bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phone-Based Parental Support Program for Caries Prevention in Children: A Randomized Controlled Trial
Authors: Brännemo I. , Hasselblad T. , Levinsson A. , Dahllöf G. , Tsilingaridis G. 
Published: December 2024

Introduction: Children referred for comprehensive dental care under general anesthesia, due to severe early childhood caries, have a high risk of continued caries progression in posttreatment years. Objectives: To assess the effect of a phone-delivered, motivational interviewing–based parental support program on caries recurrence and oral health habits in preschool children treated under general anesthesia for severe early childhood caries. Methods: The prospective design of this 2-arm randomized clinical trial (allocation ratio 1:1; blinded outcome assessment) comprised 151 patients from pediatric dental departments in the Stockholm region of Sweden. Inclusion criteria were healthy children aged <6 y with early childhood caries who were scheduled for treatment under general anesthesia. Control group parents received standard advice on toothbrushing and sugar reduction. Intervention group parents received planned phone counseling with an oral health coach every other week for 1 y, based on motivational interviewing principles, offered in Arabic, English, Polish, Turkish, and Swedish. The primary outcome was caries progression 1 and 2 y postsurgery, assessed using the International Caries Detection and Assessment System. Secondary outcomes were parent-reported daily toothbrushing and dietary habits. Results: Sixty-five percent of the control group and 77% of the intervention group experienced caries relapse on at least 1 new surface after 1 y (nonsignificant). At the 2-y follow-up, relapse rates were 53% (control group) and 71% (intervention group; P < 0.05) compared with baseline. The intervention group was significantly less likely to engage in adverse oral health behaviors such as snacking on sweets (intervention group, 10%; control group 33%) and sweet drinks (intervention group 9%; control group, 29%) after 1 y. No group differences in daily fluoride toothpaste brushing occurred. Conclusion: The motivational interviewing–based parental support program improved dietary habits but showed no effect on caries recurrence in children treated under general anesthesia for early childhood caries. ClinicalTrials.gov NCT02487043 Knowledge Transfer Statement: The findings of this study can assist clinicians, public health leaders, and researchers in tailoring preventative behavior-focused programs for early childhood caries. These results may improve the understanding of how behavioral interventions that involve parents of young children affect caries prevention, highlighting approaches that are less likely to be effective and guiding future efforts toward more promising strategies for high-risk populations.
Targeted interferon therapy with modakafusp alfa for relapsed or refractory multiple myeloma
Authors: Vogl Dan T. , Atrash Shebli , Holstein Sarah A. , Nadeem Omar , Benson Don , Chaudry Maria , Biran Noa , Suryanarayan Kaveri , Li Cheryl , Liu Yuyin , Collins Sabrina , Parot Xavier , Kaufman Jonathan L. 
Published: December 2024

Abstract
Interferon alfa has activity against multiple myeloma (MM). Modakafusp alfa is an immunocytokine comprising 2 attenuated interferon alfa-2b molecules and an anti-CD38 immunoglobulin G4 antibody, targeting delivery of interferon alfa to CD38-expressing (CD38+) immune and myeloma cells. This phase 1/2 trial enrolled patients with relapsed/refractory multiple myeloma with ≥3 prior lines of treatment and refractory to, or intolerant of, ≥1 proteasome inhibitor and ≥1 immunomodulatory drug. During dose escalation, modakafusp alfa was administered at 10 doses in 4 schedules across 13 cohorts. The primary end point was safety for dose escalation, and overall response rate (ORR) for dose expansion. We enrolled 106 patients who had received a median of 6.5 lines of prior therapy; 84% of patients had myeloma previously refractory to an anti-CD38 antibody. The most feasible dosing schedule was every 4 weeks (Q4W), at which the maximum tolerated dose was 3 mg/kg. Among 30 patients treated at 1.5 mg/kg Q4W, the ORR was 43.3%, with a median duration of response of 15.1 months (95% confidence interval [CI], 7.1-26.1); median progression-free survival was 5.7 months (95% CI, 1.2-14). Grade ≥3 adverse events (AEs) occurred in 28 (93.3%) patients, the most common were neutropenia (66.7%) and thrombocytopenia (46.7%); infections were reported in 8 (26.7%) patients (including grade 3 in 4 [16.7%]). Modakafusp alfa therapy induced upregulation of the type 1 interferon gene signature score, increased CD38 receptor density in CD38+ cells, and innate and adaptive immune cell activation. Modakafusp alfa resulted in antitumor activity and immune activation in patients with MM. AEs were primarily hematologic. This trial was registered at www.clinicaltrials.gov as #NCT03215030.
Building capacity for pediatric hematological diseases in Sub-Saharan Africa
Authors: Chirande Lulu , Namazzi Ruth , Hockenberry Marilyn , Wasswa Peter , Kiguli Sarah , Mulemba Tadala , Gastier-Foster Julie M. , Lyimo Magdalena , Airewele Gladstone , Lubega Joseph , Ozuah Nmazuo 
Published: December 2024

