Miracle-dz/UniFAR-FTUs huggingface dataset:
Gait asymmetry in spatiotemporal and kinetic variables does not increase running-related injury risk in lower limbs: a secondary analysis of a randomised trial including 800+ recreational runners

Objective To investigate asymmetry in spatiotemporal and kinetic variables in 800+ recreational runners, identify determinants of asymmetry, investigate if asymmetry is related to greater running injury risk and compare spatiotemporal and kinetic variables between the involved and uninvolved limb at baseline in runners having sustained an injury during follow-up. Methods 836 healthy recreational runners (38.6% women) were tested on an instrumented treadmill at their preferred running speed at baseline and followed up for 6 months. From ground reaction force recordings, spatiotemporal and kinetic variables were derived for each lower limb. The Symmetry Index was computed for each variable. Correlations and multiple regression analyses were performed to identify potential determinants of asymmetry. Cox regression analyses investigated the association between asymmetry and injury risk. Analysis of variance for repeated measures was used to compare the involved and uninvolved limbs in runners who had sustained injuries during follow-up. Results 107 participants reported at least one running-related injury. Leg length discrepancy and fat mass were the most common determinants of asymmetry, but all correlation coefficients were negligible (0.01–0.13) and explained variance was very low (multivariable-adjusted R2<0.01–0.03). Greater asymmetry for flight time and peak breaking force was associated with lower injury risk (HR (95% CI): 0.80 (0.64 to 0.99) and 0.96 (0.93 to 0.98), respectively). No between-limb differences were observed in runners having sustained an injury. Conclusion Gait asymmetry was not associated with higher injury risk for investigated spatiotemporal and kinetic variables. Trial registration number NCT03115437.
Implementation of integrated maternity care in the southwestern region of the Netherlands: evaluation of its effect on preterm birth, low birthweight infants and number of secondary care consultations

Objectives To determine whether integrated maternity care is associated with reduced preterm births (PTB) and fewer small-for-gestational-age infants (SGA), and whether its implementation leads to a reduction of secondary care consultations. Design Retrospective study. Setting Integrated maternity care organisation in the southwestern region of the Netherlands. Participants All singleton pregnancies (≥24 weeks) within integrated maternity care organisation Annature between 2015 and 2020. Intervention Implementation of a shared maternity record in primary and secondary care. Methods Data of 20 818 women were derived from patient records and from the Netherlands Perinatal Registry. Intervention was the introduction of integrated maternity care in January 2018. Through multivariate logistic regression and segmented regression analysis we assessed the combined prevalence of SGA and PTB (SGA-PTB) before (2015–2017), and after the intervention (2018–2020). Regional rates were contrasted with nationwide rates (n=782 176). Main outcome measures SGA-PTB prevalence and mean number of secondary care consultations per pregnancy. Results SGA-PTB prevalence declined from 618/3443 (17.9%) in 2015 to 560/3501 (16.0%) in 2017 to 507/3459 (14.7%) in 2020 (p<0.005). Mean number of secondary care consultations declined from six per pregnancy in 2015 to three in 2020. Logistic regression demonstrated a significant decline in odds of SGA-PTB (OR 0.83 (95% CI 0.77 to 0.89)) between 2015–2017 and 2018–2020 adjusted for changes in sociodemographic characteristics over time. A statistically significant average monthly 7.3% (p=0.05) reduction in SGA-PTB prevalence and 12.4% (p<0.005) mean monthly reduction in secondary care consultations were demonstrated for 2015–2017. Immediately after the intervention, mean monthly prevalence of SGA-PTB dropped non-significantly to 14.7%. Between 2018 and 2020 a significant 15.2% (p<0.005) reduction in secondary care consultations was shown. Conclusion Our results suggest that implementation of integrated maternity care was associated with reduced PTBs and/or low birth weight, and fewer secondary care consultations. These encouraging findings were observed in a less favourable sociodemographic profile and should be confirmed in other regions with sufficiently large populations, and the possibility to test individual components of integrated maternity care.
Methylome-wide association studies of traumatic injury identifies differential DNA methylation of synaptic plasticity and GABAergic-signalling

