bluuebunny/crossref_metadata_2025_split huggingface dataset:
A primary hierarchically organized patient-derived model enables in depth interrogation of stemness driven by the coding and non-coding genome
Authors: Boutzen Héléna , Madani Tonekaboni Seyed Ali , Chan-Seng-Yue Michelle , Murison Alex , Takayama Naoya , Mbong Nathan , Wagenblast Elvin , Orouji Elias , Arruda Andrea , Mitchell Amanda , Notta Faiyaz , Minden Mark D. , Lupien Mathieu , Kaufmann Kerstin B. , Dick John E. 
Published: September 2022

AbstractMany cancers are organized as cellular hierarchies sustained by cancer stem cells (CSC), whose eradication is crucial for achieving long-term remission. Difficulties to isolate and undertake in vitro and in vivo experimental studies of rare CSC under conditions that preserve their original properties currently constitute a bottleneck for identifying molecular mechanisms involving coding and non-coding genomic regions that govern stemness. We focussed on acute myeloid leukemia (AML) as a paradigm of the CSC model and developed a patient-derived system termed OCI-AML22 that recapitulates the cellular hierarchy driven by leukemia stem cells (LSC). Through classical flow sorting and functional analyses, we established that a single phenotypic population is highly enriched for LSC. The LSC fraction can be easily isolated and serially expanded in culture or in xenografts while faithfully recapitulating functional, transcriptional and epigenetic features of primary LSCs. A novel non-coding regulatory element was identified with a new computational approach using functionally validated primary AML LSC fractions and its role in LSC stemness validated through efficient CRISPR editing using methods optimized for OCI-AML22 LSC. Collectively, OCI-AML22 constitutes a valuable resource to uncover mechanisms governing CSC driven malignancies.
Heparanase modulates the prognosis and development of BRAF V600E-mutant colorectal cancer by regulating AKT/p27Kip1/Cyclin E2 pathway
Authors: Liu Mengling , Xu Xiaojing , Peng Ke , Hou Pengcong , Yuan Yitao , Li Suyao , Sun Xun , Shi Zhongyi , Zhang Jiayu , Dong Yu , Liu Qing , Ai Luoyan , Liang Li , Gan Lu , Huang Qihong , Yu Yiyi , Liu Tianshu 
Published: September 2022

AbstractBRAF V600E-mutant colorectal cancer (CRC) is a rare subtype of colorectal cancer with poor prognosis. Compelling evidence indicates that the heparanase (HPSE) gene has multiple functions in cancer, however, its role in BRAF V600E-mutant CRC remains elusive. Differentially expressed genes between BRAF V600E-mutant and wild-type patients were explored by analyzing public data from The Cancer Genome Atlas and the Gene Expression Omnibus. Clinical samples of 172 patients with BRAF V600E-mutant CRC diagnosed at Zhongshan Hospital Fudan University were collected. Overall survival was analyzed using Kaplan–Meier curves and Cox regression models. Cell models and xenografts were utilized to investigate the effect of HPSE on tumor proliferation. HPSE was significantly highly expressed in the BRAF V600E-mutant group. High HPSE expression level was independently associated with inferior survival in the BRAF V600E-mutant cohort. HPSE knockdown impeded tumor proliferation of BRAF V600E-mutant CRC cells in vitro and in vivo. Mechanistically, HPSE silencing arrested cell cycle in G0/G1 phase by downregulating Cyclin E2 expression via the AKT/p27Kip1 pathway. These findings support a role for HPSE in promoting BRAF V600E-mutant CRC progression, which suggests it holds great promise as a prognostic biomarker and a potential therapeutic target for the aggressive CRC subtype.
Variational quantum state eigensolver
Authors: Cerezo M. , Sharma Kunal , Arrasmith Andrew , Coles Patrick J. 
Published: September 2022

AbstractExtracting eigenvalues and eigenvectors of exponentially large matrices will be an important application of near-term quantum computers. The variational quantum eigensolver (VQE) treats the case when the matrix is a Hamiltonian. Here, we address the case when the matrix is a density matrix ρ. We introduce the variational quantum state eigensolver (VQSE), which is analogous to VQE in that it variationally learns the largest eigenvalues of ρ as well as a gate sequence V that prepares the corresponding eigenvectors. VQSE exploits the connection between diagonalization and majorization to define a cost function $$C={{{\rm{Tr}}}}(\tilde{\rho }H)$$

