bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breaking down barriers to birth control access: An assessment of online platforms prescribing birth control in the USA
Authors: Zuniga Carmela , Grossman Daniel , Harrell Sara , Blanchard Kelly , Grindlay Kate 
Published: January 2019

Introduction In the USA, the requirement that individuals obtain a prescription for hormonal contraception is a significant barrier for women who lack the time, finances, insurance coverage or means of transportation to visit a provider. The emergence of telemedicine services has removed some of these barriers by providing women with the opportunity to conveniently obtain birth control prescriptions through their computer or smartphone. Methods In this article, we compare the prescribing processes and policies of online platforms that prescribe hormonal contraceptives to women in the USA, and use the recommendations of the 2016 US medical eligibility criteria for contraceptive use to evaluate whether online prescribers are providing evidence-based care. Results As of February 2018, nine online platforms prescribed hormonal birth control to women across various states in the USA. These platforms varied in regard to their prescribing processes, range of methods offered, locations of operation, fees for services, and policies regarding age restrictions. Discussion An assessment of each platform’s online health questionnaire reveals that these telemedicine services are adequately screening for contraindications and safely providing birth control methods to patients, although efforts could be made to strengthen the rigour of online health questionnaires to ensure they adequately screen for all contraindications.
Digital Problem-Based Learning: An Innovative and Efficient Method of Teaching Medicine
Authors: Mistry Khaylen , Chetty Natasha Casie , Gurung Puran , Levell Nick J 
Published: January 2019

Background: The breadth of knowledge assimilated by undergraduates is substantial. Time must be utilised to impart knowledge and skills to ensure optimal training. Dermatology comprises a large portion of work in primary care; yet UK undergraduate dermatology training is short. Digital problem-based learning (PBL) is an innovative teaching method incorporating clinical images into intense, interactive teaching sessions. Aim: To determine the efficacy of digital PBL sessions in teaching UK medical students during their dermatology module. Methods: In total, 59 second-year medical students at Norwich Medical School during their dermatology secondary care attachment completed two 2.5-h digital PBL sessions. One session was focused on lesions and the second on inflammatory diseases. During each session, students assessed 60 clinical cases each comprising an image with a brief history. In small groups, students discussed the cases, described the images, and agreed a diagnosis followed by a group discussion with the supervising clinician who provided feedback. Following each session, students completed a feedback questionnaire. Results: In total, 117 sets of feedback were received; 60% of students considered they learnt a great amount in a short time. The majority of students reported feeling more confident to make a dermatological diagnosis and more motivated in clinics as a result of the digital PBL; 64% of students found digital PBL more useful than real patient clinics. The most frequent negative comment was that 2.5 h was too long to concentrate. Conclusions: Digital PBL was a popular, effective, and efficient teaching method. Digital PBL sessions should be introduced alongside clinics and other teaching methods for undergraduates.
Genetics of MDS
Authors: Ogawa Seishi 
Published: January 2019

Abstract
Our knowledge about the genetics of myelodysplastic syndromes (MDS) and related myeloid disorders has been dramatically improved during the past decade, in which revolutionized sequencing technologies have played a major role. Through intensive efforts of sequencing of a large number of MDS genomes, a comprehensive registry of driver mutations recurrently found in a recognizable fraction of MDS patients has been revealed, and ongoing efforts are being made to clarify their impacts on clinical phenotype and prognosis, as well as their role in the pathogenesis of MDS. Among major mutational targets in MDS are the molecules involved in DNA methylations, chromatin modification, RNA splicing, transcription, signal transduction, cohesin regulation, and DNA repair. Showing substantial overlaps with driver mutations seen in acute myeloid leukemia (AML), as well as age-related clonal hematopoiesis in healthy individuals, these mutations are presumed to have a common clonal origin. Mutations are thought to be acquired and positively selected in a well-organized manner to allow for expansion of the initiating clone to compromise normal hematopoiesis, ultimately giving rise to MDS and subsequent transformation to AML in many patients. Significant correlations between mutations suggest the presence of functional interactions between mutations, which dictate disease progression. Mutations are frequently associated with specific disease phenotype, drug response, and clinical outcomes, and thus, it is essential to be familiar with MDS genetics for better management of patients. This review aims to provide a brief overview of the recent progresses in MDS genetics.
Duality of Purpose: Participant and Parent Understanding of the Purpose of Genomic Tumor Profiling Research Among Children and Young Adults With Solid Tumors
Authors: Marron Jonathan M. , Cronin Angel M. , DuBois Steven G. , Glade-Bender Julia , Kim AeRang , Crompton Brian D. , Meyer Stephanie C. , Janeway Katherine A. , Mack Jennifer W. 
Published: January 2019

Purpose
Increasing use of genomic tumor profiling may blur the line between research and clinical care. We aimed to describe perspectives of research participants about the purpose of genomic tumor profiling research in pediatric oncology.

