bluuebunny/crossref_metadata_2025_split huggingface dataset:
Encorafenib Plus Cetuximab as a New Standard of Care for Previously Treated BRAF V600E–Mutant Metastatic Colorectal Cancer: Updated Survival Results and Subgroup Analyses from the BEACON Study
Authors: Tabernero Josep , Grothey Axel , Van Cutsem Eric , Yaeger Rona , Wasan Harpreet , Yoshino Takayuki , Desai Jayesh , Ciardiello Fortunato , Loupakis Fotios , Hong Yong Sang , Steeghs Neeltje , Guren Tormod Kyrre , Arkenau Hendrik-Tobias , Garcia-Alfonso Pilar , Elez Elena , Gollerkeri Ashwin , Maharry Kati , Christy-Bittel Janna , Kopetz Scott 
Published: January 2021

PURPOSE BEACON CRC evaluated encorafenib plus cetuximab with or without binimetinib versus investigators' choice of irinotecan or FOLFIRI plus cetuximab in patients with BRAFV600E–mutant metastatic colorectal cancer (mCRC), after progression on 1-2 prior regimens. In the previously reported primary analysis, encorafenib, binimetinib plus cetuximab (ENCO/BINI/CETUX; triplet) and encorafenib plus cetuximab (ENCO/CETUX; doublet) regimens improved overall survival (OS) and objective response rate (ORR; by blinded central review) versus standard of care. The purpose of this analysis was to report updated efficacy and safety data. METHODS In this open-label, phase III trial, 665 patients with BRAF V600E–mutant mCRC were randomly assigned 1:1:1 to receive triplet, doublet, or control. Primary end points were OS and independently reviewed ORR comparing triplet to control. OS for doublet versus control was a key secondary end point. Updated analyses include 6 months of additional follow-up and ORR for all randomized patients. RESULTS Patients received triplet (n = 224), doublet (n = 220), or control (n = 221). Median OS was 9.3 months (95% CI, 8.2 to 10.8) for triplet and 5.9 months (95% CI, 5.1 to 7.1) for control (hazard ratio [HR], 0.60 [95% CI, 0.47 to 0.75]). Median OS for doublet was 9.3 months (95% CI, 8.0 to 11.3) (HR v control, 0.61 [95% CI, 0.48 to 0.77]). Confirmed ORR was 26.8% (95% CI, 21.1% to 33.1%) for triplet, 19.5% (95% CI, 14.5% to 25.4%) for doublet, and 1.8% (95% CI, 0.5% to 4.6%) for control. Adverse events were consistent with the prior primary analysis, with grade ≥ 3 adverse events in 65.8%, 57.4%, and 64.2% for triplet, doublet, and control, respectively. CONCLUSION In the BEACON CRC study, encorafenib plus cetuximab improved OS, ORR, and progression-free survival in previously treated patients in the metastatic setting compared with standard chemotherapy. Based on the primary and updated analyses, encorafenib plus cetuximab is a new standard care regimen for previously treated patients with BRAF V600E mCRC.
Radiation Therapy for Small-Cell Lung Cancer: ASCO Guideline Endorsement of an ASTRO Guideline
Authors: Daly Megan E. , Ismaila Nofisat , Decker Roy H. , Higgins Kristin , Owen Dawn , Saxena Ashish , Franklin Gregg E. , Donaldson Dusty , Schneider Bryan J. 
Published: January 2021

PURPOSE The American Society for Radiation Oncology (ASTRO) produced an evidence-based guideline on radiation therapy (RT) for small-cell lung cancer (SCLC). Because of the relevance of this topic to ASCO membership, ASCO reviewed the guideline, applying a set of procedures and policies used to critically examine guidelines developed by other organizations. METHODS The ASTRO guideline on RT for SCLC was reviewed for developmental rigor by methodologists. Then, an ASCO Expert Panel reviewed the content and the recommendations. RESULTS The ASCO Expert Panel determined that the recommendations from ASTRO guideline on RT for SCLC, published in June 2020, are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorsed ASTRO guideline on RT for SCLC with a few discussion points. RECOMMENDATIONS Recommendations addressed thoracic radiotherapy for limited-stage SCLC, role of stereotactic body radiotherapy in stage I or II node-negative SCLC, prophylactic cranial radiotherapy, and thoracic consolidation for extensive-stage SCLC. Additional information is available at www.asco.org/thoracic-cancer-guidelines .
Mutational inactivation of Apc in the intestinal epithelia compromises cellular organisation
Authors: Rannikmae Helena , Peel Samantha , Barry Simon , Senda Takao , de la Roche Marc 
Published: January 2021