C
=
Tr

(

ρ

̃

H

)

where H is a non-degenerate Hamiltonian. Due to Schur-concavity, C is minimized when $$\tilde{\rho }=V\rho {V}^{{\dagger} }$$

ρ

̃

=
V
ρ

V

†

is diagonal in the eigenbasis of H. VQSE only requires a single copy of ρ (only n qubits) per iteration of the VQSE algorithm, making it amenable for near-term implementation. We heuristically demonstrate two applications of VQSE: (1) Principal component analysis, and (2) Error mitigation.
Executable models of immune signaling pathways in HIV-associated atherosclerosis
Authors: Palshikar Mukta G. , Palli Rohith , Tyrell Alicia , Maggirwar Sanjay , Schifitto Giovanni , Singh Meera V. , Thakar Juilee 
Published: September 2022

AbstractAtherosclerosis (AS)-associated cardiovascular disease is an important cause of mortality in an aging population of people living with HIV (PLWH). This elevated risk has been attributed to viral infection, anti-retroviral therapy, chronic inflammation, and lifestyle factors. However, the rates at which PLWH develop AS vary even after controlling for length of infection, treatment duration, and for lifestyle factors. To investigate the molecular signaling underlying this variation, we sequenced 9368 peripheral blood mononuclear cells (PBMCs) from eight PLWH, four of whom have atherosclerosis (AS+). Additionally, a publicly available dataset of PBMCs from persons before and after HIV infection was used to investigate the effect of acute HIV infection. To characterize dysregulation of pathways rather than just measuring enrichment, we developed the single-cell Boolean Omics Network Invariant Time Analysis (scBONITA) algorithm. scBONITA infers executable dynamic pathway models and performs a perturbation analysis to identify high impact genes. These dynamic models are used for pathway analysis and to map sequenced cells to characteristic signaling states (attractor analysis). scBONITA revealed that lipid signaling regulates cell migration into the vascular endothelium in AS+ PLWH. Pathways implicated included AGE-RAGE and PI3K-AKT signaling in CD8+ T cells, and glucagon and cAMP signaling pathways in monocytes. Attractor analysis with scBONITA facilitated the pathway-based characterization of cellular states in CD8+ T cells and monocytes. In this manner, we identify critical cell-type specific molecular mechanisms underlying HIV-associated atherosclerosis using a novel computational method.
Evaluations of rationally designed rift valley fever vaccine candidate RVax-1 in mosquito and rodent models
Authors: Ikegami Tetsuro , Jurado-Cobena Eduardo , Alkan Cigdem , Smith Jennifer K. , Zhang Lihong , Kalveram Birte , Juelich Terry L. , Esterly Allen T. , Bhaskar Jahnavi R. , Thangamani Saravanan , Freiberg Alexander N. 
Published: September 2022

AbstractRift Valley fever (RVF) is a mosquito-borne zoonosis endemic to Africa and the Arabian Peninsula, which causes large outbreaks among humans and ruminants. Single dose vaccinations using live-attenuated RVF virus (RVFV) support effective prevention of viral spread in endemic countries. Due to the segmented nature of RVFV genomic RNA, segments of vaccine strain-derived genomic RNA could be incorporated into wild-type RVFV within co-infected mosquitoes or animals. Rationally designed vaccine candidate RVax-1 displays protective epitopes fully identical to the previously characterized MP-12 vaccine. Additionally, all genome segments of RVax-1 contribute to the attenuation phenotype, which prevents the formation of pathogenic reassortant strains. This study demonstrated that RVax-1 cannot replicate efficiently in orally fed Aedes aegypti mosquitoes, while retaining strong immunogenicity and protective efficacy in an inbred mouse model, which were indistinguishable from the MP-12 vaccine. These findings support further development of RVax-1 as the next generation MP-12-based vaccine for prevention of Rift Valley fever in humans and animals.
Exploiting interfacial polymerization to fabricate hyper-cross-linked nanofiltration membrane with a constituent linear aliphatic amine for freshwater production
Authors: Baig Umair , Waheed Abdul 
Published: September 2022

