nils-herrmann/clean_scirepeval huggingface dataset:
Preliminary validation of a mobile force Sensing device for clinical and telerehabilitation.
Venue: Journal of biomechanics

Muscle strength and force production are important measures of patient progress during physical rehabilitation. Reliable and objective measurements are important to ascertain throughout rehabilitation. Current methods-manual muscle testing, electromechanical dynamometer, and hand-held dynamometer-are accurate and reliable, but have limitations that prevent wide implementation. As healthcare systems adapt to more patient-centered outcome models, changes to the delivery of rehabilitation, whether at-home or in the clinic, must also change to become more cost effective and accessible and provide quantifiable information regarding patient progress. We developed a novel Force Sensing (FoSe) device to quantify either tensile or compressive isometric muscle strength. The device was tested in a laboratory setting with healthy participants (n = 32) and compared to the commonly used hand-held dynamometer (HHD). Participants used both devices to perform several common isometric muscle tests including: hip abduction, knee extension, knee flexion, shoulder external rotation, and shoulder internal rotation. Compared to the HHD, FoSe was found to be an accurate and reliable measurement of force production. Intraclass Correlation Coefficients ranged from 0.58 to 0.89 without a magnitude dependent variation in force measurement. A second round of clinical testing with a patient population is warranted to determine FoSe's ability to measure clinically relevant asymmetry and progress over time. Further usability testing also needs to be conducted to determine the adequacy of FoSe for at-home use by both patients and clinicians.
Dysplastic hip anatomy alters muscle moment arm lengths, lines of action, and contributions to joint reaction forces during gait.
Venue: Journal of biomechanics

Developmental dysplasia of the hip (DDH) is characterized by abnormal bony anatomy, which causes detrimental hip joint loading and leads to secondary osteoarthritis. Hip joint loading depends, in part, on muscle-induced joint reaction forces (JRFs), and therefore, is influenced by hip muscle moment arm lengths (MALs) and lines of action (LoAs). The current study used subject-specific musculoskeletal models and in-vivo motion analysis to quantify the effects of DDH bony anatomy on dynamic muscle MALs, LoAs, and their contributions to JRF peaks during early (~17%) and late-stance (~52%) of gait. Compared to healthy hips (N = 15, 16-39 y/o), the abductor muscles in patients with untreated DDH (N = 15, 16-39 y/o) had smaller abduction MALs (e.g. anterior gluteus medius, 35.3 vs. 41.6 mm in early stance, 45.4 vs. 52.6 mm late stance, p ≤ 0.01) and more medially-directed LoAs. Abduction-adduction and rotation MALs also differed for major hip flexors such as rectus femoris and iliacus. The altered MALs in DDH corresponded to higher hip abductor forces, medial JRFs (1.26 vs. 0.87 × BW early stance, p = 0.03), and resultant JRFs (5.71 vs. 4.97 × BW late stance, p = 0.05). DDH anatomy not only affected hip muscle force generation in the primary plane of function, but also their out-of-plane mechanics, which collectively elevated JRFs. Overall, hip muscle MALs and their contributions to JRFs were significantly altered by DDH bony anatomy. Therefore, to better understand the mechanisms of joint degeneration and improve the efficacy of treatments for DDH, the dynamic anatomy-force relationships and multi-planar functions of the whole hip musculature must be collectively considered.
Biomechanical characterization of a chronic type a dissected human aorta.
Venue: Journal of biomechanics

Aortic dissection is one of the most lethal cardiovascular diseases. A chronic Type A (Stanford) dissected aorta was retrieved for research from a 73-year-old male donor without diagnosed genetic disease. The aorta presented a dissection over the full length, and it reached a diameter of 7.7 cm in its ascending portion. The descending thoracic aorta underwent layer-specific quasi-static and dynamic mechanical characterizations after layer separation. Mechanical tests showed a physiological (healthy) behavior of the intima and some mechanical anomalies of the media and the adventitia. In particular, the static stiffness of both these layers at smaller strains was three times smaller than any one measured for twelve healthy aortas. When the viscoelastic properties were tested, adventitia presented a larger relative increase of the dynamic stiffness at 3 Hz with respect to most of the healthy aortas. The loss factor of the adventitia, which is associated with dissipation, was at the lower limit of those measured for healthy aortas. It seems reasonable to attribute these anomalies of the mechanical properties exhibited by the media and the adventitia to the severe remodeling secondary to the chronic nature of the dissection. However, it cannot be excluded that some of the mechanical anomalies were present before remodeling.
On the mechanical power output required for human running - Insight from an analytical model.
Venue: Journal of biomechanics

