Miracle-dz/UniFAR-FTUs huggingface dataset:
Biodegradable Ethylene‐Bis(Propyl)Disulfide‐Based Periodic Mesoporous Organosilica Nanorods and Nanospheres for Efficient In‐Vitro Drug Delivery

Periodic mesoporous organosilica nanorods and nanospheres are synthesized from 1,4-bis(triethoxysilyl)ethylene and bis(3-ethoxysilylpropyl)disulfide. The nanosystems present the long-range order of the hexagonal nanostructure. They are degraded in simulated physiological conditions. The loading and release of doxorubicin with these nanosystems are both pH dependent. These nanoparticles are endocytosed by breast cancer cells and are very efficient for doxorubicin delivery in these cells.
Pioglitazone and bladder cancer: a propensity score matched cohort study.

AIM To examine whether exposure to pioglitazone use is associated with increased incidence of bladder cancer in patients with type 2 diabetes mellitus. METHOD A cohort study was done in the General Practice Research Database (GPRD) between 2001 and 2010. Two hundred and seven thousand seven hundred and fourteen patients aged ≥40 years with type 2 diabetes were studied (23,548 exposed to pioglitazone and 184,166 exposed to other antidiabetic medications but not pioglitazone). The association between pioglitazone and risk of bladder cancer was assessed by a Cox regression model. A propensity score matched analysis was done in a group of patients without missing baseline characteristics data. RESULTS Sixty-six and 803 new cases of bladder cancer occurred in the pioglitazone and other group, respectively (rates of 80.2 (95% CI 60.8, 99.5) and 81.8 (95% CI 76.2, 87.5) per 100,000 person-years respectively). Pioglitazone did not increase the risk of bladder cancer significantly compared with the other antidiabetic drugs treatment group, (adjusted hazard ratio (HR), 1.16, 95% CI 0.83, 1.62). In a matched propensity score analysis in which both groups had similar baseline characteristics (17,249 patients in each group), the adjusted HR was 1.22 (95% CI 0.80, 1.84). CONCLUSION The results suggest that pioglitazone may not be significantly associated with an increased risk of bladder cancer in patients with type 2 diabetes.
A prominent pattern of year-to-year variability in Indian Summer Monsoon Rainfall

The dominant patterns of Indian Summer Monsoon Rainfall (ISMR) and their relationships with the sea surface temperature and 850-hPa wind fields are examined using gridded datasets from 1900 on. The two leading empirical orthogonal functions (EOFs) of ISMR over India are used as basis functions for elucidating these relationships. EOF1 is highly correlated with all India rainfall and El Niño–Southern Oscillation indices. EOF2 involves rainfall anomalies of opposing polarity over the Gangetic Plain and peninsular India. The spatial pattern of the trends in ISMR from 1950 on shows drying over the Gangetic Plain projects onto EOF2, with an expansion coefficient that exhibits a pronounced trend during this period. EOF2 is coupled with the dominant pattern of sea surface temperature variability over the Indian Ocean sector, which involves in-phase fluctuations over the Arabian Sea, the Bay of Bengal, and the South China Sea, and it is correlated with the previous winter’s El Niño–Southern Oscillation indices. The circulation anomalies observed in association with fluctuations in the time-varying indices of EOF1 and EOF2 both involve distortions of the low-level monsoon flow. EOF1 in its positive polarity represents a southward deflection of moist, westerly monsoon flow from the Arabian Sea across India, resulting in a smaller flux of moisture to the Himalayas. EOF2 in its positive polarity represents a weakening of the monsoon trough over northeastern India and the westerly monsoon flow across southern India, reminiscent of the circulation anomalies observed during break periods within the monsoon season.
Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology?

