bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance Evaluation of Montelukast Pediatric Formulations: Part I—Age-Related In Vitro Conditions
Authors: Guimarães Mariana , Somville Pascal , Vertzoni Maria , Fotaki Nikoletta 
Published: January 2022

AbstractThis study aimed to explore the potential of biopharmaceutics in vitro tools to predict drug product performance in the pediatric population. Biorelevant dissolution set-ups were used to predict how age and medicine administration practices affect the in vitro dissolution of oral formulations of a poorly water-soluble compound, montelukast. Biorelevant age-appropriate dissolution studies of Singulair® (granules and chewable tablets) were conducted with the µDISS profiler™, USP 4 apparatus, USP 2 apparatus, and mini-paddle apparatus. Biorelevant simulating fluids representative of adult and pediatric conditions were used in the dissolution studies. The biorelevant dissolution conditions were appropriately selected (i.e. volumes, transit times, etc.) to mimic the gastrointestinal conditions of each of the subpopulations tested. Partial least squares regression (PLS-R) was performed to understand the impact of in vitro variables on the dissolution of montelukast. Montelukast dissolution was significantly affected by the in vitro hydrodynamics used to perform the dissolution tests (µDISS profiler™: positive effect); choice of simulation of gastric (negative effect) and/or intestinal conditions (positive effect) of the gastrointestinal tract; and simulation of prandial state (fasted state: negative effect, fed state: positive effect). Age-related biorelevant dissolution of Singulair® granules predicted the in vivo effect of the co-administration of the formulation with applesauce and formula in infants. This study demonstrates that age-appropriate biorelevant dissolution testing can be a valuable tool for the assessment of drug performance in the pediatric population.
Graphical Abstract
Performance Evaluation of Montelukast Pediatric Formulations: Part II — a PBPK Modelling Approach
Authors: Guimarães Mariana , Vertzoni Maria , Fotaki Nikoletta 
Published: January 2022

AbstractThis study aimed to build a physiologically based pharmacokinetic (PBPK) model coupled with age-appropriate in vitro dissolution data to describe drug performance in adults and pediatric patients. Montelukast sodium was chosen as a model drug. Two case studies were investigated: case study 1 focused on the description of formulation performance from adults to children; case study 2 focused on the description of the impact of medicine co-administration with vehicles on drug exposure in infants. The PBPK model for adults and pediatric patients was developed in Simcyp® v18.2 informed by age-appropriate in vitro dissolution results obtained in a previous study. Oral administration of montelukast was simulated with the ADAM™ model. For case study 1, the developed PBPK model accurately described montelukast exposure in adults and children populations after the administration of montelukast chewable tablets. Two-stage dissolution testing in simulated fasted gastric to intestinal conditions resulted in the best description of in vivo drug performance in adults and children. For case study 2, a good description of in vivo drug performance in infants after medicine co-administration with vehicles was achieved by incorporating in vitro drug dissolution (under simulated fasted gastric to fed intestinal conditions) into a fed state PBPK model with consideration of the in vivo dosing conditions (mixing of formulation with applesauce or formula). The case studies presented demonstrate how a PBPK absorption modelling strategy can facilitate the description of drug performance in the pediatric population to support decision-making and biopharmaceutics understanding during pediatric drug development.
Graphical abstract
Scanning-probe and information-concealing machine learning intermediate hexatic phase and critical scaling of solid-hexatic phase transition in deformable particles
Authors: Guo Wei-chen , Ai Bao-quan , He Liang 
Published: January 2022

