Using deep transfer learning and satellite imagery to estimate urban air quality in data-poor regions.
Urban air pollution is a critical public health challenge in low-and-middle-income countries (LMICs). At the same time, LMICs tend to be data-poor, lacking adequate infrastructure to monitor air quality (AQ). As LMICs undergo rapid urbanization, the socio-economic burden of poor AQ will be immense. Here we present a globally scalable two-step deep learning (DL) based approach for AQ estimation in LMIC cities that mitigates the need for extensive AQ infrastructure on the ground. We train a DL model that can map satellite imagery to AQ in high-income countries (HICs) with sufficient ground data, and then adapt the model to learn meaningful AQ estimates in LMIC cities using transfer learning. The trained model can explain up to 54% of the variation in the AQ distribution of the target LMIC city without the need for target labels. The approach is demonstrated for Accra in Ghana, Africa, with AQ patterns learned and adapted from two HIC cities, specifically Los Angeles and New York.


Non-small-cell lung cancer: practice patterns of extrathoracic imaging.
The purpose of this study was to identify practice patterns of extrathoracic imaging in patients newly diagnosed with non-small-cell lung, cancer. The authors retrospectively reviewed the charts of 125 patients (71 men, 54 women; mean age, 67 years) from five hospitals (25 patients each) with newly diagnosed non-small-cell lung cancer. Charts were reviewed for cancer cell type, evidence of metastatic disease, and performance and results of extrathoracic imaging, including computed tomography (CT) and magnetic resonance (MR) imaging of the brain, bone scanning, and abdominal CT. Of 125 patients, 77 (62%) underwent extrathoracic imaging. These patients included 64 (64%) of 100 patients with clinical symptoms or laboratory signs of metastatic disease and 13 (52%) of 25 patients with no such indications. Extrathoracic imaging did not differ according to cancer cell type: It was performed for 30 (60%) of 50 patients with squamous cell carcinoma, 26 (60%) of 43 patients with adenocarcinoma, and 16 (73%) of 22 patients with non-small-cell lung cancer that was not further characterized. Brain CT or MR imaging bone scanning, or abdominal CT were performed in only 48%, 39%, and 30% of patients, respectively. Brain CT or MR images or bone scans revealed metastatic disease in seven of 20 and nine of 22 patients with clinical symptoms or laboratory signs of disease, respectively. These examinations revealed disease in four of 40 and two of 27 patients without such symptoms or signs, respectively (P < .05). No significant differences emerged among the practice patterns at the five participating hospitals. No consensus was found on performance of extrathoracic imaging in patients with newly diagnosed non-small-cell lung cancer.


A formative assessment of client characteristics associated with missed appointments in integrated primary care services in rural Arizona.
Integrating primary care services in mental healthcare facilities is an uncommon model of care in the United States that could bring several benefits (e.g., improved access to physical healthcare) for vulnerable populations experiencing mental health conditions, especially those living in underserved regions like rural Arizona. This formative assessment aimed to understand the sociodemographic and clinical characteristics of clients accessing integrated primary care (IPC) services implemented in 2021 at a community mental healthcare facility in rural Arizona and to explore the proportion of missed appointments. Additionally, we analysed the association between client characteristics and IPC missed appointments. The authors collaborated with a community mental health facility in rural Arizona, which provided deidentified data from 280 clients who accessed IPC services from June 2021 to February 2022. Most clients were White and of vulnerable socioeconomic status, with a substantial proportion of Native Americans (23.58%). The majority of clients (55.75%) had a mental health disorder (MHD), 23.74% had a substance use disorder (SUD), and 15.10% had comorbid MHD and SUD. Linear regression revealed that experiencing comorbid MHD and SUD was significantly associated with missed appointments. Compared with White clients, Native Americans missed fewer appointments. Future studies conducted from a culturally-centred perspective are crucial to guide strategies to reduce missed appointments in rural IPC services.


Activation of hypothalamic ATP-sensitive K+ channels by the aminoguanidine carboxylate BVT.12777.
Derivatives of 3-guanidinopropionic acid, such as leptin, reduce body weight in obese, diabetic mice. We have assessed whether one of these analogues, BVT.12777 activates intracellular signalling pathways in the arcuate nucleus in a manner analogous to leptin and insulin. In addition, because these hormones have been shown to activate K(ATP) channels in a subset of arcuate neurones, we examined whether this channel is also a functional endpoint for BVT.12777 in the arcuate nucleus. BVT.12777 transiently increased phosphorylation of MAPK, STAT3, PKB and GSK3, in a manner identical to that observed for leptin and insulin. BVT.12777 also hyperpolarized glucose-responsive neurones by increasing the activity of K(ATP) channels. The increase in K(ATP) activity driven by BVT.12777 was PI3-kinase independent, unlike leptin and insulin activation of this channel, and could also be elicited in isolated patches. However, K(ATP) activity induced by BVT.12777 was dependent on actin filament dynamics, both in intact neurones and isolated patches. Thus, BVT.12777 modulates arcuate neurone K(ATP) activity by re-organization of the cytoskeleton, a mechanism that has also been ascribed to leptin and insulin. Consequently, BVT.12777 appears to act as a leptin and insulin mimetic with respect to at least some elements of arcuate neurone intracellular signalling and the activation of K(ATP) channels. Resistance to leptin and insulin, associated with obesity has, at least in part, been postulated to be due to aberrant intracellular signalling in arcuate neurones. The data presented here indicate that it may be possible to develop drugs, which by-pass up-stream signalling components associated with adiposity hormone resistance, such as PI3-kinase, but can still induce functional outputs from arcuate neurones by targeting downstream components of the leptin and insulin signalling cascades.


Endogenous steroids measured by high-specificity liquid chromatography-tandem mass spectrometry and prevalent cardiovascular disease in 70-year-old men and women.
There is a need for increased knowledge about endogenous sex hormone levels and clinical outcomes of risk/benefit. Immunoassays have poor specificity to reliably measure low steroid concentrations in elderly. The objective of the study was to evaluate plasma steroid concentrations with regard to prevalent cardiovascular disease (CVD) in elderly, using mass spectrometry. The study was conducted at a university hospital research unit. Plasma samples were analyzed from 202 70-yr-olds as part of a large population-based study, Prospective Investigation of the Vasculature in Uppsala Seniors. Twenty-eight of these had prevalent CVD. Eleven steroids were quantified, using liquid chromatography-tandem mass spectrometry. Women with current/previous menopausal hormone therapy (n = 35) were excluded. Men without prevalent CVD had higher plasma 17beta-estradiol (E2), compared with women. Men with prevalent CVD, compared with those without, had lower 17-hydroxypregnenolone (17OHPregn), 17-hydroxyprogesterone, and higher estrone/androstenedione and E2/testosterone (T) (aromatase activity). Women with prevalent CVD had lower pregnenolone, 17OHPregn, and dehydroepiandrosterone (DHEA) but higher DHEA/17OHPregn, androstenedione/DHEA, E2/T, E2/estrone, and E2/SHBG. The aromatase index, E2/T, was higher for prevalent CVD in both sexes. Adjustment for statin use, smoking, and body mass index yielded additional significant differences in men, whereas some were lost in women. Logistic regression indicated strong associations between prevalent CVD and low 17OHPregn, adjusted odds ratio of 0.18, 95% confidence interval (0.06-0.61); P = 0.006, in women and low 17-hydroxyprogesterone, 0.45 (0.25-0.80); P = 0.007 in men, most likely caused by increased throughput (consumption) toward estrogen synthesis. Prevalent CVD was associated with indications of lower androgen precursors, increased aromatase activity, and higher estrogen levels in both sexes. Results might represent an endogenous response to a condition of developing atherosclerosis, rather than a causative relationship. Furthermore studies are needed.


PanDelos-frags: A methodology for discovering pangenomic content of incomplete microbial assemblies.
Pangenomics was originally defined as the problem of comparing the composition of genes into gene families within a set of bacterial isolates belonging to the same species. The problem requires the calculation of sequence homology among such genes. When combined with metagenomics, namely for human microbiome composition analysis, gene-oriented pangenome detection becomes a promising method to decipher ecosystem functions and population-level evolution. Established computational tools are able to investigate the genetic content of isolates for which a complete genomic sequence is available. However, there is a plethora of incomplete genomes that are available on public resources, which only a few tools may analyze. Incomplete means that the process for reconstructing their genomic sequence is not complete, and only fragments of their sequence are currently available. However, the information contained in these fragments may play an essential role in the analyses. Here, we present PanDelos-frags, a computational tool which exploits and extends previous results in analyzing complete genomes. It provides a new methodology for inferring missing genetic information and thus for managing incomplete genomes. PanDelos-frags outperforms state-of-the-art approaches in reconstructing gene families in synthetic benchmarks and in a real use case of metagenomics. PanDelos-frags is publicly available at https://github.com/InfOmics/PanDelos-frags.


The role of religion in heart-transplant recipients' long-term health and well-being.
While religion has long been recognized clinically to provide important coping strategies in the face of serious health problems, there has been little systematic consideration of its role in organ transplant recipients' long-term reactions and adjustment to this experience. This study examines these issues through qualitative and quantitative evaluation of longitudinal data collected from 40 adult heart recipients followed during their first year post-transplant. Large proportions of recipients expressed strong beliefs and were able to increase religious participation over the 12-month study period. They delineated specific ways in which their faith had provided them support, as well as ways in which the transplant experience itself further strengthened their beliefs. We found empirical evidence that recipients with strong beliefs who participated in religious activities had better physical and emotional well-being, fewer health worries, and better medical compliance by the final 12-month assessment. The findings suggest the development of specific nursing, social-service, or pastoral-involvement strategies, continuing staff education about the role of religion in patient care. The implications of such interventions for maximizing quality of life in transplant recipients are discussed.