Methods
We surveyed 45 participants (response rate, 85%) in a pilot study of genomic profiling in pediatric solid tumors at four academic cancer centers after the return of sequencing results. We defined understanding according to a one-item (basic) definition (recognition that the primary purpose was not to improve the patient’s treatment) and a four-item (comprehensive) definition (primary purpose was not to improve patient’s treatment; primary purpose was to improve treatment of future patients; there may not be direct medical benefit; most likely result of participation was not increased likelihood of cure).

Results

Sixty-eight percent of respondents (30 of 44 respondents) demonstrated basic understanding of the study purpose; 55% (24 of 44 respondents) demonstrated comprehensive understanding. Understanding was more frequently seen in those with higher education and greater genetic knowledge according to basic (81%
v
50% [
P
= .05]; and 82%
v
46% [
P
= .03], respectively) and comprehensive (73%
v
28% [
P
= .01]; 71%
v
23% [
P
= .01]) definitions. Ninety-three percent of respondents who believed the primary purpose was to improve the patient’s care simultaneously stated that the research also aimed to benefit future patients.

Conclusion
Most participants in pediatric tumor profiling research understand that the primary goal of this research is to improve care for future patients, but many express dual goals when they participate in sequencing research. Some populations demonstrate increased rates of misunderstanding. Nuanced participant views suggest that additional work is needed to assess and improve participant understanding, particularly as tumor sequencing moves beyond research and into clinical practice.
Validation of HER2 Amplification as a Predictive Biomarker for Anti–Epidermal Growth Factor Receptor Antibody Therapy in Metastatic Colorectal Cancer
Authors: Raghav Kanwal , Loree Jonathan M. , Morris Jeffrey S. , Overman Michael J. , Yu Ruoxi , Meric-Bernstam Funda , Menter David , Korphaisarn Krittiya , Kee Brian , Muranyi Andrea , Singh Shalini , Routbort Mark , Chen Ken , Shaw Kenna R.M. , Katkhuda Riham , Shanmugam Kandavel , Maru Dipen , Fakih Marwan , Kopetz Scott 
Published: January 2019

Purpose HER2 amplification has been implicated in resistance to therapy with anti–epidermal growth factor receptor antibodies (anti-EGFRabs) in metastatic colorectal cancer (mCRC). The purpose of the study was to validate the predictive impact of HER2 amplification in mCRC. Patients and Methods We analyzed patients with RAS/BRAF wild-type mCRC across two distinct cohorts. In cohort 1 (n = 98), HER2 amplification was tested in tumor tissue using dual in situ hybridization ( HER2 amplification: HER2/CEP17 ratio, 2.0 or greater). Cohort 2 (n = 70) included 16 patients with HER2 amplification and 54 HER2 nonamplified controls identified by next-generation sequencing ( HER2 amplification: four or more copies) who had received prior anti-EGFRabs. The primary end point was progression-free survival (PFS) on treatment with anti-EGFRab therapy, which was estimated and compared using the Kaplan-Meier method and log-rank test. Results Median PFS in cohort 1 on anti-EGFRab–based therapy was significantly shorter in patients with HER2 amplification compared with HER2 nonamplified patients (2.8 v 8.1 months, respectively; hazard ratio [HR], 7.05; 95% CI, 3.4 to 14.9; P < .001). These findings were validated in cohort 2 (median PFS for HER2 amplified v nonamplified: 2.8 v 9.3 months, respectively; HR, 10.66; 95% CI, 4.5 to 25.1; P < .001). The median PFS on therapy without anti-EGFRabs was similar among HER2-amplified and nonamplified patients in both cohort 1 (9.7 v 11.1 months, respectively; HR, 1.01; 95% CI, 0.4 to 2.4; P = .97) and cohort 2 (9.6 v 11.3 months, respectively; HR, 1.21; 95% CI, 0.5 to 3.1; P = .66). In multivariable analyses, HER2 amplification emerged as a single independent predictor of poor PFS on anti-EGFRab therapy in both cohort 1 (HR, 6.48; 95% CI, 3.1 to 13.6; P < .001) and cohort 2 (HR, 10.1; 95% CI, 4.3 to 23.9; P < .001). Conclusion HER2 amplification in RAS/RAF wild-type mCRC seems to be a predictive biomarker for lack of efficacy of anti-EGFRab therapy. Screening patients with RAS/BRAF wild-type mCRC for HER2 amplification should be considered before anti-EGFRab treatment to guide therapy and to identify patients for early referral to clinical trials.
Reconstituting the reticular ER network – mechanistic implications and open questions
Authors: Wang Ning , Rapoport Tom A. 
Published: January 2019