Abstract
We investigate the two-dimensional melting of deformable polymeric particles with multi-body interactions described by the Voronoi model. We report machine learning evidence for the existence of the intermediate hexatic phase in this system, and extract the critical exponent

for the divergence of the correlation length of the associated solid-hexatic phase transition. Moreover, we clarify the discontinuous nature of the hexatic-liquid phase transition in this system. These findings are achieved by directly analyzing system's spatial configurations with two generic machine learning approaches developed in this work, dubbed “scanning-probe” via which the possible existence of intermediate phases can be efficiently detected, and “information-concealing” via which the critical scaling of the correlation length in the vicinity of generic continuous phase transition can be extracted. Our work provides new physical insights into the fundamental nature of the two-dimensional melting of deformable particles, and establishes a new type of generic toolbox to investigate fundamental properties of phase transitions in various complex systems.
Mechanisms underlying the cooperation between loss of epithelial polarity and Notch signaling during neoplastic growth in Drosophila
Authors: Logeay Rémi , Géminard Charles , Lassus Patrice , Rodríguez-Vázquez Miriam , Kantar Diala , Heron-Milhavet Lisa , Fischer Bettina , Bray Sarah J. , Colinge Jacques , Djiane Alexandre 
Published: January 2022

ABSTRACT
Aggressive neoplastic growth can be initiated by a limited number of genetic alterations, such as the well-established cooperation between loss of cell architecture and hyperactive signaling pathways. However, our understanding of how these different alterations interact and influence each other remains very incomplete. Using Drosophila paradigms of imaginal wing disc epithelial growth, we have monitored the changes in Notch pathway activity according to the polarity status of cells (scrib mutant). We show that the scrib mutation impacts the direct transcriptional output of the Notch pathway, without altering the global distribution of Su(H), the Notch-dedicated transcription factor. The Notch-dependent neoplasms require, however, the action of a group of transcription factors, similar to those previously identified for Ras/scrib neoplasm (namely AP-1, Stat92E, Ftz-F1 and basic leucine zipper factors), further suggesting the importance of this transcription factor network during neoplastic growth. Finally, our work highlights some Notch/scrib specificities, in particular the role of the PAR domain-containing basic leucine zipper transcription factor and Notch direct target Pdp1 for neoplastic growth.
Rapid blood acid–base regulation by European sea bass (Dicentrarchus labrax) in response to sudden exposure to high environmental CO2
Authors: Montgomery Daniel W. , Kwan Garfield T. , Davison William G. , Finlay Jennifer , Berry Alex , Simpson Stephen D. , Engelhard Georg H. , Birchenough Silvana N. R. , Tresguerres Martin , Wilson Rod W. 
Published: January 2022

ABSTRACT
Fish in coastal ecosystems can be exposed to acute variations in CO2 of between 0.2 and 1 kPa CO2 (2000–10,000 µatm). Coping with this environmental challenge will depend on the ability to rapidly compensate for the internal acid–base disturbance caused by sudden exposure to high environmental CO2 (blood and tissue acidosis); however, studies about the speed of acid–base regulatory responses in marine fish are scarce. We observed that upon sudden exposure to ∼1 kPa CO2, European sea bass (Dicentrarchus labrax) completely regulate erythrocyte intracellular pH within ∼40 min, thus restoring haemoglobin–O2 affinity to pre-exposure levels. Moreover, blood pH returned to normal levels within ∼2 h, which is one of the fastest acid–base recoveries documented in any fish. This was achieved via a large upregulation of net acid excretion and accumulation of HCO3− in blood, which increased from ∼4 to ∼22 mmol l−1. While the abundance and intracellular localisation of gill Na+/K+-ATPase (NKA) and Na+/H+ exchanger 3 (NHE3) remained unchanged, the apical surface area of acid-excreting gill ionocytes doubled. This constitutes a novel mechanism for rapidly increasing acid excretion during sudden blood acidosis. Rapid acid–base regulation was completely prevented when the same high CO2 exposure occurred in seawater with experimentally reduced HCO3− and pH, probably because reduced environmental pH inhibited gill H+ excretion via NHE3. The rapid and robust acid–base regulatory responses identified will enable European sea bass to maintain physiological performance during large and sudden CO2 fluctuations that naturally occur in coastal environments.
Glucose induced ApoB100/ApoAI ratio changes in cultured HepG2 cells in vitro
Authors: Hu Minshan 
Published: January 2022

