bluuebunny/crossref_metadata_2025 huggingface dataset:
Faecal Calprotectin Predicts Endoscopic and Histological Activity in Clinically Quiescent Ulcerative Colitis
Authors: Hart Lara , Chavannes Mallory , Kherad Omar , Maedler Chelsea , Mourad Nathalie , Marcus Victoria , Afif Waqqas , Bitton Alain , Lakatos Peter L , Brassard Paul , Bessissow Talat
Published: June 2019

Introduction

Faecal calprotectin [FC] is a reliable surrogate marker for disease activity in ulcerative colitis [UC]; however, there are no consensus cut-off values for remission. The study aim was to correlate FC with Mayo Endoscopic Score [MES] and histological disease activity of UC patients in clinical remission.

Methods

Our study recruited adult UC patients at the McGill IBD Center between 2013 and 2017. Patients in clinical remission [partial Mayo score ≤2], undergoing endoscopy for disease activity or dysplasia surveillance, were enrolled. Before bowel preparation, FC was collected. MES was documented during colonoscopy. Biopsies were taken; histological activity was assessed using Geboes score and the presence of basal plasmacytosis.

Results

A total of 185 patients were recruited. The area under the curve [AUC] in receiver operating characteristic [ROC] analysis to predict MES 1–3 [from 0] was 0.743 [95% CI 0.67–0.82; p <0.001] with an FC cut-off value 170 µg/g [64% sensitivity, 74% specificity], and to predict MES 2–3 [from 0–1] was 0.722 [95% CI 0.61–0.83; p <0.001] with an FC cut-off value 170 µg/g [69% sensitivity, 65% specificity]. To differentiate MES 0 from MES 1, an FC value 130 µg/g yields a 70% sensitivity and 68% specificity. The AUC in ROC analysis to predict Geboes <3.1 was 0.627 [95% CI 0.55–0.71; p = 0.003], with an FC value 135 µg/g [54% sensitivity, 69% specificity].

Conclusions

In this large study, FC ≥170 µg/g predicts endoscopic activity and FC ≥135 µg/g predicts histological activity. Therefore in clinical practice, lower faecal calprotectin thresholds can be chosen to optimise identification of patients with ongoing endoscopic and histological disease activity.
IM-UNITI: Three-year Efficacy, Safety, and Immunogenicity of Ustekinumab Treatment of Crohn’s Disease
Authors: Hanauer Stephen B , Sandborn William J , Feagan Brian G , Gasink Christopher , Jacobstein Douglas , Zou Bin , Johanns Jewel , Adedokun Omoniyi J , Sands Bruce E , Rutgeerts Paul , de Villiers Willem J S , Colombel Jean-Frédéric , Ghosh Subrata
Published: June 2019

Background and Aims

Following induction/maintenance treatment in the UNITI/IM-UNITI studies of ustekinumab for Crohn’s disease, patients entered a long-term extension for up to 5 years from induction. Efficacy through 152 and safety through 156 weeks are reported.

Methods

At IM-UNITI Week 44, 567 ustekinumab-treated patients entered the long-term extension and continued to receive blinded subcutaneous ustekinumab on their assigned dose interval, without any subsequent dose adjustment. Placebo-treated patients discontinued after study unblinding [after IM-UNITI Week 44 analyses]. Efficacy data in the long-term extension [LTE] were collected every 12 weeks [q12w] before unblinding and then at q12w/q8w dosing visits.

Results

Through Week 156, 29.6% of ustekinumab-treated patients discontinued. In an intent-to-treat analysis of randomised patients from IM-UNITI Weeks 0–152, 38.0% of ustekinumab induction responders receiving the drug q12w and 43.0% q8w were in remission at Week 152. Among patients entering the long-term extension in their original randomised groups, 61.9% of q12w and 69.5% of q8w patients were in remission at Week 152. Across all ustekinumab-treated patients [randomised and non-randomised] entering the long-term extension, remission rates at Week 152 were 56.3% and 55.1% for q12w and q8w, respectively. Safety events [per 100 patient-years] were similar among all ustekinumab-treated patients entering the long-term extension and placebo [overall adverse events 389.70 vs 444.17; serious adverse events, 18.97 vs 19.54; serious infections, 4.21 vs 3.97]. Rates of antibodies to ustekinumab through Week 156 remained low, 4.6% in all randomised ustekinumab-treated patients; lowest among patients in the original randomised q8w group [2/82, 2.4%].

Conclusions

Continued treatment with subcutaneous ustekinumab maintained clinical response and remission through 3 years in a majority of patients who responded to induction therapy and was well-tolerated. ClinicalTrials.gov number NCT01369355.
Remission of Inflammatory Bowel Disease in Glucose-6-Phosphatase 3 Deficiency by Allogeneic Haematopoietic Stem Cell Transplantation
Authors: Bolton Chrissy , Burch Nicola , Morgan James , Harrison Beth , Pandey Sumeet , Pagnamenta Alistair T ,   Oxford IBD cohort investigators, Arancibia Carolina , Bailey Adam , Barnes Ellie , Bird-Lieberman Beth , Brain Oliver , Braden Barbara , Collier Jane , East James , Geremia Alessandra , Howarth Lucy , Leedham Simon , Palmer Rebecca , Rodrigues Astor , Simmons Alison , Sullivan Peter , Taylor Jenny C , Taylor John M , Marsh Judith C W , Potter Victoria , Travis Simon , Uhlig Holm H
Published: June 2019

