatment with a locking plate or non-operative treatment. The mean age of patients was 72 years in the non-operative group and 73 years in the operative group, with a female sex distribution of 95% and 87%, respectively. Patients were recruited between February 2011 and April 2016. The primary outcome measure was Disabilities of Arm, Shoulder, and Hand (DASH) score at 2-year follow-up. Secondary outcomes included Constant–Murley score, the visual analogue scale for pain, the quality of life questionnaire 15D, EuroQol Group's 5-dimension self-reported questionnaire EQ-5D, the Oxford Shoulder Score, and complications. The mean DASH score (0 best, 100 worst) at 2 years was 18.5 points for the operative treatment group and 17.4 points for the non-operative group (mean difference 1.1 [95% CI −7.8 to 9.4], p = 0.81). At 2 years, there were no statistically or clinically significant between-group differences in any of the outcome measures. All 3 complications resulting in secondary surgery occurred in the operative group. The lack of blinding in patient-reported outcome assessment is a limitation of the study. Our assessor physiotherapists were, however, blinded. Conclusions This trial found no significant difference in clinical outcomes at 2 years between surgery and non-operative treatment in patients 60 years of age or older with displaced 2-part fractures of the proximal humerus. These results suggest that the current practice of performing surgery on the majority of displaced proximal 2-part fractures of the humerus in older adults may not be beneficial. Trial registration ClinicalTrials.gov NCT01246167.
Heterogeneity of Plaque Structural Stress Is Increased in Plaques Leading to MACE
Authors: Charis Costopoulos, Akiko Maehara, Yuan Huang, Adam J. Brown, Jonathan H. Gillard, Zhongzhao Teng, Gregg W. Stone, Martin R. Bennett
Journal: JACC. Cardiovascular imaging (2019)

This study sought to determine if plaque structural stress (PSS) and other plaque stress parameters are increased in plaques that cause future major adverse cardiovascular event(s) (MACE) and if incorporating these parameters improves predictive capability of intravascular ultrasonography (IVUS).Less than 10% of coronary plaques identified as high-risk by intravascular imaging result in subsequent MACE. Thus, more specific measurements of plaque vulnerability are required for effective risk stratification.Propensity score matching in the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study plaque cohort resulted in 35 nonculprit lesions (NCL) associated with future MACE and 66 matched NCL that remained clinically silent. PSS was calculated by finite element analysis as the mechanical loading within the plaque structure in the periluminal region.PSS was increased in the minimal luminal area (MLA) regions of NCL MACE versus no MACE plaques for all plaques (PSS: 112.1 ± 5.5 kPa vs. 90.4 ± 3.3 kPa, respectively; p = 0.001) and virtual histology thin-cap fibroatheromas (VH-TCFAs) (PSS: 119.2 ± 6.6 kPa vs. 95.8 ± 5.0 kPa, respectively; p = 0.005). However, PSS was heterogeneous over short segments, and PSS heterogeneity index (HI) was markedly greater in NCL MACE than in no-MACE VH-TCFAs (HI: 0.43 ± 0.05 vs. 0.29 ± 0.03, respectively; p = 0.01). Inclusion of PSS in plaque assessment improved the identification of NCLs that led to MACE, including in VH-TCFAs (p = 0.03) and plaques with MLA ≤4 mm2 (p = 0.03). Incorporation of an HI further improved the ability of PSS to identify MACE NCLs in a variety of plaque subtypes including VH-TCFA (p = 0.001) and plaques with MLA ≤4 mm2 (p = 0.002).PSS and variations in PSS are increased in the peri-MLA regions of plaques that lead to MACE. Moreover, longitudinal heterogeneity in PSS is markedly increased in MACE plaques, especially VH-TCFAs, potentially predisposing to plaque rupture. Incorporation of PSS and heterogeneity in PSS may improve the ability of IVUS to predict MACE.
Patterns of docetaxel application in breast cancer patients from China: Experience in 42 cancer centers.
Authors: Binghe Xu
Journal: Journal of Clinical Oncology (2012)