Backgroundː Numerous in vivo human cohort studies have suggested that the apolipoprotein B100/apolipoprotein AI (ApoB100/ApoAI) ratio might be a risk factor in coronary heart disease. The aim of this study was to measure ApoB100/ApoAI ratio changes in cell secretions by incubating HepG2 cells with various amounts of glucose in vitro. Methods ː HepG2 cells were cultured in low-, normal- or high-glucose Dulbecco's Modified Eagle Medium (DMEM) (1, 4.5 and 10g/L, respectively). Levels of ApoAI and ApoB100 were measured with commercial sandwich enzyme-linked immunosorbent assay kits (cat#: H0123 and H0124) from ShangHai MEIXUAN Biological Science and Technology Ltd (Shanghai, China). Experiments were repeated six times for each assay. Resultsː The results showed that ApoB100/ApoAI ratio have positive correlations with the glucose concentration increase. Conclusionsː A higher concentration of glucose induced an undesirable ApoB100/ApoAI ratio change, which suggests a new regulatory pathway in lipoprotein catabolism and provides a cell model for further mechanism study. This finding may lead to novel therapeutic ways for diagnosis and treatment for coronary artery disease.
Risk factors, hematological and biochemical profile associated with colic in Delman horses in Gresik, Indonesia
Authors: Purnama Muhammad Thohawi Elziyad , Hendrawan Dodit , Wicaksono Arya Pradana , Fikri Faisal , Purnomo Agus , Chhetri Shekhar 
Published: January 2022

Background: Horses are herd animals that have been domesticated in the last century. In several countries, an overview of risk factors and clinical evaluation in horses with colic has not been well‐described. This study aimed to evaluate risk factors and hematological profiles in horses associated with colic in Gresik, East Java, Indonesia. Methods: A cross-sectional study was performed during April - October 2019. A total of 115 horses were diagnosed based on physical examination, clinical symptoms, and rectal examination. A questionnaire was asked to the horse-owners to analyze the risk factors while the clinical examination was performed and blood samples were collected for pre-treatment and 14 days post-treatment. Hematological profile was evaluated from a whole blood sample. Serum cortisol, plasma epinephrine, and norepinephrine concentrations were also evaluated after separating the aliquots. Results: Of the 115 horses, 96 were diagnosed with colic. The horses with colic showed a significant association between cases with gender (p<0.021), breed (p<0.000), wheat bran feeding (p<0.015), concentrate feeding (p<0.003), anthelmintics administration (p<0.000), gastrointestinal parasites (p<0.000), dental diseases (p<0.024), previous exposure to colic (p<0.000), body condition score (p<0.000), and access to water per day (p<0.000). Based on whole blood and serum evaluation, there were ameliorated significantly on the hematological profile (p<0.01), serum cortisol (p<0.05), and plasma epinephrine (p<0.01) at 14 days post-treatment. Conclusion: This study has identified factors associated with colic in Delman horses. The study provides crucial information to investigate cases of colic and to contribute the development of healthcare strategies during treatment and clinical evaluation.
Comparison of accidental pediatric scald burns in a tertiary care center: hot cauldron burns versus accidental spill burns
Authors: Nakarmi Kiran Kishor , Pathak Bishnu Deep , Shrestha Dhan , Budhathoki Pravash , Rai Shankar Man 
Published: January 2022

