bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of post tuberculosis lung disease on survival in HIV-infected individuals with pulmonary hypertension: Insights from the Pan African Pulmonary Hypertension Cohort (PAPUCO) study
Authors: Katoto Patrick D.M.C. , Mukasa Sandra L. , Wolmarans Karen H. , Sani Mahmoud U. , Karaye Kamilu M. , Mbanze Irina , Damasceno Albertino , Mocumbi Ana O. , Dzudie Anastase , Sliwa Karen , Thienemann Friedrich 
Published: August 2023

AbstractIntroductionPost-tuberculosis lung disease (PTLD) bears high mortality rates, primarily attributed to pulmonary vascular and cardiovascular complications. We investigated the impact of tuberculosis (TB) history on pulmonary hypertension (PH) prognosis within an HIV-burdened region.MethodsWe acquired sociodemographic, clinical, and echocardiographic data on 206 PH adults from the Pan African Pulmonary Hypertension cohort (PAPUCO), a prospective cohort study undertaken in four African countries. Cox-hazard regression models were constructed to assess how TB history interacts with diabetes, HIV-infection, and other chronic lung diseases (CLD), impacting death risks in PH patients.ResultsAmong the participants, a history of TB, diabetes, and other CLD was found in 23%, 8%, and 12% respectively. Of the 47 (35%)/134 participants living with HIV-infection, 62% exhibited HIV/TB coinfection, with 45% experiencing recurrent TB episodes. Individuals with TB history faced a 1.82-fold higher PH-related mortality risk (adjusted Hazard Ratio [aHR]: 1.84; 95%CI: 1.00, 3.39; p=0.049). Concurrent TB and comorbidities amplified death risks for PH patients, significantly affecting CLD (aHR: 3.10; 95%CI: 1.47, 6.53; p=0.003), and showing borderline impact for HIV co-infection (aHR: 2.10; 95%CI: 0.97, 4.54; p=0.059), while not significantly influenced by diabetes history (aHR: 2.39; 95%CI: 0.32, 18.00; p=0.4), although clinically relevant.ConclusionNearly one in every four patients diagnosed with PH in Africa have a history of TB and one in every three have HIV infection, which dramatically reduces their odds of survival. Our findings constitute a call to action to effectively address the neglected burden of PH among millions of patients suffering with TB diseases.
Optimising primary molecular profiling in NSCLC
Authors: Schouten R.D. , Schouten I. , Schuurbiers M.M.F. , van der Noort V. , Damhuis R.A.M. , van der Heijden E.H.F.M. , Burgers J.A. , Barlo N.P. , van Lindert A.S.R. , Maas K.W. , van den Brand J.J.G. , Smit A.A.J. , van Haarst J.M.W. , van der Maat B. , Schuuring E. , Blaauwgeers H. , Willems S.M. , Monkhorst K. , van den Broek D. , van den Heuvel M.M. 
Published: August 2023

AbstractIntroductionMolecular profiling of NSCLC is essential for optimising treatment decisions, but often incomplete. We assessed the efficacy of protocolised molecular profiling in the current standard-of-care (SoC) in a prospective observational study in the Netherlands and measured the effect of providing standardised diagnostic procedures. We also explored the potential of plasma-based molecular profiling in the primary diagnostic setting.MethodsThis multi-centre prospective study was designed to explore the performance of current clinical practice during the run-in phase using local SoC tissue profiling procedures. The subsequent phase was designed to investigate the extent to which comprehensive molecular profiling (CMP) can be maximized by protocolising tumour profiling. Successful molecular profiling was defined as completion of at leastEGFRandALKtesting. Additionally, PD-L1 tumour proportions scores were explored. Lastly, the additional value of centralised plasma-based testing forEGFRandKRASmutations using droplet digital PCR was evaluated.ResultsTotal accrual was 878 patients, 22.0% had squamous cell carcinoma and 78.0% had non-squamous NSCLC. Stage I-III was seen in 54.0%, stage IV in 46.0%. Profiling ofEGFRandALKwas performed in 69.9% of 136 patients included in the run-in phase, significantly more than real-world data estimates of 55% (p<0.001). Protocolised molecular profiling increased the rate to 77.0% (p=0.049).EGFRandALKprofiling rates increased from 77.9% to 82.1% in non-squamous NSCLC and from 43.8% to 57.5% in squamous NSCLC. Plasma-based testing was feasible in 98.4% and identified oncogenic driver mutations in 7.1% of patients for whom tissue profiling was unfeasible.ConclusionThis study shows a high success rate of tissue-based molecular profiling that was significantly improved by a protocolised approach. Tissue-based profiling remains unfeasible for a substantial proportion of patients. Combined analysis of tumour tissue and circulating tumour DNA is a promising approach to allow adequate molecular profiling of more patients.
Heterogeneous SARS-CoV-2 kinetics due to variable timing and intensity of immune responses
Authors: Owens Katherine , Esmaeili-Wellman Shadisadat , Schiffer Joshua T. 
Published: August 2023

