bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Persisting SARS-CoV-2 RNA and Pathological Findings: Lessons Learnt From a Series of 35 COVID-19 Autopsies
Authors: Maccio Umberto , Zinkernagel Annelies S. , Schuepbach Reto , Probst-Mueller Elsbeth , Frontzek Karl , Brugger Silvio D. , Hofmaenner Daniel Andrea , Moch Holger , Varga Zsuzsanna 
Published: February 2022

BackgroundLong-term sequelae of coronavirus disease 2019 (COVID-19), including the interaction between persisting viral-RNA and specific tissue involvement, pose a challenging issue. In this study, we addressed the chronological correlation (after first clinical diagnosis and postmortem) between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and organ involvement.MethodsThe presence of postmortem SARS-CoV-2 RNA from 35 complete COVID-19 autopsies was correlated with the time interval between the first diagnosis of COVID-19 and death and with its relationship to morphologic findings.ResultsSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA can be evident up to 40 days after the first diagnosis and can persist to 94 hours after death. Postmortem SARS-CoV-2 RNA was mostly positive in lungs (70%) and trachea (69%), but all investigated organs were positive with variable frequency. Late-stage tissue damage was evident up to 65 days after initial diagnosis in several organs. Positivity for SARS-CoV-2 RNA in pulmonary swabs correlated with diffuse alveolar damage (p = 0.0009). No correlation between positive swabs and other morphologic findings was present. Cerebral (p = 0.0003) and systemic hemorrhages (p = 0.009), cardiac thrombi (p = 0.04), and ischemic events (p = 0.03) were more frequent in the first wave, whereas bacterial pneumonia (p = 0.03) was more prevalent in the second wave. No differences in biometric data, clinical comorbidities, and other autopsy findings were found.ConclusionsOur data provide evidence not only of long-term postmortem persisting SARS-CoV-2 RNA but also of tissue damage several weeks after the first diagnosis of SARS-CoV-2 infection. Additional conditions, such as concomitant bacterial pulmonary superinfection, lung aspergillosis, thromboembolic phenomena, and hemorrhages can further worsen tissue damage.
Evaluation of the Ocular Surface and Meibomian Gland in Obstructive Sleep Apnea Hypopnea Syndrome
Authors: Liu Shaohua , Li Shisheng , Li Mengmeng , Zeng Shiying , Chen Baihua , Zhang Liwei 
Published: February 2022

PurposeTo assess the ocular surface and meibomian gland (MG) of patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and to explore the effects of surgery for OSAHS on the ocular surface and MG.MethodsBased on the apnea hypopnea index (AHI), 21 patients with mild OSAHS (Group A, 5/h ≤ AHI &lt; 15/h), 20 patients with moderate OSAHS (Group B, 15/h ≤ AHI &lt; 30/h), 62 patients with severe OSAHS (Group C, AHI ≥ 30/h) were examined. The ocular surface and MG were evaluated using Keratograph 5M. In addition, detailed Ophthalmic examination including visual acuity, refraction, slit-lamp examination of the anterior segment, corneal fluorescein staining (CFS), ocular surface disease index (OSDI) scoring, Schirmer I test (SIT) and serum lipid measurement was performed. For OSAHS patients with dry eye syndrome (DES) who underwent uvulopalatopharyngoplasty for improving AHI, the conditions of the ocular surface and MG were compared before surgery and 3 months after surgery. Only the data of the right eyes were analyzed.ResultsThere were no significantly different in the OSDI score, tear meniscus height (TMH), or loss ratio of the lower eyelid (LRLE) among these groups. The first non-invasive tear film breakup time (fNIBUT), average non-invasive tear film breakup time (avNIBUT), bulbar redness index (BRI), lipid layer grading (LLG), CFS, plugged orifices and distortion in MG, the loss ratio of upper eyelid (LRUE), and the incidence of DES, floppy eyelid syndrome (FES) and meibomian gland dysfunction (MGD) showed significant differences between Groups A and C (p = 0.015, p = 0.018, p &lt; 0.001, p = 0.022, p = 0.036, p = 0.007, p = 0.019, p = 0.017, p = 0.045, p = 0.013, and p = 0.029, respectively). The SIT in the Group A was significantly higher than in Group B (p = 0.025) and in Group C (p &lt; 0.001). In the correlation analyses, the fNIBUT, avNIBUT, SIT and LLG had negative correlations with the AHI (p = 0.013, p = 0.010, p = 0.003, p &lt; 0.001, and p = 0.006, respectively). The BRI, CFS and LRUE were positively correlated with the AHI (p = 0.006, p = 0.007, and p = 0.046, respectively). Three months after surgery, there were no significant differences in the ocular surface or MG.ConclusionPatients with severe OSAHS have poor stability of tear film and are prone to lipid-deficient dry eye as a result of the loss of meibomian gland. By improving the AHI, the ocular surface damage of OSAHS patients cannot be reversed in a short time.
Impact of Heterotopic Ossification on Functional Recovery in Acute Spinal Cord Injury
Authors: Franz Steffen , Rust Lukas , Heutehaus Laura , Rupp Rüdiger , Schuld Christian , Weidner Norbert 
Published: February 2022

