bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying Common Peroneal Neuropathy before Foot Drop
Authors: Lu Johnny Chuieng-Yi , Dengler Jana , Poppler Louis H. , Van Handel Amelia , Linkugel Andrew , Jacobson Lauren , Mackinnon Susan E. 
Published: May 2020

Background:
Common peroneal neuropathy shares the same pathophysiology as carpal tunnel syndrome. However, management is often delayed because of the traditional misconception of recognizing foot drop as the defining symptom for diagnosis. The authors believe recognizing common peroneal neuropathy before foot drop can relieve pain and help improve quality of life.

Methods:
One hundred eighty-five patients who underwent surgical common peroneal neuropathy decompression between 2011 and 2017 were included. The mean follow-up time was 249 ± 28 days. Patients were classified into two stages of severity based on clinical presentation: pre–foot drop and overt foot drop. Demographics, presenting symptoms, clinical signs, electrodiagnostic studies and response to surgery were compared between these two groups. Multivariate regression analysis was used to identify variables that predicted outcome following surgery.

Results:
Overt foot drop patients presented with significantly lower preoperative motor function (percentage of patients with Medical Research Council grade ≤ 1: overt foot drop, 90 percent; pre–foot drop, 0 percent; p < 0.001). Pre–foot drop patients presented with a significantly higher preoperative pain visual analogue scale score (pre–foot drop, 6.2 ± 0.2; overt foot drop, 4.6 ± 0.3; p < 0.001) and normal electrodiagnostic studies (pre–foot drop, 31.4 percent; overt foot drop, 0.1 percent). Postoperatively, both groups of patients showed significant improvement in quality-of-life score (pre–foot drop, 2.6 ± 0.3; overt foot drop, 2.7 ± 0.3). Patients with obesity or a traumatic cause for common peroneal neuropathy were less likely to have improvements in quality of life after surgical decompression.

Conclusion:
Increased recognition of common peroneal neuropathy can aid early management, relieve pain, and improve quality of life.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, II.
Metabolic Syndrome, Disease Activity, and Adipokines in Patients With Newly Diagnosed Inflammatory Joint Diseases
Authors: Kononoff Aulikki , Vuolteenaho Katriina , Hämäläinen Mari , Kautiainen Hannu , Elfving Pia , Savolainen Elina , Arstila Leena , Niinisalo Helena , Rutanen Jarno , Marjoniemi Olga , Moilanen Eeva , Kaipiainen-Seppänen Oili 
Published: May 2020

Objective
To investigate metabolic syndrome (MetS), disease activity, and adipokine levels among patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and undifferentiated arthritis (UA) at the time of diagnosis and after 1 year of follow-up.

Methods
Patients with inflammatory joint diseases participating in the Northern Savo 2010 population-based longitudinal epidemiological study were evaluated for components of MetS (by National Cholesterol Education Program's Adult Treatment Panel III) and clinical parameters of disease activity. The adipokines adiponectin, adipsin, resistin, and leptin were measured at baseline and after 1 year of treatment with disease-modifying antirheumatic drugs.

Results
Among 176 patients, MetS was detected in 42% of RA, 36% of SpA, and 51% of UA patients. Metabolic syndrome was associated with higher disease activity as measured by patient global assessment in RA and UA patients and increased pain in RA patients. Leptin levels were increased in patients with MetS, showing a linearly increasing trend with the number of components of MetS in SpA and UA, but not in RA. In RA patients, decrease in disease activity correlated with decrease in leptin levels. Resistin did not associate with MetS, but a decrease in resistin correlated with decrease in disease activity in RA and UA. In SpA, increased adiponectin level correlated with relief in disease activity, but not with MetS.

