bluuebunny/crossref_metadata_2025 huggingface dataset:
Influenza Vaccine Effectiveness Against Hospitalization in Fully and Partially Vaccinated Children in Israel: 2015–2016, 2016–2017, and 2017–2018
Authors: Segaloff Hannah E , Leventer-Roberts Maya , Riesel Dan , Malosh Ryan E , Feldman Becca S , Shemer-Avni Yonat , Key Calanit , Monto Arnold S , Martin Emily T , Katz Mark A
Published: February 2019

Background

Influenza vaccine effectiveness (VE) varies by season, circulating influenza strain, age, and geographic location. There have been few studies of influenza VE among hospitalized children, particularly in Europe and the Middle East.

Methods

We estimated VE against influenza hospitalization among children aged 6 months to 8 years at Clalit Health Services hospitals in Israel in the 2015–2016, 2016–2017, and 2017–2018 influenza seasons, using the test-negative design. Estimates were computed for full and partial vaccination.

Results

We included 326 influenza-positive case patients and 2821 influenza-negative controls (140 case patients and 971 controls from 2015–2016, 36 case patients and 1069 controls from 2016–2017, and 150 case patients and 781 controls from 2017–2018). Over all seasons, VE was 53.9% for full vaccination (95% confidence interval [CI], 38.6%–68.3%), and 25.6% for partial vaccination (−3% to 47%). In 2015–2016, most viruses were influenza A(H1N1) and vaccine lineage–mismatched influenza B/Victoria; the VE for fully vaccinated children was statistically significant for influenza A (80.7%; 95% CI, 40.3%–96.1%) but not B (23.0%; −38.5% to 59.4%). During 2016–2017, influenza A(H3N2) predominated, and VE was (70.8%; 95% CI, 17.4%–92.4%). In 2017–2018, influenza A(H3N2), H1N1 and lineage-mismatched influenza B/Yamagata cocirculated; VE was statistically significant for influenza B (63.0%; 95% CI, 24.2%–83.7%) but not influenza A (46.3%; −7.2% to 75.3%).

Conclusions

Influenza vaccine was effective in preventing hospitalizations among fully vaccinated Israeli children over 3 influenza seasons, but not among partially vaccinated children. There was cross-lineage protection in a season where the vaccine contained B/Victoria and the circulating strain was B/Yamagata, but not in a season with the opposite vaccine-circulating strain distribution.
Identification of Chitinase-3-Like Protein 1 as a Novel Neutrophil Antigenic Target in Crohn’s Disease
Authors: Deutschmann Claudia , Sowa Mandy , Murugaiyan Jayaseelan , Roesler Uwe , Röber Nadja , Conrad Karsten , Laass Martin W , Bogdanos Dimitrios , Sipeki Nora , Papp Maria , Rödiger Stefan , Roggenbuck Dirk , Schierack Peter
Published: February 2019

Background and Aims

There is an increasing incidence of inflammatory bowel disease [IBD]. Autoimmune responses are involved in the pathophysiology of IBD, but their underlying pathways and target antigens have not yet been fully elucidated.

Methods

Autoantigenic targets in IBD were identified after separation of whole cell proteins isolated from neutrophils using two-dimensional electrophoresis and matrix assisted laser desorption ionization – time of flight mass spectrometry-based protein identification of the spots that displayed Western blotting signals with anti-neutrophil cytoplasmic antibody-positive sera. The prevalence of IgG, IgA and secretory IgA [sIgA] to chitinase 3-like protein 1 [CHI3L1] was analysed by enzyme-linked immunosorbent assays using recombinant CHI3L1 in 110 patients with Crohn’s disease [CD], 95 with ulcerative colitis [UC], 126 with coeliac disease [CeD] and 86 healthy controls [HCs].

Results

The 18-glycosylhydrolase family member CHI3L1 was identified as a neutrophil autoantigenic target. CD patients displayed significantly higher levels of IgG to CHI3L1 than patients with UC and CeD (p < 0.0001, respectively). IgA and sIgA to CHI3L1 was significantly higher in CD than in UC, CeD and HCs [p < 0.0001, respectively]. IgA and sIgA to CHI3L1 demonstrated the highest prevalence in CD [25.5%, 28/110; and 41.8%%, 46/110] compared to HCs [2.3%, 2/86; and 4.7%%, 4/86; p = 0.0015 and p < 0.0001] and are associated with a more complicated progression of CD.

Conclusion

CHI3L1 is a novel neutrophil autoantigenic target in CD. IgA and sIgA to CHI3L1 may serve as novel markers for CD and may facilitate the serological diagnosis of IBD.
Handmade stent graft fenestration to preserve left subclavian artery in thoracic endovascular aortic repair†
Authors: Kuo Huey-Shiuan , Huang Jih-Hsin , Chen Jer-Shen
Published: February 2019

OBJECTIVES

This study aimed to evaluate the efficacy and safety of a handmade fenestrated stent graft over an aortic stent graft for preserving the left subclavian artery (LSA) in thoracic endovascular aortic repair (TEVAR).

METHODS

From July 2015 to October 2018, a total of 32 consecutive patients with various thoracic aortic pathologies who underwent TEVAR in which handmade fenestration over a thoracic aortic stent graft was used for LSA were included. Outcomes including technical success, procedure-related complications, perioperative mortality and morbidity and graft patency were analysed.

