nils-herrmann/clean_scirepeval huggingface dataset:
Development of a preclinical natural porcine knee simulation model for the tribological assessment of osteochondral grafts in vitro.
Venue: Journal of biomechanics

In order to pre-clinically evaluate the performance and efficacy of novel osteochondral interventions, physiological and clinically relevant whole joint simulation models, capable of reproducing the complex loading and motions experienced in the natural knee environment are required. The aim of this study was to develop a method for the assessment of tribological performance of osteochondral grafts within an in vitro whole natural joint simulation model. The study assessed the effects of osteochondral allograft implantation (existing surgical intervention for the repair of osteochondral defects) on the wear, deformation and damage of the opposing articular surfaces. Tribological performance of osteochondral grafts was compared to the natural joint (negative control), an injury model (focal cartilage defects) and stainless steel pins (positive controls). A recently developed method using an optical profiler (Alicona Infinite Focus G5, Alicona Imaging GmbH, Austria) was used to quantify and characterise the wear, deformation and damage occurring on the opposing articular surfaces. Allografts inserted flush with the cartilage surface had the lowest levels of wear, deformation and damage following the 2 h test; increased levels of wear, deformation and damage were observed when allografts and stainless steel pins were inserted proud of the articular surface. The method developed will be applied in future studies to assess the tribological performance of novel early stage osteochondral interventions prior to in vivo studies, investigate variation in surgical precision and aid in the development of stratified interventions for the patient population.
The effectiveness of scaling procedures for comparing ground reaction forces.
Venue: Journal of biomechanics

Various scaling methods are used when attempting to remove the influence of anthropometric differences on ground reaction forces (GRF) when comparing groups. Though commonly used, ratio scaling often results in an over-correction. Allometric scaling has previously been suggested for kinetic variables but its effectiveness in partialing out the effect of anthropometrics is unknown due to a lack of consistent application. This study examined the effectiveness of allometric scaling vertical, braking and propulsive GRF and loading rate for 84 males and 47 females while running at 4.0 m/s. Raw, unfiltered data were ratio scaled by body mass (BM), height (HT), and BM multiplied by HT (BM∗HT). Gender specific exponents for allometric scaling were determined by performing a log-linear (for BM and HT individually) or log-multilinear regression (BMHT). Pearson productmoment correlations were used to assess the effectiveness of each scaling method. Ratio scaling by BM, HT, or BM∗HT resulted in an over-correction of the data for most variables and left a considerable portion of the variance still attributable to anthropometrics. Allometric scaling by BM successfully removed the effect of BM and HT for all variables except for braking GRF in males and vertical GRF in females. However, allometric scaling for BMHT successfully removed the effect of BM and HT for all reactionary forces in both genders. Based on these results, allometric scaling for BMHT was the most appropriate scaling method for partialing out the effect of BM and HT on kinetic variables to allow for effective comparisons between groups or individuals.
Altered biomechanical stimulation of the developing hip joint in presence of hip dysplasia risk factors
Venue: Journal of biomechanics

Fetal kicking and movements generate biomechanical stimulation in the fetal skeleton, which is important for prenatal musculoskeletal development, particularly joint shape. Developmental dysplasia of the hip (DDH) is the most common joint shape abnormality at birth, with many risk factors for the condition being associated with restricted fetal movement. In this study, we investigate the biomechanics of fetal movements in such situations, namely fetal breech position, oligohydramnios and primiparity (firstborn pregnancy). We also investigate twin pregnancies, which are not at greater risk of DDH incidence, despite the more restricted intra-uterine environment. We track fetal movements for each of these situations using cine-MRI technology, quantify the kick and muscle forces, and characterise the resulting stress and strain in the hip joint, testing the hypothesis that altered biomechanical stimuli may explain the link between certain intra-uterine conditions and risk of DDH. Kick force, stress and strain were found to be significantly lower in cases of breech position and oligohydramnios. Similarly, firstborn fetuses were found to generate significantly lower kick forces than non-firstborns. Interestingly, no significant difference was observed in twins compared to singletons. This research represents the first evidence of a link between the biomechanics of fetal movements and the risk of DDH, potentially informing the development of future preventative measures and enhanced diagnosis. Our results emphasise the importance of ultrasound screening for breech position and oligohydramnios, particularly later in pregnancy, and suggest that earlier intervention to correct breech position through external cephalic version could reduce the risk of hip dysplasia.
Scapulothoracic kinematic pattern in the shoulder pain and scapular dyskinesis: A principal component analysis approach.
Venue: Journal of biomechanics