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n-3 fatty acids found in oily fish and fish oil supplements. These fatty acids are able to inhibit partly a number of aspects of inflammation including leucocyte chemotaxis, adhesion molecule expression and leucocyte-endothelial adhesive interactions, production of eicosanoids like prostaglandins and leukotrienes from the n-6 fatty acid arachidonic acid, production of inflammatory cytokines and T cell reactivity. In parallel, EPA gives rise to eicosanoids that often have lower biological potency than those produced from arachidonioc acid and EPA and DHA give rise to anti-inflammatory and inflammation resolving resolvins and protectins. Mechanisms underlying the anti-inflammatory actions of n-3 fatty acids include altered cell membrane phospholipid fatty acid composition, disruption of lipid rafts, inhibition of activation of the pro-inflammatory transcription factor nuclear factor kappa B so reducing expression of inflammatory genes, activation of the anti-inflammatory transcription factor NR1C3 (i.e. peroxisome proliferator activated receptor γ) and binding to the G protein coupled receptor GPR120. These mechanisms are interlinked. In adult humans, an EPA plus DHA intake greater than 2 g day⁻¹ seems to be required to elicit anti-inflammatory actions, but few dose finding studies have been performed. Animal models demonstrate benefit from n-3 fatty acids in rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and asthma. Clinical trials of fish oil in patients with RA demonstrate benefit supported by meta-analyses of the data. Clinical trails of fish oil in patients with IBD and asthma are inconsistent with no overall clear evidence of efficacy.
Activation of 5′-3′ exoribonuclease Xrn1 by cofactor Dcs1 is essential for mitochondrial function in yeast

The scavenger decapping enzyme Dcs1 has been shown to facilitate the activity of the cytoplasmic 5′-3′ exoribonuclease Xrn1 in eukaryotes. Dcs1 has also been shown to be required for growth in glycerol medium. We therefore wondered whether the capacity to activate RNA degradation could account for its requirement for growth on this carbon source. Indeed, a catalytic mutant of Xrn1 is also unable to grow in glycerol medium, and removal of the nuclear localization signal of Rat1, the nuclear homolog of Xrn1, restores glycerol growth. A cytoplasmic 5′-3′ exoribonuclease activity is therefore essential for yeast growth on glycerol, suggesting that Xrn1 activation by Dcs1 is physiologically important. In fact, Xrn1 is essentially inactive in the absence of Dcs1 in vivo. We analyzed the role of Dcs1 in the control of exoribonuclease activity in vitro and propose that Dcs1 is a specific cofactor of Xrn1. Dcs1 does not stimulate the activity of other 5′-3′ exoribonucleases, such as Rat1, in vitro. We demonstrate that Dcs1 improves the apparent affinity of Xrn1 for RNA and that Xrn1 and Dcs1 can form a complex in vitro. We examined the biological significance of this regulation by performing 2D protein gel analysis. We observed that a set of proteins showing decreased levels in a DCS deletion strain, some essential for respiration, are also systematically decreased in an XRN1 deletion mutant. Therefore, we propose that the activation of Xrn1 by Dcs1 is important for respiration.
AgRP neurons: The foes of reproduction in leptin-deficient obese subjects

Evolutionarily, the ability to regulate energy balance and reproduction in parallel is critical, because reproductive success will only occur when sufficient energy supplies are available. In periods when energy stores are depleted, reproduction is switched off in an attempt to save energy to optimize survival for subsequent reproductive success. The cellular mechanisms involved in the fine coordination of energy balance and reproduction are largely unknown. In PNAS, Wu et al. (1) shed light on a previously unsuspected neuronal population that appears to be fundamental for the coupling of energy deficit with impaired reproduction.
Reduced release probability prevents vesicle depletion and transmission failure at dynamin mutant synapses

Endocytic recycling of synaptic vesicles after exocytosis is critical for nervous system function. At synapses of cultured neurons that lack the two “neuronal” dynamins, dynamin 1 and 3, smaller excitatory postsynaptic currents are observed due to an impairment of the fission reaction of endocytosis that results in an accumulation of arrested clathrin-coated pits and a greatly reduced synaptic vesicle number. Surprisingly, despite a smaller readily releasable vesicle pool and fewer docked vesicles, a strong facilitation, which correlated with lower vesicle release probability, was observed upon action potential stimulation at such synapses. Furthermore, although network activity in mutant cultures was lower, Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity was unexpectedly increased, consistent with the previous report of an enhanced state of synapsin 1 phosphorylation at CaMKII-dependent sites in such neurons. These changes were partially reversed by overnight silencing of synaptic activity with tetrodotoxin, a treatment that allows progression of arrested endocytic pits to synaptic vesicles. Facilitation was also counteracted by CaMKII inhibition. These findings reveal a mechanism aimed at preventing synaptic transmission failure due to vesicle depletion when recycling vesicle traffic is backed up by a defect in dynamin-dependent endocytosis and provide new insight into the coupling between endocytosis and exocytosis.
Natural‐Based Nanocomposites for Bone Tissue Engineering and Regenerative Medicine: A Review

