The Allele Catalog Tool: a web-based interactive tool for allele discovery and analysis.

BACKGROUND: The advancement of sequencing technologies today has made a plethora of whole-genome re-sequenced (WGRS) data publicly available. However, research utilizing the WGRS data without further configuration is nearly impossible. To solve this problem, our research group has developed an interactive Allele Catalog Tool to enable researchers to explore the coding region allelic variation present in over 1,000 re-sequenced accessions each for soybean, Arabidopsis, and maize. RESULTS: The Allele Catalog Tool was designed originally with soybean genomic data and resources. The Allele Catalog datasets were generated using our variant calling pipeline (SnakyVC) and the Allele Catalog pipeline (AlleleCatalog). The variant calling pipeline is developed to parallelly process raw sequencing reads to generate the Variant Call Format (VCF) files, and the Allele Catalog pipeline takes VCF files to perform imputations, functional effect predictions, and assemble alleles for each gene to generate curated Allele Catalog datasets. Both pipelines were utilized to generate the data panels (VCF files and Allele Catalog files) in which the accessions of the WGRS datasets were collected from various sources, currently representing over 1,000 diverse accessions for soybean, Arabidopsis, and maize individually. The main features of the Allele Catalog Tool include data query, visualization of results, categorical filtering, and download functions. Queries are performed from user input, and results are a tabular format of summary results by categorical description and genotype results of the alleles for each gene. The categorical information is specific to each species; additionally, available detailed meta-information is provided in modal popups. The genotypic information contains the variant positions, reference or alternate genotypes, the functional effect classes, and the amino-acid changes of each accession. Besides that, the results can also be downloaded for other research purposes. CONCLUSIONS: The Allele Catalog Tool is a web-based tool that currently supports three species: soybean, Arabidopsis, and maize. The Soybean Allele Catalog Tool is hosted on the SoyKB website ( https://soykb.org/SoybeanAlleleCatalogTool/ ), while the Allele Catalog Tool for Arabidopsis and maize is hosted on the KBCommons website ( https://kbcommons.org/system/tools/AlleleCatalogTool/Zmays and https://kbcommons.org/system/tools/AlleleCatalogTool/Athaliana ). Researchers can use this tool to connect variant alleles of genes with meta-information of species.

Intrathecal and Oral Baclofen Use in Adults With Spinal Cord Injury: A Systematic Review of Efficacy in Spasticity Reduction, Functional Changes, Dosing, and Adverse Events.

OBJECTIVE: To examine the efficacy, dosing, and safety profiles of intrathecal and oral baclofen in treating spasticity after spinal cord injury (SCI). DATA SOURCES: PubMed and Cochrane Databases were searched from 1970-2018 with keywords baclofen, spinal cord injury, and efficacy. STUDY SELECTION: The database search yielded 588 sources and 10 additional relevant publications. After removal of duplicates, 398 publications were screened. DATA EXTRACTION: Data were extracted using the following population, intervention, comparator, outcomes, and study designs criteria: studies including adult patients with SCI with spasticity; the intervention could be oral or intrathecal administration of baclofen; selection was inclusive for control groups, surgical management, rehabilitation, and alternative pharmaceutical agents; outcomes were efficacy, dosing, and adverse events. Randomized controlled trials, observational studies, and case reports were included. Meta-analyses and systematic reviews were excluded. DATA SYNTHESIS: A total of 98 studies were included with 1943 patients. Only 4 randomized, double-blinded, and placebo-controlled trials were reported. Thirty-nine studies examined changes in the Modified Ashworth Scale (MAS; 34 studies) and Penn Spasm scores (Penn Spasm Frequency; 19 studies), with average reductions of 1.7±1.3 and 1.6±1.4 in individuals with SCI, respectively. Of these data, a total of 6 of the 34 studies (MAS) and 2 of the 19 studies (Penn Spasm Frequency) analyzed oral baclofen. Forty-three studies addressed adverse events with muscle weakness and fatigue frequently reported. CONCLUSIONS: Baclofen is the most commonly-prescribed antispasmodic after SCI. Surprisingly, there remains a significant lack of large, placebo-controlled, double-blinded clinical trials, with most efficacy data arising from small studies examining treatment across different etiologies. In the studies reviewed, baclofen effectively improved spasticity outcome measures, with increased efficacy through intrathecal administration. Few studies assessed how reduced neural excitability affected residual motor function and activities of daily living. A host of adverse events were reported that may negatively affect quality of life. Comparative randomized controlled trials of baclofen and alternative treatments are warranted because these have demonstrated promise in relieving spasticity with reduced adverse events and without negatively affecting residual motor function.

