bluuebunny/crossref_metadata_2025_split huggingface dataset:
The intracavitary ECG method for tip location of ultrasound-guided centrally inserted central catheter in neonates
Authors: D’Andrea Vito , Pezza Lucilla , Prontera Giorgia , Ancora Gina , Pittiruti Mauro , Vento Giovanni , Barone Giovanni 
Published: January 2022

Background: The correct position of the tip of a central venous access device is important in all patients, and especially in neonates. The traditional method of tip location (approximated intra-procedural length estimation + post procedural chest X-ray) is currently considered inaccurate and not cost-effective by most recent guidelines, which recommend the adoption of tip location by intracavitary electrocardiography (IC-ECG) whenever possible. Methods: This study prospectively investigated the applicability, the feasibility, the accuracy, and the safety IC-ECG for tip location in neonates requiring insertion of ultrasound-guided centrally inserted central venous catheters (CICCs) with caliber 3Fr or more. All catheter tip locations were verified using simultaneously both IC-ECG and ultrasound-based tip location, using the Neo-ECHOTIP protocol. Results: A total of 105 neonates were enrolled. The applicability of IC-ECG was 100% since a P wave was evident on the surface ECG of all neonates recruited for the study. The feasibility was also 100% since an increase of the P-wave was detected in all cases. The accuracy was also 100%, since a perfect match between IC-ECG based tip location and ultrasound-based tip location was found. There were no adverse events directly or indirectly related to the IC-ECG technique; no arrhythmias occurred. Conclusions: When applied to ultrasound guided CICCs, tip location by IC-ECG is applicable and feasible in neonates, and it is safe and accurate.
Difficult removal of totally implantable venous access devices in adult patients: Incidence, risk factors, and management
Authors: Chatani Shohei , Tsukii Ryota , Nagasawa Kyohei , Hasegawa Takaaki , Murata Shinichi , Kato Mina , Yamaura Hidekazu , Onaya Hiroaki , Matsuo Keitaro , Watanabe Yoshiyuki , Inaba Yoshitaka 
Published: January 2022

Background: Totally implantable venous access devices (TIVADs) have played an important role of medical oncology practice. However, operators sometimes encounter considerable difficulty when removing TIVADs. This study aimed to investigate the incidence of difficult TIVAD removal, determine associated risk factors, and investigate interventional radiology (IR) approaches to difficult removal. Methods: A total of 514 TIVAD removal procedures performed in a single-center between January 2014 and May 2021 were retrospectively analyzed to determine incidence of difficult removal and associated risk factors. IR approaches applied in difficult removal cases were also reviewed. Results: The incidence of difficult removal was 7.4% (38/514). In univariable analysis, indwelling duration, silicone catheter, and subcutaneous leakage of fluid were identified as significant risk factors for difficult removal. Multivariable analysis showed that indwelling duration per year (odds ratio (OR), 1.46; 95% confidence interval (CI), 1.28–1.67; p < 0.01) and subcutaneous leakage of fluid (OR, 6.04; 95% CI, 2.45–14.91; p < 0.01) were significantly associated with difficult removal. In the 38 difficult removal cases, 32 TIVADs could be removed using more dissection and traction than the standard removal method. In the other 6, TIVADs were successfully removed by using several IR techniques, including insertion of a guide wire ( n = 1), dissection using an introducer sheath ( n = 2), pushing with a dilator ( n = 1), and pulling with a snare ( n = 2). Conclusion: Difficult TIVAD removal is uncommon. However, operators should expect it when removing long indwelling TIVADs and those with subcutaneous leakage. IR approaches to difficult removal are minimally invasive and can be useful.
Protective Sport Bracing for Athletes With Mid-Season Shoulder Instability
Authors: Baker Hayden P. , Krishnan Pranav , Meghani Ozair , Athiviraham Aravind , Ho Sherwin , Owens Brett D. 
Published: January 2022

