bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness and mechanisms of a multimodal treatment for low back pain: a pragmatic matched cohort study
Authors: Schäfer Robin , Niederer Daniel , Levenig Claudia , Hasenbring Monika , Tas Thomas , Fett Daniela , Trompeter Katharina , Haag Thore , Schneider Christian , Floessel Philipp , Beck Heidrun , Schiltenwolf Marcus , Wippert Pia-Maria , Engel Tilman , Mayer Frank , Platen Petra 
Published: September 2022

AbstractObjectiveTo investigate the effectiveness and mechanisms of a multimodal treatment including perturbation exercise.MethodsA matched cohort study was conducted. The intervention consists of a 12-week back pain prevention course with perturbation exercise and education embedded in primary health care according to German social law. Participants from the intervention group had chronic or recurrent low back pain with heterogenous but on average rather low pain and chronification. Control groups (usual care) were matched from a multi-center RCT. Outcomes were pain, disability, isokinetic trunk strength and balance. Bayesian regression models were used to estimate the Average Treatment effect on the Treated (ATT). Further, sub-group and mediation analyses within the intervention group using the biopsychological avoidance-endurance model were conducted. Median values with highest posterior density intervals (HPDI) from baseline-adjusted analyses are presented.ResultsOver 12 weeks, intervention and control (n = 128 each) experienced a similar decrease in pain and disability, which led to negligible ATTs for pain (−0.3 (HPDI95% [-4.3, 3.4]) and disability (−0.2 (HPDI95% [-4, 3.7])). Changes in functional parameters (n=18) showed small effects in favor of the intervention group, in particular for monopedal stances (standardized mean difference: -0.5 HPDI95% [-0.79, -0.21]). Depression was higher in drop-outs and decreases in pain/disability were associated with decreases in depression. Distress-endurance subgroups experienced higher baseline pain and disability and showed the highest reductions in both parameters upon completion of the intervention.ConclusionPerturbation exercise with education yielded only small treatment effects in a heterogenous population with rather mild symptoms. Targeting distress-endurance subgroups with a multimodal treatment approach is probably an effective strategy in treatment tailoring.
Covid-19: Qualitative Change in the Behavior of the “Virus vs Human” System - From Limit Cycle to Sustained Focus
Authors: Sokolov Alexander V. 
Published: September 2022

AnnotationThe high contagiousness of the latest strains of Covid-19 qualitatively changes the behavior of the “virus vs human” system. Numerical experiments with a model of the Covid-19 epidemic in Moscow have shown that a reproduction number R0 of about 4 is critical, defining a qualitative change in the dynamics of the epidemic. Below this value (observed until 2022), the long-term forecast tends to undamped oscillations; above this value, it is described by damped oscillations: amplitudes of the epidemic waves get smaller and smaller, with a constant, very high background level of morbidity (or high-intensity vaccination) that maintains the state of natural immunity at a level close to 100% (reaching 93.7% for the current R0 value of about 16). At the limit, the system tends to a stable equilibrium point. Here we consider a reduced model of epidemic dynamics. Its study (search for equilibrium solutions, analysis of their stability, construction a bifurcation diagram and a phase portrait) confirms the presence of points of qualitative change in the behavior of the “virus vs human” system (bifurcation points). Some practical results for Moscow are given. A further increase in the contagiousness of the virus does not change the picture significantly, thus more infectious strains are not to be feared. The key parameter of the study is the function of the immunity level depending on the time after the disease. The damping of omicron waves (oscillations), observed recently in many countries, is a confirmation of the correctness of the accepted hypotheses.
Accurate Bayesian segmentation of thalamic nuclei using diffusion MRI and an improved histological atlas
Authors: Tregidgo Henry F. J. , Soskic Sonja , Althonayan Juri , Maffei Chiara , Van Leemput Koen , Golland Polina , Yendiki Anastasia , Alexander Daniel C. , Bocchetta Martina , Rohrer Jonathan D. , Iglesias Juan Eugenio ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: September 2022

