Miracle-dz/UniFAR-FTUs huggingface dataset:
Cost-effectiveness of implementing 13-valent pneumococcal conjugate vaccine for U.S. adults aged 19 years and older with underlying conditions

ABSTRACT In June 2019, the Advisory Committee on Immunization Practices (ACIP) changed the recommendation for routine 13-valent pneumococcal conjugate vaccine (PCV13) use in immunocompetent adults aged ≥65 years, including those with select chronic medical conditions (CMC). ACIP now recommends PCV13 for this group of adults based on shared clinical decision-making. Because adults with CMC continue to be at increased risk for pneumococcal disease, we assessed the cost-effectiveness of administering PCV13 in series with the recommended 23-valent pneumococcal polysaccharide vaccine (PPSV23) for adults aged ≥19 years with CMC. We used a probabilistic model following a cohort of 19-year-old adults. We used Monte Carlo simulation to estimate the impact on program, medical, and non-medical costs (in 2017 U.S. dollars [$], societal perspective), and pneumococcal disease burden when administering PCV13 in series with PPSV23. We used PCV13 efficacy and post-licensure vaccine effectiveness (VE) data to estimate VE against PCV13 type disease (separately for disease by serotype 3 [ST3], the most common PCV13 type, and all other PCV13 serotypes). We considered a range of estimates for sensitivity analyses. Analyses were performed in 2019. In the base case, assuming no PCV13 effectiveness against ST3 disease, adding a dose of PCV13 upon CMC diagnosis cost $689,299 per QALY gained. This declined to $79,416 per QALY if VE against ST3 was estimated to be equivalent to other PCV13-types. Administering PCV13 in series with the recommended PPSV23 for adults with CMC was not cost saving. Results were sensitive to estimated PCV13 VE against ST3 disease.
Protein Binder (ProBi) as a New Class of Structurally Robust Non-Antibody Protein Scaffold for Directed Evolution

Engineered small non-antibody protein scaffolds are a promising alternative to antibodies and are especially attractive for use in protein therapeutics and diagnostics. The advantages include smaller size and a more robust, single-domain structural framework with a defined binding surface amenable to mutation. This calls for a more systematic approach in designing new scaffolds suitable for use in one or more methods of directed evolution. We hereby describe a process based on an analysis of protein structures from the Protein Data Bank and their experimental examination. The candidate protein scaffolds were subjected to a thorough screening including computational evaluation of the mutability, and experimental determination of their expression yield in E. coli, solubility, and thermostability. In the next step, we examined several variants of the candidate scaffolds including their wild types and alanine mutants. We proved the applicability of this systematic procedure by selecting a monomeric single-domain human protein with a fold different from previously known scaffolds. The newly developed scaffold, called ProBi (Protein Binder), contains two independently mutable surface patches. We demonstrated its functionality by training it as a binder against human interleukin-10, a medically important cytokine. The procedure yielded scaffold-related variants with nanomolar affinity.
Cancer of Unknown Primary: Challenges and Progress in Clinical Management

Simple Summary Patients with cancer of unknown primary site suffer the burden of an uncertain disease, which is characterized by the impossibility to identify the tissue where the tumor has originated. The identification of the primary site of a tumor is of great importance for the patient to have access to site-specific treatments and be enrolled in clinical trials. Therefore, patients with cancer of unknown primary have reduced therapeutic opportunities and poor prognosis. Advancements have been made in the molecular characterization of this tumor, which could be used to infer the tumor site-of-origin and thus broaden the diagnostic outcome. Moreover, we describe here the novel therapeutic opportunities that are based on the genetic and immunophenotypic characterization of the tumor, and thus independent from the tumor type, which could provide most benefit to patients with cancer of unknown primary. Abstract Distant metastases are the main cause of cancer-related deaths in patients with advanced tumors. A standard diagnostic workup usually contains the identification of the tissue-of-origin of metastatic tumors, although under certain circumstances, it remains elusive. This disease setting is defined as cancer of unknown primary (CUP). Accounting for approximately 3–5% of all cancer diagnoses, CUPs are characterized by an aggressive clinical behavior and represent a real therapeutic challenge. The lack of determination of a tissue of origin precludes CUP patients from specific evidence-based therapeutic options or access to clinical trial, which significantly impacts their life expectancy. In the era of precision medicine, it is essential to characterize CUP molecular features, including the expression profile of non-coding RNAs, to improve our understanding of CUP biology and identify novel therapeutic strategies. This review article sheds light on this enigmatic disease by summarizing the current knowledge on CUPs focusing on recent discoveries and emerging diagnostic strategies.
Analysis of the validity of the mathematical assumptions of electrical impedance tomography for human head tissues