A comparison of amino acid arteriovenous differences across the liver and placenta of the fetal lamb.
Amino acid and ammonia concentrations as well as oxygen content were measured in either the right or left hepatic vein, the umbilical vein, and the umbilical artery in 13 fetal lambs in late gestation. There was an uptake of all of the essential and most of the nonessential amino acids by both lobes of the fetal liver. The umbilical venous-hepatic venous amino acid concentration differences were similar in the two hepatic lobes. While glutamine and glycine were taken up by both hepatic lobes, their metabolically related amino acids, glutamate and serine, were released by the fetal liver into the systemic circulation. There was a reciprocal net placental uptake from the umbilical circulation of glutamate and serine and a net fetal of glutamine and glycine, suggestive of interorgan cycling of these amino acids between the placenta and fetal liver. Total fetal umbilical nitrogen uptake was 0.91 g N.kg-1.day-1. The umbilical venous-hepatic venous differences of ammonia were positive and not significantly different in the two lobes. There was a significant umbilical uptake of ammonia (12.8 +/- 1.8 microM; 0.0078 microM NH3/microM O2). However, 0 the ratios of NH3 to O2 were much higher in each lobe (right, 0.060; left, 0.079; each P less than 0.01) than in the umbilical circulation.


Droperidol, fentanyl and morphine for i.v. surgical premedication.
Fentanyl 0.1 mg and morphine 10 mg alone and in combination with droperidol 2.5 and 5.0 mg were studied for i.v. surgical premedication in 240 patients. Relief of anxiety, sedation, lack of recall, patient acceptance and side-effects were evaluated. The addition of droperidol to fentanyl and morphine produced greater sedation and relief of anxiety before operation, but did not improve patient acceptance or lack of recall.


G-quadruplexes in H1N1 influenza genomes.
Influenza viruses are dangerous pathogens. Seventy-Seven genomes of recently emerged genotype 4 reassortant Eurasian avian-like H1N1 virus (G4-EA-H1N1) are currently available. We investigated the presence and variation of potential G-quadruplex forming sequences (PQS), which can serve as targets for antiviral treatment. PQS were identified in all 77 genomes. The total number of PQS in G4-EA-H1N1 genomes was 571. Interestingly, the number of PQS per genome in individual close relative viruses varied from 4 to 12. PQS were not randomly distributed in the 8 segments of the G4-EA-H1N1 genome, the highest frequency of PQS being found in the NP segment (1.39 per 1000 nt), which is considered a potential target for antiviral therapy. In contrast, no PQS was found in the NS segment. Analyses of variability pointed the importance of some PQS; even if genome variation of influenza virus is extreme, the PQS with the highest G4Hunter score is the most conserved in all tested genomes. G-quadruplex formation in vitro was experimentally confirmed using spectroscopic methods. The results presented here hint several G-quadruplex-forming sequences in G4-EA-H1N1 genomes, that could provide good therapeutic targets.


Food and Aeroallergen Sensitization, Eosinophils Levels and Risk of Atopic Dermatitis in Abuja.
The barrier dysfunction of atopic dermatitis (AD) promotes epicutaneous sensitization to aeroallergens. This study aimed to evaluate the prevalence of food and aeroallergen sensitization in AD and to explore the relationship between allergen sensitization and the personal or family history of allergic rhinitis, conjunctivitis, asthma, eosinophil count, and AD severity of Nigerian patients. Children and adults with AD who visited the dermatology clinic were included in this study. AD diagnosis was made using the modified Hanifin and Rajka criteria, and severity was rated and graded using the Scoring Atopic Dermatitis (SCORAD) index. Skin-prick test for 14 allergens (5 food and 9 aeroallergens) was used to assess IgE sensitization. To look for significant relationships, chi-square and odds ratio were used. Sensitization to at least one allergen was observed in 65.8% of the patients, sensitization to aeroallergen was 85% and to foods was 15%. More patients had concomitant allergic conjunctivitis (n=29) and only three had asthma. The mean age of onset of AD was 10.6±12.9 years, ranging from 2 months to 51 years, and a family history of atopy was observed in 49.4%. Majority had moderate AD and normal eosinophil count. Allergen sensitization in AD patients was significantly associated with the age of patients but not with personal or family history of allergic rhinitis, conjunctivitis, asthma, eosinophil count or AD severity. Analysis of our result showed a high prevalence of food and aeroallergen sensitization in AD. Sensitization was not influenced by the presence of other allergic diseases, eosinophils and the severity of AD.


Broiler Campylobacter contamination and human campylobacteriosis in Iceland.
To examine whether there is a relationship between the degree of Campylobacter contamination observed in product lots of retail Icelandic broiler chicken carcasses and the incidence of human disease, 1,617 isolates from 327 individual product lots were genetically matched (using the flaA short variable region [SVR[) to 289 isolates from cases of human campylobacteriosis whose onset was within approximately 2 weeks from the date of processing. When there was genetic identity between broiler isolates and human isolates within the appropriate time frame, a retail product lot was classified as implicated in human disease. According to the results of this analysis, there were multiple clusters of human disease linked to the same process lot or lots. Implicated and nonimplicated retail product lots were compared for four lot descriptors: lot size, prevalence, mean contamination, and maximum contamination (as characterized by direct rinse plating). For retail product distributed fresh, Mann-Whitney U tests showed that implicated product lots had significantly (P = 0.0055) higher mean contamination than nonimplicated lots. The corresponding median values were 3.56 log CFU/carcass for implicated lots and 2.72 log CFU/carcass for nonimplicated lots. For frozen retail product, implicated lots were significantly (P = 0.0281) larger than nonimplicated lots. When the time frame was removed, retail product lots containing Campylobacter flaA SVR genotypes also seen in human disease had significantly higher mean and maximum contamination numbers than lots containing no genotypes seen in human disease for both fresh and frozen product. Our results suggest that cases of broiler-borne campylobacteriosis may occur in clusters and that the differences in mean contamination levels may provide a basis for regulatory action that is more specific than a presence-absence standard.


Balloon angioplasty in aortic coarctation: a multicentric study in Mexico.
To analyze immediate and long-term results of balloon dilation for aortic coarctation in a three-center experience in Mexico, and to determine factors associated with increased risk. Results demonstrated that the procedure is effective and safe, however its use in some groups is still controversial, specially in neonates and infants. In a ten-year period, 333 patients with aortic coarctation on underwent balloon dilation with an immediate success rate of 93.7% and a major complication incidence of 1.8%. Of the total cohort, 272 patients were followed for a period of 24.3 +/- 20 months. Demographic and procedural data were analyzed to determine factors related to a poor outcome or to sustained high blood pressure. Cox regression analysis found age (risk ratio 3.42 p = 0.0001), isthmic hypoplasia (risk ratio 4.64, p < 0.0001), and post-dilation gradient (risk ratio 2.19, p = 0.0113) as independent risk factors for a follow-up event, mainly restenosis. Age at dilation was the only independent factor related to sustained hypertension with a seven-fold increase in the risk. Balloon dilation is an effective and safe alternative to treat aortic coarctation. Patients younger than one year of age, with severe isthmic hypoplasia and a post-dilation gradient > 20 mmHg have the highest risk to develop an event in the follow-up period. When the dilation procedure is performed in patients older than 10 years of age, and specially those older than 20 years, the probability that they remain or develop high blood pressure is increase.


Profiling of adrenocorticotropic hormone and arginine vasopressin in human pituitary gland and tumor thin tissue sections using droplet-based liquid-microjunction surface-sampling-HPLC-ESI-MS-MS.
Described here are the results from the profiling of the proteins arginine vasopressin (AVP) and adrenocorticotropic hormone (ACTH) from normal human pituitary gland and pituitary adenoma tissue sections, using a fully automated droplet-based liquid-microjunction surface-sampling-HPLC-ESI-MS-MS system for spatially resolved sampling, HPLC separation, and mass spectrometric detection. Excellent correlation was found between the protein distribution data obtained with this method and data obtained with matrix-assisted laser desorption/ionization (MALDI) chemical imaging analyses of serial sections of the same tissue. The protein distributions correlated with the visible anatomic pattern of the pituitary gland. AVP was most abundant in the posterior pituitary gland region (neurohypophysis), and ATCH was dominant in the anterior pituitary gland region (adenohypophysis). The relative amounts of AVP and ACTH sampled from a series of ACTH-secreting and non-secreting pituitary adenomas correlated with histopathological evaluation. ACTH was readily detected at significantly higher levels in regions of ACTH-secreting adenomas and in normal anterior adenohypophysis compared with non-secreting adenoma and neurohypophysis. AVP was mostly detected in normal neurohypophysis, as expected. This work reveals that a fully automated droplet-based liquid-microjunction surface-sampling system coupled to HPLC-ESI-MS-MS can be readily used for spatially resolved sampling, separation, detection, and semi-quantitation of physiologically-relevant peptide and protein hormones, including AVP and ACTH, directly from human tissue. In addition, the relative simplicity, rapidity, and specificity of this method support the potential of this basic technology, with further advancement, for assisting surgical decision-making. Graphical Abstract Mass spectrometry based profiling of hormones in human pituitary gland and tumor thin tissue sections.


Design and Validation of Exoskeleton Actuated by Soft Modules toward Neurorehabilitation-Vision-Based Control for Precise Reaching Motion of Upper Limb.
We demonstrated the design, production, and functional properties of the Exoskeleton Actuated by the Soft Modules (EAsoftM). Integrating the 3D printed exoskeleton with passive joints to compensate gravity and with active joints to rotate the shoulder and elbow joints resulted in ultra-light system that could assist planar reaching motion by using the vision-based control law. The EAsoftM can support the reaching motion with compliance realized by the soft materials and pneumatic actuation. In addition, the vision-based control law has been proposed for the precise control over the target reaching motion within the millimeter scale. Aiming at rehabilitation exercise for individuals, typically soft actuators have been developed for relatively small motions, such as grasping motion, and one of the challenges has been to extend their use for a wider range reaching motion. The proposed EAsoftM presented one possible solution for this challenge by transmitting the torque effectively along the anatomically aligned with a human body exoskeleton. The proposed integrated systems will be an ideal solution for neurorehabilitation where affordable, wearable, and portable systems are required to be customized for individuals with specific motor impairments.


Comparative Study of Tumor Targeting and Biodistribution of pH (Low) Insertion Peptides (pHLIP(®) Peptides) Conjugated with Different Fluorescent Dyes.
Acidification of extracellular space promotes tumor development, progression, and invasiveness. pH (low) insertion peptides (pHLIP(®) peptides) belong to the class of pH-sensitive membrane peptides, which target acidic tumors and deliver imaging and/or therapeutic agents to cancer cells within tumors. Ex vivo fluorescent imaging of tissue and organs collected at various time points after administration of different pHLIP(®) variants conjugated with fluorescent dyes of various polarity was performed. Methods of multivariate statistical analyses were employed to establish classification between fluorescently labeled pHLIP(®) variants in multidimensional space of spectral parameters. The fluorescently labeled pHLIP(®) variants were classified based on their biodistribution profile and ability of targeting of primary tumors. Also, submillimeter-sized metastatic lesions in lungs were identified by ex vivo imaging after intravenous administration of fluorescent pHLIP(®) peptide. Different cargo molecules conjugated with pHLIP(®) peptides can alter biodistribution and tumor targeting. The obtained knowledge is essential for the design of novel pHLIP(®)-based diagnostic and therapeutic agents targeting primary tumors and metastatic lesions.


