Miracle-dz/UniFAR-FTUs huggingface dataset:
Upconverting nanoparticles as nanotransducers for photodynamic therapy in cancer cells.

BACKGROUND Photodynamic therapy (PDT) involves killing of diseased cells by excitation of photosensitizer chemicals with high-energy light to produce cytotoxic oxygen species from surrounding dissolved oxygen. However, poor tissue penetration of high-energy light and hydrophobic photosensitizers limits the effectiveness to superficial pathologies. Upconversion phosphor nanoparticles convert low-energy radiation to higher-energy emissions. AIM To create upconverting 'nanotransducers' to enable PDT in deep tissues. RESULTS Monodisperse, 50 nm PEI/NaYF(4):Yb(3+),Er(3+) nanoparticles producing green/red emission on near-infrared (NIR) excitation were targeted to folate receptors on human colon cancer cells and imaged with high signal-to-background ratio. It was demonstrated that these particles could be excited after deep intramuscular injection in rats. On NIR excitation, the particles, modified with zinc phthalocyanin photosensitizer, released singlet oxygen and, after targeted binding to cancer cells, resulted in significant cell destruction. CONCLUSION Potential clinical use of these nanoparticles includes imaging and PDT of cancer in deep tissues.
Wound healing activity of Matricaria recutita L. extract.

OBJECTIVE To evaluate the wound healing activity of M. recutita (chamomile) extract in rats. METHOD Wound healing activity was determined using excision, incision and dead space wound models. The animals were divided into two groups of six for each model: animals in the test group were treated with the aqueous extract of M. recutita (120mg/kg/day), which was mixed in their drinking water. Animals in the control group were maintained with plain drinking water. Healing was assessed by the rate of wound contraction, period of epithelialisation, wound-breaking strength, granulation tissue weight and hydoxyproline content. Antimicrobial activity of the extract against various microorganisms was assessed. RESULTS On day 15 animals in the test group exhibited a greater reduction in the wound area when compared with the controls (61 % versus 48%), faster epithelialisation and a significantly higher wound-breaking strength (p<0.002). In addition, wet and dry granulation tissue weight and hydroxyproline content were significantly higher. CONCLUSION The increased rate of wound contraction, together with the increased wound-breaking strength, hydroxyproline content and histological observations, support the use of M. recutita in wound management. However, this needs to be studied further before it can be considered for clinical use.
Moral injury in U.S. combat veterans: Results from the national health and resilience in veterans study

Combat exposure is associated with increased risk of mental disorders and suicidality. Moral injury, or persistent effects of perpetrating or witnessing acts that violate one's moral code, may contribute to mental health problems following military service. The pervasiveness of potentially morally injurious events (PMIEs) among U.S. combat veterans, and what factors are associated with PMIEs in this population remains unknown.
Power Management for a Hybrid AC/DC Microgrid With Multiple Subgrids

This paper proposes a new topology of a hybrid ac/dc microgrid, where there are multiple subgrids connected to the common bus by bidirectional ac/dc converters (BADCs) and bidirectional dc/dc converters (BDDCs) in the system. The rated ac frequencies in different ac subgrids and the rated dc voltages in different dc subgrids can be different for different applications. All the storages in the system are concentrated to form a storage subgrid for convenient management and high efficiency, which maintains the common bus voltage. To ensure the hybrid microgrid operates well, a proper power management method is necessary to control the power flow among multiple subgrids. This paper proposes a decentralized power management method for the hybrid microgrid to make the interacted subgrids operate in coordination and support each other. First, taking the characteristics of the common bus configuration into consideration, a ${P_{{\rm{dc}}}} - v_{{\rm{dc}}}^2$ droop control strategy is proposed to maintain the common bus voltage and to realize power sharing among storages in the storage subgrid. Second, as the interaction among multiple subgrids is more complicated compared to the conventional hybrid, a coordinated power control strategy based on the common bus voltage, ac subgrid frequency, and dc subgrid voltage is designed for the BADCs and BDDCs to realize the power interaction among different subgrids. Furthermore, the proposed strategy takes the capacities and load types of each subgrid into consideration; hence, it is still suitable when the capacities of subgrids are mismatched and it can ensure the power quality of the subgrids with high proportion of critical loads. The effectiveness of the proposed power management method is verified by the real-time hardware-in-loop tests.
The evaluation of rifampicin bioavailabilities of fixed-dose combinations of anti-tuberculosis drugs: procedures for ensuring laboratory proficiency.

