bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatitis B virus prevalence in first‐time blood donors in Flanders, Belgium: Impact of universal vaccination and migration
Authors: De Brier Niels , Koc Özgür M. , De Buck Emmy , Muylaert An , Nevens Frederik , Vanbrabant Miek , Vandeloo Judith , Van Remoortel Hans , Robaeys Geert , Compernolle Veerle 
Published: May 2021

AbstractBackgroundTransfusion‐transmissible infections such as hepatitis B virus (HBV) remain a major concern for the safety of blood transfusion. This cross‐sectional study aimed to assess the trend of HBV prevalence and associated risk factors among a first‐time donor population in a low endemic country.Study Design and MethodsBetween 2010 and 2018, blood samples were collected from first‐time donors presented at donor collection sites of Belgian Red Cross‐Flanders. They were tested for hepatitis B surface antigen (HBsAg), hepatitis B core antibodies (anti‐HBc), and HBV DNA, HIV and hepatitis virus C (HCV) antibodies and RNA, and syphilis antibodies.ResultsA total of 211,331 first‐time blood donors (43.7% males, median age 25 years) were analyzed. HBsAg prevalence decreased from 0.06% in 2010 to 0.05% in 2018 (p = .004) and this declining trend was accompanied by an increased number of donors in the HBV vaccinated birth cohort (p < .001). HBsAg prevalence was 0.33% in foreign‐born donors and 0.02% in Belgian natives (p < .001). Multivariate risk profiling showed that anti‐HBc positivity was significantly associated with mainly foreign‐born donors (odds ratio [OR] = 9.24) but also with older age (OR = 1.06), male gender (OR = 1.32), year of blood donation (OR = 0.94), and co‐infections with HCV (OR = 4.31) or syphilis (OR = 4.91).DiscussionThe decreasing trend in HBV prevalence could mainly be explained by the introduction of the universal HBV vaccination. Being born in endemic areas was the most important predictor for HBV infection while the co‐infections with syphilis suggest unreported sexual risk contacts.
Therapeutic plasma exchange to mitigate flunixin meglumine overdose in a cria
Authors: Dixon Claire E. , Kelley Denise , Froehlich Jacob Michael , Gruntman Alisha , Oura Trisha , Mazan Melissa R. , Labato Mary Anna 
Published: May 2021

AbstractObjectiveTo describe the use of therapeutic plasma exchange (TPE) in the treatment of flunixin meglumine overdose in a cria.Case SummaryA 3‐day‐old alpaca cria was diagnosed with ureteral obstruction and agenesis resulting in severe bilateral hydronephrosis. During hospitalization, the cria inadvertently received a flunixin meglumine overdose of >65 mg/kg. Here, we report the use of lipid emulsion and TPE to mitigate flunixin meglumine toxicosis. TPE appeared to prevent any flunixin‐induced kidney or gastrointestinal injury, even in a patient with congenital defects of the urinary tract.New Information ProvidedThis is the first report of the use of TPE in a cria.
Novel antimicrobial ointment for infected wound healing in an in vitro and in vivo porcine model
Authors: Hachem Ray , Parikh Umang M. , Reitzel Ruth , Rosenblatt Joel , Kaul Aditya , Vargas‐Cruz Nylev , Hill Lori , Moore Lisa , Meyer Jennifer , Chaftari Anne‐Marie , Gagea Mihai , Balaji Swathi , Raad Issam I. 
Published: May 2021

AbstractMicrobial contamination of wounds is a significant problem that delays healing, particularly when bacterial biofilms are present. A novel combination of pectinic acid (PG) + caprylic acid (CAP) was previously found in vitro to be highly effective in eradicating various pathogens in biofilms with minimal cytotoxicity. In this study, a novel wound ointment was formulated with PG + CAP and first assessed in vitro using a well‐established biofilm eradication model. In vitro, the PG + CAP ointment was shown to be efficacious in reducing the microbial biofilms. This ointment was then tested in vivo in two pilot porcine wound healing models, with and without Staphylococcus aureus microbial challenge. Ointments were applied to each wound daily, and healing by wound closure area measurement was assessed weekly over 4 weeks. After 4 weeks, pigs were sacrificed and wounds were scored for reepithelialization, inflammation, granulation tissue, and collagen deposition. We compared PG + CAP to hydroxyethylcellulose + glycerol ointment base (control) and MediHoney (comparator). In the porcine microbial challenge model, the novel antimicrobial PG + CAP wound ointment rapidly eradicated bacterial organisms embedded in wounds, was safe and well‐tolerated, and was associated with enhanced healing compared to ointment base and MediHoney. Specifically, the cumulative histopathology, reepithelialization of epidermis, and mature granulation tissue in the wound bed was significantly better with PG + CAP than with control and MediHoney treatments. This ointment warrants further study as a non‐antibiotic ointment for use in treating a wide array of infected wounds.
Automated control of oxygen titration in preterm infants on non-invasive respiratory support
Authors: Dargaville Peter A , Marshall Andrew P , Ladlow Oliver J , Bannink Charlotte , Jayakar Rohan , Eastwood-Sutherland Caillin , Lim Kathleen , Ali Sanoj K M , Gale Timothy J 
Published: May 2021