Abstract
The spectrum of hematological diseases in African children includes anemias, bleeding disorders, thromboses, and oncological diseases such as leukemias. Although data are limited, outcomes for these diseases are poorer in Africa. The dearth of specialists, and lack of infrastructure that supports diagnosis and management, have been identified as key barriers to improving outcomes for childhood hematological disorders in Sub-Saharan Africa (SSA). To address these, intentional capacity building efforts addressing education and training, diagnostic capacity, and access to blood products and medicines are needed. This article explores some ongoing efforts in the region aimed at fostering the capacity to identify and treat childhood hematological disorders across a breadth of initiatives targeting the critical themes of education, diagnostic support, and treatment. We also identify existing opportunities through international partnerships, to build sustainable programs that can support children with hematological diseases in SSA.
Digital remote maintenance inhaler adherence interventions in COPD: a systematic review and meta-analysis
Authors: Aung Hnin , Tan Ronnie , Flynn Cara , Divall Pip , Wright Adam , Murphy Anna , Shaw Dominick , Ward Tom J.C. , Greening Neil J. 
Published: December 2024

IntroductionSub-optimal inhaler adherence undermines the efficacy of pharmacotherapy in COPD. Digitalised care pathways are increasingly used to improve inhaler-use behaviour remotely. This review investigated the feasibility and impact of remote electronic inhaler adherence monitoring (EIM) and intervention platforms on clinical outcomes in COPD.MethodsA literature search was conducted and studies investigating maintenance inhaler use among people with COPD using digital technology were selected. Pairwise and proportional meta-analyses were employed with heterogeneity assessed using I2statistics. When meta-analysis was not feasible, a narrative synthesis of outcomes was conducted.ResultsWe included 10 studies including 1432 people with COPD whose maintenance inhaler usage was supported by digital inhalers and apps featuring audiovisual reminders and educational content with or without engagement with healthcare providers (HCPs). Inhaler adherence rate (AR) varied with calculation methods, but an overall suboptimal adherence was observed among people with COPD. HCP-led adherence interventions alongside EIM improved mean AR by 18% (95% CI 9–27)versuspassive EIM only. Enhanced AR may reduce COPD-related healthcare utilisation with little impact on health-related quality of life and exacerbation rate. Despite encountering technical issues among 14% (95% CI 5–23%) of participants, 85% (95% CI 76–94%) found digital platforms convenient to use, while 91% (95% CI 79–100%) perceived inhaler reminders as helpful.ConclusionDigitalised interventions can enhance maintenance inhaler adherence in COPD but their overall effect on clinical outcomes remains uncertain. Further work is required to tailor interventions to individuals’ adherence behaviour and investigate their longer-term impact.
Iranian mothers’ perceptions of contextual factors helping them manage pain in labor
Authors: Ghamgosar Faeghe Deljoo , Sadra Muhammad , Yari Hassan , Honarbakhsh Mina 
Published: December 2024

Abstract
Background
The rate of caesarean section in Iran has significantly increased. The main reason cited by Iranian mothers for it is labor pain and fear of it. However, the experience of pain during childbirth has different meanings for mothers in various conditions. Therefore, this study aims to examine the components from the mothers’ perspective that helped them manage pain in labor. The findings of this article may help prevent unnecessary medical interventions.

