bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Implementation of the Government Policies on Transition Rate of ECDE Children from Public Preschools to Public Primary School in Kapseret Sub County; Uasin Gishu County
Authors: Muthoni Njuguna Mary , Bitok Esther , Matere Audrey
Published: June 2021

A child’s transition from public preschool to primary is not a single event of change that has only immediate consequences but has its effects on transition rate. The purpose of this study was to assess influence of implementation of the government policies on transition rate of ECDE children from public preschools to public primary school in Kapseret Sub County; Uasin Gishu County. The study was guided by Jean Piaget’s Construvist theory. The study adopted a descriptive survey design. The researcher sampled 171 respondents; including 86 Grade one; two; three teachers; 57 preschool teachers; and 29 headteachers. The research instruments used were questionnaires and interview schedule. The analysis of data was done using Statistical Package for Social Science (SPSS) software. Data from questionnaires was analyzed both quantitatively and qualitatively. Quantitative method involved descriptive and inferential analysis. Descriptive analysis such as frequencies; percentages were used to present quantitative data in form of tables. Qualitative data from interview schedules were analyzed thematically based on the content of qualitative data and then presented in prose form. The findings were presented in frequency distribution tables. The study findings indicated that implementation of government policies has a positive and significant influence on leaners transition. The study concluded that free primary education policy has improved learners’ transition rate to Grade one. Adoption of Early Years Education Policy has influenced transition to Grade one. Finally; free primary education policy has increased the number of learners in public pre-primary school. The study recommends that primary schools should implement all the government policies by preparing Early Child Development (ECD) children in terms of classrooms; toilets; furniture and adequate qualified teachers.
Cost‐effectiveness of precision diagnostic testing for precision medicine approaches against non‐small‐cell lung cancer: A systematic review
Authors: Henderson Raymond , Keeling Peter , French Declan , Smart Dave , Sullivan Richard , Lawler Mark
Published: June 2021

Precision diagnostic testing (PDT) employs appropriate biomarkers to identify cancer patients that may optimally respond to precision medicine (PM) approaches, such as treatments with targeted agents and immuno‐oncology drugs. To date, there are no published systematic appraisals evaluating the cost‐effectiveness of PDT in non‐small‐cell lung cancer (NSCLC). To address this gap, we conducted Preferred Reporting Items for Systematic Reviews and Meta‐Analyses searches for the years 2009–2019. Consolidated Health Economic Evaluation Reporting Standards were employed to screen, assess and extract data. Employing base costs, life years gained or quality‐adjusted life years, as well as willingness‐to‐pay (WTP) threshold for each country, net monetary benefit was calculated to determine cost‐effectiveness of each intervention. Thirty‐seven studies (50%) were included for analysis; a further 37 (50%) were excluded, having failed population‐, intervention‐, comparator‐, outcomes‐ and study‐design criteria. Within the 37 studies included, we defined 64 scenarios. Eleven scenarios compared PDT‐guided PM with non‐guided therapy [epidermal growth factor receptor (EGFR),n = 5; programmed death‐ligand 1 (PD‐L1),n = 6]. Twenty‐eight scenarios compared PDT‐guided PM with chemotherapy alone (anaplastic lymphoma kinase,n = 3;EGFR,n = 17; PD‐L1,n = 8). Twenty‐five scenarios compared PDT‐guided PM with chemotherapy alone, while varying the PDT approach. Thirty‐four scenarios (53%) were cost‐effective, 28 (44%) were not cost‐effective, and two were marginal, dependent on their country’s WTP threshold. When PDT‐guided therapy was compared with a therapy‐for‐all patients approach, all scenarios (100%) proved cost‐effective. Seven of 37 studies had been structured appropriately to assess PDT‐PM cost‐effectiveness. Within these seven studies, all evaluated scenarios were cost‐effective. However, 81% of studies had been poorly designed. Our systematic analysis implies that more robust health economic evaluation could help identify additional approaches towards PDT cost‐effectiveness, underpinning value‐based care and enhanced outcomes for patients with NSCLC.
Elevated YKL‐40 serum levels may contribute to wet age‐related macular degeneration via the ERK1/2 pathway
Authors: Bin Yue , Liu Yanyao , Jiang Shaoqiu , Peng Hui
Published: June 2021

Choroidal neovascularization (CNV) is a key characteristic of wet age‐related macular degeneration (AMD) that can lead to severe vision loss in the elderly. Anti‐VEGF therapy is currently the premier strategy for wet AMD, but it has limited efficacy. Previous studies have shown that chitinase‐3‐like‐1 (YKL‐40) can promote microangiogenesis and inflammation, but its effect on CNV formation has not yet been studied. Here, we investigated the potential role of YKL‐40 in wet AMD and the underlying mechanism(s). We report that the serum expression of YKL‐40 in wet AMD patients was significantly higher than that in control patients and was positively correlated with VEGF expression, indicating that YKL‐40 may participate in the development of wet AMD. In addition, YKL‐40 and VEGF expression levels were observed to be increased and the ERK1/2 pathway activated in the neuroretinal (NR) and RPE/choroid tissues of mice with laser‐induced CNV. The YKL‐40 and phosphorylated protein levels of the ERK1/2 pathway were decreased after intravitreal injection with an anti‐YKL‐40 antibody, suggesting that anti‐YKL‐40 could inhibit the activation of the ERK1/2 pathway. These results indicate that YKL‐40 may serve as a novel target for the diagnosis and treatment of wet AMD.
C
ox,
G
ertrude
M
ary: Her Life and Work
Authors: Anderson R. L.
Published: June 2021

Gertrude Mary Cox was one of the twentieth century pioneers in Statistics. After receiving her BS and MS degrees in Mathematics and Statistics from Iowa State, she took charge of the computing and data analysis in its Statistical Laboratory. She developed and taught classes in Design of Experiments, using real data.

