bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stimulated Raman scattering simulation for imaging optimization
Authors: Zada Liron , Fokker Bart , Leslie Heather A. , Vethaak A. Dick , de Boer Johannes F. , Ariese Freek 
Published: June 2021

AbstractTwo simulation programs of a stimulated Raman scattering microscopy (SRS) imaging system with lock-in amplifier (LIA) detection were developed. SRS is an imaging technique based on the vibrational Raman cross-section as the contrast mechanism and enables fast, label-free imaging. Most SRS implementations are based on LIA detection of a modulated signal. However, building and operating such SRS set-ups still poses a challenge when selecting the LIA parameter settings for optimized acquisition speed or image quality. Moreover, the type of sample, e.g. a sparse sample vs. a densely packed sample, the required resolution as well as the Raman cross-section and the laser powers affect the parameter choice.A simulation program was used to find these optimal parameters. The focal spot diameters of the individual lasers (pump and Stokes) were used to estimate the effective SRS signal focal spot and the (optical) spatial resolution. By calibrating the signal and noise propagation through an SRS system for a known molecule, we estimated the signal and noise input to the LIA. We used a low pass filter model to simulate the LIA behavior in order to find the optimal parameters (i.e. filter order and time constant).Optimization was done for either image quality (expressed as contrast to noise ratio) or acquisition time. The targeted object size was first determined as a measure for the required resolution. The simulation output consisted of the LIA parameters, pixel dwell time and contrast to noise ratio.In a second simulation we evaluated SRS imaging based on the same principles as the optimal setting simulation, i.e. the signals were propagated through an imaging system and LIA detection. The simulated images were compared to experimental SRS images of polystyrene beads.Finally, the same software was used to simulate multiplexed SRS imaging. In this study we modeled a six-channel frequency-encoded multiplexed SRS system demodulated with six LIA channels. We evaluated the inter-channel crosstalk as a function of chosen LIA parameters, which in multiplex SRS imaging also needs to be considered.These programs to optimize the contrast to noise ratio, acquisition speed, resolution and crosstalk will be useful for operating stimulated Raman scattering imaging setup, as well as for designing novel setups.
A single robust stability-indicating RP-HPLC analytical tool for apigenin quantification in bulk powder and in nanoliposomes: a novel approach
Authors: Shetti Priya , Jalalpure Sunil S. 
Published: June 2021

Abstract
Background
Apigenin (4′, 5, 7-trihydroxyflavone), a flavonoid, is present usually in fruits and vegetables possessing numerous biological properties like antioxidant, anti-viral, antibacterial, anti-inflammatory, and chemoprevention activity. So present study was aimed to prepare and characterize nanoliposomes of apigenin and estimate its encapsulation efficiency by stability-assisted reverse-phase (RP)-HPLC method.

Results
The stability indication of the RP-HPLC method developed for apigenin-loaded nanoliposomes was successfully demonstrated and parameters were mainly the retention time which was 4.21 min, limit of detection (LOD) 0.49 μg/mL, limit of quantification (LOQ) 1.48 μg/mL, and %relative standard deviation (RSD) less than 2%. Therefore, the stability indication of the developed reverse-phase HPLC method for apigenin-loaded nanoliposomes was demonstrated successfully and parameters like accuracy, linearity, LOD, LOQ, precision, and %RSD were within the limit range and found to be satisfactory.