Methods
The current article is one component of a mixed-method study conducted in Iran. Its primary objective was to develop protocols for maternity unit design to enhance maternal satisfaction, promote husbands’ involvement, and improve pain management. The current study focuses on examining contextual components that are effective in managing pain among 25 mothers selected through stratified purposive sampling. Data collection from mothers who gave birth in four large hospitals in Iran was carried out through unstructured in-depth interviews. The data were analyzed using interpretative phenomenological analysis.

Findings
The data show that two major environmental factors affect mothers’ perception of pain and their ability to control it: (1) Internal and (2) External environments. The main components of the internal factor are identified as “Personal beliefs”, “Self-confidence and lack of fear”, and the external environment includes three subfactors: “Spatial environment”, “Social environment”, and “Interactive environment”. The overall meaning attributed to pain caused by these factors determines how mothers can cope with it.

Conclusion
In this study, self-confidence and a positive mindset were significant factors in managing pain during labor among this group of mothers. Furthermore, each mother’s perception of pain was shaped by a combination of physical, social, and interactive influences. The research identified the importance of support during labor according to mothers’ individual, subjective needs, while improving the physical environment, with a view to reducing interventions and promoting positive experiences for mothers and husbands. Consequently, enhancing internal resources and the birthing environment during labor which involve identifying the optimal blend of physical, mental, and emotional strategies tailored to the specific needs of mothers, can be considered to a potential reduction in the perceived intensity of pain in future.
Implementing an enhanced recovery from surgery pathway to reduce hospital length of stay for primary hip or knee arthroplasty: a budget impact analysis
Authors: Lloyd Melanie , Ademi Zanfina , Harris Ian A. , Naylor Justine , Lewis Peter , de Steiger Richard , Buchbinder Rachelle , Wan Anthony , Ackerman Ilana N. 
Published: December 2024

Abstract
Background
Given growing demand for hip and knee arthroplasty and unsustainable resource requirements, safe and efficient models of care are critical. This study aims to determine the impact on healthcare costs of implementing an enhanced short-stay model of care (ESS-MOC) for arthroplasty at a national level.

Methods
A budget impact analysis was conducted for the years 2023–2030 in the setting of Australian publicly and privately funded hospitals performing hip or knee arthroplasty. The model considered population-based future arthroplasty projections, published data on healthcare costs and resource utilisation, and aggregate health insurer claims data related to minor complexity elective hip or knee arthroplasty for osteoarthritis. The ESS-MOC assigned a conservative hypothesized 30% of eligible patients to an enhanced recovery from surgery (ERAS) pathway which comprised a shortened acute ward stay (average 2 days versus 4 days with current care) and outpatient rehabilitation. The primary outcome was total healthcare cost savings post-ESS-MOC implementation, stratified by joint (knee/hip) and healthcare sector (public/private). Return on investment (ROI) ratio, measuring the return for each dollar invested in implementation, and hospital bed days utilized, were also estimated. Costs are presented in Australian dollars (AUD), at 2023 prices.

Results
Estimated cost savings for 2023–2030 from implementing the ESS-MOC pathway were AUD641 million (95% CI: AUD99 million to AUD1250 million), corresponding to a ROI ratio of AUD8.88 (AUD1.3 to AUD17.9). Total implementation costs for the ESS-MOC were estimated at AUD38 million and AUD34 million for the private and public sectors, respectively. Savings would be 8-fold higher in the private sector (AUD571 million vs. AUD70 million in the public sector), primarily attributable to the > 80,000 rehabilitation bed days saved annually in this sector. For the period 2023–2030, an estimated 337,000 (261,000 to 412,000) acute bed days could be saved (private sector 262,000 [200,000 to 324,000]; public sector 74,000 [57,000 to 92,000]). Less than 10% of eligible patients would need to move into the ERAS pathway to realise cost savings.