ABSTRACT
The adenomatous polyposis coli (Apc) protein regulates diverse effector pathways essential for tissue homeostasis. Truncating oncogenic mutations in Apc removing its Wnt pathway and microtubule regulatory domains drives intestinal epithelia tumorigenesis. Exuberant cell proliferation is one well-established consequence of oncogenic Wnt pathway activity; however, the contribution of other deregulated molecular circuits to tumorigenesis has not been fully examined. Using in vivo and organoid models of intestinal epithelial tumorigenesis we found that Wnt pathway activity controls intestinal epithelial villi and crypt structure, morphological features lost upon Apc inactivation. Although the Wnt pathway target gene c-Myc (also known as Myc) has critical roles in regulating cell proliferation and tumorigenesis, Apc specification of intestinal epithelial morphology is independent of the Wnt-responsive Myc-335 (also known as Rr21) regulatory element. We further demonstrate that Apc inactivation disrupts the microtubule cytoskeleton and consequently localisation of organelles without affecting the distribution of the actin cytoskeleton and associated components. Our data indicates the direct control over microtubule dynamics by Apc through an independent molecular circuit. Our study stratifies three independent Apc effector pathways in the intestinal epithelial controlling: (1) proliferation, (2) microtubule dynamics and (3) epithelial morphology.
This article has an associated First Person interview with the first author of the paper.
Adiposity, reproductive and metabolic health, and activity levels in zoo Asian elephant (Elephas maximus)
Authors: Chusyd Daniella E. , Nagy Tim R. , Golzarri-Arroyo Lilian , Dickinson Stephanie L. , Speakman John R. , Hambly Catherine , Johnson Maria S. , Allison David B. , Brown Janine L. 
Published: January 2021

ABSTRACTMany captive Asian elephant populations are not self-sustaining, possibly due in part to obesity-related health and reproductive issues. This study investigated relationships between estimated body composition and metabolic function, inflammatory markers, ovarian activity (females only) and physical activity levels in 44 Asian elephants (n=35 females, n=9 males). Deuterium dilution was used to measure total body water from which fat mass (FM) and fat-free mass (FFM) could be derived to estimate body composition. Serum was analyzed for progestagens and estradiol (females only), deuterium, glucose, insulin and amyloid A. Physical activity was assessed by an accelerometer placed on the elephant's front leg for at least 2 days. Relative fat mass (RFM) – the amount of fat relative to body mass – was calculated to take differences in body size between elephants into consideration. Body fat percentage ranged from 2.01% to 24.59%. Male elephants were heavier (P=0.043), with more FFM (P=0.049), but not FM (P&gt;0.999), than females. For all elephants, estimated RFM (r=0.45, P=0.004) was positively correlated with insulin. Distance walked was negatively correlated with age (r=−0.46, P=0.007). When adjusted for FFM and age (P&lt;0.001), non-cycling females had less fat compared with cycling females, such that for every 100 kg increase in FM, the odds of cycling were 3 times higher (P&lt;0.001). More work is needed to determine what an unhealthy amount of fat is for elephants; however, our results suggest higher adiposity may contribute to metabolic perturbations.
Tokay geckos (Gekkonidae: Gekko gecko) preferentially use substrates that elicit maximal adhesive performance
Authors: Garner Austin M. , Pamfilie Alexandra M. , Dhinojwala Ali , Niewiarowski Peter H. 
Published: January 2021