ABSTRACTThe human thalamus is a highly connected brain structure, which is key for the control of numerous functions and is involved in several neurological disorders. Recently, neuroimaging studies have increasingly focused on the volume and connectivity of the specific nuclei comprising this structure, rather than looking at the thalamus as a whole. However, accurate identification of cytoarchitectonically designed histological nuclei on standard in vivo structural MRI is hampered by the lack of image contrast that can be used to distinguish nuclei from each other and from surrounding white matter tracts. While diffusion MRI may offer such contrast, it has lower resolution and lacks some boundaries visible in structural imaging. In this work, we present a Bayesian segmentation algorithm for the thalamus. This algorithm combines prior information from a probabilistic atlas with likelihood models for both structural and diffusion MRI, allowing label boundaries to be informed by both modalities. We present an improved probabilistic atlas, incorporating 26 thalamic nuclei identified from histology and 45 white matter tracts identified in ultra-high gradient strength diffusion imaging. We present a family of likelihood models for diffusion tensor imaging, ensuring compatibility with the vast majority of neuroimaging datasets that include diffusion MRI data. The use of these diffusion likelihood models greatly improves identification of nuclei versus segmentation based solely on structural MRI. Dice comparison of 5 manually identifiable groups of nuclei to ground truth segmentations show improvements of up to 10 percentage points. Additionally, our chosen model shows a high degree of reliability, with median test-retest Dice scores above 0.85 for four out of five nuclei groups, whilst also offering improved detection of differential thalamic involvement in Alzheimer’s disease (AUROC 83.36%). The probabilistic atlas and segmentation tool will be made publicly available as part of the neuroimaging package FreeSurfer.
Simultaneous Inference of Past Demography and Selection from the Ancestral Recombination Graph under the Beta Coalescent
Authors: Korfmann Kevin , Sellinger Thibaut , Freund Fabian , Fumagalli Matteo , Tellier Aurélien 
Published: September 2022

AbstractThe reproductive mechanism of a species is a key driver of genome evolution. The standard Wright-Fisher model for the reproduction of individuals in a population assumes that each individual produces a number of offspring negligible compared to the total population size. Yet many species of plants, invertebrates, prokaryotes or fish exhibit neutrally skewed offspring distribution or strong selection events yielding few individuals to produce a number of offspring of up to the same magnitude as the population size. As a result, the genealogy of a sample is characterized by multiple individuals (more than two) coalescing simultaneously to the same common ancestor. The current methods developed to detect such multiple merger events do not account for complex demographic scenarios or recombination, and require large sample sizes. We tackle these limitations by developing two novel and different approaches to infer multiple merger events from sequence data or the ancestral recombination graph (ARG): a sequentially Markovian coalescent (SMβC) and a graph neural network (GNNcoal). We first give proof of the accuracy of our methods to estimate the multiple merger parameter and past demographic history using simulated data under theβ-coalescent model. Secondly, we show that our approaches can also recover the effect of positive selective sweeps along the genome. Finally, we are able to distinguish skewed offspring distribution from selection while simultaneously inferring the past variation of population size. Our findings stress the aptitude of neural networks to leverage information from the ARG for inference but also the urgent need for more accurate ARG inference approaches.
Beyond the metropolis: Street tree densities and resident perceptions on ecosystem services in small urban centers in India
Authors: Anujan Krishna , Velho Nandini , Kuriakose Giby , P J Ebin , Pandi Vivek , Nagendra Harini 
Published: September 2022

