bluuebunny/crossref_metadata_2025 huggingface dataset:
A preliminary results of assessment of BMKG-WRF numerical model daily rainfall forecasts performance using categorical verification
Authors: Fatkhuroyan  , Praja A S , Wati T
Published: May 2019

Indonesia Agency for Meteorology, Climatology and Geophysics (BMKG) has been using WRF (Weather and Research Forecasting) numerical weather model in forecasting daily rainfall accumulation. The method used to compare the daily rainfall accumulation of WRF forecast results (one to three days forecast) to rain-gauge observation data from 153 meteorological stations from March 2016 to December 2017 by using categorical verification techniques. The results show that the values of Frequency Bias Index (FBI), Proportion Correct (PC), Probability of Detection (POD), False Alarm ratio (FAR), and Threat Score (TS) for one-day forecast and three-day forecast in 2016 are mostly lower than 2017. Meanwhile, for 2-days forecast in 2016 generally lower than 2017 except PC and FAR. Molucca-Papua have the highest value of PC (0.63) for one-day forecast while Kalimantan have the highest values of PC (0.67, 0.68) for 2 and 3 days ahead forecast. In contrary, Sumatera have the lowest PC value (0.55) for one-day forecast while Bali-Nusa Tenggara have the lowest PC value (0.58, 0.59) for 2 and 3 days ahead forecast, respectively. It can be concluded that the performance of BMKG WRF quite accurate in forecasting daily rainfall up to three days ahead.
Assessing rainfall pattern, groundwater level, and peat hydraulic conductivity for effective peat prevention measure
Authors: Putra Erianto I. , Hafni Dinda A.F. , Harahap Amirah A.N. , Cochrane Mark A. , Saharjo Bambang H.
Published: May 2019

Severe drought and less precipitation during a prolonged dry season and El-Nino events has been observed as a main trigger of the decrease of groundwater level leads to the dryness of the degraded peat and exacerbates burning conditions. To get a better understanding of this issue, we studied fire conditions in a portion of the ex-Mega Rice Project (MRP) area, Central Kalimantan. Here, we examine fire season and hydrology factors affecting peat fires by using Terra/Aqua MODIS hotspots dataset and groundwater level data from 300 dipwells and 15 staff gauges established in the MRP area. We use the Interpolation Data Weighting (IDW) to explain the fire risk in the area based on its hydraulic conductivity. Our results clearly show that even the moderate to high rainfall intensity is not enough to rewet the dry-degraded peat and thus to leave them in dry condition. Here, we highlight the importance of considering the rainfall pattern of previous successive dry and rainy season for fire risk assessment. Most of the fires occurred in the area between 1.1×10−6 and 2.1×10−6 cm/s hydraulic conductivity and below -10 cm groundwater level, sharply pointing out the importance to keep degraded peat in wet condition for fire prevention.
Potential Region for development of seaweed genus Eucheuma cottonii based on ENSO variability in east coast of Tarakan Island, Indonesia
Authors: Lestari D A , Susiloningtyas D , Handayani T
Published: May 2019

Eucehuma cottonii is one of seaweed type that has high economic and important ecosystem for people living at coastal areas such as at the east coast of Tarakan island. This research aimed to analyse potential region of Eucheuma cottonii against ENSO variability. The suitability level required form calculation of sea surface temperature, total suspended solids, salinity, and dissolved oxygen (DO) in the east coast of Tarakan island. Remote sensing of Landsat 8 OLI has been applied to study environmental changes of those variables. The results showed the spatial and temporal condition of the Amal Coast conditions strongly influenced by the ENSO variability and it became barrier factor on the suitability of Eucheuma cottoni cultivation. In the In the El Nino period, the coast of northern and centre of east coast Tarakan Island shows the most potential areas for seaweed cultivation while in the period of La Nina the most potential area is along the coast and dominated in all parts of east coast Tarakan Island. Overall, in the La Nina period the potential area for seaweed cultivation was wider than El Nino.
Tidal Correlation using Altimetry Satellite
Authors: Safi’i Ayu N , Rudiastuti Aninda W.
Published: May 2019

Tides data is strongly needed especially on Indonesian Coastal Environment mapping to achieve its accuracy. Usually, tides data derived from direct or indirect measurement. From palm observation, the tides data collected directly. Indirect measurement takes the advantages of altimetry satellite, where tides data collection carried in a shorter time and large area. In the supremacy of using altimetry satellite, we could obtain tides information not only in coastal but also in open waters. Study of altimetry data is required to prove whether tides components resulted represent real tides condition in coastal or vice versa. Finding out the linkage between tidal components resulted from Jason-1 altimetry satellite became the aim of this paper. Cross-over analysis method ran to examine the linkage between each tidal constituent. The tidal correlation value determined the accuracy of amplitude result from altimetry satellite. Gaussian Distribution played a role in determining the status of cross-over point data. The amplitude will point whether the cross-over point will continue to involve in tidal amplitude gridding process. The higher value of cross-over amplitude related to influence subsists between tides components in which the emerging values do not represent each tidal constituent itself.
Nasal Cavity of Green Sea Turtles Contains 3 Independent Sensory Epithelia
Authors: Kondoh Daisuke , Kitayama Chiyo , Yamaguchi Yohei , Yanagawa Masashi , Kawai Yusuke K , Suzuki Chihiro , Itakura Raito , Fujimoto Atsuru , Satow Tadatoshi , Kondo Satomi , Sato Takayuki
Published: May 2019