Conclusion
The developed RP-HPLC method was found to be suitable for the quantification or estimation of apigenin with its stability in apigenin-loaded nanoliposomes, and this method will be a powerful tool in the future for the estimation of apigenin present in any pharmaceutical preparations.
Therapeutic Implications of Germline Testing in Patients With Advanced Cancers
Authors: Stadler Zsofia K. , Maio Anna , Chakravarty Debyani , Kemel Yelena , Sheehan Margaret , Salo-Mullen Erin , Tkachuk Kaitlyn , Fong Christopher J. , Nguyen Bastien , Erakky Amanda , Cadoo Karen , Liu Ying , Carlo Maria I. , Latham Alicia , Zhang Hongxin , Kundra Ritika , Smith Shaleigh , Galle Jesse , Aghajanian Carol , Abu-Rustum Nadeem , Varghese Anna , O'Reilly Eileen M. , Morris Michael , Abida Wassim , Walsh Michael , Drilon Alexander , Jayakumaran Gowtham , Zehir Ahmet , Ladanyi Marc , Ceyhan-Birsoy Ozge , Solit David B. , Schultz Nikolaus , Berger Michael F. , Mandelker Diana , Diaz Luis A. , Offit Kenneth , Robson Mark E. 
Published: June 2021

PURPOSE Tumor mutational profiling is increasingly performed in patients with advanced cancer. We determined the extent to which germline mutation profiling guides therapy selection in patients with advanced cancer. METHODS Patients with cancer undergoing tumor genomic profiling were prospectively consented for germline cancer predisposition gene analysis (2015-2019). In patients harboring germline likely pathogenic or pathogenic (LP/P) alterations, therapeutic actionability was classified using a precision oncology knowledge base. Patients with metastatic or recurrent cancer receiving germline genotype–directed therapy were determined. RESULTS Among 11,947 patients across > 50 malignancies, 17% (n = 2,037) harbored a germline LP/P variant. By oncology knowledge base classification, 9% (n = 1042) had an LP/P variant in a gene with therapeutic implications (4% level 1; 4% level 3B; < 1% level 4). BRCA1/2 variants accounted for 42% of therapeutically actionable findings, followed by CHEK2 (13%), ATM (12%), mismatch repair genes (11%), and PALB2 (5%). When limited to the 9,079 patients with metastatic or recurrent cancer, 8% (n = 710) harbored level 1 or 3B genetic findings and 3.2% (n = 289) received germline genotype–directed therapy. Germline genotype–directed therapy was received by 61% and 18% of metastatic cancer patients with level 1 and level 3B findings, respectively, and by 54% of BRCA1/2, 75% of mismatch repair, 43% of PALB2, 35% of RAD51C/D, 24% of BRIP1, and 19% of ATM carriers. Of BRCA1/2 patients receiving a poly(ADP-ribose) polymerase inhibitor, 45% (84 of 188) had tumors other than breast or ovarian cancer, wherein the drug, at time of delivery, was delivered in an investigational setting. CONCLUSION In a pan-cancer analysis, 8% of patients with advanced cancer harbored a germline variant with therapeutic actionability with 40% of these patients receiving germline genotype–directed treatment. Germline sequence analysis is additive to tumor sequence analysis for therapy selection and should be considered for all patients with advanced cancer.
Immediate-Release Formulations Produced via Twin-Screw Melt Granulation: Systematic Evaluation of the Addition of Disintegrants
Authors: Steffens Kristina E. , Wagner Karl G. 
Published: June 2021

AbstractThe current study evaluated the effect of location and amount of various superdisintegrants on the properties of tablets made by twin-screw melt granulation (TSMG). Sodium-croscarmellose (CCS), crospovidone (CPV), and sodium starch glycolate (SSG) were used in various proportions intra- and extra-granular. Tabletability, compactibility, compressibility as well as friability, disintegration, and dissolution performance were assessed. The extra-granular addition resulted in the fasted disintegration and dissolution. CPV performed superior to CCS and SSG. Even if the solid fraction (SF) of the granules was lower for CPV, only a minor decrease in tabletability was observed, due to the high plastic deformation of the melt granules. The intra-granular addition of CPV resulted in a more prolonged dissolution profile, which could be correlated to a loss in porosity during tableting. The 100% intra-granular addition of the CPV resulted in a distinct decrease of the disintegration efficiency, whereas the performance of SSG was unaffected by the granulation process. CCS was not suitable to be used for the production of an immediate-release formulation, when added in total proportion into the granulation phase, but its efficiency was less impaired compared to CPV. Shortest disintegration (78 s) and dissolution (Q80: 4.2 min) was achieved with CPV extra-granular. Using CPV and CCS intra-granular resulted in increased disintegration time and Q80. However, at a higher level of appx. 500 s and appx. 15 min, only SSG showed a process and location independent disintegration and dissolution performance.
Avidity and Outcomes of Radioiodine Therapy for Distant Metastasis of Distinct Types of Differentiated Thyroid Cancer
Authors: Simões-Pereira Joana , Mourinho Nádia , Ferreira Teresa C , Limbert Edward , Cavaco Branca Maria , Leite Valeriano 
Published: June 2021

