Miracle-dz/UniFAR-FTUs huggingface dataset:
The effect of strap muscle transection on voice and swallowing changes after thyroidectomy in patients without laryngeal nerve injury.

INTRODUCTION Voice and swallowing symptoms are frequently reported after thyroidectomy even without laryngeal nerve injury. We aimed to evaluate the effect of strap muscle transection on voice and swallowing outcome after thyroidectomy. METHODS Group 1 (G1) consisted of 17 patients who had their strap muscles transected during thyroidectomy and group 2 (G2) consisted of 17 patients who had their strap muscles preserved during thyroidectomy. None of the patients had laryngeal nerve injury. Voice impairment scores (VIS) and swallowing impairment scores (SIS) were obtained preoperatively and at 1 week and 1, 3 and 6 months postoperatively. Pre- and postoperative vocal cord examinations were performed for all patients. The external branch of the superior laryngeal nerve (EBSLN) was evaluated by intraoperative cricothyroid muscle electromyography. RESULTS There was no significant difference in VIS and SIS between the two groups. At postoperative week 1, the VIS and SIS for each group were above preoperative values (G1: p = 0.005 and p = 0.035; G2: p = 0.031, p = 0.346, for VIS and SIS respectively). The VIS and SIS scores at 6 months postoperatively were significantly lower than those of the first week postoperatively (G1: p = 0.04 and p = 0.001; G2: p = 0.022 and p = 0.034 respectively) and similar to preoperative values (G1: p = 0.924 and p = 0.086; G2: p = 0.822 and p = 0.187 respectively). CONCLUSION Although voice and swallowing complaints increased in the early postoperative period even without recurrent laryngeal nerve and EBSLN injuries, these symptoms are not related with the strap muscle transection.
Modeling and simulating the nerve axon as a thin-film microstrip

Since Hodgkin and Huxley described the nerve axon as a cable (H–H model), many efforts have been made to find more approximated transmission line models representing the nerve axon. This paper describes a simple model that represents the nerve axon in two parts: the internodal space as a lossy thin-film microstrip line and the node of Ranvier as an active complex load. The complex load terminating the transmission line is given by the variable impedance of a tunnel diode. First, the internodal space is circuitally analyzed and electromagnetically simulated as a lossy thin-film microstrip line terminated on a complex fixed load. The transmission line circuit theory, the two-port network analysis, and a two-dimensional finite difference time domain method are used for such a task by forcing a strip subatomic metallization. Then, the transfer function of the internodal space, cascaded with the node of Ranvier, is equated to the transfer function of a transmission line section that includes a tunnel diode. This procedure is carried out in order to obtain the diode's variable impedance. The diode was introduced by Nagumo, Arimoto, and Yoshizawa for simulating the nerve axon as an active transmission line. The active transmission line is represented by the FitzHugh simplified H–H model known as the Bonhoeffer–van der Pol model.
Maternal Swimming Exercise During Pregnancy Improves Memory Through Enhancing Neurogenesis and Suppressing Apoptosis via Wnt/β-Catenin Pathway in Autistic Mice

Purpose Wnt pathway is closely related to neurodevelopmental process associated with cognitive function. After administration of valproic acid to the pregnant mice, the effect of swimming exercise of pregnant mice on the memory, neuronal production, and apoptosis of pups was studied in relation with Wnt/β-catenin signaling pathway. Methods On day 12 of pregnancy, mice were injected subcutaneously with 400-mg/kg valproic acid. The pregnant mice in the control with swimming exercise group and in the valproic acid injection with swimming exercise group were allowed for swimming for 30 minutes one time per a day, repeated 5 days per a week, during 3 weeks. Step-through avoidance task and Morris water maze task for memory function, immunohistochemistry for 5-bromo-2’-deoxyuridine (BrdU)-positive cells and western blot for brain-derived neurotrophic factor (BDNF), Wnt, β-catenin, Bcl-2 related X protein (Bax), B-cell lymphoma 2 (Bcl-2), cleaved caspase-3 were carried out. Results Maternal swimming exercise during pregnancy improved memory function, increased BDNF expression, and neuronal proliferation in the valproic acid injected pups. Maternal swimming exercise during pregnancy suppressed Wnt expression and phosphorylation of β-catenin in the valproic acid injected pups. Maternal swimming exercise inhibited Bax and cleaved caspase-3 expression and increased Bcl-2 expression in the valproic acid injected pups. Conclusions Maternal swimming exercise during pregnancy improved memory function by increasing cell proliferation and inhibiting apoptosis through Wnt/β-catenin signaling cascade activation in the valproic acid injected pups. Maternal swimming exercise during pregnancy may have a protective effect on factors that induce autism in the fetus.
Perfusion culture of Chinese Hamster Ovary cells for bioprocessing applications

