bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metatarsalgia: Clinical Profile and Comfort from Foot Orthoses Treatment
Authors: Robb Kelly A. , Ryan Michael B. 
Published: June 2024

ABSTRACT

Introduction
The biomechanical factors influencing metatarsalgia etiology have been well documented; however, patient characteristics of individuals suffering from this condition and the effectiveness of foot orthosis therapy remain unknown.

Objectives
The objectives of this study were 1) to characterize the metatarsalgia profile of patients seeking treatment in a footwear and orthotic clinic, and 2) to explore the association between comfort and pain in patients with metatarsalgia who were treated with foot orthosis intervention.

Study Design
This study is a retrospective chart review.

Methods
Metatarsalgia assessment and follow-up data (case group n = 2137) were extracted from a research database (control group n = 82,822) from patients visiting a private foot care clinic. A clinical assessment was performed by a Canadian-certified pedorthist, and footwear recommendations and bilateral custom foot orthoses were provided to all patients. Feet were casted using a three-dimensional volumetric laser scanner. Orthoses (80% of cases) were manufactured from a direct mill polypropylene shell; additional rearfoot, forefoot postings, and/or metatarsal support was added according to the patient’s personalized treatment plan.

Results
Eighty-one percent (81%) of metatarsalgia patients reported symptom improvement following custom orthoses treatment. The average pain reduction from the orthotic intervention was 58.55%. The average self-reported comfort scores were 7.7 ± 2.2/10 at follow-up.
Compared with our control group, patients with metatarsalgia were more frequently self-identified as females, over 51 years of age, and the condition was observed in a higher prevalence of high cavus feet.

Conclusions
Our results suggest that a pes cavus foot posture is a biomechanical risk factor to the development of metatarsalgia. Custom foot orthoses that are manufactured according to a patient’s personalized treatment plan are an effective conservative treatment option for pain reduction in patients suffering from metatarsalgia.

Clinical Relevance Statement
Foot orthoses are an effective conservative treatment option for pain reduction in metatarsalgia patients.
Panacus: fast and exact pangenome growth and core size estimation
Authors: Parmigiani Luca , Garrison Erik , Stoye Jens , Marschall Tobias , Doerr Daniel 
Published: June 2024

AbstractMotivationUsing a single linear reference genome poses a limitation to exploring the full genomic diversity of a species. The release of a draft human pangenome underscores the increasing relevance of pangenomics to overcome these limitations. Pangenomes are commonly represented as graphs, which can represent billions of base pairs of sequence. Presently, there is a lack of scalable software able to perform key tasks on pangenomes, such as quantifying universally shared sequence across genomes (thecore genome) and measuring the extent of genomic variability as a function of sample size (pangenome growth).ResultsWe introduce Panacus (pangenome-abacus), a tool designed to rapidly perform these tasks and visualize the results in interactive plots. Panacus can process GFA files, the accepted standard for pangenome graphs, and is able to analyze a human pangenome graph with 110 million nodes in less than one hour.AvailabilityPanacus is implemented in Rust and is published as Open Source software under the MIT license. The source code and documentation are available athttps://github.com/marschall-lab/panacus. Panacus can be installed via Bioconda athttps://bioconda.github.io/recipes/panacus/README.html.ContactLuca Parmigiani (luca.parmigiani@uni-bielefeld.de), Daniel Doerr (daniel.doerr@hhu.de).
Mimicking physiological stiffness or oxygen levels in vitro reorganizes mesenchymal stem cells machinery toward a more naïve phenotype
Authors: Caramelo Inês , Mendes Vera M. , Domingues Catarina , Anjo Sandra I. , Geraldo Margarida , Cardoso Carla M. P. , Grãos Mário , Manadas Bruno 
Published: June 2024

