bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tartrate resistant acid phosphatase 5 (TRAP5) mediates immune cell recruitment in a murine model of pulmonary bacterial infection
Authors: Tanner Lloyd , Bergwik Jesper , Bhongir Ravi K. V. , Puthia Manoj , Lång Pernilla , Ali Mohamad N. , Welinder Charlotte , Önnerfjord Patrik , Erjefält Jonas S. , Palmberg Lena , Andersson Göran , Egesten Arne 
Published: December 2022

IntroductionDuring airway infection, upregulation of proinflammatory cytokines and subsequent immune cell recruitment is essential to mitigate bacterial infection. Conversely, during prolonged and non-resolving airway inflammation, neutrophils contribute to tissue damage and remodeling. This occurs during diseases including cystic fibrosis (CF) and COPD where bacterial pathogens, not least Pseudomonas aeruginosa, contribute to disease progression through long-lasting infections. Tartrate-resistant acid phosphatase (TRAP) 5 is a metalloenzyme expressed by alveolar macrophages and one of its target substrates is the phosphoglycoprotein osteopontin (OPN).MethodsWe used a knockout mouse strain (Trap5-/-) and BALB/c-Tg (Rela-luc)31Xen mice paired with siRNA administration or functional protein add-back to elucidate the role of Trap5 during bacterial infection. In a series of experiments, Trap5-/- and wild-type control mice received intratracheal administration of P.aerugniosa (Xen41) or LPS, with mice monitored using intravital imaging (IVIS). In addition, multiplex cytokine immunoassays, flow cytometry, multispectral analyses, histological staining were performed.ResultsIn this study, we found that Trap5-/- mice had impaired clearance of P. aeruginosa airway infection and reduced recruitment of immune cells (i.e. neutrophils and inflammatory macrophages). Trap5 knockdown using siRNA resulted in a decreased activation of the proinflammatory transcription factor NF-κB in reporter mice and a subsequent decrease of proinflammatory gene expression. Add-back experiments of enzymatically active TRAP5 to Trap5-/- mice restored immune cell recruitment and bacterial killing. In human CF lung tissue, TRAP5 of alveolar macrophages was detected in proximity to OPN to a higher degree than in normal lung tissue, indicating possible interactions.DiscussionTaken together, the findings of this study suggest a key role for TRAP5 in modulating airway inflammation. This could have bearing in diseases such as CF and COPD where excessive neutrophilic inflammation could be targeted by pharmacological inhibitors of TRAP5.
Real-world use of ustekinumab therapeutic drug monitoring in moderate to severe psoriasis
Authors: Elberdín Laida , Fernández-Torres Rosa M. , Mateos María , Outeda María , Blanco Eva , Gómez-Besteiro María I. , Martín-Herranz Isabel , Fonseca Eduardo 
Published: December 2022

IntroductionThere is growing evidence that therapeutic drug monitoring of biologic therapy is beneficial in psoriatic patients. With respect to ustekinumab, the available evidence has not shown any relationship yet. The objective of this study is to identify correlations among ustekinumab trough concentrations, anti-ustekinumab antibodies and clinical response in moderate-to-severe plaque psoriasis patients, in a real-world setting.MethodsObservational prospective follow-up study in psoriatic patients treated with ustekinumab. Patients were classified in optimal (PASI ≤ 3) and suboptimal responders (PASI &gt; 3). Mann–Whitney U test and Spearman’s rank correlation coefficient were used. Receiver-operator characteristic curve analysis was performed to identify ustekinumab concentration cut-off to achieve optimal response. A p-value &lt; 0.05 was considered statistically significant.ResultsA total of 59 patients were included. Forty-eight patients (81.4%) corresponded to optimal responders and 11 (18.6%) to suboptimal responders. There was significant difference to ustekinumab concentrations: 0.7 μg/mL (range &lt;0.1–1.8) vs. 0.4 μg/mL (range &lt;0.1–0.8) respectively (p = 0.007). Positive correlation between ustekinumab concentration and psoriasis area and severity index (PASI) value was detected (p = 0.009). A cut-off value of 0.6 μg/mL ustekinumab concentration was found to achieve clinical response. Anti-ustekinumab antibodies were detected in 2 (3.4%) samples, both suboptimal responders.ConclusionA positive correlation exits between ustekinumab concentration and clinical response (optimal response PASI values ≤ 3) in blood draws performed before drug administration. The measurement of anti-ustekinumab antibodies could be considered in treatment failure.
Acupuncture for premature ventricular complexes without ischemic or structural heart diseases: A systematic review and meta-analysis of clinical and pre-clinical evidence
Authors: Cai Yiyi , Zhang Claire Shuiqing , Liu Shaonan , Zhou Li , Tang Boyan , Chen Wensheng 
Published: December 2022

