bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoxia-induced transcription factor signaling is essential for larval growth of the mosquitoAedes aegypti
Authors: Valzania Luca , Coon Kerri L. , Vogel Kevin J. , Brown Mark R. , Strand Michael R.
Published: January 2018

Significance

Gut microbes positively affect the physiology of many animals, but the molecular mechanisms underlying these benefits remain poorly understood. Recent studies indicate that gut bacteria reduce oxygen levels in the mosquito gut, which serves as a growth signal. Here, we report that transduction of a bacteria-induced low-oxygen signal requires mosquito-encoded hypoxia-inducible transcription factors (HIFs). Our results further indicate that HIFs activate several processes with essential growth and metabolic functions. These findings can potentially be used to disrupt mosquito development into adults that transmit human diseases.
Natesto®. What Else? New Trends in Drug Naming
Authors: Faure Pascaline
Published: January 2018

This paper is a lexicological study of the brand names of newly FDA (Food and Drug Administration) approved drugs which aims at highlighting the new trends observed in drug naming. For our corpus, we used a listing of 320 drugs approved by the FDA for sale in the United States for the years 2012 to 2017. In our study, we showed that the commonly used letters X and Z were giving way to A and O endings so as to attract Romance languages speaking clients. We demonstrated that this trend matched a less recent ploy in food and automotive marketing. We focused on the “Vowel/Consonant+lexeme” matrix that is found almost exclusively in the drug industry because it permits to create a name shorter in writing – an advantage for prescribers. Although the FDA recommended that “unsubstantial beneficial” connotations be banned, we uncovered the presence of promotional affixes as well as hidden emotional contents that are meant to be persuasive.
Oligomeric forms of bacterial malate dehydrogenase: a study of the enzyme from the phototrophic non-sulfur bacterium Rhodovulum steppense A-20s
Authors: Eprintsev Alexander T , Falaleeva Marina I , Lyashchenko Maya S , Toropygin Ilya Y , Igamberdiev Abir U
Published: January 2018

Malate dehydrogenase (EC 1.1.1.37) was purified to homogeneity from the phototrophic purple non-sulfur bacterium Rhodovulum steppense A-20s. According to gel-chromatography and electrophoretic studies, malate dehydrogenase is present as a dimer, tetramer and octamer depending on cultivation conditions. In phototrophic aerobic conditions only the tetrameric form was present, in chemotrophic aerobic conditions all three forms were detected, while in the absence of oxygen the octameric form disappeared. The malate dehydrogenase oligomers are encoded by a single gene and composed of the same 35 kDa polypeptide but differ in pH and temperature optimum, in affinities to malate, oxaloacetate, NADH and NAD+ and in regulation by cations and citrate. By modulating the cultivation conditions, it has been established that the dimer participates in the glyoxylate cycle; the tetramer operates in the tricarboxylic acid cycle, and the octamer may be involved in the adaptation to oxidative stress.
Carbon-free production of 2-deoxy-scyllo-inosose (DOI) in cyanobacterium Synechococcus elongatus PCC 7942
Authors: Watanabe Satoru , Ozawa Hiroaki , Kato Hiroaki , Nimura-Matsune Kaori , Hirayama Toshifumi , Kudo Fumitaka , Eguchi Tadashi , Kakinuma Katsumi , Yoshikawa Hirofumi
Published: January 2018

Owing to their photosynthetic capabilities, there is increasing interest in utilizing cyanobacteria to convert solar energy into biomass. 2-Deoxy-scyllo-inosose (DOI) is a valuable starting material for the benzene-free synthesis of catechol and other benzenoids. DOI synthase (DOIS) is responsible for the formation of DOI from d-glucose-6-phosphate (G6P) in the biosynthesis of 2-deoxystreptamine-containing aminoglycoside antibiotics such as neomycin and butirosin. DOI fermentation using a recombinant Escherichia coli strain has been reported, although a carbon source is necessary for high-yield DOI production. We constructed DOI-producing cyanobacteria toward carbon-free and sustainable DOI production. A DOIS gene derived from the butirosin producer strain Bacillus circulans (btrC) was introduced and expressed in the cyanobacterium Synechococcus elongatus PCC 7942. We ultimately succeeded in producing 400 mg/L of DOI in S. elongatus without using a carbon source. DOI production by cyanobacteria represents a novel and efficient approach for producing benzenoids from G6P synthesized by photosynthesis.
Acoustic change complex for frequency changes
Authors: Kalaiah Mohan Kumar
Published: January 2018

Purpose:

Acoustic change complex (ACC) reflects brain’s capacity to discriminate the acoustic features present in the signal, hence serves as an index of discrimination capacity. ACC for intensity changes and gaps-in-noise have consistently shown that the ACC threshold is consistent with behavioral intensity discrimination and gap detection thresholds. While, the ACC threshold for frequency change is found to be highly variable. The present study was carried out to investigate the agreement between behavioral frequency discrimination threshold and the ACC threshold for frequency change.

Methods:

Ten young adults with normal hearing in both ears participated in the study. The ACC was elicited using frequency changing tones, with a frequency change of 5, 10, 25, 50, 100 and 200 Hz.

Results:

The present study showed that a greater frequency change is required to elicit the ACC compared to behavioral discrimination threshold. In most of the participants, a frequency change greater than 50 Hz was required to elicit the ACC. Magnitude of frequency change had effect on latency and amplitude of peaks of the ACC, amplitude was higher and latency was shorter for greater frequency change.

