bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of nutritional interventions on feathering of poultry - a review.
Authors: Emous R. A. van , Krimpen M. M. van
Published: March 2019

Feather cover of chickens can be influenced by many factors, including direct or indirect nutritional factors. Direct dietary factor effects are levels of protein/amino acids, vitamins, minerals and mycotoxins. Indirect nutritional factors will impact feather cover through their effects on feather pecking behaviour. Since feathers contain 89-97% protein, the supply of dietary amino acids plays a critical role in feather development. Particularly in the juvenile phase of broilers and breeders, low dietary crude protein intake can negatively affect feather quality. Especially the sulfur-containing amino acids methionine and cystine are indicated as necessary for the synthesis of feather keratin. Dietary deficiencies of these amino acids have been shown to result in rough feathering, as indicated by body feathers sticking out from the body, or malformed cover feathers on the wings of young and older birds. Deficiencies of vitamin E and selenium might lead to depigmentation and shorter shafts of wing feathers, whereas deficiencies of other vitamins can lead to slower feather development and swollen tip of down feathers. Mineral (zinc, tin, vanadium, chromium, nickel) deficiencies could result in delayed feather development, frayed feathers (zinc) and blisters on the shafts. Mycotoxins in the feed have been shown to cause sparse covering of feathers and sticking out of feathers from the body. In an indirect way, nutritional aspects can also affect feather cover due to feather pecking in chickens. There is strong evidence that a (very) low crude protein content (<13%) of the diet increases injurious pecking in laying hens. On the other hand, a low energy content of the diet might decrease mortality of laying hens because the dilution of the diet increases eating time. Adding roughage (maize silage, barley silage or carrots) to the daily feed decreases injurious pecking behaviour and increases plumage condition of laying hens. Adding tryptophan to layer diets reduces incidences of feather pecking, because this AA contributes to serotonin turnover in the brain, which is largely related to bird behaviour. Addition of (coarse) insoluble non-starch proteins has been shown to increase gizzard weight and its contents and to prolong mean retention time in the foregut, which is an indicator for higher levels of satiety and a reduced motivation to peck. This chapter gives an overview of the direct and indirect relationships between the effects of nutritional interventions on feathering of poultry.
Business opportunities with the integument.
Authors: Lister S.
Published: March 2019

The integument is an important organ system protecting the bird by acting as a barrier between the external environment and internal body systems, providing thermal insulation and for regulation of water loss. Arguably, as a result, the major business opportunity with the integument is to maintain the integrity of feathers, skin, scales and foot pads to protect and enhance bird health and performance, and through this boost economic return at processing. Feather cover and foot pad integrity are also used as proxy measures of animal husbandry, management, environmental control and bird health and are increasingly important as welfare outcome measures. In this way the integument acts as an important indicator of bird health and welfare. At processing, the harvesting of avian feathers, down, feet, skin and tongues can offer further business opportunities for by-products that would otherwise be considered as waste. The most profitable and widespread use of the integument as a by-product is the use of feather and down for bedding and clothing. Historically feathers were seen as an essential fashion accessory, often commanding prices of more than their weight in gold. Less obvious uses have been as an animal protein source, pet food, fertilizer, bacterial culture medium, enzyme production and adhesives. Recent interest has been in the production of biodegradable composite plastics from processed feathers. Chicken feet (paws) and duck feet, together with duck tongues, combs and wattles, have the potential to satisfy an increasing export opportunity for markets where these food choices are popular. This chapter will discuss some of these opportunities and factors that could adversely affect quality.
Protamine may have anti-atherogenic potential by inhibiting the binding of oxidized-low density lipoprotein to LOX-1
Authors: Takemura Yukitoshi , Okamoto Masaki , Hasegawa Makoto , Hatanaka Kenichi , Kubota Shunichiro
Published: March 2019

Oxidized low-density lipoprotein (ox-LDL) leads to atherosclerosis via lectin-like oxidized lipoprotein receptor-1 (LOX-1), one of the major receptor for ox-LDL. Inhibition of the binding of ox-LDL to LOX-1 decreases the proinflammatory and atherosclerotic events. The aim of the present study was to investigate whether protamine, a polybasic nuclear protein, interferes the binding of ox-LDL to LOX-1. Using sandwich ELISA with newly generated antibody, we measured the blocking effect of protamine on the binding of ox-LDL to LOX-1. Protamine dose-dependently inhibited the binding of ox-LDL to LOX-1. DiI-labeled ox-LDL uptake assay in two types of cultured human endothelial cells was performed with fluorescence microplate reader. Activation of extracellular-signal-regulated kinase (ERK)1/2 by ox-LDL was analyzed by immunoblotting. We found that protamine suppressed uptake of ox-LDL in endothelial cells and inhibited ERK1/2 activation by ox-LDL. These results suggest that protamine may possess anti-atherogenic potential by inhibiting ox-LDL binding to LOX-1 through electrostatic interactions.
Translation factor mRNA granules direct protein synthetic capacity to regions of polarized growth
Authors: Pizzinga Mariavittoria , Bates Christian , Lui Jennifer , Forte Gabriella , Morales-Polanco Fabián , Linney Emma , Knotkova Barbora , Wilson Beverley , Solari Clara A. , Berchowitz Luke E. , Portela Paula , Ashe Mark P.
Published: March 2019

mRNA localization serves key functions in localized protein production, making it critical that the translation machinery itself is present at these locations. Here we show that translation factor mRNAs are localized to distinct granules within yeast cells. In contrast to many messenger RNP granules, such as processing bodies and stress granules, which contain translationally repressed mRNAs, these granules harbor translated mRNAs under active growth conditions. The granules require Pab1p for their integrity and are inherited by developing daughter cells in a She2p/She3p-dependent manner. These results point to a model where roughly half the mRNA for certain translation factors is specifically directed in granules or translation factories toward the tip of the developing daughter cell, where protein synthesis is most heavily required, which has particular implications for filamentous forms of growth. Such a feedforward mechanism would ensure adequate provision of the translation machinery where it is to be needed most over the coming growth cycle.
THE RELATIONS OF EMBRYONIC TISSUE AND TUMOR IN MIXED GRAFTS
Authors: Rous Peyton
Published: March 2019

