bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association between household biomass fuel use and leukocyte telomere length among toddlers in Bhaktapur, Nepal
Authors: Chandyo Ram K. , Schwinger Catherine , Kvestad Ingrid , Ulak Manjeswori , Ranjitkar Suman , Shrestha Merina , Nguyen Linda Vy , Corona-Perez Diana , DeVivo Immaculata , Shrestha Laxman , Strand Tor A. 
Published: September 2022

Abstract
Background
Biomass fuels are still in use for cooking by many households in resource poor countries such as Nepal and is a major source of household air pollution (HAP). Chronic exposure to HAP has been shown to be associated with shorter telomere length in adults.

Objectives
To measure the association between exposure related to household biomass fuel in infancy and leukocyte telomere length (LTL) at 18–23 months of age among 497 children from Bhaktapur, Nepal.

Methods
In a prospective cohort study design, we have collected information on household cooking fuel use and several clinical, anthropometric, demographic, and socioeconomic variables. We estimated the association between biomass fuel use and the relative LTL in multiple linear regression models.

Results
Most of the families (78%) reported liquified petroleum gas (LPG) as the primary cooking fuel, and 18.7% used biomass. The mean relative (SD) LTL was 1.03 (0.19). Children living in households using biomass fuel had on average 0.09 (95% CI: 0.05 to 0.13) units shorter LTL than children in households with no biomass fuel use. The observed association was unaltered after adjusting for relevant confounders. The association between LTL and biomass use was strongest among children from households with ≤2 rooms and without separate kitchen.

Significance
Exposure to biomass fuel use in early life might have consequences for longevity, and risk of chronic illnesses reflected in shortening of the telomeres. Our findings support the ongoing effort to reduce exposure to biomass fuel in low-resource settings.

Impact statements
Biomass for cooking is a leading source of household air pollution in low and middle-income countries, contributing to many chronic diseases and premature deaths. Chronic exposure to biomass fuel through oxidative stress and inflammation has been associated with a shortening of the telomeres, a “biological marker” of longevity. This prospective cohort study describes the association between household biomass fuel use and leukocyte telomere length among 497 toddlers. Leukocyte telomere length was significantly shorter among children living in households with biomass fuel than in children from homes where mainly LPG was used for cooking.

Clinical Trial registration
Clinicaltrials.gov: NCT02272842, registered October 21, 2014, Universal Trial Number: U1111-1161-5187 (September 8, 2014)
Hypertension and cardiomyopathy associated with chronic kidney disease: epidemiology, pathogenesis and treatment considerations
Authors: Law Jonathan P. , Pickup Luke , Pavlovic Davor , Townend Jonathan N. , Ferro Charles J. 
Published: September 2022

AbstractChronic kidney disease (CKD) is a complex condition with a prevalence of 10–15% worldwide. An inverse-graded relationship exists between cardiovascular events and mortality with kidney function which is independent of age, sex, and other risk factors. The proportion of deaths due to heart failure and sudden cardiac death increase with progression of chronic kidney disease with relatively fewer deaths from atheromatous, vasculo-occlusive processes. This phenomenon can largely be explained by the increased prevalence of CKD-associated cardiomyopathy with worsening kidney function. The key features of CKD-associated cardiomyopathy are increased left ventricular mass and left ventricular hypertrophy, diastolic and systolic left ventricular dysfunction, and profound cardiac fibrosis on histology. While these features have predominantly been described in patients with advanced kidney disease on dialysis treatment, patients with only mild to moderate renal impairment already exhibit structural and functional changes consistent with CKD-associated cardiomyopathy. In this review we discuss the key drivers of CKD-associated cardiomyopathy and the key role of hypertension in its pathogenesis. We also evaluate existing, as well as developing therapies in the treatment of CKD-associated cardiomyopathy.
Leptin enhances social motivation and reverses chronic unpredictable stress-induced social anhedonia during adolescence
Authors: Lei Yun , Wang Dan , Bai Yu , Nougaisse Jayvon , Weintraub Neal L. , Guo Ming , Lu Xin-Yun 
Published: September 2022

