bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulated impact of lift car sizes on transport of critical care patients: Informing the design of the New Dunedin Hospital
Authors: Barnett Sheila G , Stephens Katherine M
Published: April 2024

The New Dunedin Hospital (NDH) is New Zealand’s largest health infrastructure build. Here we describe the use of a simple simulation-based hospital design exercise to inform the appropriate lift car size for critical care intrahospital transfers in the NDH. The intensive care unit (ICU) user group tested a series of entries and exits of simulated complex patient transfers in mocked-up lift cars of three different dimensions. Time taken to enter and exit the lift were recorded, reflecting the relative difficulty of transfer. Qualitative assessments were made of ease and perceived safety of transfer. These simulations demonstrated that recommended standard patient lift cars, often proposed for critical care transfers, could not physically accommodate all complex ICU transfers. A size of 1800 mm wide (W) × 3000 mm deep (D) had the physical capacity to permit all simulated ICU transfers, but with staff and patient risk. As lift car size increased to 2200 mm W × 3300 mm D, the simulation demonstrated reduced transfer times, smoother entry and exit, improved access to the head end of the bed, and reduced risk of disconnection or dislodgement of lines and airway support. The resultant clinical recommendations for the dimensions of a critical care lift car surpass current international health architecture guidelines and may help to inform future updates. The NDH project benefited from an objective assessment of risk, in language familiar to clinicians and healthcare architects. The outcome was an upsizing of the two ICU-capable lifts.
Choice of Current and Voltage for North American Commuter Rail Electrifications
Authors: Allen John G.
Published: April 2024

Engineers and planners today face challenges of assessing and adopting emerging propulsion technologies for commuter rail, particularly battery and hydrogen power. Early 20th century experiences with electrification technology may offer useful perspectives. When electrifying in the early 20th century, the most important decision facing North American commuter railroads was choosing electrical specifications—first between direct current (DC) and alternating current (AC), and then selecting a voltage. As a result, today’s electrified railroads present a sometimes-confusing array of specifications. Beneath the seeming disorder of specifications for legacy installations lies a logic based on the timing and circumstances of electrification, and on the ultimate size and purpose that railroads envisioned for these electrifications. Only low-voltage DC, delivered via third rail, was available for the earliest electrifications. By 1907, AC had entered the scene, and various overhead-wire DC specifications appeared between 1911 and 1930. Since the mid 20th century, 25,000 V AC at commercial frequency has become the default standard for new electrifications (and re-electrifications of older installations). Yet, even this standard has not been adopted for all reinforcements of overhead-wire electrifications, because of the historical overhang of earlier decisions. In situations where standardization of electrical specifications is not feasible, interoperability of equipment may be a more important priority.
Decreased Posterior Tibial Slope and Its Association With Pediatric Posterior Cruciate Ligament Injury
Authors: Vasudevan Rajiv S. , Rupp Garrett E. , Zogby Andrew M. , Wilps Tyler , Paras Tyler , Pennock Andrew T.
Published: April 2024

Background:

Recent adult studies have demonstrated that decreased posterior tibial slope angle (PTSA) may be a risk factor for posterior cruciate ligament (PCL) injury. However, there is no study investigating this phenomenon in a pediatric population. Understanding risk factors for PCL injuries among a pediatric population is important given the recent rise in athletic competition/specialization and sports-related injuries.

Hypothesis/Purpose:

The purpose of this study was to compare PTSA between pediatric patients sustaining a primary PCL tear compared with age- and sex-matched controls. It was hypothesized that pediatric patients sustaining a PCL tear would have a decreased PTSA compared with controls, with decreased PTSA being associated with higher odds of PCL injury.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

The records of all patients sustaining a PCL injury between 2006 and 2021 at a level 1 pediatric trauma center were reviewed. Patients aged ≤18 years with magnetic resonance imaging–confirmed PCL tear were included. Excluded were patients with concomitant anterior cruciate ligament tears, previous PCL reconstruction, or previous coronal plane realignment. A control cohort, with their ligament shown as intact on magnetic resonance imaging scans, was matched based on age and sex. PTSA was measured on lateral radiographs of the injured knee or tibia. The mean PTSA was compared between cohorts, and odds ratios were calculated based on the normal slope range (7°-10°) described in the literature, an upper range (>10°), and a lower range (<7°). Inter- and intrarater reliability were determined via calculation of an intraclass correlation coefficient.

Results:

Of the 98 patients who sustained a PCL injury in this study period, 59 (60%) met inclusion criteria, and 59 healthy knee controls were matched. There were no differences between the cohorts for age ( P = .90), sex ( P > .99), or body mass index ( P = .74). The PCL cohort had a lower mean ± SD PTSA compared with the control group (5.9°± 2.7° vs 7.3°± 4.3°; P = .03). PTSA <7° was associated with a 2.8 (95% CI, 1.3-6.0; P = .01) times risk of PCL tear. Conversely, PTSA >10° was associated with a 0.27 (95% CI, 0.09-0.81; P = .02) times risk of PCL tear. These PTSA measurements demonstrated acceptable intrarater and interrater reliability.

