bluuebunny/crossref_metadata_2025_split huggingface dataset:
BOXR1030, an anti-GPC3 CAR with exogenous GOT2 expression, shows enhanced T cell metabolism and improved anti-cell line derived tumor xenograft activity
Authors: Hickman Taylor L. , Choi Eugene , Whiteman Kathleen R. , Muralidharan Sujatha , Pai Tapasya , Johnson Tyler , Parikh Avani , Friedman Taylor , Gilbert Madaline , Shen Binzhang , Barron Luke , McGinness Kathleen E. , Ettenberg Seth A. , Motz Greg T. , Weiss Glen J. , Jensen-Smith Amy 
Published: May 2022

Purpose
The solid tumor microenvironment (TME) drives T cell dysfunction and inhibits the effectiveness of immunotherapies such as chimeric antigen receptor-based T cell (CAR T) cells. Early data has shown that modulation of T cell metabolism can improve intratumoral T cell function in preclinical models.

Experimental design
We evaluated GPC3 expression in human normal and tumor tissue specimens. We developed and evaluated BOXR1030, a novel CAR T therapeutic co-expressing glypican-3 (GPC3)-targeted CAR and exogenous glutamic-oxaloacetic transaminase 2 (GOT2) in terms of CAR T cell function both in vitro and in vivo.

Results
Cell surface expression of tumor antigen GPC3 was observed by immunohistochemical staining in tumor biopsies from hepatocellular carcinoma, liposarcoma, squamous lung cancer, and Merkel cell carcinoma patients. Compared to control GPC3 CAR alone, BOXR1030 (GPC3-targeted CAR T cell that co-expressed GOT2) demonstrated superior in vivo efficacy in aggressive solid tumor xenograft models, and showed favorable attributes in vitro including an enhanced cytokine production profile, a less-differentiated T cell phenotype with lower expression of stress and exhaustion markers, an enhanced metabolic profile and increased proliferation in TME-like conditions.

Conclusions
Together, these results demonstrated that co-expression of GOT2 can substantially improve the overall antitumor activity of CAR T cells by inducing broad changes in cellular function and phenotype. These data show that BOXR1030 is an attractive approach to targeting select solid tumors. To this end, BOXR1030 will be explored in the clinic to assess safety, dose-finding, and preliminary efficacy (NCT05120271).
Using machine learning to predict health-related quality of life outcomes in patients with low grade glioma, meningioma, and acoustic neuroma
Authors: Karri Roshan , Chen Yi-Ping Phoebe , Drummond Katharine J. 
Published: May 2022

Background
Predicting reduced health-related quality of life (HRQoL) after resection of a benign or low-grade brain tumour provides the opportunity for early intervention, and targeted expenditure of scarce supportive care resources. We aimed to develop, and evaluate the performance of, machine learning (ML) algorithms to predict HRQoL outcomes in this patient group.

Methods
Using a large prospective dataset of HRQoL outcomes in patients surgically treated for low grade glioma, acoustic neuroma and meningioma, we investigated the capability of ML to predict a) HRQoL-impacting symptoms persisting between 12 and 60 months from tumour resection and b) a decline in global HRQoL by more than the minimum clinically important difference below a normative population mean within 12 and 60 months after resection. Ten-fold cross-validation was used to measure the area under the receiver operating characteristic curve (AUC), area under the precision-recall curve (PR-AUC), sensitivity, and specificity of models. Six ML algorithms were explored per outcome: Random Forest Classifier, Decision Tree Classifier, Logistic Regression, K Neighbours Classifier, Support Vector Machine, and Gradient Boosting Machine.

Results
The final cohort included 262 patients. Outcome measures for which AUC>0.9 were Appetite loss, Constipation, Nausea and vomiting, Diarrhoea, Dyspnoea and Fatigue. AUC was between 0.8 and 0.9 for global HRQoL and Financial difficulty. Pain and Insomnia achieved AUCs below 0.8. PR-AUCs were similar overall to the AUC of each respective classifier.

