Miracle-dz/UniFAR-FTUs huggingface dataset:
3D bioprinting of skin: a state-of-the-art review on modelling, materials, and processes

The skin is the largest organ of the body, having a complex multi-layered structure and guards the underlying muscles, bones, ligaments, and internal organs. It serves as the first line of defence to any external stimuli, hence it is the most vulnerable to injury and warrants the need for rapid and reliable regeneration methods. Tissue engineered skin substitutes help overcome the limitations of traditional skin treatment methods, in terms of technology, time, and cost. While there is commendable progress in the treating of superficial wounds and injuries with skin substitutes, treatment of full-thickness injuries, especially with third or fourth degree burns, still looks murkier. Engineering multi-layer skin architecture, conforming to the native skin structure is a tougher goal to achieve with the current tissue engineering methods, if not impossible, restoring all the functions of the native skin. The testing of drugs and cosmetics is another area, where engineered skins are very much needed, with bans being imposed on product testing on animals. Given this greater need, 3D bioprinting is a promising technology that can achieve rapid and reliable production of biomimetic cellular skin substitutes, satisfying both clinical and industrial needs. This paper reviews all aspects related to the 3D bioprinting of skin, right from imaging the injury site, 3D model creation, biomaterials that are used and their suitability, types of cells and their functions, actual bioprinting technologies, along with the challenges and future prospects.
THE PATENT MEDICINE AND NOSTRUM EVILS.

Encouraged by a small measure of success resulting from the efforts put forth in the recent past to stamp out the "patent medicine" and secret nostrum evils, it behooves the medical profession at large to forward the beneficent effects of an awakening that has come none too early, until victory for reputable therapeutics and pharmacy is no longer in doubt. Individual members of our profession and medical organizations can aid the progress of this praiseworthy work by a calm, temperate, dispassionate discussion of the question, more particularly by pointing out the reasons for the phenomenal success of these doubtful preparations and by urging measures of relief in the interests of the public and professional weal. It is the province of the trained and disinterested physician to give appropriate and efficient direction to the movement. THE NATURE OF THE BUSINESS. It is well known that adulterants are extensively introduced into foodstuffs
Leaf-inspired microcontact printing vascular patterns

The vascularization of tissue grafts is critical for maintaining viability of the cells within a transplanted graft. A number of strategies are currently being investigated including very promising microfluidics systems. Here, we explored the potential for generating a vasculature-patterned endothelial cells that could be integrated into distinct layers between sheets of primary cells. Bioinspired from the leaf veins, we generated a reverse mold with a fractal vascular-branching pattern that models the unique spatial arrangement over multiple length scales that precisely mimic branching vasculature. By coating the reverse mold with 50 μg ml−1 of fibronectin and stamping enabled selective adhesion of the human umbilical vein endothelial cells (HUVECs) to the patterned adhesive matrix, we show that a vascular-branching pattern can be transferred by microcontact printing. Moreover, this pattern can be maintained and transferred to a 3D hydrogel matrix and remains stable for up to 4 d. After 4 d, HUVECs can be observed migrating and sprouting into Matrigel. These printed vascular branching patterns, especially after transfer to 3D hydrogels, provide a viable alternative strategy to the prevascularization of complex tissues.
Improving Liver Allocation Using Optimized Neighborhoods