Traumatic physical injury is often associated with psychological trauma and is a risk factor for major depressive disorder (MDD). In Generation Scotland traumatic injury was significantly associated with recurrent major depression (OR = 2.10, 95% CI 1.33-3.33, PLJ=LJ0.0016). and schizotypal symptoms, particularly disorganised thought (βLJ=LJ0.111, 95% CI 0.049-0.177, PLJ=LJ0.0004). We performed methylome-wide analyses of traumatic injury in individuals with MDD and controls separately to investigate the link between traumatic injury and MDD. Nominally significant differences in differential DNA methylation between MDD and control groups were identified at 40 003 CpG sites (p < 0.05). Individuals with recurrent MDD showed significantly higher levels of DNA methylation associated with traumatic injury at CpG sites at the first exon and lower levels at exon boundaries, this was significant different to the association pattern at these sites in controls (mean difference in M-value = 0.0083, P = 21.1×10-10, and -0.0125, P = 2.1×10-174, respectively). Analyses at the level of CpG site, genes and gene ontologies implicated dysregulation of processes related to synaptic plasticity, including dendrite development, excitatory synapse and GABAergic signalling (normalised enrichment values > 2, FDR q-values < 0.01). Enrichment analyses for regional brain-expression in the recurrent MDD group highlight the limbic lobe and supraoptic nuclei (recurrent MDD FWER = 0.028 and 0.034, respectively). These results suggest that traumatic injury is associated with patterns of DNA methylation differentially in individuals with MDD compared to controls, highlighting the need for novel analysis approaches.
Local delivery of cell surface-targeted immunocytokines programs systemic anti-tumor immunity

Cytokine therapies are potent immunotherapy agents but exhibit severe dose-limiting toxicities. One strategy to overcome this involves engineering cytokines for intratumoral retention following local delivery. Here, we develop a localized cytokine therapy that elicits profound anti-tumor immunity by engineered targeting to the ubiquitous leukocyte receptor CD45. We designed CD45-targeted immunocytokines (αCD45-Cyt) that, upon injection, decorated the surface of leukocytes in the tumor and tumor-draining lymph node (TDLN) without systemic exposure. αCD45-Cyt therapy eradicated both directly treated tumors and untreated distal lesions in multiple syngeneic mouse tumor models. Mechanistically, αCD45-Cyt triggered prolonged pSTAT signaling and reprogrammed tumor-specific CD8+ T cells in the TDLN to exhibit an anti-viral transcriptional signature. CD45 anchoring represents a broad platform for protein retention by host immune cells for use in immunotherapy.
Generative whole-brain dynamics models from healthy subjects predict functional alterations in stroke at the level of individual patients

Computational whole-brain models describe the resting activity of each brain region based on a local model, inter-regional functional interactions, and a structural connectome that specifies the strength of inter-regional connections. Strokes damage the healthy structural connectome that forms the backbone of these models and produce large alterations in inter-regional functional interactions. These interactions are typically measured by correlating the timeseries of activity between two brain regions, so-called resting functional connectivity. We show that adding information about the structural disconnections produced by a patient’s lesion to a whole-brain model previously trained on structural and functional data from a large cohort of healthy subjects predicts the resting functional connectivity of the patient about as well as fitting the model directly to the patient’s data. Furthermore, the model dynamics reproduce functional connectivity-based measures that are typically abnormal in stroke patients as well as measures that specifically isolate these abnormalities. Therefore, although whole-brain models typically involve a large number of free parameters, the results show that even after fixing those parameters, the model reproduces results from a population very different than the population on which the model was trained. In addition to validating the model, these results show that the model mechanistically captures relationships between the anatomical structure and functional activity of the human brain.
Biofilm formation and maize root-colonization of seed-endophytic Bacilli isolated from native maize landraces