Predictors of volitional motor recovery with epidural stimulation in individuals with chronic spinal cord injury.

Spinal cord epidural stimulation (scES) has enabled volitional lower extremity movements in individuals with chronic and clinically motor complete spinal cord injury and no clinically detectable brain influence. The aim of this study was to understand whether the individuals' neuroanatomical characteristics or positioning of the scES electrode were important factors influencing the extent of initial recovery of lower limb voluntary movements in those with clinically motor complete paralysis. We hypothesized that there would be significant correlations between the number of joints moved during attempts with scES prior to any training interventions and the amount of cervical cord atrophy above the injury, length of post-traumatic myelomalacia and the amount of volume coverage of lumbosacral enlargement by the stimulation electrode array. The clinical and imaging records of 20 individuals with chronic and clinically motor complete spinal cord injury who underwent scES implantation were reviewed and analysed using MRI and X-ray integration, image segmentation and spinal cord volumetric reconstruction techniques. All individuals that participated in the scES study (n = 20) achieved, to some extent, lower extremity voluntary movements post scES implant and prior to any locomotor, voluntary movement or cardiovascular training. The correlation results showed that neither the cross-section area of spinal cord at C3 (n = 19, r = 0.33, P = 0.16) nor the length of severe myelomalacia (n = 18, r = -0.02, P = 0.93) correlated significantly with volitional lower limb movement ability. However, there was a significant, moderate correlation (n = 20, r = 0.59, P = 0.006) between the estimated percentage of the lumbosacral enlargement coverage by the paddle electrode as well as the position of the paddle relative to the maximal lumbosacral enlargement and the conus tip (n = 20, r = 0.50, P = 0.026) with the number of joints moved volitionally. These results suggest that greater coverage of the lumbosacral enlargement by scES may improve motor recovery prior to any training, possibly because of direct modulatory effects on the spinal networks that control lower extremity movements indicating the significant role of motor control at the level of the spinal cord.

Machine Learning in Neuro-Oncology, Epilepsy, Alzheimer's Disease, and Schizophrenia.

Applications of machine learning (ML) in translational medicine include therapeutic drug creation, diagnostic development, surgical planning, outcome prediction, and intraoperative assistance. Opportunities in the neurosciences are rich given advancement in our understanding of the brain, expanding indications for intervention, and diagnostic challenges often characterized by multiple clinical and environmental factors. We present a review of ML in neuro-oncology, epilepsy, Alzheimer's disease, and schizophrenia to highlight recent progression in these field, optimizing machine learning capabilities in their current forms. Supervised learning models appear to be the most commonly incorporated algorithm models for machine learning across the reviewed neuroscience disciplines with primary aim of diagnosis. Accuracy ranges are high from 63% to 99% across all algorithms investigated. Machine learning contributions to neurosurgery, neurology, psychiatry, and the clinical and basic science neurosciences may enhance current medical best practices while also broadening our understanding of dynamic neural networks and the brain.

Geographic distribution of the E1 family of genes and their effects on reproductive timing in soybean.

BACKGROUND: Soybean is an economically important crop which flowers predominantly in response to photoperiod. Several major loci controlling the quantitative trait for reproductive timing have been identified, of which allelic combinations at three of these loci, E1, E2, and E3, are the dominant factors driving time to flower and reproductive period. However, functional genomics studies have identified additional loci which affect reproductive timing, many of which are less understood. A better characterization of these genes will enable fine-tuning of adaptation to various production environments. Two such genes, E1La and E1Lb, have been implicated in flowering by previous studies, but their effects have yet to be assessed under natural photoperiod regimes. RESULTS: Natural and induced variants of E1La and E1Lb were identified and introgressed into lines harboring either E1 or its early flowering variant, e1-as. Lines were evaluated for days to flower and maturity in a Maturity Group (MG) III production environment. These results revealed that variation in E1La and E1Lb promoted earlier flowering and maturity, with stronger effects in e1-as background than in an E1 background. The geographic distribution of E1La alleles among wild and cultivated soybean revealed that natural variation in E1La likely contributed to northern expansion of wild soybean, while breeding programs in North America exploited e1-as to develop cultivars adapted to northern latitudes. CONCLUSION: This research identified novel alleles of the E1 paralogues, E1La and E1Lb, which promote flowering and maturity under natural photoperiods. These loci represent sources of genetic variation which have been under-utilized in North American breeding programs to control reproductive timing, and which can be valuable additions to a breeder's molecular toolbox.