Mendelian disorders in glucose-6-phosphate metabolism can present with inflammatory bowel disease [IBD]. Using whole genome sequencing we identified a homozygous variant in the glucose-6-phosphatase G6PC3 gene [c.911dupC; p.Q305fs*82] in an adult patient with congenital neutropenia, lymphopenia and childhood-onset, therapy-refractory Crohn’s disease. Because G6PC3 is expressed in several haematopoietic and non-haematopoietic cells it was unclear whether allogeneic stem cell transplantation [HSCT] would benefit this patient with intestinal inflammation. We show that HSCT resolves G6PC3-associated immunodeficiency and the Crohn’s disease phenotype. It illustrates how even in adulthood, next-generation sequencing can have a significant impact on clinical practice and healthcare utilization in patients with immunodeficiency and monogenic IBD.
A Spanish composite Rex Virginum Mass and the Beata Virgine Maria Mass tradition in Europe
Authors: Cuenca Rodríguez María Elena
Published: June 2019

Concepts of ‘centre’ and ‘periphery’ in Renaissance music studies have sometimes been the cause of oversights concerning points of contact and cultural exchange between the musical ‘mainstream’—represented by the northern European and Italian circles—and the Spanish kingdoms. Musicians from the Iberian Peninsula—among them, Francisco de Peñalosa—were well aware of musical developments in the Franco-Netherlandish polyphonic tradition, and incorporated some of these into their Mass composition throughout the 16th century.

This article presents a case study of the Rex Virginum composite Mass, with sections by Pedro de Escobar, Francisco de Peñalosa, Pedro Hernández [de Castilleja] and Alonso Pérez de Alba. This Mass is directly connected with the popularity of votive Beata Virgine Maria Masses composed by Franco-Netherlandish and later Spanish composers. In order to shed more light on the significance of this work, the different musical styles of each composer involved in its creation are examined, and the Mass compared with other Beata Virgine Maria models. Through this analysis, the distinct musical contribution of this Mass in the context of European Renaissance music, and its influence on later generations of Spanish composers—especially Francisco Guerrero—are examined.
MgrB affects the acid stress response of Escherichia coli by modulating the expression of iraM
Authors: Xu Jintian , Li Ting , Gao Yunrong , Deng Jiaoyu , Gu Jing
Published: June 2019

Although MgrB is established to be a feedback inhibitor of the PhoP/Q system in Escherichia coli, the biological functions of MgrB remain largely unknown. To explore new functions of MgrB, a comparative transcriptome analysis was performed (E. coli K-12 W3110 ΔmgrB vs E. coli K-12 W3110). The results showed that many genes involved in acid stress are upregulated, suggesting that MgrB is related to acid sensitivity in E. coli. The survival rates under acid stress of the ΔmgrB mutant and wild-type showed that deletion of mgrB resulted in acid resistance. According to previous research, we deleted phoP, phoQ and iraM in the ΔmgrB mutant, and found that further deletion of phoP/phoQ only partially restored acid sensitivity. Additionally, we found that deletion of mgrB resulted in increased accumulation of RpoS during the exponential growth phase, which could be blocked by further deletion of iraM. Mutation of iraM or rpoS completely suppressed the effect of mgrB mutation on acid resistance. Taken together, the data suggest that MgrB affects the acid resistance of E. coli by modulating the expression of iraM, but not completely through PhoP/Q. This indicates that MgrB may have other protein interactors aside from PhoQ, which merits further investigation.
Experimental models to study intestinal microbes–mucus interactions in health and disease
Authors: Etienne-Mesmin Lucie , Chassaing Benoit , Desvaux Mickaël , De Paepe Kim , Gresse Raphaële , Sauvaitre Thomas , Forano Evelyne , de Wiele Tom Van , Schüller Stephanie , Juge Nathalie , Blanquet-Diot Stéphanie
Published: June 2019

A close symbiotic relationship exists between the intestinal microbiota and its host. A critical component of gut homeostasis is the presence of a mucus layer covering the gastrointestinal tract. Mucus is a viscoelastic gel at the interface between the luminal content and the host tissue that provides a habitat to the gut microbiota and protects the intestinal epithelium. The review starts by setting up the biological context underpinning the need for experimental models to study gut bacteria-mucus interactions in the digestive environment. We provide an overview of the structure and function of intestinal mucus and mucins, their interactions with intestinal bacteria (including commensal, probiotics and pathogenic microorganisms) and their role in modulating health and disease states. We then describe the characteristics and potentials of experimental models currently available to study the mechanisms underpinning the interaction of mucus with gut microbes, including in vitro, ex vivo and in vivo models. We then discuss the limitations and challenges facing this field of research.
A Hierarchical View of Gecko Locomotion: Photic Environment, Physiological Optics, and Locomotor Performance
Authors: Higham Timothy E , Schmitz Lars
Published: June 2019

