ViralZone 2024 provides higher-resolution images and advanced virus-specific resources.

ViralZone (http://viralzone.expasy.org) is a knowledge repository for viruses that links biological knowledge and databases. It contains data on virion structure, genome, proteome, replication cycle and host-virus interactions. The new update provides better access to the data through contextual popups and higher resolution images in Scalable Vector Graphics (SVG) format. These images are designed to be dynamic and interactive with human viruses to give users better access to the data. In addition, a new coronavirus-specific resource provides regularly updated data on variants and molecular biology of SARS-CoV-2. Other virus-specific resources have been added to the database, particularly for HIV, herpesviruses and poxviruses.

IgG4-negative pituitary inflammatory pseudotumor with sphenoidal involvement resembling a macroadenoma.

BACKGROUND: Inflammatory pseudotumors (IPTs) are rare benign conditions of unknown etiology that can affect any part of the body. IPTs are most commonly associated with Immunoglobulin G4 (IgG4)-related disease. Central nervous system IPTs, especially with pituitary involvement, are even rarer entities. The presence of an IgG4-negative pituitary IPT with simultaneous extracranial involvement has not been reported. CASE REPORT: We present the case of a 41-year-old female with past medical history of rheumatoid arthritis and a diagnosis of pituitary IPT with coexisting sphenoidal (extracranial) involvement mimicking a pituitary macroadenoma at presentation. The patient underwent multiple consecutive biopsies, and an extensive workup prior to establishing the diagnosis. Laboratory work-up showed normal serum IgG4 and unremarkable liver function tests. CONCLUSION: Pituitary lesions with simultaneous sphenoidal involvement in patients with IgG4-negative systemic inflammatory disease should raise the clinical suspicion for intracranial IPTs, as these tumors can mimic aggressive counterparts causing adjacent bony erosion, and local invasion.

External Quality Assessment of SARS-CoV-2 Sequencing: an ESGMD-SSM Pilot Trial across 15 European Laboratories.

This first pilot trial on external quality assessment (EQA) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) whole-genome sequencing, initiated by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Genomic and Molecular Diagnostics (ESGMD) and the Swiss Society for Microbiology (SSM), aims to build a framework between laboratories in order to improve pathogen surveillance sequencing. Ten samples with various viral loads were sent out to 15 clinical laboratories that had free choice of sequencing methods and bioinformatic analyses. The key aspects on which the individual centers were compared were the identification of (i) single nucleotide polymorphisms (SNPs) and indels, (ii) Pango lineages, and (iii) clusters between samples. The participating laboratories used a wide array of methods and analysis pipelines. Most were able to generate whole genomes for all samples. Genomes were sequenced to various depths (up to a 100-fold difference across centers). There was a very good consensus regarding the majority of reporting criteria, but there were a few discrepancies in lineage and cluster assignments. Additionally, there were inconsistencies in variant calling. The main reasons for discrepancies were missing data, bioinformatic choices, and interpretation of data. The pilot EQA was overall a success. It was able to show the high quality of participating laboratories and provide valuable feedback in cases where problems occurred, thereby improving the sequencing setup of laboratories. A larger follow-up EQA should, however, improve on defining the variables and format of the report. Additionally, contamination and/or minority variants should be a further aspect of assessment.

A paramyxovirus-like model for Ebola virus bipartite promoters.

Paramyxo- and filovirus nucleocapsids (NCs) have bipartite promoters at their 3' ends to initiate RNA synthesis. The 2 elements, promoter element 1 (PE1) and promoter element 2 (PE2), are separated by a spacer region that must be exactly a multiple of 6 nucleotides (nt) long. Paramyxovirus NCs have 13 nucleoprotein (NP) subunits/turn, such that PE1 and PE2 are juxtaposed on the same face of the NC helix, for concerted recognition by the viral polymerase. Ebola virus (EBOV) NCs, in contrast, have 25 to 28 subunits/turn, meaning that PE1 and PE2 cannot be juxtaposed. However, there is evidence that the number of subunits/turn at the 3' end of the EBOV NC is variable. We propose a paramyxovirus-like model for EBOV explaining why there are 8 contiguous copies of the PE2 repeat when 3 are sufficient, why expanding this run to 13 further improves minigenome performance, and why there is a limit to the number of hexa-nt that can be inserted in the spacer region.

Long-Term Time Series Forecasting and Updates on Survival Analysis of Glioblastoma Multiforme: A 1975-2018 Population-Based Study.