The morphological and histological features of the nasal cavity are diverse among animal species, and the nasal cavities of terrestrial and semiaquatic turtles possess 2 regions lined with each different type of sensory epithelium. Sea turtles can inhale both of volatile and water-soluble odorants with high sensitivity, but details of the architectural features and the distribution of the sensory epithelia within the sea turtle nasal cavity remain uncertain. The present study analyzed the nasal cavity of green sea turtles using morphological, computed tomographic, and histological methods. We found that the middle region of the sea turtle nasal cavity is divided into anterodorsal, anteroventral, and posterodorsal diverticula and a posteroventral excavation by connective tissue containing cartilages. The posterodorsal diverticulum was lined with a thin sensory epithelium, and the anterodorsal and anteroventral diverticula were occupied by a single thick sensory epithelium. In addition, a relatively small area on the posteroventral excavation was covered by independent sensory epithelium that differed from other 2 types of epithelia, and a single thin bundle derived from the posteroventral excavation comprised the most medial nerve that joins the anterior end of the olfactory nerve tract. These findings suggested that the posteroventral excavation identified herein transfers stimuli through an independent circuit and plays different roles when odorants arise from other nasal regions.
A Structured Framework for Adaptive Management: Bridging Theory and Practice in the Olympic Experimental State Forest
Authors: Minkova Teodora V , Arnold Jennifer S
Published: May 2019

Adaptive management is a systematic approach to learning from outcomes to improve management. Although its virtues are commonly praised, it has been implemented infrequently in natural resource management because of the challenges of developing a feasible process that can be sustained over time. Our analysis of regional experiences from private, state, and federal lands in the Pacific Northwest (United States and Canada) finds that the questions addressed by private organizations tend to be more specific, associated with a narrower scope of uncertainties, and addressed in a shorter time frame with limited stakeholder involvement. On publicly managed lands, questions tend to be more complex and open-ended, usually driven by their mandate for multiple use and high level of stakeholder engagement. We present a structured adaptive management framework that translates theory into action by describing an implementation process and organizational structure, explicitly linking learning to management planning and implementation, and integrating the technical and social aspects of adaptive management. Forest managers and policymakers can customize our example according to their mandate and management objectives. The framework is particularly relevant to land management for multiple uses, where the uncertainties are abundant and complex, and the decisionmakers increasingly use mathematical modeling to inform their decisions.
Disordered gut microbiota and alterations in metabolic patterns are associated with atrial fibrillation
Authors: Zuo Kun , Li Jing , Li Kuibao , Hu Chaowei , Gao Yuanfeng , Chen Mulei , Hu Roumu , Liu Ye , Chi Hongjie , Wang Hongjiang , Qin Yanwen , Liu Xiaoyan , Li Shichao , Cai Jun , Zhong Jiuchang , Yang Xinchun
Published: May 2019

Background

With the establishment of the heart-gut axis concept, accumulating studies suggest that the gut microbiome plays an important role in the pathogenesis of cardiovascular diseases. Yet, little evidence has been reported in characterizing the gut microbiota shift in atrial fibrillation.

Methods

We include the result of the global alterations that occur in the intestinal microbiota in a cohort of 50 patients with atrial fibrillation and 50 matched controls based on a strategy of metagenomic and metabolomic analyses.

Results

The alterations include a dramatic elevation in microbial diversity and a specific perturbation of gut microbiota composition. Overgrowth of Ruminococcus, Streptococcus, and Enterococcus, as well as reduction of Faecalibacterium, Alistipes, Oscillibacter, and Bilophila were detected in patients with atrial fibrillation. A gut microbial function imbalance and correlated metabolic pattern changes were observed with atrial fibrillation in both fecal and serum samples. The differential gut microbiome signatures could be used to identify patients with atrial fibrillation.

Conclusions

Our findings characterize the disordered gut microbiota and microbial metabolite profiles in atrial fibrillation. Further research could determine whether intervention strategies targeting intestinal microbiome composition might be useful to counteract the progression of atrial fibrillation.
Long-term virological outcomes, failure and acquired resistance in a large cohort of Ugandan children
Authors: Huibers M H W , Kityo C , Boerma R S , Kaudha E , Sigaloff K C E , Balinda S N , Bertagnolio S , Nakanjako R , Mugyenyi P , Calis J C J , Boele van Hensbroek M , Rinke de Wit T F
Published: May 2019

Objectives

To evaluate long-term virological failure (VF) and drug resistance among HIV-infected Ugandan children on first-line ART.

Methods

In a multicentre prospective cohort study, viral load (VL) and drug resistance mutations (DRMs) were investigated at baseline and 6 monthly intervals in children (age ≤ 12 years). VF (two consecutive VLs >1000 copies/mL or death after 6 months of ART) was defined as early VF (0–24 months of ART) or late VF (25–48 months of ART). An active regimen was defined as partially active if the genotypic susceptibility score (GSS) was <3.