In volume XIII, Number 2; page 247, Fig. 6, lines 3 and 4, for plate X" read "XIII."
Platform-independent approach for cancer detection from gene expression profiles of peripheral blood cells
Authors: Yang Yadong , Zhang Tao , Xiao Rudan , Hao Xiaopeng , Zhang Huiqiang , Qu Hongzhu , Xie Bingbing , Wang Tao , Fang Xiangdong
Published: March 2019

Peripheral blood gene expression intensity-based methods for distinguishing healthy individuals from cancer patients are limited by sensitivity to batch effects and data normalization and variability between expression profiling assays. To improve the robustness and precision of blood gene expression-based tumour detection, it is necessary to perform molecular diagnostic tests using a more stable approach. Taking breast cancer as an example, we propose a machine learning–based framework that distinguishes breast cancer patients from healthy subjects by pairwise rank transformation of gene expression intensity in each sample. We showed the diagnostic potential of the method by performing RNA-seq for 37 peripheral blood samples from breast cancer patients and by collecting RNA-seq data from healthy donors in Genotype-Tissue Expression project and microarray mRNA expression datasets in Gene Expression Omnibus. The framework was insensitive to experimental batch effects and data normalization, and it can be simultaneously applied to new sample prediction.
National trends and perioperative outcomes of robotic resection of thymic tumours in the United States: a propensity matching comparison with open and video-assisted thoracoscopic approaches†
Authors: Kamel Mohamed K , Villena-Vargas Jonathan , Rahouma Mohamed , Lee Benjamin , Harrison Sebron , Stiles Brendon M , Abdelrahman Abdelrahman M , Altorki Nasser K , Port Jeffery L
Published: March 2019

OBJECTIVES:

Despite the recent increased rate of adoption of robotic approaches for the resection of thymic tumours, their use is still limited to large-volume academic centres. To date, a large-scale analysis of the robotic approach has not been performed. We assessed the recent trends and outcomes of robotic thymectomies in the United States compared to those of open and video-assisted thoracoscopic surgical (VATS) approaches.

METHODS:

The National Cancer Database was queried for patients who underwent resection for thymic tumours (2010–2014). Predictors of using the robotic approach were estimated by logistic regression analysis. Propensity matching analysis (robotic versus open and robotic versus VATS) was done (1:1—caliper 0.05), controlling for age, gender, comorbidity index, induction treatment, tumour size and tumour extension.

RESULTS:

A total of 2558 thymectomies were performed (robotic = 300, VATS = 280, open = 1978). The use of a robotic approach increased from 6% (2010) to 14% (2014). The number of hospitals performing at least 1 robotic thymectomy increased from 22 (2010) to 52 (2014). Independent predictors influencing the choice of a robotic approach included an academic research/integrated cancer programme [odds ratio (OR) 1.66, confidence interval (CI) 1.22–2.27], later year of diagnosis (2014; OR 2.23, CI 1.31–3.80) and a patient’s race (Asian) (OR 1.68, CI 1.05–2.69). A robotic approach was less likely to be utilized in midwestern hospitals (OR 0.65, CI 0.42–0.99), in larger tumours (cm) (OR 0.85, CI 0.80–0.90), with invasion of adjacent organs (OR 0.55, CI 0.37–0.82), thymic carcinoma (OR 0.62, CI 0.40–0.97) and following induction chemotherapy (OR 0.22, CI 0.08–0.61). In a propensity-matched analysis, there were no differences in the incidence of positive margins, nodal dissection, 30-day readmission rates and 30-/90-day mortality rates between the groups. However, a robotic approach was associated with fewer conversions compared to VATS, with a trend towards a shorter length of stay compared to an open approach. There were no differences in the 5-year overall survival rate between the matched groups (robotic 93% vs VATS 94%; P = 0.571; robotic 91% vs open 80%; P = 0.094).

CONCLUSIONS:

Over a 4-year study period, there was a significant increase in robotic utilization for thymectomies and an increase in the number of hospitals performing the procedure. In a matched analysis, a robotic approach was comparable to a VATS or an open approach. Current trends demonstrate increased robotic utilization for small thymomas with excellent perioperative results.
China's Energy Diplomacy: Does Chinese Foreign Policy Favor Oil-Producing Countries?
Authors: Lee Chia-yi
Published: March 2019

