bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying the accretion of hyperphosphorylated tau in the locus coeruleus and dorsal raphe nucleus: the pathological building blocks of early Alzheimer's disease
Authors: Ehrenberg A. J. , Nguy A. K. , Theofilas P. , Dunlop S. , Suemoto C. K. , Di Lorenzo Alho A. T. , Leite R. P. , Diehl Rodriguez R. , Mejia M. B. , Rüb U. , Farfel J. M. , de Lucena Ferretti‐Rebustini R. E. , Nascimento C. F. , Nitrini R. , Pasquallucci C. A. , Jacob‐Filho W. , Miller B. , Seeley W. W. , Heinsen H. , Grinberg L. T. 
Published: January 2017

AimsHyperphosphorylated tau neuronal cytoplasmic inclusions (ht‐NCI) are the best protein correlate of clinical decline in Alzheimer's disease (AD). Qualitative evidence identifies ht‐NCI accumulating in the isodendritic core before the entorhinal cortex. Here, we used unbiased stereology to quantify ht‐NCI burden in the locus coeruleus (LC) and dorsal raphe nucleus (DRN), aiming to characterize the impact of AD pathology in these nuclei with a focus on early stages.MethodsWe utilized unbiased stereology in a sample of 48 well‐characterized subjects enriched for controls and early AD stages. ht‐NCI counts were estimated in 60‐μm‐thick sections immunostained for p‐tau throughout LC and DRN. Data were integrated with unbiased estimates of LC and DRN neuronal population for a subset of cases.ResultsIn Braak stage 0, 7.9% and 2.6% of neurons in LC and DRN, respectively, harbour ht‐NCIs. Although the number of ht‐NCI+ neurons significantly increased by about 1.9× between Braak stages 0 to I in LC (P = 0.02), we failed to detect any significant difference between Braak stage I and II. Also, the number of ht‐NCI+ neurons remained stable in DRN between all stages 0 and II. Finally, the differential susceptibility to tau inclusions among nuclear subdivisions was more notable in LC than in DRN.ConclusionsLC and DRN neurons exhibited ht‐NCI during AD precortical stages. The ht‐NCI increases along AD progression on both nuclei, but quantitative changes in LC precede DRN changes.
The Role of Non‐Human Exemplars in Aquinas
Authors: Willows Adam M. 
Published: January 2017

AbstractIn this paper I discuss the role of non‐humans in Aquinas’ account of moral learning. I intend to show that the entire created order can play an important role in demonstrating to us the life of virtue, and argue that non‐human exemplars offer important advantages to the moral learner. I begin by addressing apparent problems with this approach, founded on the observation that human virtue, for Aquinas, is unique to humans. I resolve these by showing that Aquinas’ approach to exemplars is fundamentally analogical, meaning that exemplars point beyond themselves and need not necessarily live the good life to which they direct learners. I show that this means that Aquinas can use non‐humans as moral exemplars and offer examples of him doing just that. Finally, I offer an assessment of the benefits of this approach. Among other things, it offers ethicists new ways to focus on particular virtues and provides a plausible way to include non‐humans in the moral realm.
Insular primary glioblastomas with IDH mutations: Clinical and biological specificities
Authors: Hata Nobuhiro , Hatae Ryusuke , Yoshimoto Koji , Murata Hideki , Kuga Daisuke , Akagi Yojiro , Sangatsuda Yuhei , Suzuki Satoshi O. , Iwaki Toru , Mizoguchi Masahiro , Iihara Koji 
Published: January 2017