Results

Between 2010 and 2011, 316 children were enrolled. Viral suppression was achieved in 75.8%, 71.5%, 72.6% and 69.2% at 12, 24, 36 and 48 months. VF occurred in 111/286 (38.8%), of which 67.6% was early and 32.4% late VF. Early VF was associated with a partially active regimen at baseline (OR 6.0, 95% CI 1.9–18.5), poor adherence (OR 3.1, 95% CI 1.3–7.4) and immunodeficiency (OR 3.3, 95% CI 1.1–10.2). Late VF was associated with age >3 years (OR 2.5, 95% CI 1.0–6.6) and WHO stage 3/4 (OR 4.2, 95% CI 1.4–13.4). Acquired DRMs were detected in 27.0% before 24 months, versus 14.4% after 24 months (P < 0.001). A total of 92.2% of the children with early VF, versus 56.2% with late VF, had a partially active regimen (P < 0.001).

Conclusions

VF rates were high, occurred predominantly in the first 24 months and appeared to increase again in year four. Risk factors and patterns of early VF/DRMs were different from those of late VF/DRMs. Virological control may improve by close monitoring and prompt switching to second-line therapy in the first 24 months. Late VF may be prevented by early start of ART.
Niche overlap and ecological tolerance of non-marine Ostracoda in Turkey
Authors: Külköylüoğlu Okan , Yılmaz Ozan
Published: May 2019

We applied niche overlap indices to for the first time show possible correlational occurrences among 40 non-marine ostracod taxa from seven aquatic habitats (lakes, creeks, ponds, springs, ditches, pools, troughs) in Turkey. Ecological tolerance and optimum estimates of each species were calculated and compared to explain possible reasons for habitat utilization. Eleven species were found suitable for the application of these indices. Overlap ranges of five of the species were found suitable for five variables (pH, dissolved oxygen, water temperature, electrical conductivity, and elevation; P < 0.05). Heterocypris incongruens (Ramdohr, 1808) and H. salina (Brady, 1868) were the only two species with common overlap for all the five variables. These two species generally showed common resource-utilization curves for each of these variables along with relatively similar tolerance ranges. Complete overlap was only possible for some cosmoecious species when they displayed wide-tolerance ranges and low optimum estimates for different environmental variables. Results suggest that cosmopolitan species do not only have wide geographical distributions but tolerance ranges higher than other species. Such wide tolerance ranges seem to help species coinhabit with each other and elevate their co-occurrence probabilities in different types of habitats. Applying the first usage of overlap indices on ostracods and attempting to show the relationship between niche overlap and species ecological tolerance could nevertheless provide a new tool to apply in future studies.
POLIII-derived non-coding RNAs acting as scaffolds and decoys
Authors: Täuber Hendrik , Hüttelmaier Stefan , Köhn Marcel
Published: May 2019

A large variety of eukaryotic small structured POLIII-derived non-coding RNAs (ncRNAs) have been described in the past. However, for only few, e.g. 7SL and H1/MRP families, cellular functions are well understood. For the vast majority of these transcripts, cellular functions remain unknown. Recent findings on the role of Y RNAs and other POLIII-derived ncRNAs suggest an evolutionarily conserved function of these ncRNAs in the assembly and function of ribonucleoprotein complexes (RNPs). These RNPs provide cellular `machineries’, which are essential for guiding the fate and function of a variety of RNAs. In this review, we summarize current knowledge on the role of POLIII-derived ncRNAs in the assembly and function of RNPs. We propose that these ncRNAs serve as scaffolding factors that `chaperone’ RNA-binding proteins (RBPs) to form functional RNPs. In addition or associated with this role, some small ncRNAs act as molecular decoys impairing the RBP-guided control of RNA fate by competing with other RNA substrates. This suggests that POLIII-derived ncRNAs serve essential and conserved roles in the assembly of larger RNPs and thus the control of gene expression by indirectly guiding the fate of mRNAs and lncRNAs.
Common genetic variants in the TP53 pathway and their impact on cancer
Authors: Barnoud Thibaut , Parris Joshua L D , Murphy Maureen E
Published: May 2019

The TP53 gene is well known to be the most frequently mutated gene in human cancer. In addition to mutations, there are > 20 different coding region single-nucleotide polymorphisms (SNPs) in the TP53 gene, as well as SNPs in MDM2, the negative regulator of p53. Several of these SNPs are known to alter p53 pathway function. This makes p53 rather unique among cancer-critical genes, e.g. the coding regions of other cancer-critical genes like Ha-Ras, RB, and PI3KCA do not have non-synonymous coding region SNPs that alter their function in cancer. The next frontier in p53 biology will consist of probing which of these coding region SNPs are moderately or strongly pathogenic and whether they influence cancer risk and the efficacy of cancer therapy. The challenge after that will consist of determining whether we can tailor chemotherapy to correct the defects for each of these variants. Here we review the SNPs in TP53 and MDM2 that show the most significant impact on cancer and other diseases. We also propose avenues for how this information can be used to better inform personalized medicine approaches to cancer and other diseases.
Effects of coplanar satellite bands on galactic disc evolution
Authors: Criswell Alexander , Struck Curtis
Published: May 2019