Microplastic Pollution in Benthic Midstream Sediments of the Rhine River.
Rivers are major transport vectors for microplastics (MP) toward the sea. However, there is evidence that MP can temporarily or permanently be inhibited from migrating downstream by retention in sediments or ingestion by organisms. MP concentrations, compositions, and fate within the different compartments of the fluvial environment are poorly understood. Here, benthic, midstream sediments of two undammed, open-flowing stretches were investigated in the Rhine River, one of the world's busiest inland waterways. Twenty-five samples were collected at ten sites via riverbed access through a diving bell or dredging. We performed the first comprehensive analysis of riverbed sediment aliquots that avoids visual selection bias using state-of-the art automated micro-Fourier-transform infrared spectroscopy (μFTIR) imaging. MP numbers ranged between 0.26 ± 0.01 and 11.07 ± 0.6 × 103 MP kg-1 while MP particles <75 μm accounted for a mean numerical proportion ± SD of 96 ± 6%. MP concentrations decreased with sediment depth. Eighteen polymers were identified in the size range of 11-500 μm; the acrylates/polyurethane/varnish (APV) cluster was found at all sites (mean numerical proportion, 70 ± 19%), possibly indicating particulate pollution from ship antifouling paint. Overall, polymers denser than freshwater (>1 g cm-3) dominated (85 ± 18%), which contrasts the large proportions of low-density polymers previously reported in near-surface compartments of the Rhine.


Methods for measuring financial toxicity after cancer diagnosis and treatment: a systematic review and its implications.
Patients experiencing financial distress as a side-effect of cancer are not only reported in the United States, but also in third-party payer healthcare systems in Europe. Since validated survey instruments are a prerequisite for robust and comparable results, we aimed to compile and classify available instruments to enable both a better understanding of the underlying construct of financial toxicity and to facilitate further studies that are adjustable to various healthcare systems. We did a systematic literature search on studies that provide data on perceived cancer-related financial distress experienced by adult patients using PubMed, CINAHL and Web of Science databases up to 2018. We analyzed all detected instruments, items domains and questions with regard to their wording, scales and the domains of financial distress covered. Among 3298 records screened, 41 publications based on 40 studies matched our inclusion criteria. Based on the analysis of 352 different questions we identified 6 relevant subdomains that represent perceptions of and reactions to experienced financial distress: (i) active financial spending, (ii) use of passive financial resources, (iii) psychosocial responses, (iv) support seeking, (v) coping with care or (vi) coping with ones' lifestyle. We found an inconsistent coverage and use of these domains that makes it difficult to compare and quantify the prevalence of financial distress. Moreover, some existing instruments do not reflect relevant domains for patients in third-party payer systems. There is neither a consistent understanding of the construct of financial burden nor do available instruments cover all relevant aspects of a patients' distress perception. We encourage using the identified six domains to further develop survey instruments and adjust them to different health systems.


Homegrown perceptions about the medical use and potential abuse of CBD and THC.
Despite heightened consumer interest in cannabinoids such as cannabidiol (CBD) and tetrahydrocannabinol (THC), little is known about public perceptions regarding their medical use and potential for abuse, particularly relative to commonly used medications. Using data from 1,050 U.S. adult respondents from a national survey conducted in 2019, this study found that more than half of respondents perceived CBD, THC, hemp, and marijuana as having medical use. They also perceived the potential for abuse of CBD, THC, hemp, and marijuana as significantly less than potential for abuse of commonly prescribed anti-anxiety and pain medications. At the nexus of medical use and potential abuse, public perceptions classified CBD and hemp as similar to over-the-counter pain relief medications such as Advil and Tylenol and did not classify marijuana as a Schedule I substance. Slightly more than 20% of respondents reported having consumed CBD and/or THC. CBD was consumed more than THC to reduce pain while THC was consumed more than CBD for recreation. There were no differences in the types of medications they were replacing with CBD and THC.


Analysis of Velocity Autocorrelation Functions from Molecular Dynamics Simulations of a Small Peptide by the Generalized Langevin Equation with a Power-Law Kernel.
Internal motions play an essential role in the biological functions of proteins and have been the subject of numerous theoretical and spectroscopic studies. Such complex environments are associated with anomalous diffusion where, in contrast to the classical Brownian motion, the relevant correlation functions have power law decays with time. In this work, we investigate the presence of long memory stochastic processes through the analysis of atomic velocity autocorrelation functions. Analytical expressions of the velocity autocorrelation function spectrum obtained through a Mori-Zwanzig projection approach were shown to be compatible with molecular dynamics simulations of a small helical peptide (8-polyalanine).


CREB3L1 as a potential biomarker predicting response of triple negative breast cancer to doxorubicin-based chemotherapy.
Doxorubicin-based chemotherapy is currently the most frequently used treatment for triple negative breast cancer (TNBC), yet the response rate is not high due to the lack of a biomarker allowing identification of responsive patients before the chemotherapy is initiated. We have demonstrated that doxorubicin inhibits proliferation of cancer cells through proteolytic activation of a transcription factor called CREB3L1 (cAMP response element binding protein 3-like 1), and that CREB3L1 expression in cancer cells is a key determinant of their sensitivity to doxorubicin when they are cultured in vitro or established as xenograft tumors in mice. The purpose of this study is to determine whether CREB3L1 expression in tumor cells of TNBC patients can be established as a biomarker to predict outcomes of doxorubicin-based chemotherapy. We performed a retrospective analysis on breast core biopsy tissue samples taken from 18 TNBC patients before they were treated with doxorubicin-based chemotherapy. CREB3L1 expression in the cancer cells was analyzed by immunohistochemistry and quantified using the Immunoreactive Score (IRS). Outcomes of the chemotherapy were measured by the residual cancer burden (RCB) system. CREB3L1 expression levels in TNBC responsive to doxorubicin-based chemotherapy (RCB class 0-2) were significantly higher than that in resistant cancers (RCB class 3) (unpaired two-tailed t test, p = 0.0005; Statistical power 99.8 at 95% confidence level). All cancers expressing higher levels of CREB3L1 (IRS 4-12) responded to doxorubicin-based chemotherapy, whereas all cancers resisting the treatment expressed lower levels of CREB3L1 (IRS 0-3). These results suggest that CREB3L1 expression level may be used as a biomarker to identify TNBC patients who are more likely to benefit from doxorubicin-based chemotherapy.


Incidence and Trends in Hypoglycemia Hospitalization in Adults With Type 1 and Type 2 Diabetes in England, 1998-2013: A Retrospective Cohort Study.
To determine trends in hospitalization for hypoglycemia in adults with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in England. Adults with T1DM or T2DM were identified from 398 of the 684 practices within the Clinical Practice Research Datalink, for which linkage to the Hospital Episode Statistics was possible. Hypoglycemia as the primary reason for hospitalization between 1998 and 2013 was extracted. Trends were estimated using joinpoint regression models for adults with T1DM, young and middle-aged adults with T2DM (18-64 years), and elderly adults with T2DM (≥65 years), respectively. Among 23,246 adults with T1DM, 1,591 hypoglycemia hospitalizations occurred during 121,262 person-years. Among 241,441 adults with T2DM, 3,738 hypoglycemia hospitalizations occurred during 1,344,818 person-years. In adults with T1DM, the incidence increased 3.74% (95% CI 1.70-5.83) annually from 1998 to 2013. In young and middle-aged adults with T2DM, the annual incidence increase was 4.12% (0.61-7.75) from 1998 to 2013. In elderly adults with T2DM, the incidence increased 8.59% (5.76-11.50) annually from 1998 to 2009, and decreased 8.05% (-14.48 to -1.13) annually from 2009 to 2013, but the incidence was still higher in 2013 than 1998 (adjusted rate ratio 3.01 [1.76-5.14]). Trends in HbA1c level did not parallel trends of hypoglycemia hospitalization for both diabetes types. A possible reason for declined hypoglycemia trend in 2009-2013 in elderly adults with T2DM may be continuously decreased sulfonylurea use after 2009, which was not seen in young and middle-aged adults with T2DM. Hypoglycemia requiring hospitalization has been an increasing burden in adults with T1DM and T2DM in England in the previous two decades, with the exception of the decline in elderly adults with T2DM starting in 2009.


Analysis and enhancements to piecewise linear comparametric image registration.
This correspondence details enhancements to previous work on piecewise linear comparametric image registration. The enhancements come in the form of slope constraints and knots' location selection in the comparametric modeling. An analysis of the properties of comparametric functions leads to two general slope constraints that, along with a knot location selection based on the reference image's pixel value distribution, serves to reduce error and sensitivity to the number of segments considered as well as allow for the solution to cases in which there are gaps in the comparagram. Results on real images are presented.


Perceptions of occupational therapy threshold concepts by students in role-emerging placements in schools: A qualitative investigation.
Traversing threshold concepts has been identified as crucial in becoming an occupational therapist. To support this learning, previous research has emphasised the value of students engaging in practice-based learning, accompanying reflection, and a curriculum which makes threshold concepts explicit to students. Role-emerging placements form part of students' practice-based learning in many universities and could offer a valuable opportunity for students to learn threshold concepts. Understanding the value of threshold concepts to enhance role-emerging placement learning from both the students' and educators' perspectives warrants further research. The aim of this study was to examine how occupational therapy students on role-emerging placements in school settings experienced applying threshold concepts and how it impacted on their learning. An epistemological position of social constructionism and a qualitative research design was used. This included semi-structured focus group interviews and reflective logs that enabled exploration of 13 student's and one supervisor's perspectives of learning during the placement. Template analysis was used to analyse the data. Students spoke of their learning of the threshold concepts of client-centredness, occupation, and understanding and applying occupational therapy theory in practice. These are expressed within the three emergent themes; 'curriculum supports in placement', 'uncertainty when applying their own knowledge', and 'placement context and expectations'. Results suggest that learning happens within the liminal spaces which occurred from an intersection with the threshold concepts, the curriculum, knowledge generation and use, and the context and expectations of the role-emerging placement. Engaging with uncertainty may be considered a vital part of this process and something which should be valued.