AbstractHumanity is facing a global challenge of dwindling water resources and the situation is intensifying due to growing population leading to excessive water pollution. Nanofiltration is an important membrane-based technology for the production of clean and potable water for domestic and industrial setups. Hyper-cross-linked polyamide thin film composite nanofiltration (HCPA-TFC-NF) membranes have been fabricated by using multifunctional amine 1 (possessing two primary -NH2 and two secondary -NH groups) and bifunctional terephthaloyl chloride 2 (TPC) through interfacial polymerization. The structure of the hyper-cross-linked polyamide network has been successfully confirmed by solid (CP-MAS) 13C NMR, XPS, AFM, FT-IR, elemental mapping, and EDX analysis. The membrane features such as surface morphology and hydrophilicity have been established by FE-SEM and water contact angle measurements. The FE-SEM analysis revealed the formation of uniform polyamide active layer on the surface of PS/PET support, and the pore structure of the membranes was tuned by studying the effect of curing temperature and curing time. The nanofiltration membranes efficiently rejected a series of divalent salts including MgCl2, CaCl2, Na2SO4, MgSO4, and NaCl using cross-flow filtration setup. Based on the cross-flow filtration performance, the best conditions for the membrane fabrication were found to be curing temperature of 80 °C with a curing time of 1 h. The highest salt rejection was observed in case of MgCl2 reaching to a value of 98.11% in case of HCPA-TFC-NF@M3 and it was found to be 97.45% in case of HCPA-TFC-NF@M2 while the rejection of MgCl2 was reduced to 94.59% in case HCPA-TFC-NF@M1. HCPA-TFC-NF@M2 showed NaCl rejection of 87.36%. The hydrofluoric acid treatment of HCPA-TFC-NF-M2 increased the water flux while keeping the rejection high. The HCPA-TFC-NF@M2 showed a rejection of >99% for EBT with a permeate flux of 75 LMH.
Spatiotemporally controlled generation of NTPs for single-molecule studies
Authors: Sabantsev Anton , Mao Guanzhong , Aguirre Rivera Javier , Panfilov Mikhail , Arseniev Anatolii , Ho Oanh , Khodorkovskiy Mikhail , Deindl Sebastian 
Published: September 2022

AbstractMany essential processes in the cell depend on proteins that use nucleoside triphosphates (NTPs). Methods that directly monitor the often-complex dynamics of these proteins at the single-molecule level have helped to uncover their mechanisms of action. However, the measurement throughput is typically limited for NTP-utilizing reactions, and the quantitative dissection of complex dynamics over multiple sequential turnovers remains challenging. Here we present a method for controlling NTP-driven reactions in single-molecule experiments via the local generation of NTPs (LAGOON) that markedly increases the measurement throughput and enables single-turnover observations. We demonstrate the effectiveness of LAGOON in single-molecule fluorescence and force spectroscopy assays by monitoring DNA unwinding, nucleosome sliding and RNA polymerase elongation. LAGOON can be readily integrated with many single-molecule techniques, and we anticipate that it will facilitate studies of a wide range of crucial NTP-driven processes.
Bacteria communities and water quality parameters in riverine water and sediments near wastewater discharges
Authors: de Santana Carolina Oliveira , Spealman Pieter , Azulai Daniella , Reid Mary , Dueker M. Elias , Perron Gabriel G. 
Published: September 2022

AbstractWastewater treatment plant (WWTP) discharges alter water quality and microbial communities by introducing human-associated bacteria in the environment and by altering microbial communities. To fully understand this impact, it is crucial to study whether WWTP discharges affect water and sediments microbial communities in comparable ways and whether such effects depend on specific environmental variables. Here, we present a dataset investigating the impact of a WWTP on water quality and bacterial communities by comparing samples collected directly from the WWTP outflow to surface waters and sediments at two sites above and two sites below it over a period of five months. When possible, we measured five physicochemical variables (e.g., temperature, turbidity, conductivity, dissolved oxygen, and salinity), four bioindicators (e.g., Escherichia coli, total coliforms, Enterococcus sp., and endotoxins), and two molecular indicators (e.g., intI1’s relative abundance, and 16S rRNA gene profiling). Preliminary results suggest that bioindicators correlate with environmental variables and that bacterial communities present in the water tables, sediments, and treated water differ greatly in composition and structure.
First-principles studies of defect behaviour in bismuth germanate
Authors: Akande Salawu Omotayo , Bouhali Othmane 
Published: September 2022

AbstractIntrinsic defects are known to greatly affect the structural and electronic properties of scintillators thereby impacting performance when these materials are in operation. In order to overcome this effect, an understanding of the defect process is required for the design of more stable materials. Here we employed density functional theory calculations and the PBE0 hybrid functional to study the structural, electronic,defect process and optical properties of $$\hbox {Bi}_4\hbox {Ge}_3\hbox {O}_{{12}}$$

