bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pembrolizumab in Patients With Metastatic Breast Cancer With High Tumor Mutational Burden: Results From the Targeted Agent and Profiling Utilization Registry (TAPUR) Study
Authors: Alva Ajjai S. , Mangat Pam K. , Garrett-Mayer Elizabeth , Halabi Susan , Hansra Damien , Calfa Carmen J. , Khalil Maged F. , Ahn Eugene R. , Cannon Timothy L. , Crilley Pamela , Fisher Julie G. , Haslem Derrick S. , Shrestha Sagun , Antonelli Kaitlyn R. , Butler Nicole L. , Warren Sasha L. , Rygiel Andrew L. , Ranasinghe Shamika , Bruinooge Suanna S. , Schilsky Richard L. 
Published: April 2021

PURPOSE The TAPUR Study is a phase II basket trial that aims to identify signals of antitumor activity of commercially available targeted agents in patients with advanced cancers harboring genomic alterations known to be drug targets. Results in a cohort of patients with metastatic breast cancer (mBC) with high tumor mutational burden (HTMB) treated with pembrolizumab are reported. METHODS Patients with advanced mBC received standard doses of either 2 mg/kg or 200 mg infusions of pembrolizumab every 3 weeks. Simon's two-stage design was used with a primary study end point of disease control (DC) defined as objective response or stable disease of at least 16 weeks duration. If two or more patients in stage I achieved DC, the cohort would enroll 18 additional patients in stage II. Secondary end points include progression-free survival (PFS), overall survival, and safety. RESULTS Twenty-eight patients were enrolled from October 2016 to July 2018. All patients' tumors had HTMB ranging from 9 to 37 mutations/megabase. DC and objective response were noted in 37% (95% CI, 21 to 50) and 21% of patients (95% CI, 8 to 41), respectively. Median PFS was 10.6 weeks (95% CI, 7.7 to 21.1); median overall survival was 30.6 weeks (95% CI, 18.3 to 103.3). No relationship was observed between PFS and tumor mutational burden. Five patients experienced ≥ 1 serious adverse event or grade 3 adverse event at least possibly related to pembrolizumab consistent with the product label. CONCLUSION Pembrolizumab monotherapy has antitumor activity in heavily pretreated patients with mBC characterized by HTMB. Our findings support the recent US Food and Drug Administration approval of pembrolizumab for treatment of patients with unresectable or metastatic solid tumors with HTMB without alternative treatment options.
Cigarette consumption in adult dual users of cigarettes and e-cigarettes: a review of the evidence, including new results from the PATH study
Authors: Lee Peter N. , Fry John S. , Forey Barbara A. , Coombs Katharine J. , Thornton Alison J. 
Published: April 2021

Background: Modelling disease risk from e-cigarette use requires knowing how much e-cigarette uptake affects a smoker’s cigarette consumption. From Waves 1-3 of the US PATH study and other evidence, we sought answers to three questions: (Q1) Does consumption differ between dual users and exclusive smokers? (Q2) Does initiating e-cigarettes affect cigarette consumption? (Q3) Is baseline consumption related to later initiation of e-cigarettes? Methods: Consumption data from PATH were corrected for clear recording errors, with e-cigarette use classified as established or every day, and adjustment made for demographics, use of alcohol, drugs and other tobacco products, and age of starting smoking. Searches identified other studies published since 2008, with Q1 answered from cross-sectional studies, and Q2 and Q3 also from prospective studies. Results: (Q1) In PATH, consumption in current every day e-cigarette users was 2-3 cigarettes per day lower in dual users, with no difference seen in established users. From 31 published studies, consumption was no lower in dual users for current or ever e-cigarette users. (Q2) In PATH study consistent decreases in consumption occurred in those becoming every day dual users with increases seen in those reverting to exclusive smoking. Thirteen published studies consistently showed reduced consumption in those becoming dual users. (Q3) Three studies consistently showed greater consumption in smokers subsequently initiating e-cigarettes, but no significant difference was seen for PATH. Conclusions: Assessment is complicated by the few every day e-cigarette users in PATH, and between-study variability in quantifying e-cigarette use and presentation of results. As taking up e-cigarettes is associated with reducing consumption, finding no clear cross-sectional difference between dual users and exclusive smokers suggests smokers taking up e-cigarettes had higher consumption initially, limited evidence supporting this. Given the much lower disease risk of e-cigarettes vs. cigarettes, smokers becoming dual users should somewhat reduce their disease risk.
A new analysis approach for single nephron GFR in intravital microscopy of mice
Authors: Kessel Friederike , Kröger Hannah , Gerlach Michael , Sradnick Jan , Gembardt Florian , Todorov Vladimir , Hugo Christian 
Published: April 2021