Small dwarf companions have been long thought to have minimal influence on their host galaxy’s evolution without undergoing direct impacts to the host’s disc. However, in light of recent discoveries of coplanar, corotating satellite structures around the Milky Way, Andromeda, and Centaurus A, we use an N-body/test particle simulation to show that low-mass dwarf satellites within such structures are able to exert significant influence on their host’s disc, driving spiral waves and inducing stellar scattering. This is accomplished through quasi-periodic alignments of multiple small satellites within the structure that emulate the gravitational influence of a single, larger satellite such as Sagittarius Dwarf or the Large Magellanic Cloud. We find that the coplanar, corotational nature of such structures allows for repeated alignments on short enough time-scales to overcome damping within the disc, and in a consistent enough fashion to continually drive spiral waves over the course of 2 Gyr of simulation time. The spirals driven by this phenomenon tend to be flocculent and many armed due to the irregular intervals over which alignments occur. We additionally find that while the aligned satellites are able to induce noticeable thickening of the disc, their ability to drive surface density profile evolution is secondary to other effects.
Tidal disruptions by rotating black holes: effects of spin and impact parameter
Authors: Gafton Emanuel , Rosswog Stephan
Published: May 2019

We present the results of relativistic smoothed particle hydrodynamics simulations of tidal disruptions of stars by rotating supermassive black holes, for a wide range of impact parameters and black hole spins. For deep encounters, we find that: relativistic precession creates debris geometries impossible to obtain with the Newtonian equations; part of the fluid can be launched on plunging orbits, reducing the fallback rate and the mass of the resulting accretion disc; multiple squeezings and bounces at periapsis may generate distinctive X-ray signatures resulting from the associated shock breakout; disruptions can occur inside the marginally bound radius, if the angular momentum spread launches part of the debris on non-plunging orbits. Perhaps surprisingly, we also find relativistic effects important in partial disruptions, where the balance between self-gravity and tidal forces is so precarious that otherwise minor relativistic effects can have decisive consequences on the stellar fate. In between, where the star is fully disrupted but relativistic effects are mild, the difference resides in a gentler rise of the fallback rate, a later and smaller peak, and longer return times. However, relativistic precession always causes thicker debris streams, both in the bound part (speeding up circularization) and in the unbound part (accelerating and enhancing the production of separate transients). We discuss various properties of the disruption (compression at periapsis, shape and spread of the energy distribution) and potential observables (peak fallback rate, times of rise and decay, duration of super-Eddington fallback) as a function of the impact parameter and the black hole spin.
Effect of oxygen saturation targets on the incidence of bronchopulmonary dysplasia and duration of respiratory supports in extremely preterm infants
Authors: Hanna Youstina , Laliberté Corinne , Ben Fadel Nadya , Lemyre Brigitte , Thébaud Bernard , Barrowman Nicholas , Bijelic Vid , Hoey Lynda , Katz Sherri L
Published: May 2019

Background

Recent clinical practice changes in neonatal care resulted in higher, narrower oxygen saturation target ranges for preterm infants. The effect of targeting higher or lower oxygen saturations on respiratory outcomes of preterm infants and duration of hospitalization has not been extensively reviewed in the context of current care, but could have significant implications.

Methods

A multicentre retrospective cohort of 145 preterm infants was conducted; 105 had lower oxygen saturation targets (88 to 92%), 40 had higher targets (90 to 95%). The primary outcome was bronchopulmonary dysplasia (BPD). Secondary outcomes included duration of invasive/noninvasive respiratory support, oxygen therapy, and hospitalization. The primary outcome was compared using Fisher’s exact test. Secondary outcomes were evaluated with survival analysis and Wilcoxon rank sum test.

Results

The difference in incidence of BPD in the lower (N=56, 53.3%) and higher saturation groups (N=14, 35.0%) was not statistically significant (relative risk [RR]=0.66 [0.41, 1.04], P=0.06). The difference in duration of mechanical ventilation in the lower (median 7.8 days, interquartile range [IQR] 3.7 to 15.9) and higher saturation groups (median 4.5, IQR 1.9 to 12.3) approached statistical significance (P=0.05). There were no statistically significant differences in the durations of other respiratory supports or hospital stay between the two groups.

Conclusions

The results of this study approached statistical significance and suggest that higher, narrower oxygen saturation targets may result in a clinically important reduction in BPD incidence and duration of mechanical ventilation. These results require validation in a larger sample to refine optimal targets.
Myeloid-Derived Suppressor Cells Mediate Immunosuppression After Cardiopulmonary Bypass
Authors: Hübner Max , Tomasi Roland , Effinger David , Wu Tingting , Klein Gregor , Bender Martin , Kilger Erich , Juchem Gerd , Schwedhelm Edzard , Kreth Simone
Published: May 2019

Objectives:

Cardiopulmonary bypass is associated with severe immune dysfunctions. Particularly, a cardiopulmonary bypass–related long-lasting immunosuppressive state predisposes patients to a higher risk of postoperative complications, such as persistent bacterial infections. This study was conducted to elucidate mechanisms of post-cardiopulmonary bypass immunosuppression.

Design:

In vitro studies with human peripheral blood mononuclear cells.

Setting:

Cardiosurgical ICU, University Research Laboratory.

Patients:

Seventy-one patients undergoing cardiac surgery with cardiopulmonary bypass (enrolled May 2017 to August 2018).

Interventions:

Peripheral blood mononuclear cells before and after cardiopulmonary bypass were analyzed for the expression of immunomodulatory cell markers by real-time quantitative reverse transcription polymerase chain reaction. T cell effector functions were determined by enzyme-linked immunosorbent assay, carboxyfluorescein succinimidyl ester staining, and cytotoxicity assays. Expression of cell surface markers was assessed by flow cytometry. CD15+ cells were depleted by microbead separation. Serum arginine was measured by mass spectrometry. Patient peripheral blood mononuclear cells were incubated in different arginine concentrations, and T cell functions were tested.

