bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health-related quality of life of patients with resistant/intolerant chronic phase chronic myeloid leukemia treated with asciminib or bosutinib in the phase 3 ASCEMBL trial
Authors: Réa Delphine , Boquimpani Carla , Mauro Michael J. , Minami Yosuke , Allepuz Alex , Maheshwari Vikalp Kumar , D’Alessio Denise , Wu Ying , Lawrance Rachael , Narbutas Sarunas , Sharf Giora , Hochhaus Andreas 
Published: April 2023

AbstractIn ASCEMBL, an open-label, randomized Phase 3 study, asciminib demonstrated superior efficacy and better safety profile compared with bosutinib in patients with chronic myeloid leukemia in chronic phase (CML-CP) previously treated with ≥2 tyrosine kinase inhibitors. Health-related quality of life (HRQOL) reported by patients is key to understanding the benefit and impact of treatment on patients’ lives, and is becoming increasingly important as the life expectancy of CML-CP patients increases and patients require long-term treatment. In ASCEMBL, patients completed questionnaires to assess CML symptoms and interference with daily life (M.D. Anderson Symptom Inventory – CML [MDASI-CML]), general HRQOL (five-level EQ-5D [EQ-5D-5L], Patient Global Impression of Change – CML [PGIC-CML]), and impact of CML on working life and activity (Work Productivity and Activity Impairment questionnaire – CML [WPAI-CML]). Patients’ CML symptoms and HRQOL remained stable during 48 weeks of treatment with asciminib, with a general trend for decreased CML symptom severity, particularly for fatigue, and improvement in HRQOL. A clinically meaningful increase in diarrhea severity was observed in patients treated with bosutinib compared to asciminib. These data provide better understanding of the patient perspective and treatment impact on HRQOL in a later-line setting, where little information has been published to date.
Lycium barbarum glycopeptide targets PER2 to inhibit lipogenesis in glioblastoma by downregulating SREBP1c
Authors: Yao Jian , Hui Jian-wen , Chen Yan-jun , Luo Dong-yang , Yan Jiang-shu , Zhang Yi-fan , Lan Yuan-xiang , Yan Xiu-rui , Wang Zhi-hua , Fan Heng , Xia He-chun 
Published: April 2023

AbstractLycium barbarum polysaccharide (LBP) is a substance with various biological activities extracted from Lycium barbarum. LbGPs are peptidoglycans with a short peptide backbone and a complex, branched glycan moiety, which is further extracted and isolated from LBPs. Previous studies have shown that LbGP can inhibit cancer cell growth, but its specific mechanism is not completely clear. In this study, we found that LbGP could inhibit the proliferation of glioma cells and promote the expression of period 2 (PER2) through the PKA-CREB pathway. In addition, LbGP could inhibit the de novo synthesis of lipids by downregulating SREBP1c and its target genes, which depended on the expression of PER2. Moreover, PER2 negatively regulated the expression of SREBP1c via suppressing PI3K/AKT/mTOR pathway. In summary, LbGP may upregulate the expression of PER2 to reduce the expression of SREBP1c, inhibit lipid synthesis in glioblastoma, and inhibit glioblastoma cell proliferation. This study provides an alternative drug for the treatment of glioma and elucidates its potential mechanism.
Aflibercept monotherapy versus aflibercept with targeted retinal laser to peripheral retinal ischemia for diabetic macular oedema (LADAMO)
Authors: Cornish E. E. , Wickremasinghe S. , Mehta H. , Lim L. , Sandhu S. S. , Nguyen V. , Gillies M. C. , Fraser-Bell S. 
Published: April 2023

Abstract
Objective
We tested the hypothesis that targeted retinal laser photocoagulation (TPRP) to peripheral retinal ischaemia reduces the overall burden of aflibercept injections when treating diabetic macular oedema (DMO) over a 24-month period.