Abstract

Context
The recommendations for radioactive-iodine treatment (RAIT) in metastatic differentiated thyroid cancer (DTC) are mostly based in the experience with papillary histotype and do not consider the differences within the distinct types of DTC, in terms of RAIT uptake and response.

Objective
This work aims to investigate the association between histology and RAIT avidity and response, and to evaluate whether histotype was an independent prognostic factor in progression-free survival (PFS) and disease-specific survival (DSS) after RAIT for distant metastatic disease.

Methods
A retrospective analysis was conducted of all DTC patients who underwent RAIT for distant metastatic disease, from 2001 to 2018, at a thyroid cancer referral center. We included 126 patients: 42 (33.3%) classical variant papillary thyroid cancer (cvPTC), 45 (35.7%) follicular variant PTC (fvPTC), 17 (13.5%) follicular thyroid cancer (FTC) and 22 (17.5%) Hürthle cell carcinoma. Main outcome measures included RAIT avidity and response.

Results
RAIT avidity was independently associated with histology (P &lt; .001) and stimulated thyroglobulin (Tg) at first RAIT for distant lesions (P = .007). Avidity was lowest in HCC (13.6%), intermediate in cvPTC (21.4%), and highest in fvPTC (75.6%) and FTC (76.5%). Regarding RAIT response, HCC and FTC were not different; both showed significantly more often progression after RAIT than fvPTC and cvPTC. Histology influenced PFS (P = .014), but tumor type was not a significant prognostic factor in DSS. Instead, age at diagnosis, resection status, and stimulated Tg at the first RAIT were significantly associated with DSS.

Conclusion
DTC histotype influenced RAIT avidity and PFS. It is crucial to better detect the metastatic patients that may benefit the most from RAIT.
Hyperinsulinemic Compensation for Insulin Resistance Occurs Independent of Elevated Glycemia in Male Dogs
Authors: Ader Marilyn , Bergman Richard N 
Published: June 2021

Abstract
Insulin resistance engenders a compensatory increase in plasma insulin. Inadequate compensation is a primary element in the pathogenesis of type 2 diabetes. The signal that heralds developing insulin resistance and initiates hyperinsulinemic compensation is not known. It has often been assumed to be increased glucose. We tested this assumption by determining whether development of fasting and/or glucose-stimulated hyperinsulinemia with diet-induced insulin resistance occurs because of concomitant elevation of glycemia. Male dogs (n = 58) were fed a hypercaloric, fat-supplemented diet for 6 weeks. Dogs underwent magnetic resonance imaging to quantify total and regional (visceral, subcutaneous) adiposity as well as euglycemic hyperinsulinemic clamps. A subset of animals also underwent an insulin-modified intravenous glucose tolerance test to assess insulin sensitivity, acute insulin response (AIRg), and glucose effectiveness. Fat feeding caused modest weight gain, increased visceral and subcutaneous fat, and insulin resistance at both peripheral and hepatic levels. Hyperinsulinemic compensation was observed in fasting levels as well as increased AIRg. However, we observed absolutely no increase in carefully measured fasting, evening (6 to 8 pm) or nocturnal glycemia (2 to 4 am). Insulin resistance and hyperinsulinemia occurred despite no elevation in 24-hour glucose. Compensatory development of hyperinsulinemia during diet-induced insulin resistance occurs without elevated fasting or 24-hour glycemia. These data refute the idea that glucose itself is a requisite signal for β-cell upregulation. Alternative feedback mechanisms need to be identified.
Heart rate and startle responses in diving, captive harbour porpoises (Phocoena phocoena) exposed to transient noise and sonar
Authors: Elmegaard Siri L. , McDonald Birgitte I. , Teilmann Jonas , Madsen Peter T. 
Published: June 2021