Due to its rapid economic growth and increasing demand for energy, China has engaged in numerous efforts to sustain its energy supplies and enhance its energy security. While existing literature argues that access to energy is oftentimes the driving force behind Beijing's foreign policy behavior, little work has been done to systemically examine the bilateral relationship between China and energy-producing countries. This paper explores how China's foreign policy making is influenced by its energy security concern, focusing on three foreign policy instruments—partnerships, foreign aid, and leadership visits. Using a large-N, quantitative approach, this paper analyzes the effect of oil production on these three foreign policy indicators. The results show that Beijing is more likely to form partnerships with oil-producing countries. Top Chinese leaders are also more likely to travel to countries that produce a higher level of oil. China's aid allocation to Africa is driven by oil abundance as well, although the findings on aid are only valid in the cross-national analysis.
Advanced Parental Age at Conception and Sex Affects Mitochondrial DNA Copy Number in Human and Fruit Flies
Authors: Mengel-From Jonas , Svane Anne Marie , Pertoldi Cino , Nygaard Kristensen Torsten , Loeschcke Volker , Skytthe Axel , Christensen Kaare , Lindahl-Jacobsen Rune , Hjelmborg Jacob , Christiansen Lene
Published: March 2019

Aging is a multifactorial trait caused by early as well as late-life circumstances. A society trend that parents deliberately delay having children is of concern to health professionals, for example as advanced parental age at conception increases disease risk profiles in offspring. We here aim to study if advanced parental age at conception affects mitochondrial DNA content, a cross-species biomarker of general health, in adult human twin offspring and in a model organism. We find no deteriorated mitochondrial DNA content at advanced parental age at conception, but human mitochondrial DNA content was higher in females than males, and the difference was twofold higher at advanced maternal age at conception. Similar parental age effects and sex-specific differences in mitochondrial DNA content were found in Drosophila melanogaster. In addition, parental longevity in humans associates with both mitochondrial DNA content and parental age at conception; thus, we carefully propose that a poorer disease risk profile from advanced parental age at conception might be surpassed by superior effects of parental successful late-life reproduction that associate with parental longevity.
Elevated Plasma Growth and Differentiation Factor 15 Is Associated With Slower Gait Speed and Lower Physical Performance in Healthy Community-Dwelling Adults
Authors: Semba Richard D , Gonzalez-Freire Marta , Tanaka Toshiko , Biancotto Angelique , Zhang Pingbo , Shardell Michelle , Moaddel Ruin ,   CHI Consortium, Ferrucci Luigi
Published: March 2019

Background

Growth and differentiation factor 15 (GDF-15) has been associated with obesity, muscle wasting, and cachexia. The receptor for GDF-15 was recently identified in the brainstem and regulates food intake and metabolism. The relationship of plasma GDF-15 with the age-associated decline of muscle mass and strength, gait speed, and physical performance in adults has not been well characterized.

Methods

Plasma GDF-15, grip strength, 6-m gait speed, 400-m walking test time, lower extremity physical performance score, appendicular lean mass, and fat mass were measured in 194 healthy adult participants, aged 22–93 years, of the Baltimore Longitudinal Study of Aging.

Results

Plasma GDF-15 concentrations increased with age (p < .001) and were higher in whites compared with blacks and Asians (p = .04). Adults with higher plasma GDF-15 had slower 6-m gait speed, longer 400-m walking time, and lower physical performance score in multivariable analyses adjusting for age and race. Plasma GDF-15 was not associated with grip strength, appendicular lean mass, or fat mass.

Conclusions

Elevated plasma GDF-15 is associated with slower gait speed, higher 400-m walking time, and lower physical performance in very healthy community-dwelling adults. The relationship between plasma GDF-15 and sarcopenia-related outcomes may be stronger in the population not selected to be healthy, and this hypothesis should be tested in a representative population.
Efficacy of Primaquine in Preventing Short- and Long-Latency Plasmodium vivax Relapses in Nepal
Authors: Rijal Komal Raj , Adhikari Bipin , Ghimire Prakash , Banjara Megha Raj , Das Thakur Garib , Hanboonkunupakarn Borimas , Imwong Mallika , Chotivanich Kesinee , Day Nicholas P J , White Nicholas J , Pukrittayakamee Sasithon
Published: March 2019

Background

Plasmodium vivax is the main cause of malaria in Nepal. Relapse patterns have not been characterized previously.

Methods

Patients with P. vivax malaria were randomized to receive chloroquine (CQ; 25 mg base/kg given over 3 days) alone or together with primaquine (PQ; 0.25 mg base/kg/day for 14 days) and followed intensively for 1 month, then at 1- to 2-month intervals for 1 year. Parasite isolates were genotyped.

Results

One hundred and one (49%) patients received CQ and 105 (51%) received CQ + PQ. In the CQ + PQ arm, there were 3 (4.1%) recurrences in the 73 patients who completed 1 year of follow-up compared with 22 of 78 (28.2%) in the CQ-only arm (risk ratio, 0.146 [95% confidence interval, .046–.467]; P < .0001). Microsatellite genotyping showed relatively high P. vivax genetic diversity (mean heterozygosity, 0.843 [range 0.570–0.989] with low multiplicity of infection (mean, 1.05) reflecting a low transmission preelimination setting. Of the 12 genetically homologous relapses, 5 (42%) occurred in a cluster after 9 months, indicating long latency.