AbstractMesenchymal stem cells (MSCs) offer a promising therapeutic potential for a wide variety of pathologies. However, obtaining minimal effective doses requires an extensivein vitroexpansion, which compromises their stemness and therapeutic properties. The stiffness of the umbilical cord ranges between 2 and 5kPa, and the oxygen levels fluctuate from 2.4% to 3.8%, differing from the standardin vitroculture conditions where MSCs are exposed to the stiffness of the Petri dish (2-3 GPa) and near atmospheric oxygen levels (18.5% O2). Since MSCs can sense and respond to biomechanical and chemical characteristics of the microenvironment, it was hypothesized that expanding MSCs on 3kPa platforms – mechanomodulation – or at 5% O2levels – physioxia – could potentially impact the cellular proteome of MSCs, for long (7-10 days) or short (48h) periods. Data analysis has unveiled that culturing MSCs on soft substrates for long periods promotes the expression of various proteins related to cell redox homeostasis, such as thioredoxins and peroxiredoxins. Conversely, culturing these cells during the same period but under low oxygen levels leads to an increase in chaperone machinery proteins, such as HSP90 or TRiC. These proteins can favor the clearance of misfolded proteins and telomerase maintenance processes, possibly preventing MSCs from being driven to a senescent phenotype. Although mechanomodulation and physioxia are two distinct stimuli, both converge in downregulating the expression of histones and several ribosomal subunits, possibly decreasing translational complexity, which could hypothetically favor a more naïve phenotype for MSCs. Interestingly, priming UC-MSCs (48h) leads to a differential expression of proteins of the extracellular matrix and histone subtypes. Understanding the role of these proteins in transducing environmental cues might provide insights into how conventional culture conditions significantlyalter fundamental cellular processes and support the development of a more efficient protocol to expand and empower the therapeutic potential of MSCs. In the future, employing a combination of reduced stiffness and lower oxygen levels may present a promising strategic approach.HighlightsCulturing MSCs on a soft substrate (3kPa) enhances the expression of antioxidant proteins, such as thioredoxins and peroxiredoxinsProtein homeostasis is remodeled in MSCs cultured under physiological levels of oxygen (5% O2) through the differential expression of the chaperone machineryLowering stiffness or oxygen levels duringin vitroMSCs expansion decreases histones and ribosomal subunits expression, possibly favoring a more naïve phenotype
A snapshot of the Physcomitrella N-terminome reveals N-terminal methylation of organellar proteins
Authors: Hoernstein Sebastian N.W. , Schlosser Andreas , Fiedler Kathrin , van Gessel Nico , Igloi Gabor L. , Lang Daniel , Reski Ralf 
Published: June 2024

AbstractPost- or co-translational N-terminal modifications of proteins influence their half-life as well as mediating protein sorting to organelles via cleavable N-terminal sequences that are recognized by the respective translocation machinery. Here, we provide an overview on the current modification state of the N-termini of over 4500 proteins from the model moss Physcomitrella (Physcomitrium patens) using a compilation of 24 N-terminomics datasets. Our data reveal distinct proteoforms and modification states and confirm predicted targeting peptide cleavage sites of 1144 proteins localized to plastids and the thylakoid lumen, to mitochondria, and to the secretory pathway. Additionally, we uncover extended N-terminal methylation of mitochondrial proteins. Moreover, we identified PpNTM1 (P. patens alpha N-terminal protein methyltransferase 1) as a candidate for protein methylation in plastids, mitochondria and the cytosol. These data can now be used to optimize computational targeting predictors, for customized protein fusions and their targeted localization in biotechnology, and offer novel insights into potential dual targeting of proteins.Key messageAnalysis of the N-terminome of Physcomitrella reveals N-terminal monomethylation of nuclear encoded, mitochondria-localized proteins.Graphical abstract
Reevaluating the Neural Noise Hypothesis in Dyslexia: Insights from EEG and 7T MRS Biomarkers
Authors: Glica Agnieszka , Wasilewska Katarzyna , Jurkowska Julia , Żygierewicz Jarosław , Kossowski Bartosz , Jednoróg Katarzyna 
Published: June 2024

AbstractThe neural noise hypothesis of dyslexia posits an imbalance between excitatory and inhibitory (E/I) brain activity as an underlying mechanism of reading difficulties. This study provides the first direct test of this hypothesis using both EEG power spectrum measures in 120 Polish adolescents and young adults (60 with dyslexia, 60 controls) and glutamate (Glu) and gamma-aminobutyric acid (GABA) concentrations from magnetic resonance spectroscopy (MRS) at 7T MRI scanner in half of the sample. Our results, supported by Bayesian statistics, show no evidence of E/I balance differences between groups, challenging the hypothesis that cortical hyperexcitability underlies dyslexia. These findings suggest alternative mechanisms must be explored and highlight the need for further research into the E/I balance and its role in neurodevelopmental disorders.
Transcriptional reprogramming deploys a compartmentalized “timebomb” inCatharanthus roseusto fend off chewing herbivores
Authors: Liu Yongliang , Shi Jizhe , Patra Barunava , Singh Sanjay Kumar , Liu Xiaoyu , Li Yongqing , Wang Ying , Zhou Xuguo , Pattanaik Sitakanta , Yuan Ling 
Published: June 2024