Acute posterior reversible encephalopathy syndrome (PRES) in setting of interferon-beta use: case presentation with reduction of edema in 72 h after cessation of interferon-beta therapy with sub-clinical inflammation.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) represents a transient change in mental status with associated vasogenic edema of cortical and subcortical brain structures. It is often attributed to multifactorial etiology including hypertension and altered hemodynamics and disruption of vessel integrity. Patients with autoimmune disease and certain immune modulator therapies are at greater risk. CASE PRESENTATION: A 54-year-old female with past medical history of well-controlled multiple sclerosis on interferon-beta since 2013, presented with witnessed tonic colonic seizure. She also was noted to demonstrate left gaze deviation and left-sided hemiparesis. MRI fluid-attenuated inversion recovery sequence showed hyperintensity of the subcortical U fibers, concentrated in the occipital, parietal lobes and frontal lobes. Systolic blood pressure was 160 mmHg on arrival. The patient was started on seizure prophylxis and Interferon beta was discontinued. The patient's mentation, seizures and hemiapresis significantly improved in next 72 h with tight blood pressure control, and had notble improvement on MRI imaging and inflammatory markers. Lumbar puncture CSF results were devoid of infectious and autoimmune pathology. CONCLUSIONS: A middle-aged female with multiple sclerosis who was on chronic IFN-beta presented to the emergency room with a witnessed tonic-clonic seizure, with MRI T2 FLAIR imaging consistent with PRES. She had notable clinical improvement with decreased edema on imaging and improved inflammatory markers 72 h after cessation of IFN-beta therapy.

Insights into complication rates, reoperation rates, and healthcare utilization associated with use of recombinant human bone morphogenetic protein-2 in patients with spine infections.

OBJECTIVEUse of recombinant human bone morphogenetic protein-2 (rhBMP-2) in patients with spine infections is controversial. The purpose of this study was to identify long-term complications, reoperations, and healthcare utilization associated with rhBMP-2 use in patients with spine infections.METHODSThis retrospective study extracted data using ICD-9/10 and CPT codes from MarketScan (2000-2016). Patients were dichotomized into 2 groups (rhBMP-2, no rhBMP-2) based on whether rhBMP-2 was used during fusion surgery for spinal infections. Outcomes of interest were reoperation rates (index level, other levels), readmission rates, discharge disposition, length of stay, complications, and healthcare resource utilization at the index hospitalization and 1, 3, 6, 12, and 24 months following discharge. Outcomes were compared using nonparametric 2-group tests and generalized linear regression models.RESULTSThe database search identified 2762 patients with > 24 months' follow-up; rhBMP-2 was used in 8.4% of their cases. The patients' median age was 53 years, 52.43% were female, and 15.11% had an Elixhauser Comorbidity Index ≥ 3. Patients in the rhBMP-2 group had higher comorbidity indices, incurred higher costs at index hospitalization, were discharged home in most cases, and had lower complication rates than those in the no-rhBMP-2 group. There was no statistically significant between-groups difference in complication rates 1 month following discharge or in reoperation rates at 3, 6, 12, and 24 months following the procedure. Patients in the no-rhBMP-2 group incurred higher utilization of outpatient services and medication refill costs at 1, 3, 6, 12, and 24 months following surgery.CONCLUSIONSIn patients undergoing surgery for spine infection, rhBMP-2 use was associated with lower complication rates and higher median payments during index hospitalization compared to cases in which rhBMP-2 was not used. There was no significant between-groups difference in reoperation rates (index and other levels) at 3, 6, 12, and 24 months after the index operation. Patients treated with rhBMP-2 incurred lower utilization of outpatient services and overall payments. These results indicate that rhBMP-2 can be used safely in patients with spine infections with cost-effective utilization of healthcare resources and without an increase in complications or reoperation rates.