OBJECTIVE: Glioblastomas multiforme (GBMs) are the most common primary CNS tumors. Epidemiologic studies have investigated the effect of demographics on patient survival, but the literature remains inconclusive. METHODS: This study included all adult patients with intracranial GBMs reported in the surveillance epidemiology and end results (SEER)-9 population database (1975-2018). The sample consisted of 32,746 unique entries. We forecast the annual GBM incidence in the US population through the year 2060 using time series analysis with autoregressive moving averages. A survival analysis of the GBM-specific time to death was also performed. Multivariate Cox proportional hazards (PH) regression revealed frank violations of the PH assumption for multiple covariates. Parametric models best described the GBM population's survival pattern; the results were compared to the semi-parametric analysis and the published literature. RESULTS: We predicted an increasing GBM incidence, which demonstrated that by the year 2060, over 1,800 cases will be reported annually in the SEER. All eight demographic variables were significant in the univariable analysis. The calendar year 2005 was the cutoff associated with an increased survival probability. A male survival benefit was eliminated in the year-adjusted Cox. Infratentorial tumors, nonmetropolitan areas, and White patient race were the factors erroneously associated with survival in the multivariate Cox analysis. Accelerated Failure Time (AFT) lognormal regression was the best model to describe the survival pattern in our patient population, identifying age >30 years old as a poor prognostic and patients >70 years old as having the worst survival. Annual income >USD 75,000 and supratentorial tumors had good prognostics, while surgical intervention provided the strongest survival benefit. CONCLUSIONS: Annual GBM incidence rates will continue to increase by almost 50% in the upcoming 30 years. Cox regression analysis should not be utilized for time-to-event predictions in GBM survival statistics. AFT lognormal distribution best describes the GBM-specific survival pattern, and as an inherent population characteristic, it should be implemented by researchers for future studies. Surgical intervention provides the strongest survival benefit, while patient age >70 years old is the worst prognostic. Based on our study, the demographics such as gender, race, and county type should not be considered as meaningful prognostics when designing future trials.

Accuracy of ct evaluation for cervical spine clearance in the ground level fall population - a retrospective cohort study.

BACKGROUND: Clinically occult cervical spine (CS) injuries are well described in blunt trauma, however delay in identifying these injuries and clearing the CS can result in morbidity. Our study examines the ground level fall (GLF) population to analyze whether computed tomography (CT) alone can rule out unstable injury in this group with lower force mechanism. METHODS: This is a single center, retrospective cohort study. All GLF patients in the institutional trauma registry between 6/1/2012 through 12/31/2019 were included. These comprise all trauma patients evaluated in the emergency department with Injury Severity Score (ISS) > 0, including both activations and consults with both clinical and radiological spine evaluation. Patients who could not be cleared by National Emergency X-ray Utilization Study (NEXUS) criteria underwent CT. Patients with CT or clinical suspicion of cord or ligamentous injury underwent MRI. CT occult injuries were identified by MRI and clinical exam, with MRI identifying all unstable injuries. RESULTS: Sixty-nine (2.0%) of patients had CS injury without acute CT abnormality. Of these, 11 (0.3%) required surgery and were considered unstable. All patients who required surgery had a neurologic deficit. Negative predictive value (NPV) of CT for unstable CS injury was 99.7%. The combination of acute CT findings and neurologic deficit ruled out unstable CS injury with 100% NPV. CONCLUSION: In the GLF population, CT alone rules out unstable CS injury with high, but not perfect NPV. The combination of absence of acute CT findings and acute neurologic deficits rules out unstable CS injury with 100% NPV.

Bipartite promoters and RNA editing of paramyxoviruses and filoviruses.

A primary property of paramyxovirus bipartite promoters is to ensure that their RNA genomes are imprinted with a hexamer phase via their association with nucleoproteins, in part because this phase as well the editing sequence itself controls mRNA editing. The question then arises whether a similar mechanism operates for filoviruses that also contain bipartite promoters that are governed by the "rule of six," even though these genomes need not, and given Ebola virus biology, cannot always be of hexamer genome length. This review suggests that this is possible and describes how it might operate, and that RNA editing may play a role in Ebola virus genome interconversion that helps the virus adapt to different host environments.

Spontaneous closure of myelomeningocele.

