bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subclinical synovial proliferation in patients with severe haemophilia A: The value of ultrasound screening and biochemical markers
Authors: van Bergen Eline D. P. , van Leeuwen Flora H. P. , Foppen Wouter , Timmer Merel A. , Schutgens Roger E. G. , Mastbergen Simon C. , Lafeber Floris P. J. G. , de Jong Pim A. , Fischer Kathelijn , van Vulpen Lize F. D. 
Published: September 2023

AbstractAimSubclinical bleeding and inflammation play a role in progression of haemophilic arthropathy. Synovial proliferation is predictive of joint bleeding and its early detection may guide treatment changes and prevent arthropathy progression. This study evaluated the prevalence of active and inactive subclinical synovial proliferation and investigated potential biochemical blood/urine markers to identify patients with active subclinical synovial proliferation.MethodsThis cross‐sectional study included patients with severe haemophilia A born 1970–2006 who were evaluated during routine clinic visits. Patients with (a history of) inhibitors or recent joint bleeding were excluded. Elbows, knees and ankles were examined for subclinical synovial proliferation by ultrasound and physical examination. Active synovial proliferation was distinguished from inactive synovial proliferation using predefined criteria. Blood/urine biochemical markers (serum osteopontin, sVCAM‐1, Coll2‐1, COMP, CS846, TIMP, and urinary CTX‐II) were compared individually and as combined indexes between patients with and without active synovial proliferation.ResultsThis cohort consisted of 79 patients with a median age of 31 years (range 16.5–50.8 years) with 62/79 (78%) of the patients using continuous prophylaxis. The annualized joint bleeding rate over the last 5 years was .6 (.2–1.1). Active (17/79, 22%) and inactive subclinical synovial proliferation (17/79, 22%) were both prevalent in this cohort. Biochemical markers were not correlated with active subclinical synovial proliferation.ConclusionSubclinical synovial proliferation, both active and inactive, was prevalent in patients with severe haemophilia A with access to prophylaxis and would be overlooked without routinely performed ultrasounds. Biochemical markers were unable to identify patients with active subclinical synovial proliferation.
Island spider origins show complex vertical stratification patterns in Macaronesia
Authors: Costa R. , Cardoso P. , Rigal F. , Borges P. A. V. 
Published: September 2023

Abstract
Spiders are among the most diverse and yet threatened groups of arthropods in Macaronesia. Found in most habitat types, they occupy the vertical gradient of native forests from ground to canopy level.
We hypothesize that their vertical distribution is influenced by the colonization origin. As introduced species should arrive using shipping containers and similar means, they should mostly occupy the lower levels in the gradient, with potential negative effects on the indigenous epigean fauna.
Spiders were sampled from epigean to arboreal microhabitats (maximum height varying between 2 and 4 m) on 45 sites across five islands belonging to three archipelagos. The mean and range of vertical stratification were obtained for each captured species. These values were then compared between different colonization origins at Macaronesian and archipelagic levels.
Native non‐endemic species were found at significantly higher vertical strata than both endemic and introduced species. Likewise, native non‐endemics had a larger vertical range. These patterns were largely replicated across archipelagos, although there were exceptions.
Overall, introduced species do not seem to occur mostly at lower strata in the native forests of Macaronesia (at least in the studied vertical range) but seem to be vertically restricted in most settings with the exception of Madeira.
Defining the proteomic landscape of cultured macrophages and their polarization continuum
Authors: Oates Tiah CL , Moura Pedro L , Cross Stephen , Roberts Kiren , Baum Holly E , Haydn‐Smith Katy L , Wilson Marieangela C , Heesom Kate J , Severn Charlotte E , Toye Ashley M 
Published: September 2023

AbstractMacrophages have previously been characterized based on phenotypical and functional differences into suggested simplified subtypes of MØ, M1, M2a and M2c. These macrophage subtypes can be generated in a well‐established primary monocyte culture model that produces cells expressing accepted subtype surface markers. To determine how these subtypes retain functional similarities and better understand their formation, we generated all four subtypes from the same donors. Comparative whole‐cell proteomics confirmed that four distinct macrophage subtypes could be induced from the same donor material, with > 50% of 5435 identified proteins being significantly altered in abundance between subtypes. Functional assessment highlighted that these distinct protein expression profiles are primed to enable specific cell functions, indicating that this shifting proteome is predictive of meaningful changes in cell characteristics. Importantly, the 2552 proteins remained consistent in abundance across all macrophage subtypes examined, demonstrating maintenance of a stable core proteome that likely enables swift polarity changes. We next explored the cross‐polarization capabilities of preactivated M1 macrophages treated with dexamethasone. Importantly, these treated cells undergo a partial repolarization toward the M2c surface markers but still retain the M1 functional phenotype. Our investigation of polarized macrophage subtypes therefore provides evidence of a sliding scale of macrophage functionality, with these data sets providing a valuable benchmark resource for further studies of macrophage polarity, with relevance for cell therapy development and drug discovery.
Factors leading to diagnostic delay in tuberculosis in the tropical north of Australia
Authors: Vigneswaran Nilanthy , Parnis Roger , Lowbridge Christopher , Townsend David , Ralph Anna P. 
Published: September 2023

