bluuebunny/crossref_metadata_2025_split huggingface dataset:
Purchases dominate the carbon footprint of research laboratories
Authors: De Paepe Marianne , Jeanneau Laurent , Mariette Jerôme , Aumont Olivier , Estevez-Torres Andŕe 
Published: April 2023

AbstractDespite increasing interest for the carbon footprint of higher education institutions, little is known about the carbon footprint associated to research activities. Air travel and attendance to conferences concentrate recent data and debates but purchases have attracted little attention. Here we develop a hybrid method to estimate the greenhouse gas emissions (GHG) associated to research purchases. To do so, we combine macroe-conomic databases, research-centered companies footprints and life-cycle assesments to construct a public database of monetary emission factors (EF) for research purchases. We apply it to estimate the purchases emissions of a hundred of research laboratories in France, belonging to the Labos 1point5 network and gathering more than 20000 staff, from all disciplines. We find that purchases dominate laboratory emissions, accounting for more than 50% of emissions, with a median of 2.7 t CO2e/pers, which is 3 to 4-fold the separate contribution from travel, commutes and heating. Median electricity emissions are 5-fold lower in our dataset of laboratories using low carbon electricity but they become preponderant for high carbon electricity mixes (3.5 t CO2e/pers). Purchases emissions are very heterogeneous among laboratories and are linearly correlated with budget, with an average carbon intensity of 0.31±0.07 kg CO2e/€ and differences between research domains. Finally, we quantify the effect of a series of demand-driven mitigation strategies obtaining up to−20 % in total emissions (−40 % in purchases emissions), suggesting that effectively reducing the carbon footprint of research activities calls for systemic changes.Significance statementResearch activities are recently interrogating their contribution to global warming, mainly through the impact of air travel but neglecting the emissions embodied in scientific purchases. However, goods and services used in a research laboratory emit greenhouse gases when they are produced. Here we construct a public and robust database of emission factors to quantify purchases emissions in a laboratory and we use it to assess emissions from a hundred of laboratories in France, from all disciplines. We find that purchases emissions represent half of the of the 6.3 t CO2e/pers per year emitted on average per laboratory. Emissions, however, vary greatly between laboratories and disciplines and an analysis of mitigation strategies shows that decreasing demand may significantly reduce purchases emissions.
Pathogenesis ofAchromobacter xylosoxidansrespiratory infections: colonization and persistence of airway epithelia and differential gene expression in synthetic cystic fibrosis sputum medium
Authors: Billiot Caitlin E. , McDaniel Melissa S. , Swords W. Edward , Lindgren Natalie R. 
Published: April 2023

ABSTRACTCystic fibrosis (CF) is a genetic disease affecting epithelial ion transport, resulting in thickened mucus and impaired mucociliary clearance. Persons with CF (pwCF) experience life- long respiratory mucosal infections caused by a diverse array of opportunists, and these infections are a leading cause of morbidity and mortality for pwCF. In recent years, there has been increased appreciation for the range and diversity of microbes in CF-related respiratory infections. Introduction of new therapeutics and improved detection methodology has revealed CF related opportunists such asAchromobacter xylosoxidans(Ax).Axis a Gram-negative bacterial species that is widely distributed in the environment and has been increasingly observed in sputa and other samples from pwCF; typicallyAxinfections occur in patients in later stages of CF disease. In this study, we characterized CF clinical isolates ofAxand tested colonization and persistence ofAxin respiratory infection using immortalized human CF respiratory epithelial cells and BALB/c mice. Genomic analyses of clinicalAxisolates showed homologs for factors involved in flagellar synthesis, antibiotic resistance, and toxin secretion systems.Axisolates adhered to polarized CFBE14o- human immortalized CF bronchial epithelial cells and caused significant cytotoxicity and depolarization.Axcolonized and persisted in mouse lung for up to 72 hours post infection, with inflammatory consequences that include increased neutrophilia, lung damage, cytokine production, and mortality. Transcript profiling reveled differential expression ofAxgenes during growth in SCFM2 synthetic CF sputum media. Based on these results, we conclude thatAxis an opportunistic pathogen of significance in CF.
White matter integrity is associated with cognition and amyloid burden in older adult Koreans along the Alzheimer’s disease continuum
Authors: Hirschfeld Lauren Rose , Deardorff Rachael , Chumin Evgeny J. , Wu Yu-Chien , McDonald Brenna C. , Cao Sha , Risacher Shannon L. , Yi Dahyun , Byun Min Soo , Lee Jun-Young , Kim Yu Kyeong , Kang Koung Mi , Sohn Chul-Ho , Nho Kwangsik , Saykin Andrew J. , Lee Dong Young ,   the KBASE Research Group
Published: April 2023