Isocitrate dehydrogenase (IDH) mutation is a good prognostic marker for glioblastoma (GBM). Although it is infrequent in primary tumors, it is found in most lower‐grade gliomas. Thus, it is unclear whether IDH mutation is a marker for a specific phenotype of apparently primary de novo GBMs (pGBMs), or a marker for secondary tumors (sGBMs). We addressed this issue by analyzing clinical, radiographic and molecular findings in our institutional case series. Our cases included 92 pGBMs, with five cases of IDH1 mutations at R132 and no IDH2 mutations. The median overall survival of these five patients was 29 months (range: 4 to >40 months), which is considered good prognoses. Clinical and radiographic characteristics were distinct from IDH‐wildtype (IDH‐wt) pGBMs. IDH‐mutant (IDH‐mut) tumors consistently involved insular lesions and were subdivided into: (i) the two cases of elderly patients with long clinical histories and features implying multistep tumor development; and (ii) the three cases of younger patients with diffusely swelling insular tumors, slight contrast enhancement and no necrosis. Genetic and expression analyses of IDH‐mut pGBMs were similar to those of sGBMs, suggesting that they are indeed distinct from their IDH‐wt counterparts. TERT promoter mutation, a genetic marker of oligodendroglial derivation, was detected in one long‐surviving case, but genetic alterations in the astrocyte‐sGBM pathway were generally prevalent in IDH‐mut pGBMs. Our results present a unique phenotype of IDH‐mut pGBMs arising from insular cortex region, the molecular backgrounds of which are similar to sGBMs.
Brain networks associated with cognitive and hedonic responses to a meal
Authors: Pribic T. , Kilpatrick L. , Ciccantelli B. , Malagelada C. , Accarino A. , Rovira A. , Pareto D. , Mayer E. , Azpiroz F. 
Published: January 2017

AbstractBackgroundWe recently reported interrelated digestive, cognitive, and hedonic responses to a meal. The aim of this study was to identify brain networks related to the hedonic response to eating.MethodsThirty‐eight healthy subjects (20‐38 age range) were evaluated after a 5‐hour fast and after ingestion of a test meal (juice and warm ham and cheese sandwich, 300 mL, 425 kcal). Perceptual and affective responses (satiety, abdominal fullness, digestive well‐being, and positive mood), and resting scans of the brain using functional MRI (3T Trio, Siemens, Germany) were evaluated immediately before and after the test meal. A high‐order group independent component analysis was performed to investigate ingestion‐related changes in the intrinsic connectivity of brain networks, with a focus on thalamic and insular networks.Key ResultsIngestion induced satiation (3.3±0.4 score increase; P<.001) and abdominal fullness (2.4±0.3 score increase; P<.001). These sensations included an affective dimension involving digestive well‐being (2.8±0.3 score increase; P<.001) and positive mood (1.8±0.2 score increase; P<.001). In general, thalamo‐cortical connectivity increased with meal ingestion while insular‐cortical connectivity mainly decreased. Furthermore, larger meal‐induced changes (increase/decrease) in specific thalamic connections were associated with smaller changes in satiety/fullness. In contrast, a larger meal‐induced decrease in insular‐anterior cingulate cortex connectivity was associated with increased satiety, fullness, and digestive well‐being.Conclusions and InferencesPerceptual and emotional responses to food intake are related to brain connectivity in defined functional networks. Brain imaging may provide objective biomarkers of subjective effects of meal ingestion.
Does intentional weight loss improve daytime sleepiness? A systematic review and meta‐analysis
Authors: Ng W. L. , Stevenson C. E. , Wong E. , Tanamas S. , Boelsen‐Robinson T. , Shaw J. E. , Naughton M. T. , Dixon J. , Peeters A. 
Published: January 2017