Fetal repair of myelomeningocele has been increasingly offered to mothers of children with myelomeningocele after the seminal Management of Myelomeningocele (MOMs) trial, which demonstrated decreased reliance on ventriculoperitoneal shunt following fetal closure. We present the case of a fetus diagnosed with a lumbar myelomeningocele in utero whose mother refused in utero closure and who was subsequently born with a skin-covered defect. A fetal MRI was obtained on a mother with a male fetus diagnosed with open neural tube defect at 20 weeks of gestation. The child demonstrated spinal dysraphism extending from L2 to L5 and associated Chiari II malformation with lateral and third ventriculomegaly. Based on our institutional criteria and the criteria of the MOMs trial, the parents were offered fetal repair of the myelomeningocele; however, they declined because of concerns about risks to the mother. At birth, the patient was found to have a skin-covered meningocele. He underwent elective repair of his occult meningocele and detethering of his spinal cord. Intraoperative findings demonstrated spinal nerve roots attached to the arachnoid within the defect, and a closed, tubularized neural placode. This represents a unique case in which a fetus with a clinical picture consistent with open spinal defect was found to have a lesion more consistent with meningocele on postnatal operative interrogation. Knowledge that this can occur should be taken into consideration when discussing fetal closure, although the frequency of this occurrence is not known. Additionally, identification of this case sheds light on the mechanism by which occult myelomeningoceles form.

How I do it: lateral supra-cerebellar infra-tentorial approach for P2-P3 junction cerebral aneurysms.

BACKGROUND: P2-P3 junction aneurysms are challenging to treat surgically because of their frequent complex morphology and their location deep in close proximity to the midbrain. The sub-temporal route requires significant retraction of the temporal lobe in addition to potential injury to the vein of Labbe. We describe the technique for treating such aneurysms via a lateral supra-cerebellar infra-tentorial (LSCIT) approach, which eliminates manipulation of the temporal lobe. METHOD: Cadaveric dissection provided comprehensive understanding of relevant anatomy. Intraoperative video shows clipping of the aneurysm using a LSCIT approach. CONCLUSION: LSCIT approach allows safe clipping of P2-P3 aneurysms with minimal brain manipulation.

Association between ventricular shunt catheter calcifications and the development of shunt fracture.

BACKGROUND: Calcifications along ventricular catheters have been associated with shunt fractures although it is unknown whether their development predicts whether and when the shunts will fracture. OBJECTIVE: To determine whether extracranial calcifications found on a radiographic shunt series predicts whether a patient will experience a shunt catheter fracture or complication. MATERIALS AND METHODS: A retrospective review was performed of pediatric patients with a ventricular shunt placed before 18 years of age and radiographic shunt series. Two thousand, six hundred and thirty shunt series in 523 patients (301 male) were reviewed to identify the development of calcifications around the catheter and fracture. Fifty-one patients were excluded for preexisting calcifications with shunt fracture. (48) Absence of shunt (2) or age (1). Analysis included descriptive statistics, odds ratio and chi-square test results. RESULTS: Four hundred seventy-two patients were included. Of the 59 shunts in 58 patients that developed calcifications, 23 went on to fracture (39%). Forty shunts without calcification in 37 patients developed fractures. There is a significant positive association between calcification and fracture (Χ2=39.1, P<0.01). It is 6.12 times more likely that a fractured shunt had calcifications compared to a non-fractured shunt having calcifications. Calcifications appeared within an average of 9 years, 10 months (range: 4-14 years) after shunt insertion. Shunt fractures occurred within an average of 5 years, 2 months (range: 6 months-9 years) after the appearance of calcifications with a median patient age of 14.6 years. Nearly all fractures were at or adjacent to the calcifications, most commonly in the neck (17/23; 73.9%). CONCLUSION: Shunt calcification represents a significant risk for catheter fracture in the pediatric population. Early intervention or closer interval follow-up may be indicated in those found to have calcifications.

Morphological and functional anatomy of the trigeminal triangular plexus as an anatomical entity: a systematic review.