ABSTRACT
The endoplasmic reticulum (ER) is a major membrane-bound organelle in all eukaryotic cells. This organelle comprises morphologically distinct domains, including the nuclear envelope and peripheral sheets and tubules. The tubules are connected by three-way junctions into a network. Several membrane proteins have been implicated in network formation; curvature-stabilizing proteins generate the tubules themselves, and membrane-anchored GTPases fuse tubules into a network. Recent experiments have shown that a tubular network can be formed with reconstituted proteoliposomes containing the yeast membrane-fusing GTPase Sey1 and a curvature-stabilizing protein of either the reticulon or REEP protein families. The network forms in the presence of GTP and is rapidly disassembled when GTP hydrolysis of Sey1 is inhibited, indicating that continuous membrane fusion is required for its maintenance. Atlastin, the ortholog of Sey1 in metazoans, forms a network on its own, serving both as a fusion and curvature-stabilizing protein. These results show that the reticular ER can be generated by a surprisingly small set of proteins, and represents an energy-dependent steady state between formation and disassembly. Models for the molecular mechanism by which curvature-stabilizing proteins cooperate with fusion GTPases to form a reticular network have been proposed, but many aspects remain speculative, including the function of additional proteins, such as the lunapark protein, and the mechanism by which the ER interacts with the cytoskeleton. How the nuclear envelope and peripheral ER sheets are formed remain major unresolved questions in the field. Here, we review reconstitution experiments with purified curvature-stabilizing proteins and fusion GTPases, discuss mechanistic implications and point out open questions.
Reproducibility and Variability of Protein Analytes Measured Using a Multiplexed Modified Aptamer Assay
Authors: Tin Adrienne , Yu Bing , Ma Jianzhong , Masushita Kunihiro , Daya Natalie , Hoogeveen Ron C , Ballantyne Christie M , Couper David , Rebholz Casey M , Grams Morgan E , Alonso Alvaro , Mosley Thomas , Heiss Gerardo , Ganz Peter , Selvin Elizabeth , Boerwinkle Eric , Coresh Josef 
Published: January 2019

Abstract

Background
There is growing interest in the use of multiplexed aptamer-based assays for large-scale proteomic studies. However, the analytic, short- and long-term variation of the measured proteins is largely uncharacterized.

Methods
We quantified 4001 plasma protein analytes from 42 participants in the Atherosclerosis Risk in Communities (ARIC) Study in split samples and at multiple visits using a multiplexed modified aptamer assay. We calculated the CV, Spearman correlation, and intraclass correlation (ICC) between split samples and evaluated the short-term (4–9 weeks) and long-term (approximately 20 years) variability using paired t-tests with log-transformed protein concentrations and Bonferroni-corrected significance thresholds. We performed principal component (PC) analysis of protein analyte concentrations and evaluated their associations with age, sex, race, and estimated glomerular filtration rate (eGFR).

Results
The mean baseline age was 57 years at the first visit, 43% of participants were male and 57% were white. Among 3693 protein analytes that passed quality control, half (n = 1846) had CVs &lt; 5.0%, Spearman correlations &gt; 0.89, and ICCs &gt; 0.96 among the split samples. Over the short term, only 1 analyte had a statistically significant difference between the 2 time points, whereas, over approximately 20 years, 866 analytes (23.4%) had statistically significant differences (P &lt; 1.4 × 10−5, 681 increased, 185 decreased). PC1 had high correlations with age (−0.73) and eGFR (0.60). PC2 had moderate correlation with male sex (0.18) and white race (0.31).

Conclusions
Multiplexed modified aptamer technology can assay thousands of proteins with excellent precision. Our results support the potential for large-scale studies of the plasma proteome over the lifespan.
A Rapid Dilute-and-Shoot UPLC-MS/MS Assay to Simultaneously Measure 37 Drugs and Related Metabolites in Human Urine for Use in Clinical Pain Management
Authors: Dahlin Jayme L , Palte Michael J , LaMacchia John , Petrides Athena K 
Published: January 2019

Abstract

Background
Monitoring of medication compliance and drug abuse is used by clinicians to increase patient prescription drug compliance and reduce illicit drug abuse and diversion. Despite available immunoassays, chromatography-mass spectrometry–based methods are considered the gold standard for urine drug monitoring owing to higher sensitivities and specificities. Herein, we report a fast, convenient ultraperformance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) assay to detect or quantify 37 clinically relevant prescription drugs, drugs of abuse, and related glucuronides and other metabolites in human urine by single diluted sample injection.