Conclusion:

PTSA <7° was associated with an increased odds of PCL injury, whereas a slope >10° was associated with a decreased odds of PCL injury in a pediatric population. These findings corroborate similar outcomes in adult studies; however, further studies are needed to elucidate PTSA as a risk factor for PCL injury.
How to Make Computer-Based Feedback More Productive: The Power of Erroneous Solutions
Authors: Wang Zhen , Pei Xinrui , Zhu Hejie , Gong Shaoying , Wang Enguo
Published: April 2024

This research aims to expand our understanding of how to facilitate student feedback engagement processes in a computer-based formative assessment environment. In the present research, we designed a new type of elaborated feedback in terms of combining the correct solution and the erroneous solution, and the erroneous solution matched the student’s initial answer. Furthermore, we analyzed whether this feedback had a stronger positive effect than the other three types of feedback containing different complexities of correct information (i.e., Knowledge of Correct Response, Problem-Solving Cues, or Complete Correct Solutions). As predicted, students who received correct and erroneous solutions experienced more positive feedback perceptions, perceived lower extraneous cognitive load and higher germane cognitive load, and achieved higher transfer performance. This research is one of the first that provides empirical evidence for the positive impact of incorporating students’ errors into the feedback design, and this novel insight can extend current theories on how to optimize feedback design to promote students’ active processing and use of feedback.
CNS Aspergillosis and Cryptococcosis with Cytomegalovirus Pneumonia in a Patient with Chronic Lymphocytic Leukemia Treated with Acalabrutinib
Authors: Fallin Taylor , Thacker Erica , Sahra Syeda , Siegrist Emily A. , White Bryan P. , Summers Katherine , Shibib Dena , Sassine Joseph
Published: April 2024

Bruton’s tyrosine kinase inhibitors (BTKis) are the preferred treatment for chronic lymphocytic leukemia (CLL). Despite their therapeutic benefits, these targeted agents have been associated with an increased risk of invasive infections. We describe a 68-year-old male who developed multiple bacterial, fungal and viral infections while on treatment with acalabrutinib. To our knowledge, this is the first reported case of concomitant CNS infections with Cryptococcus neoformans and Aspergillus fumigatus, along with cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1) pneumonia while on acalabrutinib. This case adds to the scarce literature of fungal and bacterial infections associated with acalabrutinib, raising the suspicion that infection risk is a medication class effect for BTKis.
Effects of Receiving Pain-Related Support on Psychological Well-Being: The Moderating Roles of Emotional Responses to Support
Authors: Nah Suyoung , Martire Lynn M. , Felt John M.
Published: April 2024

Objectives

We investigated whether receiving greater pain-related instrumental support is associated with poorer psychological well-being among chronic pain patients who report less positive (e.g., grateful) or more negative (e.g., angry) emotional responses to support.

Methods

We conducted regression analyses, utilizing data from two waves of interviews with 152 knee osteoarthritis patients. Three indicators of psychological well-being were examined: depressive symptoms, positive affect, and negative affect.

Results

Receiving greater support was associated with poorer psychological well-being at baseline, as well as higher depressive symptoms and negative affect at the 18-month follow-up, only among patients with low positive emotional responses to support. Furthermore, receiving greater support was related to poorer psychological well-being at baseline only among patients with high negative emotional responses to support.

Discussion

Care recipients’ less positive emotional responses to support may be a risk factor for poorer psychological well-being in both the short- and long-term, when receiving greater support.
Predictors of damage accrual and its impact on health-related quality of life of thrombotic antiphospholipid syndrome: Independent validation of the damage index for antiphospholipid syndrome (DIAPS)
Authors: Gaspar Pedro , Fernandes Ana Sofia M , Abrantes Ana Mafalda , Parreira Inês , Silva Inês , Silva Ryan C , Nobre Mariana B , Martins Joana R , Mota Catarina
Published: April 2024

Objectives

We aim to independently assess the validity of the damage index for antiphospholipid syndrome (DIAPS) in thrombotic antiphospholipid syndrome (APS) patients by exploring the prevalence and risk factors of organ damage and evaluating its impact on health-related quality of life (HR-QoL).

Methods

Cross-sectional study including all thrombotic APS patients (Sydney criteria) attending a Portuguese tertiary centre. Damage was assessed using the DIAPS, and HR-QoL using the 3- and 5-level EuroQol HR-QoL (EQ-D5-3L and 5L), and Visual Analogue Scale (VAS) applied via a phone questionnaire. Spearman’s correlation between DIAPS and the HR-QoL scales was performed. Risk factors for damage accrual and HR-QoL impairment were explored using univariate and multivariate logistic regression.

Results

Among the 108 patients (female, 65.7%; white, 90.7%; primary APS, 75.9%; median disease duration, 6 years), damage (DIAPS≥1) developed in 48.2% of patients (mean ± SD DIAPS, 3.08 ± 1.83). DIAPS’s neuropsychiatric domain was the most affected (24.2%), followed by the peripheral vascular domain (20.3%). No clinical, demographic nor laboratory parameters were significantly associated with damage. Regarding HR-QoL, pain/discomfort, anxiety/depression and usual activities domains were the most frequently impaired in both scales. DIAPS’s domains correlated similarly with the EQ-5D-3L and 5L scales’ individual domains. Female sex, medical disorders, secondary APS and type of presenting thrombosis (arterial) increased the risk of HR-QoL impairment. Total DIAPS was associated with higher odds of mobility, self-care and pain/discomfort impairment in both EQ-5D-3L and 5L scales but lost its independent risk in multivariable analysis.