Tissue engineering and regenerative medicine has been providing exciting technologies for the development of functional substitutes aimed to repair and regenerate damaged tissues and organs. Inspired by the hierarchical nature of bone, nanostructured biomaterials are gaining a singular attention for tissue engineering, owing their ability to promote cell adhesion and proliferation, and hence new bone growth, compared with conventional microsized materials. Of particular interest are nanocomposites involving biopolymeric matrices and bioactive nanosized fillers. Biodegradability, high mechanical strength, and osteointegration and formation of ligamentous tissue are properties required for such materials. Biopolymers are advantageous due to their similarities with extracellular matrices, specific degradation rates, and good biological performance. By its turn, calcium phosphates possess favorable osteoconductivity, resorbability, and biocompatibility. Herein, an overview on the available natural polymer/calcium phosphate nanocomposite materials, their design, and properties is presented. Scaffolds, hydrogels, and fibers as biomimetic strategies for tissue engineering, and processing methodologies are described. The specific biological properties of the nanocomposites, as well as their interaction with cells, including the use of bioactive molecules, are highlighted. Nanocomposites in vivo studies using animal models are also reviewed and discussed.
Locomotive implication of a Pliocene three-toed horse skeleton from Tibet and its paleo-altimetry significance

The Tibetan Plateau is the youngest and highest plateau on Earth, and its elevation reaches one-third of the height of the troposphere, with profound dynamic and thermal effects on atmospheric circulation and climate. The uplift of the Tibetan Plateau was an important factor of global climate change during the late Cenozoic and strongly influenced the development of the Asian monsoon system. However, there have been heated debates about the history and process of Tibetan Plateau uplift, especially the paleo-altimetry in different geological ages. Here we report a well-preserved skeleton of a 4.6 million-y-old three-toed horse (Hipparion zandaense) from the Zanda Basin, southwestern Tibet. Morphological features indicate that H. zandaense was a cursorial horse that lived in alpine steppe habitats. Because this open landscape would be situated above the timberline on the steep southern margin of the Tibetan Plateau, the elevation of the Zanda Basin at 4.6 Ma was estimated to be ∼4,000 m above sea level using an adjustment to the paleo-temperature in the middle Pliocene, as well as comparison with modern vegetation vertical zones. Thus, we conclude that the southwestern Tibetan Plateau achieved the present-day elevation in the mid-Pliocene.
Alterations in RNA processing during immune-mediated programmed cell death

During immune-mediated death, death-inducing granzyme (Gzm) proteases concentrate in the nucleus of cells targeted for immune elimination, suggesting that nuclear processes are important targets. Here we used differential 2D proteomics of GzmA-treated nuclei to identify potential GzmA substrates. Of 44 candidates, 33 were RNA-binding proteins important in posttranscriptional RNA processing, including 14 heterogeneous nuclear ribonucleoproteins (hnRNP). Multiple hnRNPs were degraded in cells undergoing GzmA-, GzmB-, or caspase-mediated death. GzmA and caspase activation impaired nuclear export of newly synthesized RNA and disrupted pre-mRNA splicing. Expressing GzmA-resistant hnRNP A1 inhibited GzmA-mediated cell death and rescued pre-mRNA splicing, suggesting that hnRNP A1 is an important GzmA substrate. Cellular stresses are known to inhibit initiation of cap-dependent translation. Disrupting pre-mRNA processing should block further new protein synthesis and promote death by interfering with pathways induced to protect cells from death.
Ocean barrier layers’ effect on tropical cyclone intensification