Objective: In spinal cord injury (SCI), heterotopic ossification is a frequent secondary complication, commonly associated with limited range of motion of affected joints, which could lead to secondary disability in activities of daily living. Additionally, heterotopic ossifications might challenge the effect of regeneration-promoting therapies on neurological and functional recovery. This study evaluated the impact of heterotopic ossification on clinical recovery within the first year after SCI.Methods: The study was conducted as a monocentric longitudinal paired cohort study. Recruitment was based on consecutive sampling in the framework of the European Multicenter about Spinal Cord Injury (EMSCI). Recovery profiles were determined using standardized neurological and functional clinical assessments within the 1st year following SCI. All study participants underwent at least two comprehensive standardized neurological and functional clinical examinations according to the International Standards for Neurological Classification of SCI and the Spinal Cord Independence Measure, respectively. Data regarding the diagnosis and treatment of heterotopic ossification were obtained by reviewing the patient medical records. The most similar “digital twin” from the entire EMSCI database were matched in terms of age, acute neurological and functional status to each individual with SCI, and heterotopic ossification.Results: Out of 25 participants diagnosed with heterotopic ossification, 13 individuals were enrolled and matched to control individuals. Most individuals presented with motor complete injury (75%). Ossifications were most frequently located at the hip joints (92%) and mainly occurred within the first 3 months after SCI. Individuals with heterotopic ossification achieved around 40% less functional improvement over time compared to their matched counterparts, whereas neurological recovery was not altered in individuals with SCI and heterotopic ossification.Conclusion: Heterotopic ossification—a common complication of SCI—unfavorably affects functional recovery, which in the end is most relevant for the best possible degree of independence in activities of daily living. Upon presentation with heterotopic ossification, neurological improvement achieved through potential restorative therapies might not translate into clinically meaningful functional improvement. Diagnostic algorithms and effective early prevention/treatment options for heterotopic ossification need to be established to ensure the best possible functional outcome.Clinical Trial Registration: NCT01571531 (https://clinicaltrials.gov).
ASIC-E4: Interplay of Beta-Amyloid, Synaptic Density and Neuroinflammation in Cognitively Normal Volunteers With Three Levels of Genetic Risk for Late-Onset Alzheimer's Disease – Study Protocol and Baseline Characteristics
Authors: Snellman Anniina , Ekblad Laura L. , Koivumäki Mikko , Lindgrén Noora , Tuisku Jouni , Perälä Merja , Kallio Lila , Lehtonen Riina , Saunavaara Virva , Saunavaara Jani , Oikonen Vesa , Aarnio Richard , Löyttyniemi Eliisa , Parkkola Riitta , Karrasch Mira , Zetterberg Henrik , Blennow Kaj , Rinne Juha O. 
Published: February 2022