RESULTS

Twenty-four patients (75.00%) presented with aortic dissection, 5 patients (15.63%) with thoracic aortic aneurysm and 2 patients (6.25%) with penetrating aortic ulcer; 1 patient (3.13%) required re-TEVAR due to endoleak and sac expansion from previous TEVAR for thoraco-abdominal aneurysm. TEVAR was performed in a zone 2 landing with single fenestration for LSA (26 patients, 81.25%), zone 1 landing with double fenestration for both LSA and left common carotid artery (5 patients, 15.63%) or zone 1 landing with single fenestration for LSA and a chimney graft for left common carotid artery (1 patient, 3.13%). The technical success rate, defined as the successful alignment of fenestration to LSA, was 93.75%. At a mean follow-up of 17.3 months, 4 cases of endoleak and 2 cases of stent graft-induced new entry were noted, 3 of which were treated endovascularly.

CONCLUSIONS

Our preliminary results demonstrate the viability of preserving LSA blood flow in TEVAR using a handmade stent graft fenestration to treat various aortic pathologies in various clinical situations and the technical feasibility and short-term results that may justify the use of this method in emergency cases.
Real-world referral pattern and outcomes of diabetic patients who undergo revascularization: data from the prospective Multi-vessel Coronary Artery Disease (MULTICAD) Israeli Registry†
Authors: Ram Eilon , Goldenberg Ilan , Sternik Leonid , Peled Yael , Segev Amit , Kogan Alexander , Vorobeichik Pechersky Dina , Shlomo Nir , Raanani Ehud
Published: February 2019

OBJECTIVES

Diabetes mellitus patients with multivessel coronary artery disease present with a poor prognosis. We aimed to explore real-life clinical outcomes of diabetic patients who were referred for coronary revascularization.

METHODS

We used data from the Multi-vessel Coronary Artery Disease (MULTICAD) Israeli Registry. Using descriptive statistics, Kaplan–Meier, Cox and logistic regression, we described a revascularization referral pattern, short-term outcomes and long-term survival among 475 diabetic patients with multivessel and/or left main disease, 48% of whom underwent surgical and 52% percutaneous revascularization.

RESULTS

Factors independently associated with referral for surgery included the presence of left main stenosis [odds ratio (OR) 1.89; P = 0.030] and a higher Syntax score (OR 1.15 per point increment; P < 0.001), whereas an older age (OR 1.03 per 1-year increment in age; P = 0.019), prior percutaneous coronary intervention (OR 1.83; P = 0.009) and the presence of renal impairment (OR 2; P = 0.026) were associated with percutaneous coronary intervention referral. At 7 months of follow-up, multivariable analysis did not reveal any difference in mortality risk between the surgical and percutaneous revascularization groups [hazard ratio (HR) 1.23, 95% confidence interval (CI) 0.5–3.04; P = 0.649], whereas after 7 months, surgical revascularization was associated with a significant survival benefit (HR 2.24, 95% CI 1.03–4.87; P = 0.042).

CONCLUSIONS

Our observation suggests that in a real-world setting, only approximately one-half of diabetic patients with multivessel disease are referred to surgical revascularization despite guideline indications. Surgical compared to percutaneous revascularization in this population was associated with improved long-term survival that became evident 7 months after the revascularization procedure.
Chaotic dynamics from a pseudo-linear system
Authors: Ghane Hamed , Sterk Alef E , Waalkens Holger
Published: February 2019

Investigating the possibility of applying techniques from linear systems theory to the setting of non-linear systems has been the focus of many papers. The pseudo-linear (PL) form representation of non-linear dynamical systems has led to the concept of non-linear eigenvalues (NEValues) and non-linear eigenvectors (NEVectors). When the NEVectors do not depend on the state vector of the system, then the NEValues determine the global qualitative behaviour of a non-linear system throughout the state space. The aim of this paper is to use this fact to construct a non-linear dynamical system of which the trajectories of the system show continual stretching and folding. We first prove that the system is globally bounded. Next we analyse the system numerically by studying bifurcations of equilibria and periodic orbits. Chaos arises due to a period doubling cascade of periodic attractors. Chaotic attractors are presumably of Hénon-like type, which means that they are the closure of the unstable manifold of a saddle periodic orbit. We also show how PL forms can be used to control the chaotic system and to synchronize two identical chaotic systems.
A Systematic Review and Recommendation for Reporting of Surrogate Endpoint Evaluation Using Meta-analyses
Authors: Xie Wanling , Halabi Susan , Tierney Jayne F , Sydes Matthew R , Collette Laurence , Dignam James J , Buyse Marc , Sweeney Christopher J , Regan Meredith M
Published: February 2019

Background

Meta-analysis of randomized controlled trials (RCTs) has been widely conducted for the evaluation of surrogate endpoints in oncology, but little attention has been given to the adequacy of reporting and interpretation. This review evaluated the reporting quality of published meta-analyses on surrogacy evaluation and developed recommendations for future reporting.

Methods

We searched PubMed through August 2017 to identify studies that evaluated surrogate endpoints using the meta-analyses of RCTs in oncology. Both individual patient data (IPD) and aggregate data (AD) meta-analyses were included for the review.