Improving a tropical cyclone’s forecast and mitigating its destructive potential requires knowledge of various environmental factors that influence the cyclone’s path and intensity. Herein, using a combination of observations and model simulations, we systematically demonstrate that tropical cyclone intensification is significantly affected by salinity-induced barrier layers, which are “quasi-permanent” features in the upper tropical oceans. When tropical cyclones pass over regions with barrier layers, the increased stratification and stability within the layer reduce storm-induced vertical mixing and sea surface temperature cooling. This causes an increase in enthalpy flux from the ocean to the atmosphere and, consequently, an intensification of tropical cyclones. On average, the tropical cyclone intensification rate is nearly 50% higher over regions with barrier layers, compared to regions without. Our finding, which underscores the importance of observing not only the upper-ocean thermal structure but also the salinity structure in deep tropical barrier layer regions, may be a key to more skillful predictions of tropical cyclone intensities through improved ocean state estimates and simulations of barrier layer processes. As the hydrological cycle responds to global warming, any associated changes in the barrier layer distribution must be considered in projecting future tropical cyclone activity.
Activity Based Costing in Healthcare: A UK Case Study

he reduction of public funding and the emphasis on performance measurement in public services have influenced the management and accounting practices of many healthcare systems. The pressures have led many managers to search for management tools, often derived from the private sector, in the attempt to rationalize their use of resources. Activity Based Costing (ABC) is one of these techniques which has gained considerable attention both from practitioners and researchers. This paper examines the case of a UK healthcare organization which implemented ABC to provide sharper cost information for control and decision making. The paper is a longitudinal study of an accounting application which provides insights into the process of adoption and enactment of costing innovation in healthcare. ealthcare systems, internationally, face pressures to deliver cost efficient care in the face of escalating demands. These pressures have led to many initiatives to improve the management and efficiency of healthcare delivery. This paper examines the trajectory—from initial idea to implementation—of the adoption of activity based costing (ABC) to improve efficiency by one healthcare organization. The healthcare organization which is discussed in this paper is a blood transfusion service, part of the UKs National Health Service. This study reveals the challenges, the pitfalls and the problems of adopting a costing technology which is radically different from previous practices in a healthcare setting. RESEARCH CONTEXT The UK’s blood transfusion service is currently organized into four regional centers for the collection and distribution of blood (Varney & Guest, 2003). The role of these centers in the healthcare system is crucial and their management is complex from the ‘raw material’ procurement phase through to final use. The UK’s transfusion services rely on voluntary donors, who donate their blood up to three times a year. Though this
Review and expert opinion on prevention and treatment of infliximab‐related infusion reactions

Infliximab (Remicade®; Schering‐Plough, Kenilworth, NJ, U.S.A.) is a chimeric monoclonal antibody that acts as a tumour necrosis factor‐α inhibitor. Infliximab is registered for the treatment of rheumatoid arthritis, psoriatic arthritis, Crohn disease, ulcerative colitis, ankylosing spondylitis and plaque‐type psoriasis. Like other foreign protein‐derived agents, infliximab may lead to infusion reactions during and after infusion. Infusion reactions occur in 3–22% of patients with psoriasis treated with infliximab. Most of these reactions are mild or moderate and only few are severe. Nevertheless, they may lead to discontinuation of treatment. As infliximab for psoriasis is prescribed as a last resort and is in most cases very effective, discontinuation of treatment is undesirable. With proper care and prevention of the infusion reactions the need to discontinue treatment with infliximab can be diminished. The objective of this article is to present a guideline for the management of infliximab‐related infusion reactions, based on the best available evidence. This guideline can be used in patients with psoriasis as well as in dermatology patients receiving infliximab for off‐label indications such as hidradenitis suppurativa or pyoderma gangrenosum.
The remarkable, yet not extraordinary, human brain as a scaled-up primate brain and its associated cost