BackgroundGeographic disparities persist in access to liver transplantation. Candidates with similar urgency experience varying opportunities for transplants across the United States. Policymakers are poised to act and 1 proposal entails reorganizing the current Organ Procurement and Transplant Network (OPTN) of 11 regions into 8 districts. However, redistricting has the shortcomings that Organ Procurement Organizations (OPOs) are disconnected from their immediate neighbors by district borders and that it is not easily responsive to uncertainty resulting from variability in donor and listing rates. MethodsWe introduce the notion of an OPO's neighborhood—a collection of donor service areas (DSA) surrounding the OPO that acts as the OPO's region in the current local-regional-national framework. Districts and concentric circles are special cases. We design 58 neighborhoods for the DSAs with several attractive properties and optimize them to balance supplies and demands using 10 years of Organ Procurement and Transplant Network data. We conduct a simulation experiment comparing current allocation, redistricting, and neighborhoods under current sharing policies with respect to the following metrics: total mortalities, DSA-average model for end-stage liver disease (MELD) at transplant, DSA-average MELD standard deviation, and average organ transport distance. Liver-simulated allocation model cannot accommodate neighborhoods, so we programmed a discrete-event simulator, LivSim, to approximate liver-simulated allocation model. ResultsWe exhibited a neighborhood solution. Compared with the current allocation, simulation results showed that neighborhoods reduce the DSA-average MELD standard deviation by 29% and save about 65 lives annually. Compared with redistricting, the neighborhoods had smaller average transport distances that were more uniform across DSAs, saved about 20 additional lives, and reduced DSA-average MELD standard deviation by an additional 17%. ConclusionsAlternatives to redistricting with desirable properties and performance are possible and should be considered.
Comparative study of gelatin methacrylate hydrogels from different sources for biofabrication applications

Gelatin methacrylate (GelMA) hydrogel is a promising bioink for biofabrication applications due to its cost-effectiveness, ease of synthesis and biocompatibility to allow cell adhesion. However, the GelMA synthesized from a widely used porcine skin gelatin has a thermal gelation problem at room temperature. Here, we present thermally stable GelMA hydrogels at room temperature while maintaining the mechanical and biological properties comparable to porcine GelMA. The novel GelMA hydrogels were synthesized from fish skin and cold soluble gelatin. We systematically characterized the properties of the GelMA hydrogels from different sources. The properties include the degree of methacrylation, compressive Young’s modulus, mass swelling ratio, viscosity, and cell adhesion and proliferation in 2D and 3D microenvironments. It has been found that the cold soluble GelMA was comparable to the porcine skin GelMA but could offer low viscosity and thermal stability at room temperature. We performed a droplet generation experiment to demonstrate the benefit of using the cold soluble GelMA for biofabrication. The cold soluble GelMA showed a more reliable and stable droplet fabrication process. Taken together, the cold soluble GelMA is a promising bioink solution and may greatly benefit the research in biofabrication.
TGF-β induced epithelial–mesenchymal transition in an advanced cervical tumor model by 3D printing

An advanced in vitro cervical tumor model was established by 3D printing to study the epithelial-to-mesenchymal transition (EMT), which is a very important stage of dissemination of carcinoma leading to metastatic tumors. A HeLa/hydrogel grid construct composed of gelatin, alginate, Matrigel and HeLa cells was fabricated by forced extrusion in a layer-by-layer fashion. HeLa cells rapidly proliferated, formed spheroids and presented tumorigenic characteristic in the 3D-printed structure. With the supplement of TGF-β, aggregated HeLa cells started to disintegrate, and some of them changed into fibroblast-like spindle morphology, which indicated that EMT was induced. The down-regulation of epithelial marker E-cadherin, and up-regulation of mesenchymal markers such as snail, vimentin and N-cadherin were all observed in the 3D-printed model, and performed differently in 3D and 2D models. The TGF-β induced EMT was inhibited by the treatment of disulfiram and EMT pathway inhibitor C19 in a dose dependent manner, showing great potential for future studies of a therapeutic program towards cervical tumor metastasis.
Editorial: Just say “no” to drug testing in schools

Purpose – Aims to assess the merits of random drug testing in UK schools. Design/methodology/approach – Outlines the arguments for and against drug testing and draws on evidence from studies in the USA that seek to determine whether young people are deterred from using drugs by random drug testing. Findings – Both theory and practice suggest that drug testing in schools will not prevent or delay drug use in the UK. Originality/value – The balance of the argument is against drug testing in schools, and will remain so until evidence suggests otherwise.
Evaluation of a 5‐year cervical cancer prevention project in Indonesia: Opportunities, issues, and challenges

The Cervical and Breast Cancer Prevention (CECAP) Project sought to develop a national model for cervical cancer prevention in Indonesia based on visual inspection with acetic acid (VIA) to detect abnormal changes in the cervix. The purpose of this study was to evaluate a pilot project introducing VIA and cryotherapy in Indonesia and to identify lessons learned that could be applied to the national scale‐up of cervical cancer prevention services.
Analysis of complex anisotropy decays from single-frequency polarized-phasor ellipse plots