Background: Scald burns result from exposure to high-temperature fluids and are more common in the pediatric age group. They occur mainly by two mechanisms: (i) spill and (ii) immersion (hot cauldron) burns. These two patterns differ in clinical characteristics and outcomes. Scalds cause significant morbidity and mortality in children. The objective of this study was to compare accidental spill burns and hot cauldron burns in a hospital setting. Methods: An analytical cross-sectional study was conducted by reviewing the secondary data of scald cases admitted during the years 2019 and 2020 in a burn-dedicated tertiary care center. Total population sampling was adopted. Data analysis was done partly using SPSS, version-23, and Stata-15. Mann Whitney U-test and Chi-square/Fisher's exact test were done appropriately to find associations between different variables. Binary regression analysis was performed taking mortality events as the outcome of interest. Results: Out of 108 scald cases, 43 (39.8%) had hot cauldron burns and 65 (60.2%) had accidental spill burns. Overall mortality was 16 (14.8%), out of which hot cauldron burns and accidental spill burns comprised 12 (75.0%) and 4 (25.0%), respectively. Binary logistic regression analysis showed the type of scald, age, and Baux score found to be associated with mortality. Every one-year increment in age had a 29% lower odds of occurrence of mortality event (adjusted odds ratio [OR], 0.71; 95% confidence interval [CI], 0.50-0.99, p=0.042). Likewise, every one-point increment in Baux score was associated with 19% higher odds of mortality (adjusted OR, 1.190; 95% CI, 1.08-1.32; p<0.001). Conclusions: Accidental spill burn was more common but mortality was significantly higher for hot cauldron burns. The risk of mortality was significantly higher in burn events occurring outside the house, and burns involving back, buttocks, perineum, and lower extremities.
Effects of exercise-based prehabilitation in children undergoing elective surgeries: a systematic review
Authors: Noronha Jean , Samuel Stephen , Singh Vijay Pratap , Prabhu H Shivananda 
Published: January 2022

Background: Prehabilitation is a therapeutic strategy involving preoperative physical exercises, nutritional support, and stress and anxiety reduction. This approach has been gaining popularity and has been seeing effective results in adults in terms of improving pre and postoperative outcomes. The purpose of this review was to summarise the evidence about the effects of exercise-based prehabilitation programs on various outcome measures in children post elective surgeries.­­ Methods: PubMed, Scopus, Web of Science, PEDro, CINAHL/EBSCO and EMBASE electronic databases were searched from inception to June 2021. Based on the inclusion criteria, titles and abstracts were independently screened by the authors. After that, a data extraction table of the selected studies which included the participants, type, and details of exercise intervention, outcome measures and results were analysed after which the quality assessment of the studies was done. Results: The search yielded 2219 articles of which three articles fulfilled the inclusion criteria with two studies being randomized controlled trials and one being a quasi-experimental pre-post type of study. One randomized controlled trial was on the effects of exercise-based prehabilitation in reducing pulmonary complications post cardiac surgeries in children and the other two studies were on the effects of prehabilitation on functional capacity & pulmonary function. All the three articles found that exercise-based prehabilitation had a positive effect on children’s post-surgery. Conclusion: Although there is a paucity of evidence-based literature, we conclude based on the existing literature retrieved by our review that exercise-based prehabilitation improves postoperative outcomes and helps in reducing postoperative complications in children undergoing various surgeries.
Dry Bean (Phaseolus vulgaris L.) Crop Water Production Functions and Yield Response Factors in an Arid to Semi-Arid Climate
Authors: Sharma Vivek , Rai Abhijit 
Published: January 2022

HighlightsDeficit irrigation negatively affected dry bean yield and yield components.Excess irrigation increased crop ETc but not dry bean yield.Soil moisture fluctuation was greater in the top 0.3 m of the soil profile compared to deeper depths.Crop water production function had a slope of 18.9 kg ha-1 mm-1 and threshold crop evapotranspiration of 171 mm.Dry bean crop was found to be sensitive to water stress (yield response factor Ky = 1.94).Abstract. Under changing climate conditions and declining water resources, understanding crop response to water stress is critical for effective irrigation management. The objectives of this study were to quantify dry bean (Phaseolus vulgaris L., cv. Othello) soil moisture dynamics, crop evapotranspiration (ETc), and yield response factor and to develop dry bean irrigation and crop water production functions (IWPF and CWPF). Five irrigation treatments, i.e., full irrigation (FIT), 75% FIT, 50% FIT, 25% FIT, and 125% FIT, were evaluated using a randomized complete block design (RCBD) with three replications for three years (2017, 2018, and 2019) in the arid to semi-arid intermountain region of Powell, Wyoming. The results showed a significant influence of irrigation on dry bean soil moisture dynamics and ETc. The dry bean crop showed a greater soil moisture fluctuation in the top 0.3 m of the soil profile compared to 0.6 m and at 0.9 m. ETc ranged from 187 to 438 mm, from 190 to 409 mm, and from 217 to 398 mm in the 2017, 2018, and 2019 growing seasons, respectively. A positive two-segment relationship was observed between dry bean seed yield and cumulative irrigation water applied. The average cumulative seasonal irrigation of 310 mm resulted in maximum seed yield. For all three years, the seed yield increased linearly with ETc. Combining the data from the three years resulted in a CWPF with a slope of 18.9 kg ha-1 mm-1 and an offset of 171 mm of ETc (i.e., the ETc required for crop establishment before any seed yield is produced, or threshold ETc). Moreover, the dry bean crop was found to be sensitive to water stress (Ky = 1.94). These results indicated that under the typical semi-arid to arid climate conditions of the intermountain region of Wyoming, deficit irrigation of dry bean may not be a viable strategy because the yield loss outweighs water-saving benefits. Keywords: Dry bean, Crop evapotranspiration, Crop production function, Irrigation water production function.
Fabrication and analysis of enhanced thermal stability and high-sensitivity turnaround point long-period fiber grating
Authors: Mahakud R. , Kumar J. , Kumar S. , Prakash O. , Dixit S. K. , Nakhe S. V. 
Published: January 2022