"Double-Lumen Valve-Controlled Intra-Operative Pyeloplasty Stent (VIPs)": A New Technology for Post-Pyeloplasty Stenting - Proof of Concept Study in a Preclinical Large Animal Model.
Pyeloplasty is a common surgical operation with a high success rate. However, significant challenges are to be optimized in the design of stenting systems in order to improve perioperative monitoring of urine drainage and enhance patient and family comfort through easier post-operative care. In a preliminary study in six pigs, handling, mechanical and functional features of this stent system were tested. In our main study, six double-lumen stents (230 mm long each) and 6F/9F external diameter were implanted through the ureteric walls of six domestic pigs to allow postoperative drainage and monitoring following ureteroureterostomy. After a 7-day survival period, monitoring with intravenous antibiotic coverage, and pain control, contrast antegrade pyelogram, under valve control, and renal ultrasonography were conducted and stents explanted and the animals were then euthanized. The double-lumen valve-controlled stent supported the healing of the neo anastomoses and helped to monitor perioperative urine drainage and perianastomotic leakage accurately. It also guided a well-controlled more informative radiological contrast-supported imaging before removal of the stents that confirmed the healing of the neo anastomotic site and no leak formation. The double-lumen system demonstrated high feasibility regarding its insertion, functionality, and removal capacities. The excellent flexibility of the individual stents allowed exact anatomically controlled implantation. The double-lumen valve-controlled stent system was studied in a porcine model, which demonstrated its feasibility. Preclinical experience revealed favorable results concerning stent implantation, operability and functionality, in the perioperative management of pyeloplasty or ureteric surgery.


Phase I trial of the matrix metalloproteinase inhibitor marimastat combined with carboplatin and paclitaxel in patients with advanced non-small cell lung cancer.
Marimastat is an orally bioavailable inhibitor of matrix metalloproteinases. A phase I study was initiated to determine whether conventional doses of carboplatin and paclitaxel are tolerated when combined with marimastat and to assess the influence of marimastat on paclitaxel pharmacokinetics. Three dose levels were evaluated. Marimastat (10 or 20 mg oral administration b.i.d.) was administered continuously with paclitaxel (175 or 200 mg/m(2) as a 3-hour i.v. infusion) and carboplatin (at a dose providing an area under the free drug plasma concentration-time curve of 7 mg min/mL) administered each 3 weeks. Toxicity and response were evaluated throughout the intended four cycles of combined therapy. The plasma pharmacokinetics of paclitaxel was determined in each patient both without concurrent marimastat and after receiving marimastat for 1 week. Twenty-two chemotherapy-naive patients with stage IIIb (27%) or stage IV (73%) non-small cell lung cancer were enrolled. Their median age was 56 years (range, 39-73 years), 50% were female, and their performance status (Eastern Cooperative Oncology Group) ranged from 0 to 2. Treatment was well tolerated, as 18 (82%) of the patients completed all four cycles of chemotherapy without dose-limiting toxicity. Grade 2 musculoskeletal toxicities were reported in 3 of 12 patients receiving marimastat (20 mg b.i.d.). Nine patients required dose reductions, predominantly related to low-grade myelosuppression. Partial responses occurred in 12 of 21 (57%) evaluable patients with disease stabilization in another 5 (19%). Marimastat had no effect on paclitaxel pharmacokinetics. The administration of marimastat (10 mg b.i.d.) with paclitaxel (200 mg/m(2)) and carboplatin at an area under the free drug plasma concentration-time curve of 7 mg min/mL was well tolerated with no apparent pharmacokinetic interaction. Study of this drug combination in the adjuvant setting should be considered if tissue inhibition of matrix metalloproteinase activity can first be shown.


Zinc and liver cirrhosis.
We have measured zinc levels in serum and urine of healthy controls, patients with liver cirrhosis and patients with cirrhosis and hepatic cancer. In patients with ascitic fluid, we also measured zinc, total protein, albumin and alpha 2-globulin. Basal measurements were performed in blood drawn at 8.00, before the intravenous administration of 8 mg zinc in the form of zinc sulphate. Serum levels were measured at various intervals to a total time of 24 h after overload, and total urine was collected for zinc determinations 24 h before and 24 h after overload. Under basal conditions, cirrhotic patients had lower serum levels and higher rates of urinary excretion of zinc than controls. After overload, blood levels of zinc fell more rapidly in cirrhotic patients than in controls, the former group showing no concomitant rise in urinary zinc excretion, thus suggesting an organic deficit in this trace element. In ascitic fluid, the concentration of zinc was positively correlated with protein content.


Interferon-beta-1a for the treatment of steroid-refractory ulcerative colitis: a randomized, double-blind, placebo-controlled trial.
We performed a randomized, double-blind, placebo-controlled, multicenter trial to investigate the efficacy and safety of recombinant interferon-beta-1a (rIFN-beta-1a) in outpatients with active steroid-refractory ulcerative colitis. Ninety-one randomized patients subcutaneously received 3 MIU rIFN-beta-1a (group A, n = 32), 1 MIU rIFN-beta-1a (group B, n = 30), or placebo (group C, n = 29) 3 times a week over a period of 8 weeks in addition to standard therapy. An intention-to-treat analysis was performed to evaluate the efficacy and safety of treatment. In all 3 groups, the median prestudy clinical activity index (CAI) was 10. In 18 of 32 patients (56%) in group A, in 11 of 30 patients (36%) in group B, and in 10 of 29 patients (34%) in group C, a reduction of the CAI of 6 points or greater (response) was achieved (differences were not statistically significant). Complete response (reduction of CAI to < or =4) was achieved in 56%, 30%, and 38% of patients in groups A, B, and C, respectively. Compared with baseline, the median endoscopic index had been reduced by 5, 3, and 4 points in groups A, B, and C, respectively. Steroid reduction was 12 mg in group A, 6 mg in group B, and 10 mg in group C. Identical side effects occurred in all 3 groups. Seven serious adverse events were reported (1 in group A and 6 in group C). All were unrelated to therapy as judged by the investigating physicians. rIFN-beta-1a was safe but not significant, at the dosage and/or duration of treatment used, in steroid-refractory ulcerative colitis. Further studies are indicated.


Powerline right-of-way management and flower-visiting insects: How vegetation management can promote pollinator diversity.
Loss in the availability of early successional habitat is a threat to pollinator populations. Given that powerline rights-of-way (ROW) must be managed to maintain early successional habitat, preventing vegetation from interfering with electrical lines, they have the potential to provide conservation benefits for wild pollinators. Moreover, it is possible to provide conservation benefits with no additional cost to land managers. We surveyed flower-visiting insects over two years in different vegetation management treatments in a long-term research ROW to determine which best promoted pollinator abundance and species richness. We found that the ROW had stabilized in an early successional state soon after its establishment and that this early successional state could be maintained with low levels of periodic maintenance. We collected a high diversity of flower-visiting insects (126 bee species and 179 non-bee morphospecies) in six ROW plots. Higher levels of herbicide application had a negative effect on bee species richness, but low levels of herbicide application were compatible with a high abundance and species richness of flower-visiting insects, including several rare species. Moreover, this effect was seen only in the bee community, and not in non-bee flower-visiting insects. Our results suggest further research into the conservation value of ROW for pollinators is warranted. We demonstrate that there is substantial potential for pollinator conservation in ROW, compatible with low-cost vegetation management.


Prot2HG: a database of protein domains mapped to the human genome.
Genetic variation occurring within conserved functional protein domains warrants special attention when examining DNA variation in the context of disease causation. Here we introduce a resource, freely available at www.prot2hg.com, that addresses the question of whether a particular variant falls onto an annotated protein domain and directly translates chromosomal coordinates onto protein residues. The tool can perform a multiple-site query in a simple way, and the whole dataset is available for download as well as incorporated into our own accessible pipeline. To create this resource, National Center for Biotechnology Information protein data were retrieved using the Entrez Programming Utilities. After processing all human protein domains, residue positions were reverse translated and mapped to the reference genome hg19 and stored in a MySQL database. In total, 760 487 protein domains from 42 371 protein models were mapped to hg19 coordinates and made publicly available for search or download (www.prot2hg.com). In addition, this annotation was implemented into the genomics research platform GENESIS in order to query nearly 8000 exomes and genomes of families with rare Mendelian disorders (tgp-foundation.org). When applied to patient genetic data, we found that rare (<1%) variants in the Genome Aggregation Database were significantly more annotated onto a protein domain in comparison to common (>1%) variants. Similarly, variants described as pathogenic or likely pathogenic in ClinVar were more likely to be annotated onto a domain. In addition, we tested a dataset consisting of 60 causal variants in a cohort of patients with epileptic encephalopathy and found that 71% of them (43 variants) were propagated onto protein domains. In summary, we developed a resource that annotates variants in the coding part of the genome onto conserved protein domains in order to increase variant prioritization efficiency. Database URL: www.prot2hg.com.


The Long Non-Coding RNA-RoR Promotes the Tumorigenesis of Human Colorectal Cancer by Targeting miR-6833-3p Through SMC4.
Long non-coding RNA regulator of reprogramming (LINC-RoR) has shown different expressions in a variety of tumors as a stem cell inducer through reprogramming regulation. However, its role and regulation mechanisms in colorectal cancer (CRC) are still unclear. Quantitative real-time PCR and Western blot were performed to examine LINC-RoR expression in paired CRC samples and cell lines. The relationship of LINC-RoR expression with clinicopathological characteristics and clinical outcomes was analyzed. The biological functions of LINC-RoR were studied by MTS and colony formation in vitro. Cell apoptosis was analysed by the flow cytometry. The Dual-luciferase reporter assays and RIP assays were performed to explore the regulatory relationship of LINC-RoR. In this study, we found that LINC-RoR was upregulated in CRC cell lines and tissues. High expression of LINC-RoR was associated with poorer survival time and multivariate analysis results showed that LINC-RoR was an independent risk factor of tumor malignancy progression. Overexpression of LINC-RoR promoted the cell proliferation and knocked down it can reverse the effect in vitro. The regulatory network of LINC-ROR/miR-6833-3p/SMC4 was predicted with bioinformatics analysis tools and validated via dual-luciferase reporter assays and RIP. Further study revealed that in overexpression LINC-RoR cell lines the expression of miR-6833-3p was downregulated and miR-6833-3p can inhibit its target gene SMC4, the apoptosis-related protein. We concluded that LINC-RoR functions as an oncogene in CRC through the miR-6833-3p/SMC4 pathway.