Results

Eighty meta-analyses were identified: 22 used IPD and 58 used AD from multiple RCTs. We observed variability and reporting deficiencies in both IPD and AD meta-analyses, especially on reporting of trial selection, endpoint definition, study and patient characteristics for included RCTs, and important statistical methods and results. Based on these findings, we proposed a checklist and recommendations to improve completeness, consistency, and transparency of reports of meta-analytic surrogacy evaluation. We highlighted key aspects of the design and analysis of surrogate endpoints and presented explanations and rationale why these items should be clearly reported in surrogacy evaluation.

Conclusions

Our reporting of surrogate endpoint evaluation using meta-analyses (ReSEEM) guidelines and recommendations will improve the quality in reporting and facilitate the interpretation and reproducibility of meta-analytic surrogacy evaluation. Also, they should help promote greater methodological consistency and could also serve as an evaluation tool in the peer review process for assessing surrogacy research.
Ectopic cutaneous Schistosoma haematobium in the inguinal region
Authors: Slobbe Lennert , Demeyere Thomas B J , van Genderen Perry J J , Simon Cathy C , Huisman Willem J
Published: February 2019

A 66-year-old man with indolent systemic mastocytosis presented with a plaque-like cutaneous lesion at his right inguinal region. He had travelled to various African countries in the years before. Pathological examination revealed a granulomatous infiltrate surrounding eggs of Schistosoma haematobium. Ectopic cutaneous schistosomiasis was therefore diagnosed, for which he was treated with Praziquantel.
Myelomeningocele
Authors: Baird Lissa C.
Published: February 2019

Myelomeningocele classically presents as an open neural tube defect and carries an immediate risk for infection to the central nervous system. A complete preoperative evaluation for associated congenital anomalies is critical. Hydrocephalus will manifest at birth or develop postnatally in the majority of patients with open myelomeningocele. Broad spectrum antibiotic therapy prior to urgent surgical closure is standard treatment. Meticulous care should be taken when dissecting the placode in order to avoid inclusion of dermal elements or injury to the parenchyma and nerve roots. Reconstruction of the thecal sac should be carried out in a watertight fashion. Closure of myofascial and cutaneous layers may require complex repair techniques depending on the size of the defect. Meticulous closure will minimize postoperative wound healing complications.
Sagittal Synostosis
Authors: Proctor Mark , Hazama Ali
Published: February 2019

Sagittal synostosis is the most common type of craniosynostosis and classically presents with an elongated head shape combined with frontal bossing, ridging along the sagittal suture, and a narrow and prominent occiput. The fused sagittal suture limits the biparietal expansion of the head and results in the scaphocephalic head shape. Imaging is often not necessary to establish an accurate diagnosis. Both open and endoscopic minimally invasive repair can be considered for children less than 4–6 months of age. Endoscopic surgery is increasingly being performed, as this option has significantly less blood loss, requires less anesthesia time, and is well tolerated by the patient compared to the open technique. Post-operative adjuvant therapy with a cranial orthosis is essential to redirect skull growth and prevent early refusion of the craniotomy. Attentiveness to identifying air embolisms can prevent major complications during surgery.
Inflicted Traumatic Brain Injury
Authors: Costine-Bartell Beth A. , Duhaime Ann-Christine
Published: February 2019

Inflicted traumatic brain injury may present with otherwise unexplained seizures or with subtle neurological impairment. Evaluation should include assessment for non-traumatic etiologies including infection, thrombosis, coagulopathy, and metabolic disorders. A complete skeletal survey and retinal examination are essential components to an evaluation of suspected inflicted injury, and collaboration with child protection experts should be undertaken. Early MR imaging may be helpful for establishing the extent of injury, prognosis, and need for aggressive management to limit progression of the injury. The neurosurgeon should be one of the many clinicians talking to the family. Families respond best when Child Protection Services is involved from the start and can react more negatively if this new team is introduced days into the hospital stay.
Traumatic Atlanto-Axial Dislocation
Authors: Brockmeyer Douglas
Published: February 2019

The presence of atlanto-axial dislocation (AOD) must be ruled out in pediatric patients with high-energy traumatic injuries. Young children are particularly prone to AOD given the high ratio of head to body size and mass. Dynamic x-rays and distracting cervical collars should not be used if a suspicion of AOD is present, as these can lead to neurologic compromise. A condylar-C1 interval (CCI) of greater than 4 mm on cervical spine CT with coronal and sagittal reconstructions is consistent with AOD. MRI will confirm the diagnosis and extent of ligamentous injury. Careful immobilization and elevation of blood pressure should be initiated and surgical stabilization with an occiput to C2 fusion planned. Instrumentation of the craniocervical spine may be challenging based on age and anatomy. Careful intraoperative technique will result in high rates of fusion.
Spastic Quadriplegia
Authors: Harter David
Published: February 2019

The diagnosis of spastic quadriplegia due to cerebral palsy should be made only after a detailed patient history. The patient should be assessed for prior history of prematurity, intraventricular hemorrhage, or static encephalopathy following a characteristic developmental progression of neurologic findings. MR imaging is used to assess brain anatomy, and the addition of metabolic and/or genetic testing for atypical cases should be considered. Proper patient selection for intrathecal baclofen placement can be confirmed by careful preoperative evaluation and a trial of intrathecal baclofen administered by lumbar puncture. Patients in the pediatric age range with significant medical comorbidities or with low BMI are at elevated risk of baclofen pump–related complications, which should be balanced against indications for pump placement.
Ruptured Arteriovenous Malformation
Authors: Smith Edward
Published: February 2019

