bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Long-term Impact of Whiplash Injuries on Patient Symptoms and the Associated Degenerative Changes Detected Using MRI
Authors: Watanabe Kota , Daimon Kenshi , Fujiwara Hirokazu , Nishiwaki Yuji , Okada Eijiro , Nojiri Kenya , Watanabe Masahiko , Katoh Hiroyuki , Shimizu Kentaro , Ishihama Hiroko , Fujita Nobuyuki , Ichihara Daisuke , Tsuji Takashi , Nakamura Masaya , Matsumoto Morio 
Published: December 2020

Study Design.
A longitudinal, 20-year comparative study of patients with whiplash-associated disorders (WAD).

Objective.
The aim of this study was to clarify the long-term impact of WAD on patient symptoms and on magnetic resonance imaging (MRI) findings of the cervical spine, in comparison with asymptomatic volunteers.

Summary of Background Data.
The long-term impact of WAD has not been fully elucidated.

Methods.
Between 1993 and 1996, we conducted a cross-sectional comparative study of 508 acute WAD patients and 497 asymptomatic volunteers, all of whom underwent MRI on cervical spine and physical examinations. For this 20-year follow-up comparative study, 75 WAD patients and 181 control subjects aged <60 years were recruited from the original cohort. The MRI findings, including discs’ signal intensities, posterior disc protrusions, anterior dural compressions, spinal cord disc space narrowing, and foraminal stenoses, were evaluated using two to four numerical grades. The results of the WAD patients and control subjects were compared.

Results.
In this follow-up, the prevalence of shoulder stiffness (72.0% vs. 45.9%), headache (24.0% vs. 12.2%), and arm pain (13.3% vs. 3.9%) were significantly greater in WAD patients than in control subjects. The multiregression analysis revealed that a history of WAD was associated with shoulder stiffness (odds ratio [OR]: 3.36), headache (OR: 2.39), and arm pain (OR: 3.82). Although MRI findings in WAD patients were more degenerated than in control subjects in the initial study, all MRI findings were similar at the 20-year follow-up. There were no significant correlations between clinical cervical symptoms and progression in each MR finding in either group.

Conclusion.
After 20 years, whiplash injuries significantly impacted the residual symptoms of shoulder stiffness, headache, and arm pain when compared with initially asymptomatic volunteers. The progression of degenerative changes in the cervical intervertebral discs after 20 years revealed no association with existing whiplash injuries, neither did the residual cervical-related symptoms.

Level of Evidence: 3
Intradural Neuroanatomy in the Cervical Spinal Canal
Authors: Kong Chao , Liu Li , Liu Yadong , Yuan Xin , Guan Yun , Gao Yan , Chen Xueming 
Published: December 2020

Mini
This study defined different anatomic zones within the cervical spinal canal and provides detailed anatomical quantitative data for an accurate diagnosis of cervical spondylosis and a safe and effective anterior decompression surgery.

Study Design.
A dissection-based study of 10 embalmed human cadavers.

Objective.
To provide an anatomic basis to examine the underlying mechanisms of cervical spondylosis.

Summary of Background Data.
Detailed anatomical quantitative data of cervical spine is limited in current literature.

Methods.
Ten cervical spines from C2 to T1 were obtained. We defined three zones from midline to lateral part (zone I, II, and III) and two zones from cranial to caudal (zone P and zone IP) on the coronal plane within the cervical spinal canal. Quantitative anatomy of the zones at different cervical segments were measured including: (1) horizontal widths of zone I, II, and III; (2) length of the cervical spinal cord segment at the ventral rootlets (LV); (3) the pedicle height (PH, zone P) and the inter-pedicle height (IPH, zone IP); (4) the distance between the superior margin of pedicle and the exit of the uppermost ventral nerve rootlet (PN).

Results.
The value of zone II at C4 was significantly less than that at other levels. The value of zone III increases from C4 to C8, and the values at C7 and C8 were significantly higher than those at C4, C5, and C6. PHs and IPHs were not significantly different between different levels. The values of LV at C4 and C8 were smaller than those of C5, C6, and C7. The value of PN showed an increasing trend. At C4, the uppermost ventral rootlet was at about the same height as C3 pedicle, while C8 uppermost ventral rootlet was at the same level as the inferior part of C6 pedicle. Ventral intradural intersegmental connections were found in three intersegments out of 20 intersegments.