Context: In-season glenohumeral instability is a common clinical dilemma faced by physicians who care for athletes. Both nonoperative and operative management of athletes with in-season glenohumeral instability have been well described. Functional bracing remains less understood as a treatment modality. This review aims to provide an update on the most recent literature regarding the use of functional bracing for shoulder instability. Evidence Acquisition: MEDLINE (PubMed and Ovid platforms), Web of Science, Embase, and Cochrane Database of Systemic Reviews were searched for articles available in English through June 1, 2021. The search terms shoulder brace, shoulder instability, athlete, in-season, glenohumeral instability, anterior shoulder instability, posterior shoulder instability, and bracing were used. Study Design: Clinical review. Level of Evidence: Level 3. Results: Research on the clinical outcomes of functional bracing remains mixed for patients with shoulder instability. Two studies have demonstrated improved return to play with functional bracing, while 1 study demonstrated no difference in return to play between braced athletes and nonbraced athletes with anterior instability. One previous study demonstrated that prophylactic use of bilateral shoulder stabilizing braces significantly decreased time lost due to injury in athletes with posterior instability. Previous biomechanical studies have demonstrated improved proprioception with brace wear as well as successful limitation of active shoulder range of motion. Conclusion: Bracing in athletes with shoulder instability remains an important nonoperative treatment modality. While clinical benefits are yet to be validated through high-quality studies, preliminary results suggest a potential benefit to recovery, with minimal downsides. Nevertheless, the use of bracing remains an individual choice but is especially recommended in settings of high-risk sports for shoulder instability, such as football.
Comparative effectiveness and safety of cocktail therapy versus combined sodium hyaluronate and chondroitin sulphate (Ialuril): Intravesical instillation treatment of interstitial cystitis/bladder pain syndrome, which one to use?
Authors: Banakhar Mai Ahmed 
Published: January 2022

Objective: To compare effectiveness and safety of intravesical therapy (sodium hyaluronate and chondroitin sulphate) Ialuril versus cocktail therapy for treatment of interstitial cystitis (IC). Materials and methods: Prospective study from March 2013 till August 2019 including all IC patients presented to our urology clinic. All IC patients underwent basic workup including urine test, urodynamic test and gynaecological/genital exam. Postoperatively, all patients received intravesical therapy. Patients were randomly allocated to either cocktail therapy (NaOH + heparin + lidocaine) or Ialuril (Sodium hyaluronate and chondroitin sulphate) therapy as intravesical seven cycles. The primary outcome was therapy effectiveness using Interstitial Cystitis Problem Index (ICPI) and Interstitial Cystitis Symptom Index (ICSI) improvement post therapy. Secondary outcome were for complications and compliance. Results: Total of 32 patients were included (6 males, 26 females) with mean age of 43 years (24–72 years), mean follow-up 36 months (15–72 months). Cocktail intravesical therapy was used in 21 patients while 11 patients received Ialuril. All patients showed improvement on their ICSI and ICPI scores post therapy from their baseline. Statistical analysis showed no significant difference between both groups regarding improvement in ICSI and ICPI index with p-value = 0.552 and p = 0.79, respectively. Infection and non-compliance is significantly high in the cocktail arm p = 0.004, p = 0.027 Conclusions: Intravesical cocktail therapy was equally effective as Ialuril in treating IC. Ialuril was preferred over cocktail therapy because of lower side effect; when considering ulcerative IC subgroup, we need large randomised controlled trials to compare therapy benefits.
Model for surface-dependent factor XII activation: the roles of factor XII heavy chain domains
Authors: Shamanaev Aleksandr , Ivanov Ivan , Sun Mao-Fu , Litvak Maxim , Srivastava Priyanka , Mohammed Bassem M. , Shaban Rabia , Maddur Ashoka , Verhamme Ingrid M. , McCarty Owen J. T. , Law Ruby H. P. , Gailani David 
Published: January 2022

Abstract
Factor XII (FXII) is the zymogen of a plasma protease (FXIIa) that contributes to bradykinin generation by converting prekallikrein to the protease plasma kallikrein (PKa). FXII conversion to FXIIa by autocatalysis or PKa-mediated cleavage is enhanced when the protein binds to negatively charged surfaces such as polymeric orthophosphate. FXII is composed of noncatalytic (heavy chain) and catalytic (light chain) regions. The heavy chain promotes FXII surface-binding and surface-dependent activation but restricts activation when FXII is not surface bound. From the N terminus, the heavy chain contains fibronectin type 2 (FN2), epidermal growth factor-1 (EGF1), fibronectin type 1 (FN1), EGF2, and kringle (KNG) domains and a proline-rich region. It shares this organization with its homolog, pro–hepatocyte growth factor activator (Pro-HGFA). To study the importance of heavy chain domains in FXII function, we prepared FXII with replacements of each domain with corresponding Pro-HGFA domains and tested them in activation and activity assays. EGF1 is required for surface-dependent FXII autoactivation and surface-dependent prekallikrein activation by FXIIa. KNG and FN2 are important for limiting FXII activation in the absence of a surface by a process that may require interactions between a lysine/arginine binding site on KNG and basic residues elsewhere on FXII. This interaction is disrupted by the lysine analog ε-aminocaproic acid. A model is proposed in which an ε-aminocaproic acid–sensitive interaction between the KNG and FN2 domains maintains FXII in a conformation that restricts activation. Upon binding to a surface through EGF1, the KNG/FN2-dependent mechanism is inactivated, exposing the FXII activation cleavage site.
Risk profiling of patients with relapsed/refractory diffuse large B-cell lymphoma by measuring circulating tumor DNA
Authors: Herrera Alex F. , Tracy Samuel , Croft Brandon , Opat Stephen , Ray Jill , Lovejoy Alex F. , Musick Lisa , Paulson Joseph N. , Sehn Laurie H. , Jiang Yanwen 
Published: January 2022