Emergent assessment of a pediatric patient with a non-traumatic intraparenchymal brain hemorrhage should include strong consideration of arteriovenous malformation (AVM) as one of the leading diagnostic possibilities. Initial radiographic evaluation may include CT angiogram along with the initial CT. If the CT/A suggests the presence of an AVM, a more detailed assessment with digital subtraction angiography should be undertaken to evaluate for the presence of early draining veins and arterial feeders and to define the vascular anatomy of the lesion. MRI is helpful for delineating the relationship between the malformation and underlying brain structures. Multimodality treatment of pediatric AVMs is advocated. A primary surgical principle for AVM resection is obliteration of the feeding arteries prior to occlusion of the draining veins in order to avoid premature rupture. Total excision of the AVM is important to reduce the risk of rebleeding.
Hypothalamic-Chiasmatic Glioma
Authors: Rutka James , Coppola Angela
Published: February 2019

Hypothalamic-chiasmatic gliomas (HCG) are rare tumors, representing approximately 5% of all childhood brain tumors. Impairment in visual acuity is the most common clinical finding at presentation, followed by nystagmus and strabismus. Fundoscopy can reveal variable degrees of optic pallor or papilledema. Other findings may include signs and symptoms of elevated intracranial pressure or neuro-endocrinopathies. HCGs represent the most common central nervous system tumor in patients with neurofibromatosis type I. Small tumors without associated visual deficits should be monitored with surveillance imaging. Chemotherapy is the treatment of choice in younger patients, and radiotherapy should be considered only after failure of chemotherapy and surgical debulking. Primary tumor resection is not recommended unless the size of the tumor is causing significant mass effect or hydrocephalus.
Mesial Temporal Glioma
Authors: Grant Gerry
Published: February 2019

A patient with classic temporal lobe seizure semiology may present with aura, automatisms, and dystonic posturing. Video-electroencephalography (EEG) may identify the ictal onset and magnetoencephalography may further elucidate the anatomy of a temporal lobe abnormality, EEG dipoles, epileptogenic spike sources, and eloquent areas of language or motor function. Structural imaging of the temporal lobe with magnet resonance imaging (MRI) should also be obtained, as well as functional and metabolic imaging such as a subtraction single-photon emission computed tomography (SPECT) and interictal positron emission tomography (PET). Early surgery should be considered in pediatric patients for seizure control, to minimize the adverse effects of anti-epileptic drugs, maximize the child’s developmental potential, and reduce behavioral, cognitive and psychosocial problems. Intraoperative stereotactic navigation and electrocorticography (ECoG) can guide resection. Careful pre-operative planning for correct extent of surgery is key to the best possible seizure outcome.
Nasal Dermoid
Authors: Garton Hugh J. L.
Published: February 2019

Nasal dermoids are dermal sinus tracts can present along the midline anywhere from the columella to the nasofrontal suture. These lesions may follow a benign clinical course or may present with meningitis, epidural abscess, tract blockage, swelling, and infection. Nasal dermoid lesions occur due to incomplete separation between cutaneous ectoderm and a dural diverticula. MRI is the best diagnostic study to evaluate the lesion and determine intracranial extension, although CT may be necessary to demonstrate the presence of a midline bony defect. Operative intervention for complete removal of the tract is generally indicated to minimize risk of central nervous system infection or mass lesion. Postoperative cerebrospinal fluid leak should be managed by surgical re-exploration and possibly temporary cerebrospinal fluid diversion.
Sinusitus with Subdural Empyema
Authors: Sayama Christina
Published: February 2019

Subdural empyema is considered a neurosurgical emergency and, if found on neuroimaging, should prompt craniotomy for evacuation followed by broad spectrum antibiotics. In the setting of a patient with severe parenchymal swelling, a craniectomy may be indicated, as well as other modalities to lower intracranial pressure. Clinical care and decision making occurs with a multidisciplinary team of pediatric intensivists, infectious disease specialists, otolaryngologists, and neurosurgeons. Detection of recurrent subdural empyema is critical to prevent further morbidity and mortality, and surveillance of fever, neurologic examination, and follow-up imaging is critical. Timely surgical treatment of these infections can lead to good clinical outcomes.
Treating Gender and Illness Together in the Classroom
Authors: Diedrich Lisa
Published: February 2019

With an M.A. and Ph.D. in women’s, gender, and sexuality studies and with areas of specialization in medical/health humanities and disability studies, the author’s training, research, and teaching are inter- or transdisciplinary all the way down. Drawing on multiple interdisciplinary backgrounds, the author discusses ways of treating illness and disability in the classroom as women, gender, and sexuality might be treated: as categories of analysis that come into being through a multiplicity of archives, discourses, practices, and institutions. Rather than stabilize and consecrate an object as belonging to a particular field, the author is more interested in attending to the histories, methods, and political factors that bring objects and whole fields into being and sustaining or transforming them. The chapter discusses specific practical, even personal, pedagogical tactics and strategies.
Literacy Beyond the Single Story
Authors: Blackie Michael , Wear Delese , Zarconi Joseph
Published: February 2019