Conclusions

Although there may be emerging CQ resistance, the combination of CQ and the standard-dose 14-day PQ regimen is highly efficacious in providing radical cure of short- and long-latency P. vivax malaria in Nepal.
The Impact of Adverse Childhood Experiences on Burn Outcomes in Adult Burn Patients
Authors: Fassel Mikenzy , Grieve Brian , Hosseini Sameen , Oral Resmiye , Galet Colette , Ryan Colleen , Kazis Lewis , Pengsheng Ni , Wibbenmeyer Lucy A
Published: March 2019

Adverse childhood experiences (ACEs), including child maltreatment and household dysfunction, define adverse events that occur before 18 years of age. National and state data show that between 12.5 and 14.5% of the adult population report ≥4 ACEs (HIGH-ACE), respectively. HIGH-ACEs are associated with more chronic health problems. To date, the interaction between ACEs and burn injuries has not been studied. Herein, we sought to define the ACE exposure in our burn patients and its impact on early outcomes. Inpatient and outpatient adult burn survivors (≥18 years of age) were enrolled. Subjects completed surveys assessing adverse experiences (ACEs-18), needs, strengths, and resiliency at consent, and pain, depression, post-traumatic stress disorder (PTSD), and social participation surveys at 2 weeks to 3 months postinjury. Demographics, burn, and hospital course data were also collected. Chi-square and student’s t-tests were used for descriptive analysis and to compare the groups (HIGH-ACE vs LOW-ACE). The HIGH-ACE group (n = 24; 45.3%) reported more depressive symptoms (P < .04) than the LOW-ACE group (n = 29, 54.7%). HIGH-ACE patients were less resilient when facing stressful events (P ≤ .02) and more likely to screen positive for probable PTSD (P = .01) and to score lower on the Life Impact Burn Recovery Evaluation Profile (LIBRE Profile), which assesses for social participation, in the domain of Family and Friends (P = .015). Our exploratory study suggests that ACE screening may help detect burn patients at risk for a more complicated recovery, thereby promoting personalized assistance in recovery.
Disseminated Hormographiella aspergillata Infection with Lung and Brain Involvement after Allogenic Hematopoietic Stem-Cell Transplantation in a 54-Year-Old Man
Authors: Chauhan Aastha , Gruenberg Jessica , Arbefeville Sophie , Mettler Tetyana , Brent Clark H , Ferrieri Patricia
Published: March 2019

Hormographiella is a rare fungal pathogen in humans; however, case reports have described disseminated infection in immunocompromised hosts. This pathogen has been described to yield poor prognosis in patients who harbor it. Herein, we present a case report of autopsy-proven disseminated Hormographiella aspergillata infection, confirmed by DNA sequencing, in a patient experiencing a relapse of leukemia.

This 54-year-old Caucasian man with chronic myelogenous leukemia (CML) that had been diagnosed in 1989, after having received a hematopoietic cell allotransplant from a compatible sibling donor, had B-cell lymphoid-blast phase of CML in April of 2013, with multiple relapses. His most recent relapse was in September of 2016, when bone marrow biopsy showed 90% blasts. The results of bronchoalveolar lavage (BAL) cultures were positive for filamentous fungus infection. The patient developed encephalopathy and worsening respiratory statusand tachycardia with flutter and hypotension, which resulted in his death.

At autopsy, bilateral pleural effusions, multiple right pleural nodules, and subarachnoid hemorrhage were noted. Angioinvasive hyphal fungi were found in the right frontal lobe of the brain and the right upper lobe of the lung. Morphologically, the fungi had multiseptate, branching hyphae. The bronchoalveolar lavage specimen grew a fungus for which the colony morphologic characteristics and microscopic features were compatible with a Hormographiella species. H. aspergillata from the bronchoalveolar lavage was further identified by sequencing the D2 hypervariable region of the large-subunit (LSU) ribosomal DNA gene and the full internal transcribed spacer (ITS) regions.
Right to Life
Authors: Nizar Smitha
Published: March 2019

This chapter examines Article 10 of the United Nations Convention on the Rights of Persons with Disabilities (CRPD), which affirms every human being’s right to life. It first explores the efforts made by the drafters of the CRPD to frame the right to life of all human beings. It further examines the wider meaning of the right to life and its application, and traces the interpretation given by the CRPD Committee in its concluding observations. In order to understand the micro-level application of the right, the chapter examines the interpretation and its application by domestic and regional courts. Finally, it explores the individual complaints made under the optional protocol and the consequent interpretation provided. This is done to define the jurisprudence surrounding the right to life and the required measures to strengthen and facilitate its wider application as envisaged under the Convention.
Freedom of Expression and Opinion, and Access to Information
Authors: Varney Eliza
Published: March 2019

This chapter examines the effectiveness of the United Nations Convention on the Rights of Persons with Disabilities (CRPD) in promoting and protecting the equal right of persons with disabilities to freedom of expression and opinion and access to information, focusing on 21. The discussion draws links between this provision and Article 19 of the International Covenant on Civil and Political Rights, and stresses the importance of the CRPD in applying the right to freedom of expression and opinion and access to information to the specific circumstances of persons with disabilities. Links are drawn also between Article 21 and other provisions of the CRPD, particularly Article 9 on accessibility. The chapter concludes with a reflection on the opportunities and challenges associated with the implementation of Article 21 by states parties to the Convention.
Consent to Be Bound
Authors: Bantekas Ilias
Published: March 2019