The relationship between shoulder pain and scapular dyskinesis (SDK) is unclear. Differences between groups with and without SDK have been demonstrated, focusing on the amount of scapular motion at specific degrees of humeral elevation. However, this approach does not consider the temporal information and shape of the scapular motion temporal series. Principal Component Analysis (PCA) may clarify this variability and advance current understanding of 'abnormal' movement patterns. This study aimed to evaluate the scapular kinematics in patients with shoulder pain and in asymptomatic participants with and without SDK using PCA. Data were collected in 98 participants separated in four groups: Pain + SDK (n = 24), Pain (n = 25), No Pain + SDK (n = 24), and No Pain (n = 25). Scapulothoracic kinematic data were measured with an electromagnetic tracking device during arm elevation and lowering phases. PCA and analysis of variance were used to compare the groups. The No Pain + SDK group had a progressive increasing in anterior tilt over the elevation phase compared to the Pain (effect size = 0.79) and No Pain (effect size = 0.80) groups. During the arm-lowering, the Pain + SDK group had a progressive increasing in anterior tilt over this phase in comparison to the No Pain + SDK group (effect size = 0.68). Therefore, PCA demonstrated differences in the scapular anterior tilt related to SDK and shoulder pain. The presence of SDK revealed a scapular pattern with progressive increasing in anterior tilt over the elevation phase. However, during the arm-lowering phase, asymptomatic participants with SDK changed their motion pattern, unlike the symptomatic group, reinforcing the suggested association between scapular modifications and shoulder symptoms.
Residual force enhancement during submaximal and maximal effort contractions of the plantar flexors across knee angle.
Venue: Journal of biomechanics

Following active muscle lengthening, steady-state isometric force is elevated compared with an isometric contraction without prior lengthening for the same muscle length and activation level. This property of muscle contraction is known as residual force enhancement (RFE). Here, we aimed to determine whether neural factors may mask some of the mechanical benefits of RFE on plantar flexion torque production. Inherent to lengthening contractions is an increase in cortical and spinal-mediated inhibition, while knee flexion places the medial gastrocnemius at a neuromechanical disadvantage. Neuromuscular properties of the plantar flexors were investigated with a Humac Norm dynamometer in 10 males (∼27 years) with a flexed (90°) and extended (180°) knee and with or without calcaneal tendon vibration (frequency range: 80-110 Hz). There was no effect for vibration (p > 0.05), but there was an effect for knee angle (p < 0.05) such that there was a 2 fold increase in RFE with the knee flexed compared with extended. During submaximal torque matching, following active lengthening there was an activation reduction (electromyography; EMG) of 7.2 and 4.7% with the knee flexed and extended, respectively for soleus as compared with the reference isometric contraction, but no difference for the medial gastrocnemius. Despite attempting to excite Ia input onto the plantar flexor motor neuron pool, vibration had no influence on RFE. Surprisingly, RFE was elevated more for the knee flexed than extended, which was possibly owing to the activation differences across the disparate muscles of the triceps surae during the plantar flexion task.
Characterizing the balance-dexterity task as a concurrent bipedal task to investigate trunk control during dynamic balance.
Venue: Journal of biomechanics

The purpose of the study was to characterize the Balance-Dexterity Task as a means to investigate a concurrent bipedal lower-extremity task and trunk control during dynamic balance. The task combines aspects of single-limb balance and the lower-extremity dexterity test by asking participants to stand on one limb while compressing an unstable spring with the contralateral limb to an individualized target force. Nineteen non-disabled participants completed the study, and performance measures for the demands of each limb - balance and dexterous force control - as well as kinematic and electromyographic measures of trunk control were collected. Given five practice trials, participants achieved compression forces ranging from 100 to 139 N (mean 121.2 ± 12.3 N), representing 14.4-23.0% of body weight (mean 18.7 ± 2.4%), which were then presented as target forces during test trials. Dexterous force control coefficient of variation and average magnitude of the center of pressure (COP) resultant velocity were associated such that greater variability in force control was accompanied by greater COP velocity (R = 0.598, p = 0.007). Trunk coupling, quantified as the coefficient of determination (R2) of a frontal plane thorax and pelvis angle-angle plot, varied independently of any measure of balance or dexterous force control. The Balance-Dexterity Task is a continuous, dynamic balance task where bipedal coordination and trunk coupling can be concurrently observed and studied.
In-vivo 3-Dimensional gait symmetry analysis in patients with bilateral total hip arthroplasty.
Venue: Journal of biomechanics