PURPOSE: The sensory trigeminal nerve in the trigeminal cave of Meckel-which is an individualized lodge-is classically segmented into two parts: the trigeminal ganglion (TG) and the triangular plexus (TP). The TP has been defined as the portion of the trigeminal nerve from the posterior margin of the TG to the path over the upper ridge of the petrous bone. Due to its relatively unrecognized status, its morphological and functional anatomy has been reviewed by the authors through a PRISMA systematic review of the literature. METHODS: The authors have carried out a systematic review of the TP according to the PRISMA model with various bibliographical bases. Before 1947: Medic @ Library (BIU Santé Paris, 2017); Index-Catalog of the Library of the Surgeon-General's Office (US National Library of Medicine, 2017); Gallica (French National Library, 2017). After 1947: PUBMED, PubMed Central and MEDLINE. RESULTS: 56 articles were retained for full-text examination, of which 23 were chosen and included. The TP was described as having a triangular shape (30.2%), a plexual organization (97.4%) with sensory-, motor- and sympathetic-anastomoses (96.7%) that, however, respect the somatotopic trigeminal distribution (93.3%). The direct electrical stimulation of the root at the level of the TP (during radiofrequency-thermorhizotomy procedures) confirmed a clear-cut somatotopy. CONCLUSION: An understanding of both the morphological and the functional anatomy of the triangular plexus can contribute to accuracy and safety on the surgeries performed for trigeminal neuralgia and tumor removal inside the trigeminal cave.

The tethered effect of the arachnoid in vago-glossopharyngeal neuralgia: a real associated alternative mechanism?

Vago-glossopharyngeal neuralgia (VGPN) is a rarely seen disease when compared to trigeminal neuralgia. When the pain is resistant to medical therapy, microvascular decompression can be performed if a vascular conflict is suspected on magnetic resonance imaging (MRI). In addition, arachnoid pathology may play a role in VGPN. We report two cases of VGPN caused by tethered arachnoid, associated with a vascular contact in which pain was reduced by freeing rootlets from arachnoid compression. We report two cases relating to 50-year-old and 30-year-old men with a history of electric shooting pain triggered by swallowing in the right pharyngeal and auricular regions. Preoperative MRI documented a neurovascular conflict in the first case and an arachnoid cyst in the second. Surgery was performed via a retrosigmoid craniotomy. In both cases, the intraoperative findings documented a tethered arachnoid membrane compressive to cranial nerves IX and X. Untethering was performed by liberation of the rootlets from the arachnoid with microvascular decompression. No additional rhizotomy was performed. The postoperative course was uneventful and pain was relieved in the first case and decreased in the second. In VGPN, a tethered arachnoid may play a role in causing the neuralgia, either alone or associated with a neuro-vascular conflict.

Arteries and Veins of the Cerebellum.

Surgery of the posterior fossa represents a technical challenge because of the proximity of the vessels of the cerebellum. If the arterial vascularization of the cerebellum is well known, the main arterial variations and the whole venous vascularization are probably under recognized. We describe the vascular organization and the main variations through photographs of colored latex perfused brains, obtained with a surgical microscope. The arterial vascularization of the cerebellum is based on three arteries which all originate from the vertebrobasilar system: the superior cerebellar artery (SCA), the anterior and inferior cerebellar artery (AICA), and the posterior and inferior cerebellar artery (PICA). The main arterial variations involve essentially the origin of these vessels. Concerning the SCA, its origin depends on the embryology. The AICA can arise from a common trunk AICA-PICA. It can be sometimes doubled and rarely absent. The PICA also can arise from a common trunk AICA-PICA and sometimes from the extradural segment of the vertebral artery. Concerning the venous organization, we distinguish the superficial and deep veins. The superficial veins drain the cerebellar cortex and transit on the surface of the cerebellum. The deep veins refer to the veins transiting in the fissures between the cerebellum and the brainstem. All these veins terminate as bridging veins that we can divide in three groups: a superior group emptying into the great vein, a posterior group emptying into the transtentorial sinus, and a lateral group ending into the superior petrosal sinus. The surgical implications are discussed.

Management of hydrocephalus in pediatric metastatic tumors of the posterior fossa at presentation.

