bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-perceived middle-distance race pace is faster in Advanced Footwear Technology spikes
Authors: Bertschy Montgomery , Rodrigo-Carranza Victor , Wilkie Ethan W.C. , Healey Laura A. , Noble Jeremy , Albert Wayne J. , Hoogkamer Wouter 
Published: October 2023

AbstractBackgroundQuantifying the potential benefits of advanced footwear technology (AFT) track shoes (i.e., “spikes”) in middle-distance events is challenging, because repeated maximal effort trials (as in sprinting) or aerobic running economy trials (as in long-distance running) are not feasible.MethodsWe introduce a novel approach to assess the benefits of AFT spikes, consisting of a series of 200 m runs at self-perceived middle-distance race pace with 10 min recovery and conducted four experiments to evaluate its validity, sensitivity, reproducibility, and utility.ResultsIn experiment 1, participants ran 1.2% slower in spikes with 200 g added mass vs. control spikes, exactly equal to the known effects of shoe mass on running performance. In experiment 2, participants ran significantly faster in AFT prototype spikes vs. traditional spikes. In experiment 3, we compared two other AFT prototype spikes against traditional spikes, on three separate days. Group-level results were consistent across days, but our data indicates that at least two separate sessions are needed to evaluate individual responses. In experiment 4, participants ran significantly faster in two AFT spike models vs. traditional spikes (2.1% and 1.6%). Speed was similar between a third AFT spike model and the traditional spikes. These speed results were mirrored by changes in step length, as participants took significantly longer steps in the two faster AFT spike models (2.3% and 1.9%), while step length was similar between the other spikes.ConclusionOur novel, interval-based approach is a valid and reliable method to quantify differences between spikes at middle-distance running intensity.
Self-Supervised Learning Improves Accuracy and Data Efficiency for IMU-Based Ground Reaction Force Estimation
Authors: Tan Tian , Shull Peter B. , Hicks Jenifer L. , Uhlrich Scott D. , Chaudhari Akshay S. 
Published: October 2023

AbstractObjectiveRecent deep learning techniques hold promise to enable IMU-driven kinetic assessment; however, they require large extents of ground reaction force (GRF) data to serve as labels for supervised model training. We thus propose using existing self-supervised learning (SSL) techniques to leverage large IMU datasets to pre-train deep learning models, which can improve the accuracy and data efficiency of IMU-based GRF estimation.MethodsWe performed SSL by masking a random portion of the input IMU data and training a transformer model to reconstruct the masked portion. We systematically compared a series of masking ratios across three pre-training datasets that included real IMU data, synthetic IMU data, or a combination of the two. Finally, we built models that used pre-training and labeled data to estimate GRF during three prediction tasks: overground walking, treadmill walking, and drop landing.ResultsWhen using the same amount of labeled data, SSL pre-training significantly improved the accuracy of 3-axis GRF estimation during walking compared to baseline models trained by conventional supervised learning. Fine-tuning SSL model with 1–10% of walking data yielded comparable accuracy to training baseline model with 100% of walking data. The optimal masking ratio for SSL is 6.25–12.5%.ConclusionSSL leveraged large real and synthetic IMU datasets to increase the accuracy and data efficiency of deep-learning-based GRF estimation, reducing the need for labeled data.SignificanceThis work, with its open-source code and models, may unlock broader use cases of IMU-driven kinetic assessment by mitigating the scarcity of GRF measurements in practical applications.
Enhancing Hi-C contact matrices for loop detection with Capricorn, a multi-view diffusion model
Authors: Fang Tangqi , Liu Yifeng , Woicik Addie , Lu Minsi , Jha Anupama , Wang Xiao , Li Gang , Hristov Borislav , Liu Zixuan , Xu Hanwen , Noble William S. , Wang Sheng 
Published: October 2023