Outcomes of decompression and fusion for treatment of spinal infection

Objective: Spine infection including vertebral osteomyelitis, discitis, paraspinal musculoskeletal infection, and spinal abscess refractory to medical management poses significant challenges to the treating physician. Surgical management is often required in patients suffering neurological deficits or spinal deformity with significant pain. To date, best practices have not been elucidated for the optimization of health outcomes and resource utilization in the setting of surgical intervention for spinal infection. The authors conducted the present study to assess the magnitude of reoperation rates in both fusion and nonfusion groups as well as overall health resource utilization following surgical decompression for spine infection. Methods: The authors performed an analysis using MarketScan (2001­2015) to identify health outcomes and healthcare utilization metrics of spine infection following surgical intervention with decompression alone or combined with fusion. Adult patients underwent surgical management for primary or secondary spinal infection and were followed up for at least 12 months postoperatively. Assessed outcomes included reoperation, healthcare utilization and payment at the index hospitalization and within 12 months after discharge, postoperative complications, and infection recurrence. Results: A total of 2662 patients in the database were eligible for inclusion in this study. Rehospitalization for infection was observed in 3.99% of patients who had undergone fusion and in 11.25% of those treated with decompression alone. Reoperation was needed in 12.7% of the patients without fusion and 8.16% of those with fusion. Complications within 30 days were more common in the nonfusion group (24.64%) than in the fusion group (16.49%). Overall postoperative payments after 12 months totaled $33,137 for the nonfusion group and $23,426 for the fusion group. Conclusions: In this large cohort study with a 12-month follow-up, the recurrence of infection, reoperation rates, and complications were higher in patients treated with decompression alone than in those treated with decompression plus fusion. These findings along with imaging characteristics, disease severity, extent of bony resection, and the presence of instability may help surgeons decide whether to include fusion at the time of initial surgery. Further studies that control for selection bias in appropriately matched cohorts are necessary to determine the additive benefits of fusion in spinal infection management.

Variability in the utility of predictive models in predicting patient-reported outcomes following spine surgery for degenerative conditions: a systematic review.

OBJECTIVEThere is increasing emphasis on patient-reported outcomes (PROs) to quantitatively evaluate quality outcomes from degenerative spine surgery. However, accurate prediction of PROs is challenging due to heterogeneity in outcome measures, patient characteristics, treatment characteristics, and methodological characteristics. The purpose of this study was to evaluate the current landscape of independently validated predictive models for PROs in elective degenerative spinal surgery with respect to study design and model generation, training, accuracy, reliability, variance, and utility.METHODSThe authors analyzed the current predictive models in PROs by performing a search of the PubMed and Ovid databases using PRISMA guidelines and a PICOS (participants, intervention, comparison, outcomes, study design) model. They assessed the common outcomes and variables used across models as well as the study design and internal validation methods.RESULTSA total of 7 articles met the inclusion criteria, including a total of 17 validated predictive models of PROs after adult degenerative spine surgery. National registry databases were used in 4 of the studies. Validation cohorts were used in 2 studies for model verification and 5 studies used other methods, including random sample bootstrapping techniques. Reported c-index values ranged from 0.47 to 0.79. Two studies report the area under the curve (0.71-0.83) and one reports a misclassification rate (9.9%). Several positive predictors, including high baseline pain intensity and disability, demonstrated high likelihood of favorable PROs.CONCLUSIONSA limited but effective cohort of validated predictive models of spine surgical outcomes had proven good predictability for PROs. Instruments with predictive accuracy can enhance shared decision-making, improve rehabilitation, and inform best practices in the setting of heterogeneous patient characteristics and surgical factors.

Consistent anatomical relationships of pedicle, lamina, and superior articulating process in severe idiopathic scoliosis allow for safe freehand pedicle screw placement: A proof-of-concept technical study.