Measurements and Main Results:

After cardiopulmonary bypass, peripheral blood mononuclear cells exhibited significantly reduced levels of costimulatory receptors (inducible T-cell costimulator, interleukin 7 receptor), whereas inhibitory receptors (programmed cell death protein 1 and programmed cell death 1 ligand 1) were induced. T cell effector functions (interferon γ secretion, proliferation, and CD8+-specific cell lysis) were markedly repressed. In 66 of 71 patients, a not yet described cell population was found, which could be characterized as myeloid-derived suppressor cells. Myeloid-derived suppressor cells are known to impair immune cell functions by expression of the arginine-degrading enzyme arginase-1. Accordingly, we found dramatically increased arginase-1 levels in post-cardiopulmonary bypass peripheral blood mononuclear cells, whereas serum arginine levels were significantly reduced. Depletion of myeloid-derived suppressor cells from post-cardiopulmonary bypass peripheral blood mononuclear cells remarkably improved T cell effector function in vitro. Additionally, in vitro supplementation of arginine enhanced T cell immunocompetence.

Conclusions:

Cardiopulmonary bypass strongly impairs the adaptive immune system by triggering the accumulation of myeloid-derived suppressor cells. These myeloid-derived suppressor cells induce an immunosuppressive T cell phenotype by increasing serum arginine breakdown. Supplementation with L-arginine may be an effective measure to counteract the onset of immunoparalysis in the setting of cardiopulmonary bypass.
Experiencing God in Nursing
Authors: Simon Elizabeth B. , Hodges Ryan , Schoonover-Shoffner Kathy
Published: May 2019

Christian faith supports the idea that God is always at work in the world. God invites people into relationship with him and then to join in his work. Three nurses relay supernatural events where God worked in and through their nursing practice, reinforcing the understanding of what author Henry Blackaby calls experiencing God. Christian nurses are called to enter deeply into relationship with God.
Psychological Comorbidities in Childhood Celiac Disease
Authors: Coburn Shayna Skelley , Puppa Elaine Leonard , Blanchard Samra
Published: May 2019

Objectives:

Mental health disorders comorbid to chronic illness are associated with higher medical care utilization and costs for adults and children. Celiac disease (CD) has a substantial perceived treatment burden and is associated with higher rates of psychopathology in adults. However, establishing the risk for psychological comorbidities in children with CD is still needed. This study aimed to review existing research on mental health concerns in pediatric CD and propose an initial psychosocial research and clinical agenda.

Methods:

Databases, including Scopus and PubMed. Additional publications were accessed and reviewed from the references provided by initially identified publications. Two investigators screened studies using predetermined criteria (peer‐reviewed, published in English, electronically available, inclusive of child participants, and examining CD). One investigator initially extracted data, with subsequent review by the second investigator.

Results:

Twenty‐six publications met criteria for the current review (16 case‐control, 9 observational, and 1 clinical trial). Publications were heterogeneous in symptoms examined, methodology, and population characteristics. Several studies found elevated risk for psychological comorbidities and poorer quality of life in children with CD. However, many studies were limited by small sample sizes and inconsistent or nonvalidated approaches to measuring psychological symptoms.

Conclusions:

Many existing studies have found increased prevalence of comorbid CD and psychological symptoms or diagnoses. Therefore, screening for psychological symptoms in CD and also screening for CD in psychological clinic populations is needed. We have identified the importance for further study of mechanisms and risk, and identify preliminary priorities for psychosocial research and clinical care in pediatric CD.
Infant Feeding Decisions—“What’s Right for Me and My Baby?”
Authors: Sigman-Grant Madeleine
Published: May 2019

“How are you going to feed your baby?” Such a seemingly simple question. Yet, invariably, mothers will be besieged by advice as to their infant-feeding choice from well-meaning others. Such advice can be reassuring or discouraging, supportive or conflicting. Each pregnant woman deserves accurate information to form an infant-feeding decision that is right for her. That decision (whether to exclusively breastfeed, partially breastfeed, or not to breastfeed at all) will inherently conflict with the opinions of others. Only each mother is able to decide what is right for her and her infant, and that decision may need to change over time. This commentary distills the wisdom of decades of professional practice devoted to advising mothers on infant-feeding decisions.
A Comprehensive Review of Biomarker Use in the Gynecologic Tract Including Differential Diagnoses and Diagnostic Pitfalls
Authors: Hirsch Michelle S. , Watkins Jaclyn
Published: May 2019

Morphologic (ie, hematoxylin and eosin) evaluation of the Mullerian tract remains the gold standard for diagnostic evaluation; nevertheless, ancillary/biomarker studies are increasingly utilized in daily practice to assist in the subclassification of gynecologic lesions and tumors. The most frequently utilized “biomarker” technique is immunohistochemistry; however, in situ hybridization (chromogenic and fluorescence), chromosomal evaluation, and molecular analysis can also be utilized to aid in diagnosis. This review focuses on the use of immunohistochemistry in the Mullerian tract, and discusses common antibody panels, sensitivity and specificity of specific antibodies, and points out potential diagnostic pitfalls when using such antibodies.
Anatomical selectivity in overlap of chronic facial and bodily pain
Authors: Slade Gary D. , Rosen Jonathan D. , Ohrbach Richard , Greenspan Joel D. , Fillingim Roger B. , Parisien Marc , Khoury Samar , Diatchenko Luda , Maixner William , Bair Eric
Published: May 2019

Background:

Chronic facial pain often overlaps with pain experienced elsewhere in the body, although previous studies have focused on a few, selected pain conditions when assessing the degree of overlap.