Conclusion

This external validation of DIAPS reinforces the ability of the score to correlate with HR-QoL while also highlighting risk factors for HR-QoL impairment other than damage accrual.
Life Gets Better: Important Resilience Factors When Growing Up With ADHD
Authors: Dangmann Cecilie R. , Skogli Gunhild K. W. , Holthe Mira E. G. , Steffenak Anne K. M. , Andersen Per N.
Published: April 2024

Objective:

To explore emerging adults’ descriptions of important resilience factors when growing up with ADHD.

Method:

Individual interviews with 10 emerging adults (21–24 years) who participated in a 10-year follow-up study, analyzed using thematic analysis.

Results:

The main theme was that “life gets better.” Resilience factors contributing to this positive development were strategies to regulate ADHD, valuable relationships, acceptance, seeing positive attributes of ADHD, receiving tailored, non-stigmatizing support, and participating in meaningful activities.

Conclusion:

Growing up with ADHD was associated with both challenges and positives, but the main resilience theme was that life gets better. A variety of resilience factors contributed to this, but relational and environmental factors seemed particularly important. Acceptance, both from society and self-acceptance, were related to all resilience factors in various ways indicating that better knowledge of ADHD might foster better understanding and acceptance of children and adolescents with ADHD.
Exploring clinical variability in gelsolin amyloidosis: Brazilian family case study with confocal microscopy
Authors: Abreu Caio Brenno , Merlo Bárbara Flores Culau , Varandas Vinícius da Silva , Dias Juliana de Sá Freire Medrado
Published: April 2024

Introduction:

Genetic mutations or inflammatory, degenerative, or neoplastic conditions can trigger amyloidosis. Hereditary gelsolin amyloidosis is a genetic disorder primarily marked by amyloid fibrils composed of misfolded gelsolin fragments.

Case Report:

We present three sisters with AGel amyloidosis, illustrating its clinical diversity. Patient 1, a 51-year-old, had bilateral ptosis, ocular discomfort, and dry eye syndrome due to cranial nerve involvement. Patient 2, a 53-year-old, experienced progressive bilateral visual impairment. Patient 3, a 50-year-old, exhibited right eye ectropion. Genetic analysis, with the identical mutation, heterozygous c.640G > A (p.Asp214Asn) mutation, confirmed AGel amyloidosis diagnoses, with common findings including lattice corneal amyloidosis, reduced corneal sensitivity, and recurrent corneal erosions. Neurological manifestations included ataxia and peripheral neuropathy, with skin abnormalities observed in patient 1. Ocular involvement severity and distribution varied among patients.

Discussion:

Common ocular and neurological manifestations validated AGel amyloidosis diagnoses, reinforcing its hereditary basis. Neurological symptoms highlighted the disorder's impact on various organ systems, while skin abnormalities contributed to ocular discomfort. Variable ocular involvement emphasized the disorder's heterogeneity. These patients emphasize hereditary gelsolin amyloidosis's clinical diversity and suggest potential environmental influences on disease expression. Genetic confirmation and confocal microscopy findings reaffirm the genetic basis while raising questions about assessing systemic disease severity, necessitating further investigation in larger cohorts. Ophthalmologists’ specialized care is crucial for managing ocular symptoms, given the absence of a universal cure.
Teriflunomide in pediatric patients with relapsing multiple sclerosis: Open-label extension of TERIKIDS
Authors: Chitnis Tanuja , Banwell Brenda , Kappos Ludwig , Arnold Douglas L , Gücüyener Kivilcim , Deiva Kumaran , Saubadu Stephane , Hu Wenruo , Benamor Myriam , Le-Halpere Annaig , Truffinet Philippe , Tardieu Marc
Published: April 2024

Background:

The double-blind TERIKIDS study demonstrated the efficacy and safety of teriflunomide.

Objective:

To evaluate the efficacy, safety, and tolerability of continuous teriflunomide treatment in the TERIKIDS open-label extension.

Methods:

In the double-blind period, children with relapsing MS were randomized to placebo or teriflunomide (14 mg adult-equivalent dose) for ⩽ 96 weeks. Participants received teriflunomide for ⩽ 192 weeks post-randomization in the open-label extension.

Results:

The mean age at screening was 14.6 years. For teriflunomide/teriflunomide versus placebo/teriflunomide, estimated clinical relapse risk was reduced by 38% (hazard ratio (HR) 0.62; 95% confidence interval (CI) 0.39–0.98; p = 0.11) and numbers of gadolinium-enhancing T1 and new/enlarging T2 lesions were reduced by 43% (relative risk (RR) 0.570; 95% CI 0.33–0.98; p = 0.043) and 49% (RR 0.511; 95% CI 0.34–0.76; p = 0.001), respectively, in the combined double-blind and open-label periods. There was a trend toward reduced risk of 24-week sustained disability progression for teriflunomide/teriflunomide versus placebo/teriflunomide (HR 0.47; 95% CI 0.23–0.96). During the open-label extension, incidences of safety-related discontinuations were 4.0% (teriflunomide/teriflunomide) and 13.5% (placebo/teriflunomide), including two children who developed pancreatitis in the teriflunomide/teriflunomide group.

