bluuebunny/crossref_metadata_2025_split huggingface dataset:
hnRNP G/RBMX enhances HPV16 E2 mRNA splicing through a novel splicing enhancer and inhibits production of spliced E7 oncogene mRNAs
Authors: Hao Chengyu , Zheng Yunji , Jönsson Johanna , Cui Xiaoxu , Yu Haoran , Wu Chengjun , Kajitani Naoko , Schwartz Stefan 
Published: March 2022

Abstract
Human papillomavirus type 16 (HPV16) E2 is an essential HPV16 protein. We have investigated how HPV16 E2 expression is regulated and have identifed a splicing enhancer that is required for production of HPV16 E2 mRNAs. This uridine-less splicing enhancer sequence (ACGAGGACGAGGACAAGGA) contains 84% adenosine and guanosine and 16% cytosine and consists of three ‘AC(A/G)AGG’-repeats. Mutational inactivation of the splicing enhancer reduced splicing to E2-mRNA specific splice site SA2709 and resulted in increased levels of unspliced E1-encoding mRNAs. The splicing enhancer sequence interacted with cellular RNA binding protein hnRNP G that promoted splicing to SA2709 and enhanced E2 mRNA production. The splicing-enhancing function of hnRNP G mapped to amino acids 236–286 of hnRNP G that were also shown to interact with splicing factor U2AF65. The interactions between hnRNP G and HPV16 E2 mRNAs and U2AF65 increased in response to keratinocyte differentiation as well as by the induction of the DNA damage response (DDR). The DDR reduced sumoylation of hnRNP G and pharmacological inhibition of sumoylation enhanced HPV16 E2 mRNA splicing and interactions between hnRNP G and E2 mRNAs and U2AF65. Intriguingly, hnRNP G also promoted intron retention of the HPV16 E6 coding region thereby inhibiting production of spliced E7 oncogene mRNAs.
Ketogenic diet, epilepsy and cognition: what do we know so far? A systematic review
Authors: Lima Maiara Cristina , Gabiatti Mariana Papini , Moreira Júlia Dubois , Ribeiro Leticia Carina , Lunardi Mariana dos Santos , Lin Katia , Venske Débora Kurrle 
Published: March 2022

Abstract

Context
Epilepsy is a chronic neurological disorder that has social, cognitive, and psychological consequences to the patient.

Objective
The effects of the ketogenic diet (KD) in children and adults with pharmacoresistant epilepsy on cognitive function were evaluated in this systematic review.

Data Sources
The MEDLINE, Cochrane Library, Scopus, Web of Science, and LILACS databases were searched up to February 2021.

Study Selection and Data Extraction
From the 2973 records initially identified, 24 studies were included in the systematic review. These records were screened via PICO criteria, focusing on studies that evaluated the effects of KD on cognitive function of patients with pharmacoresistant epilepsy.

Results
Nineteen studies described improvements in cognitive function attributed to KD; improvements were not observed in 2 studies, but neither was aggravation. Contradictory results were reported in 3 studies, depending on the method used to assess cognition. At first glance, cognitive function appears to be associated with the number of seizures, diet effectiveness, amount of carbohydrate ingested, and antiseizure medication used. However, due to the diversity of methods used to assess cognitive function, especially self-perception of cognitive improvement by the patient, it was not possible to confirm this hypothesis.

Conclusion
It was not possible to confirm if KD itself promotes improvements in cognitive function in patients with pharmacoresistant epilepsy. Certainly, more studies are needed with better methodological quality, larger and more homogeneous samples in relation to epileptic syndrome and clinical aspects of the disease, more rigid monitoring of adherence to the diet, and use of standardized tests for neuropsychological assessment.
Systematic Review Registration: PROSPERO registration no. CRD42019129236
Slick Potassium Channels Control Pain and Itch in Distinct Populations of Sensory and Spinal Neurons in Mice
Authors: Flauaus Cathrin , Engel Patrick , Zhou Fangyuan , Petersen Jonas , Ruth Peter , Lukowski Robert , Schmidtko Achim , Lu Ruirui 
Published: March 2022

Background
Slick, a sodium-activated potassium channel, has been recently identified in somatosensory pathways, but its functional role is poorly understood. The authors of this study hypothesized that Slick is involved in processing sensations of pain and itch.

