The Impact of Bone Marrow Stimulation on Arthroscopic Rotator Cuff Repair for Small to Large Rotator Cuff Tears: A Randomized Controlled Trial.

BACKGROUND: Bone marrow stimulation (BMS), a procedure involving the creation of multiple channels in the greater tuberosity, is often performed alongside arthroscopic rotator cuff repair (ARCR). This study evaluated the effect of BMS on clinical and structural outcomes following ARCR. METHOD: This study involved 204 patients with small, medium, and large full-thickness rotator cuff tears. In all, 103 patients who underwent BMS and ARCR made up the BMS group, while the 101 patients who only had ARCR made up the control group with randomization. Clinical and functional outcomes were assessed before and at 3 months, 6 months, 1 year, and 2 years after surgery, using parameters such as range of motion, functional scores (ASES and constant score), and clinical scores (VAS). Tendon integrity was also examined postoperatively via ultrasound at 6 months and 2 years. RESULTS: There were no significant differences between the two groups concerning range of motion, functional scores (ASES score and constant score), and clinical score (VAS) during the 2-year post-surgery period (all p>0.05). Similarly, the rotator cuff retear rate, as assessed using ultrasonographic tendon integrity checks over 2 years post-surgery, did not significantly vary between the groups (all p>0.05). CONCLUSION: There were no significant disparities in functional scores and clinical outcomes between the BMS and control groups. Further, no significant differences were observed in tendon integrity post-surgery. Therefore, the inclusion or exclusion of BMS is not anticipated to influence the postoperative outcome in ARCR for patients with small, medium, or large rotator cuff tears.

Massively parallel screen uncovers many rare 3' UTR variants regulating mRNA abundance of cancer driver genes.

Understanding the function of rare non-coding variants represents a significant challenge. Using MapUTR, a screening method, we studied the function of rare 3' UTR variants affecting mRNA abundance post-transcriptionally. Among 17,301 rare gnomAD variants, an average of 24.5% were functional, with 70% in cancer-related genes, many in critical cancer pathways. This observation motivated an interrogation of 11,929 somatic mutations, uncovering 3928 (33%) functional mutations in 155 cancer driver genes. Functional MapUTR variants were enriched in microRNA- or protein-binding sites and may underlie outlier gene expression in tumors. Further, we introduce untranslated tumor mutational burden (uTMB), a metric reflecting the amount of somatic functional MapUTR variants of a tumor and show its potential in predicting patient survival. Through prime editing, we characterized three variants in cancer-relevant genes (MFN2, FOSL2, and IRAK1), demonstrating their cancer-driving potential. Our study elucidates the function of tens of thousands of non-coding variants, nominates non-coding cancer driver mutations, and demonstrates their potential contributions to cancer.

CM1, a Chrysin Derivative, Protects from Endotoxin-Induced Lethal Shock by Regulating the Excessive Activation of Inflammatory Responses.

Sepsis, a leading cause of death worldwide, is a harmful inflammatory condition that is primarily caused by an endotoxin released by Gram-negative bacteria. Effective targeted therapeutic strategies for sepsis are lacking. In this study, using an in vitro and in vivo mouse model, we demonstrated that CM1, a derivative of the natural polyphenol chrysin, exerts an anti-inflammatory effect by inducing the expression of the ubiquitin-editing protein TNFAIP3 and the NAD-dependent deacetylase sirtuin 1 (SIRT1). Interestingly, CM1 attenuated the Toll-like receptor 4 (TLR4)-induced production of inflammatory cytokines by inhibiting the extracellular-signal-regulated kinase (ERK)/MAPK and nuclear factor kappa B (NF-κB) signalling pathways. In addition, CM1 induced the expression of TNFAIP3 and SIRT1 on TLR4-stimulated primary macrophages; however, the anti-inflammatory effect of CM1 was abolished by the siRNA-mediated silencing of TNFAPI3 or by the genetic or pharmacologic inhibition of SIRT1. Importantly, intravenous administration of CM1 resulted in decreased susceptibility to endotoxin-induced sepsis, thereby attenuating the production of pro-inflammatory cytokines and neutrophil infiltration into the lung compared to control mice. Collectively, these findings demonstrate that CM1 has therapeutic potential for diverse inflammatory diseases, including sepsis.

Draft genome sequence of Limosilactobacillus fermentum isolated from subgingival biofilm.