Agricultural microbiology seeks to replace the use of agrochemicals with microbe-based products. Plant growth-promoting bacteria (PGPB) are often selected based on their functions in vitro, and then, their effect on plant development is tested. However, this approach neglects the study of their survival in soil, root-colonization, and the monitoring of beneficial functions in the rhizosphere. This could explain the recurrent lack of success in the transition from lab tests to field applications of natural isolates from novel habitats. In our recent studies, we found that native maize seeds from traditional agroecosystems carry endophytic bacterial communities that are dominated by members of the class Bacilli. As an approach to grasp their PGP potential, we developed protocols to test maize root-colonization of these natural isolates in 1) a short-term hydroponics assay in vitro and 2) a long-term assay in non-sterile soil pots. Our results show that in vitro biofilm formation was only partially associated to short-term colonization in vitro; furthermore, long-term root-colonization in soil pots was not correlated to the in vitro assays. This work highlights the necessity to incorporate root-colonization assays as part of the research strategies in the search for PGPB natural isolates from unexplored habitats, towards the generation of inoculants with increased success in the field.
Editing of endogenous tubulins reveals varying effects of tubulin posttranslational modifications on axonal growth and regeneration

Tubulin posttranslational modifications (PTMs) modulate the dynamic properties of microtubules and their interactions with other proteins. However, the effects of tubulin PTMs were often revealed indirectly through the deletion of modifying enzymes or the overexpression of tubulin mutants. In this study, we directly edited the endogenous tubulin loci to install PTM-mimicking or-disabling mutations and studied their effects on microtubule stability, neurite outgrowth, axonal regeneration, cargo transport, and sensory functions in the touch receptor neurons of Caenorhabditis elegans. We found that the status of β-tubulin S172 phosphorylation and K252 acetylation strongly affected microtubule dynamics, neurite growth, and regeneration, whereas α-tubulin K40 acetylation had little influence. Polyglutamylation and detyrosination in the tubulin C-terminal tail had more subtle effects on microtubule stability likely by modulating the interaction with kinesin-13. Overall, our study systematically assessed and compared several tubulin PTMs for their impacts on neuronal differentiation and regeneration and established an in vivo platform to test the function of tubulin PTMs in neurons.
Spatiotemporal models for multisensory integration

Multisensory integration is a process of redundancy exploitation, in which our brains combine information across the senses to obtain more reliable perceptual estimates. While the high-level computational principles of multisensory integration are well understood, little is knowns as to how the low-level properties of the signals ultimately determine the integrated percept. This study demonstrates that a bottom-up approach, based on luminance- and sound-level analyses, is sufficient to jointly explain the spatiotemporal determinants of audiovisual integration and crossmodal attention. When implemented using an architecture analogous to the motion detectors found in the insect brain, such low-level analyses can broadly reproduce human behaviour–as tested in a large-scale simulation of 42 classic experiments on the spatial, temporal and attentional aspects of multisensory integration.
Tracing India’s Canine Heritage through SNP-Based Haplotype Identification

Dog breeds/germplasm in India is mostly unexplored and the population structure of owned dogs has not been studied at all. The current study was designed to determine the haplotypes and explore the population structure among divergent breeds of dogs using genome-wide distributed SNPs, followed by validation of selected haplotypes through PCR-sequencing. The research employed custom ddRAD-GBS sequencing carried out using Illumina 150bp paired-end sequencing of 50 dog samples generated 2,18,433 high-quality SNPs meeting the screening criteria. The data was further analyzed for population structure assessment and haplotype identification using bash, and R-environment. Subsequently, three haplotypes (on AFAP1, CELSR1, and GBGT1 genes) were selected (based on SNP density and haplotype length) for validation via PCR followed by paired-end Sanger sequencing in seven different dog breeds (n=21). The results revealed notable connections between dog breeds from Punjab and Haryana, while the affiliation with Karnataka was found to be less pronounced. The sequencing results indicated that CELSR1 and GBGT1 genes contained SNPs, with the AFAP1 gene lacking SNPs. The results also provided insights into the molecular-level population structure, SNPs, and haplotypes of diverse dog breeds reared in India. This SNP variation could be used for molecular characterization of indigenous dogs.
Ancestral Sequence Reconstruction as a tool to detect and study de novo gene emergence