The anisotropy decay of a fluorescently-labelled macromolecule provides information on the internal and global dynamics of the macromolecule. Weber was a pioneer of fluorescent probes, polarization and polarized phase-modulation methods and revealed the power of combining or comparing these methods to disentangle complex modes of emission depolarization. In this paper we take a similar course and show that when measurements of dynamic depolarization are combined with steady-state anisotropy, complex anisotropy decays can be deduced from measurements at a single modulation frequency. Specifically, a double exponential anisotropy decay can be resolved by combining one of the polarized emission phasors with the steady-state anisotropy. The key is the polarized phasor ellipse plot which provides a convenient visualisation aid and reduces the dimensionality of the minimisation problem from three variables to one variable. We illustrate these concepts with an experimental measurement of the anisotropy decay of a small cytoplasmic fluorescent probe in live cells.
Dispersed dynamics of solvation in G-quadruplex DNA: comparison of dynamic Stokes shifts of probes in parallel and antiparallel quadruplex structures

G-quadruplex DNA (GqDNA) structures play an important role in many specific cellular functions and are promising anti-tumor targets for small molecules (ligands). Here, we measured the dynamic Stokes shift of a ligand (Hoechst) bound to parallel c-Myc (mPu22) GqDNA over five decades of time from 100 fs to 10 ns, and compared it with the previously reported dynamics of DAPI bound to antiparallel human telomeric (hTelo22) GqDNA (Pal et al 2015 J. Phys. Chem. Lett. 6 1754). Stokes shift data from fluorescence up-conversion and time-correlated single photon counting experiments was combined to cover the broad dynamic range. The results show that the solvation dynamics of Hoechst in parallel mPu22 GqDNA follow a power law relaxation, added to fast 2 ps exponential relaxation, from 100 fs to 10 ns, with only a subtle difference of power law exponents in the two ligand-GqDNA systems (0.06 in Hoechst-mPu22 compared to 0.16 in DAPI-hTelo22). We measured steady-state fluorescence spectra and time-resolved anisotropy decays which confirm the tight binding of Hoechst to parallel mPu22 with a binding constant of ~1 × 105 M−1. The molecular docking of Hoechst in parallel GqDNA followed by a 50 ns molecular dynamics (MD) simulation on a Hoechst-GqDNA complex reveals that Hoechst binds to one of the outer G-tetrads by end-stacking near G13 and G4, which is different from the binding site of DAPI inside a groove of antiparallel hTelo22 GqDNA. Reconciling previous experimental and simulation results, we assign the 2 ps component to the hydration dynamics of only weakly perturbed water near mPu22 and the power law relaxation to the coupled motion of water and DNA (i.e. DNA backbone, unpaired bases and loops connecting G-tetrads) which come near the Hoechst inside parallel GqDNA.
Understanding disordered and unfolded proteins using single-molecule FRET and polymer theory

Understanding protein folding and the functional properties of intrinsically disordered proteins (IDPs) requires detailed knowledge of the forces that act in polypeptide chains. These forces determine the dimensions and dynamics of unfolded and disordered proteins and have been suggested to impact processes such as the coupled binding and folding of IDPs, or the rate of protein folding reactions. Much of the progress in understanding the physical and chemical properties of unfolded and intrinsically disordered polypeptide chains has been made possible by the recent developments in single-molecule fluorescence techniques. However, the interpretation of the experimental results requires concepts from polymer physics in order to be understood. Here, I review some of the theories used to describe the dimensions of unfolded polypeptide chains under varying solvent conditions together with their more recent application to experimental data.
2004 Carolyn Sherif Award Address: Heart Disease and Gender Inequity