BackgroundDetailed characterization of early pathophysiological changes in preclinical Alzheimer's disease (AD) is necessary to enable development of correctly targeted and timed disease-modifying treatments. ASIC-E4 study (“Beta-Amyloid, Synaptic loss, Inflammation and Cognition in healthy APOE ε4 carriers”) combines state-of-the-art neuroimaging and fluid-based biomarker measurements to study the early interplay of three key pathological features of AD, i.e., beta-amyloid (Aβ) deposition, neuroinflammation and synaptic dysfunction and loss in cognitively normal volunteers with three different levels of genetic (APOE-related) risk for late-onset AD.ObjectiveHere, our objective is to describe the study design, used protocols and baseline demographics of the ASIC-E4 study.Methods/DesignASIC-E4 is a prospective observational multimodal imaging study performed in Turku PET Centre in collaboration with University of Gothenburg. Cognitively normal 60–75-year-old-individuals with known APOE ε4/ε4 genotype were recruited via local Auria Biobank (Turku, Finland). Recruitment of the project has been completed in July 2020 and 63 individuals were enrolled to three study groups (Group 1: APOE ε4/ε4, N = 19; Group 2: APOE ε4/ε3, N = 22; Group 3: APOE ε3/ε3, N = 22). At baseline, all participants will undergo positron emission tomography imaging with tracers targeted against Aβ deposition (11C-PIB), activated glia (11C-PK11195) and synaptic vesicle glycoprotein 2A (11C-UCB-J), two brain magnetic resonance imaging scans, and extensive cognitive testing. In addition, blood samples are collected for various laboratory measurements and blood biomarker analysis and cerebrospinal fluid samples are collected from a subset of participants based on additional voluntary informed consent. To evaluate the predictive value of the early neuroimaging findings, neuropsychological evaluation and blood biomarker measurements will be repeated after a 4-year follow-up period.DiscussionResults of the ASIC-E4 project will bridge the gap related to limited knowledge of the synaptic and inflammatory changes and their association with each other and Aβ in “at-risk” individuals. Thorough in vivo characterization of the biomarker profiles in this population will produce valuable information for diagnostic purposes and future drug development, where the field has already started to look beyond Aβ.
Modulation of Emotion Perception via Amygdala Stimulation in Humans
Authors: Bujarski Krzysztof A. , Song Yinchen , Xie Tiankang , Leeds Zachary , Kolankiewicz Sophia I. , Wozniak Gabriella H. , Guillory Sean , Aronson Joshua P. , Chang Luke , Jobst Barbara C. 
Published: February 2022

BackgroundMultiple lines of evidence show that the human amygdala is part of a neural network important for perception of emotion from environmental stimuli, including for processing of intrinsic attractiveness/“goodness” or averseness/“badness,” i.e., affective valence.Objective/HypothesisWith this in mind, we investigated the effect of electrical brain stimulation of the human amygdala on perception of affective valence of images taken from the International Affective Picture Set (IAPS).MethodsUsing intracranial electrodes in patients with epilepsy, we first obtained event-related potentials (ERPs) in eight patients as they viewed IAPS images of varying affective valence. Next, in a further cohort of 10 patients (five female and five male), we measured the effect of 50 Hz electrical stimulation of the left amygdala on perception of affective valence from IAPS images.ResultsWe recorded distinct ERPs from the left amygdala and found significant differences in the responses between positively and negatively valenced stimuli (p = 0.002), and between neutral and negatively valenced stimuli (p = 0.017) 300–500 ms after stimulus onset. Next, we found that amygdala stimulation did not significantly affect how patients perceived valence for neutral images (p = 0.58), whereas stimulation induced patients to report both positively (p = 0.05) and negatively (&lt; 0.01) valenced images as more neutral.ConclusionThese results render further evidence that the left amygdala participates in a neural network for perception of emotion from environmental stimuli. These findings support the idea that electrical stimulation disrupts this network and leads to partial disruption of perception of emotion. Harnessing this effect may have clinical implications in treatment of certain neuropsychiatric disorders using deep brain stimulation (DBS) and neuromodulation.
Genetically Predicted Circulating Omega-3 Fatty Acids Levels Are Causally Associated With Increased Risk for Systemic Lupus Erythematosus
Authors: Wang Peng , Xiang Kun , Xu Yuan-Yuan , He Yi-Sheng , Hu Yu-Qian , Ni Jing , Pan Hai-Feng 
Published: February 2022

