bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and tolerability of KarXT (xanomeline–trospium) in a phase 2, randomized, double-blind, placebo-controlled study in patients with schizophrenia
Authors: Correll Christoph U. , Angelov Angel S. , Miller Andrew C. , Weiden Peter J. , Brannan Stephen K. 
Published: December 2022

AbstractKarXT combines xanomeline, an M1/M4 preferring muscarinic agonist with no direct D2 receptor antagonism, with the peripherally restricted anticholinergic trospium. In EMERGENT-1 (NCT03697252), a 5-week, randomized, double-blind, placebo-controlled, phase 2 study in inpatients with schizophrenia, KarXT met the primary efficacy endpoint, numerous secondary endpoints, and was generally well tolerated. Here, we conducted additional post hoc analyses of safety and tolerability data of KarXT from EMERGENT-1 with a particular focus on adverse events (AEs) that may be associated with muscarinic receptor agonism (nausea or vomiting) or antagonism (dry mouth or constipation). A total of 179 patients received at least one dose of either KarXT (n = 89) or placebo (n = 90) and were included in the analyses. KarXT was associated with a low overall AE burden. The majority of procholinergic and anticholinergic AEs with KarXT were mild, occurred in the first 1−2 weeks of treatment, and were transient with a median duration ranging from 1 day for vomiting to 13 days for dry mouth. No patients in either treatment group discontinued the study due to any procholinergic or anticholinergic AEs. Incidence of somnolence/sedation AEs with KarXT were low and similar to those in the placebo group. KarXT was associated with no significant or clinically relevant changes in body weight, metabolic parameters, or vital signs. KarXT was generally well tolerated with an AE profile consistent with the activity of xanomeline–trospium at muscarinic receptors.
Centrin-deficient Leishmania mexicana confers protection against Old World visceral leishmaniasis
Authors: Karmakar Subir , Volpedo Greta , Zhang Wen-Wei , Lypaczewski Patrick , Ismail Nevien , Oliveira Fabiano , Oristian James , Meneses Claudio , Gannavaram Sreenivas , Kamhawi Shaden , Hamano Shinjiro , Valenzuela Jesus G. , Matlashewski Greg , Satoskar Abhay R. , Dey Ranadhir , Nakhasi Hira L. 
Published: December 2022

AbstractLeishmaniasis is one of the top neglected tropical diseases with significant morbidity and mortality in low and middle-income countries (LMIC). However, this disease is also spreading in the developed world. Currently, there is a lack of effective strategies to control this disease. Vaccination can be an effective measure to control leishmaniasis and has the potential to achieve disease elimination. Recently, we have generatedcentringene-deleted new worldL. mexicana(LmexCen−/−) parasites using CRISPR/Cas9 and showed that they protect mice against a homologousL. mexicanainfection that causes cutaneous disease. In this study, we tested whetherLmexCen−/−parasites can also protect against visceral leishmaniasis caused byL. donovaniin a hamster model. We showed that immunization withLmexCen−/−parasites is safe and does not cause lesions. Furthermore, such immunization conferred protection against visceral leishmaniasis caused by a needle-initiatedL. donovanichallenge, as indicated by a significant reduction in the parasite burdens in the spleen and liver as well as reduced mortality. Similar control of parasite burden was also observed against a sand fly mediatedL. donovanichallenge. Importantly, immunization withLmexCen−/−down-regulated the disease promoting cytokines IL-10 and IL-4 and increased pro-inflammatory cytokine IFN-γ resulting in higher IFN-γ/IL-10 and IFN-γ/IL4 ratios compared to non-immunized animals.LmexCen−/−immunization also resulted in long-lasting protection againstL. donovaniinfection. Taken together, our study demonstrates that immunization withLmexCen−/−parasites is safe and efficacious against the Old World visceral leishmaniasis.
BNT162b2 induces robust cross-variant SARS-CoV-2 immunity in children
Authors: Bartsch Yannic C. , Chen Jessica W. , Kang Jaewon , Burns Madeleine D. , St Denis Kerri J. , Sheehan Maegan L. , Davis Jameson P. , Edlow Andrea G. , Balazs Alejandro B. , Yonker Lael M. , Alter Galit 
Published: December 2022

