bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ovarian and Uterine Functions in Female Survivors of Childhood Cancers
Authors: Oktem Ozgur , Kim Samuel S. , Selek Ugur , Schatmann Glenn , Urman Bulent 
Published: November 2017

Abstract

Adult survivors of childhood cancers are more prone to developing poor reproductive and obstetrical outcomes than their siblings and the general population as a result of previous exposure to chemotherapy and radiation during childhood. Chemotherapy drugs exert cytotoxic effects systemically and therefore can damage the ovaries, leading to infertility, premature ovarian failure, and, to a lesser extent, spontaneous abortions. They have very limited or no deleterious effects on the uterus that can be recognized clinically. By contrast, radiation is detrimental to both the ovaries and the uterus, thereby causing a greater magnitude of adverse effects on the female reproductive function. These include infertility, premature ovarian failure, miscarriage, fetal growth restrictions, perinatal deaths, preterm births, delivery of small-for-gestational-age infants, preeclampsia, and abnormal placentation. Regrettably, the majority of these adverse outcomes arise from radiation-induced uterine injury and are reported at higher incidence in the adult survivors of childhood cancers who were exposed to uterine radiation during childhood in the form of pelvic, spinal, or total-body irradiation. Recent findings of long-term follow-up studies evaluating reproductive performance of female survivors provided some reassurance to female cancer survivors by documenting that pregnancy and live birth rates were not significantly compromised in survivors, including those who had been treated with alkylating agents and had not received pelvic, cranial, and total-body irradiation. We aimed in this narrative review article to provide an update on the impact of chemotherapy and radiation on the ovarian and uterine function in female survivors of childhood cancer.

Implications for Practice
Adult survivors of childhood cancers are more prone to developing a number of poor reproductive and obstetrical outcomes than their siblings and the general population as a result of previous exposure to chemotherapy and radiation during childhood. The impact of radiation therapy on the female genital system is greater than chemotherapy regimens because radiation is detrimental to both the uterus and the ovaries, whereas toxic effects of chemotherapy drugs are confined to the ovaries. Therefore, radiation-induced uterine damage accounts for most poor obstetrical outcomes in the survivors. These include infertility, miscarriages, stillbirths, fetal growth restrictions, preeclampsia, and preterm deliveries.
Revisiting Expectations in an Era of Precision Oncology
Authors: Marchiano Emily J. , Birkeland Andrew C. , Swiecicki Paul L. , Spector-Bagdady Kayte , Shuman Andrew G. 
Published: November 2017

Abstract

As we enter an era of precision medicine and targeted therapies in the treatment of metastatic cancer, we face new challenges for patients and providers alike as we establish clear guidelines, regulations, and strategies for implementation. At the crux of this challenge is the fact that patients with advanced cancer may have disproportionate expectations of personal benefit when participating in clinical trials designed to generate generalizable knowledge. Patient and physician goals of treatment may not align, and reconciliation of their disparate perceptions must be addressed. However, it is particularly challenging to manage a patient's expectations when the goal of precision medicine—personalized response—exacerbates our inability to predict outcomes for any individual patient. The precision medicine informed consent process must therefore directly address this issue. We are challenged to honestly, clearly, and compassionately engage a patient population in an informed consent process that is responsive to their vulnerability, as well as ever-evolving indications and evidence. This era requires a continual reassessment of expectations and goals from both sides of the bed.
Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of Necuparanib Combined with Nab-Paclitaxel and Gemcitabine in Patients with Metastatic Pancreatic Cancer: Phase I Results
Authors: O’Reilly Eileen M. , Roach James , Miller Paul , Yu Kenneth H. , Tjan Catherine , Rosano Molly , Krause Silva , Avery William , Wolf Julie , Flaherty Keith , Nix Darrell , Ryan David P. 
Published: November 2017