BackgroundAccumulating evidence has demonstrated the associations of omega-3 or omega-6 polyunsaturated fatty acids (PUFAs) with the disease activity and inflammatory mediators of systemic lupus erythematosus (SLE), but the evidence of causal links of omega-3 or omega-6 PUFAs on the risk for SLE remains inconclusive.ObjectivesThis study was conducted to evaluate the causal relationships between omega-3/omega-6 PUFAs and SLE by performing the Mendelian randomization (MR) analysis.MethodsGenome-wide significant single-nucleotide polymorphisms (SNPs) were obtained from genome-wide association studies (GWASs) of circulating omega-3/omega-6 levels (n = up to 13,544) and GWAS meta-analyses of SLE (n = 14,267), respectively. The bidirectional two-sample MR (TSMR) analysis was conducted to infer the causality.ResultsThe inverse-variance weighted (IVW) method revealed that genetically determined per SD increase in omega-3 levels were causally associated with an increased risk for SLE (odds ratios [ORs] = 1.49, 95% CI: 1.07, 2.08, p = 0.021), but no causal effect of omega-6 on the risk SLE was observed (IVW OR = 1.06, 95% CI: 0.72, 1.57, p = 0.759). In addition, there were no significantly causal associations in genetic predisposition to SLE with the changes of omega-3 and omega-6 levels, respectively (IVW beta for omega-3: 0.007, 95% CI: −0.006, 0.022, p = 0.299; IVW beta for omega-6: −0.008, 95% CI: −0.023, 0.006, p = 0.255).ConclusionThe present study revealed the possible causal role of omega-3 on increasing the risk for SLE, it could be the potential implications for dietary recommendations.
A Prospective Self-Controlled Study of Indocyanine Green, Radioisotope, and Methylene Blue for Combined Imaging of Axillary Sentinel Lymph Nodes in Breast Cancer
Authors: Jin Yuting , Yuan Long , Zhang Yi , Tang Peng , Yang Ying , Fan Linjun , Chen Li , Qi Xiaowei , Jiang Jun 
Published: February 2022

PurposeThis self-controlled study aimed to clarify whether indocyanine green (ICG) could be an alternative tracer in the absence of radioisotope (RI) for combined imaging of axillary sentinel lymph node (SLN) in breast cancer.MethodsPrimary breast cancer, clinically axillary node-negative patients (n = 182) were prospectively enrolled from March 2015 to November 2020. ICG, methylene blue (MB), and RI were used to perform axillary sentinel lymph node biopsy (SLNB). The main observation index was the positivity of ICG + MB vs. RI + MB in axillary SLNB; the secondary observation indicators were the axillary SLN detection rate, mean number of axillary SLNs detected, mean number of metastatic axillary SLNs detected, and safety.ResultsAll 182 patients had axillary SLNs; a total of 925 axillary SLNs were detected. Pathological examination confirmed metastatic axillary SLN in 42 patients (total of 79 metastatic SLNs). Positivity, detection rate of SLNs, detection rate of metastatic SLNs, and the number of metastatic SLNs detected were comparable with RI+MB and ICG+MB (p &gt; 0.05). The mean number of axillary SLNs detected was significantly higher with ICG+MB than with RI+MB (4.99 ± 2.42 vs. 4.02 ± 2.33, p &lt; 0.001). No tracer-related adverse events occurred.ConclusionsICG appears to be a safe and effective axillary SLN tracer, and a feasible alternative to RI in combined imaging for axillary SLN of breast cancer.
Development of Spinal Tuberculosis in an Adolescent With Crohn's Disease After Infliximab Therapy: A Case Report With Literature Review
Authors: Jung Jae Hoon , Choi Sujin , Kang Youra , Cho Dae-Chul , Lee So Mi , Park Tae In , Choe Byung-Ho , Kim Dongsub , Kang Ben 
Published: February 2022

IntroductionTuberculosis (TB) spondylitis, also known as Pott's disease, is a severe form of extrapulmonary TB. Infliximab treatment for Crohn's disease (CD) patients increases the risk of TB, and is likely to increase the risk of TB spondylitis as well.Case PresentationWe report a rare case of TB spondylitis development in a 16-year-old female with CD. She had a close household contact of active pulmonary TB and received contact investigation. She was diagnosed with latent TB 1 month before the diagnosis of CD, and had started a latent TB treatment regimen with isoniazid for 9 months. At 5 months from the start of latent TB treatment, infliximab was started. Approximately 1 year after infliximab treatment, her infusion interval was shortened from every 8 weeks to every 4 weeks owing to secondary loss of response due to nonimmunogenic pharmacokinetic failure. One month later, miliary TB developed and infliximab was stopped. She received a miliary TB treatment regimen for 6 months, curing the disease. Three months later, spinal TB was incidentally detected on abdominal computed tomography. She received a TB treatment regimen for 12 months, curing spinal TB. Currently, she is receiving vedolizumab to treat CD and is in clinical remission. Although this patient has sufficiently been treated at each stage of TB development, particularly for latent TB and miliary TB, TB spondylitis still developed.ConclusionConsidering that TB spondylitis developed despite sufficient treatment at each stage, pediatric gastroenterologists should stay cautious when using anti-tumor necrosis factor agents in patients with inflammatory bowel disease with a history of latent TB.
The Ages and Stages Questionnaire: Social-Emotional—What Is the Optimal Cut-Off for 3-Year-Olds in the Swedish Setting?
Authors: Vaezghasemi Masoud , Eurenius Eva , Ivarsson Anneli , Richter Sundberg Linda , Silfverdal Sven Arne , Lindkvist Marie 
Published: February 2022