This chapter examines two interrelated topics: the class-based disconnect between US medical students and the majority of patients in their care as they learn medicine; and the prevailing cultural mood that people can overcome most obstacles and improve their lives by sheer force of individual will. To interrogate this perception, the chapter focuses on the lived experiences of Claireece “Precious” Jones in Lee Daniels’s film Precious (2009). The film illustrates the complicated ways that class intersects with gender, race, literacy, and health and that defies “single-story” thinking. The chapter offers strategies and exercises for analyzing the film and how they can be incorporated in the classroom in order to illuminate these intersections and to enable students to recognize the structural causes of poverty.
Moving Pictures
Authors: Jones Therese
Published: February 2019

In health humanities classrooms, visual materials such as documentary films, photographs, and even YouTube videos often serve as accessible texts for the analysis and discussion of individual experiences of illness and disability or as evocative illustrations of issues such as access to care or end of life. Such works can foster empathic responses, sharpen critical thinking, and develop communication skills in health professions students. Visual materials can also serve as openings for students to critique the culture of healthcare itself and as opportunities for them to identify disparities, confront stigma and discrimination, and envision change. Thus, the visual arts not only encourage our students to see but also reveal to them how, what, and why they see what they see—sometimes prompting their action and often provoking their transformation. This chapter describes and defines visual culture and visual activism in the context of three health and human rights movements of the twentieth century—breast cancer, AIDS, and disability rights—that have all foregrounded the critical practice and political strategy of producing visibility and deploying testimony in forms such as documentary, video, photography, and poster art. It then describes health humanities methodologies and materials in three content areas—mental illness, trauma of war, and disability—used in a variety of classroom settings to enable critical analysis and explore advocacy and intervention. For example, students consider the difference between looking and witnessing, how visual images influence attitudes toward patients and impact health policy, and the balance between inciting moral outrage from exposure to images and inducing compassion fatigue from overexposure to them.
Emergencies in HIV-positive patients
Authors: Ramrakha Punit S. , Moore Kevin P. , Sam Amir H.
Published: February 2019

This chapter describes emergencies in human immunodeficiency virus (HIV)-positive patients, including emergency presentations of HIV infection, factors influencing presentation of HIV disease, HIV testing, clinical indicator diseases for adult HIV infection, primary HIV infection (PHI), acute neurological conditions in HIV-positive patients, respiratory emergencies in HIV-positive patients, gastrointestinal (GI) presentations in HIV-positive patients, pyrexia of unknown origin, immune reconstruction inflammatory syndrome (IRIS), dermatological presentations, haematological presentations, antiretroviral toxicity, drug interactions with antiretroviral therapy, and post-exposure prophylaxis (PEP).
Lung cancer in an ex-smoker with underlying lung fibrosis
Authors: Ainley Adam , Makker Himender
Published: February 2019

This case study looks at Lung cancer in an ex-smoker with underlying lung fibrosis, and provides questions with model answers.
Advanced lung cancer on CT pulmonary angiogram in a patient presenting to an accident and emergency department with chest pain and breathlessness
Authors: Ainley Adam , Makker Himender
Published: February 2019

This case study looks at Advanced lung cancer on CTPA in a patient presenting to Accident & Emergency department with chest pain and breathlessness, and provides questions with model answers.
Histology of a right hilar mass in an ex-smoker
Authors: Ainley Adam , Gillibrand Rebecca , Makker Himender
Published: February 2019

This case study looks at Histology of right hilar mass in an ex-smoker, and provides questions with model answers.
Stage IIA adenocarcinoma of the lung in a never smoker undergoing adjuvant chemotherapy
Authors: Januszewski Adam , Popat Sanjay
Published: February 2019

This case study looks at Stage IIA adenocarcinoma of lung in a never smoker undergoing adjuvant chemotherapy, and provides questions with model answers.
Left pneumonectomy in a 25 year old female with a carcinoid tumour
Authors: Hayward Martin , Panagiotopoulos Nikolaos
Published: February 2019

This case study looks at Left pneumonectomy in a 25 year old with carcinoid tumour, and provides questions with model answers.
Titration of pain relief in a patient with right lung adenocarcinoma who received local radiotherapy
Authors: Hagena Antke
Published: February 2019

This case study looks at Use of nerve block in case of Right Lung Adenocarcinoma, received local radiotherapy and nerve block, and provides questions with model answers.
Expression of ERG11 and efflux pump genes CDR1, CDR2 and SNQ2 in voriconazole susceptible and resistant Candida glabrata strains
Authors: Navarro-Rodríguez Patricia , Martin-Vicente Adela , López-Fernández Loida , Guarro Josep , Capilla Javier
Published: February 2019

Candida glabrata causes difficult to treat invasive candidiasis due to its antifungal resistance, mainly to azoles. The aim of the present work was to study the role of the genes ERG11, CDR1, CDR2, and SNQ2 on the resistance to voriconazole (VRC) in a set of C. glabrata strains with known in vitro and in vivo susceptibility to this drug. Eighteen clinical isolates of C. glabrata were exposed in vitro to VRC, and the expression of the cited genes was quantified by real time quantitative polymerase chain reaction (q-PCR). In addition, the ERG11 gene was amplified and sequenced to detect possible mutations. Ten synonymous mutations were found in 15 strains, two of them being reported for the first time; however, no amino acid changes were detected. ERG11 and CDR1 were the most expressed genes in all the strains tested, while the expression of CDR2 and SNQ2 was modest. Our results show that gene expression does not directly correlate with the VRC MIC. In addition, the expression profiles of ERG11 and efflux pump genes did not change consistently after exposure to VRC. Although individual analysis did not result in a clear correlation between MIC and gene expression, we did observe an increase in ERG11 and CDR1 expression in resistant strains. It is of interest that considering both in vitro and in vivo results, the slight increase in such gene expression correlates with the observed resistance to VRC.
Triggering magnetar outbursts in 3D force-free simulations
Authors: Carrasco Federico , Viganò Daniele , Palenzuela Carlos , Pons Jose A
Published: February 2019