Objective: To determine the validity of the key mathematical assumptions used in electrical impedance tomography for human head tissues. Approach:Conductivity and permittivity data collected from available literature for each tissue within the human head have been evaluated and critiqued. The most relevant dielectric tissue data for each tissue was then used to assess the validity of the mathematical assumptions of electrical impedance tomography in terms of their suitability for human head imaging in order to estimate related errors. Main Results:For induced currents with frequencies greater than 200 Hz the internal current source density is negligible. The assumption that magnetic effects are negligible is valid to an error of 1.7% for human head tissues for frequencies below 1 MHz. The capacitive effects are negligible for CSF, dura mater, blood, bone (cortical), and deep tissue skin for frequencies less than 3.2 MHz, 320 kHz, 25 kHz, 3.2 kHz, and 130 Hz respectively. However, the capacitive effects are not negligible for brain tissues, as the minimum error for brain tissues across the frequency range of 10 Hz to 100 GHz is 6.2% at 800 Hz, and the maximum error is 410% at 20 GHz. Significance:It is often assumed that the mathematical reduction of the base equations is valid for human head tissues over a broad frequency range; this study shows that these assumptions are not true for all tissues at all frequencies. False assumptions will result in greater errors and local distortions within tomographic images of the human head using electrical impedance tomography. This study provides the relationships between injected current frequency and the validity of the mathematical assumptions for each individual tissue, providing greater awareness of the magnitude of possible distortions.
Osteoarthritic Subchondral Bone Release Exosomes That Promote Cartilage Degeneration

Altered subchondral bone and articular cartilage interactions have been implicated in the pathogenesis of osteoarthritis (OA); however, the mechanisms remain unknown. Exosomes are membrane-derived vesicles that have recently been recognized as important mediators of intercellular communication. Herein, we investigated if OA subchondral bone derived exosomes alter transcriptional and bioenergetic signatures of chondrocytes. Exosomes were isolated and purified from osteoblasts of nonsclerotic or sclerotic zones of human OA subchondral bone and their role on the articular cartilage chondrocytes was evaluated by measuring the extent of extracellular matrix production, cellular bioenergetics, and the expression of chondrocyte activity associated marker genes. Exosomal microRNAs were analyzed using RNA sequencing and validated by quantitative real-time PCR and loss-of-function. In coculture studies, chondrocytes internalized OA sclerotic subchondral bone osteoblast derived exosomes and triggered catabolic gene expression and reduced chondrocyte-specific marker expression a phenomenon that is often observed in OA cartilage. RNA sequencing and miRNA profiling have identified miR-210-5p, which is highly enriched in OA sclerotic subchondral bone osteoblast exosomes, triggered the catabolic gene expression in articular cartilage chondrocytes. Importantly, we demonstrate that miR-210-5p suppresses the oxygen consumption rate of chondrocytes, altering their bioenergetic state that is often observed in OA conditions. These effects were markedly inhibited by the addition of a miR-210-5p inhibitor. Our study indicates that exosomes released by OA sclerotic subchondral bone osteoblasts plays a critical role in progression of cartilage degeneration and might be a potential target for therapeutic intervention in OA.
Physical Enhancement? Nanocarrier? Current Progress in Transdermal Drug Delivery

A transdermal drug delivery system (TDDS) is a method that provides drug adsorption via the skin. TDDS could replace conventional oral administration and blood administration because it is easily accessible. However, it is still difficult to design efficient TDDS due to the high barrier property of skin covered with stratum corneum, which inhibits the permeation of drug molecules. Thus far, TDDS methods by applying physical stimuli such as microneedles and chemical stimuli such as surfactants have been actively developed. However, it has been hard to avoid inflammation at the administration site because these methods partially destroy the skin tissue. On the other hand, TDDS with nanocarriers minimizing damage to the skin tissues has emerged together with the development of nanotechnology in recent years. This review focuses on current trends in TDDS.
EQUILIBRIUM ISOTHERM STUDIES ON THE BATCH SORPTION OF COPPER (II) IONS FROM AQUEOUS SOLUTION UNTO "NSU CLAY".