Terrestrial animals move in complex habitats that vary over space and time. The characteristics of these habitats are not only defined by the physical environment, but also by the photic environment, even though the latter has largely been overlooked. For example, numerous studies of have examined the role of habitat structure, such as incline, perch diameter, and compliance, on running performance. However, running performance likely depends heavily on light level. Geckos are an exceptional group for analyzing the role of the photic environment on locomotion as they exhibit several independent shifts to diurnality from a nocturnal ancestor, they are visually-guided predators, and they are extremely diverse. Our initial goal is to discuss the range of photic environments that can be encountered in terrestrial habitats, such as day versus night, canopy cover in a forest, fog, and clouds. We then review the physiological optics of gecko vision with some new information about retina structures, the role of vision in motor-driven behaviors, and what is known about gecko locomotion under different light conditions, before demonstrating the effect of light levels on gecko locomotor performance. Overall, we highlight the importance of integrating sensory and motor information and establish a conceptual framework as guide for future research. Several future directions, such as understanding the role of pupil dynamics, are dependent on an integrative framework. This general framework can be extended to any motor system that relies on sensory information, and can be used to explore the impact of performance features on diversification and evolution.
Is the Commonwealth’s approach to rights constitutionalism exportable?
Authors: Stephenson Scott
Published: June 2019

This article considers whether the Commonwealth’s approach to rights constitutionalism, associated with the bills of rights adopted in Australia, Canada, New Zealand, and the UK, might be suitable for other jurisdictions around the world. It argues that three questions are particularly relevant to evaluating the strength of the normative case for the Commonwealth’s approach. First, what is the nature of the disagreements about rights in a jurisdiction? Second, what options do institutions have to challenge the determinations on rights of other institutions? Third, what are the other objectives of the constitutional system? The article considers how the answers to these questions yield insights into the circumstances in which the Commonwealth’s approach may prove to be more attractive or unattractive. In particular, it suggests that the normative case for the Commonwealth’s approach may be weaker in dominant party systems.
Splittings and Symbolic Powers of Square-free Monomial Ideals
Authors: Montaño Jonathan , Núñez-Betancourt Luis
Published: June 2019

We study the symbolic powers of square-free monomial ideals via symbolic Rees algebras and methods in prime characteristic. In particular, we prove that the symbolic Rees algebra and the symbolic associated graded algebra are split with respect to a morphism that resembles the Frobenius map and that exists in all characteristics. Using these methods, we recover a result by Hoa and Trung that states that the normalized $a$-invariants and the Castelnuovo–Mumford regularity of the symbolic powers converge. In addition, we give a sufficient condition for the equality of the ordinary and symbolic powers of this family of ideals and relate it to Conforti–Cornuéjols conjecture. Finally, we interpret this condition in the context of linear optimization.
Do You See What I See? An Assessment of Endoscopic Lesions Recognition and Description by Gastroenterology Trainees and Staff Physicians
Authors: Hart Lara , Chavannes Mallory , Lakatos Peter L , Afif Waqqas , Bitton Alain , Bressler Brian , Bessissow Talat
Published: June 2019

Background

Gastroenterologists should accurately describe endoscopic findings and integrate them into management plans. We aimed to determine if trainees and staff are describing inflammatory bowel disease (IBD) lesions in a similar manner.

Methods

Using 20 ileocolonoscopy images, participants described IBD inflammatory burden based on physician severity rating, and Mayo endoscopic score (MES) (ulcerative colitis [UC]) or simple endoscopic score (SES-CD) (Crohn’s disease [CD]). Images were selected based on agreement by three IBD experts. Findings of varying severity were presented; 10 images included a question about management. We examined inter-observer agreement among trainees and staff, compared trainees to staff, and determined accuracy of response comparing both groups to IBD experts.

Results

One hundred and twenty-nine staff and 47 trainees participated from across Canada. There was moderate inter-rater agreement using physician severity rating (κ = 0.53 UC and 0.52 CD for staff, κ = 0.51 UC and 0.43 CD for trainees). There was moderate inter-rater agreement for MES for staff and trainees (κ = 0.49 and 0.48, respectively), but fair agreement for SES-CD (κ = 0.37 and 0.32, respectively). For accuracy of response, the mean score was 68.7% for staff and 63.7% for trainees (P = 0.028). Both groups identified healed bowel or severe disease better than mild/moderate (P < 0.05). There was high accuracy for management, but staff scored higher than trainees for UC (P < 0.01).

Conclusion

Inter-rater agreement on description of IBD lesions was moderate at best. Staff and trainees more accurately describe healed and severe disease, and better describe lesions in UC than CD.
Mortality Rate of House Flies (Diptera: Muscidae) Exposed to Insecticidal Granular Fly Baits Containing Indoxacarb, Dinotefuran, or Cyantraniliprole
Authors: Zahn Levi K , Cox David L , Gerry Alec C
Published: June 2019

The mortality rate of a field population of house fly (Musca domestica L.) was determined for a granular fly bait containing the active ingredient indoxacarb, which was compared to two commercially available granular fly baits containing either dinotefuran or cyantraniliprole. Indoxacarb was applied at three different application rates 0.498, 0.986, and 1.972 g/m2 (low, medium, and high). Time to 50% mortality was fastest for dinotefuran (5.7 h) and slowest for the low application rate of indoxacarb (10.3 h). Time to 90% mortality was fastest for the high application rate of indoxacarb (27.7 h) and slowest for dinotefuran (51.0 h) and cyantraniliprole (45.9 h). Among the three indoxacarb application rates, the high rate reached both 50 and 90% fly mortality significantly faster than the low rate. The medium rate did not significantly differ from either the high or low application rates. Dinotefuran bait produced greater fly mortality than all other treatments at 30-min post-exposure, with mortality for remaining baits exceeding controls by 3- to 6-h post-exposure. All insecticidal baits produced similar fly mortality by 6-h post-exposure and >94% fly mortality by 96-h post-exposure, indicating that each may be effective in a fly management program. Flies consumed a similar amount of the indoxacarb (regardless of application rate) and dinotefuran baits, but consumed less of the cyantraniliprole bait, suggesting a feeding irritancy or toxicity effect manifested during consumption. Nevertheless, flies consumed enough cyantraniliprole bait to cause mortality similar to other baits by 6-h post-exposure.
Resistance Risk Evaluated by Metaflumizone Selection and the Effects on Toxicities Over Other Insecticides in Spodoptera exigua (Lepidoptera: Noctuidae)
Authors: Sun Xing-Xing , Li Hong-Yang , Jiang Ying-Jie , Zhang Jun-Xi , Gu Hui-Ling , Gao Bo , Ma Jing-Jing , Wang Fan , Zhou Jia-Chun , Tian Xiang-Rui , Su Jianya , Wang Kai
Published: June 2019