AbstractHigh-resolution Hi-C contact matrices reveal the detailed three-dimensional architecture of the genome, but high-coverage experimental Hi-C data are expensive to generate. On the other hand, chromatin structure analyses struggle with extremely sparse contact matrices. To address this problem, computational methods to enhance low-coverage contact matrices have been developed, but existing methods are largely based on resolution enhancement methods for natural images and hence often employ models that do not distinguish between biologically meaningful contacts, such as loops, and other stochastic contacts. We present Capricorn, a machine learning model for Hi-C resolution enhancement that incorporates small-scale chromatin features as additional views of the input Hi-C contact matrix and leverages a diffusion probability model backbone to generate a high-coverage matrix. We show that Capricorn outperforms the state of the art in a cross-cell-line setting, improving on existing methods by 17.8% in mean squared error and 22.9% in F1 score for chromatin loop identification from the generated high-coverage data. We also demonstrate that Capricorn performs well in the cross-chromosome setting and cross-chromosome, cross-cell-line setting, improving the downstream loop F1 score by 15.7% relative to existing methods. We further show that our multi-view idea can also be used to improve several existing methods, Hi-CARN and HiCNN, indicating the wide applicability of this approach. Finally, we use DNA sequence to validate discovered loops and find that the fraction of CTCF-supported loops from Capricorn is similar to those identified from the high-coverage data. Capricorn is a powerful Hi-C resolution enhancement method that enables scientists to find chromatin features that cannot be identified in the low-coverage contact matrix. Implementation of Capricorn and source code for reproducing all figures in this paper are available athttps://github.com/CHNFTQ/Capricorn.
Back to sequences: find the origin ofk-mers
Authors: Baire Anthony , Peterlongo Pierre 
Published: October 2023

AbstractA vast majority of bioinformatics tools dedicated to the treatment of raw sequencing data heavily use the concept ofk-mers. This enables us to reduce the data redundancy (and thus the memory pressure), to discard sequencing errors, and to dispose of objects of fixed size that can be manipulated and easily compared to each others. A drawback is that the link between eachk-mer and the original set of sequences it belongs to is generally lost. Given the volume of data considered in this context, finding back this association is costly. In this work, we present “back_to_sequences”, a simple tool designed to index a set ofk-mers of interests, and to stream a set of sequences, extracting those containing at least one of the indexedk-mer. In addition, the number of occurrences ofk-mers in the sequences is provided. Our results show thatback_to_sequencesstreams≈200 short read per millisecond, enabling to searchk-mers in hundreds of millions of reads in a matter of a few minutes.Availabilitygithub.com/pierrepeterlongo/back_to_sequences
Changing variability is an overlooked aspect of protected area planning
Authors: Marcus Rekha , Noonan Michael J. 
Published: October 2023

AbstractProtected areas are widely used management tools designed to support the long-term conservation of biodiversity. The effectiveness of protected areas is being challenged by human-induced climate change, however, which is causing three broad shifts away from the current distribution of climate trends: a change in mean conditions, a change in the variance around the mean, and/or a change in symmetry. Though changes in average conditions are certainly important, the second behaviour, a change in variance, brings a unique set of challenges that species must respond to. As conditions become more variable, phenological events become less predictable, extreme weather events become more frequent, food security and ecosystem stability are compromised, and extinction risk increases. It therefore stands to reason that changes in the variance of local conditions should be a core consideration when designing protected areas.Here, we reviewed the literature to determine the extent to which changes in variance are being incorporated into protected area planning. Worryingly, we found that fewer than a quarter of the 100 studies we surveyed formally considered how climate change might change mean conditions, and only four considered climate change-induced changes in the variance around the mean. Our evaluation reveals an alarming gap in protected area research. The majority of researchers continue to make recommendations for protected areas without acknowledging that the area(s) they are recommending for protection may have markedly different conditions in the future. Whether variability is considered or not, stochastic events represent a serious threat to the persistence of species and complex ecosystems. Effective conservation requires actively considering how the stability of conditions within protected areas will be impacted by future climate change. As global climate patterns tend towards increasing unpredictability, protecting less variable habitat should be a priority to ensure local populations are not exposed to elevated extinction risk.
Rhodococcus equiEscapes Macrophage Autophagy: VapA Inhibits ATP6V0d1-Mediated Lysosomal Degradation
Authors: Luo Haixia , Feng Tingting , Xu Zhaokun 
Published: October 2023