The prevalence of obesity in children with autism: a secondary data analysis using nationally representative data from the National Survey of Children's Health.
The prevalence of childhood obesity has increased dramatically in the last two decades and numerous efforts to understand, intervene on, and prevent this significant threat to children's health are underway for many segments of the pediatric population. Understanding the prevalence of obesity in populations of children with developmental disorders is an important undertaking, as the factors that give rise to obesity may not be the same as for typically developing children, and because prevention and treatment efforts may need to be tailored to meet their needs and the needs of their families. The goal of the current study was to estimate the prevalence of obesity in children and adolescents with autism. This study was a secondary data analysis of cross-sectional nationally representative data collected by telephone interview of parents/guardians on 85,272 children ages 3-17 from the 2003-2004 National Survey of Children's Health (NSCH). Autism was determined by response to the question, "Has a doctor or health professional ever told you that your child has autism?" Children and adolescents were classified as obese according to CDC guidelines for body mass index (BMI) for age and sex. The prevalence of obesity in children with autism was 30.4% compared to 23.6% of children without autism (p = .075). The unadjusted odds of obesity in children with autism was 1.42 (95% confidence interval (CI): 1.00, 2.02, p = .052) compared to children without autism. Based on US nationally representative data, children with autism have a prevalence of obesity at least as high as children overall. These findings suggest that additional research is warranted to understand better the factors that influence the development of obesity in this population of children.


Reliability of gastric access closure with the self-approximating transluminal access technique (STAT) for NOTES.
STAT, or the self-approximating transluminal access technique, has been previously described and involves the dissection of a submucosal tunnel for peritoneal or mediastinal access from the esophagus and stomach. The objective of this study was to assess the safety and reliability of gastric access and closure in a porcine experience using STAT for natural orifice transluminal endoscopic surgery (NOTES). A review of the experience using STAT access tunnels for intraperitoneal access was performed in 39 female pigs at a university animal lab. All animals underwent a predetermined NOTES surgical procedure using a STAT transgastric access tunnel based on a specific protocol. Details of the procedure, complications, and clinical course were documented. Necropsy was performed at 2 weeks. The main outcome measurements were clinical or necropsy evidence of gastrostomy site leak or inadequate access site closure. STAT was successful in providing safe peritoneal access in all animals. The width of the tunnel ranged from 1.5 to 5.5 cm and the length was up to 27 cm. There was no evidence of gastrostomy site leak in any animals. One animal required a single laparoscopic suture to help with tunnel closure. STAT provides safe transgastric access and allows secure closure of the gastrotomy site.


Revegetation of a uranium mine dump by using fertilizer treated sessile oaks.
The rehabilitation of contaminated sites and the establishment of suitable trees for revegetation purposes is often problematic due to the mostly suboptimal nutrient supply and the poor humus reservoir. For these reasons hydrogels (Stockosorb) and novel humus substitutes (NOVIHUM), serving as long lasting fertilizer (LLF), were recently tested successfully. At the beginning of this multiyear study, those LLFs were administered to the root zone of young sessile oaks (Quercus petraea (Mattuschka) Liebl.), growing in test trials on a uranium mine dump in Schlema (Germany). To quantify the effect of LLFs on plant vitality, chlorophyll a fluorescence measurements and JIP test analyses were used. The results revealed up to 49% higher average photosynthetic vitality (PI(ABS)) of the LLF treated plants compared to controls. Particularly in the first test year, the efficiency of photosynthetic electron transport was strongly increased. This stimulation of photosynthetic activity was supported by direct measurements showing up to 129% increased diameter growth of the treated plants after a four year experimental period. Furthermore an increase of the maximum water holding capacity of the dump soil was attained by using LLFs. Overall, the findings reported here represent a feasible, ecologically justifiable reforestation method with a low environmental hazard potential.


The effect of training given to parents with mentally disabled children on their life satisfaction self-stigma of seeking help depression and stress-coping styles.
It is important to identify problem areas of parents with mentally disabled children, to support them, to address their stress sources and to effectively cope with them. The aim of this study is to evaluate the effect of training given to parents with mentally disabled children on their life satisfaction, self-stigma of seeking help, depression and stress-coping styles. Families with disabled children who continued their education at the Special Education Centers in Sivas created the sample of this pre- and post-test study (with control group). The data were collected with the Satisfaction With Life Scale (SWLS), the Beck Depression Inventory (BDI), the Self-Stigma of Seeking Psychological Help Scale (SSPHS) and the Ways of Coping Questionnaire (WCQ). The scales were re-applied to the experimental group (n = 75) after the application of scales and 5-week training. Individuals in the control group were not given any training. The Mann-Whitney U test, t test and Kruskal-Wallis variance analysis were used in the evaluation of the data. The mean SWLS score was 19.14 ± 7.24 (min: 3; max: 31) before the training and 21.68 ± 7.39 (min: 6; max: 35) after the training. The mean BDI score was 16.92 ± 10.84 (min: 1; max: 60) before the training and 10.24 ± 7.77 (min: 0; max: 33) after the training. The mean SSPHS score was 58.18 ± 9.96 (min: 32; max: 82) before the training and 52.65 ± 14.28 (min: 28; max: 84) after the training. The mean optimistic approach score of SSPHS was 9.73 ± 2.67 (min: 2; max: 15) before the training and 10.58 ± 2.19 (min: 4; max: 15) after the training. It was determined that the difference between mean scores of the control group before and after the training was not significant (p > .05). The training has positively affected the decrease in depression and self-stigmatization, and the increase in life satisfaction and stress-coping styles after the training. It is recommended to plan research studies to identify the need for support of parents, and to structure the trainings to be given according to the results of the educational intervention researches.


A guide to the new office evaluation and management codes for 1992.
The new office evaluation and management codes require an understanding of definitions that have been recently created by the Current Procedural Terminology (CPT) Editorial Panel. Code selection is based on seven components; the three key components are the history, the physical examination and medical decision making. Office visit codes are divided into five levels of visits, based on service. New-patient office visits require all three key components for any level visit; established-patient office visits require only two of the three components. The new office code descriptions were created to assist physicians in code selections. Only when counseling or coordination of care dominates the visit (e.g., more than 50 percent) is time to be considered a controlling factor. Physicians are urged not to code only from time descriptors. The 1992 CPT book will list only the new evaluation and management codes, deleting the old level-of-service codes. Physicians are encouraged to contact local insurance carriers to ensure that they will also be using the new codes in 1992.


Effects of duration of zilpaterol hydrochloride feeding and days on the finishing diet on feedlot cattle performance and carcass traits.
British and British x Continental steers (n = 560; initial BW = 339.4 +/- 1.76 kg) were used in a serial slaughter study with a completely random design to evaluate effects of zilpaterol hydrochloride (ZH; 8.33 mg/kg of dietary DM basis) on performance and carcass characteristics. Treatments were arranged in a 4 x 4 factorial (112 pens; 7 pens/treatment; 5 steers/pen) and included duration of ZH feeding (0, 20, 30, or 40 d before slaughter plus a 3-d ZH withdrawal period) and days on feed (DOF) before slaughter (136, 157, 177, and 198 d). No duration of ZH feeding x slaughter group interactions were detected for the performance measurements (P > 0.10). Final BW did not differ (P = 0.15) between the 0-d group and the average of the 3 ZH groups, but ADG was greater for the average of the 3 ZH groups during the period in which ZH diets were fed (P < 0.01) and for the overall feeding period (P = 0.05). As duration of ZH feeding increased, DMI decreased (P = 0.01) and G:F increased linearly (P < 0.01). With the exception of KPH (P = 0.022), no duration of ZH feeding x slaughter group interactions (P > 0.10) were detected for carcass characteristics. Regardless of the duration of ZH feeding, cattle fed ZH had greater HCW (P < 0.01), greater dressing percent (P < 0.01), less 12th-rib fat (P < 0.01), larger LM area (P < 0.01), less KPH (P = 0.03), and lower yield grade (P < 0.01) than the 0-d cattle. The 0-d group had greater marbling scores (P < 0.01) than cattle fed ZH diets, with a tendency for a linear decrease in marbling score (P = 0.10) as duration of ZH feeding was extended. A greater percentage of carcasses in the 0-d group graded USDA Choice or greater (P < 0.01) than in the 3 ZH groups, whereas the percentage of Select carcasses was greater (P = 0.01) for the 3 ZH groups. From d 0 to end (P = 0.04) and during the last 43 d on feed (P < 0.01), ADG responded quadratically to DOF before slaughter. No differences were detected among slaughter groups for DMI for the entire trial period; however, a quadratic response (P = 0.02) was observed for the final 43 d before slaughter. A quadratic response was also detected for the final 43 d before slaughter (P < 0.01) and from d 0 to end (P = 0.02) for G:F. Final BW, HCW, dressing percent, and 12th-rib fat increased linearly (P < 0.01) as DOF before slaughter increased. Our results indicate that no substantial effects on performance and carcass measurements were observed when ZH was fed for 30 or 40 d as opposed to 20 d, and that effects of ZH generally did not interact with DOF before slaughter.