Metaflumizone is a novel semicarbazone insecticide. It functions as a sodium channel blocker insecticide (SCBI) with excellent insecticidal activity on most economically important lepidopterous pests. This study assessed the resistance risk of Spodoptera exigua (Hübner) (Lepidoptera: Noctuidae) to metaflumizone in the laboratory and the effects of metaflumizone selection on toxicities to other insecticides. Spodoptera exigua collected from a field population at Huizhou in 2012 were successively challenged by metaflumizone to evaluate the risk of resistance evolution. Twelve generations of selection increased resistance to metaflumizone by 3.4-fold and threshold trait analysis revealed that the realized heritability (h2) of this resistance was 0.086. When h2 was equal to 0.086 and 90% of individuals were killed at each generation, LC50 to metaflumizone increased by 10-fold after 15 generations. The selection by metaflumizone did not increase the resistance to indoxacarb, chlorantraniliprole, spinosad, methomyl, or endosulfan, suggesting a lack of cross-resistance. However, metaflumizone challenge upheld the recession of resistance to emamectin benzoate, chlorfluazuron, and tebufenozide. The block of resistance drops by metaflumizone exposure implied a possible cross-resistance between metaflumizone and these three insecticides. These results contribute to integrated resistance management of S. exigua.
Update From the Advisory Committee on Immunization Practices
Authors: O’Leary Sean T , Maldonado Yvonne A , Kimberlin David W
Published: June 2019

The Advisory Committee on Immunization Practices (ACIP), a group of medical and public health experts, meets 3 times per year to develop recommendations for vaccine use in the United States. The group usually has 15 voting members, each of whom is appointed to a 4-year term. ACIP members and Centers for Disease Control and Prevention staff discuss the epidemiology of vaccine-preventable diseases and vaccine research, effectiveness, safety data, and clinical trial results. Representatives from the American Academy of Pediatrics (Y. A. M. and D. W. K.) and the Pediatric Infectious Diseases Society (S. T. O.) are present as liaisons to the ACIP. The ACIP met February 27 to 28, 2019, to discuss hepatitis A (HepA) vaccination of human immunodeficiency virus–infected persons, pneumococcal vaccination among adults aged 65 years or older, influenza vaccine effectiveness and safety, anthrax vaccination in the setting of a mass exposure, human papillomavirus vaccine, zoster vaccines, and Japanese encephalitis vaccine.
Radiation doses with various body weights of phantoms in brain 128-slice MDCT examination
Authors: Lin Hung-Chih , Lai Te-Jen , Tseng Hsien-Chun , Wang Ching-Hsiang , Tseng Yen-Ling , Chen Chien-Yi
Published: June 2019

The effective dose (HE) and organ or tissue equivalent dose (HT) for use in brain computed tomography (CT) examinations with various body weights were evaluated. Thermoluminescent dosimeters (TLD-100H) were inserted into Rando and five anthropomorphic phantoms. These phantoms were made of polymethylmethacrylate (PMMA), according to the specifications of ICRU 48, with masses from 10 to 90 kg. Brain CT examinations were conducted, scanning the maxillae from the external auditory meatus to the parietal bone using a 128-slice multi-detector CT (MDCT) scanner. To reduce errors, three independent trials were conducted. Calculated HE,TLD, based on the weighting factor recommended by ICRP 103, was 1.72 ± 0.28 mSv, which slightly exceeds the HE,DLP of 1.70 mSv, that was calculated from the dose–length product (DLP) of the Rando phantom. This experiment yielded HE,TLD values of ICRP 103 from the highest 1.85 ± 0.28 (90 kg) to the lowest 1.47 ± 0.22 (10 kg) mSv. HE,TLD (mSv) = 5.45×10−3 W(kg) + 1.361, with an R2 of 0.87667. Using the DLP protocol, HE,DLP was estimated from CTDIvol that was recorded directly from the console display of the CT unit and multiplied by the conversion coefficient (k) recommended by the ICRP 103. Finally, the experimental results obtained herein are compared with those in the literature. Physicians should choose and adjust protocols to prevent the exposure of patients to unnecessary radiation, satisfying the as low as reasonably achievable (ALARA) principle. These findings will be valuable to patients, physicians, radiologists and the public.
mRNA levels can be reduced by antisense oligonucleotides via no-go decay pathway
Authors: Liang Xue-hai , Nichols Joshua G , Hsu Chih-Wei , Vickers Timothy A , Crooke Stanley T
Published: June 2019