Conclusion:

Teriflunomide reduced the long-term risk of focal inflammatory activity, with generally manageable tolerability and no new safety signals. Further evidence would strengthen clinical efficacy findings. ClinicalTrials.gov: NCT02201108.
Therapeutic lag: Is treatment effect delayed in progressive MS?
Authors: Montobbio Noemi , Bovis Francesca , Signori Alessio , Ponzano Marta , Schiavetti Irene , Sormani Maria Pia
Published: April 2024

Background:

Randomized clinical trials (RCTs) in progressive multiple sclerosis (MS) often revealed non-significant treatment effects on disability progression.

Objectives:

To investigate whether the failure to detect a significant benefit from treatment may be motivated by a delay in treatment effect, possibly related to baseline characteristics.

Methods:

We re-analyzed data from two RCTs testing interferon-beta and glatiramer-acetate versus placebo in progressive MS with no significant effect on EDSS progression. We first designed a time-dependent Cox model with no treatment effect up to time = t0, and constant hazard ratio (HR) after time = t0. We selected the best-fitting t0 from 0 (standard Cox model) to 2.5 years. Furthermore, we modeled the delay as a function of baseline EDSS and fitted the resulting Cox model to the merged dataset.

Results:

The time-dependent Cox model revealed a significant benefit of treatment delayed by t0 = 2.5 years for the SPECTRIMS study (HR = 0.65 (0.43–0.98), p = 0.041), and delayed by t0 = 2 years for the PROMISE study (HR = 0.65, (0.42–0.99), p = 0.044). In the merged dataset, the HR for the EDSS-dependent delayed effect was 0.68 (0.56, 0.82), p < 0.001.

Conclusion:

The assumption of a delayed treatment effect improved the fit to the data of the two examined RCTs, uncovering a significant, although shifted, benefit of treatment.
Radiologically isolated syndrome in the spectrum of multiple sclerosis
Authors: Okuda Darin T , Lebrun-Frénay Christine
Published: April 2024

The radiologically isolated syndrome (RIS) currently represents the earliest detectable preclinical phase of multiple sclerosis (MS). Remarkable advancements have been recently made, including the identification of risk factors for disease evolution, revisions to the existing 2009 RIS criteria, and our understanding of the impact of early disease-modifying therapy use in the prevention/delay of symptomatic MS from two randomized clinical trials. Here, we discuss RIS in the context of the spectrum of MS, implications in the clinical management of individuals, and provide insights into future opportunities and challenges given the anticipated inclusion of asymptomatic MS in the formal definition of MS.
“Crew, don’t go anywhere near this man!” the co-construction of celebrity and responsible capitalism in broadcast interviews with a chief executive officer
Authors: Boxman-Shabtai Lillian
Published: April 2024

Celebrity CEOs espousing Corporate Social Responsibility (CSR) are receiving increasing media attention. However, researchers have not yet examined how CEOs and journalists co-create meaning about CSR in broadcast talk, an unscripted genre of news making, rife with contestation and cooperation. This paper presents a Conversation Analysis of six interviews featuring Dan Price, a CEO who pledged to “solve income inequality” by restructuring salaries in his company. Findings suggest that CSR anchored a process of double branding in which the CEO promoted himself and journalists reaffirmed their news philosophy. Price’s warm embrace by journalists across the political spectrum demonstrates a collaborative process of “celebrification”. Price created a transferable persona that appealed, through a mixture of political targeting and strategic ambiguity, to diverse audiences. Journalists elevated this persona by serving pseudo-criticism and showing identification. The story thus provided corporate media with the opportunity to reaffirm their commitment to “responsible capitalism”.
Leadership in uncertainty: Improvisation and positioning in municipal adult education
Authors: Andersen Fred Carlo , Vedøy Gunn , Dehlin Erlend
Published: April 2024

This study examines how six principals in Norwegian adult education centres (AECs) navigate and make sense of and navigate the multifaceted and uncertain environment in which they act. Specifically, the study aims to explore the significance of improvisation and positioning in the principals’ day-to-day decision-making and leadership as they address the challenges posed by complex migration patterns, shifting policies, and diverse student populations. The principles were interviewed in spring 2018, and selected to represent the diversity of such centres. Through initial analyses, the study identified that the environment of AECs was characterised by complexity, unpredictability, and uncertainty. Moreover, results indicate that improvisation and planning interplay. In addition, improvisation is strengthened by a collective focus on improvement, unpredictability as a rule and diversity as a strategy. Regarding leadership understood as positioning, we see how the principals assert their roles through power dynamics, acting on potential for change, and collaboration. Recognising the unique challenges faced by AEC principals, there is a need for targeted support and professional development that addresses the importance and understanding of improvisation and positioning in AEC-leadership. Moving forward, our findings should have implications for research, policy, and practice in municipal adult education. Key words: Principals, adult education centres, unpredictability, positioning, improvisation.
Considerations for open-label randomized clinical trials: Design, conduct, and analysis
Authors: Higgins Karen M , Levin Gregory , Busch Robert
Published: April 2024

Randomization and blinding are regarded as the most important tools to help reduce bias in clinical trial designs. Randomization is used to help guarantee that treatment arms differ systematically only by treatment assignment at baseline, and blinding is used to ensure that differences in endpoint evaluation and clinical decision-making during the trial arise only from the treatment received and not, for example, the expectation or desires of the people involved. However, given that there are times when it is not feasible or ethical to conduct fully blinded trials, we discuss what can be done to improve a trial, including conducting the trial as if it were a fully blinded trial and maintaining confidentiality of ongoing study results. In this article, we review how best to design, conduct, and analyze open-label trials to ensure the highest level of study integrity and the reliability of the study conclusions.
A Dining Experience Case Study for Hospitality Management Teaching and Learning
Authors: Atef Tamer , Al-Balushi Masooma
Published: April 2024