Conclusions
Metabolic syndrome was common in patients with newly diagnosed arthritides and associated with higher disease activity and increased leptin levels. Resistin responded to treatment of arthritis in RA and UA, leptin in RA, and adiponectin in SpA.
Usefulness of Methotrexate in the Reduction of Relapses and Recurrences in Polymyalgia Rheumatica
Authors: de la Torre María L. , Rodríguez Anabella M. , Pisoni Cecilia N. 
Published: May 2020

ObjectivesMethotrexate (MTX) has been studied with conflicting results in patients with polymyalgia rheumatica (PMR). Our objective was to evaluate the effectiveness of MTX to reduce relapses and recurrences in patients with PMR.MethodsThis observational longitudinal cohort study included 94 consecutive patients with PMR. Patients were assigned to 3 groups according to the prescribed treatment: group 1, treated with glucocorticoids (GCs) alone; group 2, treated with GCs initially plus MTX after a relapse or recurrence; and group 3, treated with GCs plus MTX since diagnosis.Factors associated with a first relapse were studied in the population. To evaluate MTX effect, patients from group 2 were evaluated comparing results from the first treatment period (GCs alone) to the second treatment period with GCs plus MTX.ResultsNinety-four patients were included. The median follow-up time was 21.3 months (interquartile range [IQR], 11.7–56.2). Fifty-three patients (56.4%) were in group 1, 33 (35.1%) in group 2, and 8 (8.5%) in group 3. We found that female sex had a tendency to be associated with a first relapse (p= 0.07).In group 2, 35 relapses were identified during the first treatment period and only 8 relapses during the combined treatment period (p< 0.001). In this group, after the addition of MTX, the GCs dose at relapse was lower (5.1 vs 3 mg/d,p= 0.02) and the time to accomplish remission was shorter (22.9 vs 8.7 months,p= 0.01). There were no differences in the number of recurrences.ConclusionsThe use of MTX in PMR patients who already had a relapse reduced the number of future relapses and decreased the time to achieve remission. Adding MTX allowed a reduction of GCs dose at relapse.
Zero Echo Time–Based PET/MRI Attenuation Correction in Patients With Oral Cavity Cancer
Authors: Tsujikawa Tetsuya , Kanno Masafumi , Ito Yumi , Oikawa Hiroshi , Rahman Mahmudur G.M. , Narita Norihiko , Fujieda Shigeharu , Okazawa Hidehiko 
Published: May 2020

Purpose
The aims of this study were to demonstrate the feasibility of zero echo time (ZTE) MRI for jawbone identification, and to evaluate the quantitative performance of 18F-FDG PET/MRI with ZTE-based attenuation correction (ZTE-AC) compared with PET/CT and PET/MRI with Dixon MR–based AC (Dixon-AC) in patients with oral cavity cancer (OCC).

Materials and Methods
Thirteen OCC patients underwent whole-body 18F-FDG PET/CT and subsequent regional PET/MRI with Dixon-AC and ZTE-AC in 1 day. SUVs of the primary OCC and metastatic cervical lymph nodes (CLNs) were measured on PET/CT (SUVCT), PET/MRI with Dixon-AC (SUVDixon), and ZTE-AC (SUVZTE). The SUVs were then compared.

Results
The ZTE MRI scans minimized the effects of metal artifacts from dentures, and ZTE-AC maps correctly delineated the jawbones. SUVDixon and SUVZTE had significant positive correlations with SUVCT (Pearson r = 0.97 and r = 0.99 for OCC, and r = 0.98 and r = 0.98 for CLNs, respectively). The mean ± SD of SUVCT, SUVDixon, and SUVZTE were 14.4 ± 8.0, 14.5 ± 8.6, and 15.6 ± 8.8 for OCC, and 6.3 ± 3.0, 8.0 ± 4.0, and 7.6 ± 3.9 for CLNs, respectively. For OCCs, SUVZTE was significantly higher than SUVCT (P < 0.05), whereas there was no significant difference between SUVCT and SUVDixon or between SUVDixon and SUVZTE. For CLNs, SUVDixon and SUVZTE were significantly higher than SUVCT (P < 0.01 and P < 0.05, respectively), and SUVDixon was significantly higher than SUVZTE (P < 0.01).