Abstract Much of the biopharmaceutical industry’s success over the past 30 years has relied on products derived from Chinese Hamster Ovary (CHO) cell lines. During this time, improvements in mammalian cell cultures have come from cell line development and process optimization suited for large-scale fed-batch processes. Originally developed for high cell densities and sensitive products, perfusion processes have a long history. Driven by high volumetric titers and a small footprint, perfusion-based bioprocess research has regained an interest from academia and industry. The recent pandemic has further highlighted the need for such intensified biomanufacturing options. In this review, we outline the technical history of research in this field as it applies to biologics production in CHO cells. We demonstrate a number of emerging trends in the literature and corroborate these with underlying drivers in the commercial space. From these trends, we speculate that the future of perfusion bioprocesses is bright and that the fields of media optimization, continuous processing, and cell line engineering hold the greatest potential. Aligning in its continuous setup with the demands for Industry 4.0, perfusion biomanufacturing is likely to be a hot topic in the years to come.
End-to-end test for fractionated online adaptive MR-guided radiotherapy using a deformable anthropomorphic pelvis phantom

Objective. In MR-guided radiotherapy (MRgRT) for prostate cancer treatments inter-fractional anatomy changes such as bladder and rectum fillings may be corrected by an online adaption of the treatment plan. To clinically implement such complex treatment procedures, however, specific end-to-end tests are required that are able to validate the overall accuracy of all treatment steps from pre-treatment imaging to dose delivery. Approach. In this study, an end-to-end test of a fractionated and online adapted MRgRT prostate irradiation was performed using the so-called ADAM-PETer phantom. The phantom was adapted to perform 3D polymer gel (PG) dosimetry in the prostate and rectum. Furthermore, thermoluminescence detectors (TLDs) were placed at the center and on the surface of the prostate for additional dose measurements as well as for an external dose renormalization of the PG. For the end-to-end test, a total of five online adapted irradiations were applied in sequence with different bladder and rectum fillings, respectively. Main results. A good agreement of measured and planned dose was found represented by high γ -index passing rates ( 3%/3mm criterion) of the PG evaluation of 98.9% in the prostate and 93.7% in the rectum. TLDs used for PG renormalization at the center of the prostate showed a deviation of −2.3%. Significance. The presented end-to-end test, which allows for 3D dose verification in the prostate and rectum, demonstrates the feasibility and accuracy of fractionated and online-adapted prostate irradiations in presence of inter-fractional anatomy changes. Such tests are of high clinical importance for the commissioning of new image-guided treatment procedures such as online adaptive MRgRT.
Reciprocal SH2-SH3 Domain Contacts between ITK Molecules Limit T Cell Receptor Signaling in Th2-type CD4+ T Cells