Case study as a teaching method has proven to be a mind stimulating technique that allows students to test different scenarios and to critically analyze practical incidents widening their knowledge perspective. Instructors achieve many goals through the application of such method where they enhance students learning by linking theory to practice in a cooperative environment based on team work, opinion sharing, and discussion. The aim of the current study is to demonstrate, analyze, and interpret a real dining experience case in order to be used in teaching by hospitality management instructors. This case as simple as it seems is a possible outcome of any service encounter. Its implications are profound on the organization image and guest loyalty. An experience that deviates away from its optimum scenario or ends with an unrecovered faulty service can render damages beyond just losing customers, to compensations, and even to law suits. It is an opportunity for hospitality management students to learn how to evade service failures, create successful memorable guest experiences, and to apply critical thinking techniques.
Fitusiran reduces bleeding in factor X–deficient mice
Authors: Verhenne Sebastien , McCluskey Geneviève , Maynadié Hortense , Adam Frédéric , Casari Caterina , Panicot-Dubois Laurence , Crescence Lydie , Dubois Christophe , Denis Cécile V. , Lenting Peter J. , Christophe Olivier D.
Published: April 2024

Factor X (FX) deficiency is a rare bleeding disorder manifesting a bleeding tendency caused by low FX activity levels. We aim to explore the use of fitusiran (an investigational small interfering RNA that silences antithrombin expression) to increase thrombin generation and the in vivo hemostatic potential under conditions of FX deficiency. We therefore developed a novel model of inducible FX deficiency, generating mice expressing <1% FX activity and antigen (f10low mice). Compared with control f10WT mice, f10low mice had sixfold and fourfold prolonged clotting times in prothrombin time and activated partial prothrombin time assays, respectively (P < .001). Thrombin generation was severely reduced, irrespective of whether tissue factor or factor XIa was used as an initiator. In vivo analysis revealed near-absent thrombus formation in a laser-induced vessel injury model. Furthermore, in 2 distinct bleeding models, f10low mice displayed an increased bleeding tendency compared with f10WT mice. In the tail-clip assay, blood loss was increased from 12 ± 16 μL to 590 ± 335 μL (P < .0001). In the saphenous vein puncture (SVP) model, the number of clots generated was reduced from 19 ± 5 clots every 30 minutes for f10WT mice to 2 ± 2 clots every 30 minutes (P < .0001) for f10low mice. In both models, bleeding was corrected upon infusion of purified FX. Treatment of f10low mice with fitusiran (2 × 10 mg/kg at 1 week interval) resulted in 17 ± 6% residual antithrombin activity and increased thrombin generation (fourfold and twofold to threefold increase in endogenous thrombin potential and thrombin peak, respectively). In the SVP model, the number of clots was increased to 8 ± 6 clots every 30 minutes (P = .0029). Altogether, we demonstrate that reduction in antithrombin levels is associated with improved hemostatic activity under conditions of FX deficiency.
Optimized cytogenetic risk-group stratification of KMT2A-rearranged pediatric acute myeloid leukemia
Authors: van Weelderen Romy E. , Harrison Christine J. , Klein Kim , Jiang Yilin , Abrahamsson Jonas , Alonzo Todd , Aplenc Richard , Arad-Cohen Nira , Bart-Delabesse Emmanuelle , Buldini Barbara , De Moerloose Barbara , Dworzak Michael N. , Elitzur Sarah , Fernández Navarro José M. , Gamis Alan , Gerbing Robert B. , Goemans Bianca F. , de Groot-Kruseman Hester A. , Guest Erin , Ha Shau-Yin , Hasle Henrik , Kelaidi Charikleia , Lapillonne Hélène , Leverger Guy , Locatelli Franco , Miyamura Takako , Norén-Nyström Ulrika , Polychronopoulou Sophia , Rasche Mareike , Rubnitz Jeffrey E. , Stary Jan , Tierens Anne , Tomizawa Daisuke , Zwaan C. Michel , Kaspers Gertjan J. L.
Published: April 2024