AbstractLessons LearnedDespite the compelling preclinical rationale of evaluating the genetically engineered heparin derivative, necuparanib, combined with standard therapy in metastatic pancreas adenocarcinoma, the results were ultimately disappointing. Safety was documented, although dose escalation was limited by the number of subcutaneous injections, the potential for skin toxicity (cellulitis), and low-level anticoagulant effect. Nonetheless, the hypothesis of targeting prothrombotic pathways in pancreas adenocarcinoma remains compelling.BackgroundNecuparanib is derived from unfractionated heparin and engineered for reduced anticoagulant activity while preserving known heparin-associated antitumor properties. This trial assessed the safety, pharmacokinetics (PK), pharmacodynamics, and initial efficacy of necuparanib combined with gemcitabine ± nab-paclitaxel in patients with metastatic pancreatic cancer.MethodsPatients received escalating daily subcutaneous doses of necuparanib plus 1,000 mg/m2 gemcitabine (days 1, 8, 15, and every 28 days). The protocol was amended to include 125 mg/m2 nab-paclitaxel after two cohorts (following release of the phase III MPACT data). The necuparanib starting dose was 0.5 mg/kg, with escalation via a modified 3 + 3 design until the maximum tolerated dose (MTD) was determined.ResultsThirty-nine patients were enrolled into seven cohorts (necuparanib 0.5, 1 mg/kg + gemcitabine; necuparanib 1, 2, 4, 6, and 5 mg/kg + nab-paclitaxel + gemcitabine). The most common adverse events were anemia (56%), fatigue (51%), neutropenia (51%), leukopenia (41%), and thrombocytopenia (41%). No deaths and two serious adverse events were potentially related to necuparanib. Measurable levels of necuparanib were seen starting at the 2 mg/kg dose. Of 24 patients who received at least one dose of necuparanib + nab-paclitaxel + gemcitabine, 9 (38%) achieved a partial response and 6 (25%) achieved stable disease (63% disease control rate). Given a cellulitis event and mild activated partial thromboplastin time increases at 6 mg/kg, the 5 mg/kg dose was considered the MTD and selected for further assessment in phase II.ConclusionAcceptable safety and encouraging signals of activity in patients with metastatic pancreatic cancer receiving necuparanib, nab-paclitaxel, and gemcitabine were demonstrated.
Phase II Trial Using a Combination of Oxaliplatin, Capecitabine, and Celecoxib with Concurrent Radiation for Newly Diagnosed Resectable Rectal Cancer
Authors: Araujo-Mino Emilio P. , Patt Yehuda Z. , Murray-Krezan Cristina , Hanson Joshua A. , Bansal Pranshu , Liem Ben J. , Rajput Ashwani , Fekrazad M. Houman , Heywood Glenory , Lee Fa Chyi 
Published: November 2017

Abstract

Lessons Learned
Colorectal cancers exhibit a high level of cyclooxygenase-2 (COX-2) expression with strong preclinical rationale for improved clinical outcomes with COX-2 inhibition. Celecoxib is a COX-2 inhibitor and we have shown that it can be safely combined with capecitabine and oxaliplatin as part of neoadjuvant treatment with radiation therapy (RT) in rectal cancer. There was a significant improvement in skin toxicity with this combination as compared with historical data. Considering the field has moved on to single-agent capecitabine, we believe future trials with capecitabine and celecoxib hold potential.

Background
Improved survival is seen among patients with rectal cancer who achieve pathologic complete response (pCR) after neoadjuvant therapy. Cyclooxygenase-2 (COX-2) expression is increased in gastrointestinal malignancies and it may serve as a target to enhance pathologic response. A trial combining chemoradiation and COX-2 inhibition was conducted to evaluate the pCR rate, surgical outcomes, survival, and treatment toxicity.

Methods
Patients with resectable (T3-4, N1-2) rectal cancer within 12 cm of the anal verge were included in this phase II clinical trial. The neoadjuvant treatment consisted of capecitabine 850 mg/m2 b.i.d. Monday through Friday for 5 weeks, weekly oxaliplatin 50 mg/m2 intravenous (IV), celecoxib 200 mg b.i.d. daily, along with concurrent 45 gray radiation therapy in 25 fractions.

Results
Thirty-two patients were included in the final analysis. The primary endpoint was pCR: 31% (95% confidence interval [CI]: 16%–50%). Secondary endpoints were surgical downstaging (SD): 75% (95% CI: 57%–89%) and sphincter-sparing surgery (SSS): 56% (95% CI: 38%–74%). Common grade &gt;3 toxicities were diarrhea and abnormal liver function tests (9% each). Grade 0 and 1 toxicities included radiation dermatitis (59% and 34%, respectively) and proctitis (63% and 28%, respectively). At 3 years, disease-free survival and overall survival (OS) were 84% (95% CI: 65%–93%) and 94% (95% CI: 77%–98%), respectively.