Methods
Prospective, double-masked, multicentre, randomised controlled trial in Australia comparing aflibercept monotherapy, following a treat-and-extend protocol, or combination therapy of aflibercept and TPRP for DMO. The aflibercept monotherapy group received placebo laser. The primary outcome measure was the mean number of intravitreal aflibercept injections for each group at 24 months. Secondary outcome included: mean change in central macular thickness (CMT) and vision at trial completion, the proportion of eyes whose DMO resolved and the mean injection treatment interval. Ocular and systemic adverse events were recorded.

Results
We enrolled 48 eyes of 47 patients; 27 eyes were randomised to combination therapy (aflibercept and TPRP) and 21 to aflibercept monotherapy. Thirty-two eyes (67%) completed the 2-year study. The number of intravitreal treatments given were similar for combination therapy (10.5 (SD 5.8) and monotherapy (11.8 (SD5.6)) (P = 0.44). The mean visual improvement (+4.0 (−1.8, 9.8) and +7.8 (2.6, 12.9) letters, P = 0.32), mean decrease in CMT (−154 (−222,−87) µm and −152 (−218,−86) µm, P = 0.96), proportion of eyes with CMT < 300 µm (48% and 67%; P = 0.50) and safety outcomes were similar in both the combination and monotherapy treatment groups (respectively).

Conclusions
Laser to areas of ischaemic peripheral retina does not reduce the burden of intravitreal aflibercept injections when treating diabetic macular oedema.
Prognostic significance of HER2-low status in HR-positive/HER2-negative advanced breast cancer treated with CDK4/6 inhibitors
Authors: Zattarin Emma , Presti Daniele , Mariani Luigi , Sposetti Caterina , Leporati Rita , Menichetti Alice , Corti Chiara , Benvenuti Chiara , Fucà Giovanni , Lobefaro Riccardo , Ligorio Francesca , Provenzano Leonardo , Vingiani Andrea , Del Vecchio Marta , Griguolo Gaia , Sirico Marianna , Bernocchi Ottavia , Marra Antonio , Zagami Paola , Agostinetto Elisa , Jacobs Flavia , Di Mauro Pierluigi , Esposito Andrea , Giorgi Carlo Alberto , Lalli Luca , Boldrini Laura , Giacchetti Pier Paolo Berton , Schianca Ambra Carnevale , Guarneri Valentina , Pedersini Rebecca , Losurdo Agnese , Zambelli Alberto , Generali Daniele , Criscitiello Carmen , Curigliano Giuseppe , Pruneri Giancarlo , de Braud Filippo , Dieci Maria Vittoria , Vernieri Claudio 
Published: April 2023

AbstractWhether Human Epidermal growth factor Receptor 2 (HER2)-low status has prognostic significance in HR + /HER2- advanced Breast Cancer (aBC) patients treated with first-line Endocrine Therapy plus CDK 4/6 inhibitors remains unclear. In 428 patients evaluated, HER2-low status was independently associated with significantly worse PFS and OS when compared with HER2-0 status. Based on our findings, HER2-low status could become a new prognostic biomarker in this clinical setting.
The effect of deep brain stimulation in Parkinson’s disease reflected in EEG microstates
Authors: Lamoš Martin , Bočková Martina , Goldemundová Sabina , Baláž Marek , Chrastina Jan , Rektor Ivan 
Published: April 2023