Introduction: Transpedicular screw placement has superior pullout strength compared to alternative forms of spinal fusion and is often performed in deformity correction surgery with navigation for optimal accuracy and reliability. Freehand technique for pedicle screws minimizes operation time and radiation exposure without fluoroscopy but is not widely adopted given the challenge of difficult anatomical corridors and accurate placement, especially in idiopathic scoliosis and advanced deformity. We used a computer-generated model to assess a proof-of-concept and anatomical feasibility of a freehand screw technique in severe scoliosis. Methods: Three-dimensional (3D) reconstructions of vertebra from a sample of two male patients with severe idiopathic scoliosis deformity (1 thoracic and 1 lumbar) with Cobb angles of 100° were used for planned placement of 17 levels of thoracolumbar (6.5 mm × 45 mm) pedicle screws. 3D reconstruction of each vertebra was created and measurements of screw entries and trajectories were reproduced with a 3D slicer software image computing platform. Results: Accurate transpedicular screw placement is possible with anatomical landmarks based on the 3D reconstructed vertebral levels. A series of 5 figures were assembled to demonstrate sagittal, coronal, and axial planes and key anatomical landmarks and trajectories of thoracic and lumbar freehand pedicle screws in severe idiopathic scoliosis. Conclusions: Anatomical landmarks for freehand transpedicular screw placement (between pedicle, lamina, and superior articulating process) are constant and reliable in severe idiopathic scoliosis as evidenced by 3D computer modeling. Preoperative computed tomography modeling may assist appropriate screw entry and trajectory based on anatomical landmarks for spine surgeons, and guide freehand technique for screw placement in adolescent idiopathic scoliosis.

Genome-wide association study reveals GmFulb as candidate gene for maturity time and reproductive length in soybeans (Glycine max).

The ability of soybean [Glycine max (L.) Merr.] to adapt to different latitudes is attributed to genetic variation in major E genes and quantitative trait loci (QTLs) determining flowering time (R1), maturity (R8), and reproductive length (RL). Fully revealing the genetic basis of R1, R8, and RL in soybeans is necessary to enhance genetic gains in soybean yield improvement. Here, we performed a genome-wide association analysis (GWA) with 31,689 single nucleotide polymorphisms (SNPs) to detect novel loci for R1, R8, and RL using a soybean panel of 329 accessions with the same genotype for three major E genes (e1-as/E2/E3). The studied accessions were grown in nine environments and observed for R1, R8 and RL in all environments. This study identified two stable peaks on Chr 4, simultaneously controlling R8 and RL. In addition, we identified a third peak on Chr 10 controlling R1. Association peaks overlap with previously reported QTLs for R1, R8, and RL. Considering the alternative alleles, significant SNPs caused RL to be two days shorter, R1 two days later and R8 two days earlier, respectively. We identified association peaks acting independently over R1 and R8, suggesting that trait-specific minor effect loci are also involved in controlling R1 and R8. From the 111 genes highly associated with the three peaks detected in this study, we selected six candidate genes as the most likely cause of R1, R8, and RL variation. High correspondence was observed between a modifying variant SNP at position 04:39294836 in GmFulb and an association peak on Chr 4. Further studies using map-based cloning and fine mapping are necessary to elucidate the role of the candidates we identified for soybean maturity and adaptation to different latitudes and to be effectively used in the marker-assisted breeding of cultivars with optimal yield-related traits.

Recurrent Gastrointestinal Stromal Tumor With Chondroid Differentiation After Imatinib Therapy: An Unusual Case and Literature Review.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the gastrointestinal tract and is most commonly seen in the stomach. The standard treatment for patients with advanced GISTs include both surgical resection and imatinib therapy. There have been cases that document the alterations of patients' GIST histomorphology both with primary GIST prior to imatinib therapy and with recurrent GIST after imatinib therapy. However, there has been no documented case of a patient who has recurrent GIST with chondroid differentiation at the primary site after imatinib therapy. In this article, we report an incidental finding of a 58-year-old patient who had two treatments of imatinib therapy prior to surgical resection of her recurrent GIST in her stomach. We also explore through a mini-literature review the various cases of GIST with chondroid differentiation that have been reported to compare the histomorphology, immunophenotype, and patient demographic of these cases. This article is significant for reporting a rare finding of GIST after imatinib therapy and highlights the various presentations that GIST could acquire after imatinib therapy that exclude another malignant process, such as chondrosarcoma.

Emergent Management of Severe Hypothermia, Acidemia, and Coagulopathy in Operative Penetrating Ballistic Cranial Trauma.