Fermentation characteristics and nutritional value of ruminal contents and blood ensiled with untreated or sodium hydroxide-treated wheat straw.
Bovine ruminal contents and blood were ensiled with wheat straw, either untreated or treated with 4% NaOH (DM basis), with and without addition of 5% dry molasses. Proportions of ruminal contents, blood, and straw were 45:15:40, wet basis, respectively. Wheat straw also was ensiled alone, and water was added to attain 43% DM. After 60 d, all silages had a desirable aroma. The pH of the ensiled mixtures of ruminal contents, blood, and untreated straw was 4.43 and 4.56, with and without molasses, respectively. Values for silages containing treated straw, with and without molasses, were 5.95 and 7.37, respectively. All silages had substantial levels of lactic acid (2.4 to 4.9%, DM basis). Addition of molasses increased (P less than .01) lactic acid concentrations. In a metabolism trial, 36 wethers were fed a 50% orchardgrass hay basal diet alone or supplemented with ensiled materials (1:1 ratio, DM basis) such that final diets had about 7 and 4% of their DM from ruminal contents and blood, respectively. Among the diets containing the ensiled mixtures, digestibilities of DM, OM, energy, NDF, ADF, cellulose, and hemicellulose were 6 to 20 percentage units higher (P less than .01) for silages containing treated vs untreated straw. Addition of molasses increased apparent digestibility only of CP and only in sheep fed ensiled mixtures with treated straw (interaction of straw treatment x molasses addition, P less than .05). Nitrogen balance was increased (P less than .05) from 1.6 g/d to 2.9 g/d by NaOH treatment of straw. Metabolizable energy was higher (P less than .05) for diets containing silages with NaOH-treated straw.(ABSTRACT TRUNCATED AT 250 WORDS)


Purification and characterization of a third glucosyltransferase from Streptococcus mutans serotype g.
Streptococcus mutans strain AHT (serotype g) secretes at least two glucosyltransferases with different pI values. A novel glucosyltransferase with a pI of 5.8 was purified 244-fold from the ammonium sulphate fraction by DEAE-cellulose chromatography, FPLC (Mono Q column, Pharmacia) and hydrophobic chromatography. The enzyme preparation gave a single protein band on analysis by both PAGE and SDS-PAGE, and did not form multiple protein bands detectable by IEF. The Mr was estimated to be about 130,000 by SDS-PAGE and about 135,000 by ultracentrifugal analysis. The apparent Km value and pH optimum of the enzyme were 3.9 +/- 0.2 mM (mean +/- SD) and about 4.7, respectively. The enzyme synthesized water-soluble glucan from sucrose, and the glucan consisted of over 90 mol% 1,6-alpha-D-glucosidic linkages. The enzyme activity was not stimulated by primer dextran. Anti-enzyme serum produced a single precipitin band with the purified enzyme preparation, whereas it did not react with either of the other two known glucosyltransferases.


Prescription of Pneumocystis Jiroveci Pneumonia Prophylaxis in HIV-Infected Patients.
The US treatment guidelines recommend Pneumocystis jiroveci pneumonia (PCP) prophylaxis for all HIV-infected persons with a CD4 count <200 cells/mm3 (ie, eligible for PCP prophylaxis). However, some studies suggest PCP prophylaxis may be unnecessary in virally suppressed patients. Using national data of HIV-infected adults receiving medical care in the United States during 2009 to 2012, the authors assessed the weighted percentage of eligible patients who were prescribed PCP prophylaxis and the independent association between PCP prophylaxis prescription and viral suppression. Overall, 81% of eligible patients were prescribed PCP prophylaxis. Virally suppressed eligible patients were less likely to be prescribed PCP prophylaxis (prevalence ratio: 0.84; 95% confidence interval: 0.80-0.89). Although guidelines recommend PCP prophylaxis for all eligible patients, some HIV care providers might not prescribe PCP prophylaxis to virally suppressed patients. Additional data on the risk for PCP among virally suppressed patients are needed to clarify this controversy.


Increased global integration in the brain after psilocybin therapy for depression.
Psilocybin therapy shows antidepressant potential, but its therapeutic actions are not well understood. We assessed the subacute impact of psilocybin on brain function in two clinical trials of depression. The first was an open-label trial of orally administered psilocybin (10 mg and 25 mg, 7 d apart) in patients with treatment-resistant depression. Functional magnetic resonance imaging (fMRI) was recorded at baseline and 1 d after the 25-mg dose. Beck's depression inventory was the primary outcome measure ( MR/J00460X/1 ). The second trial was a double-blind phase II randomized controlled trial comparing psilocybin therapy with escitalopram. Patients with major depressive disorder received either 2 × 25 mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily placebo ('psilocybin arm') or 2 × 1 mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily escitalopram (10-20 mg) ('escitalopram arm'). fMRI was recorded at baseline and 3 weeks after the second psilocybin dose ( NCT03429075 ). In both trials, the antidepressant response to psilocybin was rapid, sustained and correlated with decreases in fMRI brain network modularity, implying that psilocybin's antidepressant action may depend on a global increase in brain network integration. Network cartography analyses indicated that 5-HT2A receptor-rich higher-order functional networks became more functionally interconnected and flexible after psilocybin treatment. The antidepressant response to escitalopram was milder and no changes in brain network organization were observed. Consistent efficacy-related brain changes, correlating with robust antidepressant effects across two studies, suggest an antidepressant mechanism for psilocybin therapy: global increases in brain network integration.


Knowledge discovery and knowledge validation in intensive care.
Operational protocols are a valuable means for quality control. However, developing operational protocols is a highly complex and costly task. We present an integrated approach involving both intelligent data analysis and knowledge acquisition from experts that support the development of operational protocols. The aim is to ensure high quality standards for the protocol through empirical validation during the development, as well as lower development cost through the use of machine learning and statistical techniques. We demonstrate our approach of integrating expert knowledge with data driven techniques based on our effort to develop an operational protocol for the hemodynamic system.


Rationale and design of the Home Automatic External Defibrillator Trial (HAT).
Most cardiac arrests occur in the home, where emergency medical services (EMS) systems are challenged to provide timely care. Because a large proportion of sudden cardiac arrests (SCAs) are due to ventricular tachycardia or ventricular fibrillation, home use of an automated external defibrillator (AED) might offer an opportunity to decrease mortality in those at risk. Predicting who will have a cardiac arrest in the general population is difficult. Individuals at high risk are usually easily identified and may become candidates for implantable cardioverter defibrillators. It is within the population at lower risk where home AEDs may be most useful. The purpose of the Home Automatic External Defibrillator Trial (HAT) is to test whether providing home access to an AED can improve survival in patients at modest risk of SCA, such as those surviving an anterior myocardial infarction but in whom implantable cardioverter defibrillator therapy is not deemed necessary. Between January 23, 2003, and October 20, 2005, 7001 patients were enrolled, with completion of follow-up scheduled for September 30, 2007. Randomization was conducted in a 1:1 fashion between control therapy, comprising the standard lay response to SCA (calling the EMS and performing cardiopulmonary resuscitation), and the use of an AED first, followed by calling the EMS and performing cardiopulmonary resuscitation. The primary end point is all-cause mortality. Secondary outcomes include survival from SCA (witnessed and unwitnessed, in home and out of home), incremental cost-effectiveness, and quality of life measures for both the patient and the spouse/companion. The results of the trial should be available in mid 2008.


Bilateral breast cancer in a male patient with hepatocellular carcinoma. A case report.
Male breast cancer accounts for about 1% of all breast cancers and bilateral breast cancer in men is therefore a rare event. Data in literature indicate that approximately 20% of these tumours are due to a probable alteration in the oestrogen metabolism. Hepatocellular carcinoma (HCC) on the other hand, is a much more frequent tumour and in 70-80% of cases is associated with cirrhosis. The proven concomitance of cirrhosis and gynecomastia in HCC or previous intake of oestrogen in breast cancer, would indicate possible involvement of the hormonal metabolism in the appearance of the two neoplastic forms. To our knowledge a case with these two malignant diseases in the same male patient is an exceptional event, rarely reported in literature. The fact that the breast cancer was bilateral in a male patient, the diverse histogenesis of the two breast cancers and the association with HCC in cirrhosis, led us to investigate into any common eziopathogenetic elements.


National HIV prevalence surveillance among TB patients through periodic surveys: experience in Cambodia.
The National Tuberculosis Programme (NTP) in Cambodia, one of the countries most affected by tuberculosis (TB) and human immunodeficiency virus (HIV) infection in Asia. To conduct national HIV prevalence surveillance among TB patients, to estimate HIV prevalence among TB patients and to determine the potential of the NTP as a source for antiretroviral treatment (ART) scale-up. Anonymous unlinked cross-sectional seroprevalence surveys including all TB patients registered by the NTP in January 2003 and January 2005. HIV prevalence among all TB patients fell from 11.8% in 2003 to 9.9% in 2005 (P < 0.05). In 2003 and 2005, respectively 265 and 261 TB patients were identified as HIV-positive in a given month. Among new smear-positive pulmonary TB patients, the prevalence dropped from 8.2% to 5.2% (P < 0.01). The two periodic surveys demonstrated a high prevalence of HIV among TB patients in Cambodia. However, the declining incidence of HIV from the late 1990s might now be reflected in the HIV prevalence among new smear-positive TB patients. The NTP is a potential source of ART if HIV counselling and testing are made more widely available to TB patients.


Prepregnancy weight and the risk of adverse pregnancy outcomes.
Obesity before pregnancy is associated with an increased risk of several adverse outcomes of pregnancy. The risk profiles among lean, normal, or mildly overweight women are not, however, well established. We studied the associations between prepregnancy body-mass index (defined as the weight in kilograms divided by the square of the height in meters) and the frequency of late fetal death, early neonatal death, preterm delivery, and delivery of a small-for-gestational-age infant in a population-based cohort of 167,750 women in Sweden in 1992 and 1993. The women were categorized as follows, according to body-mass index: lean, less than 20.0; normal, 20.0 through 24.9; overweight, 25.0 through 29.9; and obese, 30.0 or more. The estimates were adjusted for maternal age, parity, smoking, education, whether the mother was living with the father, and maternal height. Among nulliparous women, the odds ratios for late fetal death were increased among women with higher body-mass-index values as compared with lean women, as follows: normal women, 2.2 (95 percent confidence interval, 1.2 to 4.1); overweight women, 3.2 (95 percent confidence interval, 1.6 to 6.2); and obese women, 4.3 (95 percent confidence interval, 2.0 to 9.3). Among parous women, only obese women had a significant increase in the risk of late fetal death (odds ratio, 2.0; 95 percent confidence interval, 1.2 to 3.3). Among nulliparous women, the risk of very preterm delivery (at < or =32 weeks' gestation) was significantly increased among obese as compared with lean women (odds ratio, 1.6; 95 percent confidence interval, 1.1 to 2.3), whereas among parous women, the risk was highest among those who were lean. The risk of delivering a small-for-gestational-age infant decreased more with increasing body-mass index among parous than among nulliparous women. Higher maternal weight before pregnancy increases the risk of late fetal death, although it protects against the delivery of a small-for-gestational-age infant.