A comprehensive international consensus on the cytogenetic risk-group stratification of KMT2A-rearranged (KMT2A-r) pediatric acute myeloid leukemia (AML) is lacking. This retrospective (2005-2016) International Berlin-Frankfurt-Münster Study Group study on 1256 children with KMT2A-r AML aims to validate the prognostic value of established recurring KMT2A fusions and additional cytogenetic aberrations (ACAs) and to define additional, recurring KMT2A fusions and ACAs, evaluating their prognostic relevance. Compared with our previous study, 3 additional, recurring KMT2A-r groups were defined: Xq24/KMT2A::SEPT6, 1p32/KMT2A::EPS15, and 17q12/t(11;17)(q23;q12). Across 13 KMT2A-r groups, 5-year event-free survival probabilities varied significantly (21.8%-76.2%; P < .01). ACAs occurred in 46.8% of 1200 patients with complete karyotypes, correlating with inferior overall survival (56.8% vs 67.9%; P < .01). Multivariable analyses confirmed independent associations of 4q21/KMT2A::AFF1, 6q27/KMT2A::AFDN, 10p12/KMT2A::MLLT10, 10p11.2/KMT2A::ABI1, and 19p13.3/KMT2A::MLLT1 with adverse outcomes, but not those of 1q21/KMT2A::MLLT11 and trisomy 19 with favorable and adverse outcomes, respectively. Newly identified ACAs with independent adverse prognoses were monosomy 10, trisomies 1, 6, 16, and X, add(12p), and del(9q). Among patients with 9p22/KMT2A::MLLT3, the independent association of French-American-British–type M5 with favorable outcomes was confirmed, and those of trisomy 6 and measurable residual disease at end of induction with adverse outcomes were identified. We provide evidence to incorporate 5 adverse-risk KMT2A fusions into the cytogenetic risk-group stratification of KMT2A-r pediatric AML, to revise the favorable-risk classification of 1q21/KMT2A::MLLT11 to intermediate risk, and to refine the risk-stratification of 9p22/KMT2A::MLLT3 AML. Future studies should validate the associations between the newly identified ACAs and outcomes and unravel the underlying biological pathogenesis of KMT2A fusions and ACAs.
Converting IMPROVE bleeding and VTE risk assessment models into a fast-and-frugal decision tree for optimal hospital VTE prophylaxis
Authors: Djulbegovic Benjamin , Boylan Alice , Kolo Shelby , Scheurer Danielle Bowen , Anuskiewicz Sydney , Khaledi Flora , Youkhana Kimberley , Madgwick Sarah , Maharjan Neema , Hozo Iztok
Published: April 2024

Current hospital venous thromboembolism (VTE) prophylaxis for medical patients is characterized by both underuse and overuse. The American Society of Hematology (ASH) has endorsed the use of risk assessment models (RAMs) as an approach to individualize VTE prophylaxis by balancing overuse (excessive risk of bleeding) and underuse (risk of avoidable VTE). ASH has endorsed IMPROVE (International Medical Prevention Registry on Venous Thromboembolism) risk assessment models, the only RAMs to assess short-term bleeding and VTE risk in acutely ill medical inpatients. ASH, however, notes that no RAMs have been thoroughly analyzed for their effect on patient outcomes. We aimed to validate the IMPROVE models and adapt them into a simple, fast-and-frugal (FFT) decision tree to evaluate the impact of VTE prevention on health outcomes and costs. We used 3 methods: the “best evidence” from ASH guidelines, a “learning health system paradigm” combining guideline and real-world data from the Medical University of South Carolina (MUSC), and a “real-world data” approach based solely on MUSC data retrospectively extracted from electronic records. We found that the most effective VTE prevention strategy used the FFT decision tree based on an IMPROVE VTE score of ≥2 or ≥4 and a bleeding score of <7. This method could prevent 45% of unnecessary treatments, saving ∼$5 million annually for patients such as the MUSC cohort. We recommend integrating IMPROVE models into hospital electronic medical records as a point-of-care tool, thereby enhancing VTE prevention in hospitalized medical patients.
Production and recovery system for furan compounds from rice straw using an ionic liquid (1-methylimidazolium hydrogen sulfate) and vacuum steam distillation
Authors: Enomoto Kota , Hosoya Takashi , Miyafuji Hisashi
Published: April 2024

Furan compounds, including 5-hydroxymethylfurfural and furfural, can be synthesized from biomass and have garnered attention for their potential applications in biofuels and resin precursors. In this study, the synthesis of the furan compounds from rice straw was explored using a combined approach of ionic liquid treatment, specifically 1-methylimidazolium hydrogen sulfate ([MIM]HSO4), and vacuum steam distillation. Through the optimization of various processing parameters, we established that the best conditions for the furan compound production include: a cold trap cooling temperature of – 196 ℃, a system pressure of 10 hPa, a treatment temperature of 180 ℃, a reaction duration of 30 min, a sample loading of 1wt%, and a particle size range of 45–90 µm. Under these conditions, the resultant yield of the furan compounds was quantified at 27.9wt%. Additionally, the recyclability of the utilized ionic liquid was evaluated. Notably, even after four recycling cycles (encompassing a total of five reactions), the yield of the furan compounds remained consistent, underscoring the viability of ionic liquid reuse.
Functionalization of niobium nitrogen-doped titanium dioxide (TiO2) nanoparticles with ethanolic extracts of Mentha arvensis
Authors: Farooqi Muhammad Awais , Farooqi Hafiz Muhammad Umer , Bhatti Theophilus , Siddiqui Ghayas Uddin , Kausar Farzana , Kang Chul Ung
Published: April 2024

