bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost‐effectiveness analysis of continuous positive airway pressure treatment for obstructive sleep apnea in Singapore from a health system perspective
Authors: Meng Fanwen , Ang Gary Yee , Chang Ruth Rui Ying , Lee Chuen Peng , Tan Kelvin Bryan , Abisheganaden John Arputhan 
Published: September 2024

SummaryThis study assessed the cost‐effectiveness of continuous positive airway pressure treatment for obstructive sleep apnea in Singapore from a health system perspective. The analysis evaluated a 5‐year care pathway using a Markov model, considering per‐patient costs of treatment, health system cost savings of obstructive sleep apnea and attributed conditions, the effectiveness measured in disability‐adjusted life years with a discount rate of 3% and a weighted 5‐year continuous positive airway pressure adherence of 74.1% from Singapore studies. Per‐patient costs of treatment were from a large public hospital in Singapore. Efficacy of continuous positive airway pressure treatment, health system costs and disability‐adjusted life years were obtained from literature; costs are in US dollars. We conducted probabilistic sensitivity analysis, one‐way sensitivity analysis and what‐if analysis. Based on a willingness‐to‐pay threshold of US $50,000 per disability‐adjusted life year in USA, continuous positive airway pressure therapy was highly cost‐effective, with an incremental cost‐effectiveness ratio of $13,822 per disability‐adjusted life year averted. Compared with the annual total costs of $856 for patients with continuous positive airway pressure treatment diagnosed by an inpatient sleep study, the total costs for those diagnosed by a home sleep test were $625, resulting in a remarkable 27% reduction per patient per year. One‐way sensitivity analysis indicated that costs of treatment, effectiveness of continuous positive airway pressure treatment and adherence had a higher impact on the cost‐effectiveness of continuous positive airway pressure therapy. The what‐if analysis suggested that for continuous positive airway pressure treatment to be cost‐effective, adherence rate should be at least 16.1%. These findings provide valuable insights for policymakers in making informed decisions on funding diagnosis and continuous positive airway pressure therapy within Singapore's healthcare system.
PRL1 interacts with and stabilizes RPA2A to regulate carbon deprivation‐induced senescence in Arabidopsis
Authors: Meng Jingjing , Zhou Wenhui , Mao Xinhao , Lei Pei , An Xue , Xue Hui , Qi Yafei , Yu Fei , Liu Xiayan 
Published: September 2024

Summary

Leaf senescence is a developmental program regulated by both endogenous and environmental cues. Abiotic stresses such as nutrient deprivation can induce premature leaf senescence, which profoundly impacts plant growth and crop yield. However, the molecular mechanisms underlying stress‐induced senescence are not fully understood.

In this work, employing a carbon deprivation (C‐deprivation)‐induced senescence assay in Arabidopsis seedlings, we identified PLEIOTROPIC REGULATORY LOCUS 1 (PRL1), a component of the NineTeen Complex, as a negative regulator of C‐deprivation‐induced senescence.

Furthermore, we demonstrated that PRL1 directly interacts with the RPA2A subunit of the single‐stranded DNA‐binding Replication Protein A (RPA) complex. Consistently, the loss of RPA2A leads to premature senescence, while increased expression of RPA2A inhibits senescence. Moreover, overexpression of RPA2A reverses the accelerated senescence in prl1 mutants, and the interaction with PRL1 stabilizes RPA2A under C‐deprivation.

In summary, our findings reveal the involvement of the PRL1‐RPA2A functional module in C‐deprivation‐induced plant senescence.
Progressing beyond colonization strategies to understand arbuscular mycorrhizal fungal life history
Authors: Camenzind Tessa , Aguilar‐Trigueros Carlos A. , Heuck Meike K. , Maerowitz‐McMahan Solomon , Rillig Matthias C. , Cornwell Will K. , Powell Jeff R. 
Published: September 2024

SummaryKnowledge of differential life‐history strategies in arbuscular mycorrhizal (AM) fungi is relevant for understanding the ecology of this group and its potential role in sustainable agriculture and carbon sequestration. At present, AM fungal life‐history theories often focus on differential investment into intra‐ vs extraradical structures among AM fungal taxa, and its implications for plant benefits. With this Viewpoint we aim to expand these theories by integrating a mycocentric economics‐ and resource‐based life‐history framework. As in plants, AM fungal carbon and nutrient demands are stoichiometrically coupled, though uptake of these elements is spatially decoupled. Consequently, investment in morphological structures for carbon vs nutrient uptake is not in competition. We argue that understanding the ecology and evolution of AM fungal life‐history trade‐offs requires increased focus on variation among structures foraging for the same element, that is within intra‐ or extraradical structures (in our view a ‘horizontal’ axis), not just between them (‘vertical’ axis). Here, we elaborate on this argument and propose a range of plausible life‐history trade‐offs that could lead to the evolution of strategies in AM fungi, providing testable hypotheses and creating opportunities to explain AM fungal co‐existence, and the context‐dependent effects of AM fungi on plant growth and soil carbon dynamics.
Parameters to assess the necessity of adjuvant therapy for early‐stage oral squamous cell carcinoma
Authors: Lu Hsueh‐Ju , Chiu Yu‐Wei , Peng Chih‐Yu , Tseng Hsien‐Chun , Hsin Chung‐Han , Chuang Chun‐Yi , Fan Sheng , Huang Wei‐Shiou , Yang Shun‐Fa 
Published: September 2024