ObjectiveTo evaluate the performance of a rapidly responsive adaptive algorithm (VDL1.1) for automated oxygen control in preterm infants with respiratory insufficiency.DesignInterventional cross-over study of a 24-hour period of automated oxygen control compared with aggregated data from two flanking periods of manual control (12 hours each).SettingNeonatal intensive care unit.ParticipantsPreterm infants receiving non-invasive respiratory support and supplemental oxygen; median birth gestation 27 weeks (IQR 26–28) and postnatal age 17 (12–23) days.InterventionAutomated oxygen titration with the VDL1.1 algorithm, with the incoming SpO2 signal derived from a standard oximetry probe, and the computed inspired oxygen concentration (FiO2) adjustments actuated by a motorised blender. The desired SpO2 range was 90%–94%, with bedside clinicians able to make corrective manual FiO2 adjustments at all times.Main outcome measuresTarget range (TR) time (SpO2 90%–94% or 90%–100% if in air), periods of SpO2 deviation, number of manual FiO2 adjustments and oxygen requirement were compared between automated and manual control periods.ResultsIn 60 cross-over studies in 35 infants, automated oxygen titration resulted in greater TR time (manual 58 (51–64)% vs automated 81 (72–85)%, p<0.001), less time at both extremes of oxygenation and considerably fewer prolonged hypoxaemic and hyperoxaemic episodes. The algorithm functioned effectively in every infant. Manual FiO2 adjustments were infrequent during automated control (0.11 adjustments/hour), and oxygen requirements were similar (manual 28 (25–32)% and automated 26 (24–32)%, p=0.13).ConclusionThe VDL1.1 algorithm was safe and effective in SpO2 targeting in preterm infants on non-invasive respiratory support.Trial registration numberACTRN12616000300471.
Effects of beta-blockers on archery performance, body sway and aiming behaviour
Authors: Ergen Emin , Hazir Tahir , Celebi Mesut , Kin-Isler Ayşe , Aritan Serdar , Yaylıoglu Volkan Daghan , Guner Rustu , Acikada Caner , Cinemre Alpan 
Published: May 2021

ObjectivesThis study aimed to determine the effect of selective (bisoprolol-5 mg) and non-selective (propranolol-40 mg) beta-blockers on archery performance, body sway and aiming behaviour.MethodsFifteen male archers participated in a randomised, double-blind, placebo-controlled, cross-over study and competed four times (control, placebo, selective (bisoprolol) and non-selective (propranolol) beta-blocker trials). Mechanical data related to the changes in the centre of pressure during body sway and aim point fluctuation and when shooting was collected. During the shots, heart rate was recorded continuously.ResultsResults indicated that, in beta-blocker trials, although shooting heart rates were lowered by 12.8% and 8.6%, respectively, for bisoprolol and propranolol, no positive effect of beta-blockers was observed on shooting scores. Also, the use of beta-blockers did not affect shooting behaviour and body sway.ConclusionThe use of either selective or non-selective single dose beta-blockers had no positive effect on shooting performance in archery during simulated match conditions.
Prognostic value of lower bone mineral density in predicting adverse cardiovascular disease in Asian women
Authors: Park Jiesuck , Yoon Yeonyee Elizabeth , Kim Kyoung Min , Hwang In-Chang , Lee Wonjae , Cho Goo-Yeong 
Published: May 2021