ABSTRACTAnthropogenic noise can alter marine mammal behaviour and physiology, but little is known about cetacean cardiovascular responses to exposures, despite evidence that acoustic stressors, such as naval sonars, may lead to decompression sickness. Here, we measured heart rate and movements of two trained harbour porpoises during controlled exposure to 6–9 kHz sonar-like sweeps and 40 kHz peak-frequency noise pulses, designed to evoke acoustic startle responses. The porpoises initially responded to the sonar sweep with intensified bradycardia despite unaltered behaviour/movement, but habituated rapidly to the stimuli. In contrast, 40 kHz noise pulses consistently evoked rapid muscle flinches (indicative of startles), but no behavioural or heart rate changes. We conclude that the autonomous startle response appears decoupled from, or overridden by, cardiac regulation in diving porpoises, whereas certain novel stimuli may motivate oxygen-conserving cardiovascular measures. Such responses to sound exposure may contribute to gas mismanagement for deeper-diving cetaceans.
The road to generating transplantable organs: from blastocyst complementation to interspecies chimeras
Authors: Zheng Canbin , Ballard Emily B. , Wu Jun 
Published: June 2021

ABSTRACT
Growing human organs in animals sounds like something from the realm of science fiction, but it may one day become a reality through a technique known as interspecies blastocyst complementation. This technique, which was originally developed to study gene function in development, involves injecting donor pluripotent stem cells into an organogenesis-disabled host embryo, allowing the donor cells to compensate for missing organs or tissues. Although interspecies blastocyst complementation has been achieved between closely related species, such as mice and rats, the situation becomes much more difficult for species that are far apart on the evolutionary tree. This is presumably because of layers of xenogeneic barriers that are a result of divergent evolution. In this Review, we discuss the current status of blastocyst complementation approaches and, in light of recent progress, elaborate on the keys to success for interspecies blastocyst complementation and organ generation.
o2geosocial: Reconstructing who-infected-whom from routinely collected surveillance data
Authors: Robert Alexis , Funk Sebastian , Kucharski Adam J 
Published: June 2021

Reconstructing the history of individual transmission events between cases is key to understanding what factors facilitate the spread of an infectious disease. Since conducting extended contact-tracing investigations can be logistically challenging and costly, statistical inference methods have been developed to reconstruct transmission trees from onset dates and genetic sequences. However, these methods are not as effective if the mutation rate of the virus is very slow, or if sequencing data is sparse.We developed the packageo2geosocialto combine variables from routinely collected surveillance data with a simple transmission process model. The model reconstructs transmission trees when full genetic sequences are unavailable, or uninformative. Our model incorporates the reported age-group, onset date, location and genotype of infected cases to infer probabilistic transmission trees. The package also includes functions to summarise and visualise the inferred cluster size distribution.The results generated byo2geosocialcan highlight regions where importations repeatedly caused large outbreaks, which may indicate a higher regional susceptibility to infections. It can also be used to generate the individual number of secondary transmissions, and show the features associated with individuals involved in high transmission events.The package is available for download from the Comprehensive R Archive Network (CRAN) and GitHub.
Worldviews of science teachers in educational-technological context as a key factor in digitalization of teaching practices
Authors: Tsybulsky Dina , Muchnik-Rozanov Yulia 
Published: June 2021

