bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathologic predictors of the 21-gene assay in a Hispanic cohort
Authors: Khan A. , Rodriguez C. , Tovar Y. E. , Rajabi B. , Mulla Z. D. , Hakim M. N. 
Published: August 2020

e22209 Background: The 21-gene recurrence score (RS) assay became commercially available (Oncotype DX) in January 2005. It is used to predict the likelihood of distant recurrence in women with estrogen-receptor (ER)-positive, lymph node-negative invasive breast cancer treated with adjuvant tamoxifen. We aimed to identify clinicopathologic predictors of an elevated recurrence score in a group of women with invasive breast cancer living in a predominantly Hispanic population on the Texas-Mexico border. Methods: A retrospective cohort study of 60 consecutive patients with primary ER-positive, lymph node-negative invasive breast cancer who had an Oncotype DX assay performed by Genomic Health, Inc. on paraffin-embedded tumor between March 2006 and November 2008. ER, PR and HER-2 was performed by immunohistochemistry. Patients were classified as low RS (<18), intermediate RS (18–30), or high RS (≥31). Ordinal logistic regression was used to calculate odds ratios (OR) for an increasing RS. Patient age and tumor pathological features were documented in each group. There was no selection bias in ordering the assay. Results: 95% of the cohort was Hispanic. Average age was 55.5 years. 29 patients (48%) had a low RS, 15 (25%) had an intermediate RS, while 16 (27%) had a high RS. HER-2 was amplified in 8 patients (13%). HER-2 positivity was strongly associated with a high RS (p<0.0001). Tumor grade and Ki-67 proliferative index were correlated with one another in a positive fashion (weighted kappa=0.46, p<0.05) and in univariate analyses both factors were significant predictors of a higher RS: tumor grade 3 vs. 1 OR=26.6 (p<0.0001) and Ki-67 proliferative index high vs. low OR=6.59 (p=0.0033). After adjustment, neither OR was significant. A negative progesterone receptor (PR) status was a strong risk factor for a higher RS (adjusted OR=21.64, p=0.0002). Univariate and multivariate ORs for higher RS for invasive ductal vs. invasive lobular carcinoma were, respectively, 4.3 (p=0.051) and 2.23 (p=0.4). Conclusions: Initially, a tumor grade of 3 and a high Ki-67 proliferative index were strong risk factors for a higher RS. However, after controlling for multiple factors, neither tumor grade nor Ki-67 proliferative index had an impact on RS in this predominantly Hispanic cohort. No significant financial relationships to disclose.
Identification of potential diagnostic markers in bronchial fluid of patients with non small cell lung cancer (NSCLC)
Authors: Lopez-Vivanco G. , Muñoz A. , Carrera S. , Zalacain R. , Uribarri M. , Algorta J. , Calvo B. , Aresti U. , Buque A. , Mielgo X. 
Published: August 2020

e22216 Background: Early diagnosis in lung cancer could improve its treatment and, subsequently, its prognosis and survival. New proteomic techniques can identify potential diagnostic and prognostic markers. The aim of this study was to find protein markers in bronchial fluid which could enable early diagnosis in NSCLC. Methods: We have included 96 patients with NSCLC diagnosed using bronchoscope (64 scamous/29 adenocarcinoma/3 others) and 49 consecutive patients with non pathological bronchoscope. Bronchial fluid was obtained from each patient and potential protein markers were studied. Bronchial fluid was centrifuged and supernatant proteins were analysed using bidimensional electrophoresis with poliacrilamid gel stained with silver nitrate. Gel was scanned and analysed with Progenesis PG6220 program, which measures intensity of each spot. Resultant intensities in each group of patients (NSCLC/non pathological bronchoscope) were compared using T-Student method. We selected as potential markers those spots with a p value of less than 0.05. We calculated “fold change” of each spot as the ratio between mean intensity in NSCLC bronchoscopes samples and non pathological bronchoscopes samples. Results: We analysed 300 spots in each sample and we found 31 potential markers whose fold-change ranges from 1.49 to 7.41; 15 of the markers were expressed in a higher level in NSCLC samples and the other 16 were expressed in a lower level. Conclusions: We have identified 31 differential protein markers in bronchial fluid among our patients. These results could lead in an early diagnostic test which must be validated in future studies. No significant financial relationships to disclose.
The prognostic importance of triple negative breast cancer: A population based study in India
Authors: Ajaikumar B. S. , Rao R. , Prabhu J. , Kulkarni J. D. , K P. , V Patil G. , Nr N. , Babu C. , Sahoo R. 
Published: August 2020