In this paper the dynamics of human running on flat terrain and the required mechanical power output with its dependency on various parameters is investigated. Knowing the required mechanical power output is of relevance due to its relationship with the metabolic power. For example, a better understanding of the dependencies of required mechanical power output on weight, running and wind speed, step frequency, ground contact time etc. is very valuable for the assessment, analysis and optimization of running performance. Therefore, a mathematical model based on very few assumptions is devised. The purpose of the proposed model is to relate running speed and required mechanical power output as an algebraic function of the runner's mass, height, step rate, ground contact time and wind speed. This is relevant in order to better understand the mechanical energy cost of locomotion, and how much it depends on which parameters. The first of the main energy dissipation mechanisms is due to vertical oscillation, i.e., during each step some of the potential energy difference gets transformed into heat. The second mechanism is due to the anterior ground reaction force during the first part of stance and the third is due to aerodynamic drag. With the approximations of constant running speed and a sinusoidal vertical ground reaction force profile one obtains closed algebraic expressions for the center of mass trajectory and the required mechanical power output. Comparisons of model predictions and reported performance data suggest that approximately a quarter of the ground impact energy is stored during the first part of ground contact and then released during the remaining stance phase. Further, one can conclude from the model that less mechanical power output is required when running with higher step rates and a higher center of mass. Non intuitive is the result that a shorter ground contact time is beneficial for fast runs, while the opposite holds for slow runs. An important advantage of the devised model compared to others is that it leads to closed algebraic expressions for the center of mass trajectory and mechanical power output, which are functions of measurable quantities, i.e., of step rate, ground contact time, running speed, runner's mass, center of mass height, aerodynamic drag at some given speed, wind speed and heart rate. Moreover, the model relies on very few assumptions, which have been verified, and the only tuning parameter is the ratio of recovered elastic energy.
On the spectrographic representation of cardiovascular flow instabilities.
Venue: Journal of biomechanics

In the past decade, high-fidelity computational fluid dynamics (CFD) has uncovered the presence of high-frequency flow instabilities (on the order of 100 s of Hz) in a variety of cardiovascular applications. These fluctuations are typically reported as pulsatile velocity-time traces or fast-Fourier-transformed power-frequency spectra, often from a single point or at most a handful of points. Originally inspired by its use in spectral Doppler ultrasound, here we demonstrate the utility of the simplest form of time-frequency representation - the spectrogram - as a more comprehensive yet still-intuitive means of visualizing the potential harmonic complexity of pulsatile cardiovascular flows. After reviewing the basic theory behind spectrograms, notably the short-time Fourier transform (STFT), we discuss the choice of input parameters that inform the appearance and trade-offs of spectrograms. We show that spectrograms using STFT were able to highlight spectral features and were representative of those obtained from more complex methods such as the Continuous Wavelet transforms (CWT). While visualization properties (colourmap, filtering, smoothing/interpolation) are shown to affect the conspicuity of spectral features, the window properties (function, size, overlap) are shown to have the greatest impact on the resulting spectrogram appearance. Using a set of cerebral aneurysm CFD cases, we show that spectrograms can readily reveal the case-specific nature of the time-varying flow instabilities, whether broadband, suggesting intermittent turbulent-like flow, or narrowband, suggesting laminar vortex shedding, or some combination thereof.
Hemodynamics alteration in patient-specific dilated ascending thoracic aortas with tricuspid and bicuspid aortic valves.
Venue: Journal of biomechanics