Individual patient records from the National Hospital Discharge Survey for 1988 and 1998 comprising approximately 10 million cases were the basis for a binary logistic regression model to predict coronary artery bypass graft. Patterns in 1988 and in 1998 indicated a dramatic and pernicious gender discrepancy in medical decisions involving bypass surgery. Overall, men were twice as likely to have bypass as were women with comparable medical profiles. This result was particularly evident for women in their 40s and 50s, when angina was a primary diagnosis, and in the presence of any comorbid condition (e.g., diabetes or hypertension). Failure to pursue proactive case management of women with heart disease costs women's lives.
Long‐term exposure of tumor necrosis factor α causes hypersensitivity to androgen and anti‐androgen withdrawal phenomenon in LNCaP prostate cancer cells

One of the mechanisms through which prostate cancers relapse during anti‐androgen therapy may involve adaptation to low concentrations of androgen induced by anti‐androgen therapies. Recent studies from our laboratory have reported that tumor necrosis factor‐α (TNFα) is secreted from prostate cancer epithelial cells and LNCaP cells. We hypothesized that TNFα changes androgen‐sensitivity in LNCaP cells.
NIR-fluorescent dye doped silica nanoparticles for in vivo imaging, sensing and theranostic

The development of nanostructures devoted to in vivo imaging and theranostic applications is one of the frontier fields of research worldwide. In this context, silica nanoparticles (SiO2-NPs) offer unquestionable positive properties: silica is intrinsically non-toxic, several versatile and accessible synthetic methods are available and many variations are possible, both in terms of porosity and functionalization for delivery and targeting purposes, respectively. Moreover, the accumulation of several dyes within a single nanostructure offers remarkable possibilities to produce very bright and photostable luminescent nanosystems. Advancements in imaging technology, bioassay, fluorescent molecular probes have boosted the efforts to develop dye doped fluorescent SiO2-NPs, but despite this, only a quite limited set of systems are applicable in vivo. Herein we discuss selected examples that appeared in the literature between 2013–17, with imaging capabilities in vivo and characterized by a significant near infrared (NIR) fluorescence emission. We present here very promising strategies to develop SiO2-NPs for diagnostic and therapeutic applications—some of which are already in clinical trials—and the possibility to develop bio-erodable SiO2-NPs. We are convinced that all these findings will be the basis for the spread of SiO2-NPs into clinical use in the near future.
Using feminist MRI brief therapy during initial contact with victims of domestic violence

This article seeks to provide an alternative approach to traditional point-of-contact crisis services for victims of domestic violence. This approach, based on a feminist Mental Research Institute brief therapy model, takes into account the many forces arrayed against battered women that influence their decisions about staying or leaving their batterers. Many service organizations provide services targeted to the woman who leaves, not the woman who stays. Thus, this approach provides a model with which to fit the services to each woman, not the woman to the services. In addition, by honoring and acknowledging the many forces that keep women from leaving, service providers may reduce their rates of burnout by redefining the meaning of successful intervention. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Reaction mechanism of core–shell MoO2/MoS2 nanoflakes via plasma-assisted sulfurization of MoO3

The sulfurization of MoO3 in an H2S/Ar plasma atmosphere has been experimentally studied and a reaction mechanism has been proposed based on the results obtained. Nanostructured thin films (NTFs) of MoO3 were sulfurized at different temperatures varying from 150 °C to 550 °C. High-resolution transmission electron microscopy (TEM) images depict core–shell nanoflakes with varying shell thicknesses as the sulfurization temperature (Tsn) is varied. The shells consist of MoS2 and the core is MoO2/MoO3. X-ray diffraction (XRD) and Raman analysis have been used to study the structural changes as MoO3 is sulfurized. The analyses showed two phases, MoO2 and MoS2, at low temperatures (≤350 °C), whereas the films sulfurized at higher temperatures show predominantly MoS2. The scanning electron microscopy (SEM) results show no noticeable changes in the surface morphology of the NTFs after sulfurization. X-ray photoelectron spectroscopy (XPS) was carried out to calculate the relative percentages of MoO3, MoO2 and MoS2. It is revealed that sulfurization of MoO3 in the plasma is affected by Tsn. The sulfurization process occurs in two steps, involving the reduction of MoO3 to form MoO2 in the first step, followed by MoO2 being converted into MoS2. It is also evident that the reduction of MoO3 is more a result of the reactive species of hydrogen (H*) than the replacement of oxygen by sulfur in the second step.
An underwater superoleophobic nanofibrous cellulosic membrane for oil/water separation with high separation flux and high chemical stability.