Conclusion:

ACC threshold for frequency change does not resemble behavioral discrimination threshold and is variable across participants.
Effectively closed subgroups of the infinite symmetric group
Authors: Greenberg Noam , Melnikov Alexander , Nies Andre , Turetsky Daniel
Published: January 2018

We apply methods of computable structure theory to study effectively closed subgroups of

S
∞

S_\infty

. The main result of the paper says that there exists an effectively closed presentation of

Z

2

\mathbb {Z}_2

which is not the automorphism group of any computable structure

M
M

. In contrast, we show that every effectively closed discrete group is topologically isomorphic to

A
u
t

(
M
)

\rm {Aut}(M)

for some computable structure

M
M

. We also prove that there exists an effectively closed compact (thus, profinite) subgroup of

S
∞

S_\infty

that has no computable Polish presentation. In contrast, every profinite computable Polish group is topologically isomorphic to an effectively closed subgroup of

S
∞

S_\infty

. We also look at oligomorphic subgroups of

S
∞

S_\infty

; we construct a

Σ
1
1

\Sigma ^1_1

closed oligomorphic group in which the orbit equivalence relation is not uniformly HYP. Our proofs rely on methods of computable analysis, techniques of computable structure theory, elements of higher recursion theory, and the priority method.
A note on the Petersen-Wilhelm conjecture
Authors: González-Álvaro David , Radeschi Marco
Published: January 2018

In this note we consider submersions from compact manifolds, homotopy equivalent to the Eschenburg or Bazaikin spaces of positive curvature. We show that if the submersion is nontrivial, the dimension of the base is greater than the dimension of the fiber. Together with previous results, this proves the Petersen-Wilhelm conjecture for all the known compact manifolds with positive curvature.
Ricci iteration on homogeneous spaces
Authors: Pulemotov Artem , Rubinstein Yanir
Published: January 2018

The Ricci iteration is a discrete analogue of the Ricci flow. We give the first study of the Ricci iteration on a class of Riemannian manifolds that are not Kähler. The Ricci iteration in the non-Kähler setting exhibits new phenomena. Among them is the existence of so-called ancient Ricci iterations. As we show, these are closely related to ancient Ricci flows and provide the first nontrivial examples of Riemannian metrics to which the Ricci operator can be applied infinitely many times. In some of the cases we study, these ancient Ricci iterations emerge (in the Gromov–Hausdorff topology) from a collapsed Einstein metric and converge smoothly to a second Einstein metric. In the case of compact homogeneous spaces with maximal isotropy, we prove a relative compactness result that excludes collapsing. Our work can also be viewed as proposing a dynamical criterion for detecting whether an ancient Ricci flow exists on a given Riemannian manifold as well as a method for predicting its limit.
On compact 3-manifolds with nonnegative scalar curvature with a CMC boundary component
Authors: Miao Pengzi , Xie Naqing
Published: January 2018

We apply the Riemannian Penrose inequality and the Riemannian positive mass theorem to derive inequalities on the boundary of a class of compact Riemannian

3
3

-manifolds with nonnegative scalar curvature. The boundary of such a manifold has a CMC component, i.e., a

2
2

-sphere with positive constant mean curvature; and the rest of the boundary, if nonempty, consists of closed minimal surfaces. A key step in our proof is the construction of a collar extension that is inspired by the method of Mantoulidis-Schoen.
PICK1 is essential for insulin production and the maintenance of glucose homeostasis
Authors: Li Jia , Mao Zhuo , Huang Jiandong , Xia Jun
Published: January 2018

Protein interacting with C-kinase 1 (PICK1) is a peripheral membrane protein that controls insulin granule formation, trafficking, and maturation in INS-1E cells. However, global Pick1-knockout mice showed only a subtle diabetes-like phenotype. This raises the possibility that compensatory effects from tissues other than pancreatic beta cells may obscure the effects of insulin deficiency. To explore the role of PICK1 in pancreatic islets, we generated mice harboring a conditional Pick1 allele in a C57BL/6J background. The conditional Pick1-knockout mice exhibited impaired glucose tolerance, profound insulin deficiency, and hyperglycemia. In vitro experiments showed that the ablation of Pick1 in pancreatic beta cells selectively decreased the initial rapid release of insulin and the total insulin levels in the islets. Importantly, the specific ablation of Pick1 induced elevated proinsulin levels in the circulation and in the islets, accompanied by a reduction in the proinsulin processing enzymes prohormone convertase 1/3 (PC1/3). The deletion of Pick1 triggered the specific elimination of chromogranin B in pancreatic beta cells, which is believed to control granule formation and release. Collectively, these data demonstrate the critical role of PICK1 in secretory granule biogenesis, proinsulin processing, and beta cell function. We conclude that the beta cell–specific deletion of Pick1 in mice led to hyperglycemia and eventually to diabetes.
How to do (or not to do) … a health financing incidence analysis
Authors: Ataguba John E , Asante Augustine D , Limwattananon Supon , Wiseman Virginia
Published: January 2018