Conclusion
Chemoradiation with celecoxib in rectal cancer was well tolerated and demonstrated high rates of pCR, SD, and SSS. Improvement in skin toxicity (34% grade 1 and no grade 3/4) as compared with historical results (43%–78% grade 3/4) seems to be a significant improvement with addition of celecoxib to neoadjuvant chemotherapy.
Time-Series Data Analysis Using Sliding Window Based SVD for Motion Evaluation
Authors: Jiang Yinlai , Hayashi Isao , Wang Shuoyu , Ishida Kenji ,   The University of Electro-Communications Chofu, Tokyo 182-8585, Japan,   Kansai University Takatsuki, Osaka 569-1095, Japan,   Kochi University of Technology Kami, Kochi 782-8502, Japan,   Kurihara Central Hospital Kurihara, Miyagi 987-2205, Japan
Published: November 2017

A method based on singular value decomposition (SVD) is proposed for extracting features from motion time-series data observed with various sensing systems. Matrices consisting of the sliding window (SW) subsets of time-series data are decomposed, yielding singular vectors as the patterns of the motion, and the singular values as a scalar, by which the corresponding singular vectors describe the matrices.The sliding window based singular value decomposition was applied to analyze acceleration during walking. Three levels of walking difficulty were simulated by restricting the right knee joint in the measurement. The accelerations of the middles of the shanks and the back of the waist were measured and normalized before the SW-SVD was performed.The results showed that the first singular values inferred from the acceleration data of the restricted side (the right shank) significantly related to the increase of the restriction among all the subjects while there were no common trends in the singular values of the left shank and the waist. The SW-SVD was suggested to be a reliable method to evaluate walking disability. Furthermore, a 2D visualization tool is proposed to provide intuitive information about walking difficulty which can be used in walking rehabilitation to monitor recovery.
Implementasi Algoritma Penjadwalan untuk pengelolaan Big Data dengan Hadoop
Authors: Prabowo Sidik 
Published: November 2017

<p>Paper ini mengusulkan skema scheduler hadoop pada penyelesaikan tipe job yang sesuai untuk peningkatan kinerja Hadoop. Kesesuaian jenis scheduler dan tipe job yang dikerjakan dapat meningkatkan throughput dan menurunkan waktu rata-rata penyelesaian job. Masalah utama pada eksekusi job adalah ketidaksesuaian antara scheduler dengan tipe job yang dikerjakan. Pada paper ini telah dilakukan pengujian terhadap beberapa algoritma scheduler Hadoop yaitu FIFO, Fair, SARS dan COSHH scheduler dengan beberapa jenis job yang ditangani dalam lingkungan hadoop. Jenis-jenis job yang diujikan adalah word count, random text writer dan grep. Pengujian dilakukan dua skenario, yaitu job homogen (satu jenis) dan heterogen (beberapa jenis job) dikerjakan bersama. Hasil pengujian menunjukan bahwa algoritma SARS cocok digunakan pada penyelesaian job yang sifatnya homogen. Sementara itu algoritma COSHH cocok digunakan pada penyelesaian job gabungan yang heterogen. </p>
A Semianalytical Methodology for Pressure-Transient Analysis of Multiwell-Pad-Production Scheme in Shale Gas Reservoirs, Part 1: New Insights Into Flow Regimes and Multiwell Interference
Authors: Xiao Cong , Dai Yu , Tian Leng , Lin Haixiang , Zhang Yayun , Yang Yaokun , Hou Tengfei , Deng Ya 
Published: November 2017

Summary
Recently, a multiwell-pad-production (MWPP) scheme has been the center of attention as a promising technology to improve shale-gas (SG) recovery. However, the increasing possibility of multiwell pressure interference (MWPI) in the MWPP scheme severely distorts flow regimes, which strongly challenges the traditional pressure-transient analysis methods that focus on single multifractured horizontal wells (SMFHWs) without MWPI. Therefore, a methodology to identify pressure-transient response of the MWPP scheme with and without MWPI is urgent. To fill this gap, a new semianalytical pressure-transient model of the MWPP scheme is established by use of superposition theory, Gauss elimination, and the Stehfest numerical algorithm. Type curves are generated, and flow regimes are identified by considering MWPI. Finally, a sensitivity analysis is conducted.
Our results show that there are good agreements between our proposed model and numerical simulation; moreover, our semianalytical approach also demonstrates a promising calculation speed compared with numerical simulation. Some expected flow regimes are significantly distorted by MWPI. In addition, well rate determines the distortion of pressure curves, whereas fracture length, well spacing, and fracture spacing determine when the MWPI occurs. The smaller the gas rate, the more severely flow regimes are distorted. As the well spacing increases, fracture length decreases, fracture spacing decreases, and the occurrence of MWPI occurs later. The stress-sensitivity coefficient has little to no influence on the occurrence of MWPI. Similar to the concept of the dual-porosity model, three new flow regimes—the single-well flow regime, MWPI flow regime, and MWPP flow regime—are artificially defined to systematically characterize the flow regimes of the MWPP scheme.
This work offers some additional insights on pressure-transient response for the MWPP scheme in the SG reservoir, which can provide considerable guidance for fracture-properties estimation and well-pattern optimization for the MWPP scheme.
Posicionamiento del patrimonio en cooperativas de intermediación financiera frente a las NIIF sobre instrumentos financieros
Authors: Martínez Batista Francisco 
Published: November 2017