ObjectiveWe investigated whether the evaluation of bone mineral density (BMD) provides independent and incremental prognostic value for predicting atherosclerotic cardiovascular disease (ASCVD) in women.MethodsA total of 12 681 women aged 50–80 years (mean, 63.0±7.8 years) who underwent dual-energy X-ray absorptiometry were retrospectively analysed. We assessed the hazard ratio (HR) for ASCVD events (ASCVD death, non-fatal myocardial infarction and ischaemic stroke) according to the BMD or a clinical diagnosis of osteopenia or osteoporosis, with adjustment for clinical risk factors, including age, body mass index, hypertension, type 2 diabetes, hyperlipidaemia, current smoking and previous fracture. We also evaluated whether the addition of BMD or a clinical diagnosis of osteopenia or osteoporosis to clinical risk factors improved the prediction for ASCVD events.ResultsIn total, 468 women (3.7%) experienced ASCVD events during follow-up (median, 9.2 years). Lower BMD at the lumbar spine, femur neck and total hip was independently associated with higher risk for ASCVD events (adjusted HR per 1-standard deviation decrease in BMD: 1.16, p<0.001; 1.29, p<0.001; 1.38, p<0.001; respectively). A clinical diagnosis of osteoporosis was also independently associated with higher risk for ASCVD events (adjusted HR: 1.79, p<0.001). The addition of BMD or a clinical diagnosis of osteopenia or osteoporosis to clinical risk factors demonstrated significant incremental value in discriminating ASCVD events (addition of total hip BMD, p for difference <0.001).ConclusionThe evaluation of BMD provides independent and incremental prognostic value for ASCVD in women and thus may improve risk stratification in women.
Predicting anti-PD-1 responders in malignant melanoma from the frequency of S100A9+ monocytes in the blood
Authors: Rad Pour Soudabeh , Pico de Coaña Yago , Demorentin Xavier Martinez , Melief Jeroen , Thimma Manjula , Wolodarski Maria , Gomez-Cabrero David , Hansson Johan , Kiessling Rolf , Tegner Jesper 
Published: May 2021

BackgroundWhile programmed cell death receptor 1 (PD-1) blockade treatment has revolutionized treatment of patients with melanoma, clinical outcomes are highly variable, and only a fraction of patients show durable responses. Therefore, there is a clear need for predictive biomarkers to select patients who will benefit from the treatment.MethodTo identify potential predictive markers for response to PD-1 checkpoint blockade immunotherapy, we conducted single-cell RNA sequencing analyses of peripheral blood mononuclear cells (PBMC) (n=8), as well as an in-depth immune monitoring study (n=20) by flow cytometry in patients with advanced melanoma undergoing treatment with nivolumab at Karolinska University Hospital. Blood samples were collected before the start of treatment and at the time of the second dose.ResultsUnbiased single-cell RNA sequencing of PBMC in patients with melanoma uncovered that a higher frequency of monocytes and a lower ratio of CD4+ T cells to monocyte were inversely associated with overall survival. Similarly, S100A9 expression in the monocytic subset was correlated inversely with overall survival. These results were confirmed by a flow cytometry-based analysis in an independent patient cohort.ConclusionOur results suggest that monocytic cell populations can critically determine the outcome of PD-1 blockade, particularly the subset expressing S100A9, which should be further explored as a possible predictive biomarker. Detailed knowledge of the biological role of S100A9+ monocytes is of high translational relevance.
Immune cell composition and functional marker dynamics from multiplexed immunohistochemistry to predict response to neoadjuvant chemotherapy in the WSG-ADAPT-TN trial
Authors: Graeser Monika , Feuerhake Friedrich , Gluz Oleg , Volk Valery , Hauptmann Michael , Jozwiak Katarzyna , Christgen Matthias , Kuemmel Sherko , Grischke Eva-Maria , Forstbauer Helmut , Braun Michael , Warm Mathias , Hackmann John , Uleer Christoph , Aktas Bahriye , Schumacher Claudia , Kolberg-Liedtke Cornelia , Kates Ronald , Wuerstlein Rachel , Nitz Ulrike , Kreipe Hans Heinrich , Harbeck Nadia 
Published: May 2021