Aim:

To quantify the degree of overlap between facial pain and pain reported at multiple locations throughout the body.

Methods:

Data were from a case–control study of US adults participating in the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) project. They were interviewed to determine the presence of chronic facial pain (n = 424 cases) or its absence (n = 912 controls). A mailed questionnaire with a body drawing asked about pain at other locations. Odds ratios (ORs) and 95% confidence limits (95% CLs) quantified the degree of overlap between facial pain and pain at other locations. For replication, cross-sectional data were analyzed from the UK Biobank study (n = 459,604 participants) and the US National Health Interview Survey (n = 27,731 participants).

Results:

In univariate analysis, facial pain had greatest overlap with headache (OR = 14.2, 95% CL = 9.7–20.8) followed by neck pain (OR = 8.5, 95% CL = 6.5–11.0), whereas overlap decreased substantially (ORs of 4.4 or less) for pain at successively remote locations below the neck. The same anatomically based ranking of ORs persisted in multivariable analysis that adjusted for demographics and risk factors for facial pain. Findings were replicated in the UK Biobank study and the US National Health Interview Survey. The observed anatomical selectivity in the degree of overlap could be a consequence of neurosensory and/or affective processes that differentially amplify pain according to its location.
Stillbirth in Women Living With HIV Delivering in the United Kingdom and Ireland: 2007–2015
Authors: Favarato Graziella , Townsend Claire L. , Peters Helen , Sconza Rebecca , Bailey Heather , Cortina-Borja Mario , Tookey Pat , Thorne Claire
Published: May 2019

Background:

Women living with HIV have a higher risk of adverse birth outcomes, but questions remain regarding their specific risk factors for stillbirth and the extent to which maternal HIV is associated with stillbirth.

Methods:

Using data on pregnant women with HIV reported within population-based surveillance in the United Kingdom/Ireland, we described stillbirth rates in 2007–2015 stratified by type of antiretroviral therapy (ART) and evaluated risk factors using Poisson regression. General population stillbirth rates by maternal world region of origin were derived from national annual birth statistics, and compared with rates in women with HIV, using standardized stillbirth ratios with the general population as the reference.

Results:

Between 2007 and 2015, there were 10,434 singleton deliveries in 8090 women with HIV; 75% of pregnancies were in women of African origin; and 49% were conceived on ART. The stillbirth rate was 8.5 (95% confidence interval: 6.9 to 10.5) per 1000 births. Risk factors for stillbirth included pre-eclampsia, diabetes, Asian maternal origin (versus United Kingdom/Ireland), CD4 count <350 cells/mm3, older maternal age, and primiparity. Conceiving on ART did not increase the risk. The stillbirth rates (per 1000 births) by type of ART were 14.3, 11.7, 8.3, and 6.0, respectively for NVP + XTC/TDF–, LPV/r + 3TC/ZDV–, NVP + XTC/ABC–, and NVP + XTC/ZDV–exposed pregnancies (P value = 0.40). The standardized stillbirth ratio was 129 (95% confidence interval: 101 to 165) in women with HIV compared with the general population.

Conclusion:

After adjusting for maternal origin, the stillbirth rate remained higher in women with HIV than the general population. We recommend further studies to understand and prevent this excess.
Plasmodium PIMMS43 is required for ookinete evasion of the mosquito complement-like response and sporogonic development in the oocyst
Authors: Ukegbu Chiamaka V. , Giorgalli Maria , Tapanelli Sofia , Rona Luisa D.P. , Jaye Amie , Wyer Claudia , Angrisano Fiona , Blagborough Andrew M. , Christophides George K. , Vlachou Dina
Published: May 2019

Malaria transmission requires Plasmodium parasites to successfully infect a female Anopheles mosquito, surviving a series of robust innate immune responses. Understanding how parasites evade these responses can highlight new ways to block malaria transmission. We show that ookinete and sporozoite surface protein PIMMS43 is required for Plasmodium ookinete evasion of the Anopheles coluzzii complement-like system and for sporogonic development in the oocyst. Disruption of P. berghei PIMMS43 triggers robust complement activation and ookinete elimination upon mosquito midgut traversal. Silencing the complement-like system restores ookinete-to-oocyst transition. Antibodies that bind PIMMS43 interfere with parasite immune evasion when ingested with the infectious blood meal and significantly reduce the prevalence and intensity of infection. PIMMS43 genetic structure across African P. falciparum populations indicates allelic adaptation to sympatric vector populations. These data significantly add to our understanding of mosquito-parasite interactions and identify PIMMS43 as a target of interventions aiming at malaria transmission blocking.