Esta investigación tiene un diseño no experimental y transeccional, se enfoca en analizar el posicionamiento patrimonial de las cooperativas de intermediación financiera (I.F.) frente a las aportaciones de sus asociados. Inicia con planteamientos teóricos de normativa contable internacional y local, la relación del Activo total invertido versus el Pasivo, Patrimonio y Aportaciones. El Estudio de Caso analizó cifras del Balance de Situación, las diferencias reales, bajo la incertidumbre de la norma plena. Los resultados arrojan desmejoramiento patrimonial de 14.8% y endeudamiento general por el mismo orden. En el Estudio de Caso la situación real, versus la norma plena, y considerando el Capital mínimo irreducible de Aportaciones, igual disminuye el Patrimonio en 10.2% y aumenta los Pasivos Financieros en 10.2%. En conclusión, se considera usar alguna estrategia que solvente la situación de la normativa contable internacional con las nacionales que converjan en beneficio de las cooperativas.
Architectures and Mechanical Properties of Drugs and Complexes of Surface-Active Compounds at Air-Water and Oil-Water Interfaces
Authors: Sarker Dipak K. 
Published: November 2017

Background:
Drugs can represent a multitude of compounds from proteins and peptides,
such as growth hormones and insulin and on to simple organic molecules such as flurbiprofen,
ibuprofen and lidocaine. Given the chemical nature of these compounds two features are always
present. A portion or portions of the molecule that has little affinity for apolar surfaces and media
and on the contrary a series of part or one large part that has considerable affinity for hydrophilic,
polar or charged media and surfaces. A series of techniques are routinely used to probe the
molecular interactions that can arise between components, such as the drug, a range of surface–
active excipients and flavor compounds, for example terpenoids and the solvent or dispersion
medium.

Results:
Fifty-eight papers were included in the review, a large number (16) being of theoretical nature
and an equally large number (14) directly pertaining to medicine and pharmacy; alongside experimental
data and phenomenological modelling. The review therefore simultaneously represents an amalgam of
review article and research paper with routinely used or established (10) and well-reported
methodologies (also included in the citations within the review). Experimental data included from
various sources as diverse as foam micro-conductivity, interferometric measurements of surface
adsorbates and laser fluorescence spectroscopy (FRAP) are used to indicate the complexity and utility
of foams and surface soft matter structures for a range of purposes but specifically, here for
encapsulation and incorporation of therapeutics actives (pharmaceutical molecules, vaccines and
excipients used in medicaments). Techniques such as interfacial tensiometry, interfacial rheology
(viscosity, elasticity and visco-elasticity) and nanoparticle particle size (hydrodynamic diameter) and
charge measurements (zeta potential), in addition to atomic force and scanning electron microscopy
have proven to be very useful in understanding how such elemental components combine, link or
replace one another (competitive displacement). They have also proven to be both beneficial and
worthwhile in the sense of quantifying the unseen actions and interplay of adsorbed molecules and the
macroscopic effects, such as froth formation, creaming or sedimentation that can occur as a result of
these interactions.