Financing incidence analysis (FIA) assesses how the burden of health financing is distributed in relation to household ability to pay (ATP). In a progressive financing system, poorer households contribute a smaller proportion of their ATP to finance health services compared to richer households. A system is regressive when the poor contribute proportionately more. Equitable health financing is often associated with progressivity. To conduct a comprehensive FIA, detailed household survey data containing reliable information on both a cardinal measure of household ATP and variables for extracting contributions to health services via taxes, health insurance and out-of-pocket (OOP) payments are required. Further, data on health financing mix are needed to assess overall FIA. Two major approaches to conducting FIA described in this article include the structural progressivity approach that assesses how the share of ATP (e.g. income) spent on health services varies by quantiles, and the effective progressivity approach that uses indices of progressivity such as the Kakwani index. This article provides some detailed practical steps for analysts to conduct FIA. This includes the data requirements, data sources, how to extract or estimate health payments from survey data and the methods for assessing FIA. It also discusses data deficiencies that are common in many low- and middle-income countries (LMICs). The results of FIA are useful in designing policies to achieve an equitable health system.
In-Store Spending Dynamics: How Budgets Invert Relative-Spending Patterns
Authors: Sheehan Daniel , Van Ittersum Koert
Published: January 2018

The authors conduct four controlled lab experiments and one field study in a brick-and-mortar grocery store to demonstrate that relative spending—the price of the purchased item relative to the mean price of the product category—evolves nonlinearly and distinctly for budget and nonbudget shoppers. While the relative spending of budget shoppers evolves in a concave manner, the relative spending of nonbudget shoppers evolves inversely in a convex manner. Thus, budget (nonbudget) shoppers spend relatively more (less) in the middle than at the beginning and toward the end of their shopping trip. Mediation analyses confirm that the pain of paying experienced while shopping drives price salience, which then drives relative spending. Moreover, manipulating shoppers’ pain of paying, by altering the opportunity costs associated with their spending or drawing shoppers’ attention to their spending via real-time spending feedback, is shown to influence these spending patterns. The research offers theoretical contributions to the in-store decision-making, budgeting, and pain-of-paying literature and has important implications for marketing and promotion strategies in retail and mobile technology environments, as it suggests when a shopper may be more sensitive to price-related factors.
Policing Intimate Partner Violence: The ‘Golden Thread’ of Discretion
Authors: Barlow Charlotte , Walklate Sandra
Published: January 2018

This paper offers a critical appreciation of pro-arrest-positive policing policies towards intimate partner violence (IPV). It examines the extent to which such policies, and the research associated with them, have operated within a partial understanding of discretion, which has paid detailed attention to the response of the front-line officer and how that response might be changed either by improved training and/or by rule tightening. Such approaches assume that policing IPV is separate and separable from policing other forms of violence(s) and fail to recognize the wider context of the policing task. This paper makes the case for a more holistic understanding of discretion (to include senior officers) as a way of promoting improved responses to IPV. This also means directing attention to policies and practices in relation to IPV to include police engagement with broader agency and societal responses to IPV. This is the point at which a holistic ‘golden thread’ of discretion can be found.
Association Between Loss of Type IV Pilus Synthesis Ability and Phenotypic Variation in the Cucurbit Pathogenic Bacterium Acidovorax citrulli
Authors: Rosenberg Tally , Salam Bolaji Babajide , Burdman Saul
Published: January 2018

Acidovorax citrulli is the causal agent of bacterial fruit blotch of cucurbits. We have shown that functional type IV pili (T4P) are required for full virulence of this bacterium. To identify A. citrulli genes required for T4P activity, we screened a library of about 10,000 transposon mutants of A. citrulli M6 for altered T4P-mediated twitching motility. This screen led to the identification of 50 mutants impaired in twitching ability due to transposon insertions into 20 different genes. Representative mutants with disruptions in these genes were further characterized. All mutants were compromised in their virulence in seed transmission and stem inoculation assays and had reduced biofilm formation ability relative to wild-type M6. When grown on nutrient agar, most mutants produced colonies with a translucent and fuzzy appearance, in contrast to the opaque and smooth appearance of wild-type colonies. The colony morphology of these mutants was identical to that of previously reported phenotypic variants of strain M6. The exceptions were M6 mutants disrupted in genes tonB, pilT, pilW, and pilX that exhibited typical wild-type colony morphology, although lacking twitching haloes surrounding the colony. Transmission electron microscopy revealed that most mutants lacked the ability to produce T4P. The exceptions were mutants with disruptions in tonB, pilT, pilW, and pilX genes that were shown to produce these appendages. These findings support the idea that colony phenotypic variation in A. citrulli is determined by the lack of ability to synthesize T4P but not by lack of T4P functionality.
Colonization and Movement of Xanthomonas fragariae in Strawberry Tissues
Authors: Wang Hehe , McTavish Christine , Turechek William W.
Published: January 2018

