Miracle-dz/UniFAR-FTUs huggingface dataset:
Do Abnormalities in Carbohydrate Metabolism and Elevated Blood Pressure Remain Prominent Risks with Oral Contraceptive Use?

Skepticism and concern were expressed in a 1969 Lancet editorial which concluded "the wisdom of administering [oral contraceptives] to healthy women for many years must be seriously questioned. " It was further concluded that the true impact of such medications on morbidity and mortality would not be known for 20 or more years. Such alarm expressed by many medical observers was predicated on the identification of relatively serious side effects associated with the ingestion of the first generation of monophasic oral contraceptives (OCs). The first marketed compound was Enovid, which contained approximately 10 mg norethynodrel and 150 μg mestranol. It received U.S. Food and Drug Administration approval as a contraceptive in 1959, and large clinical trials of this medication were undertaken in many countries. Since 1959, however, proportionate decreases in the concentration of both estrogen and progesterone in OCs have not only maintained efficacy but also dramatically lowered the risk of serious side effects (Table 1). In the earliest formulations, the average total monthly ingested steroid combination consisted of 210 mg of a 19-nortestosterone combined with 3.15 mg of an estradiol equivalent during a 21-day treatment cycle. In contrast, in a 21-day triphasic medication in 1989, the cumulative ingested steroid is 1.93 mg of progestagen equivalent and 0.68 mg of ethinyl estradiol. The proportionate decreases in each steroid are enormous, with a 50% reduction in the progesterone within the last 10 years. Yet the role of estrogen in suppressing ovulation is not denied with significant decreases in the concentration of estradiol. One must also not overlook the fold decreases in progestagen. These have been accompanied by actual changes in the steroid structure of the progestin itself. It is therefore not difficult to consider past reports of abnormal carbohydrate metabolism to be of historical rather than of practical significance to today's user of OCs. In the previous two decades, OCs have been shown to affect carbohydrate metabolism adversely. 3 , 6 8 These effects have been related to numerous factors, most of which could have been screened for prior to the use of OCs (Table 2). While such screening remains a possibility today, the increased prescribing of OCs by nonmedical personnel to women in developing countries still presents an epidemiologic challenge, since the short-term benefits of contraception appear to outweigh the long-term risks in such populations. The enormous cost in time and personnel required to perform adequate pretreatment screening programs is problematic. Thus, alterations in carbohydrate metabolism continue to be identified retrospectively on the basis of symptoms rather than prospectively by the calculation of potential risk.
Effect of Shape, Size, and Aspect Ratio on Nanoparticle Penetration and Distribution inside Solid Tissues Using 3D Spheroid Models

Efficient penetration and uniform distribution of nanoparticles (NPs) inside solid tissues and tumors is paramount to their therapeutic and diagnostic success. While many studies have reported the effect of NP size and charge on intratissue distribution, role of shape, and aspect ratio on NP transport inside solid tissues remain unclear. Here experimental and theoretical studies are reported on how nanoscale geometry of Jet and Flash Imprint Lithography‐fabricated, polyethylene‐glycol‐based anionic nanohydrogels affect their penetration and distribution inside 3D spheroids, a model representing the intervascular region of solid, tumor‐like tissues. Unexpectedly, low aspect ratio cylindrical NPs (H/D ≈0.3; disk‐like particles, 100 nm height, and 325 nm diameter) show maximal intratissue delivery (>50% increase in total cargo delivered) and more uniform penetration compared to nanorods or smaller NPs of the same shape. This is in contrast to spherical NPs where smaller NP size resulted in deeper, more uniform penetration. Our results provide fundamental new knowledge on NP transport inside solid tissues and further establish shape and aspect ratio as important design parameters in developing more efficient, better penetrating, nanocarriers for drug, or contrast‐agent delivery.
Genetically Engineered Virus Nanofibers as an Efficient Vaccine for Preventing Fungal Infection