Bi
4

Ge
3

O
12

(BGO), a well know material used as scintillator. We examined possible intrinsic defects and calculated their formation energy and their impact on the properties that affect the scintillation process. Furthermore, we investigated the effect and role of rare earth element (REE = Nd, Pr, Ce and Tm) doping on the properties of the BGO system. While the PBE functional underestimated the band gap, the PBE0 was found to adequately describe the electronic properties of the system. Out of all the defects types considered, it was found that $$\hbox {Bi}_{{Ge}}$$

Bi

Ge

antisite is the most favourable defect. Analysis of the effect of this defect on the electronic properties of BGO revealed an opening of ingap states within the valence band. This observation suggests that the $$\hbox {Bi}^{3+}$$

Bi

3
+

could be a charge trapping defect in BGO. We found that the calculated dopant substitution formation energy increases with increase in the size of the dopant and it turns out that the formation of O vacancy is easier in doped systems irrespective of the size of the dopant. We analyzed the optical spectra and noted variations in different regions of the photon energy spectra.
Reciprocating intestinal flows enhance glucose uptake in C. elegans
Authors: Suzuki Yuki , Kikuchi Kenji , Numayama-Tsuruta Keiko , Ishikawa Takuji 
Published: September 2022

AbstractDespite its physiological and pathological importance, the mechanical relationship between glucose uptake in the intestine and intestinal flows is unclear. In the intestine of the nematode Caenorhabditis elegans, the defecation motor program (DMP) causes reciprocating intestinal flows. Although the DMP is frequently activated in the intestines, its physiological function is unknown. We evaluated the mechanical signature of enhanced glucose uptake by the DMP in worms. Glucose uptake tended to increase with increasing flow velocity during the DMP because of mechanical mixing and transport. However, the increase in input energy required for the DMP was low compared with the calorie intake. The findings suggest that animals with gastrointestinal motility exploit the reciprocating intestinal flows caused by peristalsis to promote nutrient absorption by intestinal cells.
Compounds from human odor induce attraction and landing in female yellow fever mosquitoes (Aedes aegypti)
Authors: Bello Jan E. , Cardé Ring T. 
Published: September 2022

AbstractThe femaleAedes aegypti mosquito is a vector of many human diseases such as yellow fever, dengue, and Zika. Transmission of these viruses occurs when an infected female mosquito locates a suitable human host, alights, and blood feeds.Aedes aegypti use human-emitted odors, as well as heat and visual cues, for host location. However, none of the previously identified human-produced compounds induce significant orientation and landing on a human host. Here we show that female yellow fever mosquitoes orient to and land on a mixture of compounds identified from human skin rubbings. Using odor collection, extraction, a two-choice, bioassay-guided fractionation, and chemical analysis, we identified mixtures of 2-ketoglutaric acid and L-lactic acid as landing attractants for female Ae. aegypti.The mixture of pyruvic acid and L-lactic acid were also found to be weakly attractive. Using ratio-response assays, we found that the attraction and alighting behaviors of the mosquitoes were directly related to the ratio of these compounds presented on the surface of the glass assay beads, suggesting that these compounds could mediate landing on a human host even at sub-nanogram dosages. The newly identified compounds fill a gap in our knowledge of odor-mediated attraction ofAe. aegyptiand may lead to the development of new attractant-based mosquito control tactics.
Colorectal cancer incidence and survival inequalities among labour immigrants in Belgium during 2004–2013
Authors: Vanthomme Katrien , Rosskamp Michael , De Schutter Harlinde , Vandenheede Hadewijch 
Published: September 2022

AbstractColorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality. We aim to map out differences in CRC incidence and survival between first-generation traditional labour immigrants of Italian, Turkish and Moroccan descent and native Belgians; and assess the contribution of socioeconomic position (SEP) to these differences. Individually-linked data of the 2001 Belgian Census, the Crossroads Bank for Social Security and the Belgian Cancer Registry are used. Age-standardized incidence rates and incidence rate ratios are calculated by country of origin, with and without adjusting for SEP. For CRC patients, 5-year relative survival rates and the relative excess risk for dying within five years after diagnosis are calculated by migrant origin. Lower CRC incidence was observed among immigrants compared to native Belgians, in particular among non-Western immigrants, which could not be explained by SEP. Survival inequalities were less clear, yet, after adjusting for age and stage at diagnosis and educational attainment, we observed a survival advantage among Turkish and Italian immigrant men. Health gains can be made for the native population by adapting lifestyle. The later stage at diagnosis for immigrants is of concern. Barriers regarding screening as perceived by the vulnerable groups should be identified.
Expression of an extremophilic xylanase in Nicotiana benthamiana and its use for the production of prebiotic xylooligosaccharides
Authors: Talens-Perales David , Nicolau-Sanus María , Polaina Julio , Daròs José-Antonio 
Published: September 2022