AbstractBackgroundTuberculosis (TB) incidence is decreasing in the Northern Territory (NT) but still exceeds rates elsewhere in Australia. Deaths and morbidity from advanced TB continue, with delay in diagnosis a contributor to adverse outcomes.AimsWe aimed to describe the delay in diagnosis of TB, identify risk factors for delay and examine the associations between delay and clinical outcomes.MethodsWe conducted a historical cohort analysis which included adult inpatients diagnosed with TB at the Royal Darwin Hospital from 2010 to 2020. Patient delay was measured as time from symptom onset to first seeking care, and health system delay was quantified as time from first relevant clinical contact to diagnosis. The sum of these two periods was the total delay. Ethics approval was granted by NT HREC (2020‐3852).ResultsEighty‐four cases were included; the median total delay was 90 days (interquartile range (IQR): 60–121), patient delay was 53 days (IQR: 30–90), and health system delay was 21 days (IQR: 12–45). Patient delay was longer among patients with extrapulmonary (median: 100 days (IQR: 90–105) compared with pulmonary TB patients (39 days (IQR: 27–54), P < 0.0001). Health system delay was longer in those aged ≥45 years (30 days (IQR: 16–51) vs younger patients (14 days (IQR: 8–30), P = 0.007) and among non‐smokers (31 days (IQR: 21–55) vs 21 days (IQR: 10–40), P = 0.048). Median delay was longer among patients with non‐drug‐related complications of disease (P < 0.0001), those admitted to critical care (P < 0.0001), and those with respiratory failure (P = 0.001).ConclusionThe patient delays we report are longer than reported elsewhere in Australia. The next steps will require concerted efforts to improve community awareness of TB and strategies to strengthen health systems through better resourcing and healthcare provider support.
Flot2 deficiency facilitates B cell‐mediated inflammatory responses and endotoxic shock
Authors: Yang Qin , Zhang Zhenhua , Chen Ziye , Wang Yiyuan , Chen Yan , Zheng Jiehuang , Li Ruopeng , Li Lihong , Mo Lixia , Liang Qinghe , Chen Fengsheng , Wang Junjian , Li Xiaojuan 
Published: September 2023

AbstractSepsis is a life‐threatening disease characterized by multiple organ dysfunction. B cells play a pivotal role in sepsis. Here, we first observed the significantly reduced Flot2 gene expression in B cells from patients with bacterial sepsis and endotoxin‐induced septic mice. However, the effects of Flot2 on sepsis and B‐cell immunity remain unknown. Thus, we sorted B cells from Flot2 knockout (Flot2−/−) mice, RNA‐seq revealed significantly upregulated effector B cell (Beff) cytokines such as Il6, Il1b and Cxcl10 after Flot2 deficiency, while it showed no effect on the expression of regulatory B cell (Breg) cytokines such as Il10, Tgfb. Consistently, elevated Beff cytokine IL‐6 and unchanged Breg cytokine IL‐10 were shown in B cells from Flot2−/− mice. Similar results were subsequently observed in B cell‐specific Flot2 knockout chimeric mice. Notably, Flot2 deficiency aggravated sepsis with increased lung injury and shortened survival time in vivo by facilitating Beffs but not Bregs. Taken together, our data identify Flot2 as a novel controller of B cells, Flot2 deficiency amplifies inflammation by affecting Beffs to participate in the pathogenesis and progression of sepsis.
Targeted therapy for non‐small‐cell lung cancer: New insights into regulated cell death combined with immunotherapy
Authors: Li Shutong , Wang Aoxue , Wu Yongya , He Shengyuan , Shuai Wen , Zhao Min , Zhu Yumeng , Hu Xiuying , Luo Yubin , Wang Guan 
Published: September 2023