Methods
Analytes consisted of prescription and illicit opioids, benzodiazepines, and drugs of abuse, including parent compounds and glucuronidated and nonglucuronidated metabolites. Urine samples were diluted with water and supplemented with deuterated internal standards without enzymatic hydrolysis, analyte extraction, or sample purification. Analytes were separated by reversed-phase UPLC and quantified by positive-mode electrospray ionization and collision-induced dissociation MS. Assay validation followed Food and Drug Administration bioanalytical guidelines.

Results
Total analytical run time was 5.5 min. All analytes demonstrated acceptable inter- and intraassay accuracy, imprecision, and linearity throughout clinically relevant analytical ranges (1–2000 ng/mL, depending on analyte). All analytes demonstrated acceptable selectivity, stability, matrix effects, carryover, and performance compared to national reference laboratory or previously validated in-house methods. A total of 23 and 14 analytes were validated for quantitative and qualitative testing, respectively.

Conclusions
A convenient UPLC-MS/MS assay for simultaneously monitoring 37 analytes in human urine was validated for use in pain management testing. Advantages of this multiplex assay include facile sample preparation and higher-throughput definitive detection including glucuronide metabolite quantification.
Reapproaching Old Buildings within the City
Authors: Fortuna Carlos 
Published: January 2019

Suddenly for some reason I thought of Brasilia. The city of Brasilia was inaugurated in 1960. It was a perfect multidisciplinary exercise of harmonization between the urban planner (Lúcio Costa), the architect Óscar Niemeyer), and the landscape artist-architect (Roberto Burle Marx). Moreover, Brasilia was a typical construction of a city by the conquest of the open space made of sheer optimism, the triumph of talent over doubt and of the audacity over pessimism (Gorelik, 2005).
This reference to Brasilia serves as a sort of epigraph with which I will unravel some of my loose topics about the role of old buildings in reapproaching the contemporary city. I have never addressed specifically a journal for architects, city planners, or urban designers. On the contrary, I am far more used to deal with urban issues for groups of social scientists, sociologists, like myself, historians, anthropologists, geographers, and so forth. Here I am anyway, trying to address the issue of buildings and their possible reuses upon an interdisciplinary view, counting on your benevolence.
Drawing is Not Enough. Design Tools for the Reuse of Modernist Buildings
Authors: Gaenshirt Christian 
Published: January 2019

This paper[i] re-discusses the question of design tools, a metaphor that lately has been used for different things such as simple objects, media, cultural techniques, computer programs, formal principles or thinking strategies. After reviewing recent research on design tools, a taxonomy will be proposed. The key tool for the reuse of modernist buildings though remains the building itself, and its related narratives.

[i] The author would like to thank Xi'an Jiaotong-Liverpool University, in Suzhou, China, for generously founding his work on this research, as well as his travel to participate in the RMB conference in April 2018 at the University of Coimbra, Portugal. He also would like to thank Shayne Jones for disucssing and revising earlier versions of this text.
Vernakularisasi dalam Tafsir Nusantara: Kajian atas Tafsir Faid al-Rahman karya KH. Sholeh Darat al-Samarani
Authors: Faiqoh Lilik 
Published: January 2019

This research discusses about vernacularization in Tafsir Nusantara: The Study of Tafsīr Faiḍ al-Raḥmān by KH. Sholeh Darat al-Samarani. There is a Tafsir Nusan- tara which appears with title of the book is Tafsīr Faiḍ al-Raḥmān fī Tarjamāh Tafsīr Kalām Malik ad-Dayyān by KH. Sholeh Darat al-Samarani who lives in the last of 19th century and in the beginning of 20th century, as well the first mufassir who writes tafsir that use Javanese language with the alphabet letter of Arabic, the authors are interested to discuss Tafsīr Faiḍ al-Raḥmān. This research raises two form of problems about How vernacularization in Tafsīr Faiḍ al-Raḥmān in terms of language and how vernacularization in Tafsīr Faiḍ al-Raḥmān in terms of interpretation. By using vernacularization theory will be explained that to apply in Tafsīr Faiḍ al-Raḥmān appropriate with vernacularization process in the phenomena of the text which has developed in Tafsīr Faiḍ al-Raḥmān. So, this research can be concluded, first vernacularization in terms of lan- guage include word pengupo jiwo, nyumet damar, and saklas. Vernacularization in terms of language Tafsīr Faiḍ al-Raḥmān more describes about distinctive language of locality that is commonly used by local society. The second, vernacularization in terms of interpretation include Q.S. al-Fātiḥah ([1]: 2), and Q.S. al-Baqarah ([2]: 17), Q.S. al-Baqarah ([2]: 219). Vernacularisation of interpretation in Tafsīr Faiḍ al-Raḥmān more describes about localities’ expression, behaviors and attitudes of Javanese people, the nature of plants in Java and the realms of life in Java.
IDEOLOGI TAKFIRI MUHAMMAD AL-MAQDISI: Memahami Hubungan Beragama dan Bernegara Perspektif Maqāshid asy-Syarī‘ah
Authors: Widodo M. Hafidh 
Published: January 2019