AbstractThe evolutionary arms-race between plants and insects has led to key adaptive innovations that drive diversification. Alkaloids are well-documented anti-herbivory compounds in plant chemical defenses, but how these specialized metabolites are allocated to cope with both biotic and abiotic stresses concomitantly is largely unknown. To examine how plants prioritize their metabolic resources responding to herbivory and cold, we integrated dietary toxicity bioassay in insects with co-expression analysis, hierarchical clustering, promoter assay, and protein-protein interaction in plants.Catharanthus roseus,a medicinal plant known for its insecticidal property against chewing herbivores, produces two terpenoid indole alkaloid monomers, vindoline and catharanthine. Individually, they exhibited negligible toxicity againstManduca sexta,a chewing herbivore; their condensed product, anhydrovinblastine, however, was highly toxic. Such unique insecticidal mode of action demonstrates that terpenoid indole alkaloid “timebomb” can only be activated when the two spatially isolated monomeric precursors are dimerized by herbivory. Without initial selection pressure and apparent fitness costs, this adaptive chemical defense against herbivory is innovative and sustainable.The biosynthesis of insecticidal terpenoid indole alkaloids is induced by herbivory but suppressed by cold. Here, we identified a transcription factor,Herbivore InducedVindoline-geneExpression (HIVE), that coordinates the production of terpenoid indole alkaloids in response to herbivory and cold stress. The HIVE-mediated transcriptional reprogramming allows this herbaceous perennial to allocate their metabolic resources for chemical defense at a normal temperature, when herbivory pressure is high, but switches to cold tolerance under a cooler temperature, when insect infestation is secondary.
Direct computations of viscoelastic moduli of biomolecular condensates
Authors: Cohen Samuel R. , Banerjee Priya R. , Pappu Rohit V. 
Published: June 2024

ABSTRACTIn vitrofacsimiles of biomolecular condensates are formed by different types of intrinsically disordered proteins including prion-like low complexity domains (PLCDs). PLCD condensates are viscoelastic materials defined by time-dependent, sequence-specific complex shear moduli. Here, we show that viscoelastic moduli can be computed directly using a generalization of the Rouse model and information regarding intra- and inter-chain contacts that is extracted from equilibrium configurations of lattice-based Metropolis Monte Carlo (MMC) simulations. The key ingredient of the generalized Rouse model is the Zimm matrix that we compute from equilibrium MMC simulations. We compute two flavors of Zimm matrices, one referred to as the single-chain model that accounts only for intra-chain contacts, and the other referred to as a collective model, that accounts for inter-chain interactions. The single-chain model systematically overestimates the storage and loss moduli, whereas the collective model reproduces the measured moduli with greater fidelity. However, in the long time, low-frequency domain, a mixture of the two models proves to be most accurate. In line with the theory of Rouse, we find that a continuous distribution of relaxation times exists in condensates. The single crossover frequency between dominantly elastic versus dominantly viscous behaviors is influenced by the totality of the relaxation modes. Hence, our analysis suggests that viscoelastic fluid-like condensates are best described as generalized Maxwell fluids. Finally, we show that the complex shear moduli can be used to solve an inverse problem to obtain distributions of relaxation times that underlie the dynamics within condensates.
Optimized phenotype definitions boost GWAS power
Authors: Zietz Michael , Brown Kathleen LaRow , Gisladottir Undina , Tatonetti Nicholas P. 
Published: June 2024