New protein-coding genes can evolve from previously non-coding genomic regions through a process known as de novo gene emergence. Evidence suggests that this process has likely occurred throughout evolution and across the tree of life. Yet, confidently identifying de novo emerged genes remains challenging. Ancestral Sequence Reconstruction (ASR) is a promising approach for inferring whether a gene has emerged de novo or not, as it can enable us to inspect whether a given genomic locus ancestrally harbored protein-coding capacity. However, the use of ASR in the context of de novo emergence is still in its infancy and its capabilities, limitations, and overall potential are largely unknown. Notably, it is difficult to formally evaluate the protein-coding capacity of ancestral sequences, particularly when new gene candidates are short. How well-suited is ASR as a tool for the detection and study of de novo genes? Here, we address this question by designing an ASR workflow incorporating different tools and sets of parameters and by introducing a formal criterion that allows to estimate, within a desired level of confidence, when protein-coding capacity originated at a particular locus. Applying this workflow on ∼2,600 short, annotated budding yeast genes (<1,000 nucleotides), we found that ASR robustly predicts an ancient origin for most widely conserved genes, which constitute “easy” cases. For less robust cases, we calculated a randomization-based empirical P-value estimating whether the observed conservation between the extant and ancestral reading frame could be attributed to chance. This formal criterion allowed us to pinpoint a branch of origin for most of the less robust cases, identifying 33 genes that can unequivocally be considered de novo originated since the split of the Saccharomyces genus, including 20 S. cerevisiae-specific genes. We find that the remaining, equivocal cases, may be explained by different evolutionary scenarios including rapid evolution and multiple losses, as well as a very recent de novo origin. Overall, our findings suggest that ASR is a valuable tool to study de novo gene emergence but should be applied with caution and awareness of its limitations.
A Genome-Wide CRISPR Screen Identifies Sortilin as the Receptor Responsible for Galectin-1 Lysosomal Trafficking

Galectins are a family of mammalian glycan-binding proteins that have been implicated as regulators of myriad cellular processes including cell migration, apoptosis, and immune modulation. Several members of this family, such as galectin-1, exhibit both cell-surface and intracellular functions. Interestingly, galectin-1 can be found in the endomembrane system, nucleus, or cytosol, as well as on the cell surface. The mechanisms by which galectin-1 traffics between cellular compartments, including its unconventional secretion and internalization processes, are poorly understood. Here, we determined the pathways by which exogenous galectin-1 enters cells and explored its capacity as a delivery vehicle for protein and siRNA therapeutics. We used a galectin-1-toxin conjugate, modelled on antibody-drug conjugates, as a selection tool in a genome-wide CRISPR screen. We discovered that galectin-1 interacts with the endosome-lysosome trafficking receptor sortilin in a glycan-dependent manner, which regulates galectin-1 trafficking to the lysosome. Further, we show that this pathway can be exploited for delivery of a functional siRNA. This study sheds light on the mechanisms by which galectin-1 is internalized by cells and suggests a new strategy for intracellular drug delivery via galectin-1 conjugation.
Ultrasound-guided puncture drainage versus surgical incision drainage for deep neck space abscesses: a protocol for a systematic review with meta-analysis and trial sequential analysis