This paper presents a what we believe is a novel method to fabricate turnaround point
long-period gratings (TAP-LPGs) possessing enhanced thermal stability
and high sensitivity. It is shown by analysis and by experiment that
LPG resonance in photosensitive fibers can be controlled partially by
UV fluence and thermal annealing. TAP-LPGs with enhanced thermal
stability were fabricated by following three steps: (I) finding
grating period versus writing UV fluence for TAP operation; (II)
writing gratings at a relatively higher period with higher fluence, in
which case the resonance is out of phase; (III) controlled annealing
so that the postannealed LPG operates at/near TAP. The thermal
stability is enhanced. The average temperature sensitivity of dual
peak resonance measured for a typical TAP-LPG in the temperature
interval of 70°C–240°C is about 2.3 nm/°C. This study will be useful
for the development of high temperature TAP-LPG sensors.
Design and protocol for a cluster randomised trial of enhanced diagnostics for tuberculosis screening among people living with HIV in hospital in Malawi (CASTLE study)
Authors: Burke Rachael M. , Nyirenda Saulos , Twabi Hussein H. , Nliwasa Marriott , Joekes Elizabeth , Walker Naomi , Nyirenda Rose , Gupta-Wright Ankur , Fielding Katherine , MacPherson Peter , Corbett Elizabeth L. 
Published: January 2022

Background
People living with HIV (PLHIV) have a high risk of death if hospitalised in low-income countries. Tuberculosis has long been the leading cause of admission and death, in part due to suboptimal diagnostics. Two promising new diagnostic tools are digital chest Xray with computer-aided diagnosis (DCXR-CAD) and urine testing with Fujifilm SILVAMP LAM (FujiLAM). Neither test has been rigorously evaluated among inpatients. Test characteristics may be complementary, with FujiLAM especially sensitive for disseminated tuberculosis and DCXR-CAD especially sensitive for pulmonary tuberculosis, making combined interventions of interest.

Design and methods
An exploratory unblinded, single site, two-arm cluster randomised controlled trial, with day of admission as the unit of randomisation. A third, smaller, integrated cohort arm (4:4:1 random allocation) contributes to understanding case-mix, but not trial outcomes. Participants are adults living with HIV not currently on TB treatment. The intervention (DCXR-CAD plus urine FujiLAM plus usual care) is compared to usual care alone. The primary outcome is proportion of participants started on tuberculosis treatment by day 56, with secondary outcomes of mortality (time to event) measured to to 56 days from enrolment, proportions with undiagnosed tuberculosis at death or hospital discharge and comparing proportions with enrolment-day tuberculosis treatment initiation.

Discussion
Both DCXR-CAD and FujiLAM have potential clinical utility and may have complementary diagnostic performance. To our knowledge, this is the first randomised trial to evaluate these tests among hospitalised PLHIV.