Copper (II) ions adsorption from aqueous solution unto Nsu clay was studied. The aim of the experiment was to utilize the clay as a cheap alternative adsorbent compared to more expensive and relatively less effective techniques for the removal of copper (II) ions from solution. The experiment was performed using batch adsorption technique. Optimum adsorption was achieved at a pH of 5.0 and equilibrium was established within 60 minutes of the process. The equilibrium adsorption data was analyzed by the Langmuir, Freundlich, Dubinin-Radushkevich, Redlich-Peterson and Scatchard isotherm models. The values of the regression coefficient (R 2 ) of the isotherms gave the best fit (0.9842) with the Redlich-Peterson isotherm. However, all the isotherms applied were appropriate in their own merit in the description of adsorption data. The Langmuir constant values RL and Freundlich constant n showed a favourable adsorption between Nsu clay and copper (II) ions in solution. The energy of adsorption, E (15.8 KJ/mol) obtained from the DubininRadushkevich isotherm suggested a chemical ion exchange mechanism. The deviation of the Scatchard plot from linearity, R 2 (0.6634) indicated the presence of more than one type of binding sites on the clay surface. The results obtained depicts the usefulness of Nsu clay as a low-cost adsorbent for copper (II) ions.
Psychological profile and unexpected pain in oral lichen planus: a case-control multicenter SIPMO study.

OBJECTIVES To analyze psychological profiles, pain and oral symptoms in patients with oral lichen planus (OLP). MATERIALS AND METHODS 300 patients with keratotic OLP (K-OLP; reticular, papular, plaque-like subtypes), 300 patients with predominant non-keratotic OLP (nK-OLP; erythematosus atrophic, erosive, ulcerative, bullous subtypes) and 300 controls were recruited in 15 universities. The number of oral sites involved and oral symptoms were recorded. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were administered. RESULTS The OLP patients, especially the nK-OLP, showed higher scores in the NRS, T-PRI, HAM-D, HAM-A and PSQI compared with the controls (p-value<.001** ). A positive correlation between the NRS, T-PRI, HAM-A, HAM-D and PSQI was found with the number of oral symptoms and number of oral sites involved. Pain was reported in 67.3 % of nK-OLP and 49.7% of K-OLP cases with poor correspondence between the site of lesions and the site of the symptoms. CONCLUSIONS Mood disorders are frequently associated with OLP with an unexpected symptomatology correlated with the number of oral symptoms and with the extension of disease suggesting a peripheral neuropathy.
Quantum chemistry based force field for simulations of HMX

The molecular geometries and conformational energies of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) and 1,3-dimethyl-1,3-dinitro methyldiamine (DDMD) and have been determined from high-level quantum chemistry calculations and have been used in parametrizing a classical potential function for simulations of HMX. Geometry optimizations for HMX and DDMD and rotational energy barrier searches for DDMD were performed at the B3LYP/6-311G** level, with subsequent single-point energy calculations at the MP2/6-311G** level. Four unique low-energy conformers were found for HMX, two whose conformational geometries correspond closely to those found in HMX polymorphs from crystallographic studies and two additional, lower energy conformers that are not seen in the crystalline phases. For DDMD, three unique low-energy conformers, and the rotational energy barriers between them, were located. In parametrizing the classical potential function for HMX, nonbonded repulsion/dispersion parameters, valence paramete.
FMODB: The World's First Database of Quantum Mechanical Calculations for Biomacromolecules Based on the Fragment Molecular Orbital Method