Xanthomonas fragariae causes angular leaf spot of strawberry, an important disease in strawberry growing regions worldwide. To better understand how X. fragariae multiplies and moves in strawberry plants, a green fluorescent protein (GFP)-labeled strain was constructed and used to monitor the pathogen’s presence in leaf, petiole, and crown tissue with fluorescence microscopy following natural and wound inoculation in three strawberry cultivars. Taqman PCR was used to quantify bacterial densities in these same tissues regardless of the presence of GFP signal. Results showed X. fragariae colonized leaf mesophyll, the top 1 cm portion of the petiole adjacent to the leaf blade, and was occasionally found colonizing xylem vessels down to the middle of the petioles. The colonization of vascular bundles and the limited systemic movement that was observed appeared to be a passive process, of which the frequency increased with wounding and direct infiltration of bacteria into leaf veins. X. fragariae was able to directly enter petioles and colonize the space under the epidermis. Systemic movement of the bacteria into crown and other uninoculated tissues was not detected visually by GFP. However, X. fragariae was occasionally detected in these tissues by qPCR, but at quantities very near the qPCR detection limit. Petiole tissue harboring bacteria introduced either by direct entry through natural openings or wounds, or by systemic movement from infected foliar tissue, likely serves as a main source of initial inoculum in field plantings.
Mesenteric Oxygenation Changes Associated With Necrotizing Enterocolitis and Pneumoperitoneum After Multiple Blood Transfusions
Authors: Marin Terri , Moore James E.
Published: January 2018

Background:

The multifactorial pathology and broad clinical presentation of necrotizing enterocolitis (NEC) development in premature infants make prediction of disease onset extremely challenging. Over the past decade, packed red blood cell (PRBC) transfusions have been temporally linked to the development of NEC in severely anemic preterm infants, although this issue is highly controversial.

Purpose:

In this case study, we describe events of an extremely low birth-weight infant who developed NEC complicated by pneumoperitoneum after receiving multiple PRBC transfusions. Specifically, we describe mesenteric tissue oxygenation trend changes as measured by continuous near-infrared spectroscopy (NIRS) technology.

Methods:

As part of a larger prospective, observational investigation, this infant was monitored with NIRS (INVOS 5100C; Medtronic, Boulder, Colorado) before, during, and 48 hours following PRBC transfusions.

Results:

The infant demonstrated severe, prolonged, and persistent reductions in mesenteric tissue oxygenation following blood transfusions, yet routine physiologic monitoring did not indicate intestinal hypoperfusion or impending NEC onset.

Implications for Practice:

This report demonstrates the ability of NIRS to capture possible tissue ischemia during early stages of NEC that may help guide bedside therapeutic interventions.

Implications for Research:

Larger cohort studies to evaluate the ability of NIRS to capture early tissue ischemia are essential to validate the feasibility of adding this technology as a routine clinical bedside tool.

Video Abstract available at
https://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx.
Disease modifying actions of interleukin-6 blockade in a rat model of bone cancer pain
Authors: Remeniuk Bethany , King Tamara , Sukhtankar Devki , Nippert Amy , Li Nancy , Li Fuying , Cheng Kejun , Rice Kenner C. , Porreca Frank
Published: January 2018

Metastasis of cancer to the skeleton represents a debilitating turning point in the lives of patients. Skeletal metastasis leads to moderate to severe ongoing pain along with bone remodeling that can result in fracture, events that dramatically diminish quality of life. Interleukin-6 (IL-6) levels are elevated in patients with metastatic breast cancer and are associated with a lower survival rate. We therefore determined the consequences of inhibition of IL-6 signaling using a novel small molecule antagonist, TB-2-081, on bone integrity, tumor progression, and pain in a rodent model of breast cancer. Rat MAT B III mammary adenocarcinoma cells were injected and sealed within the tibia of female Fischer rats. Growth of these cells within the rat tibia elicited increased IL-6 levels both within the bone exudate and in the plasma, produced ongoing pain and evoked hypersensitivity, and bone fracture that was observed by approximately day 12. Systemic TB-2-081 delivered by subcutaneous osmotic minipumps starting at tumor implantation prevented tumor-induced ongoing bone pain and evoked hypersensitivity without altering tumor growth. Remarkably, TB-2-081 infusion significantly reduced osteolytic and osteoblastic bone remodeling and time to fracture likely by decreasing osteoclastogenesis and associated increase in bone resorption. These findings indicate that blockade of IL-6 signaling may represent a viable, disease-modifying strategy to prevent tumor-induced bone remodeling allowing for stabilization of bone and decreased fractures as well as diminished ongoing pain that may improve quality of life of patients with skeletal metastases. Notably, anti-IL-6 antibodies are clinically available allowing for rapid testing of these possibilities in humans.
Forensic Nursing State of the Science: Research and Practice Opportunities
Authors: Drake Stacy A. , Koetting Cathy , Thimsen Kathi , Downing Nancy , Porta Carolyn , Hardy Peggy , Valentine Julie L. , Finn Cris , Engebretson Joan
Published: January 2018

Introduction:

The International Association of Forensic Nurses (IAFN) is the only nursing organization advancing the forensic nursing specialty. The organization seeks to advance the profession, and one mechanism for doing so is development of a research agenda.

Methods:

The purpose of this action-based research study was to aid in the development of a forensic nursing research agenda. The study was carried out in two integral stages: (a) focus groups with IAFN members attending the annual conference and (b) reviewing posted IAFN member listserv material.

Results:

The findings of this study identified similar gaps of other nursing specialties experiencing “growing pains,” including role confusion and variation in educational preparation.