AbstractThe role of urban street trees has been extensively studied in large metropolises, where they contribute significantly to faunal habitat, provide critical ecosystem services to residents and contribute to human well-being. On the other hand, rapidly urbanizing cities in India have been poorly studied, despite multiple types of irreplaceable losses related to tree cover. However, being early in their urbanization history, these centers also represent opportunity for urban sustainability with potentially high remnant vegetation and human-nature connections. While megacities in developed countries move towards biophilic urban planning and participatory decision making, basic information on tree communities and their perceived services is a bottleneck in achieving these goals in such small urban centers. We assessed the street tree community and resident perceptions of ecosystem service values in Kochi and Panjim, two coastal cities in India under rapid development, through a combination of field measurements (258 transects, 931 trees) and semi-structured interviews (497 individuals). We found that mean street tree density is low in both cities, especially so in Kochi, and corresponds to perceptions of recent change in tree cover (−28% in Kochi, −11% in Panjim). The street tree community in both cities were dominated by ornamental avenue trees such as Albizia saman and Peltophorum pterocarpum, but native coastal species like Cocos nucifera, Terminalia catappa and Thespesia populnea were also common. Despite recent urban growth, residents in both cities reported low value of trees for food, fodder and medicine, but high value for regulating services like shade and water. Moreover, we found strong evidence for aesthetic and cultural values of trees in both cities, including through qualitative interviews. Our study establishes critical baselines for biophilic planning in these small urban centers towards urban sustainability.
Type 1 interferon perturbates clonal competition by reshaping human blood development
Authors: Lama Chhiring , Isakov Danielle , Rosenberg Shira , Quijada-Álamo Miguel , Saurty-Seerunghen Mirca S. , Moein Sara , Abera Tsega-Ab , Sakaguchi Olivia , Totwani Mansi , Freed Grace , Poon Chi-Lam , Parghi Neelang , Kubas-Meyer Andrea , Xie Amy X. , Omar Mohamed , Choi Daniel , Castillo-Tokumori Franco , Abu-Zeinah Ghaith , Dillard Alicia , Omans Nathaniel D. , Dusaj Neville , Chamely Paulina , Mimitou Eleni , Smibert Peter , Kosiorek Heidi E. , Dueck Amylou C. , Weinberg Rona , Chaligne Ronan , Marcellino Bridget , Marchionni Luigi , Patel Sanjay , Simonson Paul , Landau Dan A. , Wagenblast Elvin , Hoffman Ronald , Nam Anna S. 
Published: September 2022

AbstractInflammation perturbs evolutionary dynamics of hematopoietic stem cell (HSC) clones in clonal hematopoiesis and myeloid neoplasms. We studied HSCs, progenitors and immune cells from patients with myeloproliferative neoplasm (MPN) at baseline and following interferon-⍺ (IFN⍺) treatment, the only MPN therapy to deplete clonal stem cells. We focused on essential thrombocythemia, an informative model of early-phase neoplastic hematopoiesis. We integrated somatic genotyping, transcriptomes, immunophenotyping, and chromatin accessibility across single cells. IFN⍺ simultaneously activated HSCs into two polarized states, a lymphoid progenitor expansion associated with an anti-inflammatory state and an IFN⍺-specific inflammatory granulocytic progenitor (IGP) state derived directly from HSCs. The augmented lymphoid differentiation balanced the typical MPN-induced myeloid bias, associated with normalized blood counts. Clonal fitness upon IFN⍺ exposure was due to resistance of clonal stem cells to differentiate into IGPs. These results support a paradigm wherein inflammation perturbs clonal dynamics by HSC induction into the precipitous IGP differentiation program.One-Sentence SummaryInflammation accelerates clonal evolution by driving stem cell differentiation into an alternate interferon-⍺-induced progenitor state.
A global view of aging and Alzheimer’s pathogenesis-associated cell population dynamics and molecular signatures in the human and mouse brains
Authors: Sziraki Andras , Lu Ziyu , Lee Jasper , Banyai Gabor , Anderson Sonya , Abdulraouf Abdulraouf , Metzner Eli , Liao Andrew , Banfelder Jason , Epstein Alexander , Schaefer Chloe , Xu Zihan , Zhang Zehao , Gan Li , Nelson Peter T. , Zhou Wei , Cao Junyue 
Published: September 2022