AbstractSocial anhedonia, a loss of interest and pleasure in social interactions, is a common symptom of major depression as well as other psychiatric disorders. Depression can occur at any age, but typically emerges in adolescence or early adulthood, which represents a sensitive period for social interaction that is vulnerable to stress. In this study, we evaluated social interaction reward using a conditioned place preference (CPP) paradigm in adolescent male and female mice. Adolescent mice of both sexes exhibited a preference for the social interaction-associated context. Chronic unpredictable stress (CUS) impaired the development of CPP for social interaction, mimicking social anhedonia in depressed adolescents. Conversely, administration of leptin, an adipocyte-derived hormone, enhanced social interaction-induced CPP in non-stressed control mice and reversed social anhedonia in CUS mice. By dissecting the motivational processes of social CPP into social approach and isolation avoidance components, we demonstrated that leptin treatment increased isolation aversion without overt social reward effect. Further mechanistic exploration revealed that leptin stimulated oxytocin gene transcription in the paraventricular nucleus of the hypothalamus, while oxytocin receptor blockade abolished the leptin-induced enhancement of socially-induced CPP. These results establish that chronic unpredictable stress can be used to study social anhedonia in adolescent mice and provide evidence that leptin modulates social motivation possibly via increasing oxytocin synthesis and oxytocin receptor activation.
Mutant p53 gain of function mediates cancer immune escape that is counteracted by APR-246
Authors: Zhou Xiaolei , Santos Gema Sanz , Zhan Yue , Oliveira Mariana M. S. , Rezaei Shiva , Singh Madhurendra , Peuget Sylvain , Westerberg Lisa S. , Johnsen John Inge , Selivanova Galina 
Published: September 2022

AbstractBackgroundp53 mutants contribute to the chronic inflammatory tumour microenvironment (TME). In this study, we address the mechanism of how p53 mutants lead to chronic inflammation in tumours and how to transform it to restore cancer immune surveillance.MethodsOur analysis of RNA-seq data from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) project revealed that mutant p53 (mtp53) cancers correlated with chronic inflammation. We used cell-based assays and a mouse model to discover a novel gain of function of mtp53 and the effect of the mtp53 reactivating compound APR-246 on the anti-tumour immune response.ResultsWe found that tumour samples from patients with breast carcinoma carrying mtp53 showed elevated Interferon (IFN) signalling,TumourInflammationSignature (TIS) score and infiltration of CD8+ T cells compared to wild type p53 (wtp53) tumours. We showed that the expression of IFN and immune checkpoints were elevated in tumour cells in a mtp53-dependent manner, suggesting a novel gain of function. Restoration of wt function to mtp53 by APR-246 induced the expression of endogenous retroviruses, IFN signalling and repressed immune checkpoints. Moreover, APR-246 promoted CD4+ T cells infiltration and IFN signalling and prevented CD8+ T cells exhaustion within the TME in vivo.ConclusionsBreast carcinomas with mtp53 displayed enhanced inflammation. APR-246 boosted the interferon response or represses immune checkpoints in p53 mutant tumour cells, and restores cancer immune surveillance in vivo.
Topical application of an irreversible small molecule inhibitor of lysyl oxidases ameliorates skin scarring and fibrosis
Authors: Chaudhari Nutan , Findlay Alison D. , Stevenson Andrew W. , Clemons Tristan D. , Yao Yimin , Joshi Amar , Sayyar Sepidar , Wallace Gordon , Rea Suzanne , Toshniwal Priyanka , Deng Zhenjun , Melton Philip E. , Hortin Nicole , Iyer K. Swaminathan , Jarolimek Wolfgang , Wood Fiona M. , Fear Mark W. 
Published: September 2022

AbstractScarring is a lifelong consequence of skin injury, with scar stiffness and poor appearance presenting physical and psychological barriers to a return to normal life. Lysyl oxidases are a family of enzymes that play a critical role in scar formation and maintenance. Lysyl oxidases stabilize the main component of scar tissue, collagen, and drive scar stiffness and appearance. Here we describe the development and characterisation of an irreversible lysyl oxidase inhibitor, PXS-6302. PXS-6302 is ideally suited for skin treatment, readily penetrating the skin when applied as a cream and abolishing lysyl oxidase activity. In murine models of injury and fibrosis, topical application reduces collagen deposition and cross-linking. Topical application of PXS-6302 after injury also significantly improves scar appearance without reducing tissue strength in porcine injury models. PXS-6302 therefore represents a promising therapeutic to ameliorate scar formation, with potentially broader applications in other fibrotic diseases.
Ambipolar blend-based organic electrochemical transistors and inverters
Authors: Stein Eyal , Nahor Oded , Stolov Mikhail , Freger Viatcheslav , Petruta Iuliana Maria , McCulloch Iain , Frey Gitti L. 
Published: September 2022

