bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improvement of Long COVID symptoms over one year
Authors: Oliveira Carlos R. , Jason Leonard A. , Unutmaz Derya , Bateman Lucinda , Vernon Suzanne D. 
Published: January 2023

ImportanceEarly and accurate diagnosis and treatment of Long COVID, clinically known as post-acute sequelae of COVID-19 (PASC), may mitigate progression to chronic diseases such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Our objective was to determine the utility of the DePaul Symptom Questionnaire (DSQ) to assess the frequency and severity of common symptoms of ME/CFS, to diagnose and monitor symptoms in patients with PASC.MethodsThis prospective, observational cohort study enrolled 185 people that included 34 patients with PASC that had positive COVID-19 test and persistent symptoms of &gt;3 months and 151 patients diagnosed with ME/CFS. PASC patients were followed over 1 year and responded to the DSQ at baseline and 12 months. ME/CFS patients responded to the DSQ at baseline and 1 year later. Changes in symptoms over time were analyzed using a fixed-effects model to compute difference-in-differences estimates between baseline and 1-year follow-up assessments.ParticipantsPatients were defined as having PASC if they had a previous positive COVID-19 test, were experiencing symptoms of fatigue, post-exertional malaise, or other unwellness for at least 3 months, were not hospitalized for COVID-19, had no documented major medical or psychiatric diseases prior to COVID-19, and had no other active and untreated disease processes that could explain their symptoms. PASC patients were recruited in 2021. ME/CFS patients were recruited in 2017.ResultsAt baseline, patients with PASC had similar symptom severity and frequency as patients with ME/CFS and satisfied ME/CFS diagnostic criteria. ME/CFS patients experienced significantly more severe unrefreshing sleep and flu-like symptoms. Five symptoms improved significantly over the course of 1 year for PASC patients including fatigue, post-exertional malaise, brain fog, irritable bowel symptoms and feeling unsteady. In contrast, there were no significant symptom improvements for ME/CFS patients.Conclusion and relevanceThere were considerable similarities between patients with PASC and ME/CFS at baseline. However, symptoms improved for PASC patients over the course of a year but not for ME/CFS patients. PASC patients with significant symptom improvement no longer met ME/CFS clinical diagnostic criteria. These findings indicate that the DSQ can be used to reliably assess and monitor PASC symptoms.
Luteolin-rich fraction from Perilla frutescens seed meal inhibits spike glycoprotein S1 of SARS-CoV-2-induced NLRP3 inflammasome lung cell inflammation via regulation of JAK1/STAT3 pathway: A potential anti-inflammatory compound against inflammation-induced long-COVID
Authors: Dissook Sivamoke , Umsumarng Sonthaya , Mapoung Sariya , Semmarath Warathit , Arjsri Punnida , Srisawad Kamonwan , Dejkriengkraikul Pornngarm 
Published: January 2023