AbstractThe viral kinetics of documented SARS-CoV-2 infections exhibit a high degree of inter-individual variability. We identified six distinct viral shedding patterns, which differed according to peak viral load, duration, expansion rate and clearance rate, by clustering data from 768 infections in the National Basketball Association cohort. Omicron variant infections in previously vaccinated individuals generally led to lower cumulative shedding levels of SARS-CoV-2 than other scenarios. We then developed a mechanistic mathematical model that recapitulated 1510 observed viral trajectories, including viral rebound and cases of reinfection. Lower peak viral loads were explained by a more rapid and sustained transition of susceptible cells to a refractory state during infection, as well as an earlier and more potent late, cytolytic immune response. Our results suggest that viral elimination occurs more rapidly during omicron infection, following vaccination, and following re-infection due to enhanced innate and acquired immune responses. Because viral load has been linked with COVID-19 severity and transmission risk, our model provides a framework for understanding the wide range of observed SARS-CoV-2 infection outcomes.
Understanding the adaptive role of chromosomal inversions across large geographical scales: The potential of pool-seq data
Authors: Westram Anja M , Morales Hernán E. , Johannesson Kerstin , Butlin Roger , Faria Rui 
Published: August 2023

AbstractA growing body of research shows that chromosomal inversions, where each arrangement is associated with a certain environment and maintains a set of adaptive alleles, make an important contribution to local adaptation. However, inversions often remain unexplored across large geographical scales. It is unclear whether inversions contribute to adaptation across species ranges, which environmental factors affect arrangement frequencies, and whether the adaptive content of the same arrangement varies between locations. Here, we discuss ideas of how allele frequency data (e.g. pool-sequencing data) can be used to learn about inversions in a simple and cost-effective way. If populations connected by migration differ in arrangement frequency, plotting their SNP allele frequencies against each other will reveal a parallelogram whose corners reflect arrangement frequencies. We demonstrate the usefulness of this approach in locally-adapted populations of the intertidal snailLittorina saxatilis(Olivi). For twelve inversions, we estimate arrangement frequencies in 20 populations across the European species range. While roughly half of the inversions contribute to adaptation to the well-studied contrast between wave-exposed and crab-infested habitats, the other half likely contribute to adaptation to shore height. We also find evidence for geographical variation in arrangement content, suggesting variation in adaptive role.
Response diversity is key to buffer ecosystem productivity against multiple environmental change drivers
Authors: Tatsumi Shinichi , Punwasi Neil , Roberto Adriano , Cadotte Marc W. 
Published: August 2023

AbstractEvidence shows that biodiversity promotes primary productivity. However, it is unclear whether such biodiversity–productivity relationships persist under increasing numbers of environmental changes in the current Anthropocene. Here, we use theoretical and experimental approaches to demonstrate that variation in species’ responses to changing environments determines the ability of ecological communities to maintain productivity under multiple types of environmental change. Our theory shows that this response diversity determines whether biodiversity–productivity relationships are enhanced or impaired by environmental changes. Communities with high response diversity are expected not only to be productive in a particular environment but to maintain that productivity under multiple conditions. Nevertheless, our theory also predicts that such buffering effects fade with increasing negative environmental impacts on communities. Consistent with this prediction, our biodiversity experiment reveals impaired biodiversity–productivity relationships under multiple environmental change drivers with a negative mean impact. Our results suggest that, in the face of growing multiplicity of environmental changes, policies should encourage conservation of local biota, enabling communities to respond to unprecedented environments that may arise.
Cuticular hydrocarbon profiles of Himalayan bumble bees (Hymenoptera:BombusLatreille) are species-specific and show local and elevation related variation
Authors: Narah Jaya , Streinzer Martin , Chakravorty Jharna , Megu Karsing , Spaethe Johannes , Brockmann Axel , Schmitt Thomas 
Published: August 2023

