Deriving Vocal Fold Oscillation Information from Recorded Voice Signals Using Models of Phonation.

During phonation, the vocal folds exhibit a self-sustained oscillatory motion, which is influenced by the physical properties of the speaker's vocal folds and driven by the balance of bio-mechanical and aerodynamic forces across the glottis. Subtle changes in the speaker's physical state can affect voice production and alter these oscillatory patterns. Measuring these can be valuable in developing computational tools that analyze voice to infer the speaker's state. Traditionally, vocal fold oscillations (VFOs) are measured directly using physical devices in clinical settings. In this paper, we propose a novel analysis-by-synthesis approach that allows us to infer the VFOs directly from recorded speech signals on an individualized, speaker-by-speaker basis. The approach, called the ADLES-VFT algorithm, is proposed in the context of a joint model that combines a phonation model (with a glottal flow waveform as the output) and a vocal tract acoustic wave propagation model such that the output of the joint model is an estimated waveform. The ADLES-VFT algorithm is a forward-backward algorithm which minimizes the error between the recorded waveform and the output of this joint model to estimate its parameters. Once estimated, these parameter values are used in conjunction with a phonation model to obtain its solutions. Since the parameters correlate with the physical properties of the vocal folds of the speaker, model solutions obtained using them represent the individualized VFOs for each speaker. The approach is flexible and can be applied to various phonation models. In addition to presenting the methodology, we show how the VFOs can be quantified from a dynamical systems perspective for classification purposes. Mathematical derivations are provided in an appendix for better readability.

Efficacy and Safety of the Anti-PD-L1 mAb Socazolimab for Recurrent or Metastatic Cervical Cancer: a Phase I Dose-Escalation and Expansion Study.

PURPOSE: This study (ClinicalTrials.gov identifier, NCT03676959) is an open, phase I dose-escalation and expansion study investigating the safety and efficacy of the recombinant, fully human anti-programmed death ligand 1 (PD-L1) mAb socazolimab in patients diagnosed with recurrent or metastatic cervical cancer. PATIENTS AND METHODS: Patients received socazolimab every 2 weeks until disease progression. The study was divided into a dose-escalation phase and a dose-expansion phase. Safety and tolerability were primary endpoints of the dose-escalation phase. The primary endpoints of the dose-expansion phase were safety and the objective response rate (ORR) of the 5 mg/kg dose. Efficacy was assessed by the third-party independent review committee (IRC) using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). RESULTS: 104 patients were successfully enrolled into the study. Twelve patients were included in the dose-escalation phase, with one complete response and two partial responses in the 5 mg/kg treatment group. Ninety-two patients (5 mg/kg) were enrolled in the dose-expansion phase. Fifty-four patients (59.3%) had baseline PD-L1-positive tumor expression (combined positive score ≥1). ORR was 15.4% [95% confidence interval (CI), 8.7%-24.5%]. Median PFS was 4.44 months (95% CI, 2.37-5.75 months), and the median OS was 14.72 months (95% CI, 9.59-NE months). ORR of PD-L1-positive patients was 16.7%, and the ORR of PD-L1-negative patients was 17.9%. No treatment-related deaths occurred. CONCLUSIONS: Our study demonstrates that socazolimab has durable safety and efficacy for the treatment of recurrent or metastatic cervical cancer and exhibits a safety profile similar to other anti-PD-1/PD-L1 mAbs.

Effective Control of Molds Using a Combination of Nanoparticles.

Molds are filamentous fungi able to grow on a variety of surfaces, including constructed surfaces, food, rotten organic matter, and humid places. Mold growth is characterized by having an unpleasant odor in enclosed or non-ventilated places and a non-aesthetic appearance. They represent a health concern because of their ability to produce and release mycotoxins, compounds that are toxic to animals and humans. The aim of this study was to evaluate commercial nanoparticles (NPs) that can be used as an additive in coatings and paints to effectively control the growth of harmful molds. Four different NPs were screened for their antifungal activities against the mycotoxin producing mold strains Aspergillus flavus and A. fumigatus. The minimal inhibitory concentrations of the NPs were determined in broth media, whereas an agar diffusion test was used to assess the antimold activity on acrylic- and water-based paints. The cytotoxic activity and the inflammatory response of the NPs were also evaluated using the established human derived macrophage cell line THP-1. Results showed that a combination of mix metallic- and ZnO-NPs (50:10 µg/mL) effectively inhibited the fungal growth when exposed to fluorescent light. Neither cytotoxic effect nor inflammatory responses were recorded, suggesting that this combination can be safely used in humid or non-ventilated environments without any health concerns.