e11537 Background: Docetaxel is considered as a fundamental drug in the treatment of breast cancer. It has been extensively incorporated into the neoadjuvant, adjuvant and metastatic treatment. The aim of this study was to investigate how breast cancer patients are treated with docetaxel in China. Methods: A retrospective review of chemotherapy with docetaxel performed from 2009 to 2011 was carried out in China. Study included all patients diagnosed with invasive breast cancer and treated with docetaxel-containing regimens in forty-two cancer centers from 12 provinces in China. Regimens were compared in different subgroups based on stage, subtype, and lymph node (LN) status. Patterns of chemotherapy were also compared to published guidelines. Results: Among 2188 breast cancer patients treated with docetaxel, 1881 (86.0%) were in adjuvant or/and neoadjuvant setting (including 91 in both settings). The mean age was 48.7 (range, 14-82). Compared with 288 patients using docetaxel as single agent therapy, more patients (86.8%) used docetaxel-containing combination regimens. The mean cycle administered and dose for every cycle was 4.8 and 73.0 mg/m 2 , respectively. Dose reduction and delay occurred in 409 (19.7%) patients mainly due to non-medical factors (10.9%) and hematologic toxicity (5.9%). TAC, TA, TC, TX, and AC-T regimens were given in 34.8%, 19.7%, 17.4%, 5.3%, and 2.2% of patients respectively. TAC was used more frequently in triple-negative breast cancer (TNBC) than other patients (43.0% vs. 32.7%, P=0.004). In the (neo)adjuvant setting, TAC regimen was used more frequently in LN-positive patients than LN-negative group (44.2% vs. 30.0%, P&lt;0.001). Of 1682 patients in adjuvant setting, 729 (43.3%) were treated with triplet (TAC or AC-T). In 290 patients receiving neoadjuvant chemotherapy, only 94 (32.4%) used TAC and none used AC-T (P=0.013). Conclusions: Docetaxel was widely used in the treatment of breast cancer in China, especially in the (neo)adjuvant setting. TAC regimen was the most frequent option, especially in patients with TNBC or LN-positive BC. Although AC-T was also recommended in adjuvant setting by most guidelines, it was less commonly used compared to TAC regimen in China.
ZUMA-12: A phase 2 multicenter study of axicabtagene ciloleucel (axi-cel) as a first-line therapy in patients (pts) with high-risk large B-cell lymphoma (LBCL).
Authors: Sattva Swarup Neelapu, Julio C. Chavez, Yi Lin, Javier Munoz, Chaitra Shankar Ujjani, Peter Riedell, Sven De Vos, Olalekan O. Oluwole, Natasha Kekre, Yin Yang, Lovely Goyal, Kate Backhouse, Francesca Milletti, Jun Kawashima, Alex Francisco Herrera
Journal: Journal of Clinical Oncology (2019)

TPS7574 Background: Pts with LBCL who have persistent disease assessed by dynamic PET after rituximab-based induction therapy have an increased risk of death (Casasnovas, et al. Blood. 2017). Axi-cel is an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy approved for the treatment of pts with relapsed/refractory LBCL with ≥ 2 prior systemic therapies. In ZUMA-1, the registrational study of axi-cel in pts with refractory LBCL, the objective response rate (ORR) was 91% (70% complete response [CR] rate) in pts with double-expressor or high-grade LBCL with ongoing responses in 48% after a median follow-up of 27.1 mos (Locke FL, et al. Lancet Oncol 2019). Furthermore, pts with fewer prior lines of therapy and lower tumor burden had higher rates of ongoing responses and manageable safety (Locke et al. ASCO 2018. 3039). ZUMA-12 will investigate the efficacy and safety of axi-cel as a first-line therapy in newly diagnosed pts with high-risk LBCL who have PET-positive disease after 2 cycles of induction therapy. Methods: This Phase 2 study has a planned enrollment of ≈40 pts aged ≥ 18 y with high-risk LBCL, defined by the presence of MYC and BCL2 and/or BCL6 translocations by FISH or an IPI score ≥ 3 any time before enrollment, and an ECOG performance status of 0 – 1. Before enrollment, pts must have a Deauville score of 4 – 5 (Barrington SF et al. J Clin Oncol. 2014) after 2 cycles of chemoimmunotherapy that includes an anti-CD20 monoclonal antibody and anthracycline. After leukapheresis, pts with bulky or rapidly progressing disease may receive optional non-chemotherapy bridging therapy. Following conditioning therapy with cyclophosphamide (500 mg/m 2 ) and fludarabine (30 mg/m 2 ) for 3 days, pts will receive a single infusion of axi-cel at a target dose of 2 × 10 6 CAR T cells/kg. The primary endpoint is investigator-assessed CR rate per the Lugano classification (Cheson et al. J Clin Oncol. 2014). Key secondary endpoints include ORR, duration of response, event-free survival, progression-free survival, overall response, safety, relapse with CNS disease and levels of blood CAR T cells and serum cytokines over time. Accrual is ongoing. Clinical trial information: NCT03761056.
Abstract #2774: The fully human EGFR antibody IMC-11F8 significantly increases the antitumor effects of cisplatin+gemcitabine in human non-small cell lung cancer models
Authors: Marie Prewett, Rajiv Bassi, Hagop Youssoufian, Eric Rowinsky, James Tonra
Journal: Cancer Research (2009)