SETTING The perceived need to demonstrate whether or not the rifampicin bioavailability of commercially manufactured fixed-dose combinations is satisfactory. OBJECTIVE To establish an international laboratory network to assess rifampicin bioavailability. DESIGN Convenient assay kits were devised to evaluate the ability of laboratories in China, India, Italy, South Africa, Thailand and the USA to determine plasma and urinary concentrations of rifampicin and desacetyl-rifampicin. RESULTS Five laboratories, all of whom used high pressure liquid chromatographic methods, were shown to be able to accurately and precisely determine the two compounds. CONCLUSION Such a procedure is simple, convenient and objective and could be further employed to enlarge the intended international laboratory network.
Recent advances in the genetic neuropathies.

PURPOSE OF REVIEW Charcot-Marie-Tooth disease (CMT) is one of the commonest inherited neuromuscular diseases with a population prevalence of 1 in 2500. This review will cover recent advances in the genetics and pathomechanisms of CMT and how these are leading to the development of rational therapies. RECENT FINDINGS Pathomechanistic and therapeutic target advances in CMT include the identification of the ErbB receptor signalling pathway as a therapeutic target in CMT1A and pharmacological modification of the unfolded protein response in CMT1B. In CMT2D, due to mutations in glycyl-tRNA synthetase, vascular endothelial growth factor-mediated stimulation of the Nrp1 receptor has been identified as a therapeutic target. Preclinical advances have been accompanied by the publication of large natural history cohorts and the identification of a sensitive biomarker of disease (muscle MRI) that is able to detect disease progression in CMT1A over 1 year. SUMMARY Advances in next-generation sequencing technology, cell biology and animal models of CMT are paving the way for rational treatments. The combination of robust natural history data and the identification of sensitive biomarkers mean that we are now entering an exciting therapeutic era in the field of the genetic neuropathies.
Clinical Impact of Amino Acid PET in Gliomas

With an incidence of 20.5 per 100,000 people each year, tumors of the central nervous system are a heterogeneous group, with meningiomas (35.5%) and gliomas (30%) being the most common (1). Although 97% of meningiomas are benign, 54% of gliomas are highly malignant glioblastomas of World Health Organization (WHO) grade IV. Survival rates are 35.7% at 1 y and 4%–7% at 5 y for glioblastoma, 60%–80% at 1 y and 26%–46% at 5 y for astrocytomas and oligodendrogliomas of WHO grade III, and 94% at 1 y and 67% at 5 y for astrocytomas and oligodendrogliomas of WHO grade II (2). Additionally, the central nervous system may be invaded by metastases from other malignancies. Brain tumors create structural lesions whose diagnosis is primarily dependent on imaging with CT and MR. However, it is possible to improve clinical management by using PET to provide physiologic and biochemical information on tumor metabolism, proliferation rate, and invasiveness, as well as to determine the relationship of the tumor to important functional tissue and to monitor the effects of treatment (3). Imaging of brain tumors with 18 F-FDG was the first oncologic application of PET. As in other malignancies, glucose consumption is increased in brain tumors, especially in malignant gliomas, but differentiating tumors from normal tissue or nontumorous lesions is often difficult because of the high metabolism in normal cortex. 18 FFDG uptake in low-grade tumors is usually similar to that in normal white matter, and uptake in high-grade tumors can be less than or similar to that in normal gray matter. The sensitivity of detection of lesions is further decreased by the high variance of 18 F-FDG uptake and its heterogeneity within a single tumor. Labeled amino acids and their analogs are particularly attractive for imaging brain tumors because of the high uptake in tumor tissue and low uptake in normal brain. This increased amino acid uptake, especially in gliomas, is not a direct measure of protein synthesis or dependent on blood–brain barrier breakdown but rather is related to increased transport mediated by type L amino acid carriers: facilitated transport is upregulated because of the increased transporter expression in tumor vasculature (4). Additionally, the countertransport system A is overexpressed in neoplastic cells and seems to correlate positively with the rate of tumor cell growth (5). Therefore, elevated transport of amino acids not only is a result of increased protein synthesis but also reflects the increased demand by different types of metabolism in the tumor cell. The most frequently used radiolabeled amino acid is methyl- 11 CL-methionine (MET) (6,7). Especially in low-grade gliomas, amino acid uptake is related to prognosis a nd survival. With regard to tumor extentandinfiltrationintosurroundingtissue,assessmentofaminoacid uptake is superior to measurement of glucose consumption (8 )a nd
Genotype–Phenotype Correlations of Malignant Hyperthermia and Central Core Disease Mutations in the Central Region of the RYR1 Channel