Antisense technology can reduce gene expression via the RNase H1 or RISC pathways and can increase gene expression through modulation of splicing or translation. Here, we demonstrate that antisense oligonucleotides (ASOs) can reduce mRNA levels by acting through the no-go decay pathway. Phosphorothioate ASOs fully modified with 2′-O-methoxyethyl decreased mRNA levels when targeted to coding regions of mRNAs in a translation-dependent, RNase H1-independent manner. The ASOs that activated this decay pathway hybridized near the 3′ end of the coding regions. Although some ASOs induced nonsense-mediated decay, others reduced mRNA levels through the no-go decay pathway, since depletion of PELO/HBS1L, proteins required for no-go decay pathway activity, decreased the activities of these ASOs. ASO length and chemical modification influenced the efficacy of these reagents. This non-gapmer ASO-induced mRNA reduction was observed for different transcripts and in different cell lines. Thus, our study identifies a new mechanism by which mRNAs can be degraded using ASOs, adding a new antisense approach to modulation of gene expression. It also helps explain why some fully modified ASOs cause RNA target to be reduced despite being unable to serve as substrates for RNase H1.
Coding palindromes in mitochondrial genes of Nematomorpha
Authors: Mikhailov Kirill V , Efeykin Boris D , Panchin Alexander Y , Knorre Dmitry A , Logacheva Maria D , Penin Aleksey A , Muntyan Maria S , Nikitin Mikhail A , Popova Olga V , Zanegina Olga N , Vyssokikh Mikhail Y , Spiridonov Sergei E , Aleoshin Vladimir V , Panchin Yuri V
Published: June 2019

Inverted repeats are common DNA elements, but they rarely overlap with protein-coding sequences due to the ensuing conflict with the structure and function of the encoded protein. We discovered numerous perfect inverted repeats of considerable length (up to 284 bp) embedded within the protein-coding genes in mitochondrial genomes of four Nematomorpha species. Strikingly, both arms of the inverted repeats encode conserved regions of the amino acid sequence. We confirmed enzymatic activity of the respiratory complex I encoded by inverted repeat-containing genes. The nucleotide composition of inverted repeats suggests strong selection at the amino acid level in these regions. We conclude that the inverted repeat-containing genes are transcribed and translated into functional proteins. The survey of available mitochondrial genomes reveals that several other organisms possess similar albeit shorter embedded repeats. Mitochondrial genomes of Nematomorpha demonstrate an extraordinary evolutionary compromise where protein function and stringent secondary structure elements within the coding regions are preserved simultaneously.
Age-Related Differences in Hospitalization Rates, Clinical Presentation, and Outcomes Among Older Adults Hospitalized With Influenza—U.S. Influenza Hospitalization Surveillance Network (FluSurv-NET)
Authors: Czaja Christopher A , Miller Lisa , Alden Nisha , Wald Heidi L , Cummings Charisse Nitura , Rolfes Melissa A , Anderson Evan J , Bennett Nancy M , Billing Laurie M , Chai Shua J , Eckel Seth , Mansmann Robert , McMahon Melissa , Monroe Maya L , Muse Alison , Risk Ilene , Schaffner William , Thomas Ann R , Yousey-Hindes Kimberly , Garg Shikha , Herlihy Rachel K
Published: June 2019

Background

Rates of influenza hospitalizations differ by age, but few data are available regarding differences in laboratory-confirmed rates among adults aged ≥65 years.

Methods

We evaluated age-related differences in influenza-associated hospitalization rates, clinical presentation, and outcomes among 19 760 older adults with laboratory-confirmed influenza at 14 FluSurv-NET sites during the 2011–2012 through 2014–2015 influenza seasons using 10-year age groups.

Results

There were large stepwise increases in the population rates of influenza hospitalization with each 10-year increase in age. Rates ranged from 101–417, 209–1264, and 562–2651 per 100 000 persons over 4 influenza seasons in patients aged 65–74 years, 75–84 years, and ≥85 years, respectively. Hospitalization rates among adults aged 75–84 years and ≥85 years were 1.4–3.0 and 2.2–6.4 times greater, respectively, than rates for adults aged 65–74 years. Among patients hospitalized with laboratory-confirmed influenza, there were age-related differences in demographics, medical histories, and symptoms and signs at presentation. Compared to hospitalized patients aged 65–74 years, patients aged ≥85 years had higher odds of pneumonia (aOR, 1.2; 95% CI, 1.0–1.3; P = .01) and in-hospital death or transfer to hospice (aOR, 2.1; 95% CI, 1.7–2.6; P < .01).

Conclusions

Age-related differences in the incidence and severity of influenza hospitalizations among adults aged ≥65 years can inform prevention and treatment efforts, and data should be analyzed and reported using additional age strata.
Will China’s H7N9 Control Strategy Continue to Be Effective?
Authors: Wang Guo-Lin , Gray Gregory C , Chen Ji-Ming , Ma Mai-Juan
Published: June 2019