Background: Intravital microscopy is an emerging technique in life science with applications in kidney research. Longitudinal observation of (patho-)physiological processes in living mice is possible in the smallest functional unit of the kidney, a single nephron (sn). In particular, effects on glomerular filtration rate (GFR) - a key parameter of renal function - can be assessed. Methods: After intravenous injection of a freely filtered, non-resorbable, fluorescent dye in C57BL/6 mice, a time series was captured by multiphoton microsopy. Filtration was observed from the glomerular capillaries to the proximal tubule (PT) and the tubular signal intensity shift was analyzed to calculate the snGFR. Results: Previously described methods for snGFR analysis relied on two manually defined measurement points in the PT and the tubular volume was merely estimated in 2D images. We present an extended image processing workflow by adding continuous measurement of intensity along the PT in every frame of the time series using ImageJ. Automatic modelling of actual PT volume in a 3D dataset replaced 2D volume estimation. Subsequent data analysis in R, with a calculation of intensity shifts in every frame and normalization against tubular volume, allowed exact assessment of snGFR by linear regression. Repeated analysis of image data obtained in healthy mice showed a striking increase of reproducibility by reduction of user interaction. Conclusions: These improvements in image processing and data analysis maximize the reliability of a sophisticated intravital microscopy technique for the precise assessment of snGFR, a highly relevant predictor of kidney function.
Peripatetic teaching: what can medical education learn from ancient Greece?
Authors: Murphy John , Mannion Christopher J 
Published: April 2021

Background/Aims Peripatetic teaching originated in the Aristotelian school of ancient Greece and refers to the action of walking, discussion and deep learning. A pilot study was carried out to evaluate the educational impact of peripatetic teaching in clinical medical education. There has been no previous evaluation of this form of teaching within medical education. Methods A pilot study was carried out to evaluate small group clinical sessions encompassing peripatetic teaching. Results A total of 56 post teaching questionnaires were completed and evaluated (return rate ~95%). High levels of satisfaction (n~4.7/5) were reported from this method of teaching. On average, a total of 1420 steps were taken during each teaching session, identifying additional exercise benefits for all. Conclusions This article identifies educational and health benefits to peripatetic teaching. The authors present a simple framework to structure each teaching session using the mnemonic FIRM – Feedback, dIscussion, Reflection and Mentorship. From this pilot study, the authors conclude that there are perceived benefits for teacher and learner from this teaching method.
Risk factors associated with delayed and aseptic nonunion following tibial diaphyseal fractures managed with intramedullary nailing
Authors: Makaram Navnit S. , Leow Jun Min , Clement Nicholas D. , Oliver William M. , Ng Zhan H. , Simpson Cameron , Keating John F. 
Published: April 2021