ABSTRACTBACKGROUNDWhite matter (WM) microstructural changes in the hippocampal cingulum bundle (CBH) in Alzheimer’s disease (AD) have been described in cohorts of largely European ancestry but are lacking in other populations.METHODSWe assessed the relationship between CBH WM integrity and cognition or amyloid burden in 505 Korean older adults aged ≥55 years, including 276 cognitively normal older adults (CN), 142 mild cognitive impairment (MCI), and 87 AD, recruited as part of the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s disease (KBASE) at Seoul National University.RESULTSCompared to CN, AD and MCI subjects showed decreased WM integrity in the bilateral CBH. Cognition, mood, and higher amyloid burden were also associated with poorer WM integrity in the CBH.CONCLUSIONThese findings are consistent with patterns of WM microstructural damage previously reported in non-Hispanic White (NHW) MCI/AD cohorts, reinforcing existing evidence from predominantly NHW cohort studies.
Vagina reconstruction by decellularization of healthy human vaginal tissue
Authors: Sueters J. , Xiao F. , Roovers J.P.R.W. , Bouman M.B. , Groenman F.A. , Maas H. , Huirne J.A.F. , Smit T.H. 
Published: April 2023

AbstractWhen a healthy, full-size vagina is absent due to a disorder, various neovagina creation methods are available. Sometimes dilation or stretching of the vagina cavity is sufficient, but generally intestinal or dermal graft tissue is required. However, different inherent tissue properties cause complications. Therefore, when a body part is lost, it should be replaced by a similar material. The use of organ-specific acellular vaginal tissue carries great potential, as the similar architecture and matrix composition make it fit for vagina regeneration. We developed an optimized decellularization protocol for human vaginal tissue and determined suitability as tissue-mimicking scaffold for vagina reconstruction. Histological examination confirmed the preservation of structural features and minimal cellular residue was seen during fluorescence microscopy, DNA and RNA quantification and fragment-length examination. Biomechanical testing showed decreased (P<0,05) strain at rupture (23%), tensile stress (55%) and elastic modulus (68%) after decellularization. Fluorescence microscopy revealed preserved Fibronectin-I/II/III and Laminin-I/II, while Collagen-I and Ficolin-2B were decreased but mostly retained. The absence of cellular residue, minimally altered biomechanical ECM properties and mostly preserved structural proteins, appear to make our decellularized human vaginal matrix a suitable tissue-mimicking scaffold for vagina transplantation when tissue survival through vascularization and innervation are accomplished in the future.
Drivers of Early Childhood Vaccination Success in Nepal, Senegal, and Zambia: A Multiple Case Study Analysis Using the Consolidated Framework of Implementation Research
Authors: Escoffery Cam , Ogutu Emily , Sakas Zoe , Hester Kyra A. , Ellis Anna , Rodriguez Katie , Jaishwal Chandni , Yang Chenmua , Dixit Sameer , Bose Anindya , Sarr Moussa , Kilembe William , Bednarczyk Robert A. , Freeman Matthew C. 
Published: April 2023