In this paper, we evaluate computationally the influence of blood flow eccentricity and valve phenotype (bicuspid (BAV) and tricuspid (TAV) aortic valve) on hemodynamics in ascending thoracic aortic aneurysm (ATAA) patients. 5 TAV ATAA, 5 BAV ATAA (ascending aorta diameter >35 mm) and 2 healthy subjects underwent 4D flow MRI. The 3D velocity profiles obtained from 4D flow MRI were given as input boundary conditions to a computational fluid dynamics analysis (CFD) model. After performing the CFD analyses, we verified that the obtained time-averaged velocity profiles and flow eccentricity were in good agreement with 4D flow MRI. Then we used the CFD analyses to evaluate the time-averaged wall shear stress (TAWSS) and the local normalized helicity (LNH). We found that the flow eccentricities at the aortic root were not significantly different (p > 0.05) between TAV and BAV phenotypes. TAWSS (R2 = 0.697, p = 0.025) and absolute LNH (R2 = 0.964, p < 0.001) are in good correlation with flow eccentricity. We conclude that eccentricity at the aortic root is a major determinant of hemodynamics patterns in ATAA patients regardless of the aortic valve phenotype.
Mechanisms of reduced plantarflexor function in Cerebral palsy: smaller triceps surae moment arm and reduced muscle force.
Venue: Journal of biomechanics

Both muscle forces, and moment arm (MA) could contribute to reduced muscle moment in people with Cerebral Palsy (CP). Current reports in CP are conflicting. The tendon travel method of estimating MA requires constant force, but passive force is high and variable in CP, and range of motion is limited. Therefore, the purpose of this study was to examine triceps surae muscle MA in 12 subjects with mild to moderate CP (15-32 years) and 10 typically developing peers (TD, 17-26 years) by tendon travel and by visually measuring the apparent MA. MA was calculated at 90° and at a reference angle (∼106°) with zero net passive moment. The tendon travel (28.8 ± 5.6 mm) and visual methods (29.1 ± 5.5 mm) yielded similar MA in CP (p = 0.94) at the reference angle. TD had significantly larger triceps surae muscle MA than CP subjects (p = 0.002), 35.4 ± 4.1 mm at the reference angle for tendon travel and 35.4 ± 3.6 mm by the visual method. Test/retest revealed less bias (0.8 mm) using the visual method. Calculated active peak isometric force was significantly less in CP (1983.8 ± 887.0 N) than TD (4104.9 ± 1154.9 N, p < 0.001). There are challenges in estimating MA in CP, but the visual method is more reliable. Although a shorter moment arm would reduce the joint moment, joint angular velocity for a given velocity of muscle shortening would be enhanced. Strength training may mitigate the effects of the smaller moment arm and reduced joint moment generated in those with CP.
Effect of cracks on the local deformations of articular cartilage.
Venue: Journal of biomechanics

Despite significant evidence regarding the increased risk of cartilage degeneration due to traumatic injuries to joints, there is still a lack of understanding of the mechanisms underlying osteoarthritis development following a joint injury. Injuries in knee cartilage are often characterized by lesions or tears. In addition to acute traumatic joint injuries, microscale damages, which may form because of wear, are thought to be a contributing factor in the development of osteoarthritis. While the overall function of a joint may not be affected by the presence of microcracks, we hypothesized that strain magnification in the vicinity of microcracks might be significant. We tested this hypothesis by creating partial cuts in articular cartilages and measuring the strain within 20 µm from the edge of these cuts. Measurements were made in the superficial and middle zones of articular cartilage extract samples. We found that local strain in the vicinity of cuts is magnified by a factor of 1.2-1.6 compared to strains in intact regions for nominal compressions exceeding 5%. For nominal compressions of less than 5%, no strain magnification was detected in the vicinity of the cracks. We concluded that articular cartilage cracks magnify local strains by damaging the structural integrity and decreasing the fluid pressure in the matrix.
Weak associations between hip adduction angle and hip abductor muscle activity during running.
Venue: Journal of biomechanics