AbstractCMOS-like circuits in bioelectronics translate biological to electronic signals using organic electrochemical transistors (OECTs) based on organic mixed ionic-electronic conductors (OMIECs). Ambipolar OECTs can reduce the complexity of circuit fabrication, and in bioelectronics have the major advantage of detecting both cations and anions in one device, which further expands the prospects for diagnosis and sensing. Ambipolar OMIECs however, are scarce, limited by intricate materials design and complex synthesis. Here we demonstrate that judicious selection of p- and n-type materials for blend-based OMIECs offers a simple and tunable approach for the fabrication of ambipolar OECTs and corresponding circuits. These OECTs show high transconductance and excellent stability over multiple alternating polarity cycles, with ON/OFF ratios exceeding 103 and high gains in corresponding inverters. This work presents a simple and versatile new paradigm for the fabrication of ambipolar OMIECs and circuits with little constraints on materials design and synthesis and numerous possibilities for tunability and optimization towards higher performing bioelectronic applications.
Ubiquitination of CLIP-170 family protein restrains polarized growth upon DNA replication stress
Authors: Wang Xi , Zheng Fan , Yi Yuan-yuan , Wang Gao-yuan , Hong Li-xin , McCollum Dannel , Fu Chuanhai , Wang Yamei , Jin Quan-wen 
Published: September 2022

AbstractMicrotubules play a crucial role during the establishment and maintenance of cell polarity. In fission yeast cells, the microtubule plus-end tracking proteins (+TIPs) (including the CLIP-170 homologue Tip1) regulate microtubule dynamics and also transport polarity factors to the cell cortex. Here, we show that the E3 ubiquitin ligase Dma1 plays an unexpected role in controlling polarized growth through ubiquitinating Tip1. Dma1 colocalizes with Tip1 to cortical sites at cell ends, and is required for ubiquitination of Tip1. Although the absence ofdma1+does not cause apparent polar growth defects in vegetatively growing cells, Dma1-mediated Tip1 ubiquitination is required to restrain polar growth upon DNA replication stress. This mechanism is distinct from the previously recognized calcineurin-dependent inhibition of polarized growth. In this work, we establish a link between Dma1-mediated Tip1 ubiquitination and DNA replication or DNA damage checkpoint-dependent inhibition of polarized growth in fission yeast.
A single hole spin with enhanced coherence in natural silicon
Authors: Piot N. , Brun B. , Schmitt V. , Zihlmann S. , Michal V. P. , Apra A. , Abadillo-Uriel J. C. , Jehl X. , Bertrand B. , Niebojewski H. , Hutin L. , Vinet M. , Urdampilleta M. , Meunier T. , Niquet Y.-M. , Maurand R. , Franceschi S. De 
Published: September 2022

AbstractSemiconductor spin qubits based on spin–orbit states are responsive to electric field excitations, allowing for practical, fast and potentially scalable qubit control. Spin electric susceptibility, however, renders these qubits generally vulnerable to electrical noise, which limits their coherence time. Here we report on a spin–orbit qubit consisting of a single hole electrostatically confined in a natural silicon metal-oxide-semiconductor device. By varying the magnetic field orientation, we reveal the existence of operation sweet spots where the impact of charge noise is minimized while preserving an efficient electric-dipole spin control. We correspondingly observe an extension of the Hahn-echo coherence time up to 88 μs, exceeding by an order of magnitude existing values reported for hole spin qubits, and approaching the state-of-the-art for electron spin qubits with synthetic spin–orbit coupling in isotopically purified silicon. Our finding enhances the prospects of silicon-based hole spin qubits for scalable quantum information processing.
Metabolomic profiles predict individual multidisease outcomes
Authors: Buergel Thore , Steinfeldt Jakob , Ruyoga Greg , Pietzner Maik , Bizzarri Daniele , Vojinovic Dina , Upmeier zu Belzen Julius , Loock Lukas , Kittner Paul , Christmann Lara , Hollmann Noah , Strangalies Henrik , Braunger Jana M. , Wild Benjamin , Chiesa Scott T. , Spranger Joachim , Klostermann Fabian , van den Akker Erik B. , Trompet Stella , Mooijaart Simon P. , Sattar Naveed , Jukema J. Wouter , Lavrijssen Birgit , Kavousi Maryam , Ghanbari Mohsen , Ikram Mohammad A. , Slagboom Eline , Kivimaki Mika , Langenberg Claudia , Deanfield John , Eils Roland , Landmesser Ulf 
Published: September 2022