Conformational features of topologically classified RNA secondary structures.
Current RNA secondary structure prediction approaches predict prevalent pseudoknots such as the H-pseudoknot and kissing hairpin. The number of possible structures increases drastically when more complex pseudoknots are considered, thus leading to computational limitations. On the other hand, the enormous population of possible structures means not all of them appear in real RNA molecules. Therefore, it is of interest to understand how many of them really exist and the reasons for their preferred existence over the others, as any new findings revealed by this study might enhance the capability of future structure prediction algorithms for more accurate prediction of complex pseudoknots. A novel algorithm was devised to estimate the exact number of structural possibilities for a pseudoknot constructed with a specified number of base pair stems. Then, topological classification was applied to classify RNA pseudoknotted structures from data in the RNA STRAND database. By showing the vast possibilities and the real population, it is clear that most of these plausible complex pseudoknots are not observed. Moreover, from these classified motifs that exist in nature, some features were identified for further investigation. It was found that some features are related to helical stacking. Other features are still left open to discover underlying tertiary interactions. Results from topological classification suggest that complex pseudoknots are usually some well-known motifs that are themselves complex or the interaction results of some special motifs. Heuristics can be proposed to predict the essential parts of these complex motifs, even if the required thermodynamic parameters are currently unknown.


Choice selection and reward anticipation: an fMRI study.
We examined neural activations during decision-making using fMRI paired with the wheel of fortune task, a newly developed two-choice decision-making task with probabilistic monetary gains. In particular, we assessed the impact of high-reward/risk events relative to low-reward/risk events on neural activations during choice selection and during reward anticipation. Seventeen healthy adults completed the study. We found, in line with predictions, that (i) the selection phase predominantly recruited regions involved in visuo-spatial attention (occipito-parietal pathway), conflict (anterior cingulate), manipulation of quantities (parietal cortex), and preparation for action (premotor area), whereas the anticipation phase prominently recruited regions engaged in reward processes (ventral striatum); and (ii) high-reward/risk conditions relative to low-reward/risk conditions were associated with a greater neural response in ventral striatum during selection, though not during anticipation. Following an a priori ROI analysis focused on orbitofrontal cortex, we observed orbitofrontal cortex activation (BA 11 and 47) during selection (particularly to high-risk/reward options), and to a more limited degree, during anticipation. These findings support the notion that (1) distinct, although overlapping, pathways subserve the processes of selection and anticipation in a two-choice task of probabilistic monetary reward; (2) taking a risk and awaiting the consequence of a risky decision seem to affect neural activity differently in selection and anticipation; and thus (3) common structures, including the ventral striatum, are modulated differently by risk/reward during selection and anticipation.


New Horizons of Nonclassical Crystallization.
Nonclassical crystallization (NCC) summarizes a number of crystallization pathways, which differ from the classical layer-by-layer growth of crystals involving atomic/molecular building units. Common to NCC is that the building units are larger and include nanoparticles, clusters, or liquid droplets, providing multiple handles for their control at each elementary step. Therefore, many different pathways toward the final single crystals are possible and can be influenced by appropriate experimental parameters or additives at each step of crystal growth. NCC allows for a plethora of crystallization strategies toward complex crystalline (hybrid) materials. In this perspective, we summarize the current state of the art with a focus on the new horizons of NCC with respect to mechanistic understanding, high-performance materials, and new applications. This gives a glimpse on what will be possible in the future using these crystallization approaches: Examples are new electrodes and storage materials, (photo)catalysts, building materials, porous or crystalline materials with complex shape, structural hierarchy, and anisotropic single crystals.


Polymorphisms of the murine mitochondrial ND4, CYTB and COX3 genes impact hematopoiesis during aging.
During aging, mitochondrial DNA (mtDNA) can accumulate mutations leading to increasing levels of reactive oxygen species (ROS). Increased ROS were described to activate formerly quiescent hematopoietic stem cells (HSC). Mutations in mtDNA were shown to enhance the risk for myelodysplastic syndrome and leukemia. However, the complex relationship between mtDNA variations, ROS and aging of the hematopoietic system is not fully understood.Herein, three mouse strains with mtDNA polymorphisms in genes of respiratory chain complexes I (ND4), III (CYTB) and IV (COX3) were compared to a reference strain during aging. Analysis focused on ROS and ATP levels, bone marrow composition and blood counts. Additionally, hematopoietic restoration capacity following cytotoxic stress was tested.Mice with polymorphisms in ND4 and CYTB gene had significantly decreasing ROS levels in bone marrow cells during aging, without effecting ATP levels. In addition, the frequency of stem and progenitor cells increased during aging but the amount of lymphocytes in the peripheral blood decreased during aging.In summary, the presence of mtDNA polymorphisms affecting the respiratory chain complexes I, III and IV was associated with altered ROS levels as well as changes in BM and peripheral blood composition during aging.


The effects of fire on ant trophic assemblage and sex allocation.
Fire plays a key role in ecosystem dynamics worldwide, altering energy flows and species community structure and composition. However, the functional mechanisms underlying these effects are not well understood. Many ground-dwelling animal species can shelter themselves from exposure to heat and therefore rarely suffer direct mortality. However, fire-induced alterations to the environment may change a species' relative trophic level within a food web and its mode of foraging. We assessed how fire could affect ant resource utilization at different scales in a Mediterranean forest. First, we conducted isotopic analyses on entire ant species assemblages and their potential food resources, which included plants and other arthropods, in burned and unburned plots 1 year postfire. Second, we measured the production of males and females by nests of a fire-resilient species, Aphaenogaster gibbosa, and analyzed the differences in isotopic values among workers, males, and females to test whether fire constrained resource allocation. We found that, in spite of major modifications in biotic and abiotic conditions, fire had little impact on the relative trophic position of ant species. The studied assemblage was composed of species with a wide array of diets. They ranged from being mostly herbivorous to completely omnivorous, and a given species' trophic level was the same in burned and unburned plots. In A. gibbosa nests, sexuals had greater δ(15)N values than workers in both burned and unburned plots, which suggests that the former had a more protein-rich diet than the latter. Fire also appeared to have a major effect on A. gibbosa sex allocation: The proportion of nests that produced male brood was greater on burned zones, as was the mean number of males produced per nest with the same reproductive investment. Our results show that generalist ants with relatively broad diets maintained a constant trophic position, even following a major disturbance like fire. However, the dramatically reduced production of females on burned zones compared to unburned zones 1 year postfire may result in considerably reduced recruitment of new colonies in the mid to long term, which could yield genetic bottlenecks and founder effects. Our study paves the way for future functional analyses of fire-induced modifications in ant populations and communities.


Trends in Bone Mineral Density, Osteoporosis, and Osteopenia Among U.S. Adults With Prediabetes, 2005-2014.
We aimed to evaluate trends in bone mineral density (BMD) and the prevalence of osteoporosis/osteopenia in U.S. adults with prediabetes and normal glucose regulation (NGR) and further investigate the association among prediabetes, osteopenia/osteoporosis, and fracture. We collected and analyzed data from the U.S. National Health and Nutrition Examination Surveys during the period from 2005 to 2014. Femoral neck and lumbar spine BMD data were available for 5,310 adults with prediabetes and 5,162 adults with NGR >40 years old. A shift was observed toward a lower BMD and a higher prevalence of osteopenia/osteoporosis at the femoral neck and lumbar spine in U.S. adults >40 years old with prediabetes since 2005, especially in men <60 and women ≥60 years old. A shift toward a higher prevalence of osteopenia/osteoporosis at the femoral neck was also observed in adults >40 years old with NGR. Moreover, prediabetes was associated with a higher prevalence of hip fracture, although participants with prediabetes had higher BMD and a lower prevalence of osteopenia/osteoporosis at the femoral neck. There was a declining trend in BMD from 2005 to 2014 in U.S. adults >40 years old with prediabetes and NGR, and this trend was more significant in men <60 years old. Populations with prediabetes may be exposed to relatively higher BMD but a higher prevalence of fracture.


After over 200 years, 7 T magnetic resonance imaging reveals the foliate structure of the human corpus callosum in vivo.
A fine structure of the corpus callosum (CC), consisting of radial lines, is seen in historical anatomical atlases as far back as that of Vicq d'Azyr (1786). This study examines a similar pattern observed in vivo using high-resolution MR images at 7 T. 8 healthy subjects were examined with 7.0-T MRI. Anatomical images were collected with a gradient echo scan with 0.5-mm isotropic resolution, which were rated for visibility of the radial pattern. In addition, the second eigenvector of the diffusion tensor images was examined. The fine radial lines are detected not only in the sagittal view but also in the axial view of the in vivo MR images. From this, it is likely that these structures are two-dimensional ribbons. Interestingly, and confirming the structural nature of these stripes, the second eigenvector of the diffusion tensor imaging data shows an extremely similar pattern of oriented foliate structure. A similar modular structure involving transient septa has been observed previously in histological sections of human fetal CC. The separate sets of data-the atlas of Klingler, anatomical images and second eigenvector images-all indicate a ribbon-like arrangement of the fibres in the CC. As such, they closely match the structures shown in the drawn atlases of as old as 1786. Advances in knowledge: This ribbon arrangement of fibres in the CC, previously unseen in CT or lower field MRI, can now be observed in vivo. This appears to match over two centuries of ex vivo observations.


Personalized Non-contact Sleep Stage Estimation with Weighted Probability Estimation by Ultradian Rhythm.
This paper focused on ultradian rhythms (a sleep cycle of approximately 60 to 120 minute) for personalizing sleep stage estimation, and proposed a personalized sleep stage estimation method that weights the results estimated by machine learning with the predicted ultradian rhythms. The ultradian rhythms are predicted by the body movement density which is correlated with ultradian rhythm. To investigate the effectiveness of the proposed method, this paper conducts human subjects experiment for eight subjects.Clinical relevance- The proposed method is compared with the results estimated by conventional ML, and the result of the proposed method is competitive with their conventional counterparts. This indicates that the ultradian rhythm has the potential for developing personalized sleep stage estimation.


Fetal homologue of infant crying.
Four behavioural states are recognised in the human fetus and are comparable to those of the neonate: 1F (quiet sleep), 2F (active state), 3F (quiet awake), and 4F (active awake). State 5, or crying, is not considered to have a fetal correlate. In a study assessing the effects of exposure to tobacco and cocaine during pregnancy on fetal response and habituation to vibroacoustic stimulation, what appears to be the fetal homologue of crying was observed. These behaviours were seen on ultrasound, and have been captured on video recordings and include: an initial exhalation movement associated with mouth opening and tongue depression, followed by a series of three augmented breaths, the last breath ending in an inspiratory pause followed by an expiration and settling. This is the first report/video documenting these behaviours and suggests the possibility of a state 5F.