e22219 Background: Triple-negative (ER-negative, PR-negative, HER2/neu negative) breast cancer has distinct clinical and pathologic features, and is a clinical problem because of its typically high grade, relatively poor prognosis, aggressive behavior and lack of targeted therapies leaving chemotherapy as the mainstay of treatment. This study envisaged to analyse the influence of triple negativity status on survival and disease free survival in prospective cohort of breast cancer patients. Methods: Breast tumors of 215 women aged 30–75, diagnosed from 2004 were tested for ER, PR and HER2 positivity by immunohistochemistry and correlated with clinical outcomes such as recurrence, disease free survival and overall survival using Kaplan Meiers Survival analysis and Coxs regression analysis. The study cohort was followed up for 60 months or until death whichever was earlier. Results: Triple negativity significantly influenced disease free survival (46 ± 3, 41, 52) vs. non triple negative cohort (mean ± SE; 95%CI, 37 ± 2; 32, 40) and log rank = 2.1, p = 0.04. However triple negativity did not influence overall survival in months (56 ± 0; 55, 56) vs. non triple negative cohort (43 ± 1; 42, 45), (log rank = 1.78, p = 0.16). However, the mean disease free survival was (45 ± 7; 32, 58) months for patients >40 years age vs (37 ± 4; 33, 39) for patients < 40 years of age (log rank = 2.87, p =0.02). Stage of disease, node status, grade and menopausal status did not influence disease free survival significantly. However, Cox regression analysis did not predict significant effects of triple negativity on overall survival or disease free survival when controlled for confounding factors such as age, node status, stage etc Conclusions: Our observations suggest that triple negativity can significantly affect progression of breast cancer in Indian breast cancer patients and longer follow up is necessary (10 years) to determine its effects on survival. No significant financial relationships to disclose.
Exploratory study of the subcutaneous fat gene expression profile in patients with metastatic pancreatic carcinoma treated with standard gemcitabine chemotherapy regimen
Authors: Castellano D. E. , Gomez-Martin C. , Cubedo Cervera R. , Garcia Lopez J. , Gomez-Sanz R. , Gravalos C. , Nuñez Sobrino J. , Cortes-Funes H. 
Published: August 2020

e22220 Background: Most clinical trials are designed to assess the antitumor effect of the chemoterapeutic intervention. There are few examples where the endpoint is to assess the biology of the host response to the treatment of the tumor. A large number of patients with pancreatic cancer present features of the cachexia syndrome and specially a marked weight loss. It has been postulated that a “cytokine storm” is the cause of the profound effect that this cancer has on distant tissues. This trial analyzed changes in the subcutaneous fat gene expression profile in relation with the clinical benefit variable with standard gemcitabine (G) treatment. Methods: Patients with histology confirmed advanced pancreatic cancer, adequate organ function and written informed consent. Eligible pts were intended for a subcutaneous fat biopsy pretreatment and after 7 weeks of gemcitabine 1000 mg/m2 together with response assessment. Clinical benefit (CB) (pain, analgesic consumption, Karnofsky and weight), QLQ-C30, serum cytokines and tumor markers were evaluated pretreatment, at 4 and 8 weeks. Fat gene expression profile was analyzed using Affimetrix U133Plus2.0 with the corresponding bioinformatic software. Serum cytokines where analyzed with xMAP technology with the Luminex 200 platform. Results: 16 pts [8 m, 8 f, median age 62 yrs (range 47–72)]. Median weight change -0.75 kg (range -4.5 to 2). Nine pts had pre and post treatment biopsies and 7 only pretreatment. Three pts achieved CB at 8 weeks. Objective responses: 0 CR, 0 PR, 31% SD and 68%PD. Toxicity was similar to the one reported in gemcitabine's label. It was possible to extract quality RNA for microarray from subcutaneous fat use from all samples but 1. The limited number of samples precluded to obtain genes clearly involved in cachexia, however the IL-8 expression (p0.03) was significantly correlated with CB response either to gene and serum profile. Conclusions: It is feasible to study prospectively the impact of cancer treatment on different tissue biomarkers and correlated with standard antitumor evaluation system. The reduced number of samples in this exploratory trial precludes producing significant biological conclusions. No significant financial relationships to disclose.
Effect of erlotinib on platelet activation in patients with non-small cell lung cancer
Authors: Yamaguchi K. , Kanazawa S. , Sasada S. , Hirashima T. , Imamura F. , Nomura S. 
Published: August 2020