This chapter examines Article 43 of the United Nations Convention on the Rights of Persons with Disabilities (CRPD). The formal act by which a state consents to be bound by a treaty is expressed through ratification. The various legal terms used to denote such consent (ie acceptance, approval, or accession) produce the same functional and legal effect in the international sphere. Their differences lie chiefly in the states’ internal/constitutional sphere. Article 43 CRPD departs from equivalent provisions in other treaties under the UN aegis, as well as other multilateral treaties, at least in phrasing. Other multilateral treaties specifically distinguish between the two classical types of consent: a) that which is open to signatory states, namely ratification, acceptance and approval and; b) that which is open to non-signatories, namely accession. Article 43 does not make this distinction explicit. Its wording seems to suggest that acceptance and approval are excluded from its ambit, but given that both of these produce exactly the same legal effects as ratification, the distinction is practically meaningless.
A bibliometric analysis on cognitive processing of emotional words
Authors: Liu Jia , Fan Lin , Yin Hongshan
Published: March 2019

To investigate the growth of studies on emotional word processing, co-citations and co-occurring terms in related research were analyzed by using CiteSpace software. Through visualizing the references obtained from Web of Science (WoS) Core Collection of Thomson Reuters, the main research patterns and the hot research topics were identified. The research patterns include processing levels (implicit and explicit processing), the comparison between emotional and neutral words as well as visual emotional word processing under various tasks such as blink modification and subvocal rehearsal. The hot themes are: (1) the neural correlates of negative, positive and neutral words, (2) individual differences in trait anxiety, gender or eating disorders, and (3) audiovisual processing of emotional stimuli (words, faces, pictures, and sounds). Different from the previous review papers, the present study offers a new approach to visualizing relevant data over the past three decades to synthesize scientific research findings on emotional word processing. In addition, suggestions for future work in this area are provided.
An aero mycological analysis of Mucormycetes in indoor and outdoor environments of northern India
Authors: Prakash Hariprasath , Singh Shreya , Rudramurthy Shivaprakash Mandya , Singh Pankaj , Mehta Neha , Shaw Dipika , Ghosh Anup Kumar
Published: March 2019

Mucormycosis is an angio-invasive infection, predominantly acquired by inhalation of sporangiospores from the environment. However, the burden of Mucormycetes sporangiospores in the air is not well studied. We aimed to estimate the burden of Mucormycetes spores in the outdoor and indoor (hospital) environment across different seasons in north India. A total of 380 air samples from outdoor (n = 180) and indoor (n = 200) environment were included in the study. Air samples were suctioned using air sampler (100 l/min) and cultured on Dichloran Rose Bengal Chloramphenicol (DRBC) with benomyl for selective isolation of Mucormycetes. The isolates were identified by phenotypic and genotypic methods. The mean spore count (±SD) of Mucormycetes (cfu/m3) in outdoor samples varied from 0.73 (±0.96) to 8.60 (±5.70) across different seasons. In hospital, the mean spore count varied from 0.68 (±1.07) to 1.12 (±1.07) and 0.88 (±1.01) to 1.72 (±2.17) for air-conditioned wards and non-air-conditioned wards, respectively. Rhizopus arrhizus was the predominant agent isolated from both indoor and outdoor environment followed by Cunninghamella species. We also report a single isolate of the rare mucormycete agent, Apophysomyces variabilis from outdoor environment. The present study highlights the presence of low spore burden of Mucormycetes in outdoor and hospital settings in north India. This study also reports the first isolation of A. variabilis from air samples in the Indian subcontinent.
Microsurgical Ligation of Residual Fistulous Arteriovenous Shunt From a Radicular Artery to a Thoracic Arteriovenous Malformation: 2-Dimensional Operative Video
Authors: See Alfred Pokmeng , Fehnel Katie Pricola , Orbach Darren B , Smith Edward R
Published: March 2019

The literature has long attempted distinct classifications of arteriovenous fistulae and arteriovenous malformations of the spine.
1-3
It is worth noting that lesions can become more complex during recurrence and may not adhere to traditional definitions. In these cases, recognizing the principles of pathology and pathophysiology can guide management and treatment. We present the case of a spinal arteriovenous malformation with recurrence after prior treatment that is managed in the setting of a second opinion with a multidisciplinary approach. This case demonstrates (1) an evolution of recurrent arteriovenous shunting pathology observed both in the endovascular suite, and under direct microscopic visualization and (2) considerations in multimodal treatment with endovascular devices during microsurgical dissection and extirpation.

 This manuscript was prepared with informed assent provided by the patient (a minor) and with informed consent by the parent of the patient, who is their legal representative and health-care proxy.
Anterior Transpetrosal Approach for Trigeminal Schwannoma with Persistent Primitive Trigeminal Artery: 2-Dimensional Operative Video
Authors: Matsushima Ken , Kohno Michihiro , Izawa Hitoshi , Tanaka Yujiro
Published: March 2019

The surgical management of trigeminal schwannomas often requires complicated skull base approaches based on detailed anatomical understanding because of the involvement of multiple compartments of the trigeminal nerve from its root to the peripheral branches. When there is vital anatomical anomaly around the tumor, this can make the surgical management and anatomical understanding more difficult.
1,2
This video demonstrates the microsurgical removal of a dumbbell-shaped trigeminal schwannoma via the anterior transpetrosal transtentorial approach in a patient with a persistent primitive trigeminal artery, the most common persistent embryonic carotid-vertebrobasilar anastomosis. A 32-yr-old woman presented with progressive facial sensory impairment, dizziness, and slight diplopia because of right abducens palsy. Neuroimaging revealed a right Meckel's cave tumor extending to both the middle and posterior cranial fossae and displacing the abducens nerve inferomedially. The persistent primitive trigeminal artery, which is an anomalous communication between the cavernous carotid and basilar arteries, was identified ventral to the tumor. While preserving most of the noninvaded trigeminal nerve, gross-total resection was achieved under direct visualization of the abducens nerve and persistent primitive trigeminal artery, piercing the dura of the posterior cavernous sinus and coursing medially along the clivus. The patient's facial sensory impairment and diplopia almost disappeared without new neurological deficits or tumor recurrence during the follow-up period of 1 yr. Three-dimensional reconstructed images demonstrated the anatomical relationship of the tumor, the persistent primitive trigeminal artery, and the extent of osseous drilling of the petrosectomy. Informed consent was obtained from the patient.
Genomes from Bacteria Associated with the Canine Oral Cavity: a Test Case for Automated Genome-Based Taxonomic Assignment
Authors: Coil David A. , Jospin Guillaume , Darling Aaron E. , Wallis Corrin , Davis Ian J. , Harris Stephen , Eisen Jonathan A. , Holcombe Lucy J. , O’Flynn Ciaran
Published: March 2019