SummaryConventional single-cell genomics approaches are limited by throughput and thus may have failed to capture aspects of the molecular signatures and dynamics of rare cell types associated with aging and diseases. Here, we developedEasySci, an extensively improved single-cell combinatorial indexing strategy, for investigating the age-dependent dynamics of transcription and chromatin accessibility across diverse brain cell types. We profiled ∼1.5 million single-cell transcriptomes and ∼400,000 single-cell chromatin accessibility profiles across mouse brains spanning different ages, genotypes, and both sexes. With a novel computational framework designed for characterizing cellular subtypes based on the expression of both genes and exons, we identified > 300 cell subtypes and deciphered their underlying molecular programs and spatial locations especially for rare cell types (e.g.,pinealocytes, tanycytes). Leveraging these data, we generated a global readout of age-dependent changes at cell subtype resolution, providing insights into cell types that expand (e.g.,rare astrocytes and vascular leptomeningeal cells in the olfactory bulb, reactive microglia, and oligodendrocytes) or are depleted (e.g.,neuronal progenitors, neuroblasts, committed oligodendrocyte precursors) as age progresses. Furthermore, we explored cell-type-specific responses to genetic perturbations associated with Alzheimer’s disease (AD) and identified rare cell types depleted (e.g., mt-Cytb+, mt-Rnr2+ choroid plexus epithelial cells) or enriched (e.g., Col25a1+,Ndrg1+ interbrain and midbrain neurons) in both AD models. Key findings are consistent between males and females, validated across the transcriptome, chromatin accessibility, and spatial analyses. Finally, we profiled a total of 118,240 single-nuclei transcriptomes from twenty-four post-mortem human brain samples derived from control and AD patients, revealing highly cell-type-specific and region-specific gene expression changes associated with AD pathogenesis. Critical AD-associated gene signatures were validated in both human and mice. In summary, these data comprise a rich resource for exploring cell-type-specific dynamics and the underlying molecular mechanisms in normal and pathological mammalian aging.
Selection and adaptive introgression guided the complex evolutionary history of the European common bean
Authors: Bellucci Elisa , Benazzo Andrea , Xu Chunming , Bitocchi Elena , Rodriguez Monica , Alseekh Saleh , Vittori Valerio Di , Gioia Tania , Neumann Kerstin , Cortinovis Gaia , Frascarelli Giulia , Murube Ester , Trucchi Emiliano , Nanni Laura , Ariani Andrea , Logozzo Giuseppina , Shin Jin Hee , Liu Chaochih , Jiang Liang , Ferreira Juan José , Campa Ana , Attene Giovanna , Morrell Peter Laurent , Bertorelle Giorgio , Graner Andreas , Gepts Paul , Fernie Alisdair Robert , Jackson Scott Allen , Papa Roberto 
Published: September 2022

AbstractDomesticated crops have been disseminated by humans over vast geographic areas. After 1492, the common bean (Phaseolus vulgarisL.) was introduced in Europe. Here, we combine whole-genome profiling, metabolic fingerprinting and phenotypic characterisation, and we show that the first common bean cultigens successfully introduced into Europe were of Andean origin, after Francisco Pizarro’s expedition to northern Peru in 1529. We show that hybridisation, selection and recombination have shaped the genomic diversity of the European common bean in parallel with political constraints. There is clear evidence of adaptive introgression into the Mesoamerican-derived European genotypes, with 44 Andean introgressed genomic segments shared by more than 90% of European accessions and distributed across all chromosomes except PvChr11. Genomic scans for signatures of selection highlight the role of genes relevant to flowering and environmental adaptation, suggesting that introgression has been crucial for the dissemination of this tropical crop to the temperate regions of Europe.
Mass spectrometry of RNA-binding proteins during liquid-liquid phase separation reveals distinct assembly mechanisms and droplet architectures
Authors: Sahin Cagla , Motso Aikaterini , Gu Xinyu , Feyrer Hannes , Lama Dilraj , Arndt Tina , Rising Anna , Gese Genis Valentin , Hällberg Martin , Marklund Erik. G. , Schafer Nicholas P. , Petzold Katja , Teilum Kaare , Wolynes Peter G. , Landreh Michael 
Published: September 2022

AbstractPhase separation of heterogeneous ribonucleoproteins (hRNPs) drives the formation of membraneless organelles, but structural information about their assembled states is still lacking. Here, we address this challenge through a combination of protein engineering, native ion mobility-mass spectrometry, and molecular dynamics simulations. We used a phase separation-compatible spider silk domain and pH changes to control the self-assembly of the hRNPs FUS, TDP-43, and hCPEB3, which are implicated in neurodegeneration, cancer, and memory storage. By releasing the proteins inside the mass spectrometer from their native assemblies, we could monitor conformational changes associated with phase separation. We find that NT*-FUS monomers undergo an unfolded-to-globular transition, whereas NT*-TDP-43 oligomerizes into partially disordered dimers and trimers. NT*-hCPEB3, on the other hand, remains fully disordered with a preference for fibrillar aggregation over phase separation. The divergent assembly mechanisms result in structurally distinct complexes, indicating differences in RNA processing and translation depending on biological context.
The small-bat-in-summer paradigm: energetics and adaptive behavioural routines of bats investigated through a stochastic dynamic model
Authors: Fjelldal Mari Aas , Muller Amandine Sophie , Ratikainen Irja Ida , Stawski Clare , Wright Jonathan 
Published: September 2022