Conclusion:

Findings from this study will inform development of the IAFN 5-year research agenda to advance forensic nursing science and evidence-based practice.
Therapeutic Advances in Hyponatremia: Fluids, Diuretics, Vaptans, and More
Authors: Yang Shu , Goldin Mark
Published: January 2018

Background:

Hyponatremia is frequently encountered in geriatric patients and is associated with significant morbidity and mortality. Traditional management approaches have targeted underlying causes—such as volume repletion with normal saline in dehydrated patients, loop diuretics and fluid restriction in hypervolemic patients, and fluid restriction and salt tablets in euvolemic patients. Elderly patients are at particular risk of hypovolemic hyponatremia because of dehydration, as well as the syndrome of inappropriate antidiuretic hormone. In addition to fluid restriction, syndrome of inappropriate antidiuretic hormone may be treated with demeclocycline, lithium, and urea, although these agents are limited by side effects. Loop diuretics are standard therapy for hyponatremia in congestive heart failure, cirrhosis, or nephrotic syndrome; although these agents, and to a greater extent thiazide diuretics, can cause hyponatremia and should be used cautiously. In severe hyponatremia, standard therapy is the infusion of hypertonic (3%) saline. Judicious monitoring is paramount, as rapid overcorrection is associated with central pontine myelinolysis.

Areas of Uncertainty:

Although these therapies are well established, the gravity of improper sodium correction has led to uncertainty and varying dosing strategies. Hypertonic saline infusion rates may be weight based or standardized and can be used concurrently with deamino-delta-d-arginine vasopressin. As well, loop diuretics vary considerably in metabolism and half-life, and choice of agent may have implications for mortality in congestive heart failure. Finally, even the simple strategy of fluid restriction may not apply to patients with highly concentrated urine.

Therapeutic Advances:

Unresolved questions around treatment of hyponatremia have spurred development of newer therapeutics, notably arginine vasopressin receptor blockers or vaptans, which have been shown to be effective in the treatment of euvolemic and hypervolemic chronic hyponatremia. In 2 randomized, double-blind, placebo-controlled multicenter trials (SALT-1 and SALT-2), tolvaptan significantly increased serum sodium at days 4 and 30 in 448 patients with mean baseline serum sodium 129 meq/L. Furthermore, vaptans can cause liver damage, and the FDA has cautioned against their use in patients with underlying liver disease. The cost of vaptans has been a major barrier, but this may be offset by decreases in length of stay in hospitalized patients.

Conclusions:

Vaptans have shown promise in the treatment of euvolemic and hypervolemic chronic hyponatremia but have not shown long-term mortality benefits.
Reversal of Anticoagulation: Therapeutic Advances and Clinical Guidelines
Authors: Goldin Mark , Hughes Gregory J. , Choudhary Zunaira , Tariq Sara , Shafeeq Hira , Cohen Jessica
Published: January 2018

Background:

Anticoagulants are life-saving medications that prevent and treat thromboembolic disease and are of particular importance in the elderly population for prevention of stroke in atrial fibrillation. The advent of direct oral anticoagulants and reversal agents has yielded more options for patients, although complicating clinical decision-making.

Areas of Uncertainty:

The decision to anticoagulate in atrial fibrillation depends on the risks of stroke versus bleeding. The accompanying HAS-BLED score for predicting bleeding allows an estimation of net clinical benefit. Despite these tools, uncertainty remains. Notably, anticoagulation has traditionally been avoided in patients with recurrent falls. Yet, decision analytic modeling has shown that patients on warfarin would need hundreds of falls annually to warrant discontinuation. At the same time, direct oral anticoagulants, while theoretically simpler to dose than warfarin, should be dose-reduced or avoided in cases of renal impairment, extreme age or weight, or concomitant use of strong P-glycoprotein and/or CYP3A4 inducers/inhibitors.

Therapeutic Advances:

Prothrombin complex concentrates consist of endogenous coagulation factors and anticoagulants. One 4-factor prothrombin complex concentrates (factors II, VII, IX, X, proteins C, and S), when administered with intravenous vitamin K, effectively reversed warfarin in cases of life-threatening bleeding or need for urgent surgery/procedure in 2 phase IIIb trials, although it may be associated with thrombogenesis. Idarucizumab, a humanized monoclonal antibody, reversed dabigatran-associated bleeding in 11.4 hours in a late-stage trial and had no effect on thrombin in pharmacodynamic studies. Andexanet alfa, a recombinant molecule derived from factor X, is a class-specific reversal agent for factor Xa inhibitors. In trials of healthy individuals (ANNEXA-A, ANNEXA-R), andexanet alfa reversed apixaban and rivaroxaban, although increased levels of d-Dimer and prothrombin fragments 1 and 2, suggesting potential thrombogenesis; the later stage ANNEXA-4 trial is ongoing. Finally, ciraparantag, a small water-soluble molecule, reversed edoxaban and enoxaparin in phase 1/2 trials (by whole blood clotting time), and holds promise as a potential universal reversal agent.
KLF1 E325K-associated Congenital Dyserythropoietic Anemia Type IV: Insights Into the Variable Clinical Severity
Authors: Ravindranath Yaddanapudi , Johnson Robert M. , Goyette Gerard , Buck Steven , Gadgeel Manisha , Gallagher Patrick G.
Published: January 2018