ABSTRACT
Gecko substrate use is likely influenced by adhesive performance, yet few studies have demonstrated this empirically. Herein, we examined the substrate use, adhesive performance and vertical clinging behaviour of Gekko gecko in captivity to investigate whether adhesive performance influences patterns of substrate use. We found that geckos were observed significantly more often on the substrate (glass) that elicited maximal adhesive performance relative to its availability within our experimental enclosures, indicating that geckos preferentially use substrates on which their adhesive performance is maximal. Our work here provides additional, yet crucial data establishing connections between adhesive performance and patterns of substrate use in captivity, suggesting the hypothesis that substrate preferences of free-ranging geckos should be correlated with adhesive performance. Clearly, further experimental and field research is necessary to test this hypothesis and identify other parameters that individually and/or collectively influence the habitat use of free-ranging geckos.
Написати Лемковину
Authors: Дуць-Файфер Олена 
Published: January 2021

AbstractWriting Lemkovyna. Interwar Lemko Literature – An Outline
The aim of the text is to show the main trends in the development of the interwar Lemko literature, strongly involved in the process of shaping and expressing the ethnic identity of the represented community. Faced with the challenges of difficult community experiences, literature takes on a documentary and interpretative role, building a collective memory and a vision of history. As regards literary activity, an integration of national and émigré creative milieus takes place. Especially the two most prominent representatives of the Lemko literature of the interwar period – Ivan Rusenko and Vanio Hunianka – are an example of a creative duo cooperating for many years, outlining the project of the national homeland in line with the aspirations of the native intelligentsia. In opposition to this project, a literary action of Ukrainianization is directed to the area of Lemkovyna, creating a vision of the historical past of the Lemko lands shared with Ukraine and using the model of nationally aware and unaware characters. Apart from ethnic involvement, there is also the literary phenomenon originating from Lemkowyna in the form of the works of Ihor Bohdan Antonycz. In the interwar period, due to the involvement in specifying and strengthening the ethnic shape of Lemkovyna, a lively development of political journalism and periodicals should also be noted.
Marketing digital en micro y pequeñas empresas de publicidad de Bogotá
Authors: Uribe Clara Inés , Sabogal Neira Daniel Fernando 
Published: January 2021

Este artículo presenta resultados de una investigación realizada en micro y pequeñas empresas de publicidad de Bogotá – Colombia. Objetivo: identificar las herramientas online usadas en sus estrategias de marketing digital, entre ellas el uso de las redes sociales y acciones de social media. Metodología: tipo exploratorio - descriptivo, mediante la técnica de análisis de contenido realizado en una muestra estadísticamente representativa de 365 empresas. Se hicieron, además, 140 encuestas a empresarios como forma de contraste al análisis. Resultados principales: la mayoría de micro y pequeñas empresas publicitarias, aún no tienen plataforma de comercio electrónico ni realizan acciones de posicionamiento en buscadores. Las redes sociales más usadas son Facebook e Instagram, donde en mayor medida difunden imágenes y contenidos propios. Conclusiones: las empresas de este tamaño aún no hacen un uso eficiente o estratégico de los recursos digitales para su autopromoción. Se evidencia la necesidad de capacitación específica para los empresarios del sector, fortalecimiento en la representación gremial y se vislumbra una oportunidad para este tipo de empresas en relación con las economías creativas, si emprenden procesos de digitalización.
Assessing Farm Stress and Community Supports in a U.S.-Mexico Border County
Authors: Keeney Annie J. , Hernandez Paola J. , Meng Yu 
Published: January 2021

HighlightsOf 24 study respondents, 56.3% had clinical depression symptomatology based on the CES-D depression screening scale.Depression scores were positively correlated with respondents’ ability to obtain credit.Unpredictable factors, such as government regulations and weather, were the most prevalent farm-related stressors among respondents.Abstract. Imperial County, California, is a high-need, medically underserved area that has some of the worst overall health outcomes of all California counties. Given this and the high depression and anxiety rates in agricultural occupations, Imperial County farmers and ranchers may be at an increased risk of stress and poor mental health outcomes. An exploratory mixed methods assessment was used to collect information from 24 farmers and ranchers in Imperial County. Survey topics included questions about farm or ranch operations, farm-related stress, mental health, community support, and health behaviors. The results indicate that most respondents perceive unpredictable factors, such as government regulations, as the most impactful stressors related to their farm or ranch operations. Additionally, depression symptomatology scores were positively correlated with respondents’ ability to obtain credit. Efforts to understand farm-related stress and how community support can help Imperial County farmers and ranchers mediate adverse physical and mental health effects through formal and informal networks are considered. Keywords: Community supports, Farm-related stress, Farmers and ranchers, Mental health, U.S.-Mexico border.
Eliminating the middleman: ultraviolet scale realization using a
laser-driven plasma light source
Authors: Arp Uwe , Hagley Edward , Vest Robert 
Published: January 2021