AbstractRisk stratification is critical for the early identification of high-risk individuals and disease prevention. Here we explored the potential of nuclear magnetic resonance (NMR) spectroscopy-derived metabolomic profiles to inform on multidisease risk beyond conventional clinical predictors for the onset of 24 common conditions, including metabolic, vascular, respiratory, musculoskeletal and neurological diseases and cancers. Specifically, we trained a neural network to learn disease-specific metabolomic states from 168 circulating metabolic markers measured in 117,981 participants with ~1.4 million person-years of follow-up from the UK Biobank and validated the model in four independent cohorts. We found metabolomic states to be associated with incident event rates in all the investigated conditions, except breast cancer. For 10-year outcome prediction for 15 endpoints, with and without established metabolic contribution, a combination of age and sex and the metabolomic state equaled or outperformed established predictors. Moreover, metabolomic state added predictive information over comprehensive clinical variables for eight common diseases, including type 2 diabetes, dementia and heart failure. Decision curve analyses showed that predictive improvements translated into clinical utility for a wide range of potential decision thresholds. Taken together, our study demonstrates both the potential and limitations of NMR-derived metabolomic profiles as a multidisease assay to inform on the risk of many common diseases simultaneously.
Effectiveness of immunization with multi-component bacterial immunomodulator in foals at 35th day of life
Authors: Anna Migdał , Łukasz Migdał , Adam Okólski , Chełmońska-Soyta Anna 
Published: September 2022

AbstractThe aim of the study was to investigate the mechanisms leading to immunization through the use of a multicomponent bacterial immunomodulator and to find out the relationship between the TLR 4 receptor with selected parameters of innate immunity and to acquire immunity. The study was conducted on 18 Polish Pony Horses foals divided into two study groups: control (n = 9) and experimental (n = 9). Foals from the experimental group received intramuscular duplicate injection of 5 ml of multi-component bacterial immunomodular at 35 and 40 days of age. RNA isolated from venous blood was used to evaluate the expression ofTLR4genes using RT-PCR. Concentration of Il-6, IL-10, IgM and IgG2 was determined by the ELISA method in blood plasma. Immunostimulation had a significant impact on the level of genes expression forTLR4expression and IL-6 concentration. No effect of stimulation on IgM and IgG2 concentrations was found. The expression ofTLR4genes as well as the levels of interleukins could be modulated by stimulation with a pharmacological agent multi-component bacterial immunomodulator. The experiment demonstrated a strong positive correlation between TLR4 gene expression and IL-6 concentration and between TLR4 gene expression and IgM concentration.
Modelling response time in a mental rotation task by gender, physical activity, and task features
Authors: Fargier Patrick , Champely Stéphane , Massarelli Raphael , Ammary Laureine , Hoyek Nady 
Published: September 2022

AbstractMental rotation (MR) is a spatial skill considered to be a key-component of intellectual ability. Studies have suggested that the response time (RT) in a MR task (MRt) might be influenced, with possible gender differences, by the practice of a physical activity (PA) and depending on the plane, direction, degrees of the MR and the frame of reference to perform it. The present study aimed at examining the respective influences of all these variables on the RT by developing a linear mixed-effect model from the RTs varying according to the MR plane, direction, degrees and frame of reference. The MRt was performed by 96 males and females, all undergraduate students, distributed in three groups (sedentary subjects, artistic gymnasts, and futsal players). The results showed that only gender had a main effect (faster log RT in males), probably task-dependent. The other variables interacted among them showing that: (a) the log RT may be influenced by rotations experienced during PA, in particular during the locomotion on a horizontal ground and (b) such influence mainly depends on the compatibility of the physical rotations experienced with the plane and the degrees of the MRt.
Intratumoral heterogeneity of c-KIT mutations in a feline splenic mast cell tumor and their functional effects on cell proliferation
Authors: Hasegawa Yuki , Shosu Kazuha , Tsuji kanako , Shimoyama Yumiko , Miyama Takako Shimokawa , Baba Kenji , Okuda Masaru , Itamoto Kazuhito , Igase Masaya , Mizuno Takuya 
Published: September 2022