Toxicity evaluation of high-fluorescent rare-earth metal nanoparticles for bioimaging applications.

Research on nanometer-sized luminescent semiconductors and their biological applications in detectors and contrasting agents is an emergent field in nanotechnology. When new nanosize technologies are developed for human health applications, their interaction with biological systems should be studied in depth. Rare-earth elements are used in medical and industrial applications, but their toxic effects are not known. In this work, the biological interaction between terbium-doped gadolinium oxysulfide nanoparticles (GOSNPs) with human peripheral blood mononuclear cells (PBMC), human-derived macrophages (THP-1), and human cervical carcinoma cell (HeLa) were evaluated. The GOSNPs were synthetized using a hydrothermal method to obtain monodisperse nanoparticles with an average size of 91 ± 9 nm. Characterization techniques showed the hexagonal phase of the Gd2 O2 S:Tb3+ free of impurities, and a strong green emission at λemi = 544 nm produced by Tb3+ was observed. Toxic effects of GOSNPs were evaluated using cell viability, apoptosis, cell-cycle progression, and immunological response techniques. In addition, an Artemia model was used to assess the toxicity in vivo. Results indicated cell apoptosis in both types of cells with less sensitivity for PBMC cells compared to HeLa cells. In addition, no toxic effects were observed in the in vivo model of Artemia. Moreover, GOSNPs significantly reduced the activation and cell-cycle progression of PBMC and HeLa cells, respectively. Interestingly, an increase in proinflammatory cytokines was not observed. Our data suggest that fluorescence applications of GOSNPs for biolabeling are not toxic in primary immune cells and they may have an immunomodulatory effect. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 605-615, 2017.

Microwave spectra, ab initio calculations, and r0 structural parameters for (methylamino)thiophosphoryl difluoride.

The microwave spectra of (methylamino)thiophosphoryl difluoride, CH(3)NHP(=S)F(2), and two deuterated species, CH(3)NDP(=S)F(2) and CD(3)NHP(=S)F(2), have been investigated in the region from 26.5 to 39.0 GHz. The rotational constants of the ground vibrational state have been determined and have been shown to be only consistent with the trans conformer (CH(3) group antiperiplanar to the P=S bond) with C(s) symmetry. The a-type R branch transitions have been assigned for the trans conformer for the three isotopomers on the basis of the rigid rotor model. Near-trans and near-cis forms without molecular planes of symmetry are predicted by all ab initio calculations with the near-trans form being more stable. However, the double-well potentials governing the interchange between the two enantiomeric near-trans as well as the two near-cis forms are too shallow to accommodate the zero-point energies of the nu(24) asymmetric torsion. Thus, the trans conformation with C(s) symmetry may be more accurate in explaining the microwave experimental data. The "adjusted" r(0) structural parameters have been obtained by systematically adjusting the ab initio MP2(full)/6-311+G(d,p) structure of the trans conformer with C(s) symmetry to fit the microwave rotational constants. The determined heavy atom distances are r(C-N) = 1.459(5), r(P-N) = 1.621(5), r(P=S) = 1.879(5), and r(P-F) = 1.550(5) A, and the heavy atom angles are angleCNP = 124.7(5) degrees , angleNPS = 118.3(5) degrees , angleNPF = 103.2(5) degrees , angleFPS = 117.0(5) degrees , and angleFPF = 94.6(5) degrees . The adjusted r(0) parameters have also been obtained for aminodifluorophosphine, H(2)NPF(2), with a slightly pyramidal -PNH(2) moiety. The results indicate that the previously reported short distance of 0.981(5) A for the N-H(o)(outer) bond from the microwave study is too short, and the adjusted r(0) value of 1.007(3) A is obtained from the combined data. Adjusted r(0) parameters are also reported for (dimethylamino)difluorophosphine, (CH(3))(2)NPF(2), with C(s) symmetry with the PNC(2) portion of the molecule being planar. The previously reported C-H distances from the electron diffraction study are too long, and the anglePNC(i) and angleC(o)NC(i) angles are also found to be in error. These results provide a reasonable explanation why the microwave and electron diffraction results differ for the structures of these latter two molecules.