Neuroscientists have become used to a number of “facts” about the human brain: It has 100 billion neurons and 10- to 50-fold more glial cells; it is the largest-than-expected for its body among primates and mammals in general, and therefore the most cognitively able; it consumes an outstanding 20% of the total body energy budget despite representing only 2% of body mass because of an increased metabolic need of its neurons; and it is endowed with an overdeveloped cerebral cortex, the largest compared with brain size. These facts led to the widespread notion that the human brain is literally extraordinary: an outlier among mammalian brains, defying evolutionary rules that apply to other species, with a uniqueness seemingly necessary to justify the superior cognitive abilities of humans over mammals with even larger brains. These facts, with deep implications for neurophysiology and evolutionary biology, are not grounded on solid evidence or sound assumptions, however. Our recent development of a method that allows rapid and reliable quantification of the numbers of cells that compose the whole brain has provided a means to verify these facts. Here, I review this recent evidence and argue that, with 86 billion neurons and just as many nonneuronal cells, the human brain is a scaled-up primate brain in its cellular composition and metabolic cost, with a relatively enlarged cerebral cortex that does not have a relatively larger number of brain neurons yet is remarkable in its cognitive abilities and metabolism simply because of its extremely large number of neurons.
The Social Determinants of Routine Immunisation in Ekiti State of Nigeria

Abstract The greatest challenge to child health in sub Saharan Africa is poor immunization service for major child illnesses. The World Health Organisation’s (WHO) review of the health systems of the World, looking at various health indicators including child mortality, in the year 2003 placed Nigeria in 187th position among 191 countries, and little has been achieved since then. This paper is an overview of routine immunization in Ekiti State of Nigeria. The State serves as a case for understanding the prospects and challenges of child health care in South Nigeria. The study used qualitative data derived from focus group discussions and key informants and secondary data of state and national surveys. The findings identify factors that account for the relative poor immunization coverage. The salient issues include ignorance and social cost of access to the service. Also the quality of the immunization service: availability to the remote areas, health personnel commitment, and consistent availability account for low coverage. It is concluded and recommended that there is a need for improvement in the supply side of immunization service especially taken the service to the physically and socially marginalized areas and also extend the campaigns for immunizations beyond the current emphasis on Polio vaccination to incorporate other antigens.
Hyperglycaemic conditions decrease cultured keratinocyte mobility: implications for impaired wound healing in patients with diabetes

Background Elevated blood glucose in patients with diabetes mellitus (DM) leads to complications including poor wound healing. Proper keratinocyte migration and proliferation are the crucial steps during re‐epithelialization. We hypothesize that the impaired wound healing in patients with DM is due to the disruption of proper re‐epithelialization.
Aspirin Medication in Dogs

Summary Aspirin (acetylsalicylic acid; ASA) is widely used in both human and veterinary medicine. Therapeutic plasma salicylate concentrations (PSCs) can be reached using enteric-coated ASA tablets, but a delay in the initial rise and large fluctuations in the PSCs have been reported. From experiments described previously, the authors concluded that the large type enteric-coated ASA tablets were not suitable for use in beagle dogs. In the first experiment described here, these large type tablets were administered to large mongrel dogs. Although the mean PSC reached therapeutic levels after 44 h, in individual dogs subtherapeutic concentrations were frequently recorded. In the second experiment microgranulated type enteric-coated ASA tablets were given to beagle dogs in a crossover design study. PSCs in all dogs exceeded minimal therapeutic levels 6 h after tablet administration. Stable therapeutic PSCs were found in both groups on different feeding regimens. In the third experiment the two types of enteric-coated ASA tablets were administered to fasting beagles. Comparable therapeutic PSCs were reached with both formulations. From the present studies it can be concluded that the large type enteric-coated ASA tablet is not suitable for use in large mongrel dogs. Secondly, it can be concluded that the microgranulated type enteric-coated ASA tablet is suitable for the use in beagle dogs. In the third experiment it was proven that fasting eliminated the differences in mean PSC curves between the two types of ASA medication. On the basis of canine gastric physiology the authors expect similar types of large enteric-coated tablets of other drugs to generate comparably poor plasma concentrations. The gastric evacuation of tablets is primarily related to the tablet dimensions and digestibility, and not to the drug contained by these tablets.
Flow‐Driven Triboelectric Generator for Directly Powering a Wireless Sensor Node

A triboelectric generator (TEG) for scavenging flow-driven mechanical -energy to directly power a wireless sensor node is demonstrated for the first time. The output performances of TEGs with different dimensions are systematically investigated, indicating that a largest output power of about 3.7 mW for one TEG can be achieved under an external load of 3 MΩ.