Hypothermia in a trauma patient has been associated with increased morbidity and mortality and is more frequently seen in those sustaining traumatic brain injuries (TBIs). Acidosis is an important consequence of hypothermia that leads to derangements across the spectrum of the coagulation cascade. Here, we present a case of a 31-year-old male presented after suffering a right parietal penetrating ballistic injury with an associated subdural hematoma and 7 mm midline shift requiring decompressive craniectomy and external ventricular drain (EVD) placement in the setting of severe hypothermia (28°C) and acidosis (pH 7.12). With aggressive rewarming intraoperatively, the use of full-body forced-air warming, warmed IV fluids, and increasing the ambient room temperature, the patient's acidosis and hypothermia improved to pH 7.20 and 34°C. Despite these aggressive attempts to rewarm the patient, he developed coagulopathy in the setting of concurrent hypothermia and acidosis. This case highlights the importance of prompt reversal of hypothermia due to its potentially fatal effects, particularly in the setting of severe TBIs. We discuss the critical aspects of surgical management of the injury and anesthetic management of hypothermia, acidosis, and coagulopathy perioperatively.

Cannabis Use Disorder Trends and Health Care Utilization After Cervical and Lumbar Spine Fusions.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To identify differences in complication rates after cervical and lumbar fusion over the first postoperative year between those with and without cannabis use disorder (CUD) and to assess how CUD affects opioid prescription patterns. SUMMARY OF BACKGROUND DATA: Cannabis is legal for medical purposes in 36 states and for recreational use in 18 states. Cannabis has multisystem effects and may contribute to transient vasoconstrictive, prothrombotic, and inflammatory effects. METHODS: The IBM MarketScan Database (2009-2019) was used to identify patients who underwent cervical or lumbar fusions, with or without CUD. Exact match hospitalization and postdischarge outcomes were analyzed at index, six, and 12 months. RESULTS: Of 72,024 cervical fusion (2.0% with CUD) and 105,612 lumbar fusion patients (1.5% with CUD), individuals with CUD were more likely to be young males with higher Elixhauser index. The cervical CUD group had increased neurological complications (3% vs. 2%) and sepsis (1% vs. 0%) during the index hospitalization and neurological (7% vs. 5%) and wound complications (5% vs. 3%) at 12 months. The lumbar CUD group had increased wound (8% vs. 5%) and myocardial infarction (MI) (2% vs. 1%) complications at six months and at 12 months. For those with cervical myelopathy, increased risk of pulmonary complications was observed with CUD at index hospitalization and 12-month follow-up. For those with lumbar stenosis, cardiac complications and MI were associated with CUD at index hospitalization and 12 months. CUD was associated with opiate use disorder, decreasing postoperatively. CONCLUSIONS: No differences in reoperation rates were observed for CUD groups undergoing cervical or lumbar fusion. CUD was associated with an increased risk of stroke for the cervical fusion cohort and cardiac (including MI) and pulmonary complications for lumbar fusion at index hospitalization and six and 12 months postoperatively. Opiate use disorder and decreased opiate dependence after surgery also correlated with CUD.

Resection of a Recurrent Lumbar Chordoma With Intradural Extension and Complex Dural Repair: 2-Dimensional Operative Video.

Chordomas are derived from embryonic notochord remnants and comprise 1%-4% of all bone tumors.1 Nearly all chordomas arise in the axial skeleton, with 50% in the sacrococcygeal region, 35% in the skull base and 15% within mobile spine vertebrae.1,2 Regional recurrence after en bloc surgery is common and 30%-40% of patients develop metastatic disease.3-6 In this operative video, we present a 41-year old man who previously underwent en bloc lateral L1 corpectomy and received high-dose hybrid photon and proton radiation therapy for treatment of his L1 chordoma. On surveillance imaging, 2 years post op MRI revealed recurrence of the chordoma, now extending to the L2-3 epidural space. Further radiation alone was considered but was not performed due to lack of separation between the tumor and neural elements, thus increasing the risk of radiation-induced neurological injury. Combination revision surgical resection with subsequent boost radiation therapy was pursued instead. The technical nuances to achieve complex ventral and dorsal dural repair after removal of a transdural lumbar chordoma are shown in detail. Postoperatively, the patient had no new neurological deficits. At 13 months postoperatively, he reports no new pain, can ambulate without assistance, and completed 33 treatments of radiation therapy with proton beam. The patient consented to the procedure and to the publication of his image.