Candida albicans (CA) is a kind of fungus that can cause high morbidity and mortality in immunocompromised patients. However, preventing CA infection in these patients is still a daunting challenge. Herein, inspired from the fact that immunization with secreted aspartyl proteinases 2 (Sap2) can prevent the infection, it is proposed to use filamentous phage, a human‐safe virus nanofiber specifically infecting bacteria (≈900 nm long and 7 nm wide), to display an epitope peptide of Sap2 (EPS, with a sequence of Val–Lys–Tyr–Thr–Ser) on its side wall and thus serve as a vaccine for preventing CA infection. The engineered virus nanofibers and recombinant Sap2 (rSap2) are then separately used to immunize mice. The humoral and cellular immune responses in the immunized mice are evaluated. Surprisingly, the virus nanofibers significantly induce mice to produce strong immune response as rSap2 and generate antibodies that can bind Sap2 and CA to inhibit the CA infection. Consequently, immunization with the virus nanofibers in mice dramatically increases the survival rate of CA‐infected mice. All these results, along with the fact that the virus nanofibers can be mass‐produced by infecting bacteria cost‐effectively, suggest that virus nanofibers displaying EPS can be a vaccine candidate against fungal infection.
Bioprinting Organotypic Hydrogels with Improved Mesenchymal Stem Cell Remodeling and Mineralization Properties for Bone Tissue Engineering

3D‐manufactured hydrogels with precise contours and biological adhesion motifs are interesting candidates in the regenerative medicine field for the culture and differentiation of human bone‐marrow‐derived mesenchymal stem cells (MSCs). 3D‐bioprinting is a powerful technique to approach one step closer the native organization of cells. This study investigates the effect of the incorporation of collagen type I in 3D‐bioprinted polysaccharide‐based hydrogels to the modulation of cell morphology, osteogenic remodeling potential, and mineralization. By combining thermo‐responsive agarose hydrogels with collagen type I, the mechanical stiffness and printing contours of printed constructs can be improved compared to pure collagen hydrogels which are typically used as standard materials for MSC osteogenic differentiation. The results presented here show that MSC not only survive the 3D‐bioprinting process but also maintain the mesenchymal phenotype, as proved by live/dead staining and immunocytochemistry (vimentin positive, CD34 negative). Increased solids concentrations of collagen in the hydrogel blend induce changes in cell morphology, namely, by enhancing cell spreading, that ultimately contribute to enhanced and directed MSC osteogenic differentiation. 3D‐bioprinted agarose‐collagen hydrogels with high‐collagen ratio are therefore feasible for MSC osteogenic differentiation, contrarily to low‐collagen blends, as proved by two‐photon microscopy, Alizarin Red staining, and real‐time polymerase chain reaction.
Expanding the repertoire of DNA polymerase substrates: template-instructed incorporation of non-nucleoside triphosphate analogues by DNA polymerases β and λ

We have recently shown that neither the base nor the sugar moieties of a nucleotide is an essential feature for its incorporation by DNA polymerases (pols) λ and β. Here we present the identification of novel non-nucleoside triphosphate (NNTP) derivatives belonging to three classes: (i) non-substrate-specific inhibitors of DNA pol λ; (ii) substrate inhibitors which could preferentially be incorporated by either DNA pol λ wild type or its Y505A mutant and (iii) the substrate inhibitor N-(Biphenylcarbonyl)-4-oxobutyl triphosphate which could be incorporated exclusively by DNA pol β in a Mg2+-dependent manner, and preferentially pairs with A on the template. This compound represents the first example of a substrate lacking both nucleobase and ribose residue, showing distinct base-pairing properties with normal bases. Therefore, this NNTP analog can be considered as the prototype of an entirely novel class of DNA pol substrates.
Tuning Cell Differentiation into a 3D Scaffold Presenting a Pore Shape Gradient for Osteochondral Regeneration