In 1940, she accepted the headship of the newly established Department of Experimental Statistics at North Carolina State. She started staffing with statisticians who had strong programs in applied fields. In 1944, she became the head of an all‐university Institute of Statistics.

In 1949, Gertrude Cox gave up the Headship at NCS to help develop Statistics at the Research Triangle Park in North Carolina; Dr. Cox became RTI's first Director of Statistics Research in 1959. She had received an honorary doctor's degree from NC State in 1958. Her most treasured honor came in 1975, when she was elected to the National Academy of Science.

Dr. Cox received much outside support; a special one helped establish an outstanding statistical genetics program and the development of a strong computer program. She was a founding member of the International Biometrics Society and became President and Editor of its journal,
Biometrics
. She also became President of the American Statistical Association and consulted with many federal organizations. The building housing Statistics at NCS was named Cox Hall in 1977.

Unfortunately, Gertrude contracted leukemia and died in Duke Hospital in 1978.
G
ardner,
M
artin
J
ohn
Authors: Barker David
Published: June 2021

Although Martin Gardner achieved fame for his work at Sellafield, which showed that paternal exposure to ionizing radiation was linked to leukemia in childhood, this discovery came toward the end of a varied and highly productive career in medical statistics. After receiving a first class degree in mathematics, he joined the Medical Research Council Social Medicine Unit at the London School of Hygiene and Tropical Medicine. It was there that he became interested in the problem of why the rates of common diseases vary so much between different parts of Britain—an interest to which he returned repeatedly throughout his career. He carried out a series of novel analyses on the geographical links between socioeconomic conditions and coronary heart disease. Later, at the MRC Environmental Epidemiology Unit in Southampton, he produced two uniquely detailed atlases of mortality in England and Wales.
G
uy,
W
illiam
A
ugustus
Authors: Armitage Peter
Published: June 2021

Guy wrote on medical statistics in the mid‐nineteenth century and helped to popularize the work of P. C. A. Louis. He is commemorated in the Guy Medal of the Royal Statistical Society.
H
alley,
E
dmond
Authors: Asmar Lina
Published: June 2021

Edmond Halley was born on November 8, 1656 in Haggerton, UK. He was a major English, astronomer, mathematician, and physicist, who was also interested in demography, insurance mathematics (Actuarial Methods), geology, oceanography, geography, and navigation. Moreover, he was considered an engineer and a social statistician whose life was filled with the thrill of discovery. In 1705, he reasoned that the periodic comet—now known as Halley's comet—that appeared in 1456, 1531, 1607, and 1682, was the same comet that appears every 76 years, and accurately predicted that it would appear again in December 1758. His most notable achievements were his discoveries of the motion of stars, which were then considered fixed, and a scheme for computing the motion of comets and establishing their periodicity in elliptical orbits. Edmond Halley died on January 14, 1742 in Greenwich, UK.
Health Statistics, History of
Authors: Feinleib Manning
Published: June 2021

Early work in demography and vital statistics in the seventeenth century was influenced both by the development of probability in relation to gambling problems and by the analysis of astronomic data. The work of Graunt and Petty is described, as is the later work of Pinel and Louis in clinical statistics. In nineteenth century England, Farr's work on classification and registration of vital events was important, and similar developments took place in the United States, where extensive health surveys were established.
Automated algorithm for calculation of setup corrections and planning target volume margins for offline image‐guided radiotherapy protocols
Authors: Abubakar Auwal , Zamri Nada Alia M. , Shaukat Shazril Imran , Mohd Zin Hafiz
Published: June 2021

Purpose

Each radiotherapy center should have a site‐specific planning target volume (PTV) margins and image‐guided (IG) radiotherapy (IGRT) correction protocols to compensate for the geometric errors that can occur during treatment. This study developed an automated algorithm for the calculation and evaluation of these parameters from cone beam computed tomography (CBCT)‐based IG‐intensity modulated radiotherapy (IG‐IMRT) treatment.

Methods and materials

A MATLAB algorithm was developed to extract the setup errors in three translational directions (x, y, and z) from the data logged by the CBCT system during treatment delivery. The algorithm also calculates the resulted population setup error and PTV margin based on the van Herk margin recipe and subsequently estimates their respective values for no action level (NAL) and extended no action level (eNAL) offline correction protocols. The algorithm was tested on 25 head and neck cancer (HNC) patients treated using IG‐IMRT.

Results

The algorithms calculated that the HNC patients require a PTV margin of 3.1, 2.7, and 3.2 mm in the x‐, y‐, and z‐direction, respectively, without IGRT. The margin can be reduced to 2.0, 2.2, and 3.0 mm in the x‐, y‐, and z‐direction, respectively, with NAL and 1.6, 1.7, and 2.2 mm in the x‐, y‐, and z‐direction, respectively, with eNAL protocol. The results obtained were verified to be the same with the margins calculated using an Excel spreadsheet. The algorithm calculates the weekly offline setup error correction values automatically and reduces the risk of input data error observed in the spreadsheet.