Methods
Immunostaining, in situ hybridization, Western blot, and real-time quantitative reverse transcription polymerase chain reaction were used to investigate the expression of Slick in dorsal root ganglia and the spinal cord. Mice lacking Slick globally (Slick–/–) or conditionally in neurons of the spinal dorsal horn (Lbx1-Slick–/–) were assessed in behavioral models.

Results
The authors found Slick to be enriched in nociceptive Aδ-fibers and in populations of interneurons in the spinal dorsal horn. Slick–/– mice, but not Lbx1-Slick–/– mice, showed enhanced responses to noxious heat in the hot plate and tail-immersion tests. Both Slick–/– and Lbx1-Slick–/– mice demonstrated prolonged paw licking after capsaicin injection (mean ± SD, 45.6 ± 30.1 s [95% CI, 19.8 to 71.4]; and 13.1 ± 16.1 s [95% CI, 1.8 to 28.0]; P = 0.006 [Slick–/– {n = 8} and wild-type {n = 7}, respectively]), which was paralleled by increased phosphorylation of the neuronal activity marker extracellular signal–regulated kinase in the spinal cord. In the spinal dorsal horn, Slick is colocalized with somatostatin receptor 2 (SSTR2), and intrathecal preadministration of the SSTR2 antagonist CYN-154806 prevented increased capsaicin-induced licking in Slick–/– and Lbx1-Slick–/– mice. Moreover, scratching after intrathecal delivery of the somatostatin analog octreotide was considerably reduced in Slick–/– and Lbx1-Slick–/– mice (Slick–/– [n = 8]: 6.1 ± 6.7 bouts [95% CI, 0.6 to 11.7]; wild-type [n =8]: 47.4 ± 51.1 bouts [95% CI, 4.8 to 90.2]; P = 0.039).

Conclusions
Slick expressed in a subset of sensory neurons modulates heat-induced pain, while Slick expressed in spinal cord interneurons inhibits capsaicin-induced pain but facilitates somatostatin-induced itch.

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Anterior Approach for Fixation of Acetabular Fractures Using Anatomically Designed Plates: Accuracy of Reduction and Early Functional Outcomes With a Minimum of 1-Year Follow-Up
Authors: Khalefa Mohamed A. , El Nahal Walid A. , Abdel Karim Mahmoud , Abdel-Kader Khaled F. M. , Chesser Timothy John Sloan , Ward Anthony J. , Acharya Mehool 
Published: March 2022

Objectives:
To evaluate the results of a new plate system using anterior approaches in the management of acetabular fractures.

Design:
Retrospective case-note review.

Setting:
Pelvic and acetabular tertiary center.

Patients and intervention:
A consecutive series of acetabular fractures treated using only anterior approach and anatomical plates, at one tertiary specialist unit, were reviewed. The fracture patterns, incisions used, intraoperative and postoperative complications, reduction achieved (measured on postoperative radiographs and computed tomography scans), and early postoperative results (minimum 1-year follow-up) were recorded.

Main Outcome measurement:
Postoperative reduction (measured by postoperative plain radiographs and computed tomography).

Results:
Thirty-three patients (mean age, 57 years) underwent reconstruction with the anatomical plates using anterior approaches. Associated both columns and anterior column posterior hemitransverse represented most of the patients (85%). The fracture pattern was complex with quadrilateral plate involvement in 79% of cases. Overall, anatomic reduction was seen in 82% on plain radiographs and CT scan evaluation. Increasing age was a statistically significant variable in obtaining anatomical reduction with an age cutoff value of 70 years (P 0.012). Associated both column fractures were associated with a lower incidence of anatomical reduction (P = 0.038). Complication rates were comparable with the literature. 22 patients (71%) were symptom free, with 20 patients (62.5%) having excellent radiographic outcomes at the latest follow-up.

Conclusions:
The results suggested that using approach-specific instruments and anatomical plates through anterior approaches in a specialized unit led to anatomical reconstruction in 82% with patients demonstrating satisfactory early radiological and functional outcomes at 1 year.