AbstractObjectiveOne‐third of head and neck squamous cell carcinomas are early‐stage oral cavity squamous cell carcinomas (OCSCC). Despite a high curative rate, 20% of early‐stage OCSCC patients do not achieve long‐term survival. This study evaluates the role of adjuvant therapy (ADJ) in delaying disease progression and prolonging survival.MethodsThis single‐institute retrospective cohort study enrolled 481 early‐stage OCSCC patients, 16% (78/481) of whom received ADJ. It was reported according to the STROBE guidelines. Cox proportional hazards regression and Kaplan–Meier survival curves were employed to identify suitable candidates for ADJ.ResultsThe 5‐year locoregional recurrence‐free survival (LR‐RFS) and overall survival rates were 73.2% and 84.9%, respectively. Positive margins and advanced depth of invasion (DOI) were independent predictors of LR‐RFS. For patients with positive margins, adjuvant chemoradiotherapy (CRT) was superior to adjuvant radiotherapy alone in improving LR‐RFS (hazard ratios for adjuvant CRT vs. none, 0.042; adjuvant radiotherapy alone vs. none, 0.702). Excluding positive margins, advanced DOI was the most critical factor in assessing the need for ADJ. Positive margins and advanced DOI were more appropriate criteria than EORTC 22931/RTOG 9501 for evaluating adjuvant CRT.ConclusionsAdjuvant CRT was indicated for patients with positive margins and advanced DOI to improve survival outcomes.
What clinicians could consider in providing group interventions for people with cognitive impairments: a scoping review
Authors: Liu Karen P.Y. , Conroy Mannix , Clark Annemieke , Lim David 
Published: September 2024

AbstractThis study identified evidence and considerations for allied health clinicians in providing group interventions for people with cognitive impairment. A scoping review was conducted by searching the MEDLINE (Ovid), CINHAL (EBSCOhost), Scopus (Elsevier), Embase (Ovid) and TROVE databases from 2016. Articles of any study design in which group interventions were performed by an allied health professional with participants with cognitive impairment were included. Data on physical, cognitive, psychological, and quality of life measures were extracted from the selected articles. Standardised mean changes (SMC) were calculated. Ten articles were included in the study. No article directly compared group interventions versus one‐to‐one interventions. The results of the meta‐analysis showed significant improvements after the intervention in the physical (SMC = 0.42, P = 0.013), cognitive (SMC = 0.43, P = 0.005), psychological (SMC = 0.14, P = 0.005), and quality of life domains (SMC = 0.28, P = 0.002). This review identified considerations for clinicians when developing group interventions for people with cognitive impairments, including specific participant criteria, increasing support, modifications to intervention difficulty, and environmental considerations. Group intervention for people with cognitive impairments demonstrated moderate effectiveness in improving physical and cognitive domains and a small effect in improving psychological and quality of life domains. Specific considerations are recommended when clinicians provide group interventions for people with cognitive impairments.
PAK1 inhibition with Romidepsin attenuates H‐reflex hyperexcitability after spinal cord injury
Authors: Kauer Sierra D. , Benson Curtis A. , Carrara Jennifer M. , Tarafder Afrin A. , Ibrahim Youssef H. , Estacion Maile A. , Waxman Stephen G. , Tan Andrew M. 
Published: September 2024