Author summary

Malaria is a devastating disease transmitted among humans through mosquito bites. Mosquito control has significantly reduced clinical malaria cases and deaths in the last decades. However, as mosquito resistance to insecticides is becoming widespread impacting on current control tools, such as insecticide impregnated bed nets and indoor spraying, new interventions are urgently needed, especially those that target disease transmission. Here, we characterize a protein found on the surface of malaria parasites, which serves to evade the mosquito immune system ensuring disease transmission. Neutralization of PIMMS43, either by eliminating it from the parasite genome or by pre-incubating parasites with antibodies that bind to the protein, is shown to inhibit mosquito infection by malaria parasites. Differences in PIMMS43 detected between malaria parasite populations sampled across Africa suggest that these populations have adapted for transmission by different mosquito vectors that are also differentially distributed across the continent. We conclude that interventions targeting PIMMS43 could block malaria parasites inside mosquitoes before they can infect humans.
A compositional letter code in high-level visual cortex explains how we read jumbled words
Authors: Agrawal Aakash , Hari K.V.S. , Arun S. P.
Published: May 2019

We read words and even jubmled wrods effortlessly, but the neural representations underlying this remarkable ability remain unknown. We hypothesized that word processing is driven by a visual representation that is compositional i.e. with string responses systematically related to letters. To test this hypothesis, we devised a model in which neurons tuned to letter shape respond to longer strings by linearly summing letter responses. This letter model explained human performance in both visual search as well as word reading tasks. Brain imaging revealed that viewing a string activates this compositional letter code in the lateral occipital (LO) region, and that subsequent comparisons to known words are computed by the visual word form area (VWFA). Thus, seeing a word activates a compositional letter code that enables efficient reading.
Markov chains applied to molecular evolution simulation
Authors: Ortega Joel Valdivia
Published: May 2019

Today we are able to describe genome evolution but, there are still several open questions on this area such as: Which is the probability that a mutation occurs at a nucleotide level? Is it possible to predict the evolution of a particular genome?, or talking about preservation, is there a way to simulate the genetic diversity for endangered species? In this paper it is shown that it is possible to make a mathematical model not only of mutations on the genome of species, but of evolution itself, including factors such as artificial and natural selection. It is also presented the algorithm to obtain the probabilities of mutation for each specific part of the genome and for each specie. The potential of having this tool is giantic going from genetic engineering applied to medicine to filling up blank spaces in phylogenetic studies or preservation of endangered species due to genetic diversity.
Distinct effects of amyloid and tau deposition on eigenvector centrality during hippocampal down-regulation: a real-time fMRI virtual reality closed-loop neurofeedback study with CSF biomarkers
Authors: Skouras Stavros , Torner Jordi , Andersson Patrik , Koush Yury , Falcon Carles , Minguillon Carolina , Fauria Karine , Alpiste Francesc , Blenow Kaj , Zetterberg Henrik , Gispert Juan D. , Molinuevo José L. ,   for the ALFA Study
Published: May 2019

Hippocampal down-regulation is associated with genetic predisposition to Alzheimer’s disease (AD), neurodevelopmental processes and disease symptoms. Resting state eigenvector centrality (EC) patterns resemble those of FDG-PET in AD, they can predict self-regulation performance and they are related to functional compensation across the pathophysiological continuum of AD. We acquired cerebrospinal fluid (CSF) biomarkers from a cognitively unimpaired sample at risk for AD (N=48), to investigate the effect of β- amyloid peptide 42 (Aβ42) and phosphorylated tau (p-Tau) levels on EC during the down-regulation of hippocampal subfield cornu ammonis 1, with real-time fMRI closed-loop neurofeedback. Controlling the effects of confounding variables (age, sex, number of APOE ε4 alleles, cognitive reserve, brain reserve and hippocampal down-regulation performance), CSF Aβ42 levels correlated positively with EC in the anterior cingulate cortex (BA24, BA32) and primary motor cortex (BA4). CSF p-Tau levels correlated with EC positively in the ACC (BA32, BA10) ventral striatum (caudate, nucleus accumbens, putamen) and left primary somatosensory cortex (BA2), as well as negatively in the posterior cingulate cortex, precuneus, cuneus and left frontal pole (BA9). Controlling for CSF biomarkers and other prognosis variables, age correlated negatively with EC in the midcingulate cortex, insula, primary somatosensory cortex (BA2) and inferior parietal lobule (BA40), as well as positively with EC in the inferior temporal gyri. Taken together, we identified patterns of functional connectomics in individuals at risk of AD during hippocampal down-regulation, which resemble those found during resting state at advanced AD stages. Moreover, we provide a standard paradigm to replicate and extend this work on a global level. This opens new avenues for further research applications, which quantify and monitor disease progression, by identifying early alterations in the self-regulation of brain function, with potential for non-invasive prognostic screening.

Highlights

ACC centrality decreases with early Aβ42

ACC centrality increases with p-Tau

PCC centrality decreases with p-Tau

MCC centrality decreases in healthy aging
A Protein Kinase A-Regulated Network Encodes Short- and Long-Lived Cellular Memory
Authors: Jiang Yanfei , AkhavanAghdam Zohreh , Li Yutian , Zid Brian M. , Hao Nan
Published: May 2019