Level of Evidence:
Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
Role of Electrical Stimulation in Peripheral Nerve Regeneration: A Systematic Review
Authors: ElAbd Rawan , Alabdulkarim Abdulaziz , AlSabah Salman , Hazan Jessica , Alhalabi Becher , Thibaudeau Stephanie 
Published: March 2022

Background:
Functional recovery after peripheral nerve injury is often suboptimal despite the intrinsic permissive growth environment of the peripheral nervous system. The objective of this systematic review is to explore the use of electrical stimulation (ES) for peripheral nerve regeneration.

Methods:
A systematic literature search was conducted from inception to March 2, 2021 to retrieve articles on ES for peripheral nerve regeneration using the PubMed, Ovid MEDLINE, and Embase databases. Primary outcome measures included objective measures of motor and sensory nerve function.

Results:
Four randomized control trials, two case reports, and three case series that addressed the aims were identified. The stimulation parameters varied greatly between studies, without an apparent commonality for a given electrical conduit. Outcomes measured included motor (n = 8) and sensory (n = 7) modalities (cold detection, static two-point discrimination, tactile discrimination, and pressure detection), nerve-specific muscle function and bulk, and electromyography (EMG) motor and sensory terminal latency. Different parameters for measurement were utilized and improvement was observed across the studies compared with controls (n = 4) or pre-intervention measurements (n = 5). One randomized control trial reported no benefit of ES and attributed their findings to their stimulation protocol. Complications were documented in three patients only and included wire remnant removal, skin pigmentation, and bone formation.

Conclusions:
ES in peripheral nerve regeneration is beneficial in improving and accelerating recovery. A meta-analysis was not performed due to the heterogeneity, but all studies showed positive findings and minor to no complications. These results provide a primer for further development of delivery methods.
Distinguishing Healthy From Glaucomatous Eyes With Optical Coherence Tomography Global Circumpapillary Retinal Nerve Fiber Thickness in the Bottom 5th Percentile
Authors: Zemborain Zane Z. , Tsamis Emmanouil , La Bruna Sol , Leshno Ari , De Moraes C. Gustavo , Ritch Robert , Hood Donald C. 
Published: March 2022

Précis:
Two novel, quantitative metrics, and 1 traditional metric were able to distinguish between many, but not all healthy and glaucomatous eyes in the bottom 5th percentile of global circumpapillary retinal nerve fiber layer (cpRNFL) thickness.

Purpose:
To test the hypothesis that objective optical coherence tomography measures can distinguish between a healthy control with global cpRNFL thickness within the lower 5% of normal and a glaucoma patient with an equivalent cpRNFL thickness.

Patients and Methods:
A total of 37 healthy eyes from over 700 normative eyes fell within the bottom 5th percentile in global cpRNFL thickness. The global cpRNFL thickness of 35 glaucomatous eyes from 188 patients fell within the same range. For the traditional methods, the global cpRNFL thickness percentile and the global ganglion cell layer (GCL) thickness percentile for the central ±8 degrees, were calculated for all 72 eyes. For the novel cpRNFL method, the normalized root mean square (RMS) difference between the cpRNFL thickness profile and the global thickness–matched normative thickness profile was calculated. For the superior-inferior (SI) GCL method, the normalized mean difference in superior and inferior GCL thickness was calculated for the central ±8 degrees.

Results:
The best quantitative metric, the RMS cpRNFL method, had an accuracy of 90% compared with 81% for the SI GCL and 81% for the global GCL methods. As expected, the global cpRNFL had the worst accuracy, 72%. Similarly, the RMS cpRNFL method had an area under the curve of 0.93 compared with 0.83 and 0.84 for the SI GCL and global GCL methods, respectively. The global cpRNFL method had the worst area under the curve, 0.75.

Conclusion:
Quantitative metrics can distinguish between most of the healthy and glaucomatous eyes with low global cpRNFL thickness. However, even the most successful metric, RMS cpRNFL, missed some glaucomatous eyes.
Relationship of Cognitive and Social Engagement to Health and Psychological Outcomes in Community-Dwelling Older Adults
Authors: Liebzeit Daniel , Kuo Wan-chin , Carlson Beverly , Mueller Kimberly , Koscik Rebecca L. , Smith Marianne , Johnson Sterling , Bratzke Lisa 
Published: March 2022

Background
Cognitive and social engagement is an important yet underdocumented aspect of older adult engagement and function.