AimsThe primary aim of this study was to identify independent predictors associated with nonunion and delayed union of tibial diaphyseal fractures treated with intramedullary nailing. The secondary aim was to assess the Radiological Union Scale for Tibial fractures (RUST) score as an early predictor of tibial fracture nonunion.MethodsA consecutive series of 647 patients who underwent intramedullary nailing for tibial diaphyseal fractures were identified from a trauma database. Demographic data, comorbidities, smoking status, alcohol consumption, use of non-steroidal anti-inflammatory drugs (NSAIDs), and steroid use were documented. Details regarding mechanism of injury, fracture classification, complications, and further surgery were recorded. Nonunion was defined as the requirement for revision surgery to achieve union. Delayed union was defined as a RUST score < 10 at six months postoperatively.ResultsThere were 41 nonunions (6.3%), of which 13 were infected (31.7%), and 77 delayed unions (11.9%). There were 127 open fractures (19.6%). Adjusting for confounding variables, NSAID use (odds ratio (OR) 3.50; p = 0.042), superficial infection (OR 3.00; p = 0.026), open fractures (OR 5.44; p < 0.001), and high-energy mechanism (OR 2.51; p = 0.040) were independently associated with nonunion. Smoking (OR 1.76; p = 0.034), open fracture (OR 2.82; p = 0.001), and high-energy mechanism (OR 1.81; p = 0.030) were independent predictors associated with delayed union. The RUST score at six-week follow-up was highly predictive of nonunion (sensitivity and specificity of 75%).ConclusionNSAID use, high-energy mechanisms, open fractures, and superficial infection were independently associated with nonunion in patients with tibial diaphyseal fractures treated with intramedullary nailing. The six-week RUST score may be useful in identifying patients at risk of nonunion. Cite this article: Bone Jt Open 2021;2(4):227–235.
Axis-Switching Behavior of Liquid Jets Issued from Non-Circular Nozzles Under Low-Intermediate Pressure
Authors: Hua Lin , Li Hong , Jiang Yue 
Published: April 2021

HighlightsThe flow behavior of water jets discharged from different orifices was investigated.High-speed photography (HSP) was used to obtain surface structures and spread characteristics of water jets.The deformation process in axis switching related to the corner vortices effect of non-circular jets was researched by numerical simulation.The axis switching of non-circular jets enhances entrainment ability of the jet.ABSTRACT. Low-intermediate pressure sprinkler irrigation systems are important research topics in the field of water-saving irrigation. Non-circular nozzles improve spray uniformity at lower pressures and are key components of sprinkler irrigation systems. In this article, the behavior of discharged water jets from nozzles with circular, square, and equilateral triangular orifices designed with the same flow rate was investigated. High-speed photography (HSP) was used to capture jet characteristics in the near field (z&lt;20D). The largest spread angle was obtained for the square jet, which was on average 37% larger than that of the circular jet. In addition, numerical simulations were performed to analyze the axis-switching process using the large-eddy simulation (LES) method and the coupled level-set and volume of fluid (CLSVOF) method. The axis-switching phenomenon was observed in non-circular jets, in which surrounding air mixed with the jet and promoted the formation of thin diaphragm structures. The deformation process that occurs in axis switching is described according to the simulated vorticity and velocity fields. The research results suggest the axis-switching phenomenon is induced by corner vortex motions produced by the polygonal orifice, which accelerate the decay of the axial velocity and increase the jet entrainment rate. Thus, the effect of corner vortices should be considered in the design of polygonal nozzles. Keywords: Axis switching, High-speed photography, Liquid jet, Low-intermediate pressure sprinkler irrigation, Non-circular nozzle, Numerical simulation.
Dual-period guided-mode resonance filters for SWIR multi-spectral image sensors
Authors: Mamun Md Ataul , Sayeed Rezwan Mohammad , Gigante Michael , Özgür Ümit , Avrutin Vitaliy 
Published: April 2021

Typical guided-mode resonance (GMR) transmission filter design, which is based on a single ridge per period, necessitates multiple etching/fabrication steps for implementing an array of filters (having different transmission bands) on the same substrate. To address this problem, we demonstrate dual-period narrow bandpass GMR filters that offer more degrees of freedom, two periods and two fill-factors, for tuning the filter characteristics and achieving wider stop bands without changing the grating height. A set of six transmission filters with well-separated passbands in the short-wave infrared region was designed using COMSOL Multiphysics simulations and produced on the same silicon-on-quartz wafer in a single fabrication run. The

90

µ

m

×

90

µ

m

size filters exhibited passbands as narrow as 15 nm with peak-wavelength tunability over 200 nm, flat stop bands as wide as

∼

400

n
m

, and peak transmittance reaching 87%. The experimental transmission spectra were in good agreement with the corresponding simulations. These findings pave the way for the realization of pixel size filter arrays for multispectral image sensors.
Uht treatment of liquid egg yolk
Authors: Ayari Emna , Németh Csaba , Tóth Adrienn , Khabat Noori , Pintér Richàrd , Friedrich László 
Published: April 2021

