Miracle-dz/UniFAR-FTUs huggingface dataset:
Incorporation of transition to transversion ratio and nonsense mutations, improves the estimation of the number of synonymous and non-synonymous sites in codons

Abstract A common approach to estimate the strength and direction of selection acting on protein coding sequences is to calculate the dN/dS ratio. The method to calculate dN/dS has been widely used by many researchers and many critical reviews have been made on its application after the proposition by Nei and Gojobori in 1986. However, the method is still evolving considering the non-uniform substitution rates and pretermination codons. In our study of SNPs in 586 genes across 156 Escherichia coli strains, synonymous polymorphism in 2-fold degenerate codons were higher in comparison to that in 4-fold degenerate codons, which could be attributed to the difference between transition (Ti) and transversion (Tv) substitution rates where the average rate of a transition is four times more than that of a transversion in general. We considered both the Ti/Tv ratio, and nonsense mutation in pretermination codons, to improve estimates of synonymous (S) and non-synonymous (NS) sites. The accuracy of estimating dN/dS has been improved by considering the Ti/Tv ratio and nonsense substitutions in pretermination codons. We showed that applying the modified approach based on Ti/Tv ratio and pretermination codons results in higher values of dN/dS in 29 common genes of equal reading-frames between E. coli and Salmonella enterica. This study emphasizes the robustness of amino acid composition with varying codon degeneracy, as well as the pretermination codons when calculating dN/dS values.
Regulation by Cross-Linking Surface Molecules Independence, Partial LFA-1 Dependence, and Clusters In Vitro and In Vivo: T Cell Dendritic Cells and Resting B Cells Form

Initiation of an Ab response requires interaction between dendritic cells (DC), T cells, and B cells in a T cell area. We demonstrate that rat DC and B cells form T cell-independent clusters in vitro and in vivo. In vitro clusters form within 1 h and dissociate within 24 to 48 h. Clustering is restricted to resting B cells, is energy, cytoskeleton, and protein kinase C dependent, and is inhibited by anti-LFA-1 but not anti-ICAM-1 mAbs. Spleen and lymph node B cells cluster more strongly than those from lymph or blood, suggesting up-regulation of adhesiveness during transendothelial migration. Bone marrow B cells do not form clusters. DC from spleen and lymph nodes show the most clustering, lymph-borne DC are intermediate, and DC from lamina propria, Peyer’s patches, and those grown from bone marrow form the fewest clusters. Clustering is stimulated by cross-linking MHC class II (whole mAb or F(ab * ) 2 ) on DC or B cells or Thy-1 on DC, but not MHC class I, CD45, or CD44. Stimulation by mAb is energy, cytoskeletal, and protein kinase C dependent, but is not inhibited by anti-LFA-1 mAbs, suggesting involvement of other, unidentiﬁed adhesion molecules. We suggest that interactions between DC and B cells will occur regularly during B cell recirculation. Cross-linking of MHC class II-peptide molecules on DC by speciﬁc T cells would increase binding avidity, causing retention of Ag-speciﬁc B cells on DC long enough for the B cells to process Ag, thereby facilitating cognate interactions between T and B cells. 1998, 160: 1774–1781.
A RULE-BASED GENERATIVE MUSIC SYSTEM CONTROLLED BY DESIRED VALENCE AND AROUSAL

This paper details an emotional music synthesis (EMS) system which is designed around music theory parameters and previous research on music and emotion. This sys-tem uses a rule-based algorithm to generate the music from scratch. Results of a user study on this system show that listener ratings of emotional valence and arousal correlate with intended production of musical valence and arousal
Protein Condensate Formation via Controlled Multimerization of Intrinsically Disordered Sequences