SummaryObesity is associated with excessive daytime sleepiness, but its causality remains unclear. We aimed to assess the extent to which intentional weight loss affects daytime sleepiness. Electronic databases were searched through 24 October 2016. Studies involving overweight or obese adults, a weight loss intervention and repeated valid measures of daytime sleepiness were included in the review. Two independent reviewers extracted data on study characteristics, main outcome (change in daytime sleepiness score standardized by standard deviation of baseline sleepiness scores), potential mediators (e.g. amount of weight loss and change in apnoea–hypopnoea index) and other co‐factors (e.g. baseline demographics). Forty‐two studies were included in the review. Fifteen before‐and‐after studies on surgical weight loss interventions showed large improvements in daytime sleepiness, with a standardized effect size of −0.97 (95% confidence interval [CI] −1.21 to −0.72). Twenty‐seven studies on non‐surgical weight loss interventions showed small‐to‐moderate improvement in daytime sleepiness, with a standardized effect size of −0.40 (95%CI −0.52 to −0.27), with no difference between controlled and before‐and‐after studies. We found a nonlinear association between amount of weight loss and change in daytime sleepiness. This review suggests that weight loss interventions improve daytime sleepiness, with a clear dose–response relationship. This supports the previously hypothesized causal effect of obesity on daytime sleepiness. It is important to assess and manage daytime sleepiness in obese patients.
Frequency and fertility restoration efficiency of Rf3 and Rf4 genes in Indian rice
Authors: Katara Jawahar Lal , Verma Ram Lakhan , Nayak Debkanta , Ngangkham Umakanta , Ray Soham , Subudhi Hatanath , Behera Lambodar , Samantaray Sanghamitra , Rao Ravi Nageswara , Singh Onkar Nath , Mohapatra Trilochan 
Published: January 2017

AbstractIdentification of new parental lines is crucial for developing ecology‐specific hybrids with ideal agronomic performance. We screened a total of 570 different ecology‐specific Indian rice varieties for the presence of fertility restorer genes, Rf3 and Rf4 using tightly linked markers DRRM Rf3‐10 and RM6100, respectively. Among these varieties, 13% carried Rf3Rf3/Rf4Rf4, 31% carried rf3rf3/rf4rf4, 6% carried Rf3Rf3/rf4rf4 and remaining 50% carried Rf4Rf4/rf3rf3 allelic combinations. A mini set of 40 varieties with variable allelic combinations of fertility restorer genes were testcrossed with WA and Kalinga‐based CMS lines. All the 80 F1s were evaluated for spikelet fertility and fertility restoration ability. Rf3Rf3/rf4rf4 genotypes mostly behaved as partial maintainers or partial restorers. In contrast, rf3rf3/Rf4Rf4 genotypes were partial or effective restorers. However, double dominant genotypes showed better fertility restoration than the genotypes containing Rf3 or Rf4 individually. Some of the genotypes showed unexpected restoration pattern implying occurrence of other fertility restorer(s) apart from Rf3 and Rf4. The perfect restorers and maintainers identified in this study can be directly used in hybrid rice breeding.
Discrimination of haploid and diploid maize kernels via multispectral imaging
Authors: De La Fuente Gerald N. , Carstensen Jens Michael , Edberg Michael A. , Lü bberstedt Thomas 
Published: January 2017

AbstractThe use of doubled haploids (DHs) in maize has become ubiquitous in maize breeding programmes as it allows breeders to go from cross to evaluation in as little as 2 years. Two important aspects of the in vivo DH system used in maize are as follows: (i) the identification of haploid progeny and (ii) doubling of the haploid genome to produce fertile inbred lines. This study is focused on the first step. Currently, identification of maize haploid progeny is performed manually using the R1‐nj seed colour marker. This is a labour‐intensive and time‐consuming process; a method for automated sorting of haploids would increase the efficiency of DH line development. In this study, six inbred lines were crossed with the maternal haploid inducer ‘RWS/RWK‐76’ and a sample of seed was sorted manually for each line. Using the VideometerLab 3 system, spectral imaging techniques were applied to discriminate between haploids and hybrids. Using DNA markers to confirm the haploid/diploid state of the tested seed, for the majority of genotypes haploid identification was possible with over 50% accuracy.
Late‐onset circulatory collapse of prematurity
Authors: Kawai Masahiko 
Published: January 2017