AbstractCurrently available mRNA vaccines are extremely safe and effective to prevent severe SARS-CoV-2 infections. However, the emergence of variants of concerns (VOCs) has highlighted the importance of high population-based vaccine rates to effectively suppress viral transmission and breakthrough infections. While initially left out from vaccine efforts, children have become one of the most affected age groups and are key targets to stop community and household spread. Antibodies are central for vaccine-induced protection and emerging data points to the importance of additional Fc effector functions like opsononophagocytosis or cytotoxicity, particularly in the context of VOCs that escape neutralizing antibodies. Here, we observed delayed induction and reduced magnitude of vaccine-induced antibody titers in children 5-11 years receiving two doses of the age-recommended 10 μg dose of the Pfizer SARS-CoV-2 BNT162b2 vaccine compared to adolescents (12–15 years) or adults receiving the 30 μg dose. Conversely, children mounted equivalent or more robust neutralization and opsonophagocytic functions at peak immunogenicity, pointing to a qualitatively more robust humoral functional response in children. Moreover, broad cross-VOC responses were observed across children, with enhanced IgM and parallel IgG cross-reactivity to VOCs in children compared to adults. Collectively, these data argue that despite the lower magnitude of the BNT162b2-induced antibody response in children, vaccine-induced immunity in children target VOCs broadly and exhibit enhanced functionality that may contribute to the attenuation of disease.
A multi-omics longitudinal aging dataset in primary human fibroblasts with mitochondrial perturbations
Authors: Sturm Gabriel , Monzel Anna S. , Karan Kalpita R. , Michelson Jeremy , Ware Sarah A. , Cardenas Andres , Lin Jue , Bris Céline , Santhanam Balaji , Murphy Michael P. , Levine Morgan E. , Horvath Steve , Belsky Daniel W. , Wang Shuang , Procaccio Vincent , Kaufman Brett A. , Hirano Michio , Picard Martin 
Published: December 2022

AbstractAging is a process of progressive change. To develop biological models of aging, longitudinal datasets with high temporal resolution are needed. Here we report a multi-omics longitudinal dataset for cultured primary human fibroblasts measured across their replicative lifespans. Fibroblasts were sourced from both healthy donors (n = 6) and individuals with lifespan-shortening mitochondrial disease (n = 3). The dataset includes cytological, bioenergetic, DNA methylation, gene expression, secreted proteins, mitochondrial DNA copy number and mutations, cell-free DNA, telomere length, and whole-genome sequencing data. This dataset enables the bridging of mechanistic processes of aging as outlined by the “hallmarks of aging”, with the descriptive characterization of aging such as epigenetic age clocks. Here we focus on bridging the gap for the hallmark mitochondrial metabolism. Our dataset includes measurement of healthy cells, and cells subjected to over a dozen experimental manipulations targeting oxidative phosphorylation (OxPhos), glycolysis, and glucocorticoid signaling, among others. These experiments provide opportunities to test how cellular energetics affect the biology of cellular aging. All data are publicly available at our webtool: https://columbia-picard.shinyapps.io/shinyapp-Lifespan_Study/
EyeT4Empathy: Dataset of foraging for visual information, gaze typing and empathy assessment
Authors: Lencastre Pedro , Bhurtel Samip , Yazidi Anis , e Mello Gustavo B. M. , Denysov Sergiy , Lind Pedro G. 
Published: December 2022

AbstractWe present a dataset of eye-movement recordings collected from 60 participants, along with their empathy levels, towards people with movement impairments. During each round of gaze recording, participants were divided into two groups, each one completing one task. One group performed a task of free exploration of structureless images, and a second group performed a task consisting of gaze typing, i.e. writing sentences using eye-gaze movements on a card board. The eye-tracking data recorded from both tasks is stored in two datasets, which, besides gaze position, also include pupil diameter measurements. The empathy levels of participants towards non-verbal movement-impaired people were assessed twice through a questionnaire, before and after each task. The questionnaire is composed of forty questions, extending a established questionnaire of cognitive and affective empathy. Finally, our dataset presents an opportunity for analysing and evaluating, among other, the statistical features of eye-gaze trajectories in free-viewing as well as how empathy is reflected in eye features.
The effect of mesenchymal stem cells-derived exosomes on the prostate, bladder, and renal cancer cell lines
Authors: Rezaeian AhmadReza , Khatami Fatemeh , Heidari Keshel Saeed , Akbari Mohammad Reza , Mirzaei Akram , Gholami Keykavos , Mohammadi Farsani Reza , Aghamir Seyed Mohammad Kazem 
Published: December 2022