Type 1 ryanodine receptor (RYR1) is a Ca2+ release channel in the sarcoplasmic reticulum of skeletal muscle and is mutated in some muscle diseases, including malignant hyperthermia (MH) and central core disease (CCD). Over 200 mutations associated with these diseases have been identified, and most mutations accelerate Ca2+‐induced Ca2+ release (CICR), resulting in abnormal Ca2+ homeostasis in skeletal muscle. However, it remains largely unknown how specific mutations cause different phenotypes. In this study, we investigated the CICR activity of 14 mutations at 10 different positions in the central region of RYR1 (10 MH and four MH/CCD mutations) using a heterologous expression system in HEK293 cells. In live‐cell Ca2+ imaging, the mutant channels exhibited an enhanced sensitivity to caffeine, a reduced endoplasmic reticulum Ca2+ content, and an increased resting cytoplasmic Ca2+ level. The three parameters for CICR (Ca2+ sensitivity for activation, Ca2+ sensitivity for inactivation, and attainable maximum activity, i.e., gain) were obtained by [3H]ryanodine binding and fitting analysis. The mutant channels showed increased gain and Ca2+ sensitivity for activation in a site‐specific manner. Genotype–phenotype correlations were explained well by the near‐atomic structure of RYR1. Our data suggest that divergent CICR activity may cause various disease phenotypes by specific mutations.
Talk 1 1 Neurophysiology of gait for understanding basal ganglia motor disorders-from animal behaviors to the constructive approach -

We elucidated substrates for the execution of normal gait and to understand pathophysiological mechanisms of gait failure in basal ganglia dysfunctions. In Parkinson’s disease, volitional and emotional expressions of movement processes are seriously affected in addition to the disturbance of automatic movement processes, such as adjustment of postural muscle tone and rhythmic limb movements during walking. These patients also suffer from muscle tone rigidity and postural instability, which may also cause reduced walking capabilities. Neurophysiological and clinical studies have suggested the importance of basal ganglia connections with the cerebral cortex and limbic system in the expression of volitional and emotional behaviors. Here we hypothesize a crucial role played by the basal ganglia-brainstem system in the integrative control of muscle tone and locomotion. The hypothetical model may provide a rational explanation for the role of the basal ganglia in the control of volitional and automatic aspects of movements. It can also be beneficial for understanding pathophysiological mechanisms of basal ganglia movement disorders. A part of this hypothesis has been supported by studies utilizing a constructive simulation engineering technique that clearly shows that an appropriate level of postural muscle tone and proper acquisition and utilization of sensory information are essential to maintain adaptable bodily functions for the full execution of bipedal gait.
The Gut Hormone Peptide YY Regulates Appetite