Oil spills and an increasing demand for the treatment of industrial oily wastewater are driving the need for continuous large-scale oil/water separation processes. Herein, we report a nanofibrous cellulosic membrane (NFC membrane) for the continuous high-flux separation of large amounts of oil/water mixtures. The NFC membrane was fabricated using wet electrospinning, a facile yet effective method for stacking nanofibrous membranes with uniform porous structures on a substrate. Owing to its cellulosic nature, the membrane showed excellent underwater superoleophobicity along with robust chemical stability and was able to separate oil/water mixtures at efficiencies exceeding 99%. Repetitive oil/water separations could be performed using a single membrane, during which the oil content in the filtrate remained extremely low (<29 ppm). The nanofibrous membrane exhibited a fine porous structure that was interconnected throughout the membrane, resulting in a high oil intrusion pressure (>30 kPa) that allowed not only gravity-driven but also pressure-driven separation of oil/water mixtures. The separation flux reached 120 000 L m-2 h-1 during pressure-driven separations, which is a very promising feature for actual applications such as the large-scale treatment of industrial oily wastewater.
Determination of Bias in the Relative Abundance of Oligonucleotides in DNA Sequences

Different statistical measures of bias of oligonucleotide sequences in DNA sequences were compared, both by theoretical analysis and according to their abilities to predict the relative abundances of oligonucleotides in the genome of Escherichia coli. The expected frequency of an oligonucleotide calculated from a maximal order Markov model was shown to be a degenerate case of the expected frequency calculated from biases of all subwords arising when noncontiguous subwords exhibit no bias. Since (at least in E. coli) noncontiguous sequences exhibit significant bias, the total compositional bias approach is expected to represent biases in genomic sequences more faithfully than Markov approaches. In fact, the efficacy of statistics based on Markov analysis even at the highest order were inferior in predicting actual frequencies of oligonucleotides to methods that factored out biases of internal subwords with gaps. Using total compositional bias as a measure of relative abundance, tetranucleotide and hexanucleotide palindromes were found to be distributed differently from nonpalindromic sequences, with their means shifted somewhat towards underrepresentation. A subpopulation of palindromic hexanucleotides, however, was highly underrepresented, and this group consisted almost entirely of targets for Type II restriction enzymes found within strains of E. coli. Sites recognized by Type I endonucleases from related strains were not markedly biased, and with pentanucleotides, palindromic and nonpalindromic sequences had nearly identical distributions. The loss of restriction sites may be explained by the free transfer of plasmids encoding restriction enzymes and episodic selection for the presence of the enzymes.
The Impact of Liver Graft Injury on Cancer Recurrence Posttransplantation

Abstract Liver transplantation is the most effective treatment for selected patients with hepatocellular carcinoma. However, cancer recurrence, posttransplantation, remains to be the critical issue that affects the long-term outcome of hepatocellular carcinoma recipients. In addition to tumor biology itself, increasing evidence demonstrates that acute-phase liver graft injury is a result of hepatic ischemia reperfusion injury (which is an inevitable consequence during liver transplantation) and may promote cancer recurrence at late phase posttransplantation. The liver grafts from living donors, donors after cardiac death, and steatotic donors have been considered as promising sources of organs for liver transplantation and are associated with high incidence of liver graft injury. The acute-phase liver graft injury will trigger a series of inflammatory cascades, which may not only activate the cell signaling pathways regulating the tumor cell invasion and migration but also mobilize the circulating progenitor and immune cells to facilitate tumor recurrence and metastasis. The injured liver graft may also provide the favorable microenvironment for tumor cell growth, migration, and invasion through the disturbance of microcirculatory barrier function, induction of hypoxia and angiogenesis. This review aims to summarize the latest findings about the role and mechanisms of liver graft injury resulted from hepatic ischemia reperfusion injury on tumor recurrence posttransplantation, both in clinical and animal cohorts.