AbstractA gene construct encoding a xylanase, which is active in extreme conditions of temperature and alkaline pH (90 °C, pH 10.5), has been transitorily expressed with high efficiency in Nicotiana benthamiana using a viral vector. The enzyme, targeted to the apoplast, accumulates in large amounts in plant tissues in as little as 7 days after inoculation, without detrimental effects on plant growth. The properties of the protein produced by the plant, in terms of resistance to temperature, pH, and enzymatic activity, are equivalent to those observed when Escherichia coli is used as a host. Purification of the plant-produced recombinant xylanase is facilitated by exporting the protein to the apoplastic space. The production of this xylanase by N. benthamiana, which avoids the hindrances derived from the use of E. coli, namely, intracellular production requiring subsequent purification, represents an important step for potential applications in the food industry in which more sustainable and green products are continuously demanded. As an example, the use of the enzyme producing prebiotic xylooligosdaccharides from xylan is here reported.
Cocaine regulation of Nr4a1 chromatin bivalency and mRNA in male and female mice
Authors: Fischer Delaney K. , Krick Keegan S. , Han Chloe , Woolf Morgan T. , Heller Elizabeth A. 
Published: September 2022

AbstractCocaine epigenetically regulates gene expression via changes in histone post-translational modifications (HPTMs). We previously found that the immediate early gene Nr4a1 is epigenetically activated by cocaine in mouse brain reward regions. However, few studies have examined multiple HPTMs at a single gene. Bivalent gene promoters are simultaneously enriched in both activating (H3K4me3 (K4)) and repressive (H3K27me3 (K27)) HPTMs. As such, bivalent genes are lowly expressed but poised for activity-dependent gene regulation. In this study, we identified K4&K27 bivalency at Nr4a1 following investigator-administered cocaine in male and female mice. We applied sequential chromatin immunoprecipitation and qPCR to define Nr4a1 bivalency and expression in striatum (STR), prefrontal cortex (PFC), and hippocampus (HPC). We used Pearson’s correlation to quantify relationships within each brain region across treatment conditions for each sex. In female STR, cocaine increased Nr4a1 mRNA while maintaining Nr4a1 K4&K27 bivalency. In male STR, cocaine enriched repressive H3K27me3 and K4&K27 bivalency at Nr4a1 and maintained Nr4a1 mRNA. Furthermore, cocaine epigenetically regulated a putative NR4A1 target, Cartpt, in male PFC. This study defined the epigenetic regulation of Nr4a1 in reward brain regions in male and female mice following cocaine, and, thus, shed light on the biological relevance of sex to cocaine use disorder.
Prevalence and predictors of diabetes-related distress in adults with type 1 diabetes
Authors: Grulovic Natasa , Rojnic Kuzman Martina , Baretic Maja 
Published: September 2022

AbstractType 1 diabetes (T1DM) is a chronic disease requiring lifelong insulin therapy and rigorous self-management. As it negatively impacts the affected individuals’ quality of life, it may eventually lead to diabetes-related distress. This study evaluated the prevalence and identified the predictors of diabetes-related distress in a representative sample of adults with T1DM treated at secondary and tertiary levels in Croatia. A multicenter, cross-sectional study was conducted in adults with T1DM in Croatia (N = 100). Data were collected between January 2018 and December 2018 from medical records and interviews during a single clinical visit, when participants completed a 20-item Problem Area in Diabetes (PAID) Questionnaire. The proportion of participants with a total PAID score ≥ 40 indicating high diabetes-related distress was calculated, and binary logistic regression was run to determine predictors. High diabetes-related distress was found in 36% of participants, with a mean PAID total score of 31.9 (21.1). The predictors of diabetes-related distress were higher HbA1c level (OR = 1.491, p = 0.037, CI = 1.025–2.169) and the presence of microvascular complications (OR = 4.611, p = 0.005; 95%CI 1.546–13.754). Worrying about the future and chronic complications and feeling guilty when off-track with diabetes management were identified as items that contribute the most to distress. Diabetes-related distress is a frequent condition in adults with T1DM in Croatia. Special attention should be given to patients with suboptimal glycemic control and microvascular complications. Given the high prevalence and impact of psychosocial problems in diabetes, psychological care should be integrated into routine care for adults with type 1 diabetes.