Platinum based chemotherapy regimens have demonstrated superior or equivalent efficacy to that of alternative combination chemotherapy regimens in non-small cell lung cancer (NSCLC) patients. One agent currently combined with platinum for the treatment of NSCLC is gemcitabine, which increased response rates and median survival. In spite of the benefits of third generation chemotherapies such as gemcitabine in NSCLC patients, significant breakthroughs in reducing the poor prognosis of this disease have not occurred. The epidermal growth factor receptor (EGFR) is expressed in 40-80% of NSCLC biopsies, and agents targeting EGFR have demonstrated therapeutic benefits in NSCLC patients. IMC-11F8 is a fully human EGFR targeted monoclonal antibody developed at ImClone Systems Incorporated that is being advanced towards phase III clinical testing in metastatic colorectal cancer and NSCLC patients. In the present research, we evaluate the benefits of adding IMC-11F8 to a cisplatin+gemcitabine combination regimen in preclinical NSCLC models. We first established a maximum tolerated dose (MTD) for [cisplatin+gemcitabine] combination therapy in athymic mice by using pairwise combinations of cisplatin at 7, 5, and 3 mg/kg with gemcitabine at 500, 100, or 50 mg/kg, both administered IP, q7d. The maximum tolerated dose (MTD) of this combination in mice was determined to be cisplatin at 3mg/kg + gemcitabine at 500mg/kg. This MTD was combined with IMC-11F8 (40 mg/kg, IP, Mon-Wed-Fri) in two models of NSCLC, established by injecting A549 or NCI-H1650 human NSCLC cells subcutaneously into the left flank of female athymic nu/nu mice. Treatment with IMC-11F8 + [cisplatin+gemcitabine] significantly inhibited the growth of xenograft tumors compared to either therapy alone. In A549 tumors, the T/C% for combination therapy was 18% versus 50% and 58% for IMC-11F8 and [cisplatin+gemcitabine], respectively. Partial tumor regression occurred in 33% of IMC-11F8 +[cisplatin+gemcitabine] treated mice, but did not occur in monotherapy treated mice. In the NCI-H1650 tumor model, the T/C% for combination therapy was 16% compared to 39% for IMC-11F8 monotherapy and 54% for [cisplatin+gemcitabine]. Partial tumor regression frequency increased from 0-8% in monotherapy treated mice to 58% in mice treated with IMC-11F8 + [cisplatin+gemcitabine]. In conclusion, results support the addition of IMC-11F8 to [cisplatin+gemcitabine] for the treatment of NSCLC.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2774.
Optimization of transdermal deferoxamine leads to enhanced efficacy in healing skin wounds
Authors: Dominik Duscher, Artem A. Trotsyuk, Zeshaan N. Maan, Sun Hyung Kwon, Melanie Rodrigues, Karl Engel, Zachary A. Stern-Buchbinder, Clark A. Bonham, Janos Barrera, Alexander J. Whittam, Michael S. Hu, Mohammed Inayathullah, Jayakumar Rajadas, Geoffrey C. Gurtner
Journal: Journal of Controlled Release (2019)
Landscape of FMS-like tyrosine kinase 3 (FLT3) and associated molecular alterations in 44,766 gastrointestinal (GI) cancers
Authors: M. Salem, L. Juckett, A. Schrock, J. Ross, A. Puccini, A. Grothey, J. Lee, V. Miller, R. Madison, S. Ali
Journal: Annals of Oncology (2019)
Helical Hydrogel Nanofibers: Microfluidic Fabrication of Biomimetic Helical Hydrogel Microfibers for Blood‐Vessel‐on‐a‐Chip Applications (Adv. Healthcare Mater. 13/2019)
Authors: Luanluan Jia, Fengxuan Han, Huili Yang, Gareth Turnbull, Jiayuan Wang, Jon Clarke, Wenmiao Shu, Mingyu Guo, Bin Li
Journal: Advanced Healthcare Materials (2019)