AbstractPatients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have heterogeneous outcomes; durable remissions are infrequently observed with standard approaches. Circulating tumor DNA (ctDNA) assessment is a sensitive, potentially prognostic tool in this setting. We assessed baseline ctDNA to identify patients with R/R DLBCL at high risk of relapse after receiving polatuzumab vedotin and bendamustine plus rituximab (BR) or BR alone. Patients were transplant ineligible and had received ≥1 prior line of therapy. The ctDNA assay, based on a customized panel of recurrently mutated genes in DLBCL, measured mutant molecules per mL (MMPM) at baseline and end of treatment (EOT). Endpoints included progression-free survival (PFS) and overall survival (OS) in subgroups stratified by baseline ctDNA and log-fold change in ctDNA at EOT vs baseline. In biomarker-evaluable patients (n = 33), baseline ctDNA level correlated with serum lactate dehydrogenase (LDH) concentration, number of prior therapies, stage, and International Prognostic Index (IPI). After adjusting for number of prior therapies ≥2, IPI score ≥3, and LDH above the upper limit of normal, high (greater than median) baseline ctDNA MMPM was independently prognostic for shorter PFS (adjusted hazard ratio [HR], 0.18 [95% CI, 0.05-0.65]) and OS (adjusted HR, 0.20 [95% CI, 0.06-0.68]). In 23 patients with baseline and EOT samples, a significantly greater decrease in ctDNA MMPM was observed in patients with complete response (CR) (n = 13) than those without CR (n = 10); P = .0025. Baseline ctDNA assessment may identify patients at high risk of progression and should be further evaluated as a monitoring tool in R/R DLBCL. This trial was registered at www.clinicaltrials.gov as #NCT02257567.
Improved prediction of asthma exacerbations by measuring distal airway inflammation
Authors: Paraskakis Emmanouil , Sarikloglou Evangelia , Fouzas Sotirios , Steiropoulos Paschalis , Tsalkidis Aggelos , Bush Andrew 
Published: January 2022

IntroductionPartitioning parameters measured from exhaled nitric oxide, such as the alveolar concentration of nitric oxide (CalvNO), may provide better predictors of future asthma exacerbation than exhaled nitric oxide fraction at an expiratory flow rate of 50 mL·s−1(FENO50). We aimed to determine whether any partitioned nitric oxide parameters were more closely associated thanFENO50with subsequent asthma exacerbations.Methods68 asthmatic children (mean±sdage 9.0±2.4 years) were followed prospectively (134 visits) and exacerbations were recorded. Childhood Asthma Control Test (cACT), spirometry,FENO50,CalvNO, bronchial flux of nitric oxide (JawNO), transfer factor of nitric oxide (DawNO) and airway wall concentration of nitric oxide (CawNO) were measured.ResultsNo exacerbation was recorded in 99 visits (Group 1) and an exacerbation was recorded in 35 visits (Group 2). The median (range)FENO50,JawNO,CalvNO,DawNOandCawNOof Group 1versusGroup 2: 12.7 (4–209)versus13.5 (3.8–149.9) ppb, 715 (10–12 799)versus438 (40–7457) pL·s−1, 3.4 (0.2–10.8)versus5.2 (1.7–23.6) ppb, 38.3 (0.2–113.3)versus38 (1.3–144.5) pL·s−1·ppb−1and 26.8 (4.1–2163)versus29.9 (5.5–3054) ppb, respectively. Other than forCalvNO(p<0.001), there was no difference between the two groups.CalvNO>7 ppb predicted asthma exacerbation with specificity 90.9% and positive likelihood ratio (LR) 3.1. Conversely,CalvNO<4 ppb excluded an exacerbation with sensitivity 71.4% and negative LR 0.48. An increase ofCalvNOby 0.5 ppb between visits could also predict an exacerbation with sensitivity 92%, specificity 92%, positive LR 11.8 and negative LR 0.08.ConclusionsAssessment ofCalvNOimproved prediction of subsequent exacerbation, highlighting the importance of distal inflammation in asthma outcomes in children.
Enhanced neutrophil extracellular trap formation in COVID-19 is inhibited by the protein kinase C inhibitor ruboxistaurin
Authors: Dowey Rebecca , Cole Joby , Thompson A.A. Roger , Hull Rebecca C. , Huang Chenghao , Whatmore Jacob , Iqbal Ahmed , Bradley Kirsty L. , McKenzie Joanne , Lawrie Allan , Condliffe Alison M. , Kiss-Toth Endre , Sabroe Ian , Prince Lynne R. 
Published: January 2022