Conclusion.
The current definition of anatomic zones may be useful for an accurate diagnosis of cervical spondylosis and a safe and effective anterior decompression surgery.

Level of Evidence: N/A
PERIPHERAL OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN A CHOROIDEREMIA CARRIER
Authors: Corvi Federico , Corradetti Giulia , Wong Alice , Eng Jeffrey G. , Sadda SriniVas 
Published: December 2020

Purpose:
To describe the peripheral optical coherence tomography findings in a female choroideremia carrier.

Methods:
A 56-year-old woman was referred for visual disturbance complaining of some occasional photopsias and increasing difficulty with her vision at night in both eyes. Best-corrected visual acuity was 20/20 in the right eye and 20/150 in the left eye. Fundus examination revealed mildly tilted disks and peripapillary atrophy with subtle retinal pigment epithelial changes in the periphery.

Results:
Macular optical coherence tomography in the right eye appeared unremarkable, but the in the left eye, there was diffuse ellipsoid zone band disruption. Green-light fundus autofluorescence revealed mottled areas of decreased autofluorescence in the mid and far periphery creating an irregular mosaic pattern. Peripheral optical coherence tomography scans revealed more diffuse ellipsoid zone alterations than were apparent on the fundus autofluorescence imaging. Genetic testing revealed a heterozygous pathogenic variant in the CHM gene (c.715C>T, p.Arg239). An additional heterozygous mutation was noted in the CNGB1 gene (c.290+2T>C, splice donor).

Conclusion:
Choroideremia carriers may manifest widespread photoreceptor alterations, which may be more extensive than apparent on fundus autofluorescence imaging.
REACTIVE AMYLOID A PROTEIN AMYLOIDOSIS IN THE SETTING OF INFECTIVE ENDOCARDITIS MANIFESTING AS BILATERAL ORBITOPATHY AND CHOROIDOPATHY
Authors: Carrera William , Rosco Michael G. , Safo Myra , Peng Michelle Yun , Ng Caleb , Agarwal Anita 
Published: December 2020

Purpose:
To describe a case of amyloid A protein amyloidosis that produced an orbital inflammatory response with a novel presentation.

Methods:
Case report.

Results:
A 24-year-old Caucasian women with a history of intravenous heroin use was hospitalized for tricuspid valve endocarditis and methicillin-resistant Staphylococcus aureus bacteremia, as well as acute renal failure. She received hemodialysis and intravenous daptomycin and had negative blood cultures for 3 weeks, when she developed sudden bilateral orbital swelling and blurred vision. Visual acuity was 20/200 in the right eye and 20/400 in the left eye. Examination revealed proptosis, conjunctival chemosis and desiccation, optic disk swelling, creamy choroidal infiltrates, and inferiorly located exudative retinal detachments in both eyes. Multimodal imaging demonstrated thickening of the sclera, choroid, and choriocapillaris as well as outer retinal disruption, subretinal fluid, and deposits of hyperfluorescent debris within the choriocapillaris, outer retina, and vitreous. Oral prednisone at 60 mg per day resolved the choroidal infiltrates and exudative detachments. Persistent nephrotic syndrome called for a renal biopsy, which demonstrated amyloid A protein amyloidosis.

Conclusion:
Orbital and choroidal Amyloid A protein amyloidosis can induce a local inflammatory response manifesting as orbital swelling, papillitis, posterior scleritis, choroiditis, and exudative retinal detachment, which responds to steroid therapy. The underlying pathology is likely a reactive inflammatory, vasoocclusive process involving the choriocapillaris and orbital vasculature to the presence of amyloid fibrils.
Phenotyping peripheral neuropathic pain in male and female adolescents: pain descriptors, somatosensory profiles, conditioned pain modulation, and child–parent reported disability
Authors: Verriotis Madeleine , Peters Judy , Sorger Clarissa , Walker Suellen M. 
Published: December 2020