ObjectiveThe multi-systemic inflammation as a result of COVID-19 can persevere long after the initial symptoms of the illness have subsided. These effects are referred to as Long-COVID. Our research focused on the contribution of the Spike protein S1 subunit of SARS-CoV-2 (Spike S1) on the lung inflammation mediated by NLRP3 inflammasome machinery and the cytokine releases, interleukin 6 (IL-6), IL-1beta, and IL-18, in lung epithelial cells. This study has attempted to identify the naturally- occurring agents that act against inflammation-related long-COVID. The seed meal of Perilla frutescens (P. frutescens), which contains two major dietary polyphenols (rosmarinic acid and luteolin), has been reported to exhibit anti-inflammation activities. Therefore, we have established the ethyl acetate fraction of P. frutescens seed meal (PFEA) and determined its anti-inflammatory effects on Spike S1 exposure in A549 lung cells.MethodsPFEA was established using solvent-partitioned extraction. Rosmarinic acid (Ra) and luteolin (Lu) in PFEA were identified using the HPLC technique. The inhibitory effects of PFEA and its active compounds against Spike S1-induced inflammatory response in A549 cells were determined by RT-PCR and ELISA. The mechanistic study of anti-inflammatory properties of PFEA and Lu were determined using western blot technique.ResultsPFEA was found to contain Ra (388.70 ± 11.12 mg/g extract) and Lu (248.82 ± 12.34 mg/g extract) as its major polyphenols. Accordingly, A549 lung cells were pre-treated with PFEA (12.5-100 μg/mL) and its two major compounds (2.5-20 μg/mL) prior to the Spike S1 exposure at 100 ng/mL. PFEA dose-dependently exhibited anti-inflammatory properties upon Spike S1-exposed A549 cells through IL-6, IL-1β, IL-18, and NLRP3 gene suppressions, as well as IL-6, IL-1β, and IL-18 cytokine releases with statistical significance (p &lt; 0.05). Importantly, Lu possesses superior anti-inflammatory properties when compared with Ra (p &lt; 0.01). Mechanistically, PFEA and Lu effectively attenuated a Spike S1-induced inflammatory response through downregulation of the JAK1/STAT3-inflammasome-dependent inflammatory pathway as evidenced by the downregulation of NLRP3, ASC, and cleaved-caspase-1 of the NLRP3 inflammasome components and by modulating the phosphorylation of JAK1 and STAT3 proteins (p &lt; 0.05).ConclusionThe findings suggested that luteolin and PFEA can modulate the signaling cascades that regulate Spike S1-induced lung inflammation during the incidence of Long-COVID. Consequently, luteolin and P. frutescens may be introduced as potential candidates in the preventive therapeutic strategy for inflammation-related post-acute sequelae of COVID-19.
Inflammatory status in pediatric sickle cell disease: Unravelling the role of immune cell subsets
Authors: Marchesani Silvio , Bertaina Valentina , Marini Olivia , Cossutta Matilde , Di Mauro Margherita , Rotulo Gioacchino Andrea , Palma Paolo , Sabatini Letizia , Petrone Maria Isabella , Frati Giacomo , Monteleone Giulia , Palumbo Giuseppe , Ceglie Giulia 
Published: January 2023

Introduction: The mutation of the beta-globin gene that causes sickle cell disease (SCD) results in pleiotropic effects, such as hemolysis and vaso-occlusive crisis that can induce inflammatory mechanisms with deleterious consequences on the organism. Moreover, SCD patients display an increased susceptibility to infections. Few studies are currently available that evaluate a wide immunological profile in a pediatric population. This study proposes an evaluation of the immune profile in subjects with SCD in a pediatric population through a detailed analysis by flow cytometry.Methods and Materials: Peripheral blood samples from 53 pediatric patients with SCD (mean age 9.8 years, interquartile range 9 years) were obtained and then analyzed by flow cytometry, in order to evaluate changes in the immune populations compared to 40 healthy donors (mean age 7.3 years, interquartile range 9.5 years).Results: Our data showed an increase in neutrophils (with a reduction in the CD62L + subpopulation) and monocytes (with a decrease in HLA-DRlow monocytes) with normal values of lymphocytes in SCD patients. In the lymphocyte subpopulations analysis we observed lower values of CD4+ T cells (with higher number of memory and central memory T lymphocytes) with increased frequency of CD8+ T cells (with a predominant naive pattern). Moreover, we observed higher values of CD39+ Tregs and lower HLA-DR+ and CD39− T cells with an increased Th17, Th1-17 and Th2 response.Conclusion: We observed immunological alterations typical of an inflammatory status (increase in activated neutrophils and monocytes) associated with a peculiar Treg pattern (probably linked to a body attempt to minimize inflammation intrinsic to SCD). Furthermore, we highlighted a T helper pathway associated with inflammation in line with other studies. Our data showed that immunological markers may have an important role in the understanding the pathophysiology of SCD and in optimizing targeted therapeutic strategies for each patient.
Relationship between lower limb muscle activity and cortical activation among elderly people during walking: Effects of fast speed and cognitive dual task
Authors: Kim Jinuk , Lee Jungsoo , Lee Gihyoun , Chang Won Hyuk , Ko Myoung-Hwan , Yoo Woo-Kyoung , Ryu Gyu-Ha , Kim Yun-Hee 
Published: January 2023