Hip abductor muscle strengthening is often prescribed to reduce the peak hip adduction angle in runners with overuse knee injury. However, no evidence exists associating greater isometric hip abductor muscle strength with smaller peak hip adduction angle during running. Beyond muscle strength, muscle activation patterns may play an important role in controlling joint movement during running. Therefore, the purpose of this investigation was to determine if associations existed among hip adduction angle, hip abductor muscle activity, and isometric hip abductor muscle strength. Twenty-five currently healthy female runners participated. Average gluteus medius muscle activity and tensor fascia lata muscle activity were determined during hip abductor maximal voluntary isometric contractions. Three-dimensional kinematics and hip abductor muscle activity were collected during treadmill running. Dependent variables were analyzed via Pearson product moment correlations. Multi-variable linear regression determined muscle activity's and strength's contributions to the peak hip adduction angle. A fair positive correlation was observed between the peak hip adduction angle and average tensor fascia lata muscle activity magnitude. Additionally, there was a moderate negative correlation between isometric hip abductor muscle strength and average gluteus medius muscle activity magnitude. Tensor fascia lata activity magnitude accounted for the most variance of the peak hip adduction angle. This study adds to the literature which indicates a lack of association between isometric hip abductor muscle strength and peak hip adduction angle in healthy runners. Factors other than hip abductor muscle strength and activation may account for more of the variance in peak hip adduction angles among runners.
Role of biomechanics in vascularization of tissue-engineered bones.
Venue: Journal of biomechanics

Biomaterial based reconstruction is still the most commonly employed method of small bone defect reconstruction. Bone tissue-engineered techniques are improving, and adjuncts such as vascularization technologies allow re-evaluation of traditional reconstructive methods for healingofcritical-sized bone defect. Slow infiltration rate of vasculogenesis after cell-seeded scaffold implantation limits the use of clinically relevant large-sized scaffolds. Hence, in vitro vascularization within the tissue-engineered bone before implantation is required to overcome the serious challenge of low cell survival rate after implantation which affects bone tissue regeneration and osseointegration. Mechanobiological interactions between cells and microvascular mechanics regulate biological processes regarding cell behavior. In addition, load-bearing scaffolds demand mechanical stability properties after vascularization to have adequate strength while implanted. With the advent of bioreactors, vascularization has been greatly improved by biomechanical regulation of stem cell differentiation through fluid-induced shear stress and synergizing osteogenic and angiogenic differentiation in multispecies coculture cells. The benefits of vascularization are clear: avoidance of mass transfer limitation and oxygen deprivation, a significant decrease in cell necrosis, and consequently bone development, regeneration and remodeling. Here, we discuss specific techniques to avoid pitfalls and optimize vascularization results of tissue-engineered bone. Cell source, scaffold modifications and bioreactor design, and technique specifics all play a critical role in this new, and rapidly growing method for bone defect reconstruction. Given the crucial importance of long-term survival of vascular network in physiological function of 3D engineered-bone constructs, greater knowledge of vascularization approaches may lead to the development of new strategies towards stabilization of formed vascular structure.
Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19
Venue: Cell

Summary
 
 SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. We here systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in unexposed individuals, exposed family members, and individuals with acute or convalescent COVID-19. Acute phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative exposed family members and convalescent individuals with a history of asymptomatic and mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits robust, broad and highly functional memory T cell responses, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19.
Dual Functions of a Rubisco Activase in Metabolic Repair and Recruitment to Carboxysomes
Venue: Cell

Rubisco, the key enzyme of CO2 fixation in photosynthesis, is prone to inactivation by inhibitory sugar phosphates. Inhibited Rubisco undergoes conformational repair by the hexameric AAA+ chaperone Rubisco activase (Rca) in a process that is not well understood. Here, we performed a structural and mechanistic analysis of cyanobacterial Rca, a close homolog of plant Rca. In the Rca:Rubisco complex, Rca is positioned over the Rubisco catalytic site under repair and pulls the N-terminal tail of the large Rubisco subunit (RbcL) into the hexamer pore. Simultaneous displacement of the C terminus of the adjacent RbcL opens the catalytic site for inhibitor release. An alternative interaction of Rca with Rubisco is mediated by C-terminal domains that resemble the small Rubisco subunit. These domains, together with the N-terminal AAA+ hexamer, ensure that Rca is packaged with Rubisco into carboxysomes. The cyanobacterial Rca is a dual-purpose protein with functions in Rubisco repair and carboxysome organization.
COVID-19 Makes B Cells Forget, but T Cells Remember
Venue: Cell