Objective
The purpose of this study was to examine relationships between cognitive and social engagement and health and psychological outcomes in a cohort of community-dwelling older adults aged approximately 55–70 years.

Methods
Analysis of data from the Wisconsin Registry for Alzheimer’s Prevention, a multiwave cohort study with 1,582 participants, using a 1:1 prospective case–control design to examine whether lower cognitive and social engagement at Visit 4 (baseline) is associated with worse health and psychological outcomes at Visit 5 (2 years after Visit 4). Wisconsin Registry for Alzheimer’s Prevention participants were included in this study if they had complete data on cognitive and social engagement and self-rated health at both visits.

Results
After matching potential covariates using propensity scores, participants with low cognitive and social engagement (cases) at baseline continued to have significantly lower cognitive and social engagement than the controls (participants with high cognitive and social engagement at baseline) at Visit 5, and they had lower self-rated health and higher surgery rate. Depressive symptoms, cognitive status, and hospitalization at Visit 5 did not significantly differ between cases and controls.

Discussion
This study provides evidence supporting cognitive and social engagement as an important marker of early decline in activity engagement that may indicate a potential later decline in functional, psychological, and health outcomes.
Inflammatory and Immune Protein Pathways Possible Mechanisms for Pain Following Walking in Knee Osteoarthritis
Authors: Klinedinst N. Jennifer , Huang Weiliang , Nelson Amy K. , Resnick Barbara , Renn Cynthia , Kane Maureen A. , Dorsey Susan G. 
Published: March 2022

Abstract

Background
Knee osteoarthritis affects nearly 30% of adults aged 60 years or older and causes significant pain and disability. Walking is considered a “gold standard” treatment option for reducing knee osteoarthritis pain and maintaining joint mobility but does not reduce pain for all adults with knee osteoarthritis pain and may induce pain—particularly when starting a walking routine. The mechanism by which walking is helpful for knee osteoarthritis pain is unclear. Quantitative sensory testing has revealed that knee osteoarthritis pain has both peripheral and central components, which vary by individual.

Objective
The purpose of this study was to better understand the mechanisms underlying the value of walking for knee pain.

Methods
We conducted a pretest/posttest study using quantitative sensory testing to measure neurophysiological parameters and examined systemic protein signatures. Adults with knee osteoarthritis and healthy controls underwent quantitative sensory testing and blood draw for platelet proteomics before and after a 30-minute walk at 100 steps per minute.

Results
A single 30-minute walk moderately increased pressure pain sensitivity at the affected knee among persons with knee osteoarthritis. Healthy adults showed no difference in pain sensitivity. Protein signatures among participants with knee osteoarthritis indicated changes in inflammatory and immune pathways, including the complement system and SAA1 protein that coincided with changes in pain with walking and differed from healthy participants.

Discussion
One goal of developing individualized interventions for knee osteoarthritis pain is to elucidate the mechanisms by which self-management interventions affect pain. The addition of therapies that target the complement system or SAA1 expression may improve the pain sensitivity after a moderate walk for adults with knee osteoarthritis.
Are We Aware of the Neurological Manifestations of Cytomegalovirus Infection in Immunocompetent Individuals?
Authors: Yilmaz Murat , Halicioglu Siddika , Aydin Turkoglu Sule , Sirmatel Fatma 
Published: March 2022

Background:
While cytomegalovirus (CMV) infection usually causes disease in immunosuppressed individuals, it mostly progresses as an asymptomatic infection in healthy adults. However, very rarely, immunocompetent individuals may also suffer from encephalitis and stroke.

Methods:
Nine patients who were admitted to the Neurology Clinic of Abant Izzet Baysal University Faculty of Medicine from 2016 to 2020 who had various neurological symptoms and were diagnosed with CMV infection were retrospectively analyzed. Symptoms, examination findings, laboratory results, radiologic imaging, and treatments were recorded and evaluated.