AbstractStrong seasonality at high latitudes represents a major challenge for many endotherms as they must balance survival and reproduction in an environment that varies widely in food availability and temperature. Being heterotherms, bats spend long cold winters in hibernation, avoiding the challenges faced by many animals. To avoid energetic mismatches caused by limited foraging time and stochastic weather conditions, bats can also employ this energy-saving state of torpor during summer to save accumulated energy reserves. However, at high latitudes small-bats-in-summer face a particular challenge: as nocturnal foragers they rely on the darkness of the night to avoid predators and/or interspecific competition, but for many the summer involves short nights of mostly twilight, and even a lack of true night at the northernmost distributions of some bat species. To investigate optimal individual behaviour across diurnal cycles, we constructed a stochastic dynamic model of bats living at high latitudes. Using a detailed parameterized model framework with values that are representative for our study system, we show that individual energetic reserves are a strong driver of day-time use of torpor and night-time foraging behaviour alike, with these linked effects being both temperature and photoperiod dependent. We further used the model framework to predict survival probabilities at five locations across a latitudinal gradient (60.1°N to 70.9°N), finding that photoperiod is the main limiting factor to bat species distributions. To verify the accuracy of our model results, we compared predictions for optimal decisions with our own empirical data collected on northern bats (Eptesicus nilssonii) from two latitudes in Norway. The similarities between our predictions and observations provide strong confirmation that this model framework incorporates the most important drivers of diurnal decision-making in bat physiology and behaviour. Our model findings regarding state-dependent decisions in bats should therefore contribute to the understanding of how bats cope with the summer challenges at high latitudes.
Significantly amplified photoacoustic effect for silica-coated gold nanoparticles by interface heat transfer mechanisms
Authors: Youn Jonghae , Kang Peiyuan , Wilson Blake A. , Xie Chen , Basavarajappa Lokesh , Wang Qingxiao , Kim Moon , Hoyt Kenneth , Qin Zhenpeng 
Published: September 2022

ABSTRACTPlasmonic gold nanoparticles (AuNPs) are effective photoacoustic (PA) signal agents and have found important biomedical applications. The silica coating on the surface of AuNPs showed enhanced PA efficiency, however, the PA amplification mechanism remains unclear. Here, we systematically studied the silica coating effect on PA generation of AuNPs under different laser pulse durations. We experimentally demonstrated up to 4-fold PA amplification under thin silica coating (<5 nm) and a picosecond laser excitation. The theoretical model further suggests that the PA amplification originates from two interface heat transfer mechanisms including 1) the enhanced interface thermal conductance on the silica-water interface and 2) the electron-phonon energy transfer channel on the gold/silica interface. This study discovers a regime of large PA amplification and provides a new rationale for plasmonic nanoparticle design to achieve better PA efficiency.
Multi-modal digital pathology for colorectal cancer diagnosis by high-plex immunofluorescence imaging and traditional histology of the same tissue section
Authors: Lin Jia-Ren , Chen Yu-An , Campton Daniel , Cooper Jeremy , Coy Shannon , Yapp Clarence , Tefft Juliann B. , McCarty Erin , Ligon Keith L. , Rodig Scott J. , Reese Steven , George Tad , Santagata Sandro , Sorger Peter K. 
Published: September 2022

ABSTRACTPrecision medicine is critically dependent on better methods for diagnosing and staging disease and predicting drug response. Histopathology using Hematoxylin and Eosin (H&E) stained tissue - not genomics – remains the primary diagnostic method in cancer. Recently developed highly-multiplexed tissue imaging methods promise to enhance research studies and clinical practice with precise, spatially-resolved, single-cell data. Here we describe the “Orion” platform for collecting and analyzing H&E and high-plex immunofluorescence (IF) images from the same cells in a whole-slide format suitable for diagnosis. Using a retrospective cohort of 74 colorectal cancer resections, we show that IF and H&E images provide human experts and machine learning algorithms with complementary information that can be used to generate interpretable, multiplexed image-based models predictive of progression-free survival. Combining models of immune infiltration and tumor-intrinsic features achieves a hazard ratio of ∼0.05, demonstrating the ability of multi-modal Orion imaging to generate high-performance biomarkers.