Limosilactobacillus fermentum is generally considered beneficial for vaginal and digestive health. However, strains isolated from the oral cavity, especially from periodontitis lesions, have not been thoroughly studied. Here, we report the draft genome sequence of strain KHUD_007 isolated from the subgingival biofilm of a Korean patient with periodontitis.

Complete genome sequence of Schaalia odontolytica isolated from subgingival biofilm.

OBJECTIVE: Recent advancements in genome-based taxonomic classification propose the reclassification of certain Actinomyces species into new genera, including Schaalia. Schaalia odontolytica, the type species within this genus, is frequently found in the human oral cavity and has been associated with actinomycotic lesions. Currently, only two complete genomes of S. odontolytica strains have been reported. Recognizing the limited research on subspecies-level variation of S. odontolytica, we conducted genome sequencing of strain KHUD_008, isolated from a Korean periodontitis patient's subgingival biofilm. Additionally, we performed a comparative genome analysis using previously sequenced genomes of strain XH001 and strain FDAARGOS_732, both derived from the human oral cavity. DATA DESCRIPTION: Pacific Biosciences Sequel II sequencing generated 15,904 and 76,557 raw sequencing sub-reads, which were integrated to assemble the de novo genome using the Microbial Genome Analysis pipeline in the Single-Molecule Real-Time Analysis. The genome assembly completeness, assessed by Benchmarking Universal Single-Copy Orthologs, reached 99.2%. The genome is 2,389,595 bp with a GC content of 66.37%, and contains 2,002 protein-coding genes, 9 rRNAs, and 48 tRNA. Comparative analysis with two previously sequenced strains revealed many strain-specific genes in KHUD_008, primarily related to envelope biogenesis and replication/recombination/repair processes.

Single-cell RNA sequencing reveals heterogeneity of adipose tissue-derived mesenchymal stem cells under chondrogenic induction.

This study investigated how adipose tissue-derived mesenchymal stem cells (AT-MSCs) respond to chondrogenic induction using droplet-based single-cell RNA sequencing (scRNA-seq). We analyzed 37,219 high-quality transcripts from control cells and cells induced for 1 week (1W) and 2 weeks (2W). Four distinct cell clusters (0-3), undetectable by bulk analysis, exhibited varying proportions. Cluster 1 dominated in control and 1W cells, whereas cluster 3, 2, and 0 exclusively dominated in control, 1W, and 2W cells, respectively. Furthermore, heterogeneous chondrogenic markers expression within clusters emerged. Gene ontology (GO) enrichment analysis of differentially expressed genes unveiled cluster-specific variations in key biological processes (BP): (1) Cluster 1 exhibited upregulation of GO-BP terms related to ribosome biogenesis and translational control, crucial for maintaining stem cell properties and homeostasis; (2) Additionally, cluster 1 showed upregulation of GO-BP terms associated with mitochondrial oxidative metabolism; (3) Cluster 3 displayed upregulation of GO-BP terms related to cell proliferation; (4) Clusters 0 and 2 demonstrated similar upregulation of GO-BP terms linked to collagen fibril organization and supramolecular fiber organization. However, only cluster 0 showed a significant decrease in GO-BP terms related to ribosome production, implying a potential correlation between ribosome regulation and the differentiation stages of AT-MSCs. Overall, our findings highlight heterogeneous cell clusters with varying balances between proliferation and differentiation before and after chondrogenic stimulation. This provides enhanced insights into the single-cell dynamics of AT-MCSs during chondrogenic differentiation.

Bacterial single-cell transcriptomics: Recent technical advances and future applications in dentistry.

Metagenomics and metatranscriptomics have enhanced our understanding of the oral microbiome and its impact on oral health. However, these approaches have inherent limitations in exploring individual cells and the heterogeneity within mixed microbial communities, which restricts our current understanding to bulk cells and species-level information. Fortunately, recent technical advances have enabled the application of single-cell RNA sequencing (scRNA-seq) for studying bacteria, shedding light on cell-to-cell diversity and interactions between host-bacterial cells at the single-cell level. Here, we address the technical barriers in capturing RNA from single bacterial cells and highlight pioneering studies from the past decade. We also discuss recent achievements in host-bacterial dual transcriptional profiling at the single-cell level. Bacterial scRNA-seq provides advantages in various research fields, including the investigation of phenotypic heterogeneity within genetically identical bacteria, identification of rare cell types, detection of antibiotic-resistant or persistent cells, analysis of individual gene expression patterns and metabolic activities, and characterization of specific microbe-host interactions. Integrating single-cell techniques with bulk approaches is essential to gain a comprehensive understanding of oral diseases and develop targeted and personalized treatment in dentistry. The reviewed pioneering studies are expected to inspire future research on the oral microbiome at the single-cell level.