AbstractWe aimed to explain the role of mesenchymal stem cells (MSC-exosomes) on gene expressions of epithelial to mesenchymal transition (EMT), angiogenesis, and apoptosis. Four different cell lines were employed, including ACHN, 5637, LNCaP, and PC3, as well-known representatives for renal, bladder, hormone-sensitive, and hormone-refractory prostate cancers, respectively. Cell lines were exposed to diverse concentrations of mesenchymal stem cells-derived exosomes to find IC50 values. Percentages of apoptotic cells were evaluated by Annexin/P.I. staining. Micro Culture Tetrazolium Test assessed proliferative inhibitory effect; and prostate biomarker (KLK2), EMT (E-cadherin and Snail), angiogenesis genes (VEGF-A/VEGF-C), apoptosis genes (BAX/BCL2, P53) and Osteopontin variants (OPNa/b, and c) mRNA levels were studied by realtime PCR method. All 5637, LNCaP, and PC3 following treatment with exosomes illustrated specific responses with changes in expression of different genes. The increased TP53 and decreased BCL2 expressions were seen in 5637, LNCaP, and PC3. In PC3, OPNb and OPNc have raised more than P53; in LNCap, the increase was in VEGF-c. In 5637 cells, more than TP53 and BCL2 changes, two other genes, VEGFa and B.A.X., have decreased, suggesting exosomes’ anti-apoptotic and anti-angiogenic effects. The kidney tumor cell line saw no significant gene expression change in ten targeted genes. MSC-exosomes therapy has augmented some interesting antitumor effects on prostate, bladder, and kidney cancer cell lines. This effect which originates from exosomes’ potency to persuade apoptosis and prevent the proliferation of cancer cells simultaneously, was more substantial in bladder cancer, moderate in prostate cancer, and mild in renal cancer.
The importance of eating patterns for health-related quality of life among children aged 10–11 years in Alberta of Canada
Authors: Wu Xiu Yun , Ohinmaa Arto , Maximova Katerina , Veugelers Paul J. 
Published: December 2022

AbstractChildren with unhealthy eating behaviours are more likely to experience poor physical and mental health. Few studies have investigated the importance of eating patterns for health-related quality of life (HRQoL) among children. This study aimed to identify common eating patterns, and their associations with HRQoL among Canadian children. Data were collected from 9150 grade five students (aged 10–11 years) in repeat cross-sectional population-based surveys in Alberta, Canada. Students’ eating behaviours were analyzed using latent class analysis to identify the eating patterns. We applied multilevel multivariable logistic regression to examine the association of the eating patterns with HRQoL. We identified three groups of children with distinct eating patterns: eating healthy (52%), less healthy (31%) and unhealthy (17%). The first group had a higher proportion of students engaged in healthy eating behaviours. The unhealthy pattern group (third group) included a higher proportion of students with poor eating behaviours. Students’ eating behaviours in the second group were healthier than the third group but less healthy than the first group. Children with unhealthy and less healthy patterns were more likely to experience lower HRQoL than children with the healthy pattern. Health promotion programs effective in improving healthy eating patterns may not only reduce the risk for chronic diseases in the long term, but also improve the HRQoL in the short term.
One pot synthesis of two potent Ag(I) complexes with quinoxaline ligand, X-ray structure, Hirshfeld analysis, antimicrobial, and antitumor investigations
Authors: El-Naggar Mostafa A. , Sharaf Mona Mohammed , Albering Jörg H. , Abu-Youssef Morsy A. M. , Kassem Taher S. , Soliman Saied M. , Badr Ahmed M. A. 
Published: December 2022