AbstractIntroductionThe fundamental components of a vaccine delivery system are well-documented, but robust evidence is needed onhowthe related processes and implementation strategies - including the facilitators and barriers-contribute to improvements in childhood vaccination coverage. The purpose of this study was to identify critical facilitators and barriers to the implementation of common interventions across three countries that have dramatically increased coverage of early childhood vaccination over the past 20 years, and to qualify common or divergent themes in their success.MethodsWe conducted 277 key informant interviews and focus group discussions with public health leaders at the regional, district, and local levels and community members in Nepal, Senegal, and Zambia to identify intervention activities and the facilitators and barriers to implementation. We used thematic analysis grounded in the Consolidated Framework for Implementation Research (CFIR) to identify immunization program key facilitators and barriers.ResultsWe found that the common facilitators to program implementation across the countries were the CFIR inner setting constructs of 1) networks and communications, 2) goals and feedback, 3) relative priority, and 4) readiness for implementation; and outer setting constructs of 4) cosmopolitanism and 5) external policies and mandates. The common barriers were incentives and rewards, available resources, access to knowledge and information, and patients needs and resources. Critical to the success of these national immunization programs were prioritization and codification of health as a human right, clear chain of command and shared ownership of immunization, communication of program goals and feedback, offering of incentives at multiple levels, training of staff central to vaccination education, the provision of resources to support the program, key partnerships and guidance on implementation and adoption of vaccination policies.ConclusionAdequate organizational commitment, resources, communication, training, and partnerships were the most critical facilitators for these countries to improve childhood vaccination.
Blood biomarkers in Takotsubo syndrome point to an emerging role for inflammaging in disease pathophysiology
Authors: Nagai M. , Shityakov S. , Smetak M , Hunkler H.J. , Bär C. , Schlegel N. , Thum T. , Förster C. Y. 
Published: April 2023

AbstractTakotsubo syndrome (TTS), an acute cardiac condition characterized by transient wall motion abnormalities mostly of the left ventricle, results in difficulties in diagnosing patients. We set out to present a detailed blood analysis of TTS patients analyzing novel markers to understand the development of TTS. Significant differences in pro-inflammatory cytokine expression patterns, sex steroid and glucocorticoid receptor (GR) expression levels were observed in the TTS patient collective. Remarkably, the measured catecholamine serum concentrations determined from TTS patient blood could be shown to be two orders of magnitude lower than the levels determined from experimentally induced TTS in laboratory animals. Consequently, exposure of endothelial cells and cardiomyocytes in vitro to such catecholamine concentrations did not damage the cellular integrity or function of neither endothelial cells forming the blood brain barrier, endothelial cells derived from myocardium nor cardiomyocytes in vitro. Computational analysis was able to link the identified blood markers, specifically, the pro-inflammatory cytokines and glucocorticoid receptor GR to microRNA (miR) relevant in the ontogeny of TTS (miR-15), and inflammation (miR-21, miR-146a), respectively. Amongst the well-described risk factors of TTS (older age, female gender), inflammaging-related pathways were identified to add to these relevant risk factors or prediagnostic markers of TTS.
MRI-Guided Focused Ultrasound Blood-Brain Barrier Opening Increases Drug Delivery and Efficacy in a Diffuse Midline Glioma Mouse Model
Authors: Martinez Payton , Nault Genna , Steiner Jenna , Wempe Michael F. , Pierce Angela , Brunt Breaunna , Slade Mathew , Mongin Andrew , Song Jane , Song Kang-Ho , Ellens Nicholas , Serkova Natalie , Green Adam , Borden Mark 
Published: April 2023