Loosely synchronized activation of anterior cingulate cortical neurons for scratching response during histamine-induced itch.

Itch is a distinctive sensation that causes a specific affection and scratching reaction. The anterior cingulate cortex (ACC) has been linked to itch sensation in numerous studies; however, its precise function in processing pruritic inputs remains unknown. Distinguishing the precise role of the ACC in itch sensation can be challenging because of its capacity to conduct heterologous neurophysiological activities. Here, we used in vivo calcium imaging to examine how ACC neurons in free-moving mice react to pruritogenic histamine. In particular, we focused on how the activity of the ACC neurons varied before and after the scratching response. We discovered that although the change in neuronal activity was not synchronized with the scratching reaction, the overall activity of itch-responsive neurons promptly decreased after the scratching response. These findings suggest that the ACC does not directly elicit the feeling of itchiness.

Expression of cytokines and co-stimulatory molecules in the Toxoplasma gondii-infected dendritic cells of C57BL/6 and BALB/c mice.

Toxoplasma gondii is an intracellular protozoan parasite which can infect most warm-blooded animals and humans. Among the different mouse models, C57BL/6 mice are more susceptible to T. gondii infection compared to BALB/c mice, and this increased susceptibility has been attributed to various factors, including T-cell responses. Dendritic cells (DCs) are the most prominent type of antigen-presenting cells and regulate the host immune response, including the response of T-cells. However, differences in the DC responses of these mouse strains to T. gondii infection have yet to be characterized. In this study, we cultured bone marrow-derived DCs (BMDCs) from BALB/c and C57BL/6 mice. These cells were infected with T. gondii. The activation of the BMDCs was assessed based on the expression of cell surface markers and cytokines. In the BMDCs of both mouse strains, we detected significant increases in the expression of cell surface T-cell co-stimulatory molecules (major histocompatibility complex (MHC) II, CD40, CD80, and CD86) and cytokines (tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-12p40, IL-1ß, and IL-10) from 3 h post-T. gondii infection. The expression of MHC II, CD40, CD80, CD86, IFN-γ, IL-12p40, and IL-1ß was significantly higher in the T. gondii-infected BMDCs obtained from the C57BL/6 mice than in those from the BALB/c mice. These findings indicate that differences in the activation status of the BMDCs in the BALB/c and C57BL/6 mice may account for their differential susceptibility to T. gondii.

The CCAAT-box transcription factor, NF-Y complex, mediates the specification of the IL1 neurons in C. elegans.

Neuronal differentiation is highly coordinated through a cascade of gene expression, mediated via interactions between transacting transcription factors and cis-regulatory elements of their target genes. However, the mechanisms of transcriptional regulation that determine neuronal cell-fate are not fully understood. Here, we show that the nuclear transcription factor Y (NF-Y) subunit, NFYA-1, is necessary and sufficient to express the flp-3 neuropeptide gene in the IL1 neurons of C. elegans. flp-3 expression is decreased in dorsal and lateral, but not ventral IL1s of nfya-1 mutants. The expression of another terminally differentiated gene, eat-4 vesicular glutamate transporter, is abolished, whereas the unc-8 DEG/ENaC gene and pan-neuronal genes are expressed normally in IL1s of nfya-1 mutants. nfya-1 is expressed in and acts in IL1s to regulate flp-3 and eat-4 expression. Ectopic expression of NFYA-1 drives the expression of flp-3 gene in other cell-types. Promoter analysis of IL1-expressed genes results in the identification of several cisregulatory motifs which are necessary for IL1 expression, including a putative CCAAT-box located in the flp-3 promoter that NFYA-1 directly interacts with. NFYA-1 and NFYA-2, together with NFYB-1 and NFYC-1, exhibit partly or fully redundant roles in the regulation of flp-3 or unc-8 expression, respectively. Taken together, our data indicate that the NF-Y complex regulates neuronal subtype-specification via regulating a set of terminal-differentiation genes. [BMB Reports 2023; 56(3): 153-159].