ABSTRACTBumble bees are important pollinators in natural environments and agricultural farmlands and are in particular adapted to harsh environments like high mountain habitats. In these environments, animals are exposed to low temperature and face the risk of desiccation. The Eastern Himalayas are one of the recognized biodiversity hotspots worldwide. The area covers subtropical rainforest with warm temperature and high precipitation as well as high mountain ranges with peaks reaching up to 6000 m, shaping a diverse floral and faunal community at the different altitudinal zones. We investigated the cuticular hydrocarbon profiles of four bumble bee species occurring at different elevational ranges in Arunachal Pradesh, the northeast most state in India. At 17 locations along an elevational gradient we collected workers of two species from lower elevations (B. albopleuralisandB. breviceps;∼ 100m - 3000m asl) and two species from higher elevations (B. prshewalskyiandB. mirus; ∼ 2800m - 4,500m asl). The CHC profiles of all four species showed a significant degree of variation in the composition of hydrocarbons, indicating species specificity. We also found clear correlation with elevation. The weighted mean chain length of the hydrocarbons significantly differed between the low and high altitudinal species, and the proportion of saturated hydrocarbons in CHC profiles significantly increased with the elevational range of the bumble bee species. Thus, these four species of bumble bees in the eastern Himalayas seem to adapt their CHC composition to elevation by decreasing water permeability of their cuticle, similar to insects living in dry mountains or deserts habitats.
A noncanonical repressor function of JUN restrains YAP activity and suppresses YAP-dependent liver cancer growth
Authors: Kurlishchuk Yuliya , Vranesic Anita Cindric , Jessen Marco , Kipping Alexandra , Kim KyungMok , Cramer Paul , Eyss Björn von 
Published: August 2023

AbstractYes-associated protein (YAP) and its homologue, transcriptional coactivator with PDZ-binding motif (TAZ), are the main transcriptional downstream effector of the Hippo pathway. Decreased Hippo pathway activity leads to nuclear translocation of YAP/TAZ where they interact with TEAD transcription factors to induce target gene expression. Unrestrained YAP/TAZ activity can lead to excessive growth and tumor formation in a short time, underscoring the evolutionary need for tight control of these two transcriptional coactivators. The AP-1 complex binds together with YAP/TAZ to many common sites and they form a positive feed-forward to induce gene expression.Here, we report that the AP-1 component c-JUN acts as specific repressor of YAP/TAZ at joint target sites to decrease YAP/TAZ activity. This function of c-JUN is independent of its heterodimeric AP-1 partner c-FOS demonstrating that it is independent of the canonical AP-1 function to induce target gene expression. Since c-JUN is itself by YAP/TAZ, our work identifies a negative feedback loop that buffers YAP/TAZ activity at joint sites. This negative feedback loop needs to get disrupted in liver cancer to unlock the full oncogenic potential of YAP/TAZ.Our results thus demonstrate an additional layer of control for the important interplay of YAP/TAZ and AP-1.
Slow but flexible or fast but rigid? Discrete and continuous processes compared
Authors: Priorelli Matteo , Stoianov Ivilin Peev 
Published: August 2023