AbstractLate‐onset circulatory collapse (LCC) is a refractory hypotension occurring after the early neonatal period (>day 7), in very low‐birthweight infants. Typically, infants stabilized within the early neonatal period develop sudden onset of circulatory collapse after the early neonatal period. The underlying pathophysiology of LCC is considered to be relative adrenal insufficiency, which is well known in Japan, but is not widely accepted in North America or Europe. The current increase in LCC in Japan suggests that the principal trigger is related to recent trends in neonatal medicine and/or newly introduced treatments for preterm infants, but the pathophysiology has not been fully elucidated. In this review, based on current knowledge regarding LCC, the pathophysiology is discussed.
Transcutaneous bilirubin measurement during phototherapy in term neonates
Authors: Katayama Yoshinori , Enomoto Masahiro , Kikuchi Shin , Takei Atsuko , Ikegami Hitoshi , Minami Hirotaka , Lee Yong Kye 
Published: January 2017

AbstractBackgroundWe tested whether direct transcutaneous bilirubin (TcB) measurement from an area unexposed to phototherapy is reliable for estimation of total serum bilirubin (TSB) in neonates during phototherapy and whether it contributes to reduction in TSB blood sampling in phototherapy decision making.MethodsThis was a retrospective observational study of term neonates who received phototherapy in the mother's room. TSB and TcB from the neonate's sternum were measured before and during phototherapy and compared using linear regression analysis and Bland–Altman plot, respectively. Various cut‐offs of TcB for estimating TSB during phototherapy at >72 h after birth were analyzed.ResultsThere were moderate correlations between TSB and TcB before (r = 0.56) and during (r = 0.47) phototherapy in 125 neonates. The mean difference (TSB–TcB) before and during phototherapy was 1.2 ± 1.7 mg/dL and 1.0 ± 1.7 mg/dL, respectively. The 95% limits of agreement for the difference before and during phototherapy ranged from −2.1 to 4.5 and from −2.3 to 4.3 mg/dL, respectively. For TSB ≤18 mg/dL during phototherapy, a TcB cut‐off of 14 mg/dL had a specificity of 1.0; with this method, 43% of the TSB measurements could have been avoided.ConclusionsDirect measurement of TcB during phototherapy using a bed‐type device is a reliable method to estimate TSB in term neonates and would contribute to a reduction in blood sampling. It cannot, however, be used as a substitute for TSB measurement.
Trade Liberalization, Rival Exporters and Reallocation of Production: An Analysis of Indian Manufacturing
Authors: Edwards Lawrence , Sundaram Asha 
Published: January 2017

AbstractEmploying a difference‐in‐difference estimation technique on firm‐level data on Indian exporters, we show that the removal of US textile and apparel quotas was associated with a relative increase in sales of products where India was previously quota restricted, but a relative decrease in sales and the unit value of products where China was previously quota restricted. Our study hence highlights the importance of accounting for falling trade barriers for rival exporters in analyzing trade liberalization effects. Additionally, we find evidence indicating that quota rights were not allocated efficiently, suggesting potential gains from reallocation with the dismantling of the Indian quota licensing regime.
Transition from storm wave‐dominated outer shelf to gullied upper slope: The mid‐Pliocene Orinoco shelf margin, South Trinidad
Authors: Peng Yang , Steel Ronald J. , Olariu Cornel 
Published: January 2017