Assessing the effect of antihypertensives on plaque microbiota in patients with periodontitis and hypertension using 16S rRNA sequencing: A cross-sectional study.

BACKGROUND: Periodontitis is initiated or accelerated by dysbiosis of oral microorganisms. When hypertension is accompanied in periodontitis patients, changes of oral microbiota occur. Since there are no reports on antihypertensives, we assessed their effect on the oral microbial profiles of patients with periodontitis. METHODS: This study involved 95 participants divided into two groups: those with periodontitis and hypertension (P_HT), and those with periodontitis and taking medications for hypertension (P_mHT). Plaque samples were collected from the buccal, supragingival, and subgingival sites of the oral cavities of these patients. DNA was extracted, and the V3-V4 region of the 16S ribosomal RNA was sequenced and analyzed. RESULTS: The P_HT and P_mHT groups were similar with respect to the alpha- and beta-diversity as well as the dominant phyla and genera, but differed in the relative abundance of bacterial species (85 species). In the P_mHT group, the relative abundance of major periodontal pathogens was greatly increased. In particular, Tannerella forsythia, Treponema denticola, and Fretibacterium fastidiosum increased nearly three times in the linear discriminant analysis score in the supragingival plaque. Also, there was an increase in the relative abundance of Prevotella spp., associated with periodontitis and nitrate reduction, which was also evident in the supragingival plaque. CONCLUSIONS: These findings indicate that antihypertensives induce dysbiotic changes in the oral microbiota of patients with periodontitis, which are associated with increases in the relative abundance of periodontal pathogens. Therefore, more active periodontal treatment and supportive periodontal therapy are required in patients taking antihypertensives.

Keratin-mediated hair growth and its underlying biological mechanism.

Here we show that intradermal injection of keratin promotes hair growth in mice, which results from extracellular interaction of keratin with hair forming cells. Extracellular application of keratin induces condensation of dermal papilla cells and the generation of a P-cadherin-expressing cell population (hair germ) from outer root sheath cells via keratin-mediated microenvironmental changes. Exogenous keratin-mediated hair growth is reflected by the finding that keratin exposure from transforming growth factor beta 2 (TGFß2)-induced apoptotic outer root sheath cells appears to be critical for dermal papilla cell condensation and P-cadherin-expressing hair germ formation. Immunodepletion or downregulation of keratin released from or expressed in TGFß2-induced apoptotic outer root sheath cells negatively influences dermal papilla cell condensation and hair germ formation. Our pilot study provides an evidence on initiating hair regeneration and insight into the biological function of keratin exposed from apoptotic epithelial cells in tissue regeneration and development.

SIRT1 Promotes Host Protective Immunity against Toxoplasma gondii by Controlling the FoxO-Autophagy Axis via the AMPK and PI3K/AKT Signalling Pathways.

Sirtuin 1 (SIRT1) regulates cellular processes by deacetylating non-histone targets, including transcription factors and intracellular signalling mediators; thus, its abnormal activation is closely linked to the pathophysiology of several diseases. However, its function in Toxoplasma gondii infection is unclear. We found that SIRT1 contributes to autophagy activation via the AMP-activated protein kinase (AMPK) and PI3K/AKT signalling pathways, promoting anti-Toxoplasma responses. Myeloid-specific Sirt1-/- mice exhibited an increased cyst burden in brain tissue compared to wild-type mice following infection with the avirulent ME49 strain. Consistently, the intracellular survival of T. gondii was markedly increased in Sirt1-deficient bone-marrow-derived macrophages (BMDMs). In contrast, the activation of SIRT1 by resveratrol resulted in not only the induction of autophagy but also a significantly increased anti-Toxoplasma effect. Notably, SIRT1 regulates the FoxO-autophagy axis in several human diseases. Importantly, the T. gondii-induced phosphorylation, acetylation, and cytosolic translocation of FoxO1 was enhanced in Sirt1-deficient BMDMs and the pharmacological inhibition of PI3K/AKT signalling reduced the cytosolic translocation of FoxO1 in BMDMs infected with T. gondii. Further, the CaMKK2-dependent AMPK signalling pathway is responsible for the effect of SIRT1 on the FoxO3a-autophagy axis and for its anti-Toxoplasma activity. Collectively, our findings reveal a previously unappreciated role for SIRT1 in Toxoplasma infection.