Abstract
Neuropathic pain (NeuP) can be difficult to diagnose and manage in children. Data regarding prevalence and sex-dependent differences are limited, and more detailed phenotyping is needed. This observational cohort study recruited adolescents (10-17 years) with NeuP or complex regional pain syndrome (CRPS). After pain history and NeuP questionnaires, quantitative sensory testing was performed. Individual z-score plots were calculated with body-region control measures and matched to mechanism-related sensory profiles (sensory loss, thermal hyperalgesia, and mechanical hyperalgesia). Conditioned pain modulation was assessed with pressure pain threshold and a contralateral cold conditioning stimulus, and meaningful conditioned pain modulation defined as twice the standard error of measurement. Patients and parents completed validated questionnaires for child quality of life (QoL), pain catastrophizing, and self-reported anxiety/depression. Males (n = 23) and females (n = 43) with NeuP (n = 52) or CRPS (n = 14) reported moderate–severe pain with neuropathic sensory descriptors. Mixed patterns of sensory gain/loss at pain sites were not sex-dependent. Thermal hyperalgesia was common in both NeuP and CRPS, whereas sensory loss occurred only with NeuP and in a smaller proportion than adult cohorts. Conditioned pain modulation was inhibitory in 54%, facilitatory in 14%, and nonresponders had variable cold conditioning sensitivity. Males and females reported marked impairment of QoL, increased emotional distress, and pain catastrophising. Child–parent QoL scores correlated, but catastrophizing scores were discordant when parents or adolescents reported higher anxiety/depression. NeuP in adolescents is associated with significant pain, physical impairment, and psychosocial impairment. Quantifying alterations in somatosensory profiles, descending modulation, child and parent psychological function will inform individualized therapy and stratification for future clinical trials.
Imaging-based navigation technologies in head and neck surgery
Authors: Eu Donovan , Daly Michael J. , Irish Jonathan C. 
Published: December 2020

Purpose of review
Image guided navigation has had significant impact in head and neck surgery, and has been most prolific in endonasal surgeries. Although conventional image guidance involves static computed tomography (CT) images attained in the preoperative setting, the continual evolution of surgical navigation technologies is fast expanding to incorporate both real-time data and bioinformation that allows for improved precision in surgical guidance. With the rapid advances in technologies, this article allows for a timely review of the current and developing techniques in surgical navigation for head and neck surgery.

Recent findings
Current advances for cross-sectional-based image-guided surgery include fusion of CT with other imaging modalities (e.g., magnetic resonance imaging and positron emission tomography) as well as the uptake in intraoperative real-time ‘on the table’ imaging (e.g., cone-beam CT). These advances, together with the integration of virtual/augmented reality, enable potential enhancements in surgical navigation. In addition to the advances in radiological imaging, the development of optical modalities such as fluorescence and spectroscopy techniques further allows the assimilation of biological data to improve navigation particularly for head and neck surgery.

Summary
The steady development of radiological and optical imaging techniques shows great promise in changing the paradigm of head and neck surgery.
Targeting the Ras pathway in pediatric hematologic malignancies
Authors: Pikman Yana , Stieglitz Elliot 
Published: December 2020

Purpose of review
Ras pathway mutations are one of the most common type of alterations in pediatric hematologic malignancies and are frequently associated with adverse outcomes. Despite ongoing efforts to use targeted treatments, there remain no Food and Drug Administration (FDA)-approved medications specifically for children with Ras pathway-mutated leukemia. This review will summarize the role of Ras pathway mutations in pediatric leukemia, discuss the current state of Ras pathway inhibitors and highlight the most promising agents currently being evaluated in clinical trials.

Recent findings
Efficacy using RAF and MEK inhibitors has been demonstrated across multiple solid and brain tumors, and these are now considered standard-of-care for certain tumor types in adults and children. Clinical trials are now testing these medications for the first time in pediatric hematologic disorders, such as acute lymphoblastic leukemia, juvenile myelomonocytic leukemia, and histiocytic disorders. Novel inhibitors of the Ras pathway, including direct RAS inhibitors, are also being tested in clinical trials across a spectrum of pediatric and adult malignancies.