AbstractShelf‐edge deltas are a key depositional environment for accreting sediment onto shelf‐margin clinoforms. The Moruga Formation, part of the palaeo‐Orinoco shelf‐margin sedimentary prism of south‐east Trinidad, provides new insight into the incremental growth of a Pliocene, storm wave‐dominated shelf margin. Relatively little is known about the mechanisms of sand bypass from the shelf‐break area of margins, and in particular from storm wave‐dominated margins which are generally characterized by drifting of sand along strike until meeting a canyon or channel. The studied St. Hilaire Siltstone and Trinity Hill Sandstone succession is 260 m thick and demonstrates a continuous transition from gullied (with turbidites) uppermost slope upward to storm wave‐dominated delta front on the outermost shelf. The basal upper‐slope deposits are dominantly mass‐transport deposited blocks, as well as associated turbidites and debrites with common soft‐sediment‐deformed strata. The overlying uppermost slope succession exhibits a spectacular set of gullies, which are separated by abundant slump‐scar unconformities (tops of rotational slides), then filled with debris‐flow conglomerates and sandy turbidite beds with interbedded mudstones. The top of the study succession, on the outer‐shelf area, contains repeated upward‐coarsening, sandstone‐rich parasequences (2 to 15 m thick) with abundant hummocky and swaley cross‐stratification, clear evidence of storm‐swell and storm wave‐dominated conditions. The observations suggest reconstruction of the unstable shelf margin as follows: (i) the aggradational storm wave‐dominated, shelf‐edge delta front became unstable and collapsed down the slope; (ii) the excavated scars of the shelf margin became gullied, but gradually healed (aggraded) by repeated infilling by debris flows and turbidites, and then new gullying and further infilling; and (iii) a renewed storm wave‐dominated delta‐front prograded out across the healed outer shelf, re‐establishing the newly stabilized shelf margin. The Moruga Formation study, along with only a few others in the literature, confirms the sediment bypass ability of storm wave‐dominated reaches of shelf edges, despite river‐dominated deltas being, by far, the most efficient shelf‐edge regime for sediment bypass at the shelf break.
Cytology of the healthy canine and feline ocular surface: comparison between cytobrush and impression technique
Authors: Perazzi Anna , Bonsembiante Federico , Gelain Maria Elena , Patruno Marco , Di Iorio Enzo , Migliorati Angelo , Iacopetti Ilaria 
Published: January 2017

BackgroundImpression cytology (IC) is a noninvasive technique in which filters are used to sample superficial layers of ocular epithelium.ObjectivesThe aim of this study was to compare cytology specimens obtained by IC and cytobrush from healthy canine and feline eyes.MethodsDogs and cats were prospectively sampled using polytetrafluorethylene filters on the right eye, and cytobrush on the left eye. Wright–Giemsa‐stained specimens were evaluated by 2 observers. Cellularity, preservation, and morphology of cells and presence of goblet and inflammatory cells were scored with a 4‐grade scale. Inter‐observer agreement and effects of topical anesthesia were analyzed.ResultsIn 20 canine IC samples, 10 showed good cellularity (score 2–3) and 13 good preservation. Superficial epithelial cells (SEC) were present in 13/20 of IC, while basal‐intermediate cells (BIC) were seen in 14/20. In 6/20 and 7/20, goblet and inflammatory cells were noted, respectively. In 20 cats, 15 of IC showed good cellularity and 14 good preservation, and SEC were present in 16/20 of IC and BIC in 17/20. In 13/20 and 3/20 cats, goblet cells and inflammatory cells were noted, respectively. Canine cytobrush specimens appeared well preserved (9/20) and had good cellularity (8/20). In feline cytobrush specimens, good preservation and cellularity were observed in 16/20 and 14/20, respectively. In both species, all cell types were present without a clear separation. There was moderate to fair agreement about cellular morphology in IC between observers. Specimens obtained with and without anesthesia were comparable.ConclusionImpression cytology allowed collection of samples with maintained cytoarchitecture, while cytoplasmatic and nuclear details were often difficult to evaluate.
Clinical and Microbiological Characteristics of Breakthrough Candidemia in Allogeneic Hematopoietic Stem Cell Transplant Recipients in a Japanese Hospital
Authors: Kimura Muneyoshi , Araoka Hideki , Yamamoto Hisashi , Asano-Mori Yuki , Nakamura Shigeki , Yamagoe Satoshi , Ohno Hideaki , Miyazaki Yoshitsugu , Abe Masahiro , Yuasa Mitsuhiro , Kaji Daisuke , Kageyama Kosei , Nishida Aya , Ishiwata Kazuya , Takagi Shinsuke , Yamamoto Go , Uchida Naoyuki , Izutsu Koji , Wake Atsushi , Taniguchi Shuichi , Yoneyama Akiko 
Published: January 2017