We identified a child with KLF1-E325K congenital dyserythropoietic anemia type IV who experienced a severe clinical course, fetal anemia, hydrops fetalis, and postnatal transfusion dependence only partially responsive to splenectomy. The child also had complete sex reversal, the cause which remains undetermined. To gain insights into our patient’s severe hematologic phenotype, detailed analyses were performed. Erythrocytes from the patient and parents demonstrated functional abnormalities of the erythrocyte membrane, attributed to variants in the α-spectrin gene. Hypomorphic alleles in SEC23B and YARS2 were also identified. We hypothesize that coinheritance of variants in relevant erythrocyte genes contribute to the clinical course in our patient and other E325K-linked congenital dyserythropoietic anemia IV patients with severe clinical phenotypes.
The Effect of Music on Dyspnea Severity, Anxiety, and Hemodynamic Parameters in Patients With Dyspnea
Authors: Ergin Eda , Sagkal Midilli Tulay , Baysal Ebru
Published: January 2018

This randomized controlled study (pretest, posttest, test control group) was conducted with the aim of determining the effect of music on the severity of dyspnea, anxiety, and hemodynamic parameters in patients with dyspnea. The research was conducted in the Chest Diseases Service of a public hospital in the western region of Turkey. The number of patients included in the sample was determined by power analysis, and as a result, 60 patients were accepted, 30 in the music group and 30 in the control group. Sixty percent of the patients who took part in the study were male, their mean age was 61.21 ± 1.13 years, and their mean dyspnea severity before the intervention was 62.68 ± 22.28. The difference between the mean dyspnea severity and anxiety scores of the music group patients before and after the application of music was found to be statistically significant (P < .05), but no statistically significant difference was found in hemodynamic parameters (P > .05). In light of the research findings, it was concluded that music had an effect on anxiety and the severity of dyspnea in patients with dyspnea but that it had no effect on hemodynamic parameters.
Palliative Nursing Summit
Authors: Paice Judith A. , Battista Vanessa , Drick Carol Ann , Schreiner Ellyn
Published: January 2018

Effective pain and symptom management is a crucial part of the care of those with life-threatening illnesses and their family members. Nurses in all settings have a vital role in providing this essential care. A recent summit held on May 12, 2017, “Nurses Leading Change and Transforming Palliative Care,” convened by the Hospice and Palliative Nurses Association and attended by leaders of 26 nursing organizations strongly endorsed the importance of nursing's role in pain and symptom management and developed an agenda to advance these efforts. The agreed-upon goals of pain and symptom treatment include care that is effective (as defined by the patient), efficient (delivered in a timely manner), and safe (reduced risk of respiratory depression, prevention and early management of adverse effects, as well as attention to methods to prevent diversion such as safe storage and disposal). Through an iterative process, desired patient outcomes and nursing actions were outlined to support effective pain and symptom management in primary palliative care. These recommendations were categorized as education, clinical care, research, and regulatory concerns. This article reports on the outcomes of this summit related to pain and symptom management.
Palliative Nursing Summit
Authors: Head Barbara Anderson , Song Mi-Kyung , Wiencek Clareen , Nevidjon Brenda , Fraser Debbie , Mazanec Polly
Published: January 2018

Advance care planning (ACP) is an essential component of quality palliative care that requires expert communication skills. Nurses are often the health care provider patients and families rely on when exploring their values and preferences and making treatment decisions. Therefore, communication and ACP was one of the 3 areas of practice addressed during the Palliative Nursing Summit. This article summarizes patient outcomes and nursing actions recommended by summit participants related to communication and ACP. Areas addressed included education, clinical care, research, and policy/regulation. Recommended patient outcomes included the honoring of patient/family preferences and the inclusion of ACP discussions during routine care and across the life span. Recommended nursing actions included the following: (1) nursing education (both undergraduates and practicing nurses) and competencies related to communication and ACP be developed and implemented; (2) primary palliative care, including communication and ACP, be included in the practice standards of all nursing specialties; (3) health care systems support conversations about ACP and related documentation; (4) research be conducted related to the implementation of patient/family preferences and related health care utilization; and (5) regulation and reimbursement be crafted to support nursing practice related to ACP and related conversations at the nurses' full level of expertise.
Improving Antibiotic Prescribing for Children With Urinary Tract Infection in Emergency and Urgent Care Settings
Authors: Poole Nicole M. , Kronman Matthew P. , Rutman Lori , Weissman Scott J. , Migita Russell T. , Caglar Derya , Zerr Danielle M.
Published: January 2018

Objectives

Children with urinary tract infection (UTI) are often diagnosed in emergency and urgent care settings and increasingly are unnecessarily treated with broad-spectrum antibiotics. This study evaluated the effect of a quality improvement intervention on empiric antibiotic prescribing for the treatment of uncomplicated UTI in children.

Methods

A local clinical pathway for uncomplicated UTI, introduced in June 2010, recommended empiric treatment with cephalexin, a narrow-spectrum (first-generation) cephalosporin antibiotic. A retrospective quasi-experimental study of pediatric patients older than 1 month presenting to emergency and urgent care settings from January 1, 2009, to December 31, 2014, with uncomplicated UTI was conducted. Hospitalized patients and those with chronic conditions or urogenital abnormalities were excluded. Control charts and interrupted time-series analysis were used to analyze the primary outcome of narrow-spectrum antibiotic prescribing rates and the balancing measures of 72-hour revisits, resistant bacterial isolates, and subsequent inpatient admissions for UTI.