Conclusions
ML algorithms based on routine demographic and perioperative data show promise in their ability to predict HRQoL outcomes in patients with low grade and benign brain tumours between 12 and 60 months after surgery.
New insights into the potential utility of the left atrial function analysis in heart failure with preserved ejection fraction diagnosis
Authors: Rimbas Roxana Cristina , Visoiu Ionela Simona , Magda Stefania Lucia , Mihaila-Baldea Sorina , Luchian Maria Luiza , Chitroceanu Alexandra Maria , Hayat Memis , Mihalcea Diana Janina , Dragoi-Galrinho-Antunes-Guerra Ruxandra , Stefan Miruna , Velcea Andreea , Andronic Anca Andreea , Lungeanu-Juravle Laura , Nicula Alina Ioana , Vinereanu Dragos 
Published: May 2022

Aims
None of the conventional echocardiographic parameters alone predict increased NTproBNP level and symptoms, making diagnosis of heart failure with preserved ejection fraction (HFpEF) very difficult in some cases, in resting condition. We evaluated LA functions by 2D speckle tracking echocardiography (STE) on top of conventional parameters in HFpEF and preHF patients with diastolic dysfunction (DD), in order to establish the added value of the LA deformation parameters in the diagnosis of HFpEF.

Methods
We prospectively enrolled 125 patients, 88 with HFpEF (68±9 yrs), and 37 asymptomatic with similar risk factors with DD (preHF) (61±8 yrs). We evaluated them by NTproBNP, conventional DD parameters, and STE. Global longitudinal strain (GS) was added. LA reservoir (R), conduit (C), and pump function (CT) were assessed both by volumetric and STE. 2 reservoir strain (S) derived indices were also measured, stiffness (SI) and distensibility index (DI).

Results
LA R and CT functions were significantly reduced in HFpEF compared to preHF group (all p<0.001), whereas conduit was similarly in both groups. SI was increased, whereas DI was reduced in HFpEF group (p<0.001). By adding LA strain analysis, from all echocardiographic parameters, SR_CT<-1.66/s and DI<0.57 (AUC = 0.76, p<0.001) demonstrated the highest accuracy to identify HFpEF diagnosis. However, by multivariate logistic regression, the model that best identifies HFpEF included only SR_CT, GS and sPAP (R2 = 0.506, p<0.001). Moreover, SR_CT, DI, and sPAP registered significant correlation with NTproBNP level.

Conclusions
By adding LA functional analysis, we might improve the HFpEF diagnosis accuracy, compared to present guidelines. LA pump function is the only one able to differentiates preHF from HFpEF patients at rest. A value of SR_CT < -1.66/s outperformed conventional parameters from the scoring system, reservoir strain, and LA overload indices in HFpEF diagnosis. We suggest that LA function by STE could be incorporated in the current protocol for HFpEF diagnosis at rest as a major functional criterion, in order to improve diagnostic algorithm, and also in the follow-up of patients with risk factors and DD, as a prognostic marker. Future studies are needed to validate our findings.
Malaria transmission in Africa: Its relationship with yellow fever and measles
Authors: Okunlola Oluyemi A. , Oyeyemi Oyetunde T. 
Published: May 2022

Background
Malaria has been strongly linked to the transmission and pathophysiology of some viral diseases. Malaria and vaccine-preventable diseases often co-exist in endemic countries but the implication of their co-existence on their transmission dynamics and control is poorly understood. The study aims to evaluate the relationships between the incidence of malaria and cases of measles and yellow fever in Africa.

Methods
The malaria incidence, death due to malaria, measles and yellow fever data were sourced from the WHO database. Poisson and zero-inflated time-trend regression were used to model the relationships between malaria and the two vaccine-preventable diseases. P-values <0.05 were considered statistically significant.

Results
A significant negative relationship existed between malaria incidence and measles cases (P<0.05), however, malaria showed a positive relationship with yellow fever (P<0.05). The relationships between death due to malaria and measles/yellow fever cases followed similar trends but with a higher level of statistical significance (P<0.001).

Conclusions
Malaria varied negatively with measles cases but positively with yellow fever. The relationships observed in this study could be important for the management of malaria and the studied vaccine-preventable diseases. Increase vaccination coverage and/or malaria treatment could modulate the direction of these relationships.
Statin-Induced Rhabdomyolysis Associated With Transjugular Intrahepatic Portosystemic Shunt Placement
Authors: Swei Eric C. , Brar Anantnoor K. , Rice Jonathan D. , Kim Ike I. , Knez Virginia M. , Doe Christopher F. , Forman Lisa M. 
Published: May 2022

ABSTRACT
Rhabdomyolysis is a known rare and potentially lethal complication of statin use. This toxic effect is potentiated by alterations in hepatic physiology in patients with cirrhosis. Transjugular intrahepatic portosystemic shunt placement has the potential to further compound this effect; yet, examples of this have not previously been described in the literature. We present a case of a patient who experienced statin-induced rhabdomyolysis likely as a direct consequence of transjugular intrahepatic portosystemic shunt placement.
NR4A1 inhibits the epithelial–mesenchymal transition of hepatic stellate cells: Involvement of TGF-β–Smad2/3/4–ZEB signaling
Authors: Huang Qian , Xu Jingying , Ge Yanyan , Shi Yue , Wang Fei , Zhu Mingli 
Published: May 2022