Titanium dioxide (TiO2) nanoparticles have gained significant attention due to their wide-ranging applications. This research explores an approach to functionalize Niobium Nitrogen Titanium Dioxide nanoparticles (Nb-N-TiO2 NPs) with Mentha arvensis ethanolic leaf extracts. This functionalization allows doped NPs to interact with the bioactive compounds in extracts, synergizing their antioxidant activity. While previous studies have investigated the antioxidant properties of TiO2 NPs synthesized using ethanolic extracts of Mentha arvensis, limited research has focused on evaluating the antioxidant potential of doped nanoparticles functionalized with plant extracts. The characterization analyses are employed by Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and Ultraviolet–visible (UV–Vis) spectroscopy to evaluate these functionalized doped nanoparticles thoroughly. Subsequently, the antioxidant capabilities through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric-reducing antioxidant power (FRAP) assays have been assessed. Within functionalized Nb-N-TiO2, the FTIR has a distinctive peak at 2350, 2010, 1312, 1212, and 1010 cm−1 with decreased transmittance associated with vibrations linked to the Nb-N bond. SEM revealed a triangular aggregation pattern, 500 nm to 2 µm of functionalized Nb-N-TiO2 NPs. Functionalized doped Nb-N-TiO2 NPs at 500 µg mL−1 exhibited particularly robust antioxidant activity, achieving an impressive 79% efficacy at DPPH assessment; meanwhile, ferric reduction efficiency of functionalized doped Nb-N-TiO2 showed maximum 72.16%. In conclusion, doped Nb-N-TiO2 NPs exhibit significantly enhanced antioxidant properties when functionalized with Mentha arvensis ethanolic extract compared to pure Nb-N-TiO2 manifested that doped Nb-N-TiO2 have broad promising endeavors for various biomedicine applications.
Recent advances in membrane technologies applied in oil–water separation
Authors: Huang Jialu , Ran Xu , Sun Litao , Bi Hengchang , Wu Xing
Published: April 2024

Effective treatment of oily wastewater, which is toxic and harmful and causes serious environmental pollution and health risks, has become an important research field. Membrane separation technology has emerged as a key area of investigation in oil–water separation research due to its high separation efficiency, low costs, and user-friendly operation. This review aims to report on the advances in the research of various types of separation membranes around emulsion permeance, separation efficiency, antifouling efficiency, and stimulus responsiveness. Meanwhile, the challenges encountered in oil–water separation membranes are examined, and potential research avenues are identified.
Many purported pseudogenes in bacterial genomes are bona fide genes
Authors: Cooley Nicholas P. , Wright Erik S.
Published: April 2024

Background

Microbial genomes are largely comprised of protein coding sequences, yet some genomes contain many pseudogenes caused by frameshifts or internal stop codons. These pseudogenes are believed to result from gene degradation during evolution but could also be technical artifacts of genome sequencing or assembly.

Results

Using a combination of observational and experimental data, we show that many putative pseudogenes are attributable to errors that are incorporated into genomes during assembly. Within 126,564 publicly available genomes, we observed that nearly identical genomes often substantially differed in pseudogene counts. Causal inference implicated assembler, sequencing platform, and coverage as likely causative factors. Reassembly of genomes from raw reads confirmed that each variable affects the number of putative pseudogenes in an assembly. Furthermore, simulated sequencing reads corroborated our observations that the quality and quantity of raw data can significantly impact the number of pseudogenes in an assembler dependent fashion. The number of unexpected pseudogenes due to internal stops was highly correlated (R2 = 0.96) with average nucleotide identity to the ground truth genome, implying relative pseudogene counts can be used as a proxy for overall assembly correctness. Applying our method to assemblies in RefSeq resulted in rejection of 3.6% of assemblies due to significantly elevated pseudogene counts. Reassembly from real reads obtained from high coverage genomes showed considerable variability in spurious pseudogenes beyond that observed with simulated reads, reinforcing the finding that high coverage is necessary to mitigate assembly errors.

Conclusions

Collectively, these results demonstrate that many pseudogenes in microbial genome assemblies are actually genes. Our results suggest that high read coverage is required for correct assembly and indicate an inflated number of pseudogenes due to internal stops is indicative of poor overall assembly quality.
Genomic characterization and related functional genes of γ- poly glutamic acid producing Bacillus subtilis
Authors: Zhu Jiayue , Wang Xue , Zhao Jianan , Ji Fang , Zeng Jun , Wei Yanwen , Xu LiLi , Dong Guoying , Ma Xingyuan , Wang Chengmin
Published: April 2024

γ- poly glutamic acid (γ-PGA), a high molecular weight polymer, is synthesized by microorganisms and secreted into the extracellular space. Due to its excellent performance, γ-PGA has been widely used in various fields, including food, biomedical and environmental fields. In this study, we screened natto samples for two strains of Bacillus subtilis N3378-2at and N3378-3At that produce γ-PGA. We then identified the γ-PGA synthetase gene cluster (PgsB, PgsC, PgsA, YwtC and PgdS), glutamate racemase RacE, phage-derived γ-PGA hydrolase (PghB and PghC) and exo-γ-glutamyl peptidase (GGT) from the genome of these strains. Based on these γ-PGA-related protein sequences from isolated Bacillus subtilis and 181 B. subtilis obtained from GenBank, we carried out genotyping analysis and classified them into types 1–5. Since we found B. amyloliquefaciens LL3 can produce γ-PGA, we obtained the B. velezensis and B. amyloliquefaciens strains from GenBank and classified them into types 6 and 7 based on LL3. Finally, we constructed evolutionary trees for these protein sequences. This study analyzed the distribution of γ-PGA-related protein sequences in the genomes of B. subtilis, B. velezensis and B. amyloliquefaciens strains, then the evolutionary diversity of these protein sequences was analyzed, which provided novel information for the development and utilization of γ-PGA-producing strains.
Outlier detection in spatial error models using modified thresholding-based iterative procedure for outlier detection approach
Authors: Cai Jiaxin , Hu Weiwei , Yang Yuhui , Yan Hong , Chen Fangyao
Published: April 2024

Background

Outliers, data points that significantly deviate from the norm, can have a substantial impact on statistical inference and provide valuable insights in data analysis. Multiple methods have been developed for outlier detection, however, almost all available approaches fail to consider the spatial dependence and heterogeneity in spatial data. Spatial data has diverse formats and semantics, requiring specialized outlier detection methodology to handle these unique properties. For now, there is limited research exists on robust spatial outlier detection methods designed specifically under the spatial error model (SEM) structure.