AbstractMechanisms of deep brain stimulation (DBS) on cortical networks were explored mainly by fMRI. Advanced analysis of high-density EEG is a source of additional information and may provide clinically useful biomarkers. The presented study evaluates EEG microstates in Parkinson’s disease and the effect of DBS of the subthalamic nucleus (STN). The association between revealed spatiotemporal dynamics of brain networks and changes in oscillatory activity and clinical examination were assessed. Thirty-seven patients with Parkinson’s disease treated by STN-DBS underwent two sessions (OFF and ON stimulation conditions) of resting-state EEG. EEG microstates were analyzed in patient recordings and in a matched healthy control dataset. Microstate parameters were then compared across groups and were correlated with clinical and neuropsychological scores. Of the five revealed microstates, two differed between Parkinson’s disease patients and healthy controls. Another microstate differed between ON and OFF stimulation conditions in the patient group and restored parameters in the ON stimulation state toward to healthy values. The mean beta power of that microstate was the highest in patients during the OFF stimulation condition and the lowest in healthy controls; sources were localized mainly in the supplementary motor area. Changes in microstate parameters correlated with UPDRS and neuropsychological scores. Disease specific alterations in the spatiotemporal dynamics of large-scale brain networks can be described by EEG microstates. The approach can reveal changes reflecting the effect of DBS on PD motor symptoms as well as changes probably related to non-motor symptoms not influenced by DBS.
Genetically encoded barcodes for correlative volume electron microscopy
Authors: Sigmund Felix , Berezin Oleksandr , Beliakova Sofia , Magerl Bernhard , Drawitsch Martin , Piovesan Alberto , Gonçalves Filipa , Bodea Silviu-Vasile , Winkler Stefanie , Bousraou Zoe , Grosshauser Martin , Samara Eleni , Pujol-Martí Jesús , Schädler Sebastian , So Chun , Irsen Stephan , Walch Axel , Kofler Florian , Piraud Marie , Kornfeld Joergen , Briggman Kevin , Westmeyer Gil Gregor 
Published: April 2023

AbstractWhile genetically encoded reporters are common for fluorescence microscopy, equivalent multiplexable gene reporters for electron microscopy (EM) are still scarce. Here, by installing a variable number of fixation-stable metal-interacting moieties in the lumen of encapsulin nanocompartments of different sizes, we developed a suite of spherically symmetric and concentric barcodes (EMcapsulins) that are readable by standard EM techniques. Six classes of EMcapsulins could be automatically segmented and differentiated. The coding capacity was further increased by arranging several EMcapsulins into distinct patterns via a set of rigid spacers of variable length. Fluorescent EMcapsulins were expressed to monitor subcellular structures in light and EM. Neuronal expression in Drosophila and mouse brains enabled the automatic identification of genetically defined cells in EM. EMcapsulins are compatible with transmission EM, scanning EM and focused ion beam scanning EM. The expandable palette of genetically controlled EM-readable barcodes can augment anatomical EM images with multiplexed gene expression maps.
Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease
Authors: Duperron Marie-Gabrielle , Knol Maria J. , Le Grand Quentin , Evans Tavia E. , Mishra Aniket , Tsuchida Ami , Roshchupkin Gennady , Konuma Takahiro , Trégouët David-Alexandre , Romero Jose Rafael , Frenzel Stefan , Luciano Michelle , Hofer Edith , Bourgey Mathieu , Dueker Nicole D. , Delgado Pilar , Hilal Saima , Tankard Rick M. , Dubost Florian , Shin Jean , Saba Yasaman , Armstrong Nicola J. , Bordes Constance , Bastin Mark E. , Beiser Alexa , Brodaty Henry , Bülow Robin , Carrera Caty , Chen Christopher , Cheng Ching-Yu , Deary Ian J. , Gampawar Piyush G. , Himali Jayandra J. , Jiang Jiyang , Kawaguchi Takahisa , Li Shuo , Macalli Melissa , Marquis Pascale , Morris Zoe , Muñoz Maniega Susana , Miyamoto Susumu , Okawa Masakazu , Paradise Matthew , Parva Pedram , Rundek Tatjana , Sargurupremraj Muralidharan , Schilling Sabrina , Setoh Kazuya , Soukarieh Omar , Tabara Yasuharu , Teumer Alexander , Thalamuthu Anbupalam , Trollor Julian N. , Valdés Hernández Maria C. , Vernooij Meike W. , Völker Uwe , Wittfeld Katharina , Wong Tien Yin , Wright Margaret J. , Zhang Junyi , Zhao Wanting , Zhu Yi-Cheng , Schmidt Helena , Sachdev Perminder S. , Wen Wei , Yoshida Kazumichi , Joutel Anne , Satizabal Claudia L. , Sacco Ralph L. , Bourque Guillaume ,   the CHARGE consortium, Le Grand Quentin , Lathrop Mark , Paus Tomas , Fernandez-Cadenas Israel , Yang Qiong , Mazoyer Bernard , Boutinaud Philippe , Okada Yukinori , Grabe Hans J. , Mather Karen A. , Schmidt Reinhold , Joliot Marc , Ikram M. Arfan , Matsuda Fumihiko , Tzourio Christophe , Wardlaw Joanna M. , Seshadri Sudha , Adams Hieab H. H. , Debette Stéphanie 
Published: April 2023