AbstractComplex diseases are among the central challenges facing the world, and genetics underlie a large fraction of the risk. Observational data, such as electronic health records (EHR), offer numerous advantages in the study of complex disease genetics. These include their large scale, cost-effectiveness, information on many different conditions, and future scalability with the widespread adoption of EHRs. Observational data, however, are challenging for research as they reflect various factors including the healthcare process and access to care, as well as broader societal effects like systemic biases. Here, we introduce MaxGCP, a novel phenotyping method designed to purify the genetic signal in observational data. Our approach optimizes a phenotype definition to maximize its coheritability with the complex trait of interest. We validated the method in simulations and applied it to real data analyses of stroke and Alzheimer’s disease. We found that MaxGCP improves genomewide association study (GWAS) power compared to conventional, single-code phenotype definitions. MaxGCP is a powerful tool for genetic discovery in observational data, and we anticipate that it will be broadly useful for studying complex diseases using observational data.
A 5-day course of rTMS before pain onset ameliorates future pain and increases sensorimotor peak alpha frequency
Authors: Chowdhury Nahian S , Taseen Khandoker , Chiang Alan , Chang Wei-Ju , Millard Samantha K , Seminowicz David A , Schabrun Siobhan M 
Published: June 2024

AbstractRepetitive transcranial magnetic stimulation (rTMS) has shown promise as an intervention for pain. An unexplored research question is whether the delivery of rTMSprior to pain onsetmight protect against a future episode of prolonged pain. The present study aimed to determine i) whether 5 consecutive days of rTMS delivered prior to experimentally-induced prolonged jaw pain could reduce future pain intensity and ii) whether any effects of rTMS on pain were mediated by changes in corticomotor excitability (CME) and/or sensorimotor peak alpha frequency (PAF). On each day from Day 0-4, forty healthy individuals received a single session of active (n = 21) or sham (n = 19) rTMS over the left primary motor cortex. PAF and CME were assessed on Day 0 (before rTMS) and Day 4 (after rTMS). Prolonged pain was induced via intramuscular injection of nerve growth factor (NGF) in the right masseter muscle after the final rTMS session. From Days 5-25, participants completed twice-daily electronic dairies including pain on chewing and yawning (primary outcomes), as well as pain during other activities (e.g. talking), functional limitation in jaw function and muscle soreness (secondary outcomes). Compared to sham, individuals who received active rTMS subsequently experienced lower pain on chewing and yawning. Although active rTMS increased PAF, the effects of rTMS on pain were not mediated by changes in PAF or CME. This study is the first to show that rTMS deliveredpriorto pain onset can protect against future pain and associated functional impairment. Thus, rTMS may hold promise as a prophylactic intervention for persistent pain.
Receptor- ligand interactions in plant inmate immunity revealed by AlphaFold protein structure prediction
Authors: Wang Li , Jia Yulin , Osakina Aron , Olsen Kenneth M. , Huang Yixiao , Jia Melissa H. , Ponniah Sathish , Pedrozo Rodrigo , Nicolli Camila , Edwards Jeremy D. 
Published: June 2024

AbstractOne of the common mechanisms to trigger plant innate immunity is recognition of pathogen avirulence gene products directly by products of major resistance (R) genes in a gene for gene manner. In the USA, theRgenes,Pik-s, PiKh/m, andPi-ta, Pi-39(t), andPtrgenes have been effectively deployed to prevent the infections ofM. oryzaeraces, IB49, and IC17 for some time.Pi-9is only recently being deployed to provide overlapped and complimentary resistance toMagnaporthe oryzaeraces IB49, IC17 and IE1k in the USA. Pi-ta, Pi-39(t), Pi9 are major nuclear binding site-leucine rich (NLR) proteins, and Ptr is an atypical R protein with 4 armadillo repeats. AlphaFold is an artificial intelligence system that predicts a protein 3D structure from its amino acid sequence. Here we report genome sequence analyses of the effectors and avirulence (AVR) genes,AVR-PitaandAVR-Pik, andAVR-Pi9, in 3 differentialM. oryzaeraces. Using AlphaFold 2 and 3 we find strong evidence of direct interactions of products of resistance genesPi-taandPikwithM. oryzaeavirulence (AVR) genes,AVR-PitaandAVR-Pikrespectively. We also found that AVR-Pita interacts with Pi-39(t) and Ptr, and Pi9 interacts with both AVR-Pi9 and AVR-Pik. Validation of direct interactions of two pairs of R and AVR proteins supported a direct interaction mechanism of plant innate immunity. Detecting interaction of both Ptr and Pi39(t) with AVR-Pita, and Pi-9 with both AVR-Pi9 and AVR-Pik, revealed a new insight into recognition of pathogen signaling molecules by these host R genes in triggering plant innate immunity.
Host population structure and rare dispersal events drive leptospirosis transmission patterns amongRattus norvegicusin Boston, Massachusetts, US
Authors: Stone Nathan E. , Hamond Camila , Clegg Joel , McDonough Ryelan F. , Bourgeois Reanna M. , Ballard Rebecca , Thornton Natalie B. , Nuttall Marianece , Hertzel Hannah , Anderson Tammy , Whealy Ryann N. , Timm Skylar , Roberts Alexander K. , Barragán Verónica , Phipatanakul Wanda , Leibler Jessica H. , Benson Hayley , Specht Aubrey , White Ruairi , LeCount Karen , Furstenau Tara N. , Galloway Renee L. , Hill Nichola J. , Madison Joseph D. , Fofanov Viacheslav Y. , Pearson Talima , Sahl Jason W. , Busch Joseph D. , Weiner Zachary , Nally Jarlath E. , Wagner David M. , Rosenbaum Marieke H. 
Published: June 2024