Conclusions
ZTE MRI can correctly identify jawbones while minimizing the effects of metal artifacts. The ZTE-AC method in 18F-FDG PET/MRI reduces the underestimation of tracer uptake due to Dixon-AC jawbone errors and improves the quantitative performance of PET for OCC patients.
68Ga-FAPI PET/CT Detects Gastric Signet-Ring Cell Carcinoma in a Patient Previously Treated for Prostate Cancer
Authors: Pang Yizhen , Huang Haichao , Fu Li , Zhao Liang , Chen Haojun 
Published: May 2020

Abstract
A 75-year-old man with a history of prostate cancer (T1N0M0, Gleason score 4 + 3) was referred to radionuclide bone scan and 68Ga-PSMA PET/CT to detect recurrence. Multiple abnormal foci were observed in the axial and appendicular skeleton, which were suggestive of metastatic superscan from prostate cancer. However, histopathological examinations (from bone biopsy) did not support the metastases from prostate cancer. 68Ga-FAPI PET/CT was then performed to detect the occult tumor, which showed intense activity in the gastric wall. Subsequent gastroscopy examination revealed the diagnosis of GSRCC (gastric signet-ring cell carcinoma). The diagnosis of GSRCC with widespread bone metastases was finally made.
Pneumococcal Conjugate Vaccination Followed by Pneumococcal Polysaccharide Vaccination in Lung Transplant Candidates and Recipients
Authors: Hoffman Thijs W. , Meek Bob , Rijkers Ger T. , Grutters Jan C. , van Kessel Diana A. 
Published: May 2020

Background.
Pneumococcal conjugate vaccination as well as pneumococcal polysaccharide vaccination are recommended for lung transplant candidates and recipients, but the combination of these vaccines has not been extensively studied in these specific populations.

Methods.
Lung transplant candidates and recipients were vaccinated with a 13-valent pneumococcal conjugate vaccine, followed 8 weeks later by a pneumococcal polysaccharide vaccine. Pneumococcal antibody levels against 13 pneumococcal serotypes were measured and followed up after 1 year in the transplant recipients. These values were compared with a historical control group vaccinated with the polysaccharide vaccine alone.

Results.
Twenty-five lung transplant candidates and 23 lung transplant recipients were included. For the majority of serotypes, there was no significant increase in antibody levels after additional vaccination with the polysaccharide vaccine in both patient groups. When compared with the historical control group, the antibody response in lung transplant recipients 1 year after vaccination did not seem to have improved by vaccination with both vaccines instead of the polysaccharide vaccine alone.

Conclusions.
Serologic vaccination responses in lung transplant candidates and recipients were not improved by giving a 23-valent pneumococcal polysaccharide vaccine after a 13-valent pneumococcal conjugate vaccine. The benefit of this vaccination schedule in lung transplant recipients seems to differ from other immunocompromised populations. The optimal vaccination schedule for lung transplant candidates and recipients remains to be determined.
Association of Renin-Angiotensin-Aldosterone System Inhibition with Risk of COVID-19, Inflammation Level, Severity and Death in Patients With COVID-19: A Rapid Systematic Review and Meta-Analysis
Authors: Liu Xiao , Long Chuyan , Xiong Qinmei , Chen Chen , Ma Jianyong , Su Yuhao , Hong Kui 
Published: May 2020