Taxonomy for bacterial isolates is commonly assigned via sequence analysis. However, the most common sequence-based approaches (e.g. 16S rRNA gene-based phylogeny or whole genome comparisons) are still labor intensive and subjective to varying degrees. Here we present a set of 33 bacterial genomes, isolated from the canine oral cavity. Taxonomy of these isolates was first assigned by PCR amplification of the 16S rRNA gene, Sanger sequencing, and taxonomy assignment using BLAST. After genome sequencing, taxonomy was revisited through a manual process using a combination of average nucleotide identity (ANI), concatenated marker gene phylogenies, and 16S rRNA gene phylogenies. This taxonomy was then compared to the automated taxonomic assignment given by the recently proposed Genome Taxonomy Database (GTDB). We found the results of all three methods to be similar (25 out of the 33 had matching genera), but the GTDB approach was less subjective, and required far less labor. The primary differences in the remaining taxonomic assignments related to proposed taxonomy changes by the GTDB team.
Sickle cell disease complications: prevalence and resource utilization
Authors: Shah Nirmish , Bhor Menaka , Xie Lin , Paulose Jincy , Yuce Huseyin
Published: March 2019

This study evaluated the prevalence rate of vaso-occlusive crisis (VOC) episodes, rates of uncomplicated and complicated VOC episodes, and the primary reasons for emergency room (ER) visits and inpatient admissions for sickle cell disease (SCD) patients. The Medicaid Analytic extracts database was used to identify adult SCD patients using claims from 01JUL2009-31DEC2012. The date of the first observed SCD claim was designated as the index date. Patients were required to have continuous medical and pharmacy benefits for ≥6 months baseline and ≥12 months follow-up period. Patient demographics, baseline clinical characteristics, the rate of uncomplicated and complicated VOC (VOC with concomitant SCD complications) episodes, and reasons for ER visits and inpatient stays were analyzed descriptively. A total of 8,521 patients were included in the analysis, with a median age of 30 years. The average follow-up period was 2.7 years. The rate of VOC episodes anytime in the follow-up was 3.31 in person-years. During the first-year follow-up period, an average of 2.79 VOC episodes were identified per SCD patients, with 1.06 VOC episodes treated in inpatient setting and 0.90 VOC episodes in ER without admission. A total of 76,154 VOC episodes were identified during the entire follow-up period for the overall SCD patients. Most of the VOC episodes (70.3% [n=53,523]) were uncomplicated episodes, and 29.7% were complicated episodes. Using primary diagnosis claims only, the most frequent complications during the VOC episode were infectious diseases (25.9%), fever (21.8%), and pulmonary disorders (16.2%). Among ER and hospitalizations related to VOC or SCD complication, ~85.0% had VOCs as the primary reason for admission; 15.0% had SCD complications as the primary reason. In summary, SCD and its related comorbidities and complications result in high acute health care utilization. In addition, VOC remains the primary reason for SCD patients’ ER visits and inpatient admissions.
A non-Dicer RNase III and four other novel factors required for RNAi-mediated transposon suppression in the human pathogenic yeastC. neoformans
Authors: Burke Jordan E. , Longhurst Adam D. , Natarajan Prashanthi , Rao Beiduo , Liu S. John , Sales-Lee Jade , Mortensen Yasaman , Moresco James J. , Diedrich Jolene K. , Yates John R. , Madhani Hiten D.
Published: March 2019

The human pathogenic yeastCryptococcus neoformanssilences transposable elements using endo-siRNAs and an Argonaute, Ago1. Endo-siRNAs production requires the RNA-dependent RNA polymerase, Rdp1, and two partially redundant Dicer enzymes, Dcr1 and Dcr2, but is independent of histone H3 lysine 9 methylation. We describe here an insertional mutagenesis screen for factors required to suppress the mobilization of theC. neoformans HARBINGERfamily DNA transposonHAR1. Validation experiments uncovered five novel genes (RDE1-5) required forHAR1suppression and global production of suppressive endo-siRNAs. Loss of theRDEgenes does not impact transcript levels, suggesting the endo-siRNAs do not act by impacting target transcript synthesis or turnover.RDE3encodes a non-Dicer RNase III related toS. cerevisiaeRnt1,RDE4encodes a predicted terminal nucleotidyltransferase, whileRDE5has no strongly predicted encoded domains. Affinity purification-mass spectrometry studies reveal that Rde3 and Rde5 are physically associated.RDE1encodes a G-patch protein homologous to theS. cerevisiaeSqs1/Pfa1, a nucleolar protein that directly activates the essential helicase Prp43 during rRNA biogenesis. Rde1 copurifies Rde2, another novel protein obtained in the screen, as well as Ago1, a homolog of Prp43, and numerous predicted nucleolar proteins. We also describe the isolation of conditional alleles ofPRP43, which are defective in RNAi. This work reveals unanticipated requirements for a non-Dicer RNase III and presumptive nucleolar factors for endo-siRNA biogenesis and transposon mobilization suppression inC. neoformans.
1-Methyl-tryptophan enantiomers differently affect the cross-talking between mononuclear and tumor cells and interferon-γ production
Authors: Branquinho Maryana Stephany Ferreira , Silva Maysa Braga Barros , Clara Renan Orsati , Julio Ariane Rivellis , Engler Silvya Stuchi Maria , Junior Ernani Pinto , Campa Ana
Published: March 2019