MnCO3-mineralized polydopamine nanoparticles as an activatable theranostic agent for dual-modality imaging-guided photothermal therapy of cancers.

Background: Single imaging modality is still insufficient to evaluate the biological and anatomical structures of tumors with high accuracy and reliability. Generation of non-specific contrast, leading to a low target-to-background signal ratio, results in low imaging resolution and accuracy. Tumor environment-specific activatable multifunctional contrast agents need to maximize the contrast signals, representing a dual imaging-guided photothermal therapy (PTT) at target tumor sites. Methods: Cellular uptake, cytotoxicity assay, and in vitro photothermal conversion efficiency of MnCO3-mineralized fluorescent polydopamine nanoparticles (MnCO3-FPNPs) were evaluated using 4T1 breast cancer cells. In vivo dual-modality imaging was performed using IVIS imaging and a 4.7 T animal MRI systems after injection into 4T1 tumor-bearing nude mice. The effects of photothermal therapeutic through PTT were measured after irradiation with an 808 nm laser (1.5 W/cm2) for 10 min, measuring the size of the tumors every 2 days. Results: At physiological pH (7.4), MnCO3-FPNP is efficiently quenched. Conversely, at acidic pH (5.4), the strong fluorescence (FL) is recovered due to the dissociation of Mn2+ from the FPNPs. At pH 7.4, MnCO3-FPNP activity is silenced to enhance water proton relaxation due to unionized MnCO3 maintenance; conversely, at acidic pH (5.4), MnCO3-FPNPs efficiently release Mn2+ ions, thereby resulting in T 1-weighted magnetic resonance (MR) contrast enhancement. MnCO3-FPNPs display a promising diagnostic ability for 4T1 breast cancer xenograft models, as well as exhibit a high photothermal conversion efficiency. A successful tumor treatment via their photothermal activity is accomplished within 14 days. Conclusions: Our studies exhibited unique "OFF-ON" activation abilities in FL/MR dual imaging and PTT functions. This approach suggests that the MnCO3-FPNPs may serve as a useful platform for various mineralization-based multimodal imaging-guided PTT models for many cancer theranostic applications.

Genomic and phenotypic comparison of Prevotella intermedia strains possessing different virulence in vivo.

Prevotella intermedia readily colonizes healthy dental biofilm and is associated with periodontal diseases. The viscous exopolysaccharide (EPS)-producing capability is known as a major virulence factor of P. intermedia 17 (Pi17). However, the inter-strain difference in P. intermedia regarding virulence-associated phenotype is not well studied. We compared in vivo virulence and whole genome sequences using five wild-type strains: ATCC 49046 (Pi49046), ATCC 15032 (Pi15032), ATCC 15033 (Pi15033), ATCC 25611 (Pi25611), and Pi17. Non-EPS producing Pi25611 was the least virulent in insect and mammalian models. Unexpectedly, Pi49046 did not produce viscous EPS but was the most virulent, followed by Pi17. Genomes of the five strains were quite similar but revealed subtle differences such as copy number variations and single nucleotide polymorphisms. Variations between strains were found in genes encoding glycosyltransferases and genes involved in the acquisition of carbohydrates and iron/haem. Based on these genetic variations, further analyses were performed. Phylogenetic and structural analyses discovered phosphoglycosyltransferases of Pi49046 and Pi17 have evolved to contain additional loops that may confer substrate specificity. Pi17, Pi15032, and Pi15033 displayed increased growth by various carbohydrates. Meanwhile, Pi49046 exhibited the highest activities for haemolysis and haem accumulation, as well as co-aggregation with Porphyromonas gingivalis harbouring fimA type II, which is more tied to periodontitis than other fimA types. Collectively, subtle genetic differences related to glycosylation and acquisition of carbohydrates and iron/haem may contribute to the diversity of virulence and phenotypic traits among P. intermedia strains. These variations may also reflect versatile strategies for within-host adaptation of P. intermedia.

Whole genome and RNA sequencing of oral commensal bacterium Streptococcus anginosus subsp. anginosus with vancomycin tolerance.