Cells can store memories of prior experiences to modulate their responses to subsequent stresses, as seen for the protein kinase A (PKA)-mediated general stress response in yeast, which is required for resistance against future stressful conditions. Using microfluidics and time-lapse microscopy, we quantitatively analyzed how cellular memory of stress adaptation is encoded in single yeast cells. We found that cellular memory is biphasic. Short-lived memory was mediated by trehalose synthase and trehalose metabolism. Long-lived memory was mediated by PKA-regulated stress-responsive transcription factors and cytoplasmic messenger ribonucleoprotein (mRNP) granules. Strikingly, short- and long-lived memory could be selectively induced by different priming input dynamics. Computational modeling revealed how the PKA-mediated regulatory network could encode previous stimuli into memories with distinct dynamics. This biphasic memory-encoding scheme, analogous to innate and adaptive immune responses in mammals, might represent a general strategy to prepare for future challenges in rapidly changing environments.
Serum Alpha-2-Macroglobulin as an intrinsic radioprotective factor in patients undergoing thoracic radiation therapy
Authors: von Reibnitz Donata , Yorke Ellen D. , Oh Jung Hun , Apte Aditya P. , Yang Jie , Pham Hai , Thor Maria , Wu Abraham J. , Fleisher Martin , Gelb Emily , Deasy Joseph O. , Rimner Andreas
Published: May 2019

Objective

To investigate the impact of alpha-2-macroglobulin (A2M), a suspected intrinsic radioprotectant, on radiation pneumonitis and esophagitis. Additionally, we establish multifactorial predictive models for pneumonitis and esophagitis.

Materials/Methods

Baseline A2M levels were obtained for 258 patients prior to thoracic radiotherapy (RT). Dose-volume characteristics were extracted from treatment plans. Spearman’s correlation (Rs) test was used to correlate A2M levels, smoking status and dosimetric variables with toxicities. Esophagitis and pneumonitis prediction models were built using least absolute shrinkage and selection operator (LASSO) logistic regression on 1000 bootstrapped datasets. Models were built using 2/3 of the data for training and 1/3 for validation.

Results

There were 36 (14.0%) patients with grade ≥2 pneumonitis and 61 (23.6%) with grade ≥2 esophagitis. The median A2M level was 191 mg/dL (range: 94-511). Never/former/current smoker status was 47 (18.2%)/179 (69.4%)/32 (12.4%). We found a significant correlation between baseline A2M levels and esophagitis (Rs=-0.18/p=0.003) and between A2M and smoking status (former or current) (Rs=0.13/p=0.04) but not between A2M and pneumonitis. On univariate analysis, significant parameters for grade ≥2 esophagitis included number of fractions (Rs=0.47/p<0.0001), treatment days (Rs=0.44/p<0.0001), chemotherapy use (Rs=0.40/p<0.0001), dose per fraction (Rs=-0.34/p<0.0001), total dose (Rs=0.29/p<0.0001), age (Rs=-0.22/p=0.0003), and several dosimetric variables in esophagus with Rs>0.5 (p<0.0001). For pneumonitis, significant clinical parameters were treatment days (Rs=0.24/p=0.0001), chemotherapy use (Rs=0.22/p=0.0004), number of fractions (Rs=0.21/p=0.0007), dose per fraction (Rs=-0.18/p=0.0035), and total dose (Rs=0.15/p=0.013). The most significant dosimetric variable in lung and heart was D70 (Rs=0.28/p<0.0001) and max dose (Rs=0.27/p<0.0001), respectively. LASSO bootstrap logistic regression models on the validation data resulted in the area under the receiver operating characteristic curve of 0.84 and 0.75 for esophagitis and pneumonitis, respectively.

Conclusion

Our findings show an association of higher A2M values with lower risk of radiation esophagitis and smoking status. Multivariate predictive models also confirmed a role of heart dose in the risk of pneumonitis.
A systematic investigation on the involvement of complement pathway in diabetic retinopathy
Authors: Shahulhameed Shahna , Vishwakarma Sushma , Chhablani Jay , Tyagi Mudit , Pappuru Rajeev R , Chakrabarti Subhabrata , Kaur Inderjeet
Published: May 2019

Background

Complement system play a crucial role in retinal homeostasis. Several proteomic studies have shown deposition of complement protein in ocular tissues from diabetic retinopathy, however, their exact involvement in pathogenesis of DR remains unclear.

Methods

We evaluated major complement pathway proteins in the classical and alternative pathway including C1q, C4b, C3, CFB and CFH in vitreous humor and serum samples from PDR patients and controls by western blotting. Quantitative real time (QRT) PCR was done for PDR, NPDR and no-DM controls for correlating the expression of several key pro and anti -angiogenic genes with their correspondingprotein levels. Inflammation in the vitreous humor samples was assessed by ELISA and metalloproteinase activity measured by gelatin zymography. Glial activation and its association with complement activation in diabetic eyes was assessed by immunohistochemistry.

Results

A significant increase in C3 proteins, its activated fragment C3bα’ (110kDa) along with a concurrent up regulation of CFH was observed for PDR vitreous. QRT identified a significant upregulation of angiogenic genes and downregulation of antiangiogenic genes in PDR and NPDR cases. PDR vitreous had increased MMP9 activity and upregulation of inflammatory markers IL8, sPECAM and down regulation of anti-inflammatory marker IL-10. Increased C3 deposition and CFH upregulation were observed in DM retina. CFH was found co-localizing with CD11b+ve activated microglial cells in inner nuclear layer of DM retina.

Conclusions

The present study confirms increased activation of alternative complement pathway in PDR. The co-localization of CFH in CD11b +ve cells further suggests microglia as a source of CFH in diabetic retina. Increased CFH levels could be a feedback mechanism for arresting excessive complement activation DR eyes.