Conclusions

In conclusion, the algorithm provides an automated method for optimization and reduction of PTV margin using logged setup errors from CBCT‐based IGRT.
Fucoidan Hydrogels Significantly Alleviate Oxidative Stress and Enhance the Endocrine Function of Encapsulated Beta Cells
Authors: Reys Lara L. , Vaithilingam Vijayaganapathy , Sthijns Mireille M. J. P. E. , Soares Eduardo , Rademakers Timo , de Vries Rick , Mohammed Sami G. , de Bont Denise , Jetten Marlon J. , Hermanns Carolin , Filho Omar Paulino da Silva , Stell Adam , Mourad Nizar I. , Gianello Pierre , LaPointe Vanessa L. S. , Silva Simone S. , Reis Rui L. , Silva Tiago H. , van Apeldoorn Aart A.
Published: June 2021

Microencapsulating pancreatic islets in immunoprotective alginate hydrogels is a promising strategy for treatment of type 1 diabetes. However, this strategy is limited by inflammation and hypoxia mediated oxidative stress, due to encapsulation and the hydrogel itself, leading to impaired insulin secretion and limited short and long term cell survival. Herein, the antioxidant effect of fucoidan, an algae derived polysaccharide, on beta cells, and its positive effects on encapsulated beta cell viability and function is presented. Fucoidan from Fucus vesiculosus (FF) exhibits a high total antioxidant capacity, and free radical scavenging activity, and is able to significantly alleviate intracellular oxidative stress in rat insolinoma beta cells (INS1E). In addition, FF significantly increases insulin secretion in a dose‐ and time‐dependent manner. When FF is incorporated in ultrapure alginate used for microencapsulation of primary rat islets, both viability and glucose responsiveness of rat islets in these socalled Fucogel microcapsules (Fucocaps) are found to be significantly higher compared to islets encapsulated in alginate alone. Similar results are obtained with INS1E pseudoislets and neonatal pig islets. Fucocaps can provide a redox‐modulatory niche and an immune barrier for islets and beta cells in the same time leading to significantly improved survival and endocrine function by mitigating oxidative stress.
Aggressive T‐cell lymphomas: 2021 Updates on diagnosis, risk stratification and management
Authors: Zain Jasmine M. , Hanona Paul
Published: June 2021

Introduction

Aggressive T‐cell lymphomas continue to have a poor prognosis. There are over 27 different subtypes of peripheral T‐cell lymphoma (PTCL), and we are now beginning to understand the differences between the various subtypes beyond histologic variations.

Molecular Pathogenesis of Various Subtypes of PTCL

Gene expression profiling (GEP) can help in diagnosis and prognostication of various subtypes including PTCL‐nos and anaplastic large cell lymphoma (ALCL). In addition, mutational analysis is now being incorporated in clinical trials of novel agents to evaluate various biomarkers of response to allow better therapeutic choices for patients.

Targeted Therapies

There are many targeted agents currently in various stages of clinical trials for PTCL that take advantage of the differential expression of specific proteins or receptors in PTCL tumors. This includes the CD30 directed antibody drug conjugate brentuximab vedotin. Other notable targets are CD25, CCR4, inhibition of PI3kinase – m TOR and JAK/STAT pathways. The ALK inhibitors are promising for ALK expressing tumors.

Immunotherapies

Allogeneic stem cell transplant continues to be the curative therapy for most aggressive subtypes of PTCL. The use of checkpoint inhibitors in the treatment of PTCL is still controversial. The most promising results have been seen in cases of extranodal natural killer cell/T‐cell (ENK/T) lymphomas and cutaneous T‐cell lymphomas (CTCL). Bispecific antibody based treatments as well as CAR‐T cell based therapies are in clinical trials.
Endangered mountain gorillas and COVID‐19: One health lessons for prevention and preparedness during a global pandemic
Authors: Gilardi Kirsten , Nziza Julius , Ssebide Benard , Syaluha Eddy Kambale , Muvunyi Richard , Aruho Robert , Shalukoma Chantal , Seguya Andrew , Masozera Anna Behm
Published: June 2021

The world's 1063 mountain gorillas (Gorilla beringei beringei) live in two subpopulations at the borders of the Democratic Republic of Congo, Rwanda, and Uganda. The majority of mountain gorillas are human‐habituated to facilitate tourism and research, which brings mountain gorillas into close proximity of people daily. Wild great apes are proven to be susceptible to human pathogens, including viruses that have caused fatal respiratory disease in mountain gorillas (e.g., human metapneumovirus1). This is the result of the close genetic relatedness of humans and gorillas as species, and the structural and genetic similarity in molecular receptors that allow viruses to infect cells2. At the time of writing, there is no evidence that severe acute respiratory syndrome coronavirus 2, the coronavirus that causes coronavirus disease 19 (COVID‐19), has infected a mountain gorilla. However, due to the significant potential for human‐to‐gorilla transmission, mountain gorilla range States took immediate steps to minimize the COVID‐19 threat. These actions included a combination of preventive practice around gorillas and other great apes (e.g., mandatory face mask use, increased “social” minimum distancing from gorillas) as well as human public health measures (e.g., daily health/fever screenings, COVID‐19 screening, and quarantines). Minimization of the COVID‐19 threat also required socioeconomic decision‐making and political will, as all gorilla tourism was suspended by late March 2020 and guidelines developed for tourism reopening. A consortium that collaborates and coordinates on mountain gorilla management and conservation, working within an intergovernmental institutional framework, took a multifaceted One Health approach to address the COVID‐19 threat to mountain gorillas by developing a phased contingency plan for prevention and response. The aim of this paper is to describe how range States and partners achieved this collaborative planning effort, with intent that this real‐world experience will inform similar actions at other great ape sites.
Unraveling the heterogeneity in Alzheimer's disease progression across multiple cohorts and the implications for data‐driven disease modeling
Authors: Birkenbihl Colin , Salimi Yasamin , Fröhlich Holger ,   for the Japanese Alzheimer's Disease Neuroimaging Initiative,   the Alzheimer's Disease Neuroimaging Initiative
Published: June 2021

Introduction

Given study‐specific inclusion and exclusion criteria, Alzheimer's disease (AD) cohort studies effectively sample from different statistical distributions. This heterogeneity can propagate into cohort‐specific signals and subsequently bias data‐driven investigations of disease progression patterns.