Osteochondral regeneration remains nowadays a major problem since the outcome of current techniques is not satisfactory in terms of functional tissue formation and development. A possible solution is the combination of human mesenchymal stem cells (hMSCs) with additive manufacturing technologies to fabricate scaffolds with instructive properties. In this study, the differentiation of hMSCs within a scaffold presenting a gradient in pore shape is presented. The variation in pore shape is determined by varying the angle formed by the fibers of two consequent layers. The fiber deposition patterns are 0–90, which generate squared pores, 0–45, 0–30, and 0–15, that generate rhomboidal pores with an increasing major axis as the deposition angle decreases. Within the gradient construct, squared pores support a better chondrogenic differentiation whereas cells residing in the rhomboidal pores display a better osteogenic differentiation. When cultured under osteochondral conditions the trend in both osteogenic and chondrogenic markers is maintained. Engineering the pore shape, thus creating axial gradients in structural properties, seems to be an instructive strategy to fabricate functional 3D scaffolds that are able to influence hMSCs differentiation for osteochondral tissue regeneration.
The Genomes On Line Database (GOLD) in 2007: status of genomic and metagenomic projects and their associated metadata

The Genomes On Line Database (GOLD) in 2007: status of genomic and metagenomic projects and their associated metadata Konstantinos Liolios 1 , Konstantinos Mavromatis 2 , Nektarios Tavernarakis 3 , and Nikos C. Kyrpides 2 University of Chicago, Chicago, USA, Genome Biology Program, Joint Genome Institute, 2800 Mitchell Drive, Walnut Creek, USA, Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Heraklion, Crete, Greece. Corresponding Author: Nikos C. Kyrpides DOE Joint Genome Institute 2800 Mitchell Drive, B400 Walnut Creek, CA 94598 Phone: 925-296-5718 Fax: 925-296-5850 Email: NCKyrpides@lbl.gov
Bone Morphogenetic Protein‐2 Promotes Human Mesenchymal Stem Cell Survival and Resultant Bone Formation When Entrapped in Photocrosslinked Alginate Hydrogels

There is a substantial need to prolong cell persistence and enhance functionality in situ to enhance cell‐based tissue repair. Bone morphogenetic protein‐2 (BMP‐2) is often used at high concentrations for osteogenic differentiation of mesenchymal stem cells (MSCs) but can induce apoptosis. Biomaterials facilitate the delivery of lower doses of BMP‐2, reducing side effects and localizing materials at target sites. Photocrosslinked alginate hydrogels (PAHs) can deliver osteogenic materials to irregular‐sized bone defects, providing improved control over material degradation compared to ionically cross‐linked hydrogels. It is hypothesized that the delivery of MSCs and BMP‐2 from a PAH increases cell persistence by reducing apoptosis, while promoting osteogenic differentiation and enhancing bone formation compared to MSCs in PAHs without BMP‐2. BMP‐2 significantly decreases apoptosis and enhances survival of photoencapsulated MSCs, while simultaneously promoting osteogenic differentiation in vitro. Bioluminescence imaging reveals increased MSC survival when implanted in BMP‐2 PAHs. Bone defects treated with MSCs in BMP‐2 PAHs demonstrate 100% union as early as 8 weeks and significantly higher bone volumes at 12 weeks, while defects with MSC‐entrapped PAHs alone do not fully bridge. This study demonstrates that transplantation of MSCs with BMP‐2 in PAHs achieves robust bone healing, providing a promising platform for bone repair.
Fusing Sensor Paradigms to Acquire Chemical Information: An Integrative Role for Smart Biopolymeric Hydrogels