BackgroundWith increasing evidence suggesting potential benefits, acupuncture is often applied to the treatment of premature ventricular complexes (PVCs), particularly in symptomatic patients who fail or are unsuitable for medications or refuse catheter ablation. However, the existing clinical evidence is inconsistent.ObjectivesThis review aims to systematically evaluate the effectiveness and safety of acupuncture therapies for PVCs without ischemic or structural heart diseases, when it is compared with sham/placebo acupuncture or usual care, or used as an add-on therapy to routine care; and to summarize existing pre-clinical research evidence supporting the effects of acupuncture therapies for this clinical condition.MethodsFour English-language databases, four Chinese-language databases and seven clinical registries were searched from their inceptions to May 21, 2021 and updated to November 01, 2022. Trials comparing acupuncture with sham acupuncture or evaluating the add-on effects of acupuncture were included. Primary outcomes are the number of premature ventricular beats (PVBs) and effective rate defined as “the proportion of participants with over 50% decrease in the number of PVBs from baseline to the end of treatment measured by 24-h Holter”.ResultsA total of 479 records were identified with nine trials involving 847 participants included in this review. Meta-analysis on two sham-control trials with low risk of bias for all domains suggested that acupuncture could significantly reduce the number of PVBs (RR 3.83, 95% CI [2.19, 6.7], I2 = 0%). Moreover, the combination of acupuncture and standard treatment was superior to standard treatment alone in reducing the burden of PVBs (RR 1.21, 95% CI [1.08, 1.36], I2 = 0%). Though no treatment protocol consensus was announced, body acupuncture on point PC6, HT7, DU10, DU11, and ST36 with duration of needle retention ranging from 15 to 30 min for a 4-week treatment period is broadly used by the included trials. For experimental evidence, five studies explored the mechanisms of acupuncture for PVCs were eventually included into analysis and PC6 was the most frequently studied acupuncture point. Moreover, a reduction of electrical activity of sympathetic nerves in experimental animals undergoing electro-acupuncture was observed by four of these studies.ConclusionSham-controlled RCT evidence with moderate-level certainty suggested that acupuncture could be a therapeutic option to reduce the burden of PVBs in patients without ischemic or structural heart diseases. Further clinical studies using validated and reliable outcome measurement instruments and bench research to unveil the mechanisms of acupuncture stimulation and point-specific effects for PVCs are needed.Systematic review registration[https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=262132], identifier [CRD42021262132].
Pseudomonas aeruginosa prosthetic joint-infection outcomes: Prospective, observational study on 43 patients
Authors: Prié Héloïse , Meyssonnier Vanina , Kerroumi Younes , Heym Beate , Lidove Olivier , Marmor Simon , Zeller Valérie 
Published: December 2022