Methods

We built multi‐state models for six independent AD cohort datasets to statistically compare disease progression patterns across them. Additionally, we propose a novel method for clustering cohorts with regard to their progression signals.

Results

We identified significant differences in progression patterns across cohorts. Models trained on cohort data learned cohort‐specific effects that bias their estimations. We demonstrated how six cohorts relate to each other regarding their disease progression.

Discussion

Heterogeneity in cohort datasets impedes the reproducibility of data‐driven results and validation of progression models generated on single cohorts. To ensure robust scientific insights, it is advisable to externally validate results in independent cohort datasets. The proposed clustering assesses the comparability of cohorts in an unbiased, data‐driven manner.
Almost sure exponential stability of hybrid stochastic delayed Cohen–Grossberg neural networks
Authors: Yu Peilin , Cheng Pei , Deng Feiqi
Published: June 2021

Benefit from the significant work of Song and Mao (2018), this paper focuses on the almost sure exponential stability of hybrid stochastic delayed Cohen–Grossberg neural network (SDCGNN) with the nonlinear disturbance. By virtue of stationary distribution, Lyapunov stability theory and LMI tool, we will propose that if the corresponding delay‐free stochastic neural network is almost surely exponentially stable, then there exists a positive number τ∗ such that the SDCGNN is also almost surely exponentially stable so long as τ < τ∗. Finally, an example is given to verify the effectiveness of our results, and an implicit lower bound for τ∗ is provided.
Travelling ultrasound promotes vasculogenesis of three‐dimensional‐monocultured human umbilical vein endothelial cells
Authors: Imashiro Chikahiro , Azuma Tetsuya , Itai Shun , Kuribara Taiki , Totani Kiichiro , Onoe Hiroaki , Takemura Kenjiro
Published: June 2021

To generate three‐dimensional tissue in vitro, promoting vasculogenesis in cell aggregates is an important factor. Here, we found that ultrasound promoted vasculogenesis of human umbilical vein endothelial cells (HUVECs). Promotion of HUVEC network formation and lumen formation were observed using our method. In addition to morphological evaluations, protein expression was quantified by western blot assays. As a result, expression of proteins related to vasculogenesis and the response to mechanical stress on cells was enhanced by exposure to ultrasound. Although several previous studies have shown that ultrasound may promote vasculogenesis, the effect of ultrasound was unclear because of unregulated ultrasound, the complex culture environment, or two‐dimensional‐cultured HUVECs that cannot form a lumen structure. In this study, regulated ultrasound was propagated on three‐dimensional‐monocultured HUVECs, which clarified the effect of ultrasound on vasculogenesis. We believe this finding may be an innovation in the tissue engineering field.
On‐chip determination of tissue‐specific metastatic potential of breast cancer cells
Authors: Firatligil‐Yildirir Burcu , Bati‐Ayaz Gizem , Tahmaz Ismail , Bilgen Muge , Pesen‐Okvur Devrim , Yalcin‐Ozuysal Ozden
Published: June 2021

Metastasis is one of the major obstacles for breast cancer patients. Limitations of current models demand the development of custom platforms to predict metastatic potential and homing choices of cancer cells. Here, two organ‐on‐chip platforms, invasion/chemotaxis (IC‐chip) and extravasation (EX‐chip) were used for the quantitative assessment of invasion and extravasation towards specific tissues. Lung, liver and breast microenvironments were simulated in the chips using tissue‐specific cells embedded in matrigel. In the IC‐chip, invasive MDA‐MB‐231, but not noninvasive MCF‐7 breast cancer cells invaded into lung and liver microenvironments. In the EX‐chip, MDA‐MB‐231 cells extravasated more into the lung compared to the liver and breast microenvironments. In addition, lung‐specific MDA‐MB‐231 clone invaded and extravasated into the lung microenvironment more efficiently than the bone‐specific clone. Both invasion/chemotaxis and extravasation results were in agreement with published clinical data. Collectively, our results show that IC‐chip and EX‐chip, simulating tissue‐specific microenvironments, can distinguish different in vivo metastatic phenotypes, in vitro. Determination of tissue‐specific metastatic potential of breast cancer cells is expected to improve diagnosis and help select the ideal therapy.
Novel method for quantifying cells on carriers and its demonstration during SARS‐2 vaccine development
Authors: Rosen Osnat , Jayson Avital , Natan Niva , Monash Arik , Girshengorn Meni , Goldvaser Michael , Levin Lilach , Epstein Eyal
Published: June 2021

The most effective way to prevent and control infectious disease outbreak is through vaccines. The increasing use of vaccines has elevated the need to establish new manufacturing strategies. One of the major approaches is cell‐based production, which creates a need for high cell density to enable higher cell production levels. This has led to development of the technology of cell carriers, including micro and macro cell carriers. To follow the production process, quantifying the number of cells on these carriers is required, as well as the tracking of their viability and proliferation. However, owing to various carriers' unique structures, tracking the cell's is challenging using current traditional assays that were originally developed for monolayers of adherent cells. The current “gold standard” method is counting cell nuclei, separating cells from the carrier, staining with crystal violet, and visually counting under a microscope. This method is tedious and counts both live and dead cells. A few other techniques were developed but were specific to the carrier type and involved specialized equipment. In this study, we describe a broadly ranging method for counting cells on carriers that was developed and employed as part of the development of severe acute respiratory syndrome coronavirus 2 vaccine. The method is based on the Alamar blue dye, a well‐known, common marker for cell activity, and was found to be successful in tracking cell adsorption, cell growth, and viability on carriers. No separation of the cells from the carriers is needed, nor is any specialized equipment; the method is simple and rapid and provides comprehensive details necessary for process control of viral vaccine production in cells. This method can be easily implemented in any of a number of cell‐based processes and other unique platforms for measuring the growth of encapsulated cells.
Prehabilitation exercise therapy for cancer: A systematic review and meta‐analysis
Authors: Michael Christina M. , Lehrer Eric J. , Schmitz Kathryn H. , Zaorsky Nicholas G.
Published: June 2021

Objective

The purpose of this study was to determine the impact of prehabilitation exercise intervention with respect to (1) acceptability, feasibility, and safety; and (2) physical function, measured by 6‐minute‐walk test (6MWT).