Many proteins harboring low complexity or intrinsically disordered sequences (IDRs) are capable of undergoing liquid–liquid phase separation to form mesoscale condensates that function as biochemical niches with the ability to concentrate or sequester macromolecules and regulate cellular activity. Engineered disordered proteins have been used to generate programmable synthetic membraneless organelles in cells. Phase separation is governed by the strength of interactions among polypeptides with multivalency enhancing phase separation at lower concentrations. Previously, we and others demonstrated enzymatic control of IDR valency from multivalent precursors to dissolve condensed phases. Here, we develop noncovalent strategies to multimerize an individual IDR, the RGG domain of LAF-1, using protein interaction domains to regulate condensate formation in vitro and in living cells. First, we characterize modular dimerization of RGG domains at either terminus using cognate high-affinity coiled-coil pairs to form stable condensates in vitro. Second, we demonstrate temporal control over phase separation of RGG domains fused to FRB and FKBP in the presence of dimerizer. Further, using a photocaged dimerizer, we achieve optically induced condensation both in cell-sized emulsions and within live cells. Collectively, these modular tools allow multiple strategies to promote phase separation of a common core IDR for tunable control of condensate assembly.
Cross-cultural adaptation and psychometric evaluation of the Brazilian Portuguese version of the Vulvovaginal Symptoms Questionnaire

Vulvovaginal symptoms are common and challenging problems that can occur because of several factors, and the use of validated questionnaires is a way to evaluate both symptoms and their impact on quality of life. The Vulvovaginal Symptoms Questionnaire–Brazilian Portuguese is a valid tool to assess vulvovaginal symptoms and can be used in the daily practice of health care professionals in Brazil. Abstract Objective The aims of this study were to perform a cross-cultural adaptation of the Vulvovaginal Symptoms Questionnaire (VSQ) into Brazilian Portuguese (VSQ-Br) and evaluate its measurement properties (structural validity, construct validity, internal consistency, and reliability). Methods Cross-cultural adaptation was conducted through the translation, synthesis, and back-translation of the VSQ-Br. Subsequently, 314 women completed the Pelvic Floor Impact Questionnaire, Pelvic Floor Disorders Inventory, Medical Outcomes Study 36-Item Short-Form Health Survey, and VSQ-Br. Seven to 10 days later, participants completed the VSQ-Br for the second time. Data were submitted for confirmatory factor analysis. Cronbach α was used to verify internal consistency, and construct validity was assessed using Pearson correlation coefficient (r). Reliability was calculated using the intraclass correlation coefficient. Results Confirmatory factor analysis showed that the questions were grouped into four domains (symptoms, emotions, life impact, and sexual impact). The model showed good fit (>0.95). The Cronbach α in this study was 0.85, reflecting adequate internal consistency. Adequate reliability was confirmed, with an intraclass correlation coefficient total score of 0.80. The VSQ-Br had a weak correlation with the pelvic domain of the Pelvic Floor Disorders Inventory, the pelvic organ prolapse domain of the Pelvic Floor Impact Questionnaire, and pain, vitality, and the social aspect domains of the Medical Outcomes Study 36-Item Short-Form Health Survey. Conclusions The VSQ-Br was validated and had acceptable measurement properties for assessing vulvovaginal symptoms in Brazilian women.
Improved direct compression properties of Gardeniae fructus water extract powders via fluid bed-mediated surface engineering

Abstract Direct compression (DC) attracts increasing attention for tablet manufacturing; however, its application in medicinal plant tablets is still extremely limited. In this work, eight kinds of the Gardeniae fructus water extract powder (GF)-based composite particles (CPs) were prepared with different cohesive surface engineering materials, including dextran, inulin, hypromellose, and povidone, alone or in combination with mannitol and colloidal silica. Their physical properties and compacting parameters were characterized comprehensively. All the CPs showed marked improvement in tabletability, which is about 2–4 times higher than that of GF and physical mixtures (PMs). Specifically, the CPs showed a 7.45–26.48 times higher hardness (Ha) value and a 1.26–2.74 times higher cohesiveness (Co) value than PMs. In addition, all the CPs (angle of repose being from 34.27° to 38.46°) showed better flowability than PMs (35.49° to 53.53°) and GF (51.86°). These results demonstrated that (i) fluid-bed coating was not a simple process of superposition and transmission of the physical properties of raw materials; and (ii) all the surface engineering materials studied could improve the DC properties of problematic GF to some degree. As a whole, through the design of fluid-bed coating CPs, qualified tablets with high GF loadings (up to 93%) were produced via DC. Graphical Abstract
A look-ahead variant of the Lanczos algorithm and its application to the quasi-minimal residual method for non-Hermitian linear systems. Ph.D. Thesis - Massachusetts Inst. of Technology, Aug. 1991