Background:This research deals with science teachers' worldviews in the educational-technological context. Obtaining a deeper insight into teachers' discourse regarding school digitalization and understanding teachers' worldviews in the educational-technological context may be viewed as crucially important since the latter tends to play a central role in the process of digitalization of teaching practices.Methods:This study addresses the following questions: (1) Was there a difference between the teachers regarding their foci of attention expressed via personal pronouns? (2) Was there a difference between the teachers in terms of the quality and degree of their emotional immersion in the discussed topic expressed through the use of emotion words? (3) What are the semantic fields of the word clusters that include the lexemes technology and digital, and do they implicitly convey differences in teachers' understanding of school digitalization? The data were extracted by means of in-depth interviews with 38 Israeli science teachers. The linguistic analysis was employed to examine teachers' language behavior.Results:The results point out the differences in teachers' worldviews, manifested through language behavior. In particular, the differences between the three groups of teachers (outside observers, circumspect participants, and conscientious participants) were found regarding their foci of attention, the level of emotional immersion, and their implicitly conveyed understanding of the digitalization of teaching practices.Conclusions:The teachers' worldviews are the key element for understanding what it means to be or not to be a teacher in a digital society. In addition, our study demonstrates that linguistic analysis in educational research is a promising methodological approach that can render an in-depth and comprehensive picture of the explored phenomenon.
Case Report: Postmortem bone histomorphometric analysis in a 38-year-old Japanese man with immobilization osteoporosis because of orthostatic hypotension related to amyloid light chain amyloidosis
Authors: Hatano Masaki , Kitajima Izuru , Nakamura Masaki , Isawa Kazuya , Suwabe Tatsuya , Hoshino Junichi , Kinowaki Keiichi , Ohashi Kenichi , Sawa Naoki , Yamamoto Seizo , Ubara Yoshifumi 
Published: June 2021

We performed a postmortem bone histomorphometric analysis of iliac bone on a 38-year-old man who had been bedridden for the nine months before his death because of orthostatic hypotension and severe malnutrition related to amyloidκ-light-chain amyloidosis. Cancellous bone volume was greatly decreased, with a trabecular bone volume to total bone volume ratio of 6.77% (normal value, 19.56% ± 5.62%). Trabecular thinning was also apparent, with a trabecular thickness of 78.9 μm (normal value, 131.3 ± 28.1 μm), although the trabecula was still preserved. Cortical bone width was normal, although areas of porosity area were clear throughout the cortical bone. Our findings indicate that immobilization-related osteoporosis may be closely associated with loss of cancellous bone.
Determinants of regulatory compliance in health and social care services: a systematic review protocol
Authors: Dunbar Paul , Browne John P. , O'Connor Laura 
Published: June 2021

Background: The delivery of high quality health and social care services is a fundamental goal for health systems worldwide. Identifying the determinants of quality is a complex task as there are a myriad of variables to choose from. Researchers in this field have assessed a range of organisational and environmental factors (for example: staff composition, facility ownership, facility size) for an association with various quality metrics. Less attention has been paid to the determinants of compliance with quality regulation. Identifying the determinants of compliance has the potential to improve regulatory processes and can inform quality improvement initiatives undertaken by service providers and policy makers. This protocol describes a systematic review which will review literature from a wide range of study designs and sources to develop an overview of the determinants of regulatory compliance in health and social care services. Methods: A wide range of study designs and grey literature will be sought for this review. Searches will be conducted using PubMed, MEDLINE, PsycInfo, SocINDEX and CINAHL databases. The studies included in the review will be subject to quality appraisal with reference to the collection of tools available from the Joanna Briggs Institute. Data extraction will be informed by the Consolidated Framework for Implementation Research (CFIR). A narrative synthesis will be conducted on the barriers, facilitators and factors associated with compliance, with reference to the concepts mapped onto the CFIR. GRADE-CERQual will be used to grade the overall body of evidence. Conclusion: The findings of this review will be useful to regulators to inform regulatory policy and practice. Service providers and policy makers may also use the findings to inform quality improvement initiatives aimed at improving compliance and quality across a range of health and social care services.