ABSTRACT The nonreceptor tyrosine kinase ITK is a key component of the T cell receptor (TCR) signaling pathway and is required for cytokine production by CD4+ T cells that have differentiated into Th2 cells. Structural and biochemical studies suggest that contacts between the SH2 and SH3 domains of ITK mediate intermolecular self-association, forming a structure that restrains ITK activity by interfering with interactions between ITK and other components of the TCR signaling pathway. Wild-type (WT) ITK and a panel of ITK mutants containing amino acid substitutions in the SH2 and SH3 domains were tested for self-association and for binding to the adaptor protein SLP76, a key ligand for the ITK SH2 domain. WT and ITK mutants were also expressed in Itk-deficient CD4+ T cells via retroviral-mediated gene delivery to analyze their ability to support TCR signaling and cytokine production by Th2 cells. Specific amino acid substitutions in the ITK SH2 or SH3 domains impaired self-association, with the greatest effects being seen when both intermolecular SH2-SH3 domain contacts were disrupted. Two of the SH2 domain substitutions tested reduced ITK self-association but had no effect on binding to SLP-76. When their function was analyzed in Th2 cells, ITK proteins with diminished self-association activity supported greater IL-4 production and calcium flux in response to TCR stimulation compared to WT ITK. Our findings indicate that intermolecular contacts between ITK molecules can restrain the amplitude of TCR signaling, suggesting ITK is a limiting factor for responses by CD4+ T cells.
Self-efficacy in controlling upsetting thoughts, but not positive gains, mediates the effects of benefit-finding group intervention for Alzheimer family caregivers.

This study aimed to examine the therapeutic mechanism of the benefit-finding therapeutic (BFT) intervention that used cognitive reappraisal and alternative thinking to construct positive aspects of caregiving (PAC), in a cluster-randomized controlled trial for Alzheimer caregivers. Forty two caregivers received BFT, whereas 87 received psychoeducation as control. Depressive symptoms and global burden were outcomes measured at baseline, postintervention, and 4- and 10-month follow-up. Mediators considered included PAC (measured by benefit word count to a qualitative measure) and three self-efficacies-controlling upsetting thoughts (SE-CUT), responding to disruptive behaviors, and obtaining respite. Using mixed-effects regression, we demonstrated that benefit-finding increased caregivers' PAC and SE-CUT, but that only SE-CUT uniquely predicted depressive symptoms and global burden longitudinally. Path analyses with bootstrapped confidence intervals, using full information maximum likelihood estimation to retain the whole sample with partial missing data, showed that SE-CUT change from baseline to postintervention mediated intervention effects on depressive symptoms, but not global burden, at both follow-ups. No mediation effects were found for PAC and the other self-efficacies. The BFT effect on depressive symptoms was partly accounted for by improvement in SE-CUT. The therapeutic mechanism for the effect on burden remained unknown. The study sheds light on the importance of actively promoting positive caregiver functioning. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Comprehensive analyses of microRNA and mRNA expression in colorectal serrated lesions and colorectal cancer with a microsatellite instability phenotype

MicroRNA (miRNA) expression is dysregulated in human tumors, thereby contributing to tumorigenesis through altered expression of mRNA. Thus, identification of the relationships between miRNAs and mRNAs is important for evaluating the molecular mechanisms of tumors. In addition, elucidation of the molecular features of serrated lesions is essential in colorectal tumorigenesis. Here, we examined the relationships of miRNA and mRNA expressed in serrated lesions, including 26 sessile serrated lesions (SSLs), 12 traditional serrated adenomas (TSAs), and 11 colorectal cancers (CRCs) with a microsatellite instability (MSI) phenotype using crypt isolation. We divided the samples into the first and second cohorts for validation. Array‐based expression analyses were used to evaluate miRNAs and mRNAs with opposite expression patterns in isolated tumor glands. In addition, we validated the relationships of miRNA/mRNA pairs in the second cohort using real‐time polymerase chain reaction. We found that the expression of miRNA‐5787 was correlated with reciprocal expression of two mRNAs, that is, SRRM2 and POLR2J3, in SSL samples. In TSA samples, two pairs of miRNAs/mRNAs showing opposite expression patterns, that is, miRNA‐182‐5p/ETF1 and miRNA‐200b‐3p/MYB, were identified. Ultimately, three pairs of miRNAs/mRNAs with opposite expression patterns, including miRNA‐222‐3p/SLC26A3, miRNA‐6753‐3p/FABP1, and miRNA‐222‐3p/OLFM4, were retained in CRC with an MSI phenotype. Finally, we performed transfection with an miR‐222‐3p mimic to confirm the expression of SLC26A3 and OLFM4; the results showed that ectopic expression of miR‐222‐3p moderately suppressed OLFM4 and downregulated SLC26A3 to some extent. Overall, our results provided basic insights into the evaluation of colorectal tumorigenesis of serrated lesions and CRC with an MSI phenotype.
A tangled web: Comparing inter‐ and intraspecific mating dynamics in Anasa squash bugs