AbstractA tradeoff exists when dealing with complex tasks composed of multiple steps. High-level cognitive processes can find the best sequence of actions to achieve a goal in uncertain environments, but they are slow and require significant computational demand. In contrast, lower-level processing allows reacting to environmental stimuli rapidly, but with limited capacity to determine optimal actions or to replan when expectations are not met. Through reiteration of the same task, biological organisms find the optimal tradeoff: from action primitives, composite trajectories gradually emerge by creating task-specific neural structures. The two frameworks of active inference – a recent brain paradigm that views action and perception as subject to the samefree energy minimizationimperative – well capture high-level and low-level processes of human behavior, but how task specialization occurs in these terms is still unclear. In this study, we compare two strategies on a dynamic pick-and-place task: a hybrid (discrete-continuous) model with planning capabilities and a continuous-only model with fixed transitions. Both models rely on a hierarchical (intrinsic and extrinsic) structure, well suited for defining reaching and grasping movements, respectively. Our results show that continuous-only models perform better and with minimal resource expenditure but at the cost of less flexibility. Finally, we propose how discrete actions might lead to continuous attractors and compare the two frameworks with different motor learning phases, laying the foundations for further studies on bio-inspired task adaptation.
Inferring laminar origins of MEG signals with optically pumped magnetometers (OPMs): a simulation study
Authors: Helbling Saskia 
Published: August 2023

AbstractWe explore the potential of optically-pumped magnetometers (OPMs) to infer the laminar origins of neural activity non-invasively. OPM sensors can be positioned closer to the scalp than conventional cryogenic MEG sensors, opening an avenue to higher spatial resolution when combined with high-precision forward modelling. By simulating the forward model projection of single dipole sources onto OPM sensor arrays with varying sensor densities and measurement axes, and employing sparse source reconstruction approaches, we find that laminar inference with OPM arrays is possible at relatively low sensor counts at moderate to high signal-to-noise ratios (SNR). We observe improvements in laminar inference with increasing spatial sampling densities and number of measurement axes. Surprisingly, moving sensors closer to the scalp is less advantageous than anticipated - and even detrimental at high SNRs. Biases towards both the superficial and deep surfaces at very low SNRs and a notable bias towards the deep surface when combining empirical Bayesian beamformer (EBB) source reconstruction with a whole-brain analysis pose further challenges. Adequate SNR through appropriate trial numbers and shielding, as well as precise co-registration, is crucial for reliable laminar inference with OPMs.
Harmonic decomposition of spacetime (HADES) framework characterises the spacetime hierarchy of the DMT brain state
Authors: Vohryzek Jakub , Cabral Joana , Timmermann Christopher , Atasoy Selen , Roseman Leor , Nutt David J , Carhart-Harris Robin L , Deco Gustavo , Kringelbach Morten L 
Published: August 2023

AbstractThe human brain is a complex system, whose activity exhibits flexible and continuous reorganisation across space and time. The decomposition of whole-brain recordings into harmonic modes has revealed a repertoire of gradient-like activity patterns associated with distinct brain functions. However, the way these activity patterns are expressed over time with their changes in various brain states remains unclear. In this study, we develop the Harmonic Decomposition of Spacetime (HADES) framework that characterises how different harmonic modes defined inspaceare expressed overtime, and, as a proof-of-principle, demonstrate the sensitivity and robustness of this approach to specific changes induced by the serotonergic psychedelic N,N-Dimethyltryptamine (DMT) in healthy participants. HADES demonstrates significant decreases in contributions across most low-frequency harmonic modes in the DMT-induced brain state. When normalizing the contributions by condition (DMT and non-DMT), we detect a decrease specifically in the second functional harmonic, which represents the uni- to transmodal functional hierarchy of the brain, supporting the hypothesis that functional hierarchy is changed in psychedelics. Moreover, HADES’ dynamic spacetime measures of fractional occupancy, life time and latent space provide a precise description of the significant changes of the spacetime hierarchical organization of brain activity in the psychedelic state.
Characterisation of the butyrate production pathway in probiotic MIYAIRI588 by a combined whole genome-proteome approach
Authors: Wood Liam , Omorotionmwan Bunmi B , Blanchard Adam M , Dowle Adam , Bishop Anne L , Griffin Ruth 
Published: August 2023