Since the first outbreak of avian influenza A(H7N9) virus in China in early 2013, several interventions to control the transmission of H7N9 virus from poultry to humans have been implemented. Temporarily closing live poultry markets reduced the risk of human infection to an extent, but it did not prevent the spread of the H7N9 virus among poultry, and this spread eventually led to more human cases. Nevertheless, the mass vaccination of poultry after September 2017 has been highly effective in preventing the H7N9 virus infection in both poultry and humans. In light of the emergence of highly pathogenic H7N9 and H7N2 viruses in unimmunized ducks, vaccination among poultry, especially for ducks, should be accompanied with continued surveillance of H7N9 variants and other avian influenza A viruses that could signal a heightened pandemic risk.
Development of High-Level Echinocandin Resistance in a Patient With Recurrent Candida auris Candidemia Secondary to Chronic Candiduria
Authors: Biagi Mark J , Wiederhold Nathan P , Gibas Connie , Wickes Brian L , Lozano Victoria , Bleasdale Susan C , Danziger Larry
Published: June 2019

Objective

Candida auris is a globally emerging pathogen associated with significant mortality. This pathogen frequently is misidentified by traditional biochemical methods and is resistant to commonly used antifungals. The echinocandins currently are recommended as the first-line treatment for C. auris infections. The objective of this work is to demonstrate the challenges associated with C. auris in the real-world setting.

Methods

A 54-year-old male presented to our institution for concerns of sepsis on multiple occasions over a 5-month period. Eleven urine cultures were positive over this timeframe for yeast (9 unidentified Candida isolates and 2 C. lusitaniae isolates). On day 27, the patient developed echinocandin-susceptible candidemia, which was initially identified as C. haemulonii but later accurately identified as C. auris at an outside mycology reference laboratory. Approximately 10 weeks later, the patient had a recurrence of candidemia, this time caused by an echinocandin-resistant C. auris strain.

Results

Genomic DNA sequencing performed at the outside mycology reference laboratory identified a single serine to proline base pair change at position 639 (S639P) in the hotspot 1 region of the FKS1 gene of the echinocandin-resistant strain.

Conclusions

Our experiences highlight 4 major concerns associated with C. auris: misidentification, persistent colonization, infection recurrence despite the receipt of appropriate initial therapy, and development of resistance.
Null geodesics and repulsive behavior of gravity in $(2+1)$D massive gravity
Authors: Nakashi Keisuke , Kobayashi Shinpei , Ueda Shu , Saida Hiromi
Published: June 2019

We study the null geodesics in a static circularly symmetric (SCS) black hole spacetime, which is a solution in the $(2+1)$D massive gravity proposed by Bergshoeff, Hohm, and Townsend (BHT massive gravity). We obtain analytic solutions for the null geodesic equation in the SCS black hole background and find the explicit form of deflection angles. We see that, for various values of the impact parameter, the deflection angle can be positive, negative, or even zero in this black hole spacetime. The negative deflection angle indicates the repulsive behavior of the gravity that comes from the gravitational hair parameter that is the most characteristic quantity of the BHT massive gravity.
EVALUATING SHORT-TERM EXPOSURE TO WI-FI SIGNALS ON STUDENTS’ REACTION TIME, SHORT-TERM MEMORY AND REASONING ABILITY
Authors: Hosseini M A , Hosseini A , Jarideh S , Argasi H , Shekoohi-Shooli F , Zamani A , Taeb S , Haghani M
Published: June 2019

This study investigated the effect of short-term exposure to Wi-Fi signals on the cognitive functions of the mind. After obtaining permission from the local Ethics Committee of Shiraz University of Medical Sciences and approval by the Iranian Registry of Clinical Trials (IRCT2017041233398N1), 45 male and female students from Shiraz University of Medical Sciences volunteered to participate in this study. They were exposed to Wi-Fi signals in two sham and exposure sessions, each for 2 hours. After completion, they took part in reaction time, short-term memory, and reasoning ability tests. After scoring, the data were analysed by SPSS software. In addition, the electric field strength and power density were calculated. The results showed no statistically significant differences between the mean scores of reaction time, short-term memory, and reasoning ability in sham and exposure. Also, the obtained values from the electric field strength and power density (E = 4.1 Vm−1, P = 0.446 Wm−2) were lower than that of threshold values by the International Commission on Non-Ionizing Radiation Protection (ICNIRP). Our results can greatly reduce concerns regarding the effects of short-term exposure to Wi-Fi waves on cognitive functions.
Hot flashes and awakenings among midlife women
Authors: Thurston Rebecca C , Chang Yuefang , Buysse Daniel J , Hall Martica H , Matthews Karen A
Published: June 2019

Study Objectives

For most women, the menopause is accompanied by hot flashes and sleep problems. Although hot flashes reportedly wake women from sleep, in the few studies that have used objective measures of both sleep and hot flashes, links between hot flashes and nocturnal awakening have been inconsistent. In a well-characterized cohort of midlife women, we examined the association between objectively assessed hot flashes and actigraphically defined wake from sleep. We hypothesized that wake episodes would be more likely during an objective hot flash relative to minutes without a hot flash.

Methods

Peri- and postmenopausal midlife women underwent simultaneous objective measurement of hot flashes (sternal skin conductance) and sleep (actigraphy) over 24 hours in the home. The likelihood of waking in the minutes during the hot flash relative to the minutes preceding the hot flash was compared using generalized estimating equations.

Results

We studied 168 women with at least one objective nocturnal hot flash and actigraphy data. Actigraphy-assessed wake episodes were concurrent with 78% of the objective hot flashes. We found an increased likelihood of wake in the minutes during the objective hot flash (0 to +5 min: OR [95% CI] = 5.31 (4.46 to 6.33); p < .0001) relative to the minutes preceding it (–10 to –1 min). The increased likelihood of wake occurred irrespective of whether the women reported the objective hot flash.