Reproductive interference, reproductive interactions between heterospecific individuals including mating, is commonly reported across taxa, but its drivers are still unclear. Studying interspecific matings in the context of their conspecific mating system—by relating an individual's conspecific mating behaviour to its heterospecific interactions—offers a powerful approach to address this uncertainty. Here, we compare inter‐ and intraspecific mating dynamics in the squash bug Anasa tristis and its close relative Anasa andresii under semi‐natural conditions. Using replicated enclosures, we surveyed the mating behaviour of individually marked A. tristis and A. andresii (five males and five females of each species per trial) at hourly intervals using a robotic camera system over a 14‐day period. We uncovered high levels of reproductive interference (19% of individuals engaged in interspecific matings), but the majority of mating activity took place between conspecifics. A. tristis females which engaged in interspecific matings had comparable hatching success with those which did not. Therefore, in this system, relatively high levels of reproductive interference may emerge under semi‐natural conditions as a by‐product of limited intraspecific pre‐copulatory choice paired with limited fitness penalties for at least one of the species involved.
MG53 E3 Ligase-dead Mutant Protects Diabetic Hearts from Acute Ischemic/Reperfusion Injury and Ameliorates Diet-induced Cardiometabolic Damage.

Cardiometabolic diseases, including diabetes and its cardiovascular complications, are the global leading cause of death, highlighting a major unmet medical need. Over the last decade, MG53, also named TRIM72, has emerged as a powerful agent for myocardial membrane repair and cardioprotection, but its therapeutic value is complicated by its E3 ligase activity that mediates metabolic disorders. Here, we show that an E3 ligase-dead mutant, MG53-C14A, retains its cardioprotective function without causing metabolic side-effects. When administrated in normal animals, both recombinant human wild type MG53 protein (rhMG53-WT) and its E3 ligase-dead mutant (rhMG53-C14A) protect the heart equally from myocardial infarction and ischemia/reperfusion (I/R) injury. However, in diabetic db/db mice, rhMG53-WT treatment markedly aggravates hyperglycemia, cardiac I/R injury and mortality, whereas acute and chronic treatment of rhMG53-C14A still effectively ameliorates I/R-induced myocardial injury and mortality or diabetic cardiomyopathy, respectively, without inflicting metabolic side-effects. Furthermore, knock-in of MG53-C14A protects the mice from high-fat diet-induced metabolic disorders and cardiac damage. Thus, the E3 ligase-dead mutant MG53-C14A not only protects the heart from acute myocardial injury but also counteract metabolic stress, providing a potentially important therapy for the treatment of acute myocardial injuries amidst metabolic disorders, including diabetes and obesity.
Effect of linguistic factors on the occurrence of stuttering-like disfluency among Japanese-speaking preschool children who stutter

ABSTRACT This study aimed to investigate the linguistic factors involved in stuttering among Japanese-speaking preschool children. The participants included 10 Japanese children who stutter, with a mean age of 5 years and 9 months. Speech samples comprised spontaneous conversations of the participants with their parents for about 20 minutes. We compared the percentages of the occurrence of stuttering-like disfluencies (SLDs) at the word and sentence levels, using the Wilcoxon signed-rank test. The results showed no significant differences in SLDs based on syllable structure when comparing light and heavy syllables and comparing consonants and vowels in the initial position of each content word. SLDs occurred more frequently in the initial than non-initial position of words and in longer rather than shorter words. Additionally, SLDs occurred more frequently in sentences that contained more ‘bunsetsu’ (a kind of linguistic unit in Japanese). Our study is the first to show that both word and sentence-level factors could contribute to SLDs in preschool children who stutter in agglutinating languages, such as Japanese. This aspect is rarely reported in psycholinguistic studies based on stuttering occurrence in inflecting languages, such as English.
A growth factor–expressing macrophage subpopulation orchestrates regenerative inflammation via GDF-15