The importance of early diagnosis of acute acalculus cholecystitis.
Most observations of acute acalculus cholecystitis have been reported in patients after trauma, after unrelated surgical treatment and in critically ill patients, patient populations in whom the diagnosis of this condition is difficult. The importance of making an early diagnosis is demonstrated by the rapid development of complicated forms of cholecystitis. The results of collective reports have indicated that 40 to 100 per cent of the patients with acute acalculus cholecystitis will have advanced disease with gangrene, empyema or perforation of the gallbladder at operation. To demonstrate the importance of early suspicion and the use of sonography in making the diagnosis of this condition, a retrospective study of 40 patients with a surgical and pathologic proved diagnosis of acute acalculus cholecystitis was conducted. The fulminant nature of this disease was underscored by the fact that 70 per cent of these patients had advanced disease. Patients were divided into two groups, those who underwent operation within 48 hours of the onset of symptoms and those whose surgical treatment was delayed. Forty per cent of the patients who underwent operation more than 48 hours after the onset of symptoms had gallbladder perforation, while only 8 per cent of the patients without a delay in surgical treatment of more than 48 hours had perforations. Since advanced disease, especially perforation, carries a much higher morbidity and mortality than uncomplicated cholecystitis, making an early diagnosis is of paramount importance. Therefore, heightened awareness on the part of physicians is a key in making an early diagnosis. In 25 per cent of the patients in this study, unexplained fever was the first sign of the disease. Although most patients later presented with more classic symptoms of cholecystitis, many of these patients still presented with confusing clinical signs and symptoms leading to a delay in diagnosis due to the coexistence of the post-trauma, postsurgical or critically ill state. Ultrasound proved to be an important adjunct to the often confusing clinical clues in making an early diagnosis. Three ultrasonographic signs in the absence of stones--1, a thickened gallbladder wall; 2, an enlarged tender gallbladder, and 3, a pericholecystic collection--were suggestive of acute acalculus cholecystitis. One of these findings was present in almost 90 per cent of the patients in this study with acute acalculus cholecystitis who underwent biliary ultrasound.


The bronchiectasis severity index. An international derivation and validation study.
There are no risk stratification tools for morbidity and mortality in bronchiectasis. Identifying patients at risk of exacerbations, hospital admissions, and mortality is vital for future research. This study describes the derivation and validation of the Bronchiectasis Severity Index (BSI). Derivation of the BSI used data from a prospective cohort study (Edinburgh, UK, 2008-2012) enrolling 608 patients. Cox proportional hazard regression was used to identify independent predictors of mortality and hospitalization over 4-year follow-up. The score was validated in independent cohorts from Dundee, UK (n = 218); Leuven, Belgium (n = 253); Monza, Italy (n = 105); and Newcastle, UK (n = 126). Independent predictors of future hospitalization were prior hospital admissions, Medical Research Council dyspnea score greater than or equal to 4, FEV1 < 30% predicted, Pseudomonas aeruginosa colonization, colonization with other pathogenic organisms, and three or more lobes involved on high-resolution computed tomography. Independent predictors of mortality were older age, low FEV1, lower body mass index, prior hospitalization, and three or more exacerbations in the year before the study. The derived BSI predicted mortality and hospitalization: area under the receiver operator characteristic curve (AUC) 0.80 (95% confidence interval, 0.74-0.86) for mortality and AUC 0.88 (95% confidence interval, 0.84-0.91) for hospitalization, respectively. There was a clear difference in exacerbation frequency and quality of life using the St. George's Respiratory Questionnaire between patients classified as low, intermediate, and high risk by the score (P < 0.0001 for all comparisons). In the validation cohorts, the AUC for mortality ranged from 0.81 to 0.84 and for hospitalization from 0.80 to 0.88. The BSI is a useful clinical predictive tool that identifies patients at risk of future mortality, hospitalization, and exacerbations across healthcare systems.


A single serving of blueberry (V. corymbosum) modulates peripheral arterial dysfunction induced by acute cigarette smoking in young volunteers: a randomized-controlled trial.
Cigarette smoking causes oxidative stress, hypertension and endothelial dysfunction. Polyphenol-rich foods may prevent these conditions. We investigated the effect of a single serving of fresh-frozen blueberry intake on peripheral arterial function and arterial stiffness in young smokers. Sixteen male smokers were recruited for a 3-armed randomized-controlled study with the following experimental conditions: smoking treatment (one cigarette); blueberry treatment (300 g of blueberry) + smoking; control treatment (300 mL of water with sugar) + smoking. Each treatment was separated by one week of wash-out period. The blood pressure, heart rate, peripheral arterial function (reactive hyperemia and Framingham reactive hyperemia), and arterial stiffness (digital augmentation index, digital augmentation index normalized for a heart rate of 75 bpm) were measured before and 20 min after smoking with Endo-PAT2000. Smoking impaired the blood pressure, heart rate and peripheral arterial function, but did not affect the arterial stiffness. Blueberry consumption counteracted the impairment of the reactive hyperemia index induced by smoking (-4.4 ± 0.8% blueberry treatment vs. -22.0 ± 1.1% smoking treatment, p < 0.01) and Framingham reactive hyperemia (+28.3 ± 19.2% blueberry treatment vs. -42.8 ± 20.0% smoking treatment, p < 0.0001), and the increase of systolic blood pressure (+8.4 ± 0.02% blueberry treatment vs. +13.1 ± 0.02% smoking treatment, mmHg, p < 0.05) after cigarette smoking. No effect was observed for arterial stiffness and other vital signs. In conclusion, data obtained suggest a protective role of blueberry on reactive hyperemia, Framingham reactive hyperemia, and systolic blood pressure in subjects exposed to smoke of one cigarette. Future studies are necessary to elucidate the mechanisms involved.


The BCL-2 inhibitor APG-2575 resets tumor-associated macrophages toward the M1 phenotype, promoting a favorable response to anti-PD-1 therapy via NLRP3 activation.
The main challenges in the use of immune checkpoint inhibitors (ICIs) are ascribed to the immunosuppressive tumor microenvironment and the lack of sufficient infiltration of activated CD8+ T cells. Transforming the tumor microenvironment (TME) from "cold" to "hot" and thus more likely to potentiate the effects of ICIs is a promising strategy for cancer treatment. We found that the selective BCL-2 inhibitor APG-2575 can enhance the antitumor efficacy of anti-PD-1 therapy in syngeneic and humanized CD34+ mouse models. Using single-cell RNA sequencing, we found that APG-2575 polarized M2-like immunosuppressive macrophages toward the M1-like immunostimulatory phenotype with increased CCL5 and CXCL10 secretion, restoring T-cell function and promoting a favorable immunotherapy response. Mechanistically, we demonstrated that APG-2575 directly binds to NF-κB p65 to activate NLRP3 signaling, thereby mediating macrophage repolarization and the activation of proinflammatory caspases and subsequently increasing CCL5 and CXCL10 chemokine production. As a result, APG-2575-induced macrophage repolarization could remodel the tumor immune microenvironment, thus improving tumor immunosuppression and further enhancing antitumor T-cell immunity. Multiplex immunohistochemistry confirmed that patients with better immunotherapeutic efficacy had higher CD86, p-NF-κB p65 and NLRP3 levels, accompanied by lower CD206 expression on macrophages. Collectively, these data provide evidence that further study on APG-2575 in combination with immunotherapy for tumor treatment is required.


Aspirin use correlates with survival in women with clear cell ovarian cancer.
Data from colon, breast and prostate cancers suggest that aspirin users have reduced mortality. While the direct mechanism remains uncertain, aspirin can suppress the COX-dependent and independent pathways involved in tumor progression. We hypothesized that aspirin users with clear cell ovarian cancer would have improved survival outcomes. We performed a retrospective review of patients with clear cell ovarian cancer diagnosed between 1995 and 2010, and followed outcomes through 2016. Patients underwent primary cytoreductive surgery followed by platinum-based chemotherapy. Aspirin use was defined by medication documentation in two records more than six months apart. Statistical tests included Fisher's exact, Kaplan-Meier and Cox regression analyses. Seventy-seven patients met inclusion criteria. Fifty-four patients (70%) had stage I-II disease. Thirteen patients (17%) used aspirin. Aspirin users had a statistically longer disease-free survival compared to non-users (HR 0.13, p = .018). While median disease-free survival was not reached for either group, 1 of 13 (8%) aspirin users recurred at 24 months, compared to 18 of 64 (28%) non-users. Aspirin users demonstrated longer overall survival (HR 0.13, p = .015). Median survival was not reached for aspirin users, compared to 166 months for non-users. Aspirin use retained significance (HR 0.13, p = .044) after controlling for age, stage and cytoreductive status. In this small cohort of women with clear cell ovarian cancer, aspirin use correlated with improved disease-free and overall survival, and retained independent significance as a positive prognostic factor. Further research is warranted to confirm these findings before considering aspirin as a therapeutic intervention.


Luminescence phenomena of biodegradable photoluminescent poly(diol citrates).
The possible origin of luminescent properties of biodegradable photoluminescent polyesters (BPLPs) has been revealed by isolation and identification of luminescent agent from the hydrolyzate of BPLP. Elemental analysis, ESI-MS, (1)H, (13)C, 2D HSQC and COSY NMR spectra confirmed the chemical structure as 5-oxo-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyridine-3,7-dicarboxylic acid (TPA).


Attentional modulations of the early and later stages of the neural processing of visual completion.
The brain effortlessly recognizes objects even when the visual information belonging to an object is widely separated, as well demonstrated by the Kanizsa-type illusory contours (ICs), in which a contour is perceived despite the fragments of the contour being separated by gaps. Such large-range visual completion has long been thought to be preattentive, whereas its dependence on top-down influences remains unclear. Here, we report separate modulations by spatial attention and task relevance on the neural activities in response to the ICs. IC-sensitive event-related potentials that were localized to the lateral occipital cortex were modulated by spatial attention at an early processing stage (130-166 ms after stimulus onset) and modulated by task relevance at a later processing stage (234-290 ms). These results not only demonstrate top-down attentional influences on the neural processing of ICs but also elucidate the characteristics of the attentional modulations that occur in different phases of IC processing.