e22232 Background: Previously we reported that serum levels of soluble P-selectine and thromboxane (TX) B2 elevated in the patients with lung cancer treated with gefitinib and low dose aspirin improved skin eruption. We measured the serum levels of TXB2 in patients with NSCLC. Methods: Serial blood samples were withdrawn from each patient before and after the administration of erlotinib. TXB2 was measured by enzyme-linked immuno solvent assay. The kit was used according to the manufacturer's instructions. Results: The serum levels of TXB2 were elevated after treatment with erlotinib. Two cases developed skin lesion then treated with low dose aspirin. Skin lesions were better with improving itching without disease progression. Conclusions: We think that platelets activity, COX-1, COX-2 and PGI2 / TXA2 ratio are one of factor of anti-cancer and adverse effect for EGFR-TKI. And low dose aspirin may be useful for adverse effect of erlotinib and other EGFR-TKI. No significant financial relationships to disclose.
Adjuvant radiotherapy and regional lymph node field control in melanoma patients after lymphadenectomy: Results of an intergroup randomized trial (ANZMTG 01.02/TROG 02.01)
Authors: Henderson M. A. , Burmeister B. , Thompson J. F. , Di Iulio J. , Fisher R. , Hong A. , Scolyer R. , Shannon K. , Hoesktra H. , Ainslie J. 
Published: August 2020

LBA9084 The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology. No significant financial relationships to disclose.
Impact of Preconception Treatment Initiation for Hypothyroidism on Neurocognitive Function in Children
Authors: Zhou Qiongjie , Wang Chunfang , Xu Huan , Li Xiaotian 
Published: August 2020

Abstract

Context
Levothyroxine treatment for hypothyroidism in early pregnancy has inconsistent outcomes.

Objective
This study evaluated children’s cognitive function to ascertain the impact of preconception maternal hypothyroidism treatment on fetal neurodevelopment.

Design and Setting
This prospective, single-center cohort study was conducted at a tertiary-care hospital.

Patients
Women were assigned to the before conception (BC) and after conception (AC; 8-14 gestational weeks) groups by time point of hypothyroidism diagnosis and treatment.

Interventions
Levothyroxine treatment was adjusted based on results of a monthly thyroid function test.

Main Outcome Measures
The Gesell Development Diagnosis Scale (GDDS; Chinese version) was used to assess neurocognitive development of children at age 6, 12, and 24 months, with total score as the primary outcome.

Results
Of the 466 participants, 187 and 279 were in the BC and AC groups, respectively. Both groups were comparable at baseline antenatal visit, except for a higher proportion of thyroid peroxidase (TPO) antibody-positive participants in the BC group (P &lt; .001). No significant intergroup differences were evident on the GDDS neurodevelopmental assessment at age 6, 12, and 24 months (P &gt; .05), except for unexpected slightly lower motor ability (P = .009) and total (P = .026) scores at 12 months and adaptability at 24 months (P = .037) in the BC group. Differences for motor ability (P &lt; .001) and total score (P = .026) persisted on subgroup analysis for subclinical hypothyroidism, without significant differences in pregnancy and neonatal outcomes by severity and TPO status (P &gt; .05).

Conclusions
Preconception levothyroxine treatment did not induce significantly better cognitive outcomes in children up to age 2 than treatment initiated at 8 to 14 weeks of gestation.
Influence of Obesity in the miRNome: miR-4454, a Key Regulator of Insulin Response Via Splicing Modulation in Prostate
Authors: Herrero-Aguayo Vicente , Jiménez-Vacas Juan M , Sáez-Martínez Prudencio , Gómez-Gómez Enrique , López-Cánovas Juan L , Garrido-Sánchez Lourdes , Herrera-Martínez Aura D , García-Bermejo Laura , Macías-González Manuel , López-Miranda José , Castaño Justo P , Gahete Manuel D , Luque Raúl M 
Published: August 2020