AbstractButyrate is a short chain fatty acid with important industrial applications produced by chemical synthesis. With consumer demand for green products, the fermentative production of butyric acid by microorganisms such asClostridiumis attracting interest.Clostridium butyricumferments non-digested dietary fibre in the colon to produce butyrate which has multiple health benefits, and certain strains are exploited as probiotics, such as MIYAIRI588 (CBM588). Knowledge of the genes encoding enzymes involved in butyrate production and determining those that are rate-limiting due to low concentrations, could enable strain engineering for higher yields. To this end whole genome sequencing of CBM588 was performed and a circular chromosome, a megaplasmid and the previously reported cryptic plasmid, pCBM588, identified. All genes involved in the butyrate production pathway were found on the chromosome. To identify rate-limiting steps, the relative abundance of the encoded enzymes was assessed by liquid chromatography-mass spectrometry (LC-MS) of total cytosolic proteins. Phosphotransbutyrylase (Ptb) was the least abundant closely followed by butyrate kinase (Buk) and crotonase (Crt). Analysis of upstream regulatory sequences revealed the potential importance of an intact Shine-Dalgarno sequence. Results of this study can now guide bioengineering experiments to improve butyrate yields and enhance the performance of CBM588 as a probiotic.
Structural framework for the understanding spectroscopic and functional signatures of the cyanobacterial Orange Carotenoid Protein families
Authors: Sluchanko Nikolai N. , Maksimov Eugene G. , Slonimskiy Yury B. , Varfolomeeva Larisa A. , Bukhanko Antonina Y. , Egorkin Nikita A. , Tsoraev Georgy V. , Khrenova Maria G. , Ge Baosheng , Qin Song , Boyko Konstantin M. , Popov Vladimir O. 
Published: August 2023

ABSTRACTThe Orange Carotenoid Protein (OCP) is a unique photoreceptor crucial for cyanobacterial photoprotection. Best studiedSynechocystissp. PCC 6803 OCP belongs to the large OCP1 family. Downregulated by the Fluorescence Recovery Protein (FRP) in low-light, high-light-activated OCP1 binds to the phycobilisomes and performs non-photochemical quenching. Recently discovered families OCP2 and OCP3 remain structurally and functionally underexplored, and no systematic comparative studies have ever been conducted. Here we present two first crystal structures of OCP2 from morphoecophysiologically different cyanobacteria and provide their comprehensive structural, spectroscopic and functional comparison with OCP1, the recently described OCP3 and all-OCP ancestor. Structures enable correlation of spectroscopic signatures with the effective number of hydrogen and discovered herechalcogenbonds anchoring the ketocarotenoid in OCP and rationalize the observed differences in OCP/FRP and OCP/phycobilisome functional interactions. These data are expected to foster OCP research and applications in optogenetics, targeted carotenoid delivery and cyanobacterial biomass engineering.
Exploiting Substrate Specificities of 6-O-Sulfotransferases to Enzymatically Synthesize Keratan Sulfate Oligosaccharides
Authors: Wu Yunfei , Vos Gael , Huang Chin , Chapla Digantkumar , Kimpel Anne L.M. , Moremen Kelley W. , de Vries Robert P. , Boons Geert-Jan 
Published: August 2023

ABSTRACTKeratan sulfate (KS) is a glycosaminoglycan that is widely expressed in the extracellular matrix of various tissue types where it is involved in many biological processes. Herein, we describe a chemo-enzymatic approach to prepare well-defined KS oligosaccharides by exploiting known and newly discovered substrate specificities of relevant sulfotransferases. The premise of the approach is that recombinant GlcNAc-6-O-sulfotransferases (CHST2) only sulfates terminal GlcNAc moieties to give GlcNAc6S that can be galactosylated by B4GalT4. Furthermore, CHST1 can modify internal galactosides of a poly-LacNAc chain, however, it was found that a GlcNAc6S residue greatly increases the reactivity of CHST1 of a neighboring and internal galactoside. The presence of a 2,3-linked sialoside further modulates the site of modification by CHST1, and a galactoside flanked by 2,3-Neu5Ac and GlcNAc6S is preferentially sulfated over other Gal residues. The substrate specificities of CHST1 and 2 were exploited to prepare a panel of KS oligosaccharides including selectively sulfatedN-glycans. The compounds and several other reference derivatives were used to construct a microarray that was probed for binding by several plant lectins, Siglec proteins and hemagglutinins of influenza viruses. It was found that not only the sulfation pattern but also presentation of epitopes as part of anO- orN-glycan determines binding properties.