BackgroundAn association among the use of angiotensin-converting-enzyme(ACE) inhibitors and angiotensin-receptor blockers(ARBs) with the clinical outcomes of coronavirus disease 2019 (COVID-19) is unclear.MethodsPubMed, EMBASE, and the preprint databases MedRxiv and BioRxiv were searched for relevant studies that assessed the association among inflammation level, application of ACEI/ARB, infection severity and death in patients with COVID-19. Odd risks(OR) and 95% confidence interval (CI) were combined using random-effects or fixed models depending on heterogeneity.ResultsEleven studies were included with a total of 33,483 patients. Our review showed ACEI/ARB therapy might be associated with the reduced inflammatory factor (interleukin-6) and elevated level of immune cells(CD3, CD8). Meta-analysis showed no significant increase in the risk of COVID-19 infection(OR:0.95, 95%CI:0.89-1.05) in patients receiving ACEI/ARB therapy, and ACEI/ARB therapy was associated with a decreased risk of severe COVID-19 (OR:0.75, 95%CI: 0.59-0.96) and mortality (OR:0.52, 95%CI: 0.35-0.79). Subgroup analyses showed that, among the general population, application of ACEI/ARB therapy was associated with reduced risks of all-cause death(OR:0.31, 95%CI: 0.13-0.75), and the risk of severe COVID-19(OR:0.79, 95%CI: 0.60-1.05) infection and COVID-19 infection(OR:0.85, 95% CI: 0.66-1.08) were not increased. Among patients with hypertension, the use of an ACEI/ARB was associated with a lower severity of COVID-19(OR:0.73, 95%CI: 0.51-1.03) and lower mortality(OR:0.57, 95%CI: 0.37-0.87), without evidence of an increased risk of COVID-19 infection(OR:1.00, 95%CI: 0.90-1.12).ConclusionOn the basis of the available evidence, this is the first meta-analysis showed that, in general population, the use of ACEI/ARB therapy was safe without an increased risk of COVID-19 infection and with a decreasing trend of severe COVID-19 infection and lower mortality. In patients with hypertension, the use of ACEI/ARB therapy should be encouraged, without increased risk of COVID-19 inflection, and better prognosis (a decreasing trends of severe COVID-19 and reduced all-cause death). Overall, ACEI/ARB therapy should be continued in patients who are at risk for, or have COVID-19, either in general population or hypertension patients. Our results need to be interpreted with caution considering the potential for residual confounders, and more well-designed studies that control the clinical confounders are necessary to confirm our findings.
Gene regulatory networks controlling differentiation, survival, and diversification of hypothalamic Lhx6-expressing GABAergic neurons
Authors: Kim Dong Won , Liu Kai , Wang Zoe Qianyi , Zhang Yi Stephanie , Bathini Abhijith , Brown Matthew P , Lin Sonia Hao , Washington Parris Whitney , Sun Changyu , Lindtner Susan , Lee Bora , Wang Hong , Shimogori Tomomi , Rubenstein John L.R. , Blackshaw Seth 
Published: May 2020

AbstractGABAergic neurons of the hypothalamus regulate many innate behaviors, but little is known about the mechanisms that control their development. We previously identified hypothalamic neurons that express the LIM homeodomain transcription factor Lhx6, a master regulator of cortical interneuron development, as sleep-promoting. In contrast to telencephalic interneurons, hypothalamic Lhx6 neurons do not undergo long-distance tangential migration and do not express cortical interneuronal markers such asPvalb. Here, we show thatLhx6is necessary for the survival of hypothalamic neurons.Dlx1/2,Nkx2-2, andNkx2-1are each required for specification of spatially distinct subsets of hypothalamic Lhx6 neurons, and that Nkx2-2+/Lhx6+ neurons of the zona incerta are responsive to sleep pressure. We further identify multiple neuropeptides that are enriched in spatially segregated subsets of hypothalamic Lhx6 neurons, and that are distinct from those seen in cortical neurons. These findings identify common and divergent molecular mechanisms by which Lhx6 controls the development of GABAergic neurons in the hypothalamus.
Design and Validation of a Frugal, Automated, Solid-Phase Peptide Synthesizer
Authors: Kallmyer Nathaniel E. , Rider Nathan E. , Reuel Nigel F. 
Published: May 2020