The Information Age transformed our lives but it has had surprisingly little impact on the way chemical information (e.g., from our biological world) is acquired, analyzed and communicated. Sensor systems are poised to change this situation by providing rapid access to chemical information. This access will be enabled by technological advances from various fields: biology enables the synthesis, design and discovery of molecular recognition elements as well as the generation of cell‐based signal processors; physics and chemistry are providing nano‐components that facilitate the transmission and transduction of signals rich with chemical information; microfabrication is yielding sensors capable of receiving these signals through various modalities; and signal processing analysis enhances the extraction of chemical information. The authors contend that integral to the development of functional sensor systems will be materials that (i) enable the integrative and hierarchical assembly of various sensing components (for chemical recognition and signal transduction) and (ii) facilitate meaningful communication across modalities. It is suggested that stimuli‐responsive self‐assembling biopolymers can perform such integrative functions, and redox provides modality‐spanning communication capabilities. Recent progress toward the development of electrochemical sensors to manage schizophrenia is used to illustrate the opportunities and challenges for enlisting sensors for chemical information processing.
Selection of bacteriophage λ integrases with altered recombination specificity by in vitro compartmentalization

In vitro compartmentalization (IVC) was employed for the first time to select for novel bacteriophage λ integrase variants displaying significantly enhanced recombination activity on a non-cognate target DNA sequence. These variants displayed up to 9-fold increased recombination activity over the parental enzyme, and one mutant recombined the chosen non-cognate substrate more efficiently than the parental enzyme recombined the wild-type DNA substrate. The in vitro specificity phenotype extended to the intracellular recombination of episomal vectors in HEK293 cells. Surprisingly, mutations conferring the strongest phenotype do not occur in the λ integrase core-binding domain, which is known to interact directly with cognate target sequences. Instead, they locate to the N-terminal domain which allosterically modulates integrase activity, highlighting a previously unknown role for this domain in directing integrase specificity. The method we describe provides a robust, completely in vitro platform for the development of novel integrase reagent tools for in vitro DNA manipulation and other biotechnological applications.
Review of Flexible Temperature Sensing Networks for Wearable Physiological Monitoring

Physiological temperature varies temporally and spatially. Accurate and real‐time detection of localized temperature changes in biological tissues regardless of large deformation is crucial to understand thermal principle of homeostasis, to assess sophisticated health conditions, and further to offer possibilities of building a smart healthcare and medical system. Additionally, continuous temperature mapping in flexible and stretchable formats opens up many other potential areas, such as artificially electronic skins and reflection of emotional changes. This review exploits a comprehensive investigation onto recent advances in flexible temperature sensors, stretchable sensor networks, and platforms constructed in soft and compliant formats for wearable physiological monitoring. The most recent examples of flexible temperature sensors are first discussed regarding to their materials, structures, electrical and mechanical properties; temperature sensing network technologies in new materials and structural designs are then presented based on platforms comprised of multiple physical sensors and stretchable electronics. Finally, wearable applications of the sensing network are described, such as detection of human activities, monitoring of health conditions, and emotion‐related bodily sensations. Conclusions are made with emphasis on critical issues and new trends in the field of wearable temperature sensor network technologies.
Acute Respiratory Distress Syndrome with Septic Shock Rescued by Long-term Use of Extracorporeal Membrane Oxygenation

We report a 5-year-6-month-old case of pneumonia complicating with septic shock and acute respiratory distress syndrome. He was successfully treated with extracorporeal membrane oxygenation (ECMO). Veno-arterial mode of ECMO was used at first and it was shifted to veno-venous mode of ECMO after hemodynamics were stabilized. Total supporting duration of ECMO was 684 hours. The patient is well now, in functional class I of the New York Heart Association.
The Strong Family Program: an innovative model to engage Aboriginal and Torres Strait Islander youth and Elders with reproductive and sexual health community education