AbstractContextObesity is a major health problem associated with severe comorbidities, including type 2 diabetes and cancer, wherein microRNAs (miRNAs) might be useful as diagnostic/prognostic tools or therapeutic targets.ObjectiveTo explore the differential expression pattern of miRNAs in obesity and their putative role in obesity-related comorbidities such as insulin resistance.MethodsAn Affymetrix-miRNA array was performed in plasma samples from normoweight (n = 4/body mass index &lt; 25) and obese subjects (n = 4/body mass index &gt; 30). The main changes were validated in 2 independent cohorts (n = 221/n = 18). Additionally, in silico approaches were performed and in vitro assays applied in tissue samples and prostate (RWPE-1) and liver (HepG2) cell-lines.ResultsA total of 26 microRNAs were altered (P &lt; 0.01) in plasma of obese subjects compared to controls using the Affymetrix-miRNA array. Validation in ampler cohorts revealed that miR-4454 levels were consistently higher in obesity, associated with insulin-resistance (Homeostatic Model Assessment of Insulin Resistance/insulin) and modulated by medical (metformin/statins) and surgical (bariatric surgery) strategies. miR-4454 was highly expressed in prostate and liver tissues and its expression was increased in prostate and liver cells by insulin. In vitro, overexpression of miR-4454 in prostate cells resulted in decreased expression levels of INSR, GLUT4, and phosphorylation of AMPK/AKT/ERK, as well as in altered expression of key spliceosome components (ESRP1/ESRP2/RBM45/RNU2) and insulin-receptor splicing variants.ConclusionsObesity was associated to an alteration of the plasmatic miRNA landscape, wherein miR-4454 levels were higher, associated with insulin-resistance and modulated by obesity-controlling interventions. Insulin regulated miR-4454, which, in turn may impair the cellular response to insulin, in a cell type-dependent manner (i.e., prostate gland), by modulating the splicing process.
Development, Implementation, and Evaluation of a Telemedicine Preoperative Evaluation Initiative at a Major Academic Medical Center
Authors: Kamdar Nirav V. , Huverserian Ari , Jalilian Laleh , Thi William , Duval Victor , Beck Lauren , Brooker Lindsay , Grogan Tristan , Lin Anne , Cannesson Maxime 
Published: August 2020

BACKGROUND:
With health care practice consolidation, the increasing geographic scope of health care systems, and the advancement of mobile telecommunications, there is increasing interest in telemedicine-based health care consultations. Anesthesiology has had experience with telemedicine consultation for preoperative evaluation since 2004, but the majority of studies have been conducted in rural settings. There is a paucity of literature of use in metropolitan areas. In this article, we describe the implementation of a telemedicine-based anesthesia preoperative evaluation and report the program’s patient satisfaction, clinical case cancellation rate outcomes, and cost savings in a large metropolitan area (Los Angeles, CA).

METHODS:
This is a descriptive study of a telemedicine-based preoperative anesthesia evaluation process in an academic medical center within a large metropolitan area. In a 2-year period, we evaluated 419 patients scheduled for surgery by telemedicine and 1785 patients who were evaluated in-person.

RESULTS:
Day-of-surgery case cancellations were 2.95% and 3.23% in the telemedicine and the in-person cohort, respectively. Telemedicine patients avoided a median round trip driving distance of 63 miles (Q1 24; Q3 119) and a median time saved of 137 (Q1 95; Q3 195) and 130 (Q1 91; Q3 237) minutes during morning and afternoon traffic conditions, respectively. Patients experienced time-based savings, particularly from traveling across a metropolitan area, which amounted to $67 of direct and opportunity cost savings. From patient satisfaction surveys, 98% (129 patients out of 131 completed surveys) of patients who were consulted via telemedicine were satisfied with their experience.

CONCLUSIONS:
This study demonstrates the implementation of a telemedicine-based preoperative anesthesia evaluation from an academic medical center in a metropolitan area with high patient satisfaction, cost savings, and without increase in day-of-procedure case cancellations.
Fe65 is the sole member of its family that mediates transcription regulated by the amyloid precursor protein
Authors: Probst Sabine , Krüger Maik , Kägi Larissa , Thöni Sarina , Schuppli Daniel , Nitsch Roger M. , Konietzko Uwe 
Published: August 2020

ABSTRACT
The amyloid precursor protein (APP), a central molecule in Alzheimer's disease (AD), has physiological roles in cell adhesion and signaling, migration, neurite outgrowth and synaptogenesis. Intracellular adapter proteins mediate the function of transmembrane proteins. Fe65 (also known as APBB1) is a major APP-binding protein. Regulated intramembrane proteolysis (RIP) by γ-secretase releases the APP intracellular domain (AICD), together with the interacting proteins, from the membrane. We studied the impact of the Fe65 family (Fe65, and its homologs Fe65L1 and Fe65L2, also known as APBB2 and APBB3, respectively) on the nuclear signaling function of the AICD. All Fe65 family members increased amyloidogenic processing of APP, generating higher levels of β-cleaved APP stubs and AICD. However, Fe65 was the only family member supporting AICD translocation to nuclear spots and its transcriptional activity. Using a recently established transcription assay, we dissected the transcriptional activity of Fe65 and provide strong evidence that Fe65 represents a transcription factor. We show that Fe65 relies on the lysine acetyltransferase Tip60 (also known as KAT5) for nuclear translocation. Furthermore, inhibition of APP cleavage reduces nuclear Tip60 levels, but this does not occur in Fe65-knockout cells. The rate of APP cleavage therefore regulates the nuclear translocation of AICD–Fe65–Tip60 (AFT) complexes, to promote transcription by Fe65.
ACSL3 is a novel GABARAPL2 interactor that links ufmylation and lipid droplet biogenesis
Authors: Eck Franziska , Phuyal Santosh , Smith Matthew D. , Kaulich Manuel , Wilkinson Simon , Farhan Hesso , Behrends Christian 
Published: August 2020