AbstractDiffuse intrinsic pontine glioma (DIPG) is the most common and deadliest pediatric brainstem tumor and is difficult to treat with chemotherapy in part due to the blood-brain barrier (BBB). Focused ultrasound (FUS) and microbubbles (MBs) have been shown to cause BBB disruption (BBBD), allowing larger chemotherapeutics to enter the parenchyma. Panobinostat is an example of a promisingin vitroagent in DIPG with poor clinical efficacy due to low BBB penetrance. In this study, we hypothesized that using FUS to disrupt the BBB allows higher concentrations of panobinostat to accumulate in the tumor, providing a therapeutic effect. Mice were orthotopically injected with a patient-derived DMG cell line, BT-245. MRI was used to guide FUS/MB (1.5 MHz, 0.615 MPa PNP, 1 Hz PRF, 10 ms PL, 3 min treatment time) / (25 µL/kg, IV) targeting to the tumor location. In animals receiving panobinostat (10 mg/kg, IP) in combination with FUS/MB, a 3-fold increase in tumor panobinostat concentration was observed, with only insignificant increase of the drug in the forebrain. In mice receiving three weekly treatments, the combination of panobinostat and FUS/MB led to a 71% reduction of tumor volumes by MRI (p= 0.01). Furthermore, FUS/MB improved the mean survival from 21 to 31 days (p< 0.0001). Our study demonstrates that FUS-mediated BBBD can increase the delivery of panobinostat to an orthotopic DMG tumor, providing a strong therapeutic effect and increased survival.One Sentence SummaryFUS and microbubbles can increase the delivery of panobinostat to a patient-derived xenograft (PDX) orthotopic DMG tumor, providing a strong therapeutic effect and increased survival.
Therapeutic immunization with a whole cell vaccine reduces pneumococcal nasopharyngeal density, shedding, and middle ear infection in mice
Authors: Manning Jayne , Manna Sam , Dunne Eileen M , Bongcaron Viktoria , Pell Casey L , Patterson Natalie L , Kuil Sacha D , Dhar Poshmaal , Goldblatt David , Mulholland E Kim , Licciardi Paul V , Robins-Browne Roy M , Malley Richard , Wijburg Odilia , Satzke Catherine 
Published: April 2023

AbstractPneumococcal Conjugate Vaccines (PCVs) have substantially reduced the burden of disease caused byStreptococcus pneumoniae(the pneumococcus). However, protection is limited to vaccine serotypes, and when administered to children who are colonized with pneumococci at the time of vaccination, immune responses to the vaccine are blunted. Here, we investigate the potential of a killed whole cell pneumococcal vaccine (WCV) to reduce existing pneumococcal carriage and mucosal disease when given therapeutically to infant mice colonized with pneumococci. We show that a single dose of WCV reduced pneumococcal carriage density in an antibody-dependent manner. Therapeutic vaccination induced robust immune responses to pneumococcal surface antigens CbpA, PspA (family 1) and PiaA. In a co-infection model of otitis media, a single dose of WCV reduced pneumococcal middle ear infection. Lastly, in a two-dose model, therapeutic administration of WCV reduced nasal shedding of pneumococci. Taken together, our data demonstrate that WCV administered in colonized mice reduced pneumococcal density in the nasopharynx and the middle ear, and decreased shedding. A vaccine with similar properties in children would be beneficial in low and middle-income settings where pneumococcal carriage is high.ImportanceAlthough typically asymptomatic, pneumococcal carriage plays an essential role in transmission and the development of disease. Pneumococcal Conjugate Vaccines (PCVs) have reduced the burden of pneumococcal disease worldwide. However, their use has increased carriage and disease caused by non-vaccine serotypes, prompting investigations into serotype-independent pneumococcal vaccines. An additional limitation of PCVs is immune hypo-responsiveness to vaccines in children carrying pneumococci at the time of vaccination. Therefore, there is great interest in next generation vaccines such as whole cell vaccines. In this study we investigate a pneumococcal whole cell vaccine (WCV) for it effect on carriage in mice that are already colonized at the time of vaccination. We show that this ‘therapeutic’ vaccination of mice can reduce pneumococcal carriage density, shedding and infection of the middle ear. Our study suggests that WCV could be beneficial in high burden settings where carriage at the time of vaccination is more common.
Multiplicative Joint Coding in Preparatory Activity for Reaching Sequence in Macaque Motor Cortex
Authors: Wang Tianwei , Chen Yun , Zhang Yiheng , Cui He 
Published: April 2023