Issue addressed Aboriginal youth in Australia often experience high rates of intimate partner violence (family violence) and poorer reproductive and sexual health than their non-Aboriginal counterparts. To address some of the disparities, the Strong Family Program was developed to deliver reproductive and sexual health education to Aboriginal communities in New South Wales. Methods Development of the program was based on an extensive consultation process with Aboriginal communities. It was implemented in three communities, with two groups from each hosting Aboriginal youth and Elders in a yarning circle within the culturally respectful frameworks of 'men and boys'' and 'women and girls'' business. An evaluation was conducted to measure reproductive and sexual health knowledge and attitude changes upon program completion, using pre- and post-program surveys and yarning (focus group discussions). Results Program participants comprised 48 females and 28 males. Overall, mean knowledge and attitude scores improved upon completion of the program (from 77% to 82% and from 4.15 to 4.32 out of 5, respectively). Among participants aged 20 years and under (the youngest participant was 13 years), there was an increase in knowledge (P=0.034); among participants aged over 20 years (the oldest participant was 78 years), there was an increase in positive attitudes (P=0.001). Participants perceived the information provided to be useful and relevant, with many reporting improved knowledge and attitudes around rights and respectful relationships. Conclusions Reproductive and sexual health education in Aboriginal communities should be based on community consultations and carried out within a culturally appropriate framework to promote greater success. Continued implementation of the Strong Family Program will promote increased understanding of respectful relationships and improved health outcomes for Aboriginal young people. So what? The Strong Family Program was based on an extensive consultative process that ensured leadership and involvement from Aboriginal communities, with program content and delivery based on Aboriginal pedagogy and reflecting Aboriginal cultural values. Reproductive and sexual health promotion in Aboriginal communities should be based on community consultations and carried out within a culturally appropriate framework to promote greatest success.
Biomimetic Model of Tumor Microenvironment on Microfluidic Platform

The “Tumor microenvironment” (TME) is a complex, interacting system of the tumor and its surrounding environment. The TME has drawn more attention recently in attempts to overcome current drug resistance and the recurrence of cancer by understanding the cancer and its microenvironment systematically, beyond past reductionist approaches. However, a lack of experimental tools to dissect the intricate interactions has hampered in‐depth research into the TME. Here, a biomimetic TME model using a microfluidic platform is presented, which enables the interaction between TME constituents to be studied in a comprehensive manner. Paracrine interactions of cocultured tumor cell lines (SK‐OV‐3, MKN‐74, and SW620) with primary fibroblasts show marked morphological changes in the tumor cells, depending on the type of tumor cells, and, importantly, the composition of the extracellular matrix. Furthermore, this model allows direct observation of angiogenesis induced by the tumor–stroma interaction. Finally, reconstituting simultaneous angiogenesis and lymphangiogenesis induced by the tumor‐stromal interaction with TME mimicking extrinsic factors is enabled. It is believed that the in vitro biomimetic model and the experimental concepts described will help to shed light on the complex biology of the TME.
Genenames.org: the HGNC resources in 2015

The HUGO Gene Nomenclature Committee (HGNC) based at the European Bioinformatics Institute (EMBL-EBI) assigns unique symbols and names to human genes. To date the HGNC have assigned over 39 000 gene names and, representing an increase of over 5000 entries in the past two years. As well as increasing the size of our database, we have continued redesigning our website http://www.genenames. org and have modified, updated and improved many aspects of the site including a faster and more powerful search, a vastly improved HCOP tool and a REST service to increase the number of ways users can retrieve our data. This article provides an overview of our current online data and resources, and highlights the changes we have made in recent years.
Supercritical Fluid Technology: An Emphasis on Drug Delivery and Related Biomedical Applications

During the past few decades, supercritical fluid (SCF) has emerged as an effective alternative for many traditional pharmaceutical manufacturing processes. Operating active pharmaceutical ingredients (APIs) alone or in combination with various biodegradable polymeric carriers in high‐pressure conditions provides enhanced features with respect to their physical properties such as bioavailability enhancement, is of relevance to the application of SCF in the pharmaceutical industry. Herein, recent advances in drug delivery systems manufactured using the SCF technology are reviewed. We provide a brief description of the history, principle, and various preparation methods involved in the SCF technology. Next, we aim to give a brief overview, which provides an emphasis and discussion of recent reports using supercritical carbon dioxide (SC‐CO2) for fabrication of polymeric carriers, for applications in areas related to drug delivery, tissue engineering, bio‐imaging, and other biomedical applications. We finally summarize with perspectives.