BackgroundNeutrophil extracellular traps (NETs) are web-like DNA and protein lattices which are expelled by neutrophils to trap and kill pathogens, but which cause significant damage to the host tissue. NETs have emerged as critical mediators of lung damage, inflammation and thrombosis in coronavirus disease 2019 (COVID-19) and other diseases, but there are no therapeutics to prevent or reduce NETs that are available to patients.MethodsNeutrophils were isolated from healthy volunteers (n=9) and hospitalised patients with COVID-19 at the acute stage (n=39) and again at 3–4 months post-acute sampling (n=7). NETosis was measured by SYTOX green assays.ResultsHere, we show that neutrophils isolated from hospitalised patients with COVID-19 produce significantly more NETs in response to lipopolysaccharide (LPS) compared to cells from healthy control subjects. A subset of patients was captured at follow-up clinics (3–4 months post-acute sampling), and while LPS-induced NET formation is significantly lower at this time point, it remains elevated compared to healthy controls. LPS- and phorbol myristate acetate (PMA)-induced NETs were significantly inhibited by the protein kinase C (PKC) inhibitor ruboxistaurin. Ruboxistaurin-mediated inhibition of NETs in healthy neutrophils reduces NET-induced epithelial cell death.ConclusionOur findings suggest ruboxistaurin could reduce proinflammatory and tissue-damaging consequences of neutrophils during disease, and since it has completed phase III trials for other indications without safety concerns, it is a promising and novel therapeutic strategy for COVID-19.
Azithromycin for treatment of hospitalised COVID-19 patients: a randomised, multicentre, open-label clinical trial (DAWn-AZITHRO)
Authors: Gyselinck Iwein , Liesenborghs Laurens , Belmans Ann , Engelen Matthias M. , Betrains Albrecht , Van Thillo Quentin , Nguyen Pham Anh Hong , Goeminne Pieter , Soenen Ann-Catherine , De Maeyer Nikolaas , Pilette Charles , Papleux Emmanuelle , Vanderhelst Eef , Derweduwen Aurélie , Alexander Patrick , Bouckaert Bernard , Martinot Jean-Benoît , Decoster Lynn , Vandeurzen Kurt , Schildermans Rob , Verhamme Peter , Janssens Wim , Vos Robin 
Published: January 2022

Background and objectives
Azithromycin was rapidly adopted as a repurposed drug to treat coronavirus disease 2019 (COVID-19) early in the pandemic. We aimed to evaluate its efficacy in patients hospitalised for COVID-19.

Methods
In a series of randomised, open-label, phase 2 proof-of-concept, multicentre clinical trials (Direct Antivirals Working against the novel coronavirus (DAWn)), several treatments were compared with standard of care. In 15 Belgian hospitals, patients hospitalised with moderate to severe COVID-19 were allocated 2:1 to receive standard of care plus azithromycin or standard of care alone. The primary outcome was time to live discharge or sustained clinical improvement, defined as a two-point improvement on the World Health Organization (WHO) ordinal scale sustained for at least 3 days.

Results
Patients were included between April 22 and December 17, 2020. When 15-day follow-up data were available for 160 patients (56% of preset cohort), an interim analysis was performed at request of the independent Data Safety and Monitoring Board. Subsequently, DAWn-AZITHRO was stopped for futility. In total, 121 patients were allocated to the treatment arm and 64 patients to the standard-of-care arm. We found no effect of azithromycin on the primary outcome with a hazard ratio of 1.044 (95% CI 0.772–1.413; p=0.7798). None of the predefined subgroups showed significant interaction as covariates in the Fine–Gray regression analysis. No benefit of azithromycin was found on any of the short- and longer-term secondary outcomes.