AbstractIn one pot, the self-assembly of AgNO3 and 2-chloroquinoxaline (2Cl-quinox) in water–ethanol mixture afforded two novel crystalline Ag(I) complexes. The major product is the polymeric complex [Ag(2Cl-quinox)(NO3)]n; (1), while the minor product (2) comprises two molecules which are the monomeric [Ag(2Cl-quinox)2(NO3)]; (2a) and polymeric [Ag(2Cl-quinox)(NO3)]n; (2b) complexes. The single crystal X-ray structure revealed that 1 and 2b are made up of two-dimensional infinite sheets. In contrast, 2a is a monomeric complex which has a highly distorted tetrahedral geometry around Ag(I) center. In all cases, the 2Cl-quinox molecule acts as a terminal monodentate ligand. Complexes 1 and 2b have similar molecular structures and also have almost similar crystal packing. Using Hirshfeld surface analysis, the O…H hydrogen bonds and π–π stacking interactions contributed significantly to the molecular packing. Both complexes have broad-spectrum action towards multi drug-resistance bacteria. The most effective function of 2 is against Proteus morganii, with a MIC value of 8 μg/mL. Complex 2 (IC50 = 5.93 ± 0.52 μg/mL) has remarkably greater cytotoxic effect against lung carcinoma (A-549) than cis-platin (IC50 = 7.5 ± 0.69 μg/mL) and AgNO3 (IC50 = 14.7 ± 0.53 μg/mL). The higher Ag-content in 2 could be the main reason for its higher cytotoxicity than 1.
The inhibitory effect of agricultural fiscal expenditure on agricultural green total factor productivity
Authors: Wang Shuguang , Zhu Jiaying , Wang Lang , Zhong Shen 
Published: December 2022

AbstractSustainable development of agriculture is the basis for achieving social sustainable development. As the basic industry of national economy, green development of agriculture has become an important support for building an environment-friendly society. Agricultural fiscal expenditure is a direct channel for the government to support agriculture and promote agricultural transformation. It is important to analyze the impact of agricultural fiscal expenditure (AFE) on agricultural green total factor productivity (AGTFP) for sustainable agricultural development. Therefore, this paper employs the random effect model and spatial Durbin model to empirically analyze the direct effect and spatial spillover effect of AFE on AGTFP by using the agricultural panel data of 30 provinces in China from 2008 to 2020. Then, by taking the policy proposal as the time node, this paper also conducts a time heterogeneity analysis to measure the impact of policy enactment on AFE and AGTFP. The main conclusions are as follows: (1) AGTFP exists significant positive spatial spillover effect. The "radiation effect" of agricultural green development is significant. (2) AFE can significantly reduce the AGTFP in the local area, that is, 1% increase of AFE in the local area will reduce AGTFP by 0.037%. At present, agriculture is still yield-oriented. The improvement of AFE in the local area will lead to the expansion of local agricultural production and increase pollution emission. (3) AFE has a significant negative spatial spillover effect on AGTFP, that is, for every 1% increase in AFE, the AGTFP will decrease 0.123% in geographically similar areas, while the AGTFP will decrease by 0.116% in economically and geographically similar areas. It is obvious that AFE will promote the optimization of agricultural production conditions in the province, with the "demonstration effect" on the surrounding areas, the enthusiasm of production in the surrounding areas will increase, thus expanding the pollution emission. (4) According to the analysis of different periods, AFE has a negative impact on AGTFP mainly before the reform innovation is proposed in 2015. It indicates that reform policies have a significant impact on agricultural sustainability.
Transcriptomics indicate nuclear division and cell adhesion not recapitulated in MCF7 and MCF10A compared to luminal A breast tumours
Authors: Goh Jeremy Joon Ho , Goh Corinna Jie Hui , Lim Qian Wei , Zhang Songjing , Koh Cheng-Gee , Chiam Keng-Hwee 
Published: December 2022

AbstractBreast cancer (BC) cell lines are useful experimental models to understand cancer biology. Yet, their relevance to modelling cancer remains unclear. To better understand the tumour-modelling efficacy of cell lines, we performed RNA-seq analyses on a combined dataset of 2D and 3D cultures of tumourigenic MCF7 and non-tumourigenic MCF10A. To our knowledge, this was the first RNA-seq dataset comprising of 2D and 3D cultures of MCF7 and MCF10A within the same experiment, which facilitates the elucidation of differences between MCF7 and MCF10A across culture types. We compared the genes and gene sets distinguishing MCF7 from MCF10A against separate RNA-seq analyses of clinical luminal A (LumA) and normal samples from the TCGA-BRCA dataset. Among the 1031 cancer-related genes distinguishing LumA from normal samples, only 5.1% and 15.7% of these genes also distinguished MCF7 from MCF10A in 2D and 3D cultures respectively, suggesting that different genes drive cancer-related differences in cell lines compared to clinical BC. Unlike LumA tumours which showed increased nuclear division-related gene expression compared to normal tissue, nuclear division-related gene expression in MCF7 was similar to MCF10A. Moreover, although LumA tumours had similar cell adhesion-related gene expression compared to normal tissues, MCF7 showed reduced cell adhesion-related gene expression compared to MCF10A. These findings suggest that MCF7 and MCF10A cell lines were limited in their ability to model cancer-related processes in clinical LumA tumours.
The impact of driving pressure on postoperative pulmonary complication in patients with different respiratory spirometry
Authors: Oh Eun Jung , Kim Bo-Guen , Park Sukhee , Han Sangbin , Shin Beomsu , Lee Hyun , Shin Sun Hye , Kim Jeayoun , Choi Dancheong , Choi Eun Ah , Park Hye Yun 
Published: December 2022