The Lanczos algorithm can be used both for eigenvalue problems and to solve linear systems. However, when applied to non-Hermitian matrices, the classical Lanczos algorithm is susceptible to breakdowns and potential instabilities. In addition, the biconjugate gradient (BCG) algorithm, which is the natural generalization of the conjugate gradient algorithm to non-Hermitian linear systems, has a second source of breakdowns, independent of the Lanczos breakdowns. Here, we present two new results. We propose an implementation of a look-ahead variant of the Lanczos algorithm which overcomes the breakdowns by skipping over those steps where a breakdown or a near-breakdown would occur. The new algorithm can handle look-ahead steps of any length and requires the same number of matrix-vector products and inner products per step as the classical Lanczos algorithm without look-ahead. Based on the proposed look-ahead Lanczos algorithm, we then present a novel BCG-like approach, the quasi-minimal residual (QMR) method, which avoids the second source of breakdowns in the BCG algorithm. We present details of the new method and discuss some of its properties. In particular, we discuss the relationship between QMR and BCG, showing how one can recover the BCG iterates, when they exist, from the QMR iterates. We also present convergence results for QMR, showing the connection between QMR and the generalized minimal residual (GMRES) algorithm, the optimal method in this class of methods. Finally, we give some numerical examples, both for eigenvalue computations and for non-Hermitian linear systems.
Neuroinflammation and HIV-Associated Cognitive Impairment

Modern antiretroviral treatments slow viral replication and improve the immune function of people living with HIV infection (PWH), and they now have an increased life expectancy and a better quality of life. However, continuous low-level viral replication or production of viral toxins may contribute to chronic inflammation and is associated with comorbidities such as obesity, cardiovascular diseases, metabolic disturbances (e.g., diabetes and insulin resistance) and, eventually, brain injury. In the brain, HIV infection promotes and perpetuates chronic neuroinflammation with an eventual irreversible brain injury and HIV-associated neurocognitive disorder (HAND). 1,2
Impact of program characteristics on weight loss in adult behavioral weight management interventions: systematic review and component network meta‐analysis

Behavioral weight management programs (BWMPs) for adults lead to greater weight loss at 12 months than minimal‐intervention control treatments. However, there is considerable heterogeneity in the content of BWMPs and outcomes of treatment. This study assessed the contribution of individual components of BWMPs, using Bayesian component network meta‐analysis.
A method of classification decision based on multi-BiLSTMs for physical loads hierarchy

Abstract Human gait is systematically deformed by physical loads, this study constructs and evaluates an algorithm for classifying different levels of physical loads. The algorithm uses wearable IMUs data to classify different levels of loads. We aim to evaluate classification as strategy for multi-loads recognition for the control of wearable exoskeletons. 10 adults participated in the experiment. In the experiment, the subjects walked on flat ground carrying a backpack with different weight of loads (0, 15 and 25 kg), and three sensors on the lower limbs collected the subjects' gait data in real time. In this study, a method of classification decision based on multiple bidirectional long short-term memory(multi-BiLSTMs) was proposed which was used to classify the load level of the collected data. The classification accuracy of this method reached 94.1%, and the F-score was 0.935–0.952. Compared with LSTM and BiLSTM, the proposed method has better performance in accuracy of load classification. The results of this study contribute to quantify the load, which has promising applications in the medical and labor protection fields.
A prospective, randomized, parallel group, double blind, multicenter study to compare the efficacy, safety and immunogenicity of Lupin’s Ranibizumab with Lucentis® in patients with neovascular age-related macular degeneration