Data sources

PRISMA guidelines were used to systematically search PubMed, Embase, and CINAHL databases evaluating prehabilitation exercise interventions.

Study selection

The inclusion criteria were studies investigating patients who underwent surgery for their cancer and underwent prehabilitation exercise.

Data extraction and synthesis

Guidelines were applied by independent extraction by multiple observers. Data were pooled using a random‐effects model.

Main outcome(s) and measure(s)

Acceptability, feasibility, and safety rates were calculated. 6MWT (maximum distance a person can walk at their own pace on a hard, flat surface, measured in meters, with longer distance indicative of better performance status) was compared using two arms using the DerSimonian and Laird method.

Results

Objective 1. Across 21 studies included in this review, 1564 patients were enrolled, 1371 (87.7%) accepted the trial; of 1371, 1230 (89.7% feasibility) completed the intervention. There was no grade 3+ toxicities. Objective 2. Meta‐analysis of five studies demonstrated a statistically significant decrease in 6MWT distance postoperatively in the control group (mean difference = +27.9 m; 95% confidence interval (CI): 9.3; 46.6) and a significant improvement postoperatively in the prehabilitation group (mean difference = −24.1 m; 95% CI: −45.7; −2.6). Meta‐analysis demonstrated improvements in 6MWT distance 4–8 weeks postoperatively in the prehabilitation group compared to the control group (mean difference = −58.0 m, 95% CI: −92.8; −23.3).

Conclusions and relevance

Prehabilitation exercise for cancer patients undergoing surgery was found to be safe, acceptable, and feasible with a statistically significant improvement in the 6MWT, indicating that prehabilitation can improve postoperative functional capacity.
Using choice query to persuade consumers with different construal of self: Purchase uncertainty as a mediator
Authors: Ku Hsuan‐Hsuan
Published: June 2021

Queries about choices inviting recipients to reflect on purchase decisions are widely used in advertising. This study adopts purchase uncertainty as a foundation for evaluating how promotional messages designed as choice queries could predispose responses by individuals identifying as either an independent or interdependent self‐view. The results of three experiments show that independents are more readily persuaded by queries phrased in abstract rather than concrete terms, while the reverse occurs for interdependents; purchase uncertainty mediates the results. Furthermore, when physical risk is high, a choice query represented at a low level of construal stimulates greater purchase uncertainty and more favorable product evaluation, regardless of the type of self‐construal. Expanding knowledge of how query performs in promotional communication will aid in better message structuring for advertisements and meeting more goals for persuasion.
Blame it on the pump
Authors: Levins Kirk John , Khan Mohamed , Drago Thomas , Roman Elena , Suiter Cillian , Nasa Anurag , Roddy Darren William , Murphy Paul
Published: June 2021

Although intrathecal pumps may lead to spinal symptoms that are likely related to the pump itself, the case presented herein underscores the importance of casting a broad differential diagnosis at the time of initial presentation.
Multifocal tuberculosis on certolizumab pegol in a patient followed for rheumatoid arthritis
Authors: Hannech Emna , Boussaid Soumaya , Rekik Sonia , Jemmali Samia , Ajlani Houda , Cheour Elhem , Sahli Hela , Elleuch Mohamed
Published: June 2021

Tuberculosis must be considered in front of deterioration in general condition in patient with rheumatic disease under biological therapy. Rheumatologists may pay attention and screen infections before and after prescribing biological therapy.
Autoimmune hemolytic anemia associated with vitamin B12 deficiency and viral illness in DiGeorge syndrome. Case report and literature review
Authors: Yousaf Zohaib , Ata Fateen , Iqbal Phool , Muthanna Bassam , Khan Adeel Ahmad , Akram Jaweria , Kartha Anand
Published: June 2021

Vitamin B12 plays a crucial role in cell maturation and differentiation. Its deficiency can lead to cytopenias and even hemolysis. We suggest regular monitoring and maintenance of Vit B12 levels in DiGeorge syndrome patients to prevent such triggers.
Percutaneous treatment of acute axillary artery occlusion after percutaneous coronary intervention: A case report
Authors: Umeno Akihiro , Tsuda Shigeyasu
Published: June 2021

The JR guide catheter is preferred for operability; however, we should pay more attention to the guide catheter in the case of radial artery approach with severe vessel tortuosity especially in patients with hypertension or in older female patients.
Neonate with chikungunya
Authors: Gupta Vishal , Gupta Nitin , Pandita Aakash
Published: June 2021

Chikungunya although rare should be considered in any neonate presenting with fever and facial hyperpigmentation or encephalopathy especially in endemic areas.
Chylopericardium associated with constrictive pericarditis assessed by multimodality imaging
Authors: Androulakis Emmanuel , Bratis Konstantinos , Chua TP , Chandrasekaran Venkatachalam
Published: June 2021

Acute‐onset presentation with breathlessness and calcific pericardial thickening encapsulating the heart. Extremely chylous pericardium, which is by itself rare, in combination with constriction assessed with multiple imaging modalities.
Differentiation of Epoxide Enantiomers in the Confined Spaces of an Homochiral Cu(II) Metal‐Organic Framework by Kinetic Resolution
Authors: Cabezas‐Giménez Juanjo , Lillo Vanesa , Luis Núñez‐Rico José , Nieves Corella‐Ochoa M. , Jover Jesús , Galán‐Mascarós José Ramón , Vidal‐Ferran Anton
Published: June 2021