Abstract
This study aimed to examine whether nuclear receptor 4a1 (NR4A1) is involved in inhibiting hepatic stellate cell (HSC) activation and liver fibrosis through the epithelial–mesenchymal transition (EMT). HSC-T6 cells were divided into the control group, the acetaldehyde (200 μM, an EMT activator) group, and the NR4A1 activation group (Cytosporone B; 1 μM). The expression levels of the epithelial marker E-cadherin, the mesenchymal markers fibronectin (FN), vimentin, smooth muscle alpha-actin (α-SMA), and fibroblast-specific protein 1 (FSP-1), and the components of the transforming growth factor (TGF)-β pathway were detected by real-time polymerase chain reaction and western blotting. Compared with the control group, E-cadherin in the acetaldehyde group was downregulated, whereas FN, FSP-1, vimentin, α-SMA, and COL1A1/COL1A2 were upregulated (P < 0.05). Compared with the acetaldehyde group, NR4A1 agonist upregulated E-cadherin and downregulated FN, FSP-1, vimentin, α-SMA, and COL1A1/COL1A2 (P < 0.05). After acetaldehyde stimulation, TGF-β, Smad2/3/4, and zinc finger E-box-binding homeobox (ZEB) were upregulated, while Smad7 mRNA levels were downregulated (all P < 0.05). Compared with acetaldehyde alone, NR4A1 agonist increased Smad7 mRNA levels and reduced TGF-β, Smad2/3/4, and ZEB mRNA levels (all P < 0.05). NR4A1 activation suppresses acetaldehyde-induced EMT, as shown by epithelial and mesenchymal marker expression. The inhibition of the TGF-β–Smad2/3/4–ZEB signaling during HSC activation might be involved.
Ten year analysis of the clinic profile of the tertiary paediatric endocrine service in Western Australia
Authors: Birdus Nadya , Grant Maree , Stevenson Paul G. , Choong Catherine S. Y. , Siafarikas Aris 
Published: May 2022

Abstract

Objectives
There is a paucity of information regarding the profile of entire paediatric endocrine clinics and how they are changing. This study aimed to analyse the clinic profile of the Western Australian tertiary paediatric endocrine outpatient service over 10 years and compare to national and international data.

Methods
Retrospective analysis of the Western Australian Paediatric Endocrine Database (WAPED) between 2007 and 2017 looking at the frequency, proportion and longitudinal change of diagnosis categories, specific diagnoses, and gender breakdown.

Results
In total, 2,791 endocrine diagnoses were recorded for 2,312 patients. The most frequent reason for referral (22.1% of patients), was for evaluation of abnormalities in thyroid function. The most common diagnosis being hypothyroidism (76.7%). Evaluation of short stature was the reason for referral in 19.2% of patients, 14.6% of whom were diagnosed with growth hormone deficiency. Evaluation of puberty disorders, syndromes with endocrine features and disorders of calcium and phosphate metabolism were other common reasons for clinic referral, seen in 11.3, 9.8 and 8.2% of patients respectively. Between 2007 and 2017, the odds ratio of a thyroid diagnosis increased by 1.07 per year (95% CI: 1.02–1.12), whilst the odds ratio of a short stature diagnosis decreased by 0.91 per year (95% CI: 0.87–0.95).

Conclusions
The profile of the WAPED is similar to previously published national and international data. The analysis of the profile of diagnoses and its longitudinal change over a ten-year period offer a unique opportunity to guide clinic planning, resource allocation and future research.
Crystal structure of 5-(adamantan-1-yl)-3-[(4-trifluoromethylanilino)methyl]-2,3-dihydro-1,3,4-oxadiazole-2-thione, C20H22F3N3OS
Authors: Al-Wahaibi Lamya H. , Ghabbour Hazem A. , Al-Omary Fatmah A. M. , Tiekink Edward R. T. , El-Emam Ali A. 
Published: May 2022

Abstract
C20H22F3N3OS, triclinic, P1 (no. 1), a = 6.9678(8) Å, b = 10.7614(14) Å, c = 13.0503(14) Å, α = 76.870(3)°, β = 88.004(4)°, γ = 87.275(4)°, V = 951.60(19) Å3, Z = 2, R

gt
(F) = 0.0629, wR

ref
(F
2) = 0.1626, T = 100 K.
Physical properties of kraft pulp oxidized by hydrogen peroxide under mildly acidic conditions
Authors: Martinsson Axel , Hasani Merima , Theliander Hans 
Published: May 2022