Purpose: The present study compares the efficacy, safety, and immunogenicity of Lupin’s biosimilar ranibizumab with that of Lucentis® in patients with neovascular age-related macular degeneration. Methods: This prospective, double-blind, multi-centric phase-III study was conducted across 19 centers in India. A total of 202 patients with neovascular age-related macular degeneration were randomized (1:1) to receive either Lupin’s biosimilar ranibizumab or Lucentis®, 0.5 mg, as an intravitreous injection once every month for 3 months. The primary efficacy endpoint was the proportion of patients who lost fewer than 15 letters from baseline in best-corrected visual acuity. The safety profile included assessment of adverse events, ophthalmic examination, physical and systemic examination, and vital parameters. The immunogenicity assessment was based on evaluation of anti-drug antibodies. Results: Overall, 174 patients (87 [86.14%] in each group) completed the study. The demographics and baseline characteristics were comparable between the treatment groups. The proportion of patients losing fewer than 15 letters from baseline best corrected visual acuity score in the study eye was comparable between two groups. The difference between Lupin’s ranibizumab and Lucentis® for the proportion of patients who lost fewer than 15 letters was within the predefined equivalence margin (intention-to-treat population: 1.0%; 95% confidence interval [CI], −3.3% to 5.4% and per protocol population: 1.2%; 95% CI, −3.2% to 6.4%). The incidence of treatment-emergent adverse events was comparable, and 11 (10.89%) patients in Lupin’s ranibizumab and 19 (18.81%) patients in Lucentis® group had at least one treatment-emergent adverse event. The immunogenicity incidence as assessed by proportion of patients with positive anti-drug antibodies was numerically lower in Lupin’s ranibizumab (4.95%) than Lucentis® (12.87%). Conclusion: Lupin’s biosimilar ranibizumab demonstrated therapeutic equivalence, desirable safety, and favorable immunogenicity profile compared to Lucentis®.
Hybrid extracellular vesicles-liposome incorporated advanced bioink to deliver microRNA

In additive manufacturing, bioink formulations govern strategies to engineer 3D living tissues that mimic the complex architectures and functions of native tissues for successful tissue regeneration. Conventional 3D-printed tissues are limited in their ability to alter the fate of laden cells. Specifically, the efficient delivery of gene expression regulators (i.e. microRNAs (miRNAs)) to cells in bioprinted tissues has remained largely elusive. In this study, we explored the inclusion of extracellular vesicles (EVs), naturally occurring nanovesicles (NVs), into bioinks to resolve this challenge. EVs show excellent biocompatibility, rapid endocytosis, and low immunogenicity, which lead to the efficient delivery of miRNAs without measurable cytotoxicity. EVs were fused with liposomes to prolong and control their release by altering their physical interaction with the bioink. Hybrid EVs-liposome (hEL) NVs were embedded in gelatin-based hydrogels to create bioinks that could efficiently encapsulate and deliver miRNAs at the target site in a controlled and sustained manner. The regulation of cells’ gene expression in a 3D bioprinted matrix was achieved using the hELs-laden bioink as a precursor for excellent shape fidelity and high cell viability constructs. Novel regulatory factors-loaded bioinks will expedite the translation of new bioprinting applications in the tissue engineering field.
High-velocity features of calcium and silicon in the spectra of Type Ia supernovae

"High-velocity features" (HVFs) are spectral features in Type Ia supernovae (SNe Ia) that have minima indicating significantly higher (by greater than about 6000 km/s) velocities than typical "photospheric-velocity features" (PVFs). The PVFs are absorption features with minima indicating typical photospheric (i.e., bulk ejecta) velocities (usually ~9000-15,000 km/s near B-band maximum brightness). In this work we undertake the most in-depth study of HVFs ever performed. The dataset used herein consists of 445 low-resolution optical and near-infrared (NIR) spectra (at epochs up to 5 d past maximum brightness) of 210 low-redshift SNe Ia that follow the "Phillips relation. " A series of Gaussian functions is fit to the data in order to characterise possible HVFs of Ca II H&K, Si II {\lambda}6355, and the Ca II NIR triplet. The temporal evolution of the velocities and strengths of the PVFs and HVFs of these three spectral features is investigated, as are possible correlations with other SN Ia observables. We find that while HVFs of Ca II are regularly observed (except in underluminous SNe Ia, where they are never found), HVFs of Si II {\lambda}6355 are significantly rarer, and they tend to exist at the earliest epochs and mostly in objects with large photospheric velocities. It is also shown that stronger HVFs of Si II {\lambda}6355 are found in objects that lack C II absorption at early times and that have red ultraviolet/optical colours near maximum brightness. These results lead to a self-consistent connection between the presence and strength of HVFs of Si II {\lambda}6355 and many other mutually correlated SN~Ia observables, including photospheric velocity.
fNIRS-based brain state transition features to signify functional degeneration after Parkinson’s disease