Egg and its product are easily perishable items because of their high moisture content, although they have a very high amount of nutrients, especially protein. Many efforts have been channelled to increase the shelf-life of these products but heat treatment according to literature is the most promising although egg and its products are heat-sensitive. Thus, a very low temperature is needed or a high temperature for a very short time. Ultra-Heat Treatment (UHT) is one of the known technologies that we used for heat-sensitive products.
The aim of the study was to investigate the effect of UHT treatment (approximately 67 °C for 190 seconds) on Liquid Egg Yolk (LEY) and Liquid Egg Yolk with additive (LEYA). During twenty-one days, the pH and colour were measured every seven days for all the samples. Emulsion stability was also studied by the methods of heat stability for mayonnaise. pH and colour measurements were used assess the quality of liquid egg yolks after 21 days of storage. From the results, raw LEY had the shortest shelf life and gave off a foul smell after 14 days of storage with significant colour changes. Addition of citric acid as an additive however improved the shelf life of the LEY with a relatively low pH. UHT treated LEY also showed improved shelf life of the LEY with a relatively constant pH from day 14 until the end of the experiment (day 21). UHT treatment of LEY with addition of addition of citric acid as an additive may help optimise the shelf life of the product.
Underlying causes of global food price changes
Authors: Gombkötő Nóra 
Published: April 2021

There is a significant increase in food prices all over the world. Rate of annual increases in prices of all kinds of food is more than 100 percent. However, this can lead to long-term food crisis. The research aims to find out the factors that contribute to a large increase in food prices, as well as to predict the likely consequences of food price increases. Then potential solutions related to specific problems should be highlighted. In this study several factors were determined, which were contributed to central (global food price increase) and general problems. These problems were separated by cause and consequences, they were structured and ordered hierarchically. Through outline the problems it can be improved that in global market of foods both demand and supply are influenced by many factors. The most important factors affected demand are: increase of population and urban population all over the world and increase of income level and internal migration in emerging countries. Supply is influenced by the following factors: a decrease in the yield of agricultural crops, low level of productivity in agricultural sector, as well as reduction in food crops production area because of unfavourable weather and increased production of biofuels. Most of general and specific factors, which affect food price increase, are related to each other causally but there are also separate factors. The most effective solution to the problem is increasing of agricultural productivity at the same time investments into agricultural researches and rural infrastructure.
Application of some lactic acid bacteria strains to improve fermentation and aerobic stability of maize silage
Authors: Peter Szucs Judit , Suli Agnes , Suli Zakar Timea , Berecz Elizabet , Pek Mate 
Published: April 2021

The object of the trial was to study the effect of some lactic acid bacteria strains on the fermentation and aerobic stability of whole plant maize silages.The whole plant maize raw material was 32% DM, in soft cheddar stage of grain ripeness. It was ensiled in 4.2 litre capacity glass micro-size silos in 5 replicates /each treatment and stored on constant air conditioned room temperature (22 oC) during 95 days. The average packing density of raw material was 211 kg DM/m3.The applied treatments: 1. Untreated control maize, 2. Enterococcus faecium 100,000 CFU/g fresh maize (FM), 3. Lactobacillus plantarum 50,000 CFU/g FM + Enterococcus faecium 50,000 CFU/g FM, 4. Lactococcus lactis 100,000 CFU/g FM, 5. Lactobacillus plantarum 50,000 CFU/g FM + Lactococcus lactis 50,000 CFU/g FM, 6. Lactobacillus plantarum 100,000 CFU/g FM.Aerobic stability study: Applied Honig (1990 system).The main experiences are the following: Applied lactic acid bacteria strains improved the quality of fermentation of maize in general compare to untreated control one.Lactic acid bacteria strains significantly stimulated lactic acid production and decreased propionic and butyric acid production. The origin of ammonia decreased also under influence of lactic acid bacteria strains in unaerobic conditions.Enterococcus faecium and.Lactococcus lactis are not able to protect the maize silages against the aerobic deterioration with the applied dosage. Lactobacillus plantarum itself produced the most favourable fermentation characteristics and protected the aerobic stability of silage the most effectively (during 4 day) compare to all other treated maize silages.
Relation of wheat species and genomes in amino-acid composition
Authors: Pepo Pal 
Published: April 2021