AbstractPerivascular space (PVS) burden is an emerging, poorly understood, magnetic resonance imaging marker of cerebral small vessel disease, a leading cause of stroke and dementia. Genome-wide association studies in up to 40,095 participants (18 population-based cohorts, 66.3 ± 8.6 yr, 96.9% European ancestry) revealed 24 genome-wide significant PVS risk loci, mainly in the white matter. These were associated with white matter PVS already in young adults (N = 1,748; 22.1 ± 2.3 yr) and were enriched in early-onset leukodystrophy genes and genes expressed in fetal brain endothelial cells, suggesting early-life mechanisms. In total, 53% of white matter PVS risk loci showed nominally significant associations (27% after multiple-testing correction) in a Japanese population-based cohort (N = 2,862; 68.3 ± 5.3 yr). Mendelian randomization supported causal associations of high blood pressure with basal ganglia and hippocampal PVS, and of basal ganglia PVS and hippocampal PVS with stroke, accounting for blood pressure. Our findings provide insight into the biology of PVS and cerebral small vessel disease, pointing to pathways involving extracellular matrix, membrane transport and developmental processes, and the potential for genetically informed prioritization of drug targets.
CarbonMonitor-Power near-real-time monitoring of global power generation on hourly to daily scales
Authors: Zhu Biqing , Deng Zhu , Song Xuanren , Zhao Wenli , Huo Da , Sun Taochun , Ke Piyu , Cui Duo , Lu Chenxi , Zhong Haiwang , Hong Chaopeng , Qiu Jian , Davis Steven J. , Gentine Pierre , Ciais Philippe , Liu Zhu 
Published: April 2023

AbstractWe constructed a frequently updated, near-real-time global power generation dataset: CarbonMonitor-Power since January, 2016 at national levels with near-global coverage and hourly-to-daily time resolution. The data presented here are collected from 37 countries across all continents for eight source groups, including three types of fossil sources (coal, gas, and oil), nuclear energy and four groups of renewable energy sources (solar energy, wind energy, hydro energy and other renewables including biomass, geothermal, etc.). The global near-real-time power dataset shows the dynamics of the global power system, including its hourly, daily, weekly and seasonal patterns as influenced by daily periodical activities, weekends, seasonal cycles, regular and irregular events (i.e., holidays) and extreme events (i.e., the COVID-19 pandemic). The CarbonMonitor-Power dataset reveals that the COVID-19 pandemic caused strong disruptions in some countries (i.e., China and India), leading to a temporary or long-lasting shift to low carbon intensity, while it had only little impact in some other countries (i.e., Australia). This dataset offers a large range of opportunities for power-related scientific research and policy-making.
Building a second-opinion tool for classical polygraph
Authors: Asonov Dmitri , Krylov Maksim , Omelyusik Vladimir , Ryabikina Anastasiya , Litvinov Evgeny , Mitrofanov Maksim , Mikhailov Maksim , Efimov Albert 
Published: April 2023