Trends and Outcomes in Patients with Dementia Undergoing Spine Fusions: A Matched Nationwide Inpatient Sample Analysis.

BACKGROUND: The aim of our study was to define the trends and outcomes in patients with a preexisting diagnosis of dementia who underwent spine fusions using a large national database. METHODS: The Nationwide Inpatient Sample database was queried using the International Classification of Diseases, Ninth Revision and Tenth Revision, from 1998 to 2018. We included patients who underwent spine fusions with or without the diagnosis of dementia. Outcomes were trends, complications, length of stay (LOS), discharge disposition, and mortality. RESULTS: A cohort of 4495 patients (N = 1,390,657; 0.32%) with dementia who underwent spine fusions was identified. There was an increasing trend of spine fusions in patients with the diagnosis of dementia. Most patients with dementia were white (77% vs. 69%), with ≥3 comorbidities (70% vs. 23%), had Medicare insurance (83% vs. 34%) compared with patients without dementia (P < 0.0001). Overall, 38% of patients had complications after spine fusions compared with 21% of patients without dementia during the study period. Median LOS was significantly longer in patients with dementia compared with patients without dementia (6 vs. 4 days). Patients with dementia were less likely to be discharged home (19% vs. 40%) and incurred higher in-hospitalization charges ($139,101 vs. $101,629) compared with patients without dementia. No differences in terms of in-hospital mortality were noted across the cohorts (1.4% vs. 1.6%). CONCLUSIONS: Patients with dementia had 1.5 times longer LOS and 1.4 times higher index hospitalization charges and were 2.5 times more likely to have complications and 71% less likely to be discharged home, with no difference in mortality compared with patients without dementia after spine fusions.

The modified occipital condyle screw: A quantitative anatomic study investigating the feasibility of a novel instrumented fixation technique for craniocervical fusion.

Study Design: Prospective human anatomical study. Objective: Occipitocervical fusion with occipital plate or condyle screws has shown higher failure rates in those with skeletal dysplasia. The modified occipital condyle screw connects the occipital condyle to the pars basilaris of the occipital bone that may achieve fortified bony purchase and serve as a more rigid fixation point. We evaluate anatomical feasibility of a novel cranial fixation technique designed to decrease risk of pseudarthrosis. Materials and Methods: Occipital condyles were analyzed morphologically using multiplanar three-dimensional reconstructed, ultra-thin section computed tomography. The following parameters were obtained: occipital condyle length, maximal cross section, location of hypoglossal canal, axial and sagittal orientation of the long axis, occipital condyle pedicle (OCP) diameter, maximal length of OCP screw, and entry point. Results: Forty patients with total of 80 occipital condyles were analyzed and the following measurements were obtained: occipital condyle length 24.1 mm (20.5-27.7, standard deviation [SD]: 2.2); condyle maximum axial cross-section 12.6 mm (9-15.8, SD: 1.9); length of OCP screw 38.9 mm (29.3-44, SD: 5.7); diameter of OCP 3.4 mm (3.2-3.6, SD: 0.2); clearance below hypoglossal canal 4.5 mm (3.4-7, SD: 1.1); and distance of screw entry point from condylar foramen 2 mm (range 0-4, SD 1.6). Conclusion: The modified occipital condyle screw connects the condyle with the clivus through the pars basilaris and represents a safe and technically feasible approach to achieve craniocervical fusion in skeletally mature individuals. This cephalad anchor point serves as an alternate fixation point of the occipitocervical junction with increased strength of construct and decreased risk of hardware failure or pseudarthrosis given cortical bone purchase and longer screw instrumentation.

Immune-Mediated Necrotizing Myopathy With Concurrent Statin Use After Routine COVID-19 Inoculation: A Case Report.