Understanding which arms of the immune response are responsible for protection against SARS-CoV-2 infection is key to predicting long-term immunity and to inform vaccine design. Two studies in this issue of Cell collectively suggest that although SARS-CoV-2 infection may blunt long-lived antibody responses, immune memory might still be achieved through virus-specific memory T cells.
Onco-fetal Reprogramming of Endothelial Cells Drives Immunosuppressive Macrophages in Hepatocellular Carcinoma
Venue: Cell

We employed scRNA sequencing to extensively characterize the cellular landscape of human liver from development to disease. Analysis of ∼212,000 cells representing human fetal, hepatocellular carcinoma (HCC), and mouse liver revealed remarkable fetal-like reprogramming of the tumor microenvironment. Specifically, the HCC ecosystem displayed features reminiscent of fetal development, including re-emergence of fetal-associated endothelial cells (PLVAP/VEGFR2) and fetal-like (FOLR2) tumor-associated macrophages. In a cross-species comparative analysis, we discovered remarkable similarity between mouse embryonic, fetal-liver, and tumor macrophages. Spatial transcriptomics further revealed a shared onco-fetal ecosystem between fetal liver and HCC. Furthermore, gene regulatory analysis, spatial transcriptomics, and in vitro functional assays implicated VEGF and NOTCH signaling in maintaining onco-fetal ecosystem. Taken together, we report a shared immunosuppressive onco-fetal ecosystem in fetal liver and HCC. Our results unravel a previously unexplored onco-fetal reprogramming of the tumor ecosystem, provide novel targets for therapeutic interventions in HCC, and open avenues for identifying similar paradigms in other cancers and disease.
The Self-Organizing Genome: Principles of Genome Architecture and Function
Venue: Cell

Genomes have complex three-dimensional architectures. The recent convergence of genetic, biochemical, biophysical, and cell biological methods has uncovered several fundamental principles of genome organization. They highlight that genome function is a major driver of genome architecture and that structural features of chromatin act as modulators, rather than binary determinants, of genome activity. The interplay of these principles in the context of self-organization can account for the emergence of structural chromatin features, the diversity and single-cell heterogeneity of nuclear architecture in cell types and tissues, and explains evolutionarily conserved functional features of genomes, including plasticity and robustness.
Structurally Resolved SARS-CoV-2 Antibody Shows High Efficacy in Severely Infected Hamsters and Provides a Potent Cocktail Pairing Strategy
Venue: Cell

Understanding how potent neutralizing antibodies (NAbs) inhibit SARS-CoV-2 is critical for effective therapeutic development. We previously described BD-368-2, a SARS-CoV-2 NAb with high potency; however, its neutralization mechanism is largely unknown. Here we report the 3.5-Å cryo-EM structure of BD-368-2/trimeric-spike complex, revealing that BD-368-2 fully blocks ACE2 recognition by occupying all three receptor-binding domains (RBDs) simultaneously, regardless of their “up” or “down” conformations. Also, BD-368-2 treats infected adult hamsters at low dosages and at various administering windows, in contrast to placebo hamsters that manifested severe interstitial pneumonia. Moreover, BD-368-2’s epitope completely avoids the common binding site of VH3-53/VH3-66 recurrent NAbs, evidenced by tripartite co-crystal structures with RBD. Pairing BD-368-2 with a potent recurrent NAb neutralizes SARS-CoV-2 pseudovirus at pM level and rescues mutation-induced neutralization escapes. Together, our results rationalized a new RBD epitope that leads to high neutralization potency and demonstrated BD-368-2’s therapeutic potential in treating COVID-19.