ObjectiveGait is a complex behavior that involves not only the musculoskeletal system, but also higher-order brain functions, including cognition. This study was performed to investigate the correlation between lower limb muscle activity and cortical activation during treadmill walking in two groups of elderly people: the young-old (aged 65–74 years) and the old-old (aged 75–84 years).MethodsThirty-one young-old and 31 old-old people participated in this study. All participants were sequentially subjected to three gait conditions on a treadmill: (1) comfortable walking, (2) fast walking, and (3) cognitive dual-task walking. During treadmill walking, the activity of the lower limb muscles was measured using a surface electromyography system, and cortical activation was measured using a functional near-infrared spectroscopy system. The correlation between muscle activity and cortical activation during treadmill walking was analyzed and compared between the two groups.ResultsDuring comfortable walking, lower extremity muscle activity had a strong correlation with cortical activation, especially in the swing phase; this was significantly stronger in the young-old than the old-old. During fast walking, the correlations between lower limb muscle activity and cortical activation were stronger than those during comfortable walking in both groups. In cognitive dual-task walking, cortical activation in the frontal region and motor area was increased, although the correlation between muscle activity and cortical activation was weaker than that during comfortable walking in both groups.ConclusionThe corticomotor correlation differed significantly between the old-old and the young-old. These results suggest that gait function is compensated by regulating corticomotor correlation as well as brain activity during walking in the elderly. These results could serve as a basis for developing gait training and fall prevention programs for the elderly.
The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway
Authors: Ortiz-Leal Irene , Torres Mateo V. , Vargas-Barroso Víctor , Fidalgo Luis Eusebio , López-Beceiro Ana María , Larriva-Sahd Jorge A. , Sánchez-Quinteiro Pablo 
Published: January 2023

Introduction: The olfactory system in most mammals is divided into several subsystems based on the anatomical locations of the neuroreceptor cells involved and the receptor families that are expressed. In addition to the main olfactory system and the vomeronasal system, a range of olfactory subsystems converge onto the transition zone located between the main olfactory bulb (MOB) and the accessory olfactory bulb (AOB), which has been termed the olfactory limbus (OL). The OL contains specialized glomeruli that receive noncanonical sensory afferences and which interact with the MOB and AOB. Little is known regarding the olfactory subsystems of mammals other than laboratory rodents.Methods: We have focused on characterizing the OL in the red fox by performing general and specific histological stainings on serial sections, using both single and double immunohistochemical and lectin-histochemical labeling techniques.Results: As a result, we have been able to determine that the OL of the red fox (Vulpes vulpes) displays an uncommonly high degree of development and complexity.Discussion: This makes this species a novel mammalian model, the study of which could improve our understanding of the noncanonical pathways involved in the processing of chemosensory cues.
Rescue stenting after the failure of mechanical thrombectomy to treat acute intracranial atherosclerotic occlusion
Authors: Guo Shunyuan , Jin Tianyu , Xu Chao , Huang Wei , Shi Zongjie , Geng Yu 
Published: January 2023

BackgroundAcute ischemic stroke (AIS) with intracranial large vessel occlusion (LVO) is refractory to reperfusion because of the underlying intracranial atherosclerosis (ICAS), and this condition often requires salvage methods such as balloon angioplasty and rescue stenting (RS). In this study, we investigated the short-term outcomes of RS after failed mechanical thrombectomy (MT) for the treatment of acute intracranial atherosclerotic occlusion.MethodsWe retrospectively evaluated the clinical data of 127 patients who underwent MT for acute intracranial atherosclerotic occlusion in our hospital between August 2018 and January 2022. The degree of recanalization was evaluated immediately after the treatment by Modified Thrombolysis in Cerebral Infarction (mTICI). The modified Rankin Scale (mRS) was used 90 days after treatment to evaluate the neurological functions. In addition, the incidence of symptomatic intracranial hemorrhage (sICH) and postoperative mortality within 90 days of treatment were calculated.ResultsAmong the 127 patients, 86 patients (67.7%) had revascularization (mTICI 2b-3) immediately after MT (non-RS group), and RS was performed in 41 patients (32.3%) after MT failure (RS group). No difference in the sICH rate was observed between the two groups (17.1 vs. 16.3%, p = 0.91). There was a slightly higher mortality rate in the RS group (14.6 vs. 12.8%, p = 0.71); however, the difference was not significant. There was no difference in the proportion of patients in the RS and non-RS groups who had a 90-day mRS score of 0–2 (48.8 vs. 52.3%, p = 0.76).ConclusionsRescue stenting after MT failure might be a feasible rescue modality for treating acute intracranial atherosclerotic occlusion.
ADAMTS-13 activity in stroke of known and unknown cause: Relation to vascular risk factor burden
Authors: Grosse Gerrit M. , Leotescu Andrei , Sieweke Jan-Thorben , Schneppenheim Sonja , Budde Ulrich , Ziegler Nora L. , Biber Saskia , Gabriel Maria M. , Ernst Johanna , Schuppner Ramona , Lichtinghagen Ralf , Bavendiek Udo , Widder Julian , Weissenborn Karin 
Published: January 2023