AbstractClassical polygraph screenings are routinely used by critical businesses such as banking, law enforcement agencies, and federal governments. A major concern of scientific communities is that screenings are prone to errors. However, screening errors are not only due to the method, but also due to human (polygraph examiner) error. Here we show application of machine learning (ML) to detect examiner errors. From an ML perspective, we trained an error detection model in the absence of labeled errors. From a practical perspective, we devised and tested successfully a second-opinion tool to find human errors in examiners’ conclusions, thus reducing subjectivity of polygraph screenings. We report novel features that uplift the model’s accuracy, and experimental results on whether people lie differently on different topics. We anticipate our results to be a step towards rethinking classical polygraph practices.
Source connectivity patterns in the default mode network differ between elderly golf-novices and non-golfers
Authors: Gowik J. K. , Goelz C. , Vieluf S. , van den Bongard F. , Reinsberger C. 
Published: April 2023

AbstractLearning to play golf has high demands on attention and therefore may counteract age-related changes of functional brain networks. This cross-sectional study compared source connectivity in the Default Mode Network (DMN) between elderly golf novices and non-golfers. Four-minute resting-state electroencephalography (128 channels) from 22 elderly people (mean age 67 ± 4.3 years, 55% females) were recorded after completing a 22-week golf learning program or after having continued with normal life. Source connectivity was assessed after co-registration of EEG data with native MRI within pre-defined portions of the DMN in the beta band (14–25 Hz). Non-golfers had significantly higher source connectivity values in the anterior DMN compared to non-golfers. Exploratory correlation analyses did not indicate an association to cognitive performance in either group. Inverse correlations between a marker of external attention with source connectivity of the anterior DMN may suggest a trend in the golf group only, but have to be replicated in future studies. Clinical relevance of these findings remains to be elucidated, but the observed difference in the anterior DMN may provide a starting point to further investigate if and how learning golf may have an impact on physiological age-related cognitive changes.
Outbreak report of polymyxin-carbapenem-resistant Klebsiella pneumoniae causing untreatable infections evidenced by synergy tests and bacterial genomes
Authors: Gomes Marisa Zenaide Ribeiro , de Lima Elisangela Martins , Martins Aires Caio Augusto , Pereira Polyana Silva , Yim Juwon , Silva Fernando Henrique , Rodrigues Caio Augusto Santos , Oliveira Thamirys Rachel Tavares e , da Silva Priscila Pinho , Eller Cristiane Monteiro , de Souza Claudio Marcos Rocha , Rybak Michael J. , Albano Rodolpho Mattos , de Miranda Antonio Basílio , Machado Edson , Catanho Marcos ,   Nucleus of Hospital Research (NPH) study collaborators, Dutra Vitoria Pinson Ruggi , de Mello Luciana Sênos , Tonhá João Pedro Silva , Castro Murillo Marçal , da Silva Machado Amanda Aparecida , da Silva Maxuel Cassiano , Mathuiy Yann Rodrigues , Tozo Thaisa Medeiros 
Published: April 2023

AbstractPolymyxin-carbapenem-resistant Klebsiella pneumoniae (PCR-Kp) with pan (PDR)- or extensively drug-resistant phenotypes has been increasingly described worldwide. Here, we report a PCR-Kp outbreak causing untreatable infections descriptively correlated with bacterial genomes. Hospital-wide surveillance of PCR-Kp was initiated in December-2014, after the first detection of a K. pneumoniae phenotype initially classified as PDR, recovered from close spatiotemporal cases of a sentinel hospital in Rio de Janeiro. Whole-genome sequencing of clinical PCR-Kp was performed to investigate similarities and dissimilarities in phylogeny, resistance and virulence genes, plasmid structures and genetic polymorphisms. A target phenotypic profile was detected in 10% (12/117) of the tested K. pneumoniae complex bacteria recovered from patients (8.5%, 8/94) who had epidemiological links and were involved in intractable infections and death, with combined therapeutic drugs failing to meet synergy. Two resistant bacterial clades belong to the same transmission cluster (ST437) or might have different sources (ST11). The severity of infection was likely related to patients’ comorbidities, lack of antimicrobial therapy and predicted bacterial genes related to high resistance, survival, and proliferation. This report contributes to the actual knowledge about the natural history of PCR-Kp infection, while reporting from a time when there were no licensed drugs in the world to treat some of these infections. More studies comparing clinical findings with bacterial genetic markers during clonal spread are needed.
Imbalanced expression of cation-chloride cotransporters as a potential therapeutic target in an Angelman syndrome mouse model
Authors: Egawa Kiyoshi , Watanabe Miho , Shiraishi Hideaki , Sato Daisuke , Takahashi Yukitoshi , Nishio Saori , Fukuda Atsuo 
Published: April 2023