The term "kaafir" (infidel) has existed since the time of the Prophet Muhammad. In the Koran, it is stated that kaafir is a person who does not believe that Allah Swt. as God Almighty, people who worship idols, and Ahl Kitab (Jewish and Christian). The meaning of this term then changed, not only aimed at non-Muslims but also addressed to Muslims themselves. Muhammad al- Maqdisi accused kaafir of those who did bid'ah, for those who made laws and those who followed laws other than the laws of the Koran and al-Hadith—then the Law, the 1945 Constitution, and Pancasila included kaafir products. As a consequence, they have been considered apostates and truly have become non-Muslims, and their blood is halal to be killed. The question is "how did the takfiri ideological concept according to Muhammad al-Maqdisi relate to religion and state".
Reverse Stein–Weiss Inequalities on the Upper Half Space and the Existence of Their Extremals
Authors: Chen Lu , Lu Guozhen , Tao Chunxia 
Published: January 2019

Abstract
The purpose of this paper is four-fold. First, we employ the reverse weighted Hardy inequality in the form of high dimensions to establish the following reverse Stein–Weiss inequality on the upper half space:

∫

ℝ
+
n

∫

∂
⁡

ℝ
+
n

|
x

|
α

|
x
-
y

|
λ

f

(
x
)

g

(
y
)

|
y

|
β

d

y

d
x
≥

C

n
,
α
,
β
,
p
,

q
′

∥
f

∥

L

q
′

⁢

(

ℝ
+
n

)

∥
g

∥

L
p

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∂
⁡

ℝ
+
n

)

\int_{\mathbb{R}^{n}_{+}}\int_{\partial\mathbb{R}^{n}_{+}}\lvert x|^{\alpha}|x% -y|^{\lambda}f(x)g(y)|y|^{\beta}\,dy\,dx\geq C_{n,\alpha,\beta,p,q^{\prime}}\|% f\/\|_{L^{q^{\prime}}(\mathbb{R}^{n}_{+})}\|g\|_{L^{p}(\partial\mathbb{R}^{n}_% {+})}

for any nonnegative functions

f
∈

L

q
′

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(

ℝ
+
n

)

{f\in L^{q^{\prime}}(\mathbb{R}^{n}_{+})}

,

g
∈

L
p

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(

∂
⁡

ℝ
+
n

)

{g\in L^{p}(\partial\mathbb{R}^{n}_{+})}

, and

p
,

q
′

∈

(
0
,
1
)

{p,q^{\prime}\in(0,1)}

,

β
<

1
-
n

p
′

{\beta<\frac{1-n}{p^{\prime}}}

or

α
<

-

n
q

{\alpha<-\frac{n}{q}}

,

λ
>
0

{\lambda>0}

satisfying

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1

n

⁢

1
p

+

1

q
′

-

α
+
β
+
λ

-
1

n

=
2

.

\frac{n-1}{n}\frac{1}{p}+\frac{1}{q^{\prime}}-\frac{\alpha+\beta+\lambda-1}{n}% =2.

Second, we show that the best constant of the above inequality can be attained. Third, for a weighted system analogous to the Euler–Lagrange equations of the reverse Stein–Weiss inequality, we obtain the necessary conditions of existence for any positive solutions using the Pohozaev identity. Finally, in view of the stereographic projection, we give a spherical form of the Stein–Weiss inequality and reverse Stein–Weiss inequality on the upper half space

ℝ
+
n

{\mathbb{R}^{n}_{+}}

.
On p-Robust Saturation on Quadrangulations
Authors: Westerdiep Jan 
Published: January 2019

Abstract
For the Poisson problem in two dimensions, posed on a domain partitioned into
axis-aligned rectangles with up to one hanging node per edge, we envision an
efficient error reduction step in an instance-optimal hp-adaptive finite
element method. Central to this is the problem: Which increase in local polynomial degree
ensures p-robust contraction of the error in energy norm? We reduce this problem to a small
number of saturation problems on the reference square, and provide strong numerical
evidence for their solution.