Conclusion:
The disclosures and evaluations presented in this review confirm the importance of a
theoretical understanding of a complex model of the molecular interactions, network and present a
framework for the understanding of really very complex physical forms. Future therapeutic
developers rely on an understanding of such complexity to garner a route to a more successful
administration and formulation of a new generation of therapeutic delivery systems for use in
medicine.
Forced Degradation Study for Tenofovir DF, Lamivudine and Efavirenz in Triple Combination Anti-Retroviral Tablets and Development of Validated Stability Indicating Assay Method by UPLC
Authors: Murali Krishna Mantripragada V.V.N. , Rao Sumathi Vinay , Venugopal Nutulapati V.S. 
Published: November 2017

Introduction:
Tenofovir Disoproxil Fumarate/Lamivudine/Efavirenz Tablets are a pharmaceutical
dosage form indicated for the treatment of Human Immunodeficiency Virus (HIV) infection.

Methods:
A simple, time efficient and stability indicating Reverse Phase Ultra Performance Liquid
Chromatography (RP – UPLC) method was developed for the simultaneous determination of the three
drugs present in the tablets. Mobile phase-A is 0.1% Trifluoro Acetic acid in water and mobile phase-B
is acetonitrile in gradient elution mode. Flow rate at 0.4 mL/min was fixed in the method. Acquity BEH
Phenyl (100 mm × 2.1 mm), 1.7 µ column was used for the separation of analytes at 260 nm wavelength.
The developed method has been validated as specified in International Conference on Harmonization
(ICH) guideline. Forced degradation study was conducted for Tenofovir Disoproxil fumarate
(TDF), Lamivudine (LAM) and Efavirenz (EFA) pharmaceutical tablets to identify the degradation
behaviour of individual drugs under stress study.

Results:

The method was observed to be linear from 6-90 µg/mL concentration for TDF & LAM and
12-180 µg/mL for EFA with correlation coefficient values of more than 0.999. The method was found
to be precise with RSD (Relative standard deviation) values of below 2% for replicate measurements.
Recovery results were found to be between 99.0 and 100.8%. LOQ values for TDF, LAM & EFA were
0.041 µg/mL, 0.034 µg/mL & 0.053 µg/mL, respectively. Specificity of the analytical method was
checked by injecting the stressed samples and evaluating the homogeneity of peaks using Photo Diode
Array (PDA) detector. Peak purity results indicated that no interference was observed from degradation
impurities for the quantification of TDF, LAM and EFA in the dosage form. The method was found to
be robust under the deliberately modified chromatographic parameters.

Conclusion:
The developed UPLC method is stability indicating, successfully validated and suitable for
quantification purpose.
Olive Oil-related Anti-inflammatory Effects on Atherosclerosis: Potential Clinical Implications
Authors: Wongwarawipat Tanakal , Papageorgiou Nikolaos , Bertsias Dimitrios , Siasos Gerasimos , Tousoulis Dimitris 
Published: November 2017

Background and Objective:
Atherosclerosis is characterized by a chronic low-grade inflammatory
process which can result in atherothrombosis and a number of cardiovascular diseases
(CVD). It is believed to be caused by multiple processes that involve inflammation and immunity.
Mediterranean Diet (MedD) has been discovered to possess anti-inflammatory properties and associated
with a reduction in the CVD risk and mortality. Its main component, extra-virgin olive oil
(EVOO), is believed to be largely responsible for these effects and therefore, has been investigated in
various studies. The present review article aims to summarize the available literature on the antiinflammatory
and cardio-protective effects of EVOO.

Methods:
A search based on the key concepts “olive oil”, “atherosclerosis”, “inflammation” and “cardiovascular
disease” was performed to retrieve relevant studies and articles on the association between
the consumption of EVOO and the levels of inflammatory biomarkers as well as CVD incidence and
mortality from online databases; Pubmed, Embase and Cochrane Library.

Results:
Consumption of EVOO is associated with a reduction in inflammatory biomarkers and molecules
implicated in atherosclerosis as well as CVD incidence and mortality as well as other complications
such as heart failure and atrial fibrillation. Moreover, these anti-inflammatory and
cardioprotective effects of EVOO are mostly attributable to its high content of polyphenol molecules.

Conclusion:
Currently available evidence supports the anti-inflammatory and cardio-protective roles
of EVOO. However, there is limited amount of available randomized controlled trials especially lacking
those investigating the use of EVOO as secondary prevention, heterogeneity of study design, limited
generalization to wide population groups, and inability to determine the minimum intake of EVOO
required to clinically achieve the anti-inflammatory and cardioprotective effects. Therefore, more highquality
randomized controlled trials still need to be carried out to overcome these challenges to further
assess the health benefits of EVOO consumption and potentially translate it into clinical practice as
primary or secondary prevention of atherosclerosis-related conditions.