BackgroundThe association of early changes in the immune infiltrate during neoadjuvant chemotherapy (NACT) with pathological complete response (pCR) in triple-negative breast cancer (TNBC) remains unexplored.MethodsMultiplexed immunohistochemistry was performed in matched tumor biopsies obtained at baseline and after 3 weeks of NACT from 66 patients from the West German Study Group Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early Breast Cancer - Triple Negative Breast Cancer (WSG-ADAPT-TN) trial. Association between CD4, CD8, CD73, T cells, PD1-positive CD4 and CD8 cells, and PDL1 levels in stroma and/or tumor at baseline, week 3 and 3-week change with pCR was evaluated with univariable logistic regression.ResultsCompared with no change in immune cell composition and functional markers, transition from ‘cold’ to ‘hot’ (below-median and above-median marker level at baseline, respectively) suggested higher pCR rates for PD1-positive CD4 (tumor: OR=1.55, 95% CI 0.45 to 5.42; stroma: OR=2.65, 95% CI 0.65 to 10.71) and PD1-positive CD8 infiltrates (tumor: OR=1.77, 95% CI 0.60 to 5.20; stroma: OR=1.25, 95% CI 0.41 to 3.84; tumor+stroma: OR=1.62, 95% CI 0.51 to 5.12). No pCR was observed after ‘hot-to-cold’ transition in PD1-positive CD8 cells. pCR rates appeared lower after hot-to-cold transitions in T cells (tumor: OR=0.26, 95% CI 0.03 to 2.34; stroma: OR=0.35, 95% CI 0.04 to 3.25; tumor+stroma: OR=0.00, 95% CI 0.00 to 1.04) and PD1-positive CD4 cells (tumor: OR=0.60, 95% CI 0.11 to 3.35; stroma: OR=0.22, 95% CI 0.03 to 1.92; tumor+stroma: OR=0.32, 95% CI 0.04 to 2.94). Higher pCR rates collated with ‘altered’ distribution (levels below-median and above-median in tumor and stroma, respectively) of T cell (OR=3.50, 95% CI 0.84 to 14.56) and PD1-positive CD4 cells (OR=4.50, 95% CI 1.01 to 20.14).ConclusionOur exploratory findings indicate that comprehensive analysis of early immune infiltrate dynamics complements currently investigated predictive markers for pCR and may have a potential to improve guidance for individualized de-escalation/escalation strategies in TNBC.
Effect of nusinersen on respiratory function in paediatric spinal muscular atrophy types 1–3
Authors: Chacko Archana , Sly Peter D , Ware Robert S , Begum Nelufa , Deegan Sean , Thomas Nicole , Gauld Leanne M 
Published: May 2021

IntroductionNusinersen is used in spinal muscular atrophy (SMA) to improve peripheral muscle function; however, respiratory effects are largely unknown.AimTo assess the effects of nusinersen on respiratory function in paediatric SMA during first year of treatment.MethodsA prospective observational study in paediatric patients with SMA who began receiving nusinersen in Queensland, Australia, from June 2018 to December 2019. Outcomes assessed were the age-appropriate respiratory investigations: spirometry, oscillometry, sniff nasal inspiratory pressure, mean inspiratory pressure, mean expiratory pressure, lung clearance index, as well as polysomnography (PSG) and muscle function testing. Lung function was collected retrospectively for up to 2 years prior to nusinersen initiation. Change in lung function was assessed using mixed effects linear regression models, while PSG and muscle function were compared using the Wilcoxon signed-rank test.ResultsTwenty-eight patients (15 male, aged 0.08–18.58 years) were enrolled: type 1 (n=7); type 2 (n=12); type 3 (n=9). The annual rate of decline in FVC z-score prior to nusinersen initiation was −0.58 (95% CI −0.75 to −0.41), and post initiation was −0.25 (95% CI −0.46 to −0.03), with a significant difference in rate of decline (0.33 (95% CI 0.02 to 0.66) (p=0.04)). Most lung function measures were largely unchanged in the year post nusinersen initiation. The total Apnoea–Hypopnoea Index (AHI) was reduced from a median of 5.5 events/hour (IQR 2.1–10.1) at initiation to 2.7 events/hour (IQR 0.7–5.3) after 1 year (p=0.02). All SMA type 1% and 75% of SMA types 2 and 3 had pre-defined peripheral muscle response to nusinersen.ConclusionThe first year of nusinersen treatment saw reduced lung function decline (especially in type 2) and improvement in AHI.
Histopathology Findings of the Lunate in Stage III Kienböck’s Disease
Authors: Xiong Ge , Liu Baoyue , Ding Yi 
Published: May 2021