Abstract
The objective of this study is to gain further insight into the compositional and physical changes of kraft pulp caused by oxidation with hydrogen peroxide under acidic conditions. A softwood kraft pulp has been subjected to varying degrees of oxidation. Changes in the composition, as well as resulting physical properties of laboratory sheets were investigated. Findings indicated that the oxidation resulted in an increased carbonyl group content, a decrease in intrinsic viscosity and a change in hemicellulose composition. The oxidized pulps were found to have a reduced water retention value and a slightly reduced tensile strength (4–11 % at the investigated conditions). However, a substantial increase in wet web tensile strength (6–23 %) and wet tensile strength (134–242 %) of the sheets was obtained. The sheets could easily be repulped and an increased wet strength maintained to a large extent, even after recycling of the sheets.
Agrobiodiversity and perceived climatic change effect on family farming systems in semiarid tropics of Kenya
Authors: Njeru Ezekiel Mugendi , Awino Richard Otieno , Kirui Kibet Charles , Koech Kipkorir , Jalloh Abdul Alhaji , Muthini Morris 
Published: May 2022

Abstract
The steady decline in agrobiodiversity is not only a significant threat to the genetic stability of the rural agroecosystems but also places a huge impediment to the realization of global food security. Climate change and decline in arable land is forcing subsistence farmers to abandon the less productive but well-adapted local crops for the newer short term and drought-tolerant crops decimating agrobiodiversity further. This study sought to establish the on-farm species and genetic diversity status among the family farming systems of semiarid areas of Eastern Kenya and effect on food security, agrobiodiversity management strategies, their perception of climate change, and climate change coping strategies. Structured questionnaires were administered to 92 active farmers in Embu, Kitui, and Tharaka Nithi Counties of Eastern Kenya. On-farm diversity, socio-economic factors, and their impact on agrobiodiversity were determined. Possible correlations were established using Spearman’s Rank Correlation Coefficient. Remarkably, 26 crop species were recorded where legumes and cereals were dominant. According to the Shannon–Wiener Diversity index (H′), Tharaka Nithi County recorded the highest legumes and cereals diversity indices of 3.436 and 3.449, respectively. Food shortage was reported by over 50% of the respondents in the study area. The existence of weaker adaptive measures in response to climate change was evident. Family farming systems that had higher crop diversification and integrated livestock rearing in their farms were more food secure. Improved mitigation to climate change and diversification of farming systems among the smallholder farms is essential not only in boosting the food security but also in establishment of sustainable farming systems resilient to climate change.
Nonlocal magneto-thermoelastic infinite half-space due to a periodically varying heat flow under Caputo–Fabrizio fractional derivative heat equation
Authors: Abouelregal Ahmed E. , Ahmad Hijaz , Aldahlan Maha A. , Zhang Xiao-Zhong 
Published: May 2022

Abstract
This article deals with a new modified heat conduction model with fractional order that includes the Caputo–Fabrizio differential operator (CF) and the thermal relaxation time. This new approach to the CF fractional derivative has attracted many researchers because it includes a nonsingular kernel. The nonlocal theory proposed by Eringen has also been applied to demonstrate the effect of scale-dependent thermoelastic materials. The problem of thermal isotropic semi-infinite space is addressed as an application of the presented model. The medium is exposed to regularly changing heat sources and is initially placed in a continuous external magnetic field. The system of governing equations was expressed in the field of the Laplace transform, and the problem in this field was solved by the state-space operation. The inverse of the transformed expressions of physical quantities is found numerically using Zakian’s algorithm. The effects of the nonlocal parameter, the fractal order parameter, and the magnetic field were graphically presented and analyzed in detail. Some of the previous investigations were extracted in some special cases.
Phosphorylation of myosin A regulates gliding motility and is essential for Plasmodium transmission
Authors: Ripp Johanna , Smyrnakou Xanthoula , Neuhoff Marie‐Therese , Hentzschel Franziska , Frischknecht Friedrich 
Published: May 2022