ObjectivesAnalysis the outcomes of Pseudomonas aeruginosa prosthetic joint infection (PJI), and of their clinical and microbiological characteristics, surgical strategies and antibiotic treatments.MethodsMonocenter cohort study in a Bone-and-Joint-Infection Referral Center (08/2004 to 10/2018) including all consecutive P. aeruginosa PJIs. Data were extracted from the prospective database, including the following events: relapses, new PJIs, related deaths.ResultsMedian [IQR]: among the 43 patients included (28 females; 72 [63–80] years old; 27 hip, 15 knee, and 1 shoulder PJIs), 29 (67%) had underlying comorbidities, 12 (28%) had previously been treated for another PJI and 9 (21%) had undergone previous surgeries for their P. aeruginosa PJI. Eleven (26%) PJIs were polymicrobial, 16 (37%) strains were wild type, 8 (19%) ciprofloxacin-resistant. PJIs were classified as late chronic (n = 33), early postoperative (n = 9) or acute hematogenous infection (n = 1). Forty patients underwent surgery: 27 one-stage and 5 two-stage exchanges, 3 debridement and implant retention, and 5 other surgical strategies. Antibiotic treatments were: 29 received 41 [37–43] days of combination therapy (IV anti-pseudomonal β-lactam and 3–5 days of amikacin, then β-lactam and oral ciprofloxacin), followed by oral ciprofloxacin for a total of 12 weeks; 10 received only IV antibiotics for 83 [77–86] days, including 37 [32–46] days of combination therapy; 49 days of ceftazidime alone for 1. During follow-up lasting 33 [24–64.5] months, 2 relapses, 3 new PJIs, and 2 related deaths occurred. Thirty-three (82%) patients and 93% of those managed with one-stage exchange experienced no event.ConclusionOutcomes of our cohort’s P. aeruginosa PJIs—predominantly monomicrobial, chronic, ciprofloxacin-susceptible, treated with one-stage exchange and prolonged IV antibiotics—were 82% favorable.
Case report: Bullous pemphigoid arising in a patient with scleroderma and multiple sclerosis
Authors: Moro Francesco , Mariotti Feliciana , Pira Anna , De Luca Naomi , Didona Biagio , Pagnanelli Gianluca , Di Zenzo Giovanni 
Published: December 2022

BackgroundBullous pemphigoid (BP) is the most common autoimmune-blistering disease, clinically characterized by erythematous urticarial plaques, blisters, and intense pruritus, induced by autoantibodies against two proteins of the dermo-epidermal junction, BP180 and BP230. A large number of autoimmune diseases are reported in the literature as BP comorbidities, such as multiple sclerosis, but only a few cases are in association with scleroderma and none in association with both.Case presentationWe present the case of a 68-year-old woman affected by multiple sclerosis and scleroderma who developed severe bullous pemphigoid with a bullous pemphigoid disease area index of 60 and high titers of anti-BP180 and anti-BP230 autoantibodies by enzyme-linked immunosorbent assays. After 2 months of therapy with both intravenous and oral corticosteroids, the active lesions of bullous pemphigoid were remitted with no relapse.ConclusionAutoimmune diseases affecting the skin or organs where BP180 and BP230 are present could trigger an immune response to these antigens through an epitope-spreading phenomenon and, over the years, induce bullous pemphigoid onset.
Sex difference in circulating soluble form of ACE2 protein in moderate and severe COVID-19 and healthy controls
Authors: Robertson Josefina , Nellgård Bengt , Hultén Lillemor Mattsson , Nilsson Staffan , Dalla Keti , Börjesson Mats , Zetterberg Henrik , Svanvik Joar , Gisslén Magnus 
Published: December 2022