AbstractSolid phase peptide synthesis (SPPS) has enabled widespread use of synthetic peptides in applications ranging from pharmaceuticals to materials science. The demand for synthetic peptides has driven recent efforts to produce automated SPPS synthesizers which utilize fluid-handling components common to chemistry laboratories to drive costs down to several thousand dollars. Herein, we describe the design and validation of a more ‘frugal’ SPPS synthesizer that uses inexpensive, consumer-grade fluid-handling components to achieve a prototype price point between US$300 and $600. We demonstrated functionality by preparing and characterizing peptides with a variety of distinct properties including binding functionality, nanoscale self-assembly, and oxidation-induced fluorescence. This system yielded micromoles of peptide at a cost of approximately $1/residue, a cost which may be further reduced by optimization and bulk purchasing.
Inferring Telomerase Enzymatic Activity from Expression Data
Authors: Noureen Nighat , Wu Shaofang , Lyu Yingli , Yang Juechen , Yung WK Alfred , Gelfond Jonathan , Wang Xiaojing , Koul Dimpy , Ludlow Andrew , Zheng Siyuan 
Published: May 2020

AbstractActive telomerase is essential for stem cells and most cancers to maintain telomeres. The enzymatic activity of telomerase is related but not equivalent to the expression of TERT, the catalytic subunit of the complex. Here we show that telomerase enzymatic activity can be robustly estimated from the expression of a 13-gene signature. We demonstrate the validity of the expression-based approach, named EXTEND, using cell lines, cancer samples, and non-neoplastic samples. When applied to over 9,000 tumors and single cells, we find a strong correlation between telomerase activity and cancer stemness. This correlation is largely driven by a small proliferating cancer cell population that exhibits both high telomerase activity and cancer stemness. This study establishes a novel computational framework for quantifying telomerase enzymatic activity and provides new insights into the relationships among telomerase, cancer proliferation, and stemness.
Application of Generalized Concentration Addition to Predict Mixture Effects of Glucocorticoid Receptor Ligands
Authors: de la Rosa Rosemarie , Schlezinger Jennifer J. , Smith Martyn T. , Webster Thomas F. 
Published: May 2020

AbstractEnvironmental exposures often occur in complex mixtures and at low concentrations. Generalized concentration addition (GCA) is a method used to estimate the joint effect of receptor ligands that vary in efficacy. GCA models have been successfully applied to mixtures of aryl hydrocarbon receptor (AhR) and peroxisome proliferator-activated receptor gamma (PPARγ) ligands, each of which can be modeled as a receptor with a single binding site. Here, we evaluated whether GCA could be applied to homodimer nuclear receptors, which have two binding sites, to predict the combined effect of full glucocorticoid receptor (GR) agonists with partial agonists. We measured transcriptional activation of GR using a cell-based bioassay. Individual dose response curves for dexamethasone (full agonist), prednisolone (full agonist), and medroxyprogesterone 17-acetate (partial agonist) were generated and applied in three additivity models, GCA, effect summation (ES), and relative potency factor (RPF), to generate response surfaces. GCA and RPF yielded adequate predictions of the experimental data for two full agonists. However, GCA fit experimental data significantly better than ES and RPF for all other binary mixtures. This work extends the application of GCA to homodimer nuclear receptors and improves prediction accuracy of mixture effects of GR agonists.
Microstructural integrity of the major nuclei of the thalamus in Parkinson’s disease
Authors: Borlase Nadia , Myall Daniel , Melzer Tracy R. , Livingston Leslie , Watts Richard , Keenan Ross J , MacAskill Michael , Anderson Tim , Dalrymple-Alford John C. 
Published: May 2020