Conclusions
Implementation of an enhanced short-stay model of care for eligible arthroplasty patients in Australia would generate significant cost and resource savings, particularly for the private hospital sector.
Exploring key challenges for healthcare providers and stakeholders in delivering adolescent sexual and reproductive health services and information during the COVID-19 pandemic in Malawi, Zambia and Zimbabwe: a qualitative study
Authors: Munakampe Margarate Nzala , Matenga Tulani Francis L. , Chewe Mwimba , Gold-Watts Anise , Lahidji Reza 
Published: December 2024

Abstract
Introduction
This study aimed to explore the direct and indirect influences of COVID-19-related restrictions on adolescents and young people’s (AYP’s) sexual and reproductive health and rights (SRHR) in Malawi, Zambia, and Zimbabwe, with a focus on teenage pregnancy and access to and utilization of HIV testing and counselling services.

Methods
Thirty-four purposively sampled interviews that comprised of selected representatives of organizations involved in activities aimed at addressing adolescent sexual and reproductive health and rights (ASRHR), teenage pregnancies, and HIV testing were conducted in Malawi, Zambia and Zimbabwe. In Zambia, the study conducted an additional four group discussions with adolescents and young people. Adolescents and young people were asked to describe their experience and perceptions of the impact of COVID-19 on their SRHR. Thematic analysis was used to analyze the data.

Results
Priority shifts resulted in the focus of service provision to the COVID-19 response. This led to shortages of already insufficient human resources due to infection and/or isolation, supply chain disruptions leading to shortages of important sexual and reproductive health (SRH)-related commodities and supplies, compromised quality of services such as counselling for HIV and overall limited AYP’s access to SRH information. Suggestions for interventions to improve SRH services include the need for a disaster preparedness strategy, increased funding for ASRHR, the use of community health workers and community-based ASRHR strategies, and the use of technology and social media platforms such as mHealth.

Conclusion
Disruption of SRH services for adolescents and young people due to pandemic related-restrictions, and diversion of resources/funding has had a ripple effect that may have long-term consequences for adolescents and young people throughout the East and Southern African region. This calls for further investment in adolescents and young people’s access to SRHR services as progress made may have been deterred.
Aging-associated sensory decline and Alzheimer’s disease
Authors: Hong Suji , Baek Seung-Hyun , Lai Mitchell K. P. , Arumugam Thiruma V. , Jo Dong-Gyu 
Published: December 2024

Abstract
Multisensory decline is common as people age, and aging is the primary risk of Alzheimer’s Disease (AD). Recent studies have begun to shed light on the possibility that age-related sensory decline could accelerate AD pathogenesis, or be a prodromal indicator of AD. Sensory impairments, specifically in taste and smell, often emerge before cognitive symptoms in AD, indicating their potential as early biomarkers. Olfactory dysfunction has been frequently associated with AD and may offer valuable insights into early detection. Hearing impairment is significantly associated with AD, but its causal impact on AD progression remains unclear. The review also discusses visual and tactile deficits in AD, including retinal thinning and changes in tactile perception, highlighting their links to disease progression. Focusing on molecular mechanisms, the review explores the roles of amyloid-β (Aβ) accumulation and tau protein pathology in sensory decline and their bidirectional relationship with AD. In summary, the evidence presented conclusively supports advocating for an integrated approach to understanding AD and sensory decline, to enhance early detection, implementing preventive strategies, and developing therapeutic interventions for AD. This approach underscores the significance of sensory health in addressing neurodegenerative diseases, particularly AD.
A review of UK publicly funded non-inferiority trials: is the design more inferior than it should be?
Authors: Totton Nikki , Julious Steven , Walters Stephen , Coates Elizabeth 
Published: December 2024

Abstract

Background
The number of non-inferiority (NI) trials, those aiming to show a new treatment is no worse than a comparator, is increasing. However, their added complexity over superiority trials can create confusion. Most guidance and reviews to date have an industry focus with research suggesting these trials may differ from publicly funded NI trials. The aim of this work is to review the design and reporting characteristics of UK publicly funded NI trials. This assessment will show how well recommendations from industry are translating to publicly funded trials.