BackgroundThe identification of the underlying mechanism in ischemic stroke has important implications for secondary prevention. A disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS-13) has antithrombotic properties and was repeatedly implicated in the pathophysiology of stroke. In this study, we, therefore, aimed to investigate whether ADAMTS-13 is associated with stroke etiology and the burden of vascular risk factors.MethodsWe determined ADAMTS-13 activity in two prospectively recruited stroke cohorts in the long-term course after the event. Cohort 1 (n = 88) consisted of patients who suffered a stroke due to embolic stroke of undetermined source (ESUS), cardioembolic stroke due to atrial fibrillation (AF), large-artery atherosclerosis, or small vessel disease. In cohort 2, patients with cryptogenic stroke and patent foramen ovale (PFO) scheduled for PFO closure (n = 38) were enrolled. As measures of vascular risk factor burden, the CHA2DS2VASC score, the Essen Stroke Risk Score (ESRS), and the Risk of Paradoxical Embolism (RoPE) score were calculated, as appropriate.ResultsADAMTS-13 activity was lower in patients with AF-related stroke compared to patients with ESUS (p = 0.0227), which was, however, due to confounding by vascular risk factors. ADAMTS-13 activity inversely correlated with the ESRS (r = −0.452, p &lt; 0.001) and CHA2DS2VASC (r = −0.375, p &lt; 0.001) in cohort 1. In accordance with these findings, we found a positive correlation between ADAMTS-13 activity and the RoPE score in cohort 2 (r = 0.413, p = 0.010).ConclusionADAMTS-13 activity is inversely correlated with the number of vascular risk factors across different stroke etiologies. Further study is warranted to establish ADAMTS-13 as a mediator of cerebrovascular risk.
Newborn screening for X-linked adrenoleukodystrophy in Italy: Diagnostic algorithm and disease monitoring
Authors: Bonaventura Eleonora , Alberti Luisella , Lucchi Simona , Cappelletti Laura , Fazzone Salvatore , Cattaneo Elisa , Bellini Matteo , Izzo Giana , Parazzini Cecilia , Bosetti Alessandra , Di Profio Elisabetta , Fiore Giulia , Ferrario Matilde , Mameli Chiara , Sangiorgio Arianna , Masnada Silvia , Zuccotti Gian Vincenzo , Veggiotti Pierangelo , Spaccini Luigina , Iascone Maria , Verduci Elvira , Cereda Cristina , Tonduti Davide ,   XALD-NBS Study Group
Published: January 2023

IntroductionX-linked adrenoleukodystrophy (X-ALD) is the most common inherited peroxisomal disorder caused by variants in the ABCD1 gene. The main phenotypes observed in men with X-ALD are primary adrenal insufficiency, adrenomyeloneuropathy, and cerebral ALD (cALD). Cerebral ALD consists of a demyelinating progressive cerebral white matter (WM) disease associated with rapid clinical decline and is fatal if left untreated. Hematopoietic stem cell transplantation is the standard treatment for cALD as it stabilizes WM degeneration when performed early in the disease. For this reason, early diagnosis is crucial, and several countries have already implemented their newborn screening programs (NBS) with the assessment of C26:0-lysophosphatidylcholine (C26:0-LPC) values as screening for X-ALD.MethodsIn June 2021, an Italian group in Lombardy launched a pilot study for the implementation of X-ALD in the Italian NBS program. A three-tiered approach was adopted, and it involved quantifying the values of C26:0-LPC and other metabolites in dried blood spots with FIA-MS/MS first, followed by the more specific ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technique and, finally, the genetic confirmation via focused NGS.DiscussionGenetically confirmed patients are set to undergo a follow-up protocol and are periodically evaluated to promptly start a specific treatment if and when the first signs of brain damage appear, as suggested by international guidelines. A specific disease monitoring protocol has been created based on literature data and personal direct experience.ConclusionThe primary aim of this study was to develop a model able to improve the early diagnosis and subsequent follow-up and timely treatment of X-ALD.EthicsThe study was approved by the local ethics committee. The research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.
Novel heterozygous mutation in alpha-2-macroglobulin (A2M) suppressing the binding of amyloid-β (Aβ)
Authors: Qiu Guozhen , Cao Liming , Chen Yong-Jun 
Published: January 2023