AbstractBackgroundPrevious research has shown an association between thalamus and cognition in Parkinson’s disease (PD).ObjectivesTo investigate the microstructural integrity of the nuclei of the thalamus and relationship with cognition.MethodsLevel II Movement Disorder Society Task Force Criteria characterised patients with Parkinson’s disease as cognitively normal (PDN, n=51); with mild cognitive impairment (PD-MCI, n=16) or with dementia (PDD, n=15). Twenty-three healthy control subjects were included for comparison. Ak-means clustering approach segmented the thalamus into regions representing nine major nuclei. Volume, fractional anisotropy and mean diffusivity of nuclei were compared between cognitive groups and the relationship with cognitive domain z-scores investigated using hierarchical Bayesian regression models.ResultsThere was an overall progressive increase in mean diffusivity as cognition deteriorated (PDN: 1.4 µm2/s (95% uncertainty interval [0.2, 2.7]), PDMCI: 2.4 µm2/s [0.8,4.0], PDD: 4.5 µm2/s [2.8, 6.3]). The largest increase was in the lateral dorsal nucleus (PDN: 0.3 µm2/s [-6.7, 7.2], PDMCI: 5.4 µm2/s [-4.7, 16.1], PDD: 14.8 µm2/s [5.0, 25.0]). Fractional anisotropy showed minimal change between cognitive groups (PDN: 0.001 [-0.005, 0,007], PDMCI: −0.005 [-0.013, 0.003], PDD: −0.005 [-0.014, 0.003]). Increase in mean diffusivity of the thalamus is associated with a global decline in cognition, the magnitude of the effect was greatest in lateral dorsal nucleus. Fractional anisotropy only showed evidence of a relationship with cognitive domain scores in the lateral dorsal nucleus.ConclusionsThe relationship between lateral dorsal nucleus integrity and cognitive changes is likely due to its primary connectivity with frontal and temporal regions.
Subcellular resolution 3D light field imaging with genetically encoded voltage indicators
Authors: Quicke Peter , Howe Carmel L. , Song Pingfan , Jadan Herman Verinaz , Song Chenchen , Knöpfel Thomas , Neil Mark , Dragotti Pier Luigi , Schultz Simon R. , Foust Amanda J. 
Published: May 2020

AbstractLight field microscopy (LFM) enables high signal-to-noise ratio (SNR), light efficient volume imaging at fast frame rates, and has been successfully applied to single-cell resolution functional neuronal calcium imaging. Voltage imaging with genetically encoded voltage indicators (GEVIs) stands to particularly benefit from light field microscopy’s volumetric imaging capability due to high required sampling rates, and limited probe brightness and functional sensitivity. Previous LFM studies have imaged GEVIs to track population-level interactions only in invertebrate preparations and without single cell resolution. Here we demonstrate sub-cellular resolution GEVI light field imaging in acute mouse brain slices resolving dendritic voltage signals localized in three dimensions. We characterize the effects of different light field reconstruction techniques on the SNR and signal localization and compare the SNR to fluorescence transients imaged in wide field. Our results demonstrate the potential of light field voltage imaging for studying dendritic integration and action potential propagation and backpropagation in 3 spatial dimensions.
A ‘Naturalistic Neuroimaging Database’ for understanding the brain using ecological stimuli
Authors: Aliko Sarah , Huang Jiawen , Gheorghiu Florin , Meliss Stefanie , Skipper Jeremy I 
Published: May 2020

AbstractNeuroimaging has advanced our understanding of human psychology using reductionist stimuli that often do not resemble information the brain naturally encounters. It has improved our understanding of the network organization of the brain mostly through analyses of ‘resting-state’ data for which the functions of networks cannot be verifiably labelled. We make a ‘Naturalistic Neuroimaging Database’ (NNDb v1.0) publically available to allow for a more complete understanding of the brain under more ecological conditions during which networks can be labelled. Eighty-six participants underwent behavioural testing and watched one of 10 full-length movies while functional magnetic resonance imaging was acquired. Resulting timeseries data are shown to be of high quality, with good signal-to-noise ratio, few outliers and low movement. Data-driven functional analyses provide further evidence of data quality. They also demonstrate accurate timeseries/movie alignment and how movie annotations might be used to label networks. The NNDb can be used to answer questions previously unaddressed with standard neuroimaging approaches, progressing our knowledge of how the brain works in the real world.