Introduction Deep neck space abscesses (DNAs) are serious surgical emergencies, associated with life-threatening complications. Surgical incision and drainage combined with antibiotics is the main treatment for DNAs, but drawbacks still exist. Ultrasound-guided puncture drainage is an alternative treatment for some DNAs with limited clinical evidence. Hence, the optimal drainage technique for the treatment of DNAs remains unclear. Therefore, we will perform a protocol for a systematic review and meta-analysis to identify the efficacy of ultrasound-guided puncture drainage for DNAs. Methods and analysis PubMed, Ovid Medline, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang database, VIP database and trial registry databases will be searched from inception to September 2023 to identify randomised controlled trials of patients diagnosed with DNAs accepting ultrasound-guided puncture drainage. The primary outcome will be the length of hospital stay. The secondary outcomes will be the cure rate, incidence of retreatment, complications and overall cost to the healthcare system. Fixed-effects or random-effects model will be used according to the statistical heterogeneity. Mean differences or standardised mean differences with 95% CIs for continuous data and risk ratio (RR) with 95% CIs for dichotomous data. The Cochrane risk-of-bias tool 2, Grading of Recommendations Assessment, Development and Evaluation (GRADE) and trial sequential analysis will be conducted to evaluate the evidence quality and control the random errors. Funnel plots and Egger’s regression test will be performed to evaluate publication bias. Ethics and dissemination Ethical approval was not required for this systematic review protocol. The results will be disseminated through peer-reviewed publications. PROSPERO registration number CRD42023441031.
Holographic aspects of quantum information theory and condensed matter theory

Holography is an umbrella term covering conjectures relating strongly coupled quantum field theories and classical gravity theories. While originally intended to provide information about quantum gravity and string theories, the AdS/CFT correspondence has been applied to study many difficult problems in quantum field theories by considering suitable gravity duals. There are many long-standing problems in theoretical physics that have been hard to tackle. These include the confining nature of QCD and gluons, and the strange behaviour of some phases of high-temperature superconductors. These problems are not expected to have a valid quasiparticle description so a new paradigm might be needed to study these systems. A strong coupling approach via holography might be able to provide insight into these problems. Another new paradigm is provided by quantum information theory. Entanglement is important not only in quantum computing but also in describing fundamental properties of quantum field theories and states of systems. Our tools of choice are Rényi entropy, entanglement entropy and capacity of entanglement. This thesis provides a brief introduction to the methods of holography. We introduce important quantum information concepts and relate these to holographic quantities. We also provide evidence, why new physics is needed in condensed matter theory and provide two holographic approaches, the Einstein-Maxwell dilaton theory and the probe brane approximation. The latter saw extensive use in our research.
Optimal Spectrum Sensing Policy in RF-Powered Cognitive Radio Networks

An orthogonal frequency division multiple access-based primary user (PU) network is considered, which provides different spectral access/energy harvesting opportunities in RF-powered cognitive radio networks. In this scenario, we propose an optimal spectrum sensing policy for opportunistic spectrum access/energy harvesting under both the PU collision and energy causality constraints. PU subchannels can have different traffic patterns and exhibit distinct idle/busy frequencies, due to which the spectral access/energy harvesting opportunities are application specific. Secondary user (SU) collects traffic pattern information through observation of the PU subchannels and classifies the idle/busy period statistics for each subchannel. Based on the statistics, we invoke stochastic models for evaluating SU capacity by which the energy detection threshold for spectrum sensing can be adjusted with higher sensing accuracy. To this end, we employ the Markov decision process model obtained by quantizing the amount of SU battery and the duty cycle model obtained by the ratio of average harvested energy and energy consumption rates. We demonstrate the effectiveness of the proposed stochastic models through comparison with the optimal one obtained from an exhaustive method.
Factors Associated with Evacuation from Hurricane Isabel in North Carolina, 2003

Important differences in evacuation exist across households. This study describes associations between social factors and evacuation from Hurricane Isabel by residents of North Carolina in 2003. Census blocks in three affected counties were stratified by flood zone and 30 census blocks were selected probability proportionate to population size from each flood zone. Within selected blocks, 7 random interview locations were chosen using a geographic information systems-based site selection tool. Risk differences and 95% confidence intervals for evacuation were calculated. High levels of neighborhood social cohesion, markers of territoriality (e.g., no trespassing signs), membership in church or civic organization, volunteerism, neighbors’ evacuation, and longer length of residence were associated with reduced hurricane evacuation. Differential levels of social capital, social cohesion, and related social factors contributed to differential rates of evacuation from Hurricane Isabel. Those who reported closer relationships with neighbors and were active volunteers in the community may be more susceptible to evacuation failure and should receive targeted messages regarding evacuation from officials.