IntroductionMembrane-bound angiotensin-converting enzyme-2 (ACE2) in epithelial cells is the main receptor for SARS-CoV-2. The extracellular portion of ACE2 may be shedded to plasma in which process ADAM17 (a disintegrin and metalloproteinase 17) is important. Results on the relationship between circulating levels of the soluble form of ACE2 (sACE2) and disease severity are inconclusive. This study investigates if sACE2 concentration correlates with COVID-19 severity, and whether this is affected by sex.Materials and methodsSoluble form of ACE2 was analyzed in three groups: 104 patients (23 women and 81 men) with severe COVID-19 admitted to an intensive care unit (ICU), patients with moderate COVID-19 who required hospital care (n = 19, 4 women and 15 men), and age and sex matched healthy controls (n = 20, 4 women and 16 men). Blood samples were collected at hospital admission between 18 March 2020, and 3 May 2021, and at follow-up between 27 October 2020, and 19 October 2021. Circulating sACE2 (μg/L) was measured in EDTA plasma with a sensitive enzyme-linked immunosorbent assay. Additionally, CRP, ferritin, and lymphocyte count were analyzed during hospital stay.ResultsIn total, 23 patients (22%) died in the ICU. When comparing healthy controls [mean age 58.1 (SD 11.4) years] and patients with moderate COVID-19 [mean age 61.0 (SD 13.2) years] with patients in the ICU [mean age 63.6 (SD 11.6) years], we found that sACE2 concentration decreased (70% reduction) with disease severity in men (p = 0.002) but increased 3.7-fold with severity in women (p = 0.043), suggesting a sex-related difference in how COVID-19 severity is related to sACE2 concentration. Moreover, we identified a relationship between inflammatory biomarkers and sACE2 concentration during the intensive care treatment, such that higher CRP and higher ferritin concentration correlated with lower sACE2 concentration in men.ConclusionThe decrease in sACE2 concentration, selectively in men, in severe COVID-19 is of pathophysiological interest since men are affected more severely by the disease compared to women. Additionally, the inflammatory biomarkers, CRP and ferritin, correlated inversely with sACE2 concentration, suggesting a role in severe disease. Our findings imply that sACE2 is a possible biomarker of disease severity in a sex-specific manner.
Sugammadex versus neostigmine for neuromuscular blockade reversal in outpatient surgeries: A randomized controlled trial to evaluate efficacy and associated healthcare cost in an academic center
Authors: Fiorda Diaz Juan , Echeverria-Villalobos Marco , Esparza Gutierrez Alan , Dada Olufunke , Stoicea Nicoleta , Ackermann Wiebke , Abdel-Rasoul Mahmoud , Heard Jarrett , Uribe Alberto , Bergese Sergio D. 
Published: December 2022

IntroductionNeuromuscular blockade is an essential component of the general anesthesia as it allows for a better airway management and optimal surgical conditions. Despite significant reductions in extubation and OR readiness-for-discharge times have been associated with the use of sugammadex, the cost-effectiveness of this drug remains controversial. We aimed to compare the time to reach a train-of-four (TOF) response of ≥0.9 and operating room readiness for discharge in patients who received sugammadex for moderate neuromuscular blockade reversal when compared to neostigmine during outpatient surgeries under general anesthesia. Potential reduction in time for OR discharge readiness as a result of sugammadex use may compensate for the existing cost-gap between sugammadex and neostigmine.MethodsWe conducted a single-center, randomized, double arm, open-label, prospective clinical trial involving adult patients undergoing outpatient surgeries under general anesthesia. Eligible subjects were randomized (1:1 ratio) into two groups to receive either sugammadex (Groups S), or neostigmine/glycopyrrolate (Group N) at the time of neuromuscular blockade reversal. The primary outcome was the time to reverse moderate rocuronium-induced neuromuscular blockade (TOF ratio ≥0.9) in both groups. In addition, post-anesthesia care unit (PACU)/hospital length of stay (LOS) and perioperative costs were compared among groups as secondary outcomes.ResultsThirty-seven subjects were included in our statistical analysis (Group S= 18 subjects and Group N= 19 subjects). The median time to reach a TOF ratio ≥0.9 was significantly reduced in Group S when compared to Group N (180 versus 540 seconds; p = 0.0052). PACU and hospital LOS were comparable among groups. Postoperative nausea and vomiting was the main adverse effect reported in Group S (22.2% versus 5.3% in Group N; p = 0.18), while urinary retention (10.5%) and shortness of breath (5.3%) were only experienced by some patients in Group N. Moreover, no statistical differences were found between groups regarding OR/anesthesia, PACU, and total admission costs.DiscussionSugammadex use was associated with a significantly faster moderate neuromuscular blockade reversal. We found no evidence of increased perioperative costs associated with the use of sugammadex in patients undergoing outpatient surgeries in our academic institution.Clinical trial registration[https://clinicaltrials.gov/] identifier number [NCT03579589].
Case series of progressive familial intrahepatic cholestasis type 3: Characterization of variants in ABCB4 in China
Authors: Cheng Jinlin , Gong Ling , Mi Xiaoxiao , Wu Xiangyan , Zheng Jun , Yang Wenjun 
Published: December 2022