Results

A total of 2134 patients were included. There was an immediate and sustained significant increase in cephalexin prescribing before (19.2%) versus after (79.6%) pathway implementation and a concurrent significant decline in oral third-generation cephalosporin (cefixime) prescribing from 50.3% to 4.0%. There was no significant increase in 72-hour revisits, resistant bacterial isolates, or inpatient admissions for UTI.

Conclusions

A clinical pathway produced a significant and sustained increase in narrow-spectrum empiric antibiotic prescribing for pediatric UTI. Increased empiric cephalexin prescribing did not result in increased treatment failures or adverse patient outcomes. Future studies on implementing clinical pathways for children outside a pediatric hospital network are needed.
The Effect of Early Knowledge of Respiratory Syncytial Virus Positivity on Medical Decision Making and Throughput Time Within the Pediatric Emergency Department
Authors: Schnell Jessica , Schroeder Lisa , Sinclair Kelly , Patel Lina , Dowd Denise
Published: January 2018

Objective

The aim of this study was to evaluate whether early knowledge of respiratory syncytial virus (RSV) positivity by rapid triage-based testing protocol improved emergency department (ED) throughput time and decreased ED ancillary testing and antibiotic administration.

Methods

A retrospective cohort study was performed of ED patients aged 2 to 12 months, presenting November 1 to March 31 for the years 2008–2013. Included patients presented with fever and upper respiratory tract symptoms. Patients were excluded if they tested positive for influenza, had chronic underlying medical problems, or were admitted or transferred from an outside facility or if no RSV result was documented. The study group was compared with infants who tested negative for RSV by the triage-based protocol and were diagnosed as having (1) bronchiolitis and (2) a viral illness.

Results

Of 899 patients tested for RSV within triage, the study included 713 (79%); 231 (35.3%) tested positive for RSV. When comparing children diagnosed as having bronchiolitis, there was no statistically significant difference between RSV positive and negative in ED throughput time, ED administered antibiotics, or chest radiographs, urine analyses, blood cultures, or lumbar punctures obtained. When comparing children diagnosed as having a viral illness, RSV-positive patients had less chest radiographs, urine analysis, and blood cultures performed.

Conclusions

Identifying the virus responsible for bronchiolitis through a triage-based protocol does not decrease ED throughput time, antibiotic administration, or chest radiographs, urine analysis, or blood cultures obtained. In infants presenting with upper respiratory tract symptoms and fever, knowing RSV infectivity through a triage-based protocol does significantly decrease chest radiographs, urine analysis, and blood cultures obtained.
Accessory Spleen Fracture
Authors: Chauvet Eline , Spyropoulou Vasiliki , Anooshiravani-Dumont Mehrak , Sanchez Oliver , Lacroix Laurence
Published: January 2018

Accessory spleen rupture may occur after blunt abdominal trauma or, more rarely, spontaneously. Although only few cases are described in adults, it is even more uncommon in children. We report the case of a 13-year-old boy with traumatic accessory spleen fracture. After a review of the literature, we discuss the diagnostic points that should raise the suspicion for accessory spleen fracture as well as how challenging the diagnosis by computed tomography can be.
Deletion/loss of bone morphogenetic protein 7 changes tooth morphology and function in
Mus musculus:
implications for dental evolution in mammals
Authors: Zurowski Chelsey , Jamniczky Heather , Graf Daniel , Theodor Jessica
Published: January 2018

Quantifying regulatory gene effects on dental morphology and function has implications for the underlying mechanisms that generated dental diversity in mammals. We tested the hypothesis that regulatory gene expression changes lead to differences in molars using a neural crest knockout of bone morphogenetic protein 7 (BMP7) in
Mus musculus
. Three-dimensional geometric morphometric methods were used to quantify the shape of the molar toothrow. BMP7 mutants have extra cusps on the first upper and lower molars, and alterations in cusp orientation and morphology. Furthermore, significant shape differences between control and mutant were found for upper and lower toothrows. Mutant mice also exhibited differences in attrition facets, indicating functional changes that could lead to advantages in chewing new food resources and eventually niche diversification. The size ratio of the molars in the toothrow remained unchanged, implying that BMP7-induced changes in molar size ratio are a result of knocking out epithelial, rather than neural crest, expression of BMP7. Our results indicate that changes in BMP7 expression are sufficient to alter the morphology and function of the toothrow, suggesting that BMP7 or genes affecting its function could have played a role in structuring the dental diversity of extinct and extant mammals.
Stabilization of golden cages by encapsulation of a single transition metal atom
Authors: Li Hui-Fang , Wang Huai-Qian
Published: January 2018

Golden cage-doped nanoclusters have attracted great attention in the past decade due to their remarkable electronic, optical and catalytic properties. However, the structures of large golden cage doped with Mo and Tc are still not well known because of the challenges in global structural searches. Here, we report anionic and neutral golden cage doped with a transition metal atom MAu
16
(M = Mo and Tc) using Saunders ‘Kick' stochastic automation search method associated with density-functional theory (DFT) calculation (SK-DFT). The geometric structures and electronic properties of the doped clusters, MAu
16

q

(M = Mo and Tc;
q
 = 0 and −1), are investigated by means of DFT theoretical calculations. Our calculations confirm that the 4d transition metals Mo and Tc can be stably encapsulated in the Au
16
−
cage, forming three different configurations, i.e. endohedral cages, planar structures and exohedral derivatives. The ground-state structures of endohedral cages
C
2v
Mo@Au
16
−
-(a) and C
1
Tc@Au
16
−
-(b) exhibit a marked stability, as judged by their high binding energy per atom (greater than 2.46 eV), doping energy (0.29 eV) as well as a large HOMO–LUMO gap (greater than 0.40 eV). The predicted photoelectron spectra should aid in future experimental characterization of MAu
16
−
(M = Mo and Tc).
Matter rogue waves for the three-component Gross–Pitaevskii equations in the spinor Bose–Einstein condensates
Authors: Sun Wen-Rong , Wang Lei
Published: January 2018