As regards wheat varieties constituting a natural ploid series the issue of analysing diploid, tetraploid and hexaploid species is topical since ancient varieties can play significant roles in contemporary agriculture as well. Seventeen winter wheat varieties, out of which 2 diploid varieties carried genome A, 9 diploidic types had genomes AB, two varieties had genomes AG and four varieties were hexaploid ones with genomes ABD, were analysed from the point of view of their amino acid compositions. The amino acid contents of Asp, Thr, Ser, Glu, Gly, Ala, Cys, Val, Met, Ile, Leu, Tyr, Phe, His, Lys, Arg, Pro (a total of 17) were determined in the varieties listed above.
It has been found that the amino acid contents of the grains genotype AA Triticum boeticum and T. monococcum exceeded the amino acid content of T. aestivum in respect of all the amino acids analysed in this experiment, with Glu being the only exception. In comparison with the aestivum wheat, essential amino acid contents showed a similarly favourable picture in the diploidic varieties mentioned. As regards type AB tetraploid varieties excesses of 13-16%, in comparison to the aestivum wheat, were found in essential amino acid contents. The amounts of non-essential amino acids in all the winter wheat varieties showed decreases irrespective of the ploid level.
What concerns the total amino acid content, all the winter wheat varieties with the exception of T. monococcum (A), T. dicoccoides (AB) and T. dicoccum (AB) contained less amino acid than the aestivum wheat. All the monocarbonic acid and aromatic as well as heterocyclic amino acid contents of the wildly growing Triticum boeticum (A) and the grown Triticum monococcum (A) (with polaric, apolaric R groups, diamino radicles) exceeded the same contents of T. aestivum. The value of the monoamino-dicarbonic acid, however, was lower in our experiment.
Development of Lycoriella ingenua and Bradysia impatiens on different phases of agaricus composts
Authors: Kecskeméti Sándor , Fail József , Geösel András 
Published: April 2021

Fungus gnats are small, dark colored, mosquito like fragile insects. They can be encountered all around the world, excluding places with extreme climate. Gnats prefer habitats that are damp with high relative humidity and rich in organic debris. Most of the species are not considered to be harmful in agriculture, but some may cause serious damage, especially in forcing of vegetable or ornamental plants. In mushroom production, however, they are considered as the most destructive pests; the damage caused by them alone can result in huge loss for mushroom farmers. In the Hungarian mushroom industry, fungus gnats damage mainly white-button mushroom, oyster mushroom and pioppino productions. Lycoriella ingenua (Dufour, 1839) and Bradysia impatiens (Johannsen, 1912) are the two most commonly found fungus gnat species from the family Sciaridae on Hungarian mushroom farms.
We have conducted an experiment with the two aforementioned species, to find out, whether they can fully develop into adults, feeding purely on Agaricus compost diet. We used unspawned white button mushroom compost (phase 2) and spawned compost which has been colonized by the mycelia of Agaricus bisporus (phase 3). We did not conduct any experiment with the first compost phase, as it undergoes pasteurization, which eliminates any pests in it. We recorded emerging gnats only from phase 2 compost. Neither L. ingenua, nor B. impatiens could complete its development on phase 3 compost diet, furthermore not even pupae were observed in these breeding pots. From pots containing phase 2 compost, a total of 1607 adults emerged. The number of B. impatiens adults was 653, and 954 for L. ingenua. Sex ratios for the two species were different. For B. impatiens, the number of females was 1.36 times greater than that of males, in L. ingenua there were 1.7 times more males than females in total. Swarming took approximately 6 days for B. impatiens and 10 days for L. ingenua. From the experiment we can conclude that phase 3 compost, which is well interwoven with Agaricus bisporus mycelia is not suitable for B. impatiens and L. ingenua to complete their whole life cycle.