TAMOF‐1, a homochiral metal‐organic framework (MOF) constructed from an amino acid derivative and Cu(II), was investigated as a heterogeneous catalyst in kinetic resolutions involving the ring opening of styrene oxide with a set of anilines. The branched products generated from the ring opening of styrene oxide with anilines and the unreacted epoxide were obtained with moderately high enantiomeric excesses. The linear product arising from the attack on the non‐benzylic position of styrene oxide underwent a second kinetic resolution by reacting with the epoxide, resulting in an amplification of its final enantiomeric excess and a concomitant formation of an array of isomeric aminodiols. Computational studies confirmed the experimental results, providing a deep understanding of the whole process involving the two successive kinetic resolutions. Furthermore, TAMOF‐1 activity was conserved after several catalytic cycles. The ring opening of a meso‐epoxide with aniline catalyzed by TAMOF‐1 was also studied and moderate enantioselectivities were obtained.
Access to Indole‐Fused Benzannulated Medium‐Sized Rings through a Gold(I)‐Catalyzed Cascade Cyclization of Azido‐Alkynes
Authors: Greiner Luca C. , Inuki Shinsuke , Arichi Norihito , Oishi Shinya , Suzuki Rikito , Iwai Tomohiro , Sawamura Masaya , Hashmi A. Stephen K. , Ohno Hiroaki
Published: June 2021

Because benzannulated and indole‐fused medium‐sized rings are found in many bioactive compounds, combining these fragments might lead to unexplored areas of biologically relevant and uncovered chemical space. Herein is shown that α‐imino gold carbene chemistry can play an important role in solving the difficulty in the formation of medium‐sized rings. Namely, phenylene‐tethered azido‐alkynes undergo arylative cyclization through the formation of a gold carbene intermediate to afford benzannulated indole‐fused medium‐sized tetracycles. The reactions allow a range of different aryl substitution patterns and efficient access to these otherwise difficult‐to‐obtain medium‐sized rings. This study also demonstrates the feasibility of the semihollow‐shaped C‐dtbm ligand for the construction of a nine‐membered ring.
Effect of Leptolyngbya sp. Biofilm and Vallisneria natans Growth on Nutrient Release from Sediment
Authors: Wang Tao , Xie Chunlin , Shu Rou , Yan Chunlan , Pei Guofeng
Published: June 2021

Nutrients supplied by sediment of lakes and light are likely important factors determining the growth balance between Leptolyngbya sp. biofilm and Vallisneria natans. Therefore, experiments with varying light are conducted to compare the effect of nutrient release from surface sediment on their growth. The results show that changes in pH, dissolved oxygen (DO) and redox potential (Eh) are significantly correlated with the changes in nitrogen(N) and phosphorus (P) concentrations in the water (p < 0.05). The optimum light intensity for the growth of Leptolyngbya sp. and V. natans is different. The biomass of Leptolyngbya sp. biofilm is higher at 2–27 µmol m−2·s−1, but the biomass of V. natans is positively correlated with light intensity (2–54 µmol m−2·s−1) (p < 0.05). The Leptolyngbya sp. biofilm and V. natans can retain P from sediment and significantly remove N in the overlying water. The total P amounts retained by V. natans are significantly higher than that of Leptolyngbya sp. biofilm in all treatments, and the potential for P retention of V. natans increases with the increase of light intensity. The retention of P amounts in the Leptolyngbya sp. biofilm mainly formed 47.8% Fe‐bound P, but 57% NH4CI‐bound P in the V. natans.
Structural Development of Salicylanilide‐Based SPAK Inhibitors as Candidate Antihypertensive Agents
Authors: Fujii Shinya , Kikuchi Eriko , Suzuyama Honoka , Watanabe Yuko , Ishigami‐Yuasa Mari , Masuno Hiroyuki , Mori Takayasu , Isobe Kiyoshi , Uchida Shinichi , Kagechika Hiroyuki
Published: June 2021

Hypertension is an important target for drug discovery. We have focused on the with‐no‐lysine kinase (WNK)‐oxidative stress‐responsive 1 (OSR1) and STE20/SPS1‐related proline‐alanine‐rich protein kinase (SPAK)‐NaCl cotransporter (NCC) signal cascade as a potential target, and we previously developed a screening system for inhibitors of WNK‐OSR1/SPAK‐NCC signaling. Herein we used this system to examine the structure‐activity relationship (SAR) of salicylanilide derivatives as SPAK kinase inhibitors. Structural design and development based on our previous hit compound, aryloxybenzanilide derivative 2, and the veterinary anthelmintic closantel (3) led to the discovery of compound 10 a as a potent SPAK inhibitor with reduced toxicity. Compound 10 a decreased the phosphorylation level of NCC in mouse kidney in vivo, and appears to be a promising lead compound for a new class of antihypertensive drugs.
Effect of Upadacitinib on the Pharmacokinetics of Rosuvastatin or Atorvastatin in Healthy Subjects
Authors: Mohamed Mohamed‐Eslam F. , Coppola Sheryl , Feng Tian , Camp Heidi S. , Kim Elaine , Othman Ahmed A.
Published: June 2021