ObjectiveTo improve the accuracy of the diagnosis of familial progressive intrahepatic cholestasis type 3 (PFIC3, https://www.omim.org/entry/602347).Materials and methodsBetween September 2019 and March 2021, we recruited four patients with PFIC3 from two liver centers in East China. Molecular genetic findings of ATP-binding cassette subfamily B member 4 [ATP binding cassette transporter A4 (ABCB4), https://www.omim.org/entry/171060] were prospectively examined, and clinical records, laboratory readouts, and macroscopic and microscopic appearances of the liver were analyzed.ResultsFour patients experienced cholestasis, mild jaundice, and elevated levels of serum direct bilirubin, γ-glutamyltransferase, or total bile acids. All patients had moderate-to-severe liver fibrosis or biliary cirrhosis, and their liver biopsy specimens stained positive with rhodamine. Molecular immunohistochemistry revealed reduced or absent MDR3 expression in all liver specimens. A novel mutation of ABCB4 (c.1560 + 2T &gt; A) was identified in patients with PFIC3, which is of high clinical significance and may help understand mutant ABCB4 pathogenesis.ConclusionMDR3 immunohistochemistry and molecular genetic analyses of ABCB4 are essential for the accurate diagnosis of PFIC3.
The effects of microbiota abundance on symptom severity in Parkinson’s disease: A systematic review
Authors: Papić Eliša , Rački Valentino , Hero Mario , Tomić Zoran , Starčević-Čižmarević Nada , Kovanda Anja , Kapović Miljenko , Hauser Goran , Peterlin Borut , Vuletić Vladimira 
Published: December 2022

IntroductionParkinson’s disease (PD) is neurodegenerative disease with a multifactorial etiopathogenesis with accumulating evidence identifying microbiota as a potential factor in the earliest, prodromal phases of the disease. Previous research has already shown a significant difference between gut microbiota composition in PD patients as opposed to healthy controls, with a growing number of studies correlating gut microbiota changes with the clinical presentation of the disease in later stages, through various motor and non-motor symptoms. Our aim in this systematic review is to compose and assess current knowledge in the field and determine if the findings could influence future clinical practice as well as therapy in PD.MethodsWe have conducted a systematic review according to PRISMA guidelines through MEDLINE and Embase databases, with studies being selected for inclusion via a set inclusion and exclusion criteria.Results20 studies were included in this systematic review according to the selected inclusion and exclusion criteria. The search yielded 18 case control studies, 1 case study, and 1 prospective case study with no controls. The total number of PD patients encompassed in the studies cited in this review is 1,511.ConclusionThe link between gut microbiota and neurodegeneration is a complex one and it depends on various factors. The relative abundance of various microbiota taxa in the gut has been consistently shown to have a correlation with motor and non-motor symptom severity. The answer could lie in the products of gut microbiota metabolism which have also been linked to PD. Further research is thus warranted in the field, with a focus on the metabolic function of gut microbiota in relation to motor and non-motor symptoms.
Pre-attentive fundamental frequency processing in Mandarin-speaking children with cochlear implants as revealed by the peak latency of positive mismatch response
Authors: Huang Wanting , Wong Lena L. N. , Chen Fei 
Published: December 2022

IntroductionFundamental frequency (F0) serves as the primary acoustic cue for Mandarin tone perception. Recent behavioral studies suggest that F0 information may be differently processed between Mandarin-speaking normal-hearing (NH) children and children with cochlear implants (CIs), which may partially explain the unsatisfactory outcome of lexical tone recognition using CIs with tonal language-oriented speech processing strategies. The aim of the current study was to provide neural evidence of F0 processing in Mandarin-speaking kindergarten-aged children with CIs compared with NH children.MethodsPositive mismatch responses (p-MMRs) to the change of the two acoustic dimensions of F0 (F0 contour and F0 level) in Mandarin-speaking kindergarten-aged children with CIs (n = 19) and their age-matched NH peers (n = 21).ResultsThe two groups of children did not show any significant difference on the mean amplitude of p-MMR to either F0 contour or F0 level change. While the CI group exhibited a significantly shorter peak latency of p-MMR to F0 contour change than to F0 level change, an opposite pattern was observed in the NH group.DiscussionThis study revealed a higher sensitivity to F0 contour change than to F0 level change in children with CIs, which was different from that in NH children. The neural evidence of discrepant F0 processing between children with CIs and NH children in this study was consistent with the previously reported behavioral findings and may serve as a reference for the development and improvement of tonal language-oriented speech processing strategies.