AbstractMalaria‐causing parasites rely on an actin–myosin‐based motor for the invasion of different host cells and tissue traversal in mosquitoes and vertebrates. The unusual myosin A of Plasmodium spp. has a unique N‐terminal extension, which is important for red blood cell invasion by P. falciparum merozoites in vitro and harbors a phosphorylation site at serine 19. Here, using the rodent‐infecting P. berghei we show that phosphorylation of serine 19 increases ookinete but not sporozoite motility and is essential for efficient transmission of Plasmodium by mosquitoes as S19A mutants show defects in mosquito salivary gland entry. S19A along with E6R mutations slow ookinetes and salivary gland sporozoites in both 2D and 3D environments. In contrast to data from purified proteins, both E6R and S19D mutations lower force generation by sporozoites. Our data show that the phosphorylation cycle of S19 influences parasite migration and force generation and is critical for optimal migration of parasites during transmission from and to the mosquito.
Application of visual simulation in the activation of historical district
Authors: Zixin Liang , Várady Géza , Zagorácz Márk Balázs 
Published: May 2022

Abstract
With the rapid development of China’s urbanization, a large number of people have moved from rural to urban areas. People have proposed higher and more urgent needs for the urban environment. Particularly, the urban street landscape is close to people’s lives, and the upgrading of design methods can improve the quality of life. Besides, the application of artificial intelligence design has become possible as information technology develops. In this paper, a visual simulator is established through algorithm models and applied to street landscape design.
Análisis de las condiciones laborales, trabajo y de salud del estudiantes trabajador del Programa Seguridad y Salud en el Trabajo de la Universidad Francisco de Paula Santander 2020
Authors: Carvajalino Rueda Manuel Vicente , Carvajal Villamizar Henny patricia 
Published: May 2022

La dinámica socioeconómica actual, exige para el mercado laboral perfiles cada vez más especializados, lleva a la población que inviertan en su formación profesional obligando a muchos a combinar los estudios con el trabajo para lograr dichas exigencias laborales insertándose en un mercado competido. La Organización Internacional del Trabajo, OIT destaca que alrededor del 93% de los jóvenes ocupados se encuentran en el sector informal de la economía, donde son comunes las condiciones precarias de empleo, la falta de garantías laborales y la baja productividad y remuneración del trabajo. La presente investigación se centró en analizar las condiciones laborales, trabajo y de salud de estudiantes del pregrado de seguridad y salud en el trabajo de la universidad Francisco de Paula Santander.
Se empleará una metodología cualitativa, de corte transversal y de tipo descriptivo, método indagación y sondeo; la población constituye los 274 estudiantes del programa de pregrado de seguridad y salud en el trabajo de la UFPS matriculados en el 2 semestre académicos 2020. El tipo de muestreo
aleatorio simple para poblaciones finitas y la muestra está constituida por 161 estudiantes. La técnica utilizada para la recolección de datos es la encuesta, se aplicará el cuestionario “II Encuesta Nacional de Condiciones de Seguridad y Salud en el Trabajo en el sistema general de riesgos laborales de Colombia. 2013”. El análisis se realizará en dos momentos, el primero el análisis de las condiciones laborales y de trabajo respecto a cuestiones como salario, jornada laboral, prestaciones sociales, contrato de trabajo y condiciones de trabajo. En un segundo momento se analizan los aspectos de condiciones de salud.
Evaluación de riesgos para el trabajo en casa, experiencia de colaboradores del Politécnico Grancolombiano 2020
Authors: Quiroz Rubiano Monica 
Published: May 2022

Resaltando esas pandemias a las cuales la humanidad ha estado sometida a través de la historia y sobre las cuales quizá, algunas personas se hicieron alguna pregunta en algún momento de su vida y sobre todo ¿qué tan bueno habrá sido vivir en ese momento ese evento histórico? De lo anterior, es importante generar primero un contexto sobre que se está viviendo, ya porque hay unos términos específicos relacionados con el tema de la pandemia que, realmente muchos o pocos lo pueden conocer, como, por ejemplo, ¿qué es una endemia? O ¿qué es una pandemia?
De ello, se realizó un recuento histórico de las pandemias más importantes que han ocurrido a lo largo de la historia y cómo se ha repuesto de ellas el ser humano, todo ello con el fin de decantar en cómo la humanidad se ve en la necesidad de adaptarse poco a poco a los diferentes cambios, por lo cual, ante la actual pandemia por SARS-CoV-2, los colaboradores de las diferentes entidades, empresas u organizaciones debieron cambiar sus lugares de trabajo por el trabajo en casa, de ello, surgió la necesidad de evaluar el riesgo al cual sometido el trabajador en casa del Politécnico Grancolombiano, para lo cual se desarrolló una herramienta que permita la medición de esas condiciones.