AbstractRhodococcus equiis a gram-positive actinomycetales bacterial, which cause a pneumonia in foals and in immunocompromised humans. Virulence associated protein A (VapA) encoded from virulence plasmid is essential for intracellular proliferation in macrophage. It has reported that VapA participates in exclusion of proton-pumping vacuolar-ATPase complex from phagosome and causes membrane permeabilization, thus contributing to a pH-neutral phagosome lumen. However, there have been no reports about VapA-induced autophagy or its mechanism. In this study, we sought to determine the role of VapA in macrophage autophagy using western blotting, immunofluorescence, pull-down, Co-IP, LS/MS, pH detection LysoTracker and CFU analysis. We show that VapA inhibiting the macrophage autophagy by detecting the expression of autophagy related protein LC3II and P62 and autophagy flux in VapA treated macrophage. Furthermore, we using pull-down and MS analysis to selected ATP6V0D1 could interact with VapA, Co-IP was used to confirm its interaction. Furthermore, VapA treatment in ATP6V0D1 overexpressed cells weaken the lyso Tracker red stain comparing with ATP6V0D1 overexpressed J774A.1 cells. In addition, the expression of ATP6V0D1 significantly increased in J774A.1 post infected with vapA deletion strain,R. equi 103+/ΔVapA by comparing with wild typeR. equi 103+post-infection. And raise of raise of ATP6V0D1 actually reduceR. equi 103+intracellular multiplication. These results further suggesting a decrease of ATP6V0D1 were caused the exit of VapA inR. equi. Taken those date together, we reported that VapA mediated lysosome acidification by inhibiting the expression of ATP6V0D1, which contributing theR. equiescape macrophage autophagy.
Kinetics and functional consequences of BK Channels activation by N-type Ca2+channels in the dendrite of mouse neocortical layer-5 pyramidal neurons
Authors: Blömer Laila Ananda , Giacalone Elisabetta , Abbas Fatima , Filipis Luiza , Tegolo Domenico , Migliore Michele , Canepari Marco 
Published: October 2023

AbstractThe back-propagation of an action potential (AP) from the axon/soma to the dendrites plays a central role in dendritic integration. This process involves an intricate orchestration of various ion channels, but a comprehensive understanding of the contribution of each channel type remains elusive. In this study, we leverage ultrafast membrane potential recordings (Vm) and Ca2+imaging techniques to shed light on the involvement of N-type voltage-gated Ca2+channels (VGCCs) in layer-5 neocortical pyramidal neurons’ apical dendrites. We found a selective interaction between N-type VGCCs and large-conductance Ca2+-activated K+ channels (BK CAKCs). Remarkably, we observe that BK CAKCs are activated within a mere 500 µs after the AP peak, preceding the peak of the Ca2+current triggered by the AP. Consequently, when N-type VGCCs are inhibited, the early broadening of the AP shape amplifies the activity of other VGCCs, leading to an augmented total Ca2+influx. A NEURON model, constructed to replicate and support these experimental results, reveals the critical coupling between N-type and BK channels. This study not only redefines the conventional role of N-type VGCCs as primarily involved in presynaptic neurotransmitter release but also establishes their distinct and essential function as activators of BK CAKCs in neuronal dendrites. Furthermore, our results provide original functional validation of a physical interaction between Ca2+and K+channels, elucidated through ultrafast kinetic reconstruction. This insight enhances our understanding of the intricate mechanisms governing neuronal signaling and may have far-reaching implications in the field.
Selected Laboratory Equipment and Kitchen Utensils as an Alternative Sterilization Method for Sterilizing Plant Tissue Culture Media
Authors: Pamplona Reniel S. , Dela Cruz Christopher DV , Tayangona Maria Angie 
Published: October 2023

ABSTRACTPlant Tissue Culture (PTC) is defined as a technique in culturing different plant partsin vitrounder sterile conditions, and supplemented with optimum nutrients. Due to COVID-19 pandemic which forced everyone to isolate and lock up themselves inside their respective homes, this PTC, which is a heavily laboratory-dependent activity of the students, professors, researchers, and other PTC enthusiasts, was halted. As a response to continuing the PTC remotely, the alternative options for sterilizing PTC media using inexpensive and commercially available laboratory equipment (UV ray and microwave) and kitchen utensils (steamer and casserole) were explored in this study. The commercially available 30mL hinge sauce cup was selected as anin vitromedia container. The addition of the autoclavable plastic or ziplock significantly reduced the deformity of the containers, and contamination rate of the media. Among the laboratory set-up, the two-minute exposure of PTC media to the microwave produced almost the same sterile media in the autoclave method (control). On the other hand, both boiling, and steaming methods had no significant difference compared with the control. Among all the treatments, the steaming method for 20 min had maintained sterile cultures for 3 weeks, and consistent pH like in the control, making it highly recommended for sterilizing PTC media at remote places, particularly at home. Thus, the alternative sterilization protocol of PTC media has been established through this study.
Characterizing Treatment Non-responders vs. Responders in Completed Alzheimer’s Disease Clinical Trials
Authors: Wang Dulin , Ling Yaobin , Harris Kristofer , Schulz Paul E. , Jiang Xiaoqian , Kim Yejin 
Published: October 2023