After we replaced the argon mini-arc with a laser-driven light source
in the Ultraviolet Spectral Comparator Facility at the National
Institute of Standards and Technology (NIST), we realized that the
optical power should be sufficient to use the comparator system for
absolute-cryogenic radiometry. Calibrating working standard detectors
directly against an absolute-cryogenic radiometer in the system used
for calibrations would eliminate all uncertainties resulting from the
use of transfer standards, which were calibrated in a separate system
using a different light source and optics. The transfer standards are
the middlemen we refer to in the title. Any uncertainty caused by
differences in bandpass, out-off-band radiation, spectral purity,
collimation, or data interpolation would be removed. In the end, we
successfully set up a twin system resembling the Ultraviolet Spectral
Comparator Facility and used this system to perform a primary
calibration of several photodiodes, based on an absolute-cryogenic
radiometer. Using this system, we were able to reduce relative
standard uncertainties at wavelengths below 220 nm from above 1 % (

k

=

1

) to below 0.5%. We refer to this
system as the Ultraviolet Scale Realization Facility or UV-SRF.
Joint estimation of self-mixing interferometry parameters and displacement reconstruction based on local normalization
Authors: Kim Jin-Hyok , Kim Chol-Hyon , Yun Tu-Hon , Hong Hui-Sung , Ho Kwang-Myong , Kim Kwang-Ho 
Published: January 2021

It is not easy to estimate self-mixing interferometry parameters, namely, the optical feedback factor and the linewidth enhancement factor from the self-mixing signals (SMSs) affected by noise such as speckle. These SMSs call for normalization, which is not only difficult, but also apt to distort the intrinsic information of the signals, thereby resulting in incorrect estimation of the parameters and the displacement reconstruction. In this paper, we present what we believe is a novel normalization method we call “local normalization,” which enables more exact and simpler estimation and displacement retrieval compared to previous methods, for it is based on an analytic relation instead of approximation. The method is very noise-proof, and especially speckle-noise-proof as well. The method proposed can be applied to moderate and strong feedback regimes. The simplicity and accuracy of the method will provide a fine tool for a low-cost self-mixing displacement sensor with a high resolution of about 40 nm.
AlGaAs-on-insulator waveguide for highly efficient photon-pair generation via spontaneous four-wave mixing
Authors: Mahmudlu Hatam , May Stuart , Angulo Alí , Sorel Marc , Kues Michael 
Published: January 2021

We report on the generation of correlated photon pairs in AlGaAs-on-insulator (AlGaAs-OI) waveguides through nonlinear spontaneous four-wave-mixing (SFWM). Our measurements reveal an SFWM pair generation efficiency of

∼

0.096
×

10

12

p
a
i
r
s

/

(

s
W

2

)

at a wavelength of 1550 nm. This is one of the highest efficiencies achieved to date for integrated SFWM sources. A maximal coincidence-to-accidental ratio of

∼

122

is measured. A spectral characterization of the device’s pair emission at the quantum level demonstrates a broad generation bandwidth of 2.0 THz, which is important for frequency multiplexing applications. Our results indicate that AlGaAs-OI is an efficient material platform for integrated quantum photonics at telecom wavelengths.
Trends and patterns of antibiotic prescribing at orthopedic inpatient departments of two private-sector hospitals in Central India: A 10-year observational study
Authors: Skender Kristina , Singh Vivek , Stalsby-Lundborg Cecilia , Sharma Megha 
Published: January 2021

Background
Frequent antibiotic prescribing in departments with high infection risk like orthopedics prominently contributes to the global increase of antibiotic resistance. However, few studies present antibiotic prescribing patterns and trends among orthopedic inpatients.