AbstractRisk factors for postoperative pulmonary complication (PPC) have not been determined according to preoperative respiratory spirometry. Thus, we aimed to find contributors for PPC in patients with restrictive or normal spirometric pattern. We analyzed 654 patients (379 with normal and 275 with restrictive spirometric pattern). PPCs comprised respiratory failure, pleural effusion, atelectasis, respiratory infection, and bronchospasm. We analyzed the association between perioperative factors and PPC using binary logistic regression. In particular, we conducted subgroup analysis on the patients stratified according to preoperative spirometry. Of 654 patients, 27/379 patients (7.1%) with normal spirometric pattern and 33/275 patients (12.0%) with restrictive spirometric pattern developed PPCs. Multivariable analysis demonstrated that high driving pressure was the only intraoperative modifiable factor increasing PPC risk (OR = 1.13 [1.02–1.25], p = 0.025). In the subgroup of patients with restrictive spirometric pattern, intraoperative driving pressure was significantly associated with PPC (OR = 1.21 [1.05–1.39], p = 0.009), whereas driving pressure was not associated with PPC in patients with normal spirometric pattern (OR = 1.04 [0.89–1.21], p = 0.639). In patients with restrictive spirometric pattern, greater intraoperative driving pressure is significantly associated with increased PPC risk. In contrast, intraoperative driving pressure is not associated with PPC in patients with normal spirometric pattern.
NGS-based targeted gene mutational profiles in Korean patients with pancreatic cancer
Authors: Jung Kwangrok , Lee Sejoon , Na Hee Young , Kim Ji-Won , Lee Jong-Chan , Hwang Jin-Hyeok , Kim Jin Won , Kim Jaihwan 
Published: December 2022

AbstractAccording to molecular profiling studies, a considerable number of patients with pancreatic cancer harbor potentially actionable mutations. However, there are limited relevant data from the Korean population. We assessed the molecular profiles of patients with pancreatic cancer in Korea. This study collected molecular profiling data from patients with pancreatic cancer who visited Seoul National University Bundang Hospital between March 2018 and August 2020. Formalin-fixed, paraffin-embedded tumor specimens were sequenced using a targeted next-generation sequencing (NGS) platform. Cancer-associated mutations were analyzed, and potentially actionable mutations were identified. Potentially actionable mutations were classified into “highly actionable” and “modifies options” based on the Know Your Tumor registry study. In total, 87 patients with NGS tumor panel data were identified. Sixty-one patients (70.1%) had metastatic disease at the time of tissue acquisition. Tissues were obtained from the primary tumors and metastatic sites in 41 (47.1%) and 46 (52.9%) patients, respectively. At least one pathogenic mutation was reported in 86 patients (98.9%). The frequencies of four common mutations in our cohort were similar to those in The Cancer Genome Atlas data. Potentially actionable mutations were identified in 27 patients (31.0%). Of these, mutations categorized as highly actionable and modifies options were identified in 12 (13.8%) and 18 patients (20.7%), respectively. The most frequent highly actionable mutations were located in DNA damage response genes, such as BRCA1, BRCA2, or ATM (n = 6, 6.9%). Two patients with germline BRCA1 mutations received maintenance poly(adenosine diphosphate-ribose) polymerase inhibitor therapy. One patient has been receiving maintenance treatment for 18 months while remaining in radiologically complete remission. Mutational profiles using targeted NGS in Korean patients with pancreatic cancer were similar to those in Western patients. The present study supports the clinical potential and possible expanded clinical use of genetic profiling.