In this letter, we present the first 3D force-free general relativity simulations of the magnetosphere dynamics related to the magnetar outburst/flare phenomenology. Starting from an initial dipole configuration, we adiabatically increase the helicity by twisting the footprints of a spot on the stellar surface and follow the succession of quasi-equilibrium states until a critical twist is reached. Twisting beyond that point triggers instabilities that results in the rapid expansion of magnetic field lines, followed by reconnection, as observed in previous axi-symmetric simulations. If the injection of magnetic helicity goes on, the process is recurrent, periodically releasing a similar amount of energy, of the order of a few per cent of the total magnetic energy. From our current distribution, we estimate the local temperature assuming that dissipation occurs mainly in the highly resistive outermost layer of the neutron star. We find that the temperature smoothly increases with injected twist, being larger for spots located in the tropical regions than in polar regions, and rather independent of their sizes. After the injection of helicity ceases, the magnetosphere relaxes to a new stable state, in which the persistent currents maintain the footprints area slightly hotter than before the onset of the instability.
Comparison of polarization at two lunar eclipse events
Authors: Takahashi Jun , Itoh Yoichi , Watanabe Makoto , Akitaya Hiroshi , Takaki Katsutoshi , Kawabata Koji S , Itoh Ryosuke , Oasa Yumiko
Published: February 2019

We present the results of imaging polarimetry of the eclipsed Moon on 2014 October 8. The observed polarization degree was less than 1% in both the V and R bands, which contrasts with the reported 2%–3% polarization during the eclipse of 2015 April 4. We examined the Earth’s atmospheric data on the two dates and found that the high (≥7 km) cloud distribution was more inhomogeneous for the 2015 eclipse than it was for the 2014 eclipse. The polarization position angle observed during the 2015 eclipse can be explained if the major polarizing source was high clouds with an intermediate horizontal optical thickness. We suggest a possible dependence of the lunar eclipse polarization on the Earth’s high cloud distribution.
Assessing Combinability of Phylogenomic Data Using Bayes Factors
Authors: Neupane Suman , Fučíková Karolina , Lewis Louise A , Kuo Lynn , Chen Ming-Hui , Lewis Paul O
Published: February 2019

With the rapid reduction in sequencing costs of high-throughput genomic data, it has become commonplace to use hundreds of genes to infer phylogeny of any study system. While sampling a large number of genes has given us a tremendous opportunity to uncover previously unknown relationships and improve phylogenetic resolution, it also presents us with new challenges when the phylogenetic signal is confused by differences in the evolutionary histories of sampled genes. Given the incorporation of accurate marginal likelihood estimation methods into popular Bayesian software programs, it is natural to consider using the Bayes Factor (BF) to compare different partition models in which genes within any given partition subset share both tree topology and edge lengths. We explore using marginal likelihood to assess data subset combinability when data subsets have varying levels of phylogenetic discordance due to deep coalescence events among genes (simulated within a species tree), and compare the results with our recently described phylogenetic informational dissonance index (D) estimated for each data set. BF effectively detects phylogenetic incongruence and provides a way to assess the statistical significance of D values. We use BFs to assess data combinability using an empirical data set comprising 56 plastid genes from the green algal order Volvocales. We also discuss the potential need for calibrating BFs and demonstrate that BFs used in this study are correctly calibrated.
Robust Design for Coalescent Model Inference
Authors: Parag Kris V , Pybus Oliver G
Published: February 2019

The coalescent process describes how changes in the size or structure of a population influence the genealogical patterns of sequences sampled from that population. The estimation of (effective) population size changes from genealogies that are reconstructed from these sampled sequences is an important problem in many biological fields. Often, population size is characterized by a piecewise-constant function, with each piece serving as a population size parameter to be estimated. Estimation quality depends on both the statistical coalescent inference method employed, and on the experimental protocol, which controls variables such as the sampling of sequences through time and space, or the transformation of model parameters. While there is an extensive literature on coalescent inference methodology, there is comparatively little work on experimental design. The research that does exist is largely simulation-based, precluding the development of provable or general design theorems. We examine three key design problems: temporal sampling of sequences under the skyline demographic coalescent model, spatio-temporal sampling under the structured coalescent model, and time discretization for sequentially Markovian coalescent models. In all cases, we prove that 1) working in the logarithm of the parameters to be inferred (e.g., population size) and 2) distributing informative coalescent events uniformly among these log-parameters, is uniquely robust. “Robust” means that the total and maximum uncertainty of our parameter estimates are minimized, and made insensitive to their unknown (true) values. This robust design theorem provides rigorous justification for several existing coalescent experimental design decisions and leads to usable guidelines for future empirical or simulation-based investigations. Given its persistence among models, this theorem may form the basis of an experimental design paradigm for coalescent inference.
Addressing the New Global Threat of Xylella fastidiosa
Authors: Almeida R. P. P. , De La Fuente L. , Koebnik R. , Lopes J. R. S. , Parnell S. , Scherm H.
Published: February 2019