This phase 1, 2‐part, 2‐period, open‐label, drug‐drug interaction study evaluated the potential for pharmacokinetic interactions between upadacitinib and rosuvastatin, an organic anion transporting polypeptide (OATP) 1B1 and breast cancer resistance protein substrate, or atorvastatin, a cytochrome P450 3A, OATP1B1, and OATP1B3 substrate, in 36 healthy volunteers. During period 1, a single dose of rosuvastatin (5 mg; part 1) or atorvastatin (10 mg; part 2) was administered on day 1, followed by a washout period of 5 days. During period 2, once‐daily doses of upadacitinib extended‐release (30 mg) were administered on days 1 to 10, and a single dose of rosuvastatin (5 mg; part 1) or atorvastatin (10 mg; part 2) was administered 1 hour after the upadacitinib dose on day 7. Serial blood samples were collected for assays of drug concentrations. In Part 1, rosuvastatin maximum observed plasma concentration (Cmax) and area under the plasma concentration–time curve from time 0 to infinity (AUCinf) were 23% and 33% lower, respectively, when administered with upadacitinib relative to when administered alone. In part 2, atorvastatin Cmax and AUCinf was 11% and 23% lower, respectively, when administered with upadacitinib relative to when administered alone. The Cmax and AUCinf of the active metabolite ortho‐hydroxyatorvastatin remained unchanged. Administration of a single 5‐mg dose of rosuvastatin or a single 10‐mg dose of atorvastatin had no relevant effect on upadacitinib Cmax or area under the plasma concentration–time curve. These results demonstrated that upadacitinib has no clinically relevant effect on the pharmacokinetics of rosuvastatin and atorvastatin or on substrates transported by OATP1B or breast cancer resistance protein.
Machine learning approaches to predicting amyloid status using data from an online research and recruitment registry: The Brain Health Registry
Authors: Albright Jack , Ashford Miriam T. , Jin Chengshi , Neuhaus John , Rabinovici Gil D. , Truran Diana , Maruff Paul , Mackin R. Scott , Nosheny Rachel L. , Weiner Michael W.
Published: June 2021

Introduction

This study investigated the extent to which subjective and objective data from an online registry can be analyzed using machine learning methodologies to predict the current brain amyloid beta (Aβ) status of registry participants.

Methods

We developed and optimized machine learning models using data from up to 664 registry participants. Models were assessed on their ability to predict Aβ positivity using the results of positron emission tomography as ground truth.

Results

Study partner–assessed Everyday Cognition score was preferentially selected for inclusion in the models by a feature selection algorithm during optimization.

Discussion

Our results suggest that inclusion of study partner assessments would increase the ability of machine learning models to predict Aβ positivity.
Readmission following both cardiac and non‐cardiac acute dyspnoea is associated with a striking risk of death
Authors: Čerlinskaitė Kamilė , Mebazaa Alexandre , Cinotti Raphaël , Matthay Michael , Wussler Desiree N. , Gayat Etienne , Juknevičius Vytautas , Kozhuharov Nikola , Dinort Julia , Michou Eleni , Gualandro Danielle M. , Palevičiūtė Eglė , Alitoit‐Marrote Irina , Kablučko Denis , Bagdonaitė Loreta , Balčiūnas Mindaugas , Vaičiulienė Dovilė , Jonauskienė Ieva , Motiejūnaitė Justina , Stašaitis Kęstutis , Kukulskis Audrys , Damalakas Šarūnas , Laucevičius Aleksandras , Mueller Christian , Kavoliūnienė Aušra , Čelutkienė Jelena ,   GREAT network
Published: June 2021

Aims

Readmission and mortality are the most common and often combined endpoints in acute heart failure (AHF) trials, but an association between these two outcomes is poorly investigated. The aim of this study was to determine whether unplanned readmission is associated with a greater subsequent risk of death in patients with acute dyspnoea due to cardiac and non‐cardiac causes.

Methods and results

Derivation cohort (1371 patients from the LEDA study) and validation cohort (1986 patients from the BASEL V study) included acute dyspnoea patients admitted to the emergency department. Cox regression analysis was used to determine the association of 6 month readmission and the risk of 1 year all‐cause mortality in AHF and non‐AHF patients and those readmitted due to cardiovascular and non‐cardiovascular causes. In the derivation cohort, 666 (49%) of patients were readmitted at 6 months and 282 (21%) died within 1 year. Six month readmission was associated with an increased 1 year mortality risk in both the derivation cohort [adjusted hazard ratio (aHR) 3.0 (95% confidence interval, CI 2.2–4.0), P < 0.001] and the validation cohort (aHR 1.8, 95% CI 1.4–2.2, P < 0.001). The significant association was similarly observed in AHF (aHR 3.2, 95% CI 2.1–4.9, P < 0.001) and other causes of acute dyspnoea (aHR 2.9, 95% CI 1.9–4.5, P < 0.001), and it did not depend on the aetiology [aHR 2.2, 95% CI 1.6–3.1 for cardiovascular readmissions; aHR 4.1, 95% CI 2.9–5.7 for non‐cardiovascular readmissions (P < 0.001 for both)] or timing of readmission.

Conclusion​s

Our study demonstrated a long‐lasting detrimental association between readmission and death in AHF and non‐AHF patients with acute dyspnoea. These patients should be considered ‘vulnerable patients’ that require personalized follow‐up for an extended period.
Circulating growth differentiation factor‐15 as a novel biomarker in heart transplant
Authors: Tokavanich Nithi , Sinphurmsukskul Supanee , Kongruttanachok Narisorn , Thammanatsakul Kanokwan , Sritangsirikul Supaporn , Ariyachaipanich Aekarach , Ongcharit Pat , Siwamogsatham Sarawut , Boonyaratavej Smonporn , Puwanant Sarinya
Published: June 2021

Aims

This study aimed to examine (i) whether circulating growth differentiation factor‐15 (GDF‐15) is associated with acute cellular cardiac allograft rejection (ACR); (ii) a longitudinal trend of GDF‐15 after heart transplantation; and (iii) the prognostic value of GDF‐15 in predicting a composite outcome of severe primary graft dysfunction (PGD) and 30 day mortality post‐transplant.