SummaryNon‐small‐cell lung cancer (NSCLC), which has a high rate of metastatic spread and drug resistance, is the most common subtype of lung cancer. Therefore, NSCLC patients have a very poor prognosis and a very low chance of survival. Human cancers are closely linked to regulated cell death (RCD), such as apoptosis, autophagy, ferroptosis, pyroptosis, and necroptosis. Currently, small‐molecule compounds targeting various types of RCD have shown potential as anticancer treatments. Moreover, RCD appears to be a specific part of the antitumor immune response; hence, the combination of RCD and immunotherapy might increase the inhibitory effect of therapy on tumor growth. In this review, we summarize small‐molecule compounds used for the treatment of NSCLC by focusing on RCD and pharmacological systems. In addition, we describe the current research status of an immunotherapy combined with an RCD‐based regimen for NSCLC, providing new ideas for targeting RCD pathways in combination with immunotherapy for patients with NSCLC in the future.
Effect of photobiomodulation on the efficacy of anesthesia in maxillary permanent molar teeth with molar incisor hypomineralization: A randomized clinical trial
Authors: Aykanat Berkehan , Elbay Mesut 
Published: September 2023

AbstractBackgroundDifficulty in anesthetizing teeth that have been diagnosed with molar incisor hypomineralization (MIH) is a frequently reported clinical problem. The effects of low‐level laser application (photobiomodulation) on the efficacy of anesthesia during the dental treatment of patients with MIH have not yet been studied.AimTo assess the effects of photobiomodulation therapy (PBMT) on the efficacy of anesthesia in maxillary permanent molar teeth with MIH.DesignThis prospective, parallel‐arm control, randomized, triple‐blind clinical trial included children aged 7–12 years. Maxillary permanent first molar teeth with MIH that required pulpotomy treatment were included. Seventy participants were randomly divided into two groups: experimental (with PBMT) and control (placebo). In the experimental group, before the administration of local infiltration anesthesia, PBMT (diode laser: 940 nm; continuous mode; 0.5 W; 78 J/cm2) was applied to the oral mucosa for 60 s each. In the control group, the laser probe was channeled toward the mucosa but was not activated. Pain scores were evaluated during the access cavity preparation of the pulpotomy treatment (when using the dentin cutting handpiece and while entering into the pulp) using the Face, Legs, Activity, Cry, Consolability (FLACC) scale. Additional anesthesia requirements were assessed in both groups. The data obtained were analyzed for statistical significance (p < .05). The chi‐squared test was used to determine the effect of PBMT on categorical outcomes.ResultsThe no‐pain scores of the experimental group were higher than those of the control group (29% vs. 20%). Moderate‐to‐high pain was more frequent in the control group than in the experimental group (43% vs. 20%). While 31% of the experimental group required supplemental anesthesia, 49% of the control group required supplemental anesthesia during pulpotomy of the tooth with MIH. No statistical difference, however, was found between the two groups in terms of pain scores and the need for supplemental anesthesia (p = .235, p = .143).ConclusionsAnesthesia with and without PBMT caused no difference in pain during the treatment of maxillary molar teeth with MIH.
Presenting points or rank: The impacts of leaderboard elements on English vocabulary learning through video lectures
Authors: Pi Zhongling , Yu Qiuchen , Zhang Yi , Li Yan , Chen Hui , Yang Jiumin 
Published: September 2023

AbstractBackgroundLeaderboards are a highly popular gamification component used in student learning to enhance motivation, attentional engagement, and learning performance. However, few studies have examined the effects of individual leaderboard elements on English vocabulary learning through video lectures.ObjectivesThe present study aimed to examine how different leaderboard elements (i.e., points and rank) may affect students' English vocabulary learning through video lectures.MethodsA total of 34 students were assigned to groups using different leaderboard elements in a counterbalanced order. Participants' motivation, eye movements, and learning performance were measured and analysed.Results and ConclusionsStudents' leaderboard rank was shown to increase their motivation regardless of whether other elements were present. Eye movement tracking revealed that the presence of the leaderboard increased students' saccades between the questions and the options, and lengthened their dwell time on the learning materials while reducing their dwell time on the non‐learning‐related screen areas. Presenting students' rank alone also improved their learning performance.ImplicationsOur findings strongly support the use of video lectures for English vocabulary learning, with the following recommendations: (1) Instructors should present students' rank on the leaderboard to enhance students' motivation and engagement; (2) Instructors should present only the students' rank on the leaderboard to also enhance students' learning performance.
Learning from screencast software tutorials: A comparison of cognitive load in dual and single‐monitor learning environments
Authors: Kueker Doug , Moore Joi 
Published: September 2023