AbstractA cat was presented with mast cell tumors (MCTs) of the skin and spleen. During the initial diagnosis, the exon 8 mutation of c-KIT was detected in the masses from skin and spleen by a commercial laboratory test. Consequently, treatment with toceranib was started. After complete remission, because of recurrence on day 117, the spleen and skin tumors were removed, but the cat eventually died on day 191. The analysis of ten cDNA clones of the c-KIT gene cloned from the surgically removed spleen revealed that seven different cDNA patterns were included, indicating the heterogeneity of this gene in the splenic MCT. The seven cDNA nucleotide patterns can be classified into four protein sequence patterns. In addition to the previously known mutations in exon 8, we identified novel mutations in exons 9, 10, and 18; four amino acids deletion in exon 9, and a point mutation in exons 10 and 18. Mouse IL-3-dependent cell line, Ba/F3, was transduced with these mutant clones, and c-KIT phosphorylation and proliferation assays were performed. We found that certain mutations affected the c-KIT phosphorylation status and cell proliferation. This suggests that heterogeneity among the population of tumor cells exists in MCTs, and that the dominant clones of this heterogeneity may contribute to the subsequent tumor cell growth.
Measurement of subcutaneous fat tissue: reliability and comparison of caliper and ultrasound via systematic body mapping
Authors: Hoffmann Jana , Thiele Jens , Kwast Stefan , Borger Michael Andrew , Schröter Thomas , Falz Roberto , Busse Martin 
Published: September 2022

AbstractCaliper and ultrasound (US) are used to measure subcutaneous fat tissue depth (SFT) and then to calculate total body fat. There is no evidence-based recommendation as to whether caliper or US are equally accurate. The aim of this paper was therefore to compare reliability of both methods. In this methodical study, 54 participants (BMI: 24.8 ± 3.5 kg/m2; Age: 43.2 ± 21.7 years) were included. Using systematic body mapping, the SFT of 56 areas was measured. We also analyzed 4 body sites via MRI. A comparison between caliper and US detected clear differences in mean SFT of all areas (0.83 ± 0.33 cm vs. 1.14 ± 0.54 cm; p < 0.001) showing moderate reliability (ICC 0.669, 95%CI: 0.625–0.712). US and MRI revealed in the abdominal area a SFT twice as thick as caliper (2.43 ± 1.36 cm vs. 2.26 ± 1.32 cm vs. 1.15 ± 0.66 cm; respectively). Caliper and US revealed excellent intrarater (ICC caliper: 0.944, 95%CI: 0.926–0.963; US: 0.934, 95%CI: 0.924–0.944) and good interrater reliability (ICC caliper: 0.794, 95%CI: 0.754–0.835; US: 0.825, 95%CI: 0.794–0.857). Despite the high reliability in measuring SFT that caliper and US show, our comparison of the two methods yielded clear differences in SFT, particularly in the abdominal area. In accuracy terms, US is preferable for most mapping areas.
Municipal and neighbourhood level wastewater surveillance and subtyping of an influenza virus outbreak
Authors: Mercier Elisabeth , D’Aoust Patrick M. , Thakali Ocean , Hegazy Nada , Jia Jian-Jun , Zhang Zhihao , Eid Walaa , Plaza-Diaz Julio , Kabir Md Pervez , Fang Wanting , Cowan Aaron , Stephenson Sean E. , Pisharody Lakshmi , MacKenzie Alex E. , Graber Tyson E. , Wan Shen , Delatolla Robert 
Published: September 2022

AbstractRecurrent influenza epidemics and pandemic potential are significant risks to global health. Public health authorities use clinical surveillance to locate and monitor influenza and influenza-like cases and outbreaks to mitigate hospitalizations and deaths. Currently, global integration of clinical surveillance is the only reliable method for reporting influenza types and subtypes to warn of emergent pandemic strains. The utility of wastewater surveillance (WWS) during the COVID-19 pandemic as a less resource intensive replacement or complement for clinical surveillance has been predicated on analyzing viral fragments in wastewater. We show here that influenza virus targets are stable in wastewater and partitions favorably to the solids fraction. By quantifying, typing, and subtyping the virus in municipal wastewater and primary sludge during a community outbreak, we forecasted a citywide flu outbreak with a 17-day lead time and provided population-level viral subtyping in near real-time to show the feasibility of influenza virus WWS at the municipal and neighbourhood levels in near real time using minimal resources and infrastructure.