Regenerative inflammation in skeletal muscle drives macrophage specification via a regeneration-promoting program. A growth factor–expressing macrophage population develops, producing GDF-15 under the control of RXR and PPARγ. GDF-15 acts as an autocrine and paracrine factor coordinating myoblast proliferation and myeloid cell invasion and activity.
Structural dynamics in the evolution of a bilobed protein scaffold

Significance Proteins conduct numerous complex biological functions by use of tailored structural dynamics. The molecular details of how these emerged from ancestral peptides remains mysterious. How does nature utilize the same repertoire of folds to diversify function? To shed light on this, we analyzed bilobed proteins with a common structural core, which is spread throughout the tree of life and is involved in diverse biological functions such as transcription, enzymatic catalysis, membrane transport, and signaling. We show here that the structural dynamics of the structural core differentiate predominantly via terminal additions during a long-period evolution. This diversifies substrate specificity and, ultimately, biological function. Novel biophysical tools allow the structural dynamics of proteins and the regulation of such dynamics by binding partners to be explored in unprecedented detail. Although this has provided critical insights into protein function, the means by which structural dynamics direct protein evolution remain poorly understood. Here, we investigated how proteins with a bilobed structure, composed of two related domains from the periplasmic-binding protein–like II domain family, have undergone divergent evolution, leading to adaptation of their structural dynamics. We performed a structural analysis on ∼600 bilobed proteins with a common primordial structural core, which we complemented with biophysical studies to explore the structural dynamics of selected examples by single-molecule Förster resonance energy transfer and Hydrogen–Deuterium exchange mass spectrometry. We show that evolutionary modifications of the structural core, largely at its termini, enable distinct structural dynamics, allowing the diversification of these proteins into transcription factors, enzymes, and extracytoplasmic transport-related proteins. Structural embellishments of the core created interdomain interactions that stabilized structural states, reshaping the active site geometry, and ultimately altered substrate specificity. Our findings reveal an as-yet-unrecognized mechanism for the emergence of functional promiscuity during long periods of evolution and are applicable to a large number of domain architectures.
Effects of cross-sectional area and aspect ratio coupled with orientation on mechanical properties and deformation behavior of Cu nanowires

Metal nanomaterials exhibit excellent mechanical properties compared with corresponding bulk materials and have potential applications in various areas. Despite a number of studies of the size effect on Cu nanowires mechanical properties with square cross-sectional, investigations of them in rectangular cross-sectional with various sizes at constant volume are rare, and lack of multifactor coupling effect on mechanical properties and quantitative investigation. In this work, the dependence of mechanical properties and deformation mechanisms of Cu nanowires/nanoplates under tension on cross-sessional area, aspect ratio of cross-sectional coupled with orientation were investigated using molecular dynamics simulations and the semi-empirical expressions related to mechanical properties were proposed. The simulation results show that the Young’s modulus and the yield stress sharply increase with the aspect ratio except for the 〈110〉{110}{001} Cu nanowires/nanoplates at the same cross-sectional area. And the Young’s modulus increases while the yield stress decreases with the cross-sectional area of Cu nanowires. However, both of them increase with the cross-sectional area of Cu nanoplates. Besides, the Young’s modulus increases with the cross-sectional area at all the orientations. The yield stress shows a mildly downward trend except for the 〈111〉 Cu nanowires with increased cross-sectional area. For the Cu nanowires with a small cross-sectional area, the surface force increases with the aspect ratio. In contrast, it decreases with the aspect ratio increase at a large cross-sectional area. At the cross-sectional area of 13.068 nm2, the surface force decreases with the aspect ratio of the 〈110〉 Cu nanowires while it increases at other orientations. The surface force is a linearly decreasing function of the cross-sectional area at different orientations. Quantitative studies show that Young’s modulus and yield stress to the aspect ratio of the Cu nanowires satisfy exponent relationship. In addition, the main deformation mechanism of Cu nanowires is the nucleation and propagation of partial dislocations while it is the twinning-dominated reorientation for Cu nanoplates.