Background: The etiology and natural history of Kienböck’s disease remain unclear. Traditionally it has been defined as avascular necrosis of the lunate. The authors tried to demonstrate different tissue distribution, the area ratio of necrotic tissue and vessel counts inside the whole Kienböck lunate to reveal a dynamic process of the lunate collapse. Methods: Five lunates from patients with stage III Kienböck’s disease and one cadaveric lunate not involved by Kienböck’s disease were sampled. They were sectioned, H&E stained, and evaluated. The thickness of trabecular bone and the area of necrotic tissue were measured with Image-Pro Plus. The number of vessels was counted manually. Results: In the normal lunate, the bone trabeculae showed a uniform distribution with fatty marrow filled the interspace between the trabeculae. In the lunates with Kienböck disease, the trabeculae fracture and necrosis located in the central part with massive fibrous granular tissue proliferation. There were also some chondroid metaplasia at the palmar and dorsal ends. The trabeculae of the lunates of the Kienböck’s disease [0.188 mm (0.153 mm, 0.236 mm)] was significantly thicker than the normal lunates [0.146 mm (0.124 mm, 0.164 mm)]. The necrosis was localized around the fracture sites instead of the whole lunate. The mean necrosis area only accounts for 16.3% ± 8.9% of the whole section. Such kind of focal necrosis is quite similar to those around the traumatic fracture ends of other bones. Even in stage III Kienböck lunates, the vessels are quite abundant (221 ± 42 in one sagittal section), while the vessels inside the normal lunate were 352 ± 28. Conclusions: There is neither massive nor obvious generalized avascular bone necrosis in our histopathology observations. The focal necrosis and vessel damage were more likely associated with the broken trabeculae inside the lunate. Based on our histopathology observations, we suggested that the progressive process of Kienböck’s disease could be described as lunate nonunion advanced collapse instead of avascular necrosis.
Which Fracture Types Are Associated with Widening of the Scapholunate Distance? A CT-Scan Study of Acute Intraarticular Distal Radius Fractures
Authors: Cromheecke Michiel , Vergison Laurence , Benis Szabolcs , Vermue Hannes , Vanhove Wim , Hollevoet Nadine 
Published: May 2021

Background: Scapholunate injuries in distal radius fractures may frequently be overlooked. The aims of this study were to measure the scapholunate distance in intraarticular distal radius fractures and to find out which fracture types were associated with an increased scapholunate width. Methods: Measurements of the scapholunate distance were performed on computed tomography scans of 143 intraarticular distal radius fractures in 140 patients. The fractures were classified according to the AO classification. The morphology of AO type B fractures was further analysed according to the Bain classification. Results: In 43 AO type B fractures mean scapholunate distance measured 2.1 mm and in 100 type C fractures 1.6 mm. The difference between partial and complete intraarticular fractures was significant. A trend towards a greater scapholunate distance was found in AO type B1 and radial styloid oblique fractures. Conclusions: In this study, partial intraarticular distal radius fractures, especially with a sagittal split, had a greater scapholunate distance and may be at risk for ligamentous injury.
Single-cell Profiles and Prognostic Impact of Tumor-Infiltrating Lymphocytes Coexpressing CD39, CD103, and PD-1 in Ovarian Cancer
Authors: Laumont Céline M. , Wouters Maartje C.A. , Smazynski Julian , Gierc Nicole S. , Chavez Elizabeth A. , Chong Lauren C. , Thornton Shelby , Milne Katy , Webb John R. , Steidl Christian , Nelson Brad H. 
Published: May 2021

Abstract

Purpose:
Tumor-infiltrating lymphocytes (TIL) are strongly associated with survival in most cancers; however, the tumor-reactive subset that drives this prognostic effect remains poorly defined. CD39, CD103, and PD-1 have been independently proposed as markers of tumor-reactive CD8+ TIL in various cancers. We evaluated the phenotype, clonality, and prognostic significance of TIL expressing various combinations of these markers in high-grade serous ovarian cancer (HGSC), a malignancy in need of more effective immunotherapeutic approaches.

Experimental Design:
Expression of CD39, CD103, PD-1, and other immune markers was assessed by high-dimensional flow cytometry, single-cell sequencing, and multiplex immunofluorescence of primary and matched pre/post-chemotherapy HGSC specimens.

Results:
Coexpression of CD39, CD103, and PD-1 (“triple-positive” phenotype) demarcated subsets of CD8+ TIL and CD4+ regulatory T cells (Treg) with a highly activated/exhausted phenotype. Triple-positive CD8+ TIL exhibited reduced T-cell receptor (TCR) diversity and expressed genes involved in both cytolytic and humoral immunity. Triple-positive Tregs exhibited higher TCR diversity and a tumor-resident phenotype. Triple-positive TIL showed superior prognostic impact relative to TIL expressing other combinations of these markers. TIGIT was uniquely upregulated on triple-positive CD8+ effector cells relative to their CD4+ Treg counterparts.

Conclusions:
Coexpression of CD39, CD103, and PD-1 demarcates highly activated CD8+ and CD4+ TIL with inferred roles in cytolytic, humoral, and regulatory immune functions. Triple-positive TIL demonstrate exceptional prognostic significance and express compelling targets for combination immunotherapy, including PD-1, CD39, and TIGIT.