AbstractLeptospirosis (caused by pathogenic bacteria in the genusLeptospira) is prevalent worldwide but more common in tropical and subtropical regions. Transmission can occur following direct exposure to infected urine from reservoir hosts, such as rats, or a urine-contaminated environment, which then can serve as an infection source for additional rats and other mammals, including humans. The brown rat,Rattus norvegicus, is an important reservoir of leptospirosis in urban settings. We investigated leptospirosis among brown rats in Boston, Massachusetts and hypothesized that rat dispersal in this urban setting influences the movement, persistence, and diversity ofLeptospira. We analyzed DNA from 328 rat kidney samples collected from 17 sites in Boston over a seven-year period (2016–2022); 59 rats representing 12 of 17 sites were positive forLeptospira. We used 21 neutral microsatellite loci to genotype 311 rats and utilized the resulting data to investigate genetic connectivity among sampling sites. We generated whole genome sequences for 28Leptospiraisolates obtained from frozen and fresh tissue from some of the 59Leptospira-positive rat kidneys. When isolates were not obtained, we attemptedLeptospiragenomic DNA capture and enrichment, which yielded 14 additionalLeptospiragenomes from rats. We also generated an enrichedLeptospiragenome from a 2018 human case in Boston. We found evidence of high genetic structure and limited dispersal among rat populations that is likely influenced by major roads and/or other unknown dispersal barriers, resulting in distinct rat population groups within the city; at certain sites these groups persisted for multiple years. We identified multiple distinct phylogenetic clades ofL. interrogansamong rats, with specific clades tightly linked to distinct rat populations. This pattern suggestsL. interroganspersists in local rat populations and movement of leptospirosis in this urban rat community is driven by rat dispersal. Finally, our genomic analyses of the 2018 human leptospirosis case in Boston suggests a link to rats as the source. These findings will be useful for guiding rat control and human leptospirosis mitigation efforts in this and other urban settings.
A commensal-derived sugar protects against metabolic disease
Authors: Tan Chin Yee , Jiang Danting , Theriot Barbara S. , Rao Meghana V. , Surana Neeraj K. 
Published: June 2024

SUMMARYObesity is a worsening global epidemic that is regulated by the microbiota through unknown bacterial factors. We discovered a human-derived commensal bacterium,Clostridium immunis, that protects against metabolic disease by secreting a phosphocholine-modified exopolysaccharide. Genetic interruption of the phosphocholine biosynthesis locus (licABC) results in a functionally inactive exopolysaccharide, which demonstrates the critical requirement for this phosphocholine moiety. ThisC. immunisexopolysaccharide acts via group 3 innate lymphoid cells and modulating IL-22 levels, which results in a reduction in serum triglycerides, body weight, and visceral adiposity. Importantly, phosphocholine biosynthesis genes are less abundant in humans with obesity or hypertriglyceridemia, findings that suggest the role of bacterial phosphocholine is conserved across mice and humans. These results define a bacterial molecule—and its key structural motif—that regulates host metabolism. More broadly, they highlight how small molecules, such as phosphocholine, may help fine-tune microbiome– immune–metabolism interactions.