Conclusion

Among these women who underwent objective measurement of sleep and hot flashes, nocturnal wakefulness was observed with the majority of hot flashes.
Demyelination-remyelination in the Central Nervous System: Ligand-dependent Participation of the Notch Signaling Pathway
Authors: Mathieu Patricia A , Almeira Gubiani María F , Rodríguez Débora , Gómez Pinto Laura I , Calcagno María de Luján , Adamo Ana M
Published: June 2019

Multiple sclerosis (MS) is an immune-mediated central nervous system disease mostly affecting young people. Multiple sclerosis and other neurodegenerative and white matter disorders involve oligodendrocyte (OL) damage and demyelination. Therefore, elucidating the signaling pathways involved in the remyelination process through the maturation of OL progenitor cells (OPCs) may contribute to the development of new therapeutic approaches. In this context, this paper further characterizes toxic cuprizone (CPZ)-induced demyelination and spontaneous remyelination in rats and investigates the role of ligand-dependent Notch signaling activation along demyelination/remyelination both in vivo and in vitro. Toxic treatment generated an inflammatory response characterized by both microgliosis and astrogliosis. Interestingly, early demyelination revealed an increase in the proportion of Jagged1+/GFAP+ cells, which correlated with an increase in Jagged1 transcript and concomitant Jagged1-driven Notch signaling activation, particularly in NG2+ OPCs, in both the corpus callosum (CC) and subventricular zone (SVZ). The onset of remyelination then exhibited an increase in the proportion of F3/contactin+/NG2+ cells, which correlated with an increase in F3/contactin transcript during ongoing remyelination in the CC. Moreover, neurosphere cultures revealed that neural progenitor cells present in the brain SVZ of CPZ-treated rats recapitulate in vitro the mechanisms underlying the response to toxic injury observed in vivo, compensating for mature OL loss. Altogether, the present results offer strong evidence of cell-type and ligand-specific Notch signaling activation and its time- and area-dependent participation in toxic demyelination and spontaneous remyelination.
Location, seasonal and functional characteristics of water-holding containers with juvenile Aedes albopictus in urban southern Taiwan: a cross-sectional study
Authors: Lin Chia-Hsien , Schiøler Karin L , Konradsen Flemming
Published: June 2019

Background

Urban Kaohsiung City (KC), in southern Taiwan, has experienced annual dengue epidemics for decades despite considerable vector control efforts. Substantial research has been undertaken to characterize Aedes aegypti breeding habitats, but no systematic assessment has been completed for Aedes albopictus present in KC.

Methods

A cross-sectional survey was conducted from 2013 to 2015 in a predefined area of KC. Each identified container was characterised by season, location, ownership, function and number of juvenile A. aegypti. Negative binomial hurdle analyses were applied to evaluate the association between the number of juvenile A. albopictus and the characteristics of each identified container.

Results

For all containers, high numbers of A. albopictus were significantly predicted by containers identified during the wet season (vs dry), located on government (vs private) property and classified as a discarded item (vs water storage). For outdoor containers, more A. albopictus were significantly predicted by wet season (vs dry) and discarded item (vs container in use).

Conclusions

In order to improve dengue prevention in KC, we propose that vector control efforts be expanded to include A. albopictus through an increased focus during the wet season on discarded containers that are located outdoors and on government property.
StrainHub: A phylogenetic tool to construct pathogen transmission networks
Authors: de Bernardi Schneider Adriano , Ford Colby T. , Hostager Reilly , Williams John , Cioce Michael , Çatalyürek Ümit V. , Wertheim Joel O. , Janies Daniel
Published: June 2019

In exploring the epidemiology of infectious diseases, networks have been used to reconstruct contacts among individuals and/or populations. Summarizing networks using pathogen metadata (e.g., host species and place of isolation) and a phylogenetic tree is a nascent, alternative approach. In this paper, we introduce a tool for reconstructing transmission networks in arbitrary space from phylogenetic information and metadata. Our goals are to provide a means of deriving new insights and infection control strategies based on the dynamics of the pathogen lineages derived from networks and centrality metrics. We created a web-based application, called StrainHub, in which a user can input a phylogenetic tree based on genetic or other data along with characters derived from metadata using their preferred tree search method. StrainHub generates a transmission network based on character state changes in meta-data, such as place or source of isolation, mapped on the phylogenetic tree. The user has the option to calculate centrality metrics on the nodes including betweenness, closeness, degree, and a new metric, the source/hub ratio. The outputs include the network with values for metrics on its nodes and the tree with characters reconstructed. All of these results can be exported for further analysis.

Availability

https://github.com/abschneider/StrainHub and strainhub.io
Genotyping structural variants in pangenome graphs using the vg toolkit
Authors: Hickey Glenn , Heller David , Monlong Jean , Sibbesen Jonas A. , Sirén Jouni , Eizenga Jordan , Dawson Eric T. , Garrison Erik , Novak Adam M. , Paten Benedict
Published: June 2019