Summary
Activation of the Ras pathway is a common finding in pediatric hematologic neoplasms. Implementation of precision medicine with a goal of improving outcomes for these patients will require testing of Ras pathway inhibitors in combination with other drugs in the context of current and future clinical trials.
New approaches to risk stratification for Wilms tumor
Authors: Nelson Marie V. , van den Heuvel-Eibrink Marry M. , Graf Norbert , Dome Jeffrey S. 
Published: December 2020

Purpose of review
The treatment of Wilms tumor is one of the great achievements in the field of oncology. One of the key success factors has been improved risk stratification, enabling augmentation or reduction of therapy depending on a patient's risk of relapse. This article highlights the evolution of clinical and biological prognostic markers that have been applied in the treatment of Wilms tumor.

Recent findings
Historically, tumor stage and histology were the sole determinants of Wilms tumor treatment. Recent clinical trials conducted by the Children's Oncology Group (COG) and the International Society of Pediatric Oncology (SIOP) Renal Tumor Study Group have expanded the menu of prognostic factors to include histologic and volumetric response to therapy and tumor-specific loss of heterozygosity (LOH) at chromosomes 1p and 16q. Augmentation of therapy has been able to overcome the adverse risk factors. An emerging prognostic marker is chromosome 1q gain, will be incorporated into future clinical trials.

Summary
The application of new clinical and biological prognostic factors has created unprecedented ability to tailor therapy for Wilms tumor, accompanied with improved outcomes. Current and future trials will continue to enhance precision medicine for Wilms tumor.
Immunotherapy in Bacillus Calmette–Guerin (BCG) unresponsive nonmuscle invasive bladder cancer
Authors: Hugar Lee A. , Gilbert Scott M. , Sexton Wade J. , Kamat Ashish M. , Li Roger 
Published: December 2020

Purpose of review
A number of promising therapies for Bacillus Calmette–Guerin (BCG) unresponsive nonmuscle invasive bladder cancer (NMIBC) are in the pipeline. In this review, we discuss the history of immunotherapy for the treatment of NMIBC and future developments, focusing on novel intravesical treatments.

Recent findings
The term BCG unresponsive NMIBC encompasses patients with both BCG refractory and BCG relapsing disease. This definition was adopted to standardize inclusion criteria for patients enrolling in clinical trials in this setting. A host of intravesical immuno-oncologic therapies that include gene therapies, oncolytic viruses, cell surface molecule delivered immunotoxins, and cytokine driven agonism of cellular immunity, are in various phases of the drug development pipeline. In addition, pembrolizumab, an immune-checkpoint inhibitor, has recently been approved as a treatment option for BCG unresponsive NMIBC.

Summary
Patients with BCG unresponsive disease face many difficulties. Although radical cystectomy is the most effective treatment option for these patients, it is associated with significant morbidity, difficult recovery challenges, and refusal by many patients. Cancer immunotherapies may provide bladder sparing options for some patients who develop BCG unresponsive disease.
Paired SARS-CoV-2 Spike Protein Mutations Observed During Ongoing SARS-CoV-2 Viral Transfer from Humans to Minks and Back to Humans
Authors: Burkholz Scott , Pokhrel Suman , Kraemer Benjamin R. , Mochly-Rosen Daria , Carback Richard T. , Hodge Tom , Harris Paul , Ciotlos Serban , Wang Lu , Herst CV , Rubsamen Reid 
Published: December 2020

AbstractA mutation analysis of SARS-CoV-2 genomes collected around the world sorted by sequence, date, geographic location, and species has revealed a large number of variants from the initial reference sequence in Wuhan. This analysis also reveals that humans infected with SARS-CoV-2 have infected mink populations in the Netherlands, Denmark, United States, and Canada. In these animals, a small set of mutations in the spike protein receptor binding domain (RBD), often occurring in specific combinations, has transferred back into humans. The viral genomic mutations in minks observed in the Netherlands and Denmark show the potential for new mutations on the SARS-CoV-2 spike protein RBD to be introduced into humans by zoonotic transfer. Our data suggests that close attention to viral transfer from humans to farm animals and pets will be required to prevent build-up of a viral reservoir for potential future zoonotic transfer.
Analysis and Forecasting of Global RT-PCR Primers for SARS-CoV-2
Authors: Nayar Gowri , Seabolt Edward E. , Kunitomi Mark , Agarwal Akshay , Beck Kristen L. , Mukherjee Vandana , Kaufman James H. 
Published: December 2020