Objective. Parkinson’s disease (PD) is a common neurodegenerative brain disorder, and early diagnosis is of vital importance for treatment. Existing methods are mainly focused on behavior examination, while the functional neurodegeneration after PD has not been well explored. This paper aims to investigate the brain functional variation of PD patients in comparison with healthy controls. Approach. In this work, we propose brain hemodynamic states and state transition features to signify functional degeneration after PD. Firstly, a functional near-infrared spectroscopy (fNIRS)-based experimental paradigm was designed to capture brain activation during dual-task walking from PD patients and healthy controls. Then, three brain states, named expansion, contraction, and intermediate states, were defined with respect to the oxyhemoglobin and deoxyhemoglobin responses. After that, two features were designed from a constructed transition factor and concurrent variations of oxy- and deoxy-hemoglobin over time, to quantify the transitions of brain states. Further, a support vector machine classifier was trained with the proposed features to distinguish PD patients and healthy controls. Main results. Experimental results showed that our method with the proposed brain state transition features achieved classification accuracy of 0.8200 and F score of 0.9091, and outperformed existing fNIRS-based methods. Compared with healthy controls, PD patients had significantly smaller transition acceleration and transition angle. Significance. The proposed brain state transition features well signify functional degeneration of PD patients and may serve as promising functional biomarkers for PD diagnosis.
Salivary bypass tube in total laryngectomy: Systematic review and meta‐analysis

The aim of this study is to determine whether the preventive positioning of a salivary bypass tube (SBT) after total laryngectomy (TL) reduces the incidence of postoperative pharyngocutaneous fistula (PCF) and pharyngeal stenosis (PS). This study was conducted in conformity with the PRISMA statement. 1960 patients with a median age of 62.0 years were included. A SBT was placed in 980 (50%) patients (SBT group). The cumulative PCF incidence in the SBT group was 15.8% (95% CI: 9.3–23.6). The measured pooled OR comparing PCF incidence in patients with SBT compared to those without was 0.40 (95% CI: 0.24–0.65). The pooled PS incidence in the SBT group was 12.3% (95% CI: 5.4–21.6). The measured pooled OR comparing PS incidence in patients with SBT compared to those without was 0.43 (95% CI: 0.24–0.65). PCF and PS could be prevented by the intra‐operative placement of a SBT.
Breaking the Iron Homeostasis: A “Trojan Horse” Self-Assembled Nanodrug Sensitizes Homologous Recombination Proficient Ovarian Cancer Cells to PARP Inhibition

Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors are used in ovarian cancer treatment and have greatly improved the survival rates for homologous recombination repair (HRR)-deficient patients. However, their therapeutic efficacy is limited in HRR-proficient ovarian cancer. Thus, sensitizing HRR-proficient ovarian cancer cells to PARP inhibitors is important in clinical practice. Here, a nanodrug, olaparib-Ga, was designed using self-assembly of the PARP inhibitor olaparib into bovine serum albumin through gallic acid gallium(III) coordination via a convenient and green synthetic method. Compared with olaparib, olaparib-Ga featured an ultrasmall size of 7 nm and led to increased suppression of cell viability, induction of DNA damage, and enhanced cell apoptosis in the SKOV3 and OVCAR3 HRR-proficient ovarian cancer cells in vitro. Further experiments indicated that the olaparib-Ga nanodrug could suppress RRM2 expression, activate the Fe2+/ROS/MAPK pathway and HMOX1 signaling, inhibit the PI3K/AKT signaling pathway, and enhance the expression of cleaved-caspase 3 and BAX protein. This, in turn, led to increased cell apoptosis in HRR-proficient ovarian cancer cells. Moreover, olaparib-Ga effectively restrained SKOV3 and OVCAR3 tumor growth and exhibited negligible toxicity in vivo. In conclusion, we propose that olaparib-Ga can act as a promising nanodrug for the treatment of HRR-proficient ovarian cancer.