We developed the world's first web-based public database for the storage, management, and sharing of fragment molecular orbital (FMO) calculation data sets describing the complex interactions between biomacromolecules, named FMO Database (https://drugdesign.riken.jp/FMODB/). Each entry in the database contains relevant background information on how the data was compiled as well as the total energy of each molecular system and interfragment interaction energy (IFIE) and pair interaction energy decomposition analysis (PIEDA) values. Currently, the database contains more than 13 600 FMO calculation data sets, and a comprehensive search function implemented at the front-end. The procedure for selecting target proteins, preprocessing the experimental structures, construction of the database, and details of the database front-end were described. Then, we demonstrated a use of the FMODB by comparing IFIE value distributions of hydrogen bond, ion-pair, and XH/π interactions obtained by FMO method to those by molecular mechanics approach. From the comparison, the statistical analysis of the data provided standard reference values for the three types of interactions that will be useful for determining whether each interaction in a given system is relatively strong or weak compared to the interactions contained within the data in the FMODB. In the final part, we demonstrate the use of the database to examine the contribution of halogen atoms to the binding affinity between human cathepsin L and its inhibitors. We found that the electrostatic term derived by PIEDA greatly correlated with the binding affinities of the halogen containing cathepsin L inhibitors, indicating the importance of QM calculation for quantitative analysis of halogen interactions. Thus, the FMO calculation data in FMODB will be useful for conducting statistical analyses to drug discovery, for conducting molecular recognition studies in structural biology, and for other studies involving quantum mechanics-based interactions.
Usefulness of the ratio of brachial pre-ejection period to brachial ejection time in prediction of cardiovascular and overall mortality in patients with acute myocardial infarction

Left ventricular systolic function is a good indicator of cardiac function and a powerful predictor of adverse cardiovascular (CV) outcomes. High ratio of pre-ejection period (PEP) to ejection time (ET) is associated with reduced left ventricular systolic function. Brachial PEP (bPEP) and brachial ET (bET) can be automatically calculated from an ankle-brachial index (ABI)-form device and bPEP/bET was recently reported to be a new and useful parameter of cardiac performance. However, there were no studies evaluating the utility of bPEP/bET for prediction of CV and overall mortality in patients with acute myocardial infarction (AMI). We included 139 cases of AMI admitted to our cardiac care unit consecutively. ABI, bPEP, and bET were obtained from the ABI-form device within the 24 hours of admission. There were 87 overall and 22 CV mortality and the median follow-up to mortality event was 98 months. After multivariable analysis, high bPEP/bET was not only associated with increased long-term CV mortality (hazard ratio (HR) = 1.046; 95% confidence interval (CI): 1.005–1.088; P = 0.029), but also associated with long-term overall mortality (HR = 1.023; 95% CI: 1.001–1.045; P = 0.042). In addition, age was also a significant predictor for CV and overall mortality after the multivariable analysis. In conclusion, bPEP/bET was shown to be a significant predictor for CV and overall mortality in AMI patients after multivariable analysis. Therefore, by means of this novel parameter, we could easily find out the high-risk AMI patients with increased CV and overall mortality.
Feasibility of Harmonic Motion Imaging Using a Single Transducer: In Vivo Imaging of Breast Cancer in a Mouse Model and Human Subjects

Harmonic motion imaging (HMI) interrogates the mechanical properties of tissues by simultaneously generating and tracking harmonic oscillation using focused ultrasound and imaging transducers, respectively. Instead of using two transducers, the objective of this work is to develop a single transducer HMI (ST-HMI) to both generate and track harmonic motion at “on-axis” to the force for facilitating data acquisition. In ST-HMI, the amplitude-modulated force was generated by modulating excitation pulse duration and tracking of motion was performed by transmitting tracking pulses interleaved between excitation pulses. The feasibility of ST-HMI was performed by imaging two elastic phantoms with three inclusions (N = 6) and comparing it with acoustic radiation force impulse (ARFI) imaging, in vivo longitudinal monitoring of 4T1, orthotropic breast cancer mice (N = 4), and patients (N = 3) with breast masses in vivo. Six inclusions with Young’s moduli of 8, 10, 15, 20, 40, and 60 kPa were embedded in a 5 kPa background. The ST-HMI-derived peak-to-peak displacement (P2PD) successfully detected all inclusions with $\text{R}^{2}=0.93$ of the linear regression between the P2PD ratio of background to inclusion versus Young’s moduli ratio of inclusion to background. The contrasts of 10 and 15 kPa inclusions were higher in ST-HMI than ARFI-derived images. In the mouse study, the median P2PD ratio of tumor to non-cancerous tissues was 3.0, 5.1, 6.1, and 7.7 at 1, 2, 3, and 4 weeks post-injection of the tumor cells, respectively. In the clinical study, ST-HMI detected breast masses including fibroadenoma, pseudo angiomatous stromal hyperplasia, and invasive ductal carcinoma with a P2PD ratio of 1.37, 1.61, and 1.78, respectively. These results indicate that ST-HMI can assess the mechanical properties of tissues via generation and tracking of harmonic motion “on-axis” to the ARF. This study is the first step towards translating ST-HMI in clinics.
Victim Number Effects in Charitable Giving: Joint Evaluations Promote Egalitarian Decisions