The inhibition of the enzyme indoleamine-2,3-dioxygenase (IDO), that catalyzes the oxidation of the amino acid tryptophan to kynurenine (KYN), is considered a good target for immunoadjuvants in antineoplastic therapy. 1-Methyl-tryptophan (1-MT) is the most studied molecule for this purpose. Although L-1-MT is better than D-1-MT in inhibiting IDO, for an unknown reason the D-enantiomer has higher clinical efficacy. Here we took advantage of co-cultures of tumor cells (SK-Mel 19 melanoma line; 1×105 cells/well) with peripheral blood mononuclear cells (PBMC; 5×106 cells/well) to verify the effect of 1-MT enantiomers on cytokine production and tumoricidal activity. At a concentration that did not affect KYN production, 1-MT (50 µM) affected the production of TNF-α, IL-10, and IFN-γ measured in co-cultures supernatants. Stereospecificity was only observed for IFN-γ production. D-1-MT inhibited more than 30% of IFN-γ production, while L-1-MT had no effect. Stereospecific effect was also seen in PBMC tumoricidal activity, estimated by tumor cell viability (Trypan assay). The racemic mixture DL- and D-1-MT almost doubled the tumoricidal activity of PBMCs, while L-1-MT had no effect. These are previous unknown off-target effects of D-1-MT. Our data suggest the modulation of IFN-γ and the activation of tumor recognition and killing processes by immune cells as important features for the in vivo effects of the D-1-MT. These findings should be considered in future studies of immunoadjuvants for cancer treatment.
Constitutive Siglec-1 expression by human dendritic cell precursors enables HIV-1 replication and transmission
Authors: Ruffin Nicolas , Gea-Mallorquí Ester , Brouiller Flavien , Jouve Mabel , Silvin Aymeric , See Peter , Dutertre Charles-Antoine , Ginhoux Florent , Benaroch Philippe
Published: March 2019

Human dendritic cell (DC) lineage has been recently unraveled by high dimensional mapping revealing the existence of a discrete new population of blood circulating DC precursor (pre-DC also referred to as AS DC). Among all blood DC subsets, only pre-DC highly express Siglec-1, a lectin-like receptor able to bind HIV-1. We show that pre-DC are uniquely equipped among blood DC populations to promote HIV-1 replication and dissemination. Pre-DC stands out as the most susceptible DC population to infection by both HIV-1 CXCR4- and CCR5-tropic viral particles in a Siglec-1-dependent manner. HIV-1-infected pre-DC produce new viral progeny and transmit the virus to CD4+T cells. Upon TLR activation, pre-DC become resistant to HIV-1 fusion and thus to infection and switch to a replication-independent mechanism of virus transfer to activated primary T lymphocytes mediated by Siglec-1. Thus, beside their role in DC ontogeny, blood pre-DC possess stage-specific properties that HIV-1 may exploit for viral spreading and modulation of the immune response.
Changes in gene expression shift and switch genetic interactions
Authors: Li Xianghua , Lalic Jasna , Baeza-Centurion Pablo , Dhar Riddhiman , Lehner Ben
Published: March 2019

An important goal in disease genetics and evolutionary biology is to understand how mutations combine to alter phenotypes and fitness. Non-additive interactions between mutations occur extensively and change across conditions, cell types, and species, making genetic prediction a difficult challenge. To understand the reasons for this, we reduced the problem to a minimal system where we combined mutations in a single protein performing a single function (a transcriptional repressor inhibiting a target gene). Even in this minimal system, a change in gene expression altered both the strength and type of genetic interactions. These seemingly complicated changes could, however, be predicted by a mathematical model that propagates the effects of mutations on protein folding to the cellular phenotype. We show that similar changes will be observed for many genes. These results provide fundamental insights into genotype-phenotype maps and illustrate how changes in genetic interactions can be predicted using hierarchical mechanistic models.

One sentence Summary

Deep mutagenesis of the lambda repressor reveals that changes in gene expression will alter the strength and direction of genetic interactions between mutations in many genes.