Xylella fastidiosa is one of the most important threats to plant health worldwide. This bacterial pathogen has a long history, causing disease in the Americas on a range of agricultural crops and trees, with severe economic repercussions particularly on grapevine and citrus. In Europe, X. fastidiosa was detected for the first time in 2013 in association with a severe disease affecting olive trees in southern Italy. Subsequent mandatory surveys throughout Europe led to discoveries in France and Spain in various host species and environments. Detection of additional introductions of X. fastidiosa continue to be reported from Europe, for example from northern Italy in late 2018. These events are leading to a sea change in research, monitoring and management efforts as exemplified by the articles in this Focus Issue . X. fastidiosa is part of complex pathosystems together with hosts and vectors. Although certain X. fastidiosa subspecies and environments have been well studied, particularly those that pertain to established disease in North and South America, this represents only a fraction of the existing genetic, epidemiological, and ecological diversity. This Focus Issue highlights some of the key challenges that must be overcome to address this new global threat, recent advances in understanding the pathosystem, and steps toward improved disease control. It brings together the broad research themes needed to address the global threat of X. fastidiosa, encompassing topics from host susceptibility and resistance, genome sequencing, detection methods, transmission by vectors, epidemiological drivers, chemical and biological control, to public databases and social sciences. Open communication and collaboration among scientists, stakeholders, and the general public from different parts of the world will pave the path to novel ideas to understand and combat this pathogen.
The anterior insula channels prefrontal expectancy signals during affective processing
Authors: Teckentrup Vanessa , Meer Johan N. van der , Borchardt Viola , Fan Yan , Neuser Monja P. , Tempelmann Claus , Herrmann Luisa , Walter Martin , Kroemer Nils B.
Published: February 2019

Expectancy shapes our perception of impending events. Although such an interplay between cognitive and affective processes is often impaired in mental disorders, it is not well understood how top-down expectancy signals modulate future affect. We therefore track the information flow in the brain during cognitive and affective processing segregated in time using task-specific cross-correlations. Participants in two independent fMRI studies (N1 = 37 & N2 = 55) were instructed to imagine a situation with affective content as indicated by a cue, which was then followed by an emotional picture congruent with expectancy. To correct for intrinsic covariance of brain function, we calculate resting-state cross-correlations analogous to the task. First, using factorial modeling of delta cross-correlations (task-rest) of the first study, we find that the magnitude of expectancy signals in the anterior insula cortex (AIC) modulates the BOLD response to emotional pictures in the anterior cingulate and dorsomedial prefrontal cortex in opposite directions. Second, using hierarchical linear modeling of lagged connectivity, we demonstrate that expectancy signals in the AIC indeed foreshadow this opposing pattern in the prefrontal cortex. Third, we replicate the results in the second study using a higher temporal resolution, showing that our task-specific cross-correlation approach robustly uncovers the dynamics of information flow. We conclude that the AIC arbitrates the recruitment of distinct prefrontal networks during cued picture processing according to triggered expectations. Taken together, our study provides new insights into neuronal pathways channeling cognition and affect within well-defined brain networks. Better understanding of such dynamics could lead to new applications tracking aberrant information processing in mental disorders.
Estrogenic action by tris(2,6-dimethylphenyl) phosphate, an impurity in resorcinol bis[di(2,6-dimethylphenyl) phosphate] flame retardant formulations, impairs the development of female reproductive functions
Authors: Sano Kazuhiro , Matsukami Hidenori , Suzuki Go , Htike Nang Thinn Thinn , Morishita Masahiro , Shwe Tin Tin Win , Hashimoto Shunji , Kawashima Takaharu , Isobe Tomohiko , Nakayama Shoji F. , Tsukahara Shinji , Maekawa Fumihiko
Published: February 2019

Background

Developmental exposure to environmental chemicals with estrogen-like activity has been suspected to permanently impair women’s health.

Objectives

In this study, we used a mouse model to evaluate whether a chemical having putative estrogen-like action detected by in vitro study, namely tris(2,6-dimethylphenyl) phosphate (TDMPP) impairs sexual differentiation of the brain.

Methods

To induce developmental exposure, TDMPP was administered subcutaneously to dams from gestational day 14 to parturition and to pups from postnatal day 0 to 9 at two different doses (TDMPP-high and TDMPP-low groups, respectively). To compare the results between TDMPP and typical estrogen exposures, 17β-estradiol was administered at two different doses on the same treatment schedule (E2-low and E2-high groups, respectively). A vehicle control group was formed by administering an equivalent volume of sesame oil to dams and to pups.

Results

Although there was no specific impairment in female ovary morphology, precocious puberty, detected by vaginal opening, and irregular estrous cycles, detected by vaginal cytology after sexual maturation, were found in TDMPP- and E2-treated groups, but not in the vehicle control group. In addition, lower lordosis response during reproductive behavioral tests was found in TDMPP- or E2-treated groups. To further clarify whether TDMPP directly affects sexual differentiation of the brain, we evaluated the transfer of TDMPP into the brain and the formation of sexual dimorphic nuclei. We detected a certain amount of TDMPP and its metabolites in the mouse brain after treatment, and masculinization of sexual dimorphic nuclei in the hypothalamus of female mice, suggesting the direct impact of TDMPP in developing brain.