Abstract: The gut hormone peptide YY (PYY) belongs to the pancreatic polypeptide (PP) family along with PP and neuropeptide Y (NPY). These peptides mediate their effects through the NPY receptors of which there are several subtypes (Y1, Y2, Y4, and Y5). The L cells of the gastrointestinal tract are the major source of PYY, which exists in two endogenous forms: PYY1–36 and PYY3–36. The latter is produced by the action of the enzyme dipeptidyl peptidase‐IV (DPP‐IV). PYY1–36 binds to and activates at least three Y receptor subtypes (Y1, Y2, and Y5), whereas PYY3–36 is more selective for Y2 receptor (Y2R). The hypothalamic arcuate nucleus, a key brain area regulating appetite, has access to nutrients and hormones within the peripheral circulation. NPY neurons within the arcuate nucleus express the Y2R. In response to food ingestion plasma PYY3–36 concentrations rise within 15 min and plateau by approximately 90 min. The peak PYY3–36 level achieved is proportional to the calories ingested, suggesting that PYY3–36 may signal food ingestion from the gut to appetite‐regulating circuits within the brain. We found that peripheral administration of PYY3–36 inhibited food intake in rodents and increased C‐Fos immunoreactivity in the arcuate nucleus. Moreover, direct intra‐arcuate administration of PYY3–36 inhibited food intake. We have shown that Y2R null mice are resistant to the anorectic effects of peripherally administered PYY3–36, suggesting that PYY3–36 inhibits food intake through the Y2R.
Switching between the Forest and the Trees: Brain Systems Involved in Local/Global Changed-Level Judgments

Visual targets can be coded, in relative terms, at either the local or the global level of stimuli. Previous studies have indicated that targets are identified more slowly when they appear at a new hierarchical level, compared to when they reappear at the same level as in the previous trial. In the present study, we used measures of reaction time and event-related fMRI to investigate factors affecting this switch cost. In particular, we examined the effects of the number of repeated-level trials preceding a switch and whether the cue to switch was either externally or internally mediated. At the behavioral level we found that (1) the time taken to identify a target on a changed-level trial is longer following four repeated-level trials compared to two repeated-level trials, but that runs of six do not produce additional costs over four, and (2) targets can be identified faster following externally cued switches compared to internally mediated switches. We then show that these behavioral effects are associated with distinct patterns of neural activation. Switches performed after two repeated-level trials preferentially activated the precuneus, while those performed after both four and six activated bilateral inferior parietal cortex and motor hand area. Relative to external switches, internal switches activated the putamen, while both kinds of switch conjointly activated the large-scale network proposed to underlie internal/external switches in nonhierarchical tasks. Our data further clarify the mechanisms mediating hierarchical selection.
HOST-AGENT INTERACTION IN EXPERIMENTAL TUBERCULOSIS IN GUINEA PIGS, WITH SPECIAL REFERENCE TO THE EFFECTS OF BCG VACCINATION.

Valuable contributions for the understanding of host-agent interaction in experimental tuberculosis have been made by detailed histologic and bacteriologic studies (1-11). Important as the findings of such studies are, it would nevertheless seem that their significance must eventually be evaluated in terms of the final outcome of the infection, that is, in terms of tuberculous disease and death. Justification for this view, especially for the studies of the mechanisms of immunity, may be found in the enormous literature on experimental tuberculosis, all of which indicates that the final outcome of a virulent tuberculous infection in naturally susceptible laboratory animals, whether immunized or not, is disease and eventual death from tuberculosis (12-16). In these terms, immunization prolongs life, and thus, in the end, its effect apparently is to reduce the speed with which the virulent infection progresses. Immunization, however, is not the only factor that can influence the pro-
DISCUSS: A dialogue move taxonomy layered over semantic representations

In this paper we describe DISCUSS, a dialogue move taxonomy layered over semantic representations. We designed this scheme to enable development of computational models of tutorial dialogues and to provide an intermediate representation suitable for question and tutorial act generation. As such, DISCUSS captures semantic and pragmatic elements across four dimensions: Dialogue Act, Rhetorical Form, Predicate Type, Semantic Roles. Together these dimensions provide a summary of an utterance's propositional content and how it may change the underlying information state of the conversation. This taxonomy builds on previous work in both general dialogue act taxonomies as well as work in tutorial act and tutorial question categorization. The types and values found within our taxonomy are based on preliminary observations and on-going annotation from our corpus of multimodal tutorial dialogues for elementary school science education.
Clinical and professional role development among experienced pediatric nurses: the pediatric medical nursing certificate program.