Highlights

Deep mutagenesis of the lambda repressor at two expression levels reveals extensive changes in mutational effects and genetic interactions

Genetic interactions can switch from positive (suppressive) to negative (enhancing) as the expression of a gene changes

A mathematical model that propagates the effects of mutations on protein folding to the cellular phenotype accurately predicts changes in mutational effects and interactions

Changes in expression will alter mutational effects and interactions for many genes

For some genes, perfect mechanistic models will never be able to predict how mutations of known effect combine without measurements of intermediate phenotypes
Spheroplast-mediated carbapenem tolerance in Gram-negative pathogens
Authors: Cross Trevor , Ransegnola Brett , Shin Jung-Ho , Weaver Anna , Fauntleroy Kathy , VanNieuwenhze Michael , Westblade Lars F. , Dörr Tobias
Published: March 2019

Antibiotic tolerance, the ability to temporarily sustain viability in the presence of bactericidal antibiotics, constitutes an understudied, yet likely widespread cause of antibiotic treatment failure. We have previously shown that the Gram-negative pathogen Vibrio cholerae is able to tolerate exposure to the typically bactericidal β-lactam antibiotics by assuming a spherical morphotype devoid of detectable cell wall material. However, it is unclear how widespread tolerance is. Here, we have tested a panel of clinically significant Gram-negative pathogens for their response to the potent, broad-spectrum carbapenem antibiotic meropenem. We show that clinical isolates of Enterobacter cloacae, Klebsiella pneumoniae, and Klebsiella aerogenes, but not Escherichia coli, exhibit moderate to high levels of tolerance to meropenem, both in laboratory growth medium and in human serum. Importantly, tolerance was mediated by cell wall-deficient spheroplasts, which readily recovered to wild-type morphology and exponential growth upon removal of antibiotic. Our results suggest that carbapenem tolerance is prevalent in clinically significant bacterial species, and we suggest that this could contribute to treatment failure associated with these organisms.
An open resource of structural variation for medical and population genetics
Authors: Collins Ryan L. , Brand Harrison , Karczewski Konrad J. , Zhao Xuefang , Alföldi Jessica , Francioli Laurent C. , Khera Amit V. , Lowther Chelsea , Gauthier Laura D. , Wang Harold , Watts Nicholas A. , Solomonson Matthew , O’Donnell-Luria Anne , Baumann Alexander , Munshi Ruchi , Walker Mark , Whelan Christopher , Huang Yongqing , Brookings Ted , Sharpe Ted , Stone Matthew R. , Valkanas Elise , Fu Jack , Tiao Grace , Laricchia Kristen M. , Ruano-Rubio Valentin , Stevens Christine , Gupta Namrata , Margolin Lauren ,   Genome Aggregation Database Production Team,   Genome Aggregation Database Consortium, Taylor Kent D. , Lin Henry J. , Rich Stephen S. , Post Wendy , Chen Yii-Der Ida , Rotter Jerome I. , Nusbaum Chad , Philippakis Anthony , Lander Eric , Gabriel Stacey , Neale Benjamin M. , Kathiresan Sekar , Daly Mark J. , Banks Eric , MacArthur Daniel G. , Talkowski Michael E.
Published: March 2019

Structural variants (SVs) rearrange large segments of the genome and can have profound consequences for evolution and human diseases. As national biobanks, disease association studies, and clinical genetic testing grow increasingly reliant on genome sequencing, population references such as the Genome Aggregation Database (gnomAD) have become integral for interpreting genetic variation. To date, no large-scale reference maps of SVs exist from high-coverage sequencing comparable to those available for point mutations in protein-coding genes. Here, we constructed a reference atlas of SVs across 14,891 genomes from diverse global populations (54% non-European) as a component of gnomAD. We discovered a rich landscape of 433,371 distinct SVs, including 5,295 multi-breakpoint complex SVs across 11 mutational subclasses, and examples of localized chromosome shattering, as in chromothripsis. The average individual harbored 7,439 SVs, which accounted for 25-29% of all rare protein-truncating events per genome. We found strong correlations between constraint against damaging point mutations and rare SVs that both disrupt and duplicate protein-coding sequence, suggesting intolerance to reciprocal dosage alterations for a subset of tightly regulated genes. We also uncovered modest selection against noncoding SVs in cis-regulatory elements, although selection against protein-truncating SVs was stronger than any effect on noncoding SVs. Finally, we benchmarked carrier rates for medically relevant SVs, finding very large (≥1Mb) rare SVs in 3.8% of genomes (~1:26 individuals) and clinically reportable incidental SVs in 0.18% of genomes (~1:556 individuals). These data have been integrated directly into the gnomAD browser (https://gnomad.broadinstitute.org) and will have broad utility for population genetics, disease association, and diagnostic screening.
Selection of a Malignant Subpopulation from a Colorectal Cancer Cell Line
Authors: Lai Pei-Lun , Chen Ting-Chun , Feng Chun-Yen , Lin Hsuan , Wu Ng , Chen Yun , Hsiao Michael , Lu Jean , Huang Hsiao-Chun
Published: March 2019

Colorectal cancer (CRC) is a leading cause of death from cancer worldwide. Thus, there is an emerging need for new experimental models that allow identification and validation of biomarkers for CRC-specific progression. In this study, we propose a repeated sphere-forming assay as a strategy to select a malignant subpopulation from a CRC line, HCT116. We validated our assay by confirming that three canonical stemness markers, Nanog, Oct4, and Lgr5, were up-regulated in the sphere state at every generation of the selection assay. The resulting line, after eight rounds of selection, exhibited an increased sphere-forming capacityin vitroand tumorgenicityin vivo. Furthermore, dipeptidase 1 (DPEP1) was identified as the major differentially expressed gene in the selected clone, and depletion of DPEP1 suppressed the elevated sphere-forming capacityin vitroand tumorgenicityin vivo. Overall, we have established an experimental strategy for the isolation of a malignant subpopulation from a CRC cell line. Results from our model also suggested that DPEP1 can serve as a promising prognostic biomarker for CRC.