Conclusion
Time to clinical improvement is not influenced by azithromycin in patients hospitalised with moderate to severe COVID-19.
Uncovering the first complete plastome genomics, comparative analyses, and phylogenetic dispositions of endemic medicinal plant Ziziphus hajarensis (Rhamnaceae)
Authors: Asaf Sajjad , Ahmad Waqar , Al-Harrasi Ahmed , Khan Abdul Latif 
Published: January 2022

Abstract
Background
Ziziphus hajarensis is an endemic plant species well-distributed in the Western Hajar mountains of Oman. Despite its potential medicinal uses, little is known regarding its genomic architecture, phylogenetic position, or evolution. Here we sequenced and analyzed the entire chloroplast (cp) genome of Z. hajarensis to understand its genetic organization, structure, and phylogenomic disposition among Rhamnaceae species.

Results
The results revealed the genome of Z. hajarensis cp comprised 162,162 bp and exhibited a typical quadripartite structure, with a large single copy (LSC) region of 895,67 bp, a small single copy (SSC) region of 19,597 bp and an inverted repeat (IR) regions of 26,499 bp. In addition, the cp genome of Z. hajarensis comprises 126 genes, including 82 protein-coding genes, eight rRNA genes, and 36 tRNA genes. Furthermore, the analysis revealed 208 microsatellites, 96.6% of which were mononucleotides. Similarly, a total of 140 repeats were identified, including 11 palindromic, 24 forward, 14 reverse, and 104 tandem repeats. The whole cp genome comparison of Z. hajarensis and nine other species from family Rhamnaceae showed an overall high degree of sequence similarity, with divergence among some intergenic spacers. Comparative phylogenetic analysis based on the complete cp genome, 66 shared genes and matK gene revealed that Z. hajarensis shares a clade with Z. jujuba and that the family Rhamnaceae is the closest family to Barbeyaceae and Elaeagnaceae.

Conclusion
All the genome features such as genome size, GC content, genome organization and gene order were highly conserved compared to the other related genomes. The whole cp genome of Z. hajarensis gives fascinating insights and valuable data that may be used to identify related species and reconstruct the phylogeny of the species.
Population structure analysis to explore genetic diversity and geographical distribution characteristics of cultivated-type tea plant in Guizhou Plateau
Authors: Zhao Zhifei , Song Qinfei , Bai Dingchen , Niu Suzhen , He Yingqin , Qiao Dahe , Chen Zhengwu , Li Caiyun , Luo Jing , Li Fang 
Published: January 2022

AbstractBackgroundTea plants originated in southwestern China. Guizhou Plateau is an original center of tea plants, and is rich in germplasm resources. However, the genetic diversity, population structure and distribution characteristics of cultivated-type tea plants in the region are unknown. In this study, we explored the genetic diversity and geographical distribution of cultivated-type tea accessions in Guizhou Plateau.ResultsWe used 112,072 high-quality genotyping-by-sequencing to analyze the genetic diversity, principal components, phylogeny, population structure, and linkage disequilibrium, and develop a core collection of 253 cultivated-type tea plant accessions from Guizhou Plateau. The results showed Genetic diversity of the cultivated-type tea accessions of the Pearl River Basin was significantly higher than that of the cultivated-type tea accessions of the Yangtze River Basin. Three inferred pure groups (CG-1, CG-2 and CG-3) and one inferred admixture group (CG-4), were identified by a population structure analysis, and verified by principal component and phylogenetic analyses. The highest genetic distance and differentiation coefficients were determined for CG-2 vs CG-3. The lower genetic distance and differentiation coefficients were determined for CG-4 vs CG-2 and CG-4 vs CG-3, respectively. We developed a core set and a primary set. The primary and core sets contained 77.0 and 33.6% of all individuals in the initial set, respectively. The primary set may serve as the primary population in genome-wide association studies, while the core collection may serve as the core population in multiple treatment setting studies.ConclusionsThe present study demonstrated the genetic diversity and geographical distribution characteristics of cultivated-type tea plants in Guizhou Plateau. Significant differences in genetic diversity and evolutionary direction were detected between the ancient landraces of the Pearl River Basin and the those of the Yangtze River Basin. Major rivers and ancient hubs were largely responsible for the genetic exchange between the Pearl River Basin and the Yangtze River Basin ancient landraces as well as the formation of the ancient hubs evolutionary group. Genetic diversity, population structure and core collection elucidated by this study will facilitate further genetic studies, germplasm protection, and breeding of tea plants.