ABSTRACTRapid tests for active SARS-CoV-2 infections rely on reverse transcription polymerase chain reaction (RT-PCR). RT-PCR uses reverse transcription of RNA into complementary DNA (cDNA) and amplification of specific DNA (primer and probe) targets using polymerase chain reaction (PCR). The technology makes rapid and specific identification of the virus possible based on sequence homology of nucleic acid sequence and is much faster than tissue culture or animal cell models. However the technique can lose sensitivity over time as the virus evolves and the target sequences diverge from the selective primer sequences. Different primer sequences have been adopted in different geographic regions. As we rely on these existing RT-PCR primers to track and manage the spread of the Coronavirus, it is imperative to understand how SARS-CoV-2 mutations, over time and geographically, diverge from existing primers used today. In this study, we analyze the performance of the SARS-CoV-2 primers in use today by measuring the number of mismatches between primer sequence and genome targets over time and spatially. We find that there is a growing number of mismatches, an increase by 2% per month, as well as a high specificity of virus based on geographic location.
Open-top axially swept light sheet microscopy
Authors: Kim Bumju , Na Myeongsu , Park Soohyun , Kim Kitae , Park Jeong-Hoon , Chung Euiheon , Chang Sunghoe , Kim Ki Hean 
Published: December 2020

AbstractOpen-top light sheet microscopy (OT-LSM) is a specialized microscopy for the high throughput cellular imaging of large tissues including optically cleared tissues by having all the optical setup below the sample stage. Current OT-LSM systems had relatively low axial resolutions by using weakly focused light sheets to cover the imaging field of view (FOV). In this report, open-top axially swept LSM (OTAS-LSM) was developed for high-throughput cellular imaging with the improved axial resolution. OTAS-LSM swept the tightly focused excitation light sheet across the imaging FOV by using an electro tunable lens (ETL) and collected emission light at the focus of light sheet with a camera in the rolling shutter mode. OTAS-LSM was developed by using air objective lenses and a water prism for simplicity and it had on-axis optical aberration associated with the mismatch of refractive indices between air and immersion medium. The effects of optical aberration were analyzed by both simulation and experiment. The image resolutions were 1.5-1.6μm, and approximately 140% of the aberration-free theoretical values. The newly developed OTAS-LSM was applied to the imaging of optically cleared mouse brain and small intestine and it could visualize neuronal networks in the single cell level. OTAS-LSM might be useful for the high-throughput cellular examination of optically cleared large tissues.
Activation of TIR signaling is required for pattern-triggered immunity
Authors: Tian Hainan , Chen Siyu , Wu Zhongshou , Ao Kevin , Yaghmaiean Hoda , Sun Tongjun , Huang Weijie , Xu Fang , Zhang Yanjun , Wang Shucai , Li Xin , Zhang Yuelin 
Published: December 2020

AbstractPlant immune responses are mainly activated by two types of receptors. Plasma membrane-localized pattern recognition receptors (PRRs) recognize conserved features of microbes, and intracellular nucleotide-binding leucine rich repeat receptors (NLRs) recognize effector proteins from pathogens. NLRs possessing N-terminal Toll/interleukin-1 receptor (TIR) domains (TNLs) activate two parallel signaling pathways via the EDS1/PAD4/ADR1s and the EDS1/SAG101/NRG1s modules. The relationship between PRR-mediated pattern-triggered immunity (PTI) and TIR signaling is unclear. Here we report that activation of TIR signaling plays a key role in PTI. Blocking TIR signaling by knocking out components of the EDS1/PAD4/ADR1s and EDS1/SAG101/NRG1s modules results in attenuated PTI responses such as reduced salicylic acid (SA) levels and expression of defense genes, and compromised resistance against pathogens. Consistently, PTI is attenuated in transgenic plants that have reduced accumulation of NLRs. Upon treatment with PTI elicitors such as flg22 and nlp20, a large number of genes encoding TNLs or TIR domain-containing proteins are rapidly induced, likely responsible for activating TIR signaling during PTI. In support, overexpression of some of these genes results in activation of defense responses. Overall, our study reveals that TIR signaling activation is an important mechanism for boosting plant defense during PTI.