Results:
Although severe infections because of CMV generally occur in newborns and immunosuppressed adults, it is estimated that the disease is more common in immunocompetent adults than known. This may be associated with unrecognized risks, in part because of immune dysfunction or comorbidities such as renal failure or diabetes mellitus. Also, CMV replication in arterial endothelial cells can restrict blood flow, inducing an atherosclerotic environment and causing stroke. Diagnosis is based on clinical suspicion and serology. Ganciclovir is administered for treatment.

Conclusion:
CMV infection should be considered in the differential diagnosis of patients presenting with neurological symptoms, even among immunocompetent individuals, because of the high possibility that patients can greatly benefit from antiviral treatment at the early stage.
A Retrospective Analysis of Clinical Utilization between Patients who used Telemedicine and Office Visits in Outpatient Physical Medicine & Rehabilitation Clinics during the COVID-19 Pandemic
Authors: Gilmer Gabrielle , Jackson Natalie , Koscumb Stephen , Marroquin Oscar , Sowa Gwendolyn 
Published: March 2022

Abstract

Objective
To describe the demographic characteristics of patients who used telemedicine and office visits in Physical Medicine and Rehabilitation (PM&R) during the COVID-19 pandemic and to quantify differences in clinical utilization between groups. Clinical utilization was defined as emergency department, urgent care, and hospital visits.

Design
Retrospective cohort study of 1,096 patients who used telemedicine and 1,171 patients who used office visits from April to June 2020 in outpatient PM&R at UPMC for musculoskeletal-related complaints

Results
The telemedicine groups contained proportionally more people of color and higher comorbidities than the office visit groups. Patients who were seen in the telemedicine groups were more likely to be prescribed opioids than the office visit group. There were no differences in clinical utilizations between the telemedicine and office visit groups.

Conclusions
The higher use of telemedicine in patients of color suggests a need for studying long-term outcomes to evaluate differences in care standards. We also identified that there is an urgent need to understand how telemedicine affects opioid prescribing practices. Lastly, future studies are needed to understand why there were no differences in clinical utilization between the telemedicine and office visit groups.
Glocal dendritic spikes: variation in branch activity during dendritic spiking indicates multiple functional units in the pyramidal neuron apical tuft
Authors: Geron Erez 
Published: March 2022

AbstractThere is a lively debate on how many functional units exist within the dendritic tree of pyramidal neurons (PNs). The classical view that the PN’s dendritic tree comprises several computational units 1-4 was challenged by recent in-vivo studies that identified mainly widespread dendritic spikes 5-10, suggesting a low degree of dendritic compartmentalization. We reasoned that global spikes do not rule out dendritic compartmentalization if these spikes contain a high variation in branch activity. Therefore, we turned to image Ca2+ activity in many apical dendrites from individual layer (L) 5 PNs of the primary motor cortex (M1). For proper dendritic morphology and Ca2+ activity analysis, we used mice with sparse double labeling of PNs with a structural marker (tdTomato) and a GCaMP6s probe. We first collected data for complete registration of the apical tuft dendritic structure. We then used 3D two-photon microscopy to image Ca2+ activity within these tufts during treadmill running. Using these, we imaged up to 30 apical branches from individual L5 PNs, including branches separated by as many as 11 bifurcations and more than 1000 µm of intracellular distance. We found that local spikes were rare, but global spikes often displayed heterogeneous Ca2+ elevation across branches, giving rise to an activity pattern across the tuft. This spiking pattern was dynamic and according to unsupervised hierarchical cluster analysis, fitted to 2-6 distinct patterns, even over short imaging periods. Taken together, we find a considerable variation in branch activity within and between global dendritic spikes, supporting multiple dendritic functional units.Graphical abstractWe detected three main spike types. Local spikes were evident in a minority of the branches and had low amplitude. Contrastingly, global spikes often displayed homogeneous levels of branch activity and were the strongest and most prolonged spikes. An intermediate pattern was the “glocal spike,” where a global spike exhibited heterogeneous branch activity. Spikes with heterogeneous Ca2+ elevation across branches constituted at least a quarter of all spikes. In the social sciences, the term “glocalization” refers to global phenomena that are adjusted locally, such as food items sold worldwide but attuned to local tastes 11. Influenced by that, we refer to global spikes with heterogeneous branch activity as “glocal spikes.”