To show the existence and properties of matter rogue waves in an
F
=1 spinor Bose–Einstein condensate (BEC), we work on the three-component Gross–Pitaevskii (GP) equations. Via the Darboux-dressing transformation, we obtain a family of rational solutions describing the extreme events, i.e. rogue waves. This family of solutions includes bright–dark–bright and bright–bright–bright rogue waves. The algebraic construction depends on Lax matrices and their Jordan form. The conditions for the existence of rogue wave solutions in an
F
=1 spinor BEC are discussed. For the three-component GP equations, if there is modulation instability, it is of baseband type only, confirming our analytic conditions. The energy transfers between the waves are discussed.
Does flutter prevent drag reduction by reconfiguration?
Authors: Leclercq T. , Peake N. , de Langre E.
Published: January 2018

The static reconfiguration of flexible beams exposed to transverse flows is classically known to reduce the drag these structures have to withstand. But the more a structure bends, the more parallel to the flow it becomes, and flexible beams in axial flows are prone to a flutter instability that is responsible for large inertial forces that drastically increase their drag. It is, therefore, unclear whether flexibility would still alleviate, or on the contrary enhance, the drag when flapping occurs on a reconfiguring structure. In this article, we perform numerical simulations based on reduced-order models to demonstrate that the additional drag induced by the flapping motion is almost never significant enough to offset the drag reduction due to reconfiguration. Isolated and brief snapping events may transiently raise the drag above that of a rigid structure in the particular case of heavy, moderately slender beams. But apart from these short peak events, the drag force remains otherwise always significantly reduced in comparison with a rigid structure.
Comparative RNA-seq based transcriptomic analysis of Aspergillus nidulans recombinant strains overproducing heterologous glycoside hydrolases
Authors: Calzado Felipe , Zubieta Mariane P. , Persinoti Gabriela F. , Fanchini Terrasan Cesar Rafael , Rubio Marcelo V. , Contesini Fabiano J. , Squina Fabio M. , Damasio André
Published: January 2018

Filamentous fungi are important cellular factories for the production and secretion of homologous and heterologous enzymes such as carbohydrate-active enzymes. However, the regulation of protein secretion in these microorganisms requires more profound studies since the enzyme levels produced are usually below the levels required by industry for profitable processes. Genomic and transcriptomic approaches have been used to understand the overexpression and production of heterologous enzymes and their capacity to induce different cellular biological processes. To investigate this regulation, Aspergillus nidulans recombinant strains were analyzed by transcriptomics. We designed three A. nidulans recombinant strains producing the following heterologous proteins: alpha-arabinofuranosidase (AbfA), beta-glucosidase (BglC) and thermophilic mannanase (Tp-Man5). The heterologous genes abfA and bglC were highly expressed, while tp-man5 mRNA levels were low and similar to those of a reference gene. There was an indirect relationship between mRNA and protein secretion levels, suggesting that transcription is not a bottleneck for target gene expression in this system. Despite the distinct features of the recombinant proteins, 30 differentially expressed genes were common to all the recombinant strains, suggesting that these genes represent a general response to the expression of heterologous genes. We also showed that the early activation of the canonical unfolded protein response (UPR) pathway by hacA alternative splicing was normalized after 8h, except in the strain expressing BglC, suggesting either no accumulation of the BglC misfolded form or the presence of an alternative endoplasmic reticulum (ER) stress and UPR pathway. Finally, to focus our analysis on the secretion pathway, a set of 374 genes was further evaluated. Seventeen genes were common to all the recombinant strains, suggesting again that these genes represent a general response of A. nidulans cells to the overexpression of recombinant genes, even thermophilic genes. Additionally, we reported the possible genetic interactions of these 17 genes based on coexpression network calculations. Interestingly, protein improvements are nongeneric, and improvements in the production of one target protein are not necessarily transferable to another one. Thus, this study may provide genetic and cellular background and targets for genetic manipulation to improve protein secretion by A. nidulans.
DAtest: a framework for choosing differential abundance or expression method
Authors: Russel Jakob , Thorsen Jonathan , Brejnrod Asker D. , Bisgaard Hans , Sørensen Søren J. , Burmølle Mette
Published: January 2018

DAtest is an R package for directly comparing different statistical methods for differential abundance and expression analysis on a dataset of interest; be it data from RNA-seq, proteomics, metabolomics or a microbial marker-gene survey. A myriad of statistical methods exists for conducting these analyses, and with this tool we give the analyst an empirical foundation for choosing a method suitable for a specific dataset. The package supports categorical and quantitative variables, paired/block experimental designs, and the inclusion of covariates. It is freely available at GitHub: https://github.com/Russel88/DAtest along with detailed instructions.