Method

We propose the Spatial-Θ-Iterative Procedure for Outlier Detection (Spatial-Θ-IPOD), which utilizes a mean-shift vector to identify outliers within the SEM. Our method enables an effective detection of spatial outliers while also providing robust coefficient estimates. To assess the performance of our approach, we conducted extensive simulations and applied it to a real-world empirical study using life expectancy data from multiple countries.

Results

Simulation results showed that the masking and JD (Joint Detection) indicators of our Spatial-Θ-IPOD method outperformed several commonly used methods, even in high-dimensional scenarios, demonstrating stable performance. Conversely, the Θ-IPOD method proved to be ineffective in detecting outliers when spatial correlation was present. Moreover, our model successfully provided reliable coefficient estimation alongside outlier detection. The proposed method consistently outperformed other models (both robust and non-robust) in most cases. In the empirical study, our proposed model successfully detected outliers and provided valuable insights in the modeling process.

Conclusions

Our proposed Spatial-Θ-IPOD offers an effective solution for detecting spatial outliers for SEM while providing robust coefficient estimates. Notably, our approach showcases its relative superiority even in the presence of high leverage points. By successfully identifying outliers, our method enhances the overall understanding of the data and provides valuable insights for further analysis.
Determinants of early chronic kidney disease in patients with recently diagnosed type 2 diabetes mellitus: a retrospective study from the Taiwan Diabetes Registry
Authors: Yeh Yun-Kai , Lin Kuan-Hung , Sheu Wayne Huey-Herng , Lo Su-Huey , Yeh Yen-Po , Huang Chien-Ning , Hwu Chii-Min , Lu Chieh-Hsiang
Published: April 2024

Background

We tried to identify the risk factor associate with early chronic kidney disease (CKD) in recently diagnosed type 2 diabetes mellitus patients by utilizing real-world data from Taiwan Diabetes Registry.

Materials and methods

Patients with type 2 diabetes mellitus recently diagnosed within 1 year. We divided the study participants into control group and early CKD group. Early CKD was defined as either CKD stage G1 with albuminuria, CKD stage G2 with albuminuria, or CKD stage G3a regardless of albuminuria (Urine-albumin to creatinine ratio (UACR) ≥ 3 mg/mmol). Control group was defined as CKD G1 or CKD G2 without albuminuria. Logistic regression analyses were used to compare differences in clinical characteristics between the subgroups. Linear regression models were employed to examine the factors predicting estimated glomerular filtration rate (eGFR) and UACR.

Results

Total 2217 patients with recently diagnosed type 2 diabetes mellitus were included. 1545 patients were assigned to control group and 618 patients were assigned to the early CKD group. Age (odds ratio (OR) 1.215, 95% confidence interval [CI] 1.122–1.316), systolic blood pressure (OR 1.203, 95% CI 1.117–1.296), glycated hemoglobin (OR 1.074, 95% CI 1.023–1.129) and triglyceride (OR 2.18, 95% CI 1.485–3.199) were found to be significant risk factors. Further, presence of bidirectional association between UACR and eGFR was found.

Conclusions

We reported factors associated with early CKD in recently diagnosed type 2 diabetes mellitus patients. Variables that associated with eGFR and UACR were identified respectively, included a mutual influence between UACR and eGFR.
Prognostic value of pre-treatment [18F] FDG PET/CT in recurrent nasopharyngeal carcinoma without distant metastasis
Authors: Dong Zhe , Wang Gao-Yuan , Dai Dong-Yu , Qin Guan-Jie , Tang Ling-Long , Xu Cheng , Ma Jun
Published: April 2024

Background

[18 F]-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) has the ability to detect local and/or regional recurrence as well as distant metastasis. We aimed to evaluate the prognosis value of PET/CT in locoregional recurrent nasopharyngeal (lrNPC).

Methods

A total of 451 eligible patients diagnosed with recurrent I-IVA (rI-IVA) NPC between April 2009 and December 2015 were retrospectively included in this study. The differences in overall survival (OS) of lrNPC patients with and without PET/CT were compared in the I-II, III-IVA, r0-II, and rIII-IVA cohorts, which were grouped by initial staging and recurrent staging (according to MRI).

Results

In the III-IVA and rIII-IVA NPC patients, with PET/CT exhibited significantly higher OS rates in the univariate analysis (P = 0.045; P = 0.009; respectively). Multivariate analysis revealed that with PET/CT was an independent predictor of OS in the rIII-IVA cohort (hazard ratio [HR] = 0.476; 95% confidence interval [CI]: 0.267 to 0.847; P = 0.012). In the rIII-IVA NPC, patients receiving PET/CT sacns before salvage surgery had a better prognosis compared with MRI alone (P = 0.036). The recurrent stage (based on PET/CT) was an independent predictor of OS. (r0-II versus [vs]. rIII-IVA; HR = 0.376; 95% CI: 0.150 to 0.938; P = 0.036).

Conclusion

The present study showed that with PET/CT could improve overall survival for rIII-IVA NPC patients. PET/CT appears to be an effective method for assessing rTNM staging.