Studies of victim number effects in charitable giving consistently find that people care more and help more when presented with an appeal to help an individual compared with an appeal to help multiple people in need. Across three online experiments (N = 1,348), Bayesian estimation revealed the opposite pattern when people responded to multiple appeals to help targets of different sizes (1, 2, 5, 7, and 12). In this joint evaluation context, participants donated more to larger groups, when appeals were presented in both ascending order (Study 1) and random order (Study 2). The pattern held whether or not participants saw an overview of all appeals at the start of the study and when a single individual was added to the array (Study 3). These results clarify how compassion fade findings typical of separate evaluations may not generalize to contexts in which people encounter multiple appeals within a short temporal window.
Studies of Element Concentration in the Lymphocytes, Erythrocytes, and Plasma of Healthy Human Donors Using Total Reflection X-ray Fluorescence

In this article, the total reflection X-ray fluorescence (TXRF) analysis was used for determination of element concentrations in three isolated peripheral blood components: lymphocytes, erythrocytes, and plasma, collected from 36 healthy donors (15 men and 21 women) from eastern Poland. The studied blood components were isolated from whole peripheral blood using Histopaque-1077 density gradient centrifugation. In the lymphocytes, the following elements were measured: P, S, Cl, K, Ca, Fe, Zn, Br, Sr, and Pb. In the erythrocytes: P, S, Cl, K, Cr, Mn, Fe, Cu, Zn, Se, Br, Rb, and Pb, while in the plasma samples: P, S, Cl, K, Ti, V, Cr, Fe, Co, Ni, Cu, Zn, Br, Se, Sr, and Pb. The descriptive statistics parameters of concentration such as: mean value, standard deviation, median, first and third quartiles, 10th and 90th percentiles were calculated for all samples of the studied blood components, as well as separately for male and female groups. The measured element concentrations and calculated parameters can be used as the reference values. Element concentration distributions for male and female groups were statistically compared using the non-parametric Mann–Whitney test and statistical significance differences (α = 0.05) were found for: P (in lymphocytes), Se and Rb (in erythrocytes), and V (in plasma). The multigroup statistical comparison of element concentration distribution for different blood components was also done (Mann–Whitney and Kruskal–Wallis tests). The statistical tests show that the concentration levels are usually different, except in the following cases: Zn, Fe (lymphocytes and plasma, Fe only for female group), Cr (erythrocytes and plasma). The obtained concentration ranges were compared with literature-based data available for element concentration in lymphocytes, erythrocytes, and plasma. In this work, the application of the TXRF method allowed additionally for the simultaneous determination of the concentrations of such elements as: P, S, Cl, Br, Sr and Pb in lymphocytes, S, Cl and Br in erythrocytes, and P, S, Cl, K, Ti, Br and Pb in plasma. From an analytical point of view, the article describes in detail the measurement procedure including the isolation of blood components and samples preparation for TXRF measurements, and later the detection limit of the method is discussed. Graphical Abstract
Electrospun and solution blown three-dimensional carbon fiber nonwovens for application as electrodes in microbial fuel cells

Three-dimensional carbon fiber electrodes prepared by electrospinning and solution blowing are shown to be excellent electrode materials for bioelectrochemical systems such as microbial fuel cells or microbial electrolysis cells. The bioelectrocatalytic anode current density is shown to reach values of up to 30 A m−2, which represents the highest reported values for electroactive microbial biofilms.