AbstractBackgroundLearning to use software using screencast videos with worked examples in the corresponding practice files presents a classic split‐attention problem that requires learners to mentally integrate information from the video with a target application. While there is evidence that splitting attention either temporally or spatially adversely impacts learning, it is unclear if there is a meaningful difference in the load imposed by splitting attention in different ways. Furthermore, while much is known about effective screencast design, little is known about how learning environment features, such as the monitor configuration, influence learning from this form of instruction.ObjectiveAn experiment was conducted with 42 novice learners to compare the effects of two common monitor configurations that divided attention differently on three physiological measures of cognitive load.MethodsEffects due to the monitor setup were assessed using a 2 × 2 study design that controlled for task order and working memory capacity. In one condition, subjects split attention temporally by toggling back and forth between the video and target application on one monitor. In contrast, the other condition required subjects to split attention spatially by shifting their gaze between the video and target application displayed on two side‐by‐side monitors.Results and ConclusionsResults indicated that cognitive load as measured through task‐evoked pupil response was significantly higher, p < 0.05, for groups with two monitors during both instruction and testing, even after controlling for working memory capacity.
Guiding ablation strategies for ventricular tachycardia in patients with structural heart disease by analyzing links and conversion patterns of traceable abnormal late potential zone
Authors: Song Xudong , Que Dongdong , Zhu Yingqi , Yu Wenjie , Xu Haoran , Zhang Xiuli , Yan Jing , Wang Yuxi , Rui Bowen , Yang Yashu , Zhuang Zhenyu , Huang Guanlin , Zhao Xiaoqing , Yang Chaobo , Cai Yanbin , Yang Pingzhen 
Published: September 2023

AbstractBackgroundSubstrate‐based ablation can treat uninducible or hemodynamically instability scar‐related ventricular tachycardia (VT). However, whether a correlation exists between the critical VT isthmus and late activation zone (LAZ) during sinus rhythm (SR) is unknown.ObjectiveTo demonstrate the structural and functional properties of abnormal substrates and analyze the link between the VT circuit and abnormal activity during SR.MethodsThirty‐six patients with scar‐related VT (age, 50.0 ± 13.7 years and 86.1% men) who underwent VT ablation were reviewed. The automatic rhythmia ultrahigh resolution mapping system was used for electroanatomic substrate mapping. The clinical characteristics and mapping findings, particularly the LAZ characteristics during SR and VT, were analyzed. To determine the association between the LAZ during the SR and VT circuits, the LAZ was defined as five activation patterns: entrance, exit, core, blind alley, and conduction barrier.ResultsForty‐five VTs were induced in 36 patients, 91.1% of which were monomorphic. The LAZ of all patients was mapped during the SR and VT circuits, and the consistency of the anatomical locations of the LAZ and VT circuits was analyzed. Using the ultrahigh resolution mapping system, interconversion patterns, including the bridge, T, puzzle, maze, and multilayer types, were identified. VT ablation enabled precise ablation of abnormal late potential conduction channels.ConclusionFive interconversion patterns of the LAZ during the SR and VT circuits were summarized. These findings may help formulate more precise substrate‐based ablation strategies for scar‐related VT and shorter procedure times.
The impact of age on ablation outcomes in AF‐mediated cardiomyopathy
Authors: Segan Louise , Chieng David , Sugumar Hariharan , Voskoboinik Aleksandr , Ling Liang‐Han , Costello Ben , Azzopardi Sonia , Nderitu Ziporah , Parameswaran Ramanathan , Amerena John , McLellan Alex J. , Lee Geoffrey , Morton Joseph , Joseph Stephen , Wong Michael , Taylor Andrew , Kalman Jonathan M. , Kistler Peter M. , Prabhu Sandeep 
Published: September 2023