Methods and results

Serum samples were collected before heart transplantation and at every endomyocardial biopsy (EMB) post‐heart transplantation in de novo transplant patients. A total of 60 post‐transplant serum samples were matched to the corresponding EMBs. Seven (12%) were considered International Society for Heart Lung Transplantation Grade 1R ACR, and one (2%) was identified as Grade 2R ACR. GDF‐15 levels in patients with ACR were not different from those in the non‐rejection group (6230 vs. 6125 pg/mL, P = 0.27). GDF‐15 concentration gradually decreased from 8757 pg/mL pre‐transplant to 5203 pg/mL at 4 weeks post‐transplant. The composite adverse outcome of PGD and 30 day mortality was significantly associated with increased post‐operative GDF‐15 (odds ratio: 40; 95% confidence interval: 2.01–794.27; P = 0.005) and high inotrope score post‐transplant (odds ratio: 18; 95% confidence interval: 1.22–250.35; P = 0.01).

Conclusions

Circulating GDF‐15 concentration was markedly elevated in patients with end‐stage heart failure and decreased after heart transplantation. GDF‐15 was significantly associated with post‐transplant PGD and mortality. A lack of association between ACR and GDF‐15 did not support routine use of GDF‐15 as a biomarker to detect ACR. However, GDF‐15 may be potentially useful to determine heart transplant recipients at high risk for adverse post‐transplant outcomes. We suggest that GDF‐15 levels in recipient serum can provide risk stratification for severe PGD including death during post‐operative period. This novel biomarker may serve to inform and guide timely interventions against severe PGD and adverse outcomes during the first 4 weeks after transplantation. Further studies to support the utility of GDF‐15 in heart transplantation are required.
Variation on the π‐Acceptor Ligand within a RhI−N‐Heterocyclic Carbene Framework: Divergent Catalytic Outcomes for Phenylacetylene‐Methanol Transformations
Authors: Galiana‐Cameo María , Passarelli Vincenzo , Pérez‐Torrente Jesús J. , Di Giuseppe Andrea , Castarlenas Ricardo
Published: June 2021

A series of neutral and cationic rhodium complexes bearing IPr {IPr=1,3‐bis‐(2,6‐diisopropylphenyl)imidazolin‐2‐carbene} and π‐acceptor ligands are reported. Cationic species [Rh(η4‐cod)(IPr)(NCCH3)]+ and [Rh(CO)(IPr)(L)2]+ (L=pyridine, CH3CN) were obtained by chlorido abstraction in suitable complexes, whereas the cod‐CO derivative [Rh(η4‐cod)(IPr)(CO)]+ was formed by the carbonylation of [Rh(η4‐cod)(IPr)(NCCH3)]+. Alternatively, neutral derivatives of type RhCl(IPr)(L)2 {L=tBuNC or P(OMe)3} can be accessed from [Rh(μ‐Cl)(η2‐coe)(IPr)]2. In addition, the mononuclear species Rh(CN)(η4‐cod)(IPr) was prepared by cyanide‐chlorido anion exchange, which after carbonylation afforded the unusual trinuclear compound [Rh{1κC,2κN‐(CN)}(CO)(IPr)]3. Divergent catalytic outcomes in the phenylacetylene‐methanol transformations have been observed. Thus, enol ethers, arisen from hydroalkoxylation of the alkyne, were obtained with neutral Rh−CO catalyst precursors whereas dienol ethers were formed with cationic catalysts. Variable amounts of alkyne dimerization, cyclotrimerization or polymerization products were obtained in the absence of a strong π‐acceptor ligand on the catalyst.
Enantioseparation of solriamfetol and its major impurity phenylalaninol by capillary electrophoresis using sulfated gamma cyclodextrin
Authors: Fejős Ida , Tóth Gergő , Várnai Bianka , Szabó Zoltán István , Köteles István , Malanga Milo , Béni Szabolcs
Published: June 2021

R‐solriamfetol is a recently approved drug used for the treatment of excessive sleepiness associated with narcolepsy and sleep apnea. Herein, a capillary electrophoretic method was developed, enabling the simultaneous analysis of the API and its S‐enantiomer in addition to the enantiomers of its major impurity phenylalaninol. Twenty‐nine different cyclodextrins (CDs), including native, neutral, and charged ones were screened as potential chiral selectors, and the best results were obtained with sulfated CDs. Randomly sulfated‐β‐CD exhibited outstanding enantioresolution, the peaks of phenylalaninol enantiomers inserted between the two peaks of solriamfetol enantiomers, while sulfated‐γ‐CD (S‐γ‐CD) showed remarkable resolution values in a much shorter analysis time with the optimal enantiomer migration order. Among the single isomer sulfated CD derivatives, substituent dependent enantiomer migration order reversal could also be observed in the case of heptakis(6‐O‐sulfo)‐β‐CD (HS‐β‐CD) or heptakis(2,3‐O‐dimethyl‐6‐O‐sulfo)‐β‐CD (HDMS‐β‐CD) with R‐,S‐solriamfetol, and heptakis(2,3‐O‐diacetyl‐6‐O‐sulfo)‐β‐CD (HDAS‐β‐CD) resulting S‐,R‐solriamfetol migration order. The sulfated‐γ‐CD system was chosen for method optimization applying orthogonal experimental design. The optimized method (45 mM Tris‐acetate buffer, pH 4.5, 4 mM S‐γ‐CD, 21°C, +19.5 kV) was capable for the baseline separation of solriamfetol and phenylalaninol enantiomers within 7 min. The optimized method was validated according to the ICH guidelines and successfully applied for the analysis of pharmaceutical preparation (Sunosi® 75 mg tablet), thus it may serve as a routine procedure for the laboratories of regulatory authorities as well as in Pharmacopoeias.