PURPOSE: Presence of metastases in newly diagnosed pediatric posterior fossa tumors (PFT) is not a rare situation, but optimal treatment of associated hydrocephalus in these children has remained undetermined. METHODS: Twenty-nine children treated between January 2005 and December 2015 for a metastatic PFT associated with hydrocephalus constituted the study cohort. Patients were divided into three groups: ventriculoperitoneal shunt (VPS), endoscopic third ventriculostomy (ETV), and temporary ventricular drainage before or during tumor resection (PVD). RESULTS: There were 4 VPS, 18 ETV, and 7 PVD. The global incidence of CSF diversion failure was 52%. No case of dysfunction or dissemination of metastatic cells occurred in the VPS group. Recurrence of hydrocephalus occurred in 55% of the ETV group. Presence of multiple macroscopic metastases and CSF metastatic cells after tumor surgery was associated with ETV failure. Fifty-seven percent of the children in the PVD group were reoperated after an average time of 53 days. Specific oncologic treatment was initiated earlier in the VPS group (11 days) compared to ETV (27 days) and PVD (23 days) groups. CONCLUSIONS: ETV should be avoided in cases of multiple macroscopic metastases, and children who underwent ETV must be followed carefully when metastatic cells are present in CSF after tumor surgery. External ventricular drainage before or during surgical removal should not be considered as a final option to treat hydrocephalus. VPS remains a safe alternative in this situation and allows an early specific oncologic treatment.

Arteries and Veins of the Sylvian Fissure and Insula: Microsurgical Anatomy.

We present a vascular anatomical study of the arteries and veins of the sylvian fissure and insula.A good knowledge of the sylvian fissure, the insula, and their vascular relationship would seem mandatory before performing surgery in this area, whatever the type of surgery (aneurysms, arteriovenous malformations, insular tumors).We start with the sylvian fissure and insula morphology, followed by the MCA description and its perforators, with special attention paid to the insular perforators. We demonstrate that the long insular perforators penetrating in the superior part of the posterior short gyrus and long gyri vascularize, respectively, the corticonuclear and corticospinal fasciculi. We particularly insist too on three anatomical constants regarding the vascularization of the insula, already described in the literature: The superior periinsular sulcus is the only sulcus on the lateral surface of the brain without an artery along its axis; the superior branch of the MCA supplies the anterior insular pole and both the anterior and middle short gyri in 100 % of cases; in at least 90 % of cases, the artery that supplied the central insular sulcus continued on to become the central artery.We end with the anatomical study of the veins and cisterns.

Fifteen years SIB Swiss Institute of Bioinformatics: life science databases, tools and support.

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) was created in 1998 as an institution to foster excellence in bioinformatics. It is renowned worldwide for its databases and software tools, such as UniProtKB/Swiss-Prot, PROSITE, SWISS-MODEL, STRING, etc, that are all accessible on ExPASy.org, SIB's Bioinformatics Resource Portal. This article provides an overview of the scientific and training resources SIB has consistently been offering to the life science community for more than 15 years.

ViralZone: recent updates to the virus knowledge resource.

ViralZone (http://viralzone.expasy.org) is a knowledge repository that allows users to learn about viruses including their virion structure, replication cycle and host-virus interactions. The information is divided into viral fact sheets that describe virion shape, molecular biology and epidemiology for each viral genus, with links to the corresponding annotated proteomes of UniProtKB. Each viral genus page contains detailed illustrations, text and PubMed references. This new update provides a linked view of viral molecular biology through 133 new viral ontology pages that describe common steps of viral replication cycles shared by several viral genera. This viral cell-cycle ontology is also represented in UniProtKB in the form of annotated keywords. In this way, users can navigate from the description of a replication-cycle event, to the viral genus concerned, and the associated UniProtKB protein records.

Comparison of injection/dissection and injection/corrosion methods: example of vertebral veins in the transverse canal.

PURPOSE: In order to contribute some new elements to the discussion on the organization of the vertebral veins inside the transverse canal, we compared two dissection techniques: injection/dissection and injection/corrosion. The aim of this study was to compare these two techniques to study the vertebral veins, and also to emphasize the importance of preserving specimens in anatomical museums. METHODS: Using the injection/dissection technique, latex was injected into ten specimens, then the transverse canal was opened to expose the vertebral veins and their anastomoses. Using the injection/corrosion technique, altufix was injected into eight specimens that were afterwards plunged in sulfuric acid and washed daily until complete corrosion was obtained. RESULTS: Both techniques showed concordant results. The vertebral veins were plexuous, located ventro-laterally to the artery and received constant metamerical branches at each level. The injection/dissection technique conserved the anatomical relationships allowing metamerical analysis of the vertebral veins. The injection/corrosion technique, however, failed to conserve these relationships but provided a precise visualization of smaller anastomosis. CONCLUSIONS: By analyzing different aspects of the vertebral veins anatomy in the transverse canal, the two techniques complete each other. This study emphasizes the importance of preserving the anatomical preparations: in addition to the historical and cultural value of these preparations, they contain precious information that furthers our anatomical knowledge.