Structural variants (SVs) remain challenging to represent and study relative to point mutations despite their demonstrated importance. We show that variation graphs, as implemented in the vg toolkit, provide an effective means for leveraging SV catalogs for short-read SV genotyping experiments. We benchmarked vg against state-of-the-art SV genotypers using three sequence-resolved SV catalogs generated by recent long-read sequencing studies. In addition, we use assemblies from 12 yeast strains to show that graphs constructed directly from aligned de novo assemblies improve genotyping compared to graphs built from intermediate SV catalogs in the VCF format.
Novel genome-wide associations for anhedonia, genetic correlation with psychiatric disorders, and polygenic association with brain structure
Authors: Ward Joey , Lyall Laura M. , Bethlehem Richard A. I. , Ferguson Amy , Strawbridge Rona J. , Lyall Donald M. , Cullen Breda , Graham Nicholas , Johnston Keira J.A. , Bailey Mark E.S. , Murray Graham K. , Smith Daniel J.
Published: June 2019

Anhedonia is a core feature of several psychiatric disorders but its biological underpinnings are poorly understood. We performed a genome-wide association study of anhedonia in 375,275 UK Biobank participants and assessed for genetic correlation between anhedonia and neuropsychiatric conditions (major depressive disorder, schizophrenia, bipolar disorder, obsessive compulsive disorder and Parkinson’s Disease). We then used a polygenic risk score approach to test for association between genetic loading for anhedonia and both brain structure and brain function. This included: magnetic resonance imaging (MRI) assessments of total grey matter volume, white matter volume, cerebrospinal fluid volume, and 15 cortical/subcortical regions of interest; diffusion tensor imaging (DTI) measures of white matter tract integrity; and functional MRI activity during an emotion processing task. We identified 11 novel loci associated at genome-wide significance with anhedonia, with a SNP heritability estimate (h2SNP) of 5.6%. Strong positive genetic correlations were found between anhedonia and major depressive disorder, schizophrenia and bipolar disorder; but not with obsessive compulsive disorder or Parkinson’s Disease. Polygenic risk for anhedonia was associated with poorer brain white matter integrity, smaller total grey matter volume, and smaller volumes of brain regions linked to reward and pleasure processing, including nucleus accumbens, caudate and medial frontal cortex. In summary, the identification of novel anhedonia-associated loci substantially expands our current understanding of the biological basis of anhedonia and genetic correlations with several psychiatric disorders confirm the utility of this trait as a transdiagnostic marker of vulnerability to mental illness. We also provide the first evidence that genetic risk for anhedonia influences brain structure, particularly in regions associated with reward and pleasure processing.
Rapid Online Changes of Mind during Value-based Action Decisions
Authors: Martí-Marca Angela , Deco Gustavo , Cos Ignasi
Published: June 2019

While the principles of decision-making are often expressed in terms of benefit-cost trade-off, reasonable doubt remains as to how the cognitive value and motor cost associated to several options may be computed across several brain areas, ultimately leading to a decision. Furthermore, does the assessment of non-chosen options continue after the decision has been made and the selected movement is already ongoing? Does the planning of several motor options depend on a unique parallel process or are there some elements within the sensorimotor loop requiring a sequential processing? Our hypothesis is that a change of available prospects at any point in time should dynamically adjust the desirability for each option, implying a fast reassessment of values and costs across prefrontal and motor cortical areas, even after an initial decision has been made and its associated response movement is ongoing. To test this, we performed a decision-making task in which human participants were instructed to select a reaching path trajectory from an origin to a wide rectangular target to gain the most reward. Reward delivery was contingent upon the distribution of value and upon precise target arrival. The original value distribution was altered during the ongoing movement in one third of the trials. Our results show that participants changed their movement trajectories towards the target position offering a better prospect, as presented by the second distribution. The changes of mind occurred more frequently for slow movements, had a duration in average inferior to the reaction time, and altered the initial timing and movement velocity. Although reward is the main factor guiding the selection of a specific movement in our experiment, our results indicate that the motor system was biased towards early changes of mind, given that the amplitude of the first acceleration and velocity peaks was significantly smaller in trials in which the participant switched target side and those in which they stuck to their original choice. Finally, the short latency of the recorded changes of mind strongly supports the hypothesis that, for the experimental conditions hereby considered, value considerations occur in parallel to motor planning.
Seasonal and spatial variation in growth and abundance of zebra mussel (Dreissena polymorpha) in a recently invaded lake: implications for management
Authors: Rolla Matteo , Consuegra Sonia , Hall David J. , de Leaniz Carlos Garcia
Published: June 2019

The control of the highly invasive zebra mussel (Dreissena polymorpha) has been flagged as a priority but success has been variable. A better understanding of the growth and drivers of settlement of zebra mussel is necessary for a more efficient management of this invasive species, but seasonal data are still relatively scant. We monitored the seasonal changes in settlement rates, density, and growth of zebra mussel in artificial substrates over one year in Cardiff Bay (UK), an artificial amenity lake invaded by zebra mussels in 2003 and where the species is rapidly expanding. Mean settling rates varied from 4,200 to 6,200 mussel m−2over June to September mirroring changes in water temperature, and peaked at 17,960 mussels m−2, the highest density reported in Britain. Density was highest at the deepest panels (3 m). Growth varied significantly among sampling stations, with growth taking place during the summer and ceasing during winter and spring. Mixture analysis reveals the existence of multiple cohorts displaying different growth and settling rates and that follow different density dependent mechanisms, being positive density-dependent at low densities, and negative density-dependent at high densities. We suggest this creates the conditions necessary for source and sink metapopulations to develop which may need to be taken into account in management. Targeting mussels for removal in deep waters during the summer and early autumn might prove beneficial, but the existence of contrasting density-dependent mechanisms suggests that removal may be beneficial or counterproductive depending on local conditions.