Although three-dimensional (3D) asymmetry has been reported in unilateral THA patients during gait, it is not well understood whether asymmetric hip kinematics during gait persist in bilaterally operated THA patients. The purpose of this study was to compare the in vivo 3D kinematics and component placement between bilateral and unilateral THA patients during gait. Eight bilateral and thirty-three unilateral THA patients were evaluated for both hips during treadmill gait using a validated combination of 3D computer tomography-based modeling and dual fluoroscopic imaging system (DFIS). The in vivo 3D kinematics of the unilateral THA group was first assessed. The magnitudes of kinematics and component placement difference between implanted hips in the bilateral THA group and between the implanted and non-implanted hips in the unilateral THA group were compared. The study results showed asymmetric gait kinematics in the unilateral THA group. Although the magnitude of kinematics differences between sides for both the bilateral and unilateral THA groups did not change significantly for hip rotations (p > 0.05), the bilaterally operated THA group has significantly lower magnitude of hip gait translation difference. Significant reduction in the magnitude of the acetabular cup adduction, stem adduction, and combine hip anteversion and adduction difference was observed in the bilateral THA group (p < 0.05). Our findings demonstrated that despite significant improvements of component placement and reduced magnitude of hip gait translation difference between implanted hips in the bilateral THA group, asymmetric hip kinematic rotations persisted in patients with bilateral THA during gait.
Alterations in trunk bending stiffness following changes in stability and equilibrium demands of a load holding task.
Venue: Journal of biomechanics

The contribution of the trunk neuromuscular system (TNS) to spine stability has been shown in earlier studies by characterizing changes in antagonistic activity of trunk muscles following alterations in stability demands of a task. Whether and/or how much such changes in the response of TNS to alteration in stability demand of the task alter spinal stiffness remains unclear. To address this research gap, a repeated measure study was conducted on twenty gender-balanced asymptomatic individuals to evaluate changes in trunk bending stiffness throughout the lumbar spine's range of flexion following alterations in both stability and equilibrium demands of a load holding task. Trunk bending stiffness was determined using trunk stiffness tests in upright posture on a rigid metal frame under different equilibrium and stability demands on the lower back. Increasing the stability demand by increasing the height of lifted load ∼30 cm only increased trunk bending stiffness (∼39%) over the lower range of lumbar flexion and under the low equilibrium demand condition. Similarly, increasing the equilibrium demand of the task by increasing the weight of lifted load by 3.5 kg only increased trunk bending stiffness (55%) over the low range of lumbar flexion and under the low stability demand condition. Our results suggest a non-linear relationship between changes in stability and equilibrium demands of a task and the contribution of TNS to trunk bending stiffness. Specifically, alterations in TNS response to changes in stability and equilibrium demand of a given task will increase stiffness of the trunk only if the background stiffness is low.
Plugging in to Human Memory: Advantages, Challenges, and Insights from Human Single-Neuron Recordings
Venue: Cell

We describe single-neuron recordings in the human hippocampal formation, performed in epileptic patients for clinical reasons, and highlight their advantages, challenges, and limitations compared with non-invasive recordings in humans and invasive recordings in animals. We propose a unified framework to explain different findings—responses to novel stimuli, spatial locations, and specific concepts—linking the rodent and human literature regarding the function of the hippocampal formation. Moreover, we propose a model of how memories are encoded in this area, suggesting that the context-independent, invariant coding by concept cells may provide a uniquely human neural mechanism underlying memory representations.
Dynamic Modeling of a 100-Million-Atom Organelle at the Source of Life
Venue: Cell

In this issue of Cell, Singharoy et al. present a rate kinetic model for the chromatophore of photosynthetic purple bacteria generated from molecular dynamics simulations. It shows that the chromatophore's architecture is optimized for producing bioenergy under low light typical of the natural bacterial habitat while minimizing photodamage under stress conditions.
Multisystem Toxicity in Cancer: Lessons from NASA’s Countermeasures Program
Venue: Cell

Astronauts and cancer patients are subject to similar multisystem physiological toxicities. Over the past sixty years, NASA developed a state-of-the-art countermeasures program (CMP) to characterize and mitigate the physiological consequences of spaceflight. Here, we propose a NASA-modeled CMP to elucidate and abrogate physiological toxicities in patients with cancer.
Long-Term Culture Captures Injury-Repair Cycles of Colonic Stem Cells
Venue: Cell

The colonic epithelium can undergo multiple rounds of damage and repair, often in response to excessive inflammation. The responsive stem cell that mediates this process is unclear, in part because of a lack of in vitro models that recapitulate key epithelial changes that occur in vivo during damage and repair. Here, we identify a Hopx+ colitis-associated regenerative stem cell (CARSC) population that functionally contributes to mucosal repair in mouse models of colitis. Hopx+ CARSCs, enriched for fetal-like markers, transiently arose from hypertrophic crypts known to facilitate regeneration. Importantly, we established a long-term, self-organizing two-dimensional (2D) epithelial monolayer system to model the regenerative properties and responses of Hopx+ CARSCs. This system can reenact the “homeostasis-injury-regeneration” cycles of epithelial alterations that occur in vivo. Using this system, we found that hypoxia and endoplasmic reticulum stress, insults commonly present in inflammatory bowel diseases, mediated the cyclic switch of cellular status in this process.
Cryo-EM Structure of the Human FLCN-FNIP2-Rag-Ragulator Complex
Venue: Cell