Methods
The International Standard Randomised Controlled Trial Number web registry and the National Institute for Health and Care Research’s Funding and Awards Library and Journals Library were searched using the term non-inferiority and logical synonyms. Inclusion requirements were a UK publicly funded NI randomised controlled trial. Characteristics of the design, analyses and results as available were recorded on a dedicated data extraction spreadsheet. Appropriate summary statistics were used to present the results.

Results
Searches completed on the 14th of January 2022 identified 477 potential trials which after exclusions resulted in a database of 114 NI trials to be summarised. Non-inferiority margins were defined for most trials with a median of 8% (IQR: 3–10%) used for risk differences (n = 58) and 0.35 (IQR: 0.26–0.43) standardised mean difference for continuous outcomes (n = 30). Justifications for the margin chosen (n = 62) were more commonly based on the clinical importance (49/62) and less commonly using statistical considerations (13/62). The most prevalent primary analysis population was solely on an intention-to-treat basis (49/114). The superiority of the treatment was well described but not always included as an outcome and only powered for in about a third of cases.

Conclusions
Aspects of NI trial design are well described but not always in line with current recommendations. Of particular note, is the absence of statistical considerations when setting the non-inferiority margin, which eliminates the ability to confirm indirect superiority over placebo for the new treatment. Additionally, despite suggestions that it can increase the type 1 error in NI trials, the use of the intention-to-treat alone is the most common analysis population.

Trial registration
Research on Research ID: 3171 (registration date: 31st May 2023).
Thermobifida fusca Cel6B moves bidirectionally while processively degrading cellulose
Authors: Johnson Madeline M. , DeChellis Antonio , Nemmaru Bhargava , Chundawat Shishir P. S. , Lang Matthew J. 
Published: December 2024

Abstract
Background
Cellulose, an abundant biopolymer, has great potential to be utilized as a renewable fuel feedstock through its enzymatic degradation into soluble sugars followed by sugar fermentation into liquid biofuels. However, crystalline cellulose is highly resistant to hydrolysis, thus industrial-scale production of cellulosic biofuels has been cost-prohibitive to date. Mechanistic studies of enzymes that break down cellulose, called cellulases, are necessary to improve and adapt such biocatalysts for implementation in biofuel production processes. Thermobifida fusca Cel6B (TfCel6B) is a promising candidate for industrial use due to its thermostability and insensitivity to pH changes. However, mechanistic studies probing TfCel6B hydrolytic activity have been limited to ensemble-scale measurements.

Results
We utilized optical tweezers to perform single-molecule, nanometer-scale measurements of enzyme displacement during cellulose hydrolysis by TfCel6B. Records featured forward motility on the order of 0.17 nm s−1 interrupted by backward motions and long pauses. Processive run lengths were on the order of 5 nm in both forward and backward directions. Motility records also showed rapid bidirectional displacements greater than 5 nm. Single-enzyme velocity and bulk ensemble activity were assayed on multiple crystalline cellulose allomorphs revealing that the degree of crystallinity and hydrogen bonding have disparate effects on the single-molecule level compared to the bulk scale. Additionally, we isolated and monitored the catalytic domain of TfCel6B and observed a reduction in velocity compared to the full-length enzyme that includes the carbohydrate-binding module. Applied force has little impact on enzyme velocity yet it readily facilitates dissociation from cellulose. Preliminary measurements at elevated temperatures indicated enzyme velocity strongly increases with temperature.

Conclusions
The unexpected motility patterns of TfCel6B are likely due to previously unknown mechanisms of processive cellulase motility implicating irregularities in cellulose substrate ultrastructure. While TfCel6B is processive, it has low motility at room temperature. Factors that most dramatically impact enzyme velocity are temperature and the presence of its native carbohydrate-binding module and linker. In contrast, substrate ultrastructure and applied force did not greatly impact velocity. These findings motivate further study of TfCel6B for its engineering and potential implementation in industrial processes.