IntroductionMany studies have suggested that the alpha-2-macroglobulin (A2M) gene may be involved in the pathogenesis of Alzheimer's disease (AD). A2M encoded by the A2M gene can specifically bind to the β-amyloid peptide and prevent fiber formation.MethodsThe patient in this study had progressive memory loss at the age of 60 years and underwent a series of neuropsychological tests, cranial magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) biomarker analysis, and whole-exome sequencing (WES) to evaluate possible mutations. We used in silico tools and three-dimensional (3D) protein structure prediction to analyze the pathogenicity of the mutation and used a co-immunoprecipitation experiment to study the effect of mutations on amyloid-β (Aβ) binding.ResultsBased on neuropsychological tests, cranial MRI, and CSF biomarker analysis, the patient was diagnosed with AD. WES showed that there was a missense mutation in A2M (c.1229A&gt;C, p.N410T). Bioinformatics analysis showed that this mutation was pathogenic. Moreover, 3D protein structure analysis showed that the A2M Asn410 residue was an N-glycosylation site, which was necessary for A2M activation to bind to Aβ. Missense mutations led to the loss of glycosylation at this site, which suppressed the binding of Aβ. The functional experiment also confirmed the prediction: the interaction between A2M and Aβ from the patient's plasma was weakened.ConclusionsOur results demonstrate that this novel A2M p.N410T mutation may have a pathogenic role in AD, by altering the binding interactions between A2M and Aβ.
Outcomes in acute ischemic stroke patients undergoing endovascular thrombectomy: Cervical internal carotid artery pseudo-occlusion vs. true occlusion
Authors: Ni Heng , Yang Tao , Jia Zhenyu , Shi Haibin , Liu Sheng , Zhao Linbo 
Published: January 2023

Background and purposePseudo-occlusion of the cervical internal carotid artery (cICA) refers to an absence of intraluminal contrast on computed tomography angiography (CTA), while the artery is patent on digital subtraction angiography during endovascular thrombectomy. We aimed to compare the outcomes between the cICA pseudo-occlusion and true occlusion after thrombectomy.MethodsWe retrospectively analyzed patients with apparent cICA occlusion on CTA who underwent thrombectomy between January 2016 and August 2021, and divided them into the pseudo-occlusion and true occlusion groups based on angiographic exploration. Recanalization failure was defined as a modified Thrombolysis in Cerebral Infarction score of 0–2a. Poor outcome was defined as a 90-day modified Rankin Scale score of 3–6. Propensity score matching was performed to compare the outcomes. Sensitivity analysis using multivariate-adjusted regression in the original cohort was conducted to test the robustness of the findings.ResultsOf the 146 patients included, 79 patients (54.1%) had cICA pseudo-occlusion and 67 patients (45.9%) had true occlusion. Following 1:1 propensity score-matched analysis, patients with pseudo-occlusion had an increased likelihood of recanalization failure (OR, 3.18; 95% CI, 1.06–9.59; P = 0.040) and poor outcome (OR, 2.80; 95% CI, 1.07–7.30; P = 0.035) compared with patients with true occlusion. Sensitivity analysis showed that cICA pseudo-occlusion remained independently associated with recanalization failure (OR, 2.55; 95% CI, 1.07–6.09; P = 0.036) and poor outcome (OR, 2.48; 95% CI, 1.08–5.67; P = 0.032).ConclusionsPatients with cICA pseudo-occlusion on CTA treated with thrombectomy had an increased risk of reperfusion failure and poor outcome compared with true occlusion patients.