ABSTRACT

Few data on breakthrough candidemia (BC), defined as candidemia that develops on administration of antifungal agents (AFAs), in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are available. The medical and microbiological records of recipients of an allo-HSCT obtained between December 2008 and December 2014 were reviewed. Of 768 allo-HSCT cases, 26 developed BC. Among the 26 causative strains, 22 strains were stored and identified by sequencing. The following species were isolated:
Candida parapsilosis
(9 strains),
C. glabrata
(4 strains),
C. guilliermondii
(3 strains), and other
Candida
species (6 strains). The AFAs being used when BC developed were micafungin (17 cases), liposomal amphotericin B (5 cases), itraconazole (2 cases), and voriconazole (2 cases). All 17 cases who developed BC during micafungin administration were administered 150 mg/day of micafungin. The susceptibilities of the causative
Candida
species to the administered AFAs when breakthrough occurred ranged from susceptible to resistant. Especially, 85% of the
Candida
species that caused BC during micafungin administration were susceptible to micafungin. Additionally, 75% of the strains were wild type for susceptibility to the administered AFAs when breakthrough occurred. Systemic steroid administration and a longer severe neutropenic phase (≥5 days) were independent risk factors for BC (
P
= 0.016 and
P
= 0.015, respectively). BC developed in allo-HSCT recipients even when they received a sufficient dose of AFA, including micafungin, to which the causative
Candida
species were susceptible and/or had wild-type susceptibility
in vitro
. Systemic steroid administration and a longer severe neutropenic phase were host-based factors associated with BC.
Evolution of the Sterol Biosynthetic Pathway of Pythium insidiosum and Related Oomycetes Contributes to Antifungal Drug Resistance
Authors: Lerksuthirat Tassanee , Sangcakul Areeporn , Lohnoo Tassanee , Yingyong Wanta , Rujirawat Thidarat , Krajaejun Theerapong 
Published: January 2017

ABSTRACT

Pythiosis is a life-threatening infectious disease caused by the oomycete
Pythium insidiosum
. Direct exposure to
Py. insidiosum
zoospores can initiate infections of the eye, limb, gastrointestinal tract, or skin/subcutaneous tissue. Treatments for pythiosis have mostly relied on surgery. Antifungal drugs are generally ineffective against
Py. insidiosum
. However, one patient with an invasive
Py. insidiosum
infection recovered completely following treatment with terbinafine and itraconazole. Additionally, the drug target sterol biosynthetic enzymes have been identified in the oomycete
Aphanomyces euteiches
. It remains an open question whether
Py. insidiosum
is susceptible to the antifungal drugs and harbors any of the known drug target enzymes. Here, we determined the
in vitro
susceptibilities of terbinafine and itraconazole against 30 isolates of
Py. insidiosum
. We also analyzed endogenous sterols and searched for genes encoding the sterol biosynthetic enzymes in the genomes of
Py. insidiosum
and related oomycetes. The susceptibility assay showed that the growth of each of the
Py. insidiosum
isolates was inhibited by the antifungal agents, but only at difficult-to-achieve concentrations, which explains the clinical resistance of the drugs in the treatment of pythiosis patients. Genome searches of
Py. insidiosum
and related oomycetes demonstrated that these organisms contained an incomplete set of sterol biosynthetic enzymes. Gas chromatographic mass spectrometry did not detect any sterol end products in
Py. insidiosum
. In conclusion,
Py. insidiosum
possesses an incomplete sterol biosynthetic pathway. Resistance to antifungal drugs targeting enzymes in the ergosterol biosynthetic pathway in
Py. insidiosum
was due to modifications or losses of some of the genes encoding the drug target enzymes.