Discussion

Taken together, the experimental evidence demonstrates that TDMPP directly enters the fetal and neonatal brain, inducing changes of sex-related brain structures, and impairing female reproductive functions.
Root density sensing allows pro-active modulation of shoot growth to avoid future resource limitation
Authors: Wheeldon Cara D. , Walker Catriona H. , Bennett Tom
Published: February 2019

Plants use environmental cues to determine their optimal root and shoot growth. It is well known to gardeners and horticulturists alike that soil volume – most commonly in the form of pot size – strongly restricts plant growth, but the mechanisms by which this effect occurs remain unclear. Here, we show that shoot growth scales directly with soil volume, independently of the nutritional content of the soil, and that plants can become ‘volume restricted’ even in the presence of abundant resources. We show that plants can detect their soil volume as early as 3 weeks post germination, and that shoot growth restriction therefore constitutes a pro-active ‘decision’ by the plant to avoid resource limitation later in the life cycle. Shoot growth restriction is not directly linked to root growth restriction, and does not occur in response to the mechanical detection of the pot walls. Rather, we show that plants detect their soil volume by detecting the density of roots in the proximity of their root system. As such, volume restriction may be intimately connected with the mechanism by which plants sense and respond to the roots of other plants in the rhizosphere. Our work demonstrates the remarkable ability of plants to make pro-active decisions about their growth to ensure they can complete their cycle, and has important implications for agricultural practise regarding both nutrient use efficiency and yield.
Unmasking of novel mutations within XK gene that could be used as Diagnostic Markers to Predict McLeod syndrome: Using in silico analysis
Authors: Mustafa Mujahed I. , Hassan Mohamed A.
Published: February 2019

Background

McLeod neuroacanthocytosis syndrome is a rare X-linked recessive multisystem disorder affecting the peripheral and central nervous systems, red blood cells, and internal organs.

Methods

We carried out in silico analysis of structural effect of each SNP using different bioinformatics tools to predict substitution influence on protein structural and functional level.

Result

2 novel mutations out of 104 nsSNPs that are found to be deleterious effect on the XK structure and function.

Conclusion

The present study provided a novel insight into the understanding of McLeod syndrome, SNPs occurring in coding and non-coding regions, may lead to RNA alterations and should be systematically verified. Functional studies can gain from a preliminary multi-step approach, such as the one proposed here; we prioritize SNPs for further genetic mapping studies. This will be a valuable resource for neurologists, hematologists, and clinical geneticists on this rare and debilitating disease.
Comparison of muscle activity, strength and balance, before and after a 6-month training using the FIFA11+ program (part 2)
Authors: Oshima Takeshi , Nakase Junsuke , Inaki Anri , Mochizuki Takafumi , Takata Yasushi , Shimozaki Kengo , Kinuya Seigo , Tsuchiya Hiroyuki
Published: February 2019

Purpose

Sports injuries can significantly impact an athlete’s career, as well as impose a high financial burden on teams. Therefore, the prevention of sports injuries is an essential aspect of sports medicine. To evaluate the effects of a 6-month training period, using part 2 of the FIFA11+, on the activation and strength of core and lower limb muscles, and on static and dynamic balance performance.

Materials and Methods

Eight college male soccer players, 20.4±0.5 years old, completed the FIFA11+ program (part 2) at least 3x per week for 6 months. The following variables were measured, before and after the 6-month training program: activity of more than 30 muscles (with a focus on core and lower limb muscles), measured using the standardized uptake values of 18F-fluorodeoxyglucose (FDG) on positron emission tomography (PET-CT); isokinetic strength of the knee flexor and extensor and hip abductor muscles, measured at 60°/s; static balance over a 60-s period, measured using a Gravicorder; and dynamic balance, measured using the Star Excursion Balance Test.

Results

Training improved activity levels of core (obliquus externus abdominis and erector spinae) and lower limb (tibialis anterior of the both legs) muscles (p≤0.03), corrected the between-limb difference in activation of the semimembranosus and improved dynamic balance, with a greater training effect on the non-dominant limb (p≤0.02). Training also improved knee flexor force of the non-dominant lower limb (p=0.02).

Conclusion

Routine performance of the FIFA11+ (part 2) program can improve activation of core and lower limb muscles, with a concomitant improvement in dynamic balance.
Low-dimensional Dynamics of Two Coupled Biological Oscillators
Authors: Droin Colas , Paquet Eric R , Naef Felix
Published: February 2019

The circadian clock and the cell cycle are two biological oscillatory processes that coexist within individual cells. These two oscillators were found to interact, which can lead to their synchronization. Here, we develop a method to infer their coupling and non-linear dynamics from thousands of mouse and human single-cell microscopy traces. This coupling predicts multiple phase-locked states showing different degrees of robustness against molecular fluctuations inherent to cellular scale biological oscillators. Moreover, the phase–locked states were temperature-independent and evolutionarily conserved from mouse to human, hinting at a common underlying dynamical mechanism. Finally, we detected a signature of the coupled dynamics in a physiological context, where tissues with different proliferation states exhibited shifted circadian clock phases.