AbstractAngelman syndrome is a neurodevelopmental disorder caused by loss of function of the maternally expressed UBE3A gene. Treatments for the main manifestations, including cognitive dysfunction or epilepsy, are still under development. Recently, the Cl− importer Na+-K+-Cl− cotransporter 1 (NKCC1) and the Cl− exporter K+-Cl− cotransporter 2 (KCC2) have garnered attention as therapeutic targets for many neurological disorders. Dysregulation of neuronal intracellular Cl− concentration ([Cl−]i) is generally regarded as one of the mechanisms underlying neuronal dysfunction caused by imbalanced expression of these cation-chloride cotransporters (CCCs). Here, we analyzed the regulation of [Cl−]i and the effects of bumetanide, an NKCC1 inhibitor, in Angelman syndrome models (Ube3am−/p+ mice). We observed increased NKCC1 expression and decreased KCC2 expression in the hippocampi of Ube3am−/p+ mice. The average [Cl−]i of CA1 pyramidal neurons was not significantly different but demonstrated greater variance in Ube3am−/p+ mice. Tonic GABAA receptor-mediated Cl− conductance was reduced, which may have contributed to maintaining the normal average [Cl−]i. Bumetanide administration restores cognitive dysfunction in Ube3am−/p+ mice. Seizure susceptibility was also reduced regardless of the genotype. These results suggest that an imbalanced expression of CCCs is involved in the pathophysiological mechanism of Ube3am−/p+ mice, although the average [Cl−]i is not altered. The blockage of NKCC1 may be a potential therapeutic strategy for patients with Angelman syndrome.
Identification and characterization of miRNAs in spleens of sheep subjected to repetitive vaccination
Authors: Varela-Martínez Endika , Bilbao-Arribas Martin , Abendaño Naiara , Asín Javier , Pérez Marta , Luján Lluís , Jugo Begoña M. 
Published: April 2023

AbstractAccumulative evidence has shown that short non-coding RNAs such as miRNAs can regulate the innate and adaptive immune responses. Aluminium hydroxide is a commonly used adjuvant in human and veterinary vaccines. Despite its extended use, its mechanism of action is not fully understood and very few in vivo studies have been done to enhance understanding at the molecular level. In this work, we took advantage of a previous long-term experiment in which lambs were exposed to three different treatments by parallel subcutaneous inoculations with aluminium-containing commercial vaccines, an equivalent dose of aluminium or mock injections. Spleen samples were used for miRNA-seq. A total of 46 and 16 miRNAs were found differentially expressed when animals inoculated with commercial vaccines or the adjuvant alone were compared with control animals, respectively. Some miRNAs previously related to macrophage polarization were found dysregulated exclusively by the commercial vaccine treatment but not in the aluminium inoculated animals. The dysregulated miRNAs in vaccine group let-7b-5p, miR-29a-3p, miR-27a and miR-101-3p are candidates for further research, since they may play key roles in the immune response induced by aluminium adjuvants added to vaccines. Finally, protein–protein interaction network analysis points towards leucocyte transendothelial migration as a specific mechanism in animals receiving adjuvant only.