Aim
To compare and present the patterns and trends of antibiotic prescription over 10 years for orthopedic inpatients in a teaching (TH) and a non-teaching hospital (NTH) in Central India.

Methods
Data from orthopedic inpatients (TH-6446; NTH-4397) were collected using a prospective cross-sectional study design. Patterns were compared based on the indications and corresponding antibiotic treatments, mean Defined Daily Doses (DDD)/1000 patient-days, adherence to the National List of Essential Medicines India (NLEMI) and the World Health Organization Model List of Essential Medicines (WHOMLEM). Antibiotic prescriptions were analyzed separately for the operated and the non-operated inpatients. Linear regression was used to analyze the time trends of antibiotic prescribing; in total through DDD/1000 patient-days and by antibiotic groups.

Results
Third generation cephalosporins were the most prescribed antibiotic class (TH-39%; NTH-65%) and fractures were the most common indications (TH-48%; NTH-48%). Majority of the operated inpatients (TH-99%; NTH-97%) were prescribed pre-operative prophylactic antibiotics. The non-operated inpatients were also prescribed antibiotics (TH-40%; NTH-75%), although few of them had infectious diagnoses (TH-8%; NTH-14%). Adherence to the NLEMI was lower (TH-31%; NTH-34%) than adherence to the WHOMLEM (TH-65%; NTH-62%) in both hospitals. Mean DDD/1000 patient-days was 16 times higher in the TH (2658) compared to the NTH (162). Total antibiotic prescribing increased over 10 years (TH-β = 3.23; NTH-β = 1.02).

Conclusion
Substantial number of inpatients were prescribed antibiotics without clear infectious indications. Adherence to the NLEMI and the WHOMLEM was low in both hospitals. Antibiotic use increased in both hospitals over 10 years and was higher in the TH than in the NTH. The need for developing and implementing local antibiotic prescribing guidelines is emphasized.
LOOP, a cross-sectional, observational study investigating the clinical specialty setting as a determinant of disease management in psoriatic arthritis: Subgroup analysis results from Japan
Authors: Okada Masato , Kurimoto Sarina , Ganz Fabiana , Boehncke Wolf-Henning 
Published: January 2021

Background
Psoriatic arthritis (PsA) is a progressive erosive joint disorder that causes functional impairment; therefore, early diagnosis and management are essential. This study evaluated the association between clinical specialty and the time to management in patients with PsA in Japan.

Methods
This was a subgroup analysis of a cross-sectional, multicenter, observational study that was conducted in 17 countries outside the United States, including 17 sites at 8 institutions in Japan, from June 2016 to October 2017. Data from consecutive patients (age ≥18 years) with a suspected or established diagnosis of PsA on a routine visit to a participating rheumatology/orthopedic or dermatology clinic in Japan were analyzed. The primary endpoints were time from onset of inflammatory musculoskeletal symptoms to PsA diagnosis, PsA diagnosis to first conventional synthetic disease-modifying antirheumatic drug (csDMARD), PsA diagnosis to first biologic DMARD (bDMARD), and first csDMARD to first bDMARD.

Results
Of 109 patients with a confirmed diagnosis of PsA, 39.4% (n = 43) and 60.6% (n = 66) were recruited by rheumatologists/orthopedists and dermatologists, respectively. Most patients were prescribed tumor necrosis factor inhibitors (58.7%) or methotrexate (56.0%). The mean duration from symptom onset to PsA diagnosis was significantly longer (p = 0.044) for patients treated by rheumatologists/orthopedists (70.6 months) than those treated by dermatologists (30.1 months). In the rheumatology/orthopedic and dermatology settings, the mean time from PsA diagnosis to first csDMARD administration was −0.9 and −2.9 months, and from PsA diagnosis to first bDMARD 21.4 and 14.9 months, respectively. The mean duration from administration of first csDMARD to first bDMARD was comparable in the rheumatology/orthopedic (31.8 months) and dermatology (31.5 months) settings.

Conclusions
Treatment approach was slightly different between rheumatology/orthopedic and dermatology setting in clinical practice in Japan, suggesting that an integrated dermo-rheumatologic approach can optimize the management of patients with PsA.