SARS-CoV-2 has been associated with multiple disease processes and chronic sequela. Much less understood are the neurological effects, ranging from headaches, pro-thrombotic state, encephalitis, and myopathic processes. Many case reports have documented post-SARS-CoV-2 virus effects; however, this case highlights the possibility of a less commonly described neurological manifestation possibly related to the BNT162b2 mRNA Pfizer vaccine. There is scant literature on immune-mediated necrotizing myopathy (IMNM) triggered after COVID-19 vaccination. The BNT162b2 mRNA COVID-19 vaccine (Pfizer, BioNTech) has proven to be safe and effective in reducing transmission of COVID-19, but post-vaccination neurological events, including venous sinus thrombosis, transverse myelitis, and immune-mediated diseases, such as Guillain-Barré syndrome, have been reported. We report a case of IMNM with HMG-CoA reductase antibody positivity in the setting of BNT162b2 vaccination. The patient presented with progressive muscle weakness with rhabdomyolysis and necrotizing autoimmune myopathy proven on muscle biopsy after the second dose of the BNT162b2 vaccine. Ultimately, this case report highlights the importance of clinical suspicion for early diagnosis and initiation of treatment after symptoms concerning necrotizing myopathy.

AccuCalc: A Python Package for Accuracy Calculation in GWAS.

The genome-wide association study (GWAS) is a popular genomic approach that identifies genomic regions associated with a phenotype and, thus, aims to discover causative mutations (CM) in the genes underlying the phenotype. However, GWAS discoveries are limited by many factors and typically identify associated genomic regions without the further ability to compare the viability of candidate genes and actual CMs. Therefore, the current methodology is limited to CM identification. In our recent work, we presented a novel approach to an empowered "GWAS to Genes" strategy that we named Synthetic phenotype to causative mutation (SP2CM). We established this strategy to identify CMs in soybean genes and developed a web-based tool for accuracy calculation (AccuTool) for a reference panel of soybean accessions. Here, we describe our further development of the tool that extends its utilization for other species and named it AccuCalc. We enhanced the tool for the analysis of datasets with a low-frequency distribution of a rare phenotype by automated formatting of a synthetic phenotype and added another accuracy-based GWAS evaluation criterion to the accuracy calculation. We designed AccuCalc as a Python package for GWAS data analysis for any user-defined species-independent variant calling format (vcf) or HapMap format (hmp) as input data. AccuCalc saves analysis outputs in user-friendly tab-delimited formats and also offers visualization of the GWAS results as Manhattan plots accentuated by accuracy. Under the hood of Python, AccuCalc is publicly available and, thus, can be used conveniently for the SP2CM strategy utilization for every species.

Genomic Variations Explorer (GenVarX): a toolset for annotating promoter and CNV regions using genotypic and phenotypic differences.

The rapid growth of sequencing technology and its increasing popularity in biology-related research over the years has made whole genome re-sequencing (WGRS) data become widely available. A large amount of WGRS data can unlock the knowledge gap between genomics and phenomics through gaining an understanding of the genomic variations that can lead to phenotype changes. These genomic variations are usually comprised of allele and structural changes in DNA, and these changes can affect the regulatory mechanisms causing changes in gene expression and altering the phenotypes of organisms. In this research work, we created the GenVarX toolset, that is backed by transcription factor binding sequence data in promoter regions, the copy number variations data, SNPs and Indels data, and phenotypes data which can potentially provide insights about phenotypic differences and solve compelling questions in plant research. Analytics-wise, we have developed strategies to better utilize the WGRS data and mine the data using efficient data processing scripts, libraries, tools, and frameworks to create the interactive and visualization-enhanced GenVarX toolset that encompasses both promoter regions and copy number variation analysis components. The main capabilities of the GenVarX toolset are to provide easy-to-use interfaces for users to perform queries, visualize data, and interact with the data. Based on different input windows on the user interface, users can provide inputs corresponding to each field and submit the information as a query. The data returned on the results page is usually displayed in a tabular fashion. In addition, interactive figures are also included in the toolset to facilitate the visualization of statistical results or tool outputs. Currently, the GenVarX toolset supports soybean, rice, and Arabidopsis. The researchers can access the soybean GenVarX toolset from SoyKB via https://soykb.org/SoybeanGenVarX/, rice GenVarX toolset, and Arabidopsis GenVarX toolset from KBCommons web portal with links https://kbcommons.org/system/tools/GenVarX/Osativa and https://kbcommons.org/system/tools/GenVarX/Athaliana, respectively.