ABSTRACT
While studies of the autophagy-related (ATG) genes in knockout models have led to an explosion of knowledge about the functions of autophagy components, the exact roles of LC3 and GABARAP family proteins (human ATG8 equivalents) are still poorly understood. A major drawback in understanding their roles is that the available interactome data has largely been acquired using overexpression systems. To overcome these limitations, we employed CRISPR/Cas9-based genome-editing to generate a panel of cells in which human ATG8 genes were tagged at their natural chromosomal locations with an N-terminal affinity epitope. This cellular resource was employed to map endogenous GABARAPL2 protein complexes using interaction proteomics. This approach identified the ER-associated protein and lipid droplet (LD) biogenesis factor ACSL3 as a stabilizing GABARAPL2-binding partner. GABARAPL2 bound ACSL3 in a manner dependent on its LC3-interacting regions, whose binding site in GABARAPL2 was required to recruit the latter to the ER. Through this interaction, the UFM1-activating enzyme UBA5 became anchored at the ER. Furthermore, ACSL3 depletion and LD induction affected the abundance of several ufmylation components and ER-phagy. Together these data allow us to define ACSL3 as a novel regulator of the enigmatic UFM1 conjugation pathway.
Microtubule polyglutamylation is important for regulating cytoskeletal architecture and motility in Trypanosoma brucei
Authors: Jentzsch Jana , Sabri Adal , Speckner Konstantin , Lallinger-Kube Gertrud , Weiss Matthias , Ersfeld Klaus 
Published: August 2020

ABSTRACT
The shape of kinetoplastids, such as Trypanosoma brucei, is precisely defined during the stages of the life cycle and governed by a stable subpellicular microtubule cytoskeleton. During the cell cycle and transitions between life cycle stages, this stability has to transiently give way to a dynamic behaviour to enable cell division and morphological rearrangements. How these opposing requirements of the cytoskeleton are regulated is poorly understood. Two possible levels of regulation are activities of cytoskeleton-associated proteins and microtubule post-translational modifications (PTMs). Here, we investigate the functions of two putative tubulin polyglutamylases in T. brucei, TTLL6A and TTLL12B. Depletion of both proteins leads to a reduction in tubulin polyglutamylation in situ and is associated with disintegration of the posterior cell pole, loss of the microtubule plus-end-binding protein EB1 and alterations of microtubule dynamics. We also observe a reduced polyglutamylation of the flagellar axoneme. Quantitative motility analysis reveals that the PTM imbalance correlates with a transition from directional to diffusive cell movement. These data show that microtubule polyglutamylation has an important role in regulating cytoskeletal architecture and motility in the parasite T. brucei.
This article has an associated First Person interview with the first author of the paper.
Intraflagellar transport during assembly of flagella of different length in Trypanosoma brucei isolated from tsetse flies
Authors: Bertiaux Eloïse , Mallet Adeline , Rotureau Brice , Bastin Philippe 
Published: August 2020

ABSTRACT
Multicellular organisms assemble cilia and flagella of precise lengths differing from one cell to another, yet little is known about the mechanisms governing these differences. Similarly, protists assemble flagella of different lengths according to the stage of their life cycle. Trypanosoma brucei assembles flagella of 3 to 30 µm during its development in the tsetse fly. This provides an opportunity to examine how cells naturally modulate organelle length. Flagella are constructed by addition of new blocks at their distal end via intraflagellar transport (IFT). Immunofluorescence assays, 3D electron microscopy and live-cell imaging revealed that IFT was present in all T. brucei life cycle stages. IFT proteins are concentrated at the base, and IFT trains are located along doublets 3–4 and 7–8 and travel bidirectionally in the flagellum. Quantitative analysis demonstrated that the total amount of flagellar IFT proteins correlates with the length of the flagellum. Surprisingly, the shortest flagellum exhibited a supplementary large amount of dynamic IFT material at its distal end. The contribution of IFT and other factors to the regulation of flagellum length is discussed.