In article number 1900435 by Bin Li and co-workers, various complex helical structures and cell-laden hydrogel microfibers are fabricated using microfluidics-based technology. Human umbilical vein endothelial cells (HUVECs) can grow in the inner wall of hollow microfibers and form lumen similar to natural blood vessels. Helical cell tubes can also be prepared to mimic helical blood vessels. Such cell-laden microfibers hold great potential in blood-vessel-on-a-chip applications.
William Charles Donald Lovett
Authors: Jonathan Lovett
Journal: BMJ (2019)

William Charles Donald Lovett (“Donald”) was born in Ystradowen in the Vale of Glamorgan, the eldest son of two school teachers. He was educated at Caerleon, where his father was headmaster, and then at West Monmouthshire Grammar School in Pontypool. He obtained his undergraduate medical degrees at the Welsh National School of Medicine, Cardiff and, as an external student, at London University, both in 1942. Wartime demands for army doctors led to a shortened period as a qualified house officer (three months), and in November 1942 he was called up for military service. Training at the Royal Army Medical Corps depot at Aldershot ensued; his memoirs note that this was on an entirely gender mixed basis. He was posted to Nigeria, where he was initially put in charge of Number 1 Detention Hospital in Zungeru. He was scathing about such “detention hospitals,” which seemed to have no function and limited equipment. Consequently he spent most of his time assisting the regimental medical officer of the locally based pioneer unit. After an inspection by the director of medical services the hospital was closed down, and Donald was posted to Number 1 Primary Training Centre at Zaria. He dealt with all medical aspects relating to recruits to the Nigerian part of the West African Frontier Force, which served principally in Burma. While there he learned to ride by playing polo. He commented that it was fortunate that this was during the wet season when the ground was soft!

In April 1945 Donald returned to the UK on leave and then was posted to the 47th Light Division. These airborne troops were intended to land behind Japanese lines to assist the re-conquest of Malaysia. However, while Donald was on embarkation leave, the atom bomb was dropped and the war ended. Donald was then …
A C19MC-LIN28A-MYCN Oncogenic Circuit Driven by Hijacked Super-enhancers Is a Distinct Therapeutic Vulnerability in ETMRs: A Lethal Brain Tumor
Authors: Patrick Sin-Chan, Iqra Mumal, Tannu Suwal, Ben Ho, Xiaolian Fan, Irtisha Singh, Yuchen Du, Mei Lu, Neilket Patel, Jonathon Torchia, Dean Popovski, Maryam Fouladi, Paul Guilhamon, Jordan R. Hansford, Sarah Leary, Lindsey M. Hoffman, Jean M. Mulcahy Levy, Alvaro Lassaletta, Palma Solano-Paez, Eloy Rivas, Alyssa Reddy, G. Yancey Gillespie, Nalin Gupta, Timothy E. Van Meter, Hideo Nakamura, Tai-Tong Wong, Young-Shin Ra, Seung-Ki Kim, Luca Massimi, Richard G. Grundy, Jason Fangusaro, Donna Johnston, Jennifer Chan, Lucie Lafay-Cousin, Eugene I. Hwang, Yin Wang, Daniel Catchpoole, Jean Michaud, Benjamin Ellezam, Ramya Ramanujachar, Holly Lindsay, Michael D. Taylor, Cynthia E. Hawkins, Eric Bouffet, Nada Jabado, Sheila K. Singh, Claudia L. Kleinman, Dalia Barsyte-Lovejoy, Xiao-Nan Li, Peter B. Dirks, Charles Y. Lin, Stephen C. Mack, Jeremy N. Rich, Annie Huang
Journal: Cancer Cell (2019)