"Antibiotic tolerance" promotes the rapid subsequent evolution of "antibiotic resistance," however, it is often overlooked because it is difficult to distinguish between tolerant and susceptible organisms. A commensal bacterium S. anginosus subsp. anginosus strain KHUD_S1, isolated from dental biofilm was found to exhibit a high MBC/MIC ratio of 32 against vancomycin. We observed KHUD_S1 cells exposed to vancomycin did not grow but maintained viability. Transmission electron microscope showed KHUD_S1 cells possessed a dense, thick capsule and maintained the cell wall integrity upon vancomycin exposure. To infer the underlying mechanisms of the vancomycin tolerance in KHUD_S1, we performed whole genome sequencing and RNA sequencing. The KHUD_S1 genome carried three genes encoding branching enzymes that can affect peptidoglycan structure through interpeptide bridge formation. Global gene expression profiling revealed that the vancomycin-induced downregulation of carbohydrate and inorganic ion transport/metabolism as well as translation is less prominent in KHUD_S1 than in the vancomycin susceptible strain KHUD_S3. Based on the transcriptional levels of genes related to peptidoglycan synthesis, KHUD_S1 was determined to have a 3D peptidoglycan architecture distinct from KHUD_S3. It was found that, under vancomycin exposure, the peptidoglycan was remodeled through changes in the interpeptide bridge and transpeptidation reactions. Collectively, these features of S. anginosus KHUD_S1, including a dense capsule and differential gene expression in peptidoglycan synthesis, may contribute to vancomycin tolerance. Our results showing the occurrence of vancomycin tolerance amongst oral commensal bacteria highlight the need for considering future strategies for screening of antibiotic tolerance as an effort to reduce antibiotic resistance.

Copper arsenite-complexed Fenton-like nanoparticles as oxidative stress-amplifying anticancer agents.

We report copper(II) arsenite (CuAS)-integrated polymer micelles (CuAS-PMs) as a new class of Fenton-like catalytic nanosystem that can display reactive oxygen species (ROS)-manipulating anticancer therapeutic activity. CuAS-PMs were fabricated through metal-catechol chelation-based formation of the CuAS complex on the core domain of poly (ethylene glycol)-b-poly(3,4-dihydroxy-L-phenylalanine) (PEG-PDOPA) copolymer micelles. CuAS-PMs maintained structural robustness under serum conditions. The insoluble state of the CuAS complex was effectively retained at physiological pH, whereas, at endosomal pH, the CuAS complex was ionized to release arsenite and cuprous Fenton catalysts (Cu+ ions). Upon endocytosis, CuAS-PMs simultaneously released hydrogen peroxide (H2O2)-generating arsenite and Fenton-like reaction-catalyzing Cu+ ions in cancer cells, which synergistically elevated the level of highly cytotoxic hydroxyl radicals (•OH), thereby preferentially killing cancer cells. Animal experiments demonstrated that CuAS-PMs could effectively suppress the growth of solid tumors without systemic in vivo toxicity. The design rationale of CuAS-PMs may provide a promising strategy to develop diverse oxidative stress-amplifying agents with great potential in cancer-specific therapy.

Quantification of Upper Limb Isometric Force Control Abilities for Evaluating Upper Limb Functions Among Prosthetic Users.

Force control abilities are essential to interact with objects in our environments. However, there is a lack of evaluation tools and methods to test the force control abilities of the upper limb in evaluating the upper limb functions of prosthetic users. This study aimed to quantify upper limb isometric force control abilities in healthy individuals and prosthetic users using a custom-built handle with a 6-axis force/torque sensor and visual cue, namely an Upper Limb End-effector type Force control test device (ULEF). Feasibilities of the test device were demonstrated through experiments by holding the ULEF with an intact hand among healthy subjects and transradial and wrist amputees with a myoelectric powered prosthetic hand, the bebionic hand. Compared to the healthy individuals, the prosthetic user group demonstrated poor isometric force control abilities in terms of higher control instability during the lateral direction task ( [Formula: see text]). Significantly higher variability in force-generating rates was also found in all task directions in the prosthetic user group ( [Formula: see text]). Compared to the healthy group, the prosthetic user group showed significant small peak biceps activities during the posterior task ( [Formula: see text]) and anterior task ( [Formula: see text]). Quantification of isometric upper limb force control abilities can potentially be beneficial to develop evaluation and research tools for investigating mechanisms underlying force control abilities of prosthetic users and provide guidelines for targeted isometric force control training and prosthesis development.