ISSUES AND PURPOSE The development of a multiunit-based certificate program to promote retention by increasing experienced pediatric nurses' knowledge, skills, and professional role development through a blend of didactic, clinical, and mentoring components. CONCLUSIONS The certificate group demonstrated an increase in knowledge and skill, advanced leadership role acquisition, promotion, certification, and graduate school matriculation, and achieved a 95% retention rate within the organization. PRACTICE IMPLICATIONS With support from management and multidisciplinary team members, a certificate program like this can be implemented in a variety of settings and specialties.
Ocular Hypertension Treatment Study (OHTS) commentary

Purpose of review To summarize the major findings of the Ocular Hypertension Treatment Study (OHTS). Recent findings Ocular hypertensive subjects who received topical glaucoma medication experienced conversion to glaucoma at less than half the rate of subjects who were monitored without treatment. Risk factors for converting to glaucoma included older age, higher intraocular pressure, larger cup-disc ratio, higher pattern SD, and thinner central corneal thickness. Summary The OHTS clearly established that medically treating ocular hypertension is efficacious in delaying or preventing the onset of glaucoma. Further, the results may assist in providing useful guidelines for determining who with ocular hypertension should be offered medical treatment.
HIPERINSULINISMO FISIOPATOLOGIA Y MANIFESTACIONES CLINICAS EN OBSTETRICIA Y GINECOLOGIA

Se revisa la fisiopatologia del hiperinsulinismo, los mecanismos celulares involucrados, sus manifestaciones clinicas mas frecuentes en Obstetricia y Ginecologia, reuniendo informacion dispersa en la literatura. El objetivo es comprender el nexo entre este trastorno y las patologias mencionadas, de modo de aplicar conducta preventiva, terapeutica y visualizar eventuales terapias futuras
Monocyte Trafficking to Hepatic Sites of Bacterial Infection Is Chemokine Independent and Directed by Focal Intercellular Adhesion Molecule-1 Expression

Recruitment of CCR2+Ly6Chigh monocytes to sites of infection is essential for efficient clearance of microbial pathogens. Although CCR2-mediated signals promote monocyte emigration from bone marrow, the contribution of CCR2 to later stages of monocyte recruitment remains unresolved. In this article, we show that CCR2 deficiency markedly worsens hepatic Listeria monocytogenes infection because Ly6Chigh monocytes are retained in the bone marrow. Intravenously transferred, CCR2-deficient Ly6Chigh monocytes traffic normally to hepatic foci of infection and contribute to bacterial clearance. Pertussis toxin treatment of adoptively transferred monocytes does not impair their intrahepatic trafficking, suggesting that chemokine signaling, once CCR2+Ly6Chigh monocytes emigrate from the bone marrow, is not required for monocyte localization to sites of bacterial infection in the liver. Expression of ICAM-1 is induced in close proximity to foci of bacterial infection in the liver, including on CD31+ endothelial cells, and blockade of CD11b and CD44 diminishes monocyte localization to these hepatic foci. Our studies demonstrated that Ly6Chigh monocyte recruitment from the bloodstream to the L. monocytogenes-infected liver does not require chemokine receptor-mediated signals but instead is principally dependent on integrin- and extracellular matrix-mediated monocyte adhesion.
Thermic transition and glycolytic capacity as critical events in the survival of rat liver slices after overnight cold hypoxic preservation

Cellular survival and hypoxia–reoxygenation injury in overnight cold‐preserved liver slices (±20 h at 4°C) were investigated. Increased cell death after overnight cold hypoxia depended more on temperature than on the reoxygenation process itself. Fructose (at 50 mM) added before the onset of hypoxia improved survival at the end of 20 h of cold hypoxia over Krebs‐ or glucose‐treated slices. Such a protective effect by fructose was also seen during the normothermic (37°C) reoxygenation of previously cold hypoxic‐preserved slices, but only in the absence and not in the presence of tert‐butyl hydroperoxide, a model compound widely used to induce an oxidative stress. The protection by fructose was equivalent to that observed when liver slices were incubated in the University of Wisconsin solution (UW). Finally, the morphological study of haematoxylin and eosin (H & E)‐stained slices has shown cytoplasmic vacuoles during the reoxygenation step, which were more pronounced in UW‐treated than in fructose‐treated slices. © 1998 John Wiley & Sons, Ltd.