mTORC1 controls anabolic and catabolic processes in response to nutrients through the Rag GTPase heterodimer, which is regulated by multiple upstream protein complexes. One such regulator, FLCN-FNIP2, is a GTPase activating protein (GAP) for RagC/D, but despite its important role, how it activates the Rag GTPase heterodimer remains unknown. We used cryo-EM to determine the structure of FLCN-FNIP2 in a complex with the Rag GTPases and Ragulator. FNIP2 adopts an extended conformation with two pairs of heterodimerized domains. The Longin domains heterodimerize and contact both nucleotide binding domains of the Rag heterodimer, while the DENN domains interact at the distal end of the structure. Biochemical analyses reveal a conserved arginine on FLCN as the catalytic arginine finger and lead us to interpret our structure as an on-pathway intermediate. These data reveal features of a GAP-GTPase interaction and the structure of a critical component of the nutrient-sensing mTORC1 pathway.
Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa
Venue: Cell

Genomic studies in African populations provide unique opportunities to understand disease etiology, human diversity, and population history. In the largest study of its kind, comprising genome-wide data from 6,400 individuals and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically correlated fine-scale population substructure. Historically, the ancestry of modern Ugandans was best represented by a mixture of ancient East African pastoralists. We demonstrate the value of the largest sequence panel from Africa to date as an imputation resource. Examining 34 cardiometabolic traits, we show systematic differences in trait heritability between European and African populations, probably reflecting the differential impact of genes and environment. In a multi-trait pan-African GWAS of up to 14,126 individuals, we identify novel loci associated with anthropometric, hematological, lipid, and glycemic traits. We find that several functionally important signals are driven by Africa-specific variants, highlighting the value of studying diverse populations across the region.
Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma
Venue: Cell

To elucidate the deregulated functional modules that drive clear cell renal cell carcinoma (ccRCC), we performed comprehensive genomic, epigenomic, transcriptomic, proteomic, and phosphoproteomic characterization of treatment-naive ccRCC and paired normal adjacent tissue samples. Genomic analyses identified a distinct molecular subgroup associated with genomic instability. Integration of proteogenomic measurements uniquely identified protein dysregulation of cellular mechanisms impacted by genomic alterations, including oxidative phosphorylation-related metabolism, protein translation processes, and phospho-signaling modules. To assess the degree of immune infiltration in individual tumors, we identified microenvironment cell signatures that delineated four immune-based ccRCC subtypes characterized by distinct cellular pathways. This study reports a large-scale proteogenomic analysis of ccRCC to discern the functional impact of genomic alterations and provides evidence for rational treatment selection stemming from ccRCC pathobiology.
Active and Repressed Chromatin Domains Exhibit Distinct Nucleosome Segregation during DNA Replication
Venue: Cell

Chromatin domains and their associated structures must be faithfully inherited through cellular division to maintain cellular identity. However, accessing the localized strategies preserving chromatin domain inheritance, specifically the transfer of parental, pre-existing nucleosomes with their associated post-translational modifications (PTMs) during DNA replication, is challenging in living cells. We devised an inducible, proximity-dependent labeling system to irreversibly mark replication-dependent H3.1 and H3.2 histone-containing nucleosomes at desired loci in mouse embryonic stem cells so that their fate after DNA replication could be followed. Strikingly, repressed chromatin domains are preserved through local re-deposition of parental nucleosomes. In contrast, nucleosomes decorating active chromatin domains do not exhibit such preservation. Notably, altering cell fate leads to an adjustment of the positional inheritance of parental nucleosomes that reflects the corresponding changes in chromatin structure. These findings point to important mechanisms that contribute to parental nucleosome segregation to preserve cellular identity.
Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow
Venue: Cell

Cell-cell junctions respond to mechanical forces by changing their organization and function. To gain insight into the mechanochemical basis underlying junction mechanosensitivity, we analyzed tight junction (TJ) formation between the enveloping cell layer (EVL) and the yolk syncytial layer (YSL) in the gastrulating zebrafish embryo. We found that the accumulation of Zonula Occludens-1 (ZO-1) at TJs closely scales with tension of the adjacent actomyosin network, revealing that these junctions are mechanosensitive. Actomyosin tension triggers ZO-1 junctional accumulation by driving retrograde actomyosin flow within the YSL, which transports non-junctional ZO-1 clusters toward the TJ. Non-junctional ZO-1 clusters form by phase separation, and direct actin binding of ZO-1 is required for stable incorporation of retrogradely flowing ZO-1 clusters into TJs. If the formation and/or junctional incorporation of ZO-1 clusters is impaired, then TJs lose their mechanosensitivity, and consequently, EVL-YSL movement is delayed. Thus, phase separation and flow of non-junctional ZO-1 confer mechanosensitivity to TJs.