AbstractHyperreflexia associated with spasticity is a prevalent neurological condition characterized by excessive and exaggerated reflex responses to stimuli. Hyperreflexia can be caused by several diseases including multiple sclerosis, stroke and spinal cord injury (SCI). Although we have previously identified the contribution of the RAC1‐PAK1 pathway underlying spinal hyperreflexia with SCI‐induced spasticity, a feasible druggable target has not been validated. To assess the utility of targeting PAK1 to attenuate H‐reflex hyperexcitability, we administered Romidepsin, a clinically available PAK1 inhibitor, in Thy1‐YFP reporter mice. We performed longitudinal EMG studies with a study design that allowed us to assess pathological H‐reflex changes and drug intervention effects over time, before and after contusive SCI. As expected, our results show a significant loss of rate‐dependent depression – an indication of hyperreflexia and spasticity – 1 month following SCI as compared with baseline, uninjured controls (or before injury). Romidepsin treatment reduced signs of hyperreflexia in comparison with control cohorts and in pre‐ and post‐drug intervention in SCI animals. Neuroanatomical study further confirmed drug response, as romidepsin treatment also reduced the presence of SCI‐induced dendritic spine dysgenesis on α‐motor neurons. Taken together, our findings extend previous work demonstrating the utility of targeting PAK1 activity in SCI‐induced spasticity and support the novel use of romidepsin as an effective tool for managing spasticity.
imageKey points
PAK1 plays a role in contributing to the development of spinal cord injury (SCI)‐induced spasticity by contributing to dendritic spine dysgenesis.
In this study, we explored the preclinical utility of inhibiting PAK1 to reduce spasticity and dendritic spine dysgenesis in an SCI mouse model.
Romidepsin is a PAK1 inhibitor approved in the US in 2009 for the treatment of cutaneous T‐cell lymphoma.
Here we show that romidepsin treatment after SCI reduced SCI‐induced H‐reflex hyperexcitability and abnormal α‐motor neuron spine morphology.
This study provides compelling evidence that romidepsin may be a promising therapeutic approach for attenuating SCI‐induced spasticity.
Disordered eating behaviours during the menopausal transition: a systematic review
Authors: Vincent Coralie , Bodnaruc Alexandra M. , Prud'homme Denis , Guenette Jacob , Giroux Isabelle 
Published: September 2024

Disordered eating refers to a range of eating behaviours and attitudes towards weight and food that can negatively influence physical and psychosocial well-being. The menopausal transition could be a vulnerable period for disordered eating due to major hormonal fluctuations, menopausal symptoms, common body composition shifts, and an increased risk of psychological challenges. This systematic review aimed to summarize evidence on the associations between the menopausal transition and disordered eating. Records published before October 2023 were identified through MEDLINE, PsycINFO, Scopus, Embase, and CINAHL. Studies investigating associations between menopausal status, menopausal symptoms, or reproductive hormone levels, and disordered eating during the menopausal transition were sought. A total of 1301 non-duplicate records were screened, with 10 studies deemed eligible for inclusion. Most included studies used a cross-sectional design ( n = 9). Findings include potentially higher levels of binge eating during the perimenopausal stage, whereas restrictive eating behaviours appeared more common during postmenopause compared to premenopause. Both studies investigating menopausal symptoms found strong positive associations with disordered eating. Nonetheless, findings are equivocal with contrasting results and limited methodological quality across studies. Further research is needed to verify these findings and better assist health professionals in supporting healthy eating behaviours in menopausal women during this complex transition. (PROSPERO ID: CRD42021290736)
Immediate and Long‐Term Pull‐Out Bond Strength of 3D‐Printed Provisional Crowns
Authors: dos S. Siqueira Joyce R. C. , Rodriguez Rita M. M. , de C. Ramos Nathalia , Bottino Marco A. , Tribst João P. M. 
Published: September 2024

Background: Over the past decade, 3D printing technology has revolutionized various fields, including dentistry. Provisional restorations play a crucial role in prosthetic rehabilitation, necessitating the evaluation of their bond strength with different provisional cement agents.Aims: This study is aimed at assessing the immediate and long‐term bond strength of 3D‐printed dental crowns using three provisional cement agents.Materials and Methods: Provisional crowns (N = 36) were manufactured using 3D modeling software and cemented in dentin analogues (G10 Nema resin). After the crowns’ fabrication, they were randomly divided into three groups (n = 12) for cementation with Relyx Temp 3M ESPE, Provicol—VOCO, and Meron—VOCO. Tensile strength tests were conducted using a universal testing machine, with half of the specimens subjected to 2000 thermal cycles before testing. Finite element analysis was employed to assess tensile stress distribution.Results: Statistical analysis (two‐way ANOVA and Tukey’s test at a 95% confidence level) revealed significant effects of cement type (p = 0.006) and thermal aging (p = 0.001) on bond strength. Glass ionomer cement exhibited the highest immediate resistance, while all types of cement were adversely affected by thermal aging, resulting in decreased bond strength.Conclusion: Thermal aging significantly alters the properties of 3D printing resin and affects the bond strength of provisional cement with 3D‐printed crowns. Despite the adverse effects of thermal aging, glass ionomer cement demonstrated the highest immediate resistance. Clinicians should carefully consider these findings when selecting provisional cements for 3D‐printed crowns.
FDA Approval Summary: Enfortumab Vedotin plus Pembrolizumab for Locally Advanced or Metastatic Urothelial Carcinoma
Authors: Brave Michael H. , Maguire William F. , Weinstock Chana , Zhang Hui , Gao Xin , Li Fang , Yu