AbstractIntroductionThe absence of ventricular scar in patients with atrial fibrillation (AF) and systolic heart failure (HF) predicts left ventricular (LV) recovery following AF ablation. It is unknown whether age impacts the degree of LV recovery, reverse remodeling, or AF recurrence following catheter ablation (CA) among this population.ObjectivesTo evaluate the impact of age on LV recovery and AF recurrence in a population with AF and systolic HF without fibrosis (termed AF‐mediated cardiomyopathy) following CA.MethodsConsecutive patients undergoing CA between 2013 and 2021 with LV ejection fraction (LVEF) < 45% and absence of cardiac magnetic resonance imaging (CMR) detected LV myocardial fibrosis were stratified by age (<65 vs. ≥65 years). Following CA, participants underwent remote rhythm monitoring for 12 months with repeat CMR for HF surveillance.ResultsThe study population consisted of 70 patients (10% female, mean LVEF 33 ± 9%), stratified into younger (age < 65 years, 63%) and older (age ≥ 65 years, 37%) cohorts. Baseline comorbidities, LVEF (34 ± 9 vs. 33 ± 8 ≥65 years, p = .686), atrial and ventricular dimensions (left atrial volume index: 55 ± 21 vs. 56 ± 14 mL/m2 age ≥ 65, p = .834; indexed left ventricular end‐diastolic volume: 108 ± 40 vs. 104 ± 28 mL/m2 age ≥ 65, p = .681), pharmacotherapy and ablation strategy (pulmonary vein isolation in all; posterior wall isolation in 27% vs. 19% age ≥ 65, p = .448; cavotricuspid isthmus in 9% vs. 11.5% age ≥ 65) were comparable (all p > .05) albeit a higher CHADS2VASc score in the older cohort (2.7 ± 0.9 vs. 1.6 ± 0.6 age < 65, p < .001). Freedom from AF was comparable (hazard ratio: 0.65, 95% confidence interval: 0.38–1.48, LogRank p = .283) as was AF burden [0% (interquartile range, IQR: 0.0–2.1) vs. age ≥ 65: [0% (IQR 0.0–1.7), p = .516], irrespective of age. There was a significant improvement in LV systolic function in both groups (ΔLVEF + 21 ± 14% vs. +21 ± 12% age ≥ 65, p = .913), with LV recovery in the vast majority (73% vs. 69%, respectively, p = .759) at 13 (IQR: 12–16) months. This was accompanied by comparable improvements in functional status (New York Heart Association class p = .851; 6‐min walk distance 50 ± 61 vs. 93 ± 134 m in age ≥ 65, p = .066), biomarkers (ΔN‐terminal‐pro brain natriuretic peptide −139 ± 246 vs. −168 ± 181 age ≥ 65,p = .629) and HF symptoms (Short Form‐36 survey Δphysical component summary p = .483/Δmental component summary, p = .841).ConclusionIn patients undergoing CA for AF with systolic HF in the absence of ventricular scar, comparable improvements in ventricular function, symptoms, and freedom from AF are achieved irrespective of age.
Local low‐frequency vibration accelerates healing of full‐thickness wounds in a hyperglycemic rat model
Authors: Haba Daijiro , Qin Qi , Takizawa Chihiro , Tomida Sanai , Minematsu Takeo , Sanada Hiromi , Nakagami Gojiro 
Published: September 2023

AbstractAims/IntroductionLocal low‐frequency vibration (LLFV) promotes vasodilation and blood flow, enhancing wound healing in diabetic foot ulcers with angiopathy. However, vibration‐induced vasodilation does not occur, owing to chronic hyperglycemia and inflammation. We hypothesized that LLFV improves glycometabolism and inflammation, leading to vasodilation and angiogenesis in diabetic wounds. Therefore, this study investigated the effect of LLFV on wound healing in hyperglycemic rats, primarily focusing on glycometabolism, inflammation, vasodilation, and angiogenesis.Materials and MethodsStreptozotocin‐induced hyperglycemic Sprague–Dawley rats were used in this study. We applied LLFV to experimentally‐induced wounds at 50 Hz and 0, 600, 1,000 or 1,500 mVpp for 40 min/day from post‐wounding days (PWD) 1–14.ResultsThe relative wound areas in the 600 and 1,000 mVpp groups on PWD 5–7 were significantly smaller than those at 0 mVpp. The expression of Glo‐1 (1,500 mVpp) and Slc2A4 (1,000 and 1,500 mVpp) was upregulated on PWD 4 and 14, respectively. However, there was no difference in methylglyoxal expression levels in any group until PWD 14. At 1,000 mVpp, the expression of Tnfa on PWD 4, and that of Ptx3 and Ccl2 on PWD 14 was downregulated. Furthermore, the M1/M2 macrophage ratio was considerably decreased on both days. The expression of Nos3, Vegfa and vascular endothelial growth factor A was upregulated on PWD 4. In addition, vasodilation and angiogenesis were more obvious on PWD 14 with 1,000 mVpp.ConclusionsThe results suggest that LLFV promotes wound healing, improves glycometabolism and inflammation, and enhances vasodilation and angiogenesis in hyperglycemic wounds.