AbstractAlthough motor cortex has been found to be modulated by sensory or cognitive sequences, the linkage between multiple movement elements and sequence-related responses is not yet understood. Here, we recorded neuronal activity from the motor cortex with implanted micro-electrode arrays and single electrodes while monkeys performed a double-reach task that was instructed by simultaneously presented memorized cues. We found that there existed a substantial multiplicative component jointly tuned to impending and subsequent reaches during preparation, then the coding mechanism transferred to an additive manner during execution. Multiplicative joint coding, which also spontaneously emerged in a recurrent neural network trained for double-reach, enriches neural patterns for sequential movement, and might explain the linear readout of elemental movements.
Vocal complexity in the long calls of Bornean orangutans
Authors: Erb Wendy M. , Ross Whitney , Kazanecki Haley , Setia Tatang Mitra , Madhusudhana Shyam , Clink Dena J. 
Published: April 2023

AbstractVocal complexity is central to many evolutionary hypotheses about animal communication. Yet, quantifying and comparing complexity remains a challenge, particularly when vocal types are highly graded. Male Bornean orangutans (Pongo pygmaeus wurmbii) produce complex and variable “long call” vocalizations comprising multiple sound types that vary within and among individuals. Previous studies described six distinct call (or pulse) types within these complex vocalizations, but none quantified their discreteness or the ability of human observers to reliably classify them. We studied the long calls of 13 individuals to: 1) evaluate and quantify the reliability of audio-visual classification by three well-trained observers, 2) distinguish among call types using supervised classification and unsupervised clustering, and 3) compare the performance of different feature sets. Using 46 acoustic features, we applied machine learning (i.e., support vector machines, affinity propagation, and fuzzy c-means) to identify call types and assess their discreteness. We additionally used Uniform Manifold Approximation and Projection (UMAP) to visualize the separation of pulses using both extracted features and spectrogram representations. Supervised approaches showed low inter-observer reliability and poor classification accuracy, indicating that pulse types were not discrete. We propose an updated pulse classification approach that is highly reproducible across observers and exhibits strong classification accuracy using support vector machines. Although the low number of call types suggests long calls are fairly simple, the continuous gradation of sounds seems to greatly boost the complexity of this system. This work responds to calls for more quantitative research to define call types and quantify gradedness in animal vocal systems and highlights the need for a more comprehensive framework for studying vocal complexity vis-à-vis graded repertoires.
Functional characterization of five triterpene synthases through De-novo assembly and transcriptome analysis ofEuphorbia grantiiandEuphorbia tirucalli
Authors: Kumar Ashish , Mulge Dhanashri S. , Thakar Kalyani J. , Pandreka Avinash , Warhekar Amruta D. , Ramkumar Sudha , Sharma Poojadevi , Upadrasta Sindhuri , Shanmugam Dhanasekaran , Thulasiram Hirekodathakallu V. 
Published: April 2023

SummaryEuphorbia grantiiandEuphorbia tirucalliknown to synthesize diverse triterpenes including euphol and tirucallol. These two triterpenes known to possess potent anti-cancer, anti-bacterial, and anti-fungal properties along with various other biological activities. In this study, De-novo assembly and comparative transcriptome analysis of leaf and stem tissues ofE. tirucalliandE. grantiiwere carried out to identify thirteen triterpene synthases from 1,40,227 in correlation with the metabolic profiling. Comparative transcriptome analysis indicated that EutTTS4 and EutTTS5 genes which encodes for euphol/tirucallol and tirucallol synthase were highly expressed in leaf and stem tissue. The genes which encodes α-amyrin synthase (EutTTS1) and lupeol synthase (EutTTS2) were characterized by overexpressing them in YPH499 yeast strain. We have developed using hem1 and erg7 knock yeast strain of lanosterol deficient yeast (TMBL17) and used for over expression of friedelin synthase (EutTTS3), and two novel triterpenes synthases such as euphol/tirucallol synthase (EutTTS4) and tirucallol synthase (EutTTS5). These results are very useful in large scale production of triterpenes by genomic integration of respective triterpene synthases in TMBL yeast strain developed in this study.Significance StatementWe have functionally characterized triterpene synthases fromE. tirucalliandE. grantiiand developed a hem1 and erg7 knock out of lanosterol deficient yeast (TMBL17) for the large-scale production of triterpene and triterpene related products.