ObjectiveExpressions of emotional and behavioral symptoms in preschool age can predict mental health problems in adolescence and adulthood. The Ages and Stages Questionnaires: Social-Emotional (ASQ:SE) has been successful in detecting social and emotional problems in young children in some countries but had not been tested in Sweden. The objective of this study was to determine the optimal cut-off for the ASQ:SE instrument when administered to 3-year-old children in a northern Swedish setting, using the Strengths and Difficulties Questionnaire (SDQ) as the reference.MethodsThe ASQ:SE (36-month interval, first edition) was administered at routine 3-year-olds' visits to Child Health Care centers in Region Västerbotten, Sweden. During the study period (September 2017 to March 2018) parents were invited to also fill out the SDQ (2–4 year version). In the final analyses 191 children fulfilled the criteria for inclusion in the study sample. Non-parametric Receiver Operating Characteristic analysis was performed to quantify the discriminatory accuracy of ASQ:SE based on SDQ.ResultsThe Pearson correlation between ASQ:SE and SDQ indicated strong correlation between the two instruments. The Receiver Operating Characteristic curve showed good accuracy of ASQ:SE in relation to SDQ. However, our results suggest that the existing ASQ:SE cut-off score of 59 was not optimal in the Swedish context. Changing the cut-off from 59 to 50 would allow us to detect 100% (n = 14) of children with problems according to SDQ, compared to 64% (n = 9) when the cut-off was 59. However, the proportion of false positives would be higher (9% compared to 3%).ConclusionThe main finding was that for 3-year-olds in Sweden a decreased ASQ:SE cut-off score of 50 would be optimal. This would increase the detection rate of at-risk children according to SDQ (true positive), thus prioritizing sensitivity. Our conclusion is that, although this change would result in more false positives, this would be justifiable.
Receptor Interaction Profiles of 4-Alkoxy-3,5-Dimethoxy-Phenethylamines (Mescaline Derivatives) and Related Amphetamines
Authors: Kolaczynska Karolina E. , Luethi Dino , Trachsel Daniel , Hoener Marius C. , Liechti Matthias E. 
Published: February 2022

3,4,5-Trimethoxyphenethylamine (mescaline) is a psychedelic alkaloid found in peyote cactus. Related 4-alkoxy-3,5-dimethoxy-substituted phenethylamines (scalines) and amphetamines (3C-scalines) are reported to induce similarly potent psychedelic effects and are therefore potential novel therapeutics for psychedelic-assisted therapy. Herein, several pharmacologically uninvestigated scalines and 3C-scalines were examined at key monoamine targets in vitro. Binding affinity at human serotonergic 5-HT1A, 5-HT2A, and 5-HT2C, adrenergic α1A and α2A, and dopaminergic D2 receptors, rat and mouse trace amine-associated receptor 1 (TAAR1), and human monoamine transporters were assessed using target specific transfected cells. Furthermore, activation of human 5-HT2A and 5-HT2B receptors, and TAAR1 was examined. Generally, scalines and 3C-scalines bound with weak to moderately high affinity to the 5-HT2A receptor (Ki = 150–12,000 nM). 3C-scalines showed a marginal preference for the 5-HT2A vs the 5-HT2C and 5-HT1A receptors whereas no preference was observed for the scalines. Extending the 4-alkoxy substituent increased 5-HT2A and 5-HT2C receptors binding affinities, and enhanced activation potency and efficacy at the 5-HT2A but not at the 5-HT2B receptor. Introduction of fluorinated 4-alkoxy substituents generally increased 5-HT2A and 5-HT2C receptors binding affinities and increased the activation potency and efficacy at the 5-HT2A and 5-HT2B receptors. Overall, no potent affinity was observed at non-serotonergic targets. As observed for other psychedelics, scalines and 3C-scalines interacted with the 5-HT2A and 5-HT2C receptors and bound with higher affinities (up to 63-fold and 34-fold increase, respectively) when compared to mescaline.