AbstractAlzheimer’s disease (AD) patients have varying responses to AD drugs and there may be no single treatment for all AD patients. Trial after trial shows that identifying non-responsive and responsive subgroups and their corresponding moderators will provide better insights into subject selection and interpretation in future clinical trials. We aim to extensively investigate pre-treatment features that moderate treatment effect of Galantamine, Bapineuzumab, and Semagacestat from completed trial data. We obtained individual-level patient data from ten randomized clinical trials. Six Galantamine trials and two Bapineuzumab trials were from Yale University Open Data Access Project and two Semagacestat trials were from the Center for Global Clinical Research Data. We included a total of 10,948 subjects. The trials were conducted worldwide from 2001 to 2012. We estimated treatment effect using causal forest modeling on each trial. Finally, we identified important pre-treatment features that determine treatment efficacy and identified responsive or nonresponsive subgroups. As a result, patient’s pre-treatment conditions that determined the treatment efficacy of Galantamine differed by dementia stages, but we consistently observed that non-responders in Galantamine trials had lower BMI (25 vs 28,P< .001) and increased ages (74 vs 68,P< .001). Responders in Bapineuzumab and Semagacestat trials had lower Aβ42levels (6.41 vs 6.53 pg/ml,P< .001) and smaller whole brain volumes (983.13 vs 1052.78 ml,P< .001). 6 ‘positive’ treatment trials had subsets of patients who had, in fact, not responded. 4 “negative” treatment trials had subsets of patients who had, in fact, responded. This study suggests that analyzing heterogeneity in treatment effects in “positive” or “negative” trials may be a very powerful tool for identifying distinct subgroups that are responsive to treatments, which may significantly benefit future clinical trial design and interpretation.
ProA and ProB repeat sequences shape genome organization, and enhancers open domains
Authors: Bonnet Konstantinn Acen , Hulo Nicolas , Mourad Raphaël , Ewing Adam , Croce Olivier , Naville Magali , Vassetzky Nikita , Gilson Eric , Picard Didier , Fourel Geneviève 
Published: October 2023

SUMMARYThere is a growing awareness that repeat sequences (RepSeq) - the main constituents of the human genome - are also prime players in its organization. Here we propose that the genome should be envisioned as a supersystem with three main subsystems, each composed of functionally redundant, cooperating elements. We define herein ProA and ProB RepSeqs as sequences that promote either the A/euchromatin or the B/heterochromatin compartment. ProA and ProB RepSeqs shape A/B partitioning, such that the relative proportions of ProA and ProB RepSeqs determine the propensity of a chromosome segment to adopt either an A or a B configuration. In human, core ProA RepSeqs are essentially made of Alu elements, whereas core ProB RepSeqs consist of young L1 and some Endogenous Retroviruses (ERVs) as well as a panel of AT-rich microsatellites and pericentromeric and telomeric satellites. Additionally, RepSeqs with more indefinite character and, importantly, their derivatives known as “transcriptional enhancers”, can shift between ProA and ProB functions and thus act to open or close specific chromatin domains depending on the cellular context. In this framework, genes and their promoters appear as a special class of RepSeqs that, in their active, transcribed state, reinforce the openness of their surroundings. Molecular mechanisms involve cooperativity between ProB elements, presumably underpinned by the condensate-like properties of heterochromatin, which ProA elements oppose in several ways. We provide strong arguments that altered CpG methylation patterns in cancer including a marked loss in the B compartment, result primarily from a global imbalance in the process of CpG methylation and its erasure. Our results suggest that the resulting altered methylation and impaired function of ProB RepSeqs globally weaken the B compartment, rendering it more plastic, which in turn may confer fate plasticity to the cancer cell.
Calcitriol treatment is safe and increases frataxin levels in Friedreich Ataxia patients
Authors: Alemany Perna Berta , Tamarit Jordi , López Domínguez Daniel , Quiroga-Varela Anna , Merchan Ruiz Miguel , Ramió i Torrentà Lluís , Genís David , Ros Joaquim 
Published: October 2023

ABSTRACTBackgroundCalcitriol, the active form of vitamin D (also known as 1,25-dihydroxycholecalciferol), improves the phenotype and increases frataxin levels in cell models of Friedreich Ataxia (FRDA).MethodsBased on these results, we started a pilot clinical trial in which a dose of 0.25mcg/24h was administered to 15 FRDA patients for a year. Evaluations of neurological function changes (SARA scale, 9-HPT, 8-MWT, PATA test) and quality of life (Barthel Scale and SF-36 quality of life questionnaire) were performed. Frataxin amounts were measured in isolated platelets obtained from these FRDA patients, from heterozygous FRDA carriers (relatives of the FA patients) and from non-heterozygous sex and age matched controls.ResultsAlthough the patients did not experience any observable neurological improvement, there was a statistically significant increase in frataxin levels from initial values, 5,6 pg/μg, to 7,0 pg/μg after 12 months. Differences in frataxin levels referred to total protein amounts were observed amongst sex and age matched controls (18.11 pg/μg), relative controls (10.07 pg/μg), and FRDA patients (5.71 pg/μg). The treatment was well tolerated by most patients, and only some of them experienced minor adverse effects at the beginning of the trial.ConclusionCalcitriol dosage used (0.25mcg/24h) is safe for FRDA patients and it increases frataxin levels. We cannot rule out that higher doses administered longer could yield neurological benefits.
Post-pandemic memory T-cell response to SARS-CoV-2 is durable, broadly targeted and cross-reactive to hypermutated BA.2.86
Authors: Nesamari Rofhiwa , Omondi Millicent A. , Höft Maxine A. , Ngomti Amkele , Baguma Richard , Nkayi Anathi A. , Besethi Asiphe S. , Magugu Siyabulela F. J. , Mosala Paballo , Walters Avril , Clark Gesina M. , Mennen Mathilda , Skelem Sango , Adriaanse Marguerite , Grifoni Alba , Sette Alessandro , Keeton Roanne S. , Ntusi Ntobeko A.B. , Riou Catherine , Burgers Wendy A. 
Published: October 2023

SUMMARYThe COVID-19 post-pandemic period is characterised by infection waves of uncertain size (due to low rates of SARS-CoV-2 testing and notification), as well as limited uptake or global access to updated variant vaccines. Ongoing SARS-CoV-2 evolution has given rise to recombinant Omicron lineages that dominate globally (XBB.1), as well as the emergence of hypermutated variants (BA.2.86). In this context, durable and cross-reactive T-cell immune memory is critical for continued protection against severe COVID-19. We examined T-cell responses to SARS-CoV-2 approximately 1.5 years since Omicron first emerged. We describe sustained CD4+ and CD8+ spike-specific T-cell memory responses in healthcare workers in South Africa (n=39), most of whom had received 2 doses of Ad26.CoV2.S (Johnson & Johnson/Janssen) vaccine and experienced at least one SARS-CoV-2 infection. Spike-specific T cells were highly cross-reactive with all Omicron variants tested, including BA.2.86. Abundant non-spike (nucleocapsid and membrane)-specific T cells were detectable in most participants, augmenting the total T-cell resources available for protection. The bulk of SARS-CoV-2-specific T-cell responses had an early-differentiated phenotype, explaining their persistent nature. Thus, hybrid immunity leads to the accumulation of spike and non-spike T cells evident 3.5 years after the start of the pandemic, with preserved recognition of highly mutated SARS-CoV-2 variants. Long-term T-cell immune memory is likely to provide continued protection against severe outcomes of COVID-19.In BriefNesamariet al.investigate T-cell responses in the context of hybrid immunity 3.5 years after the start of the COVID-19 pandemic. They show that T-cell memory is highly durable and cross-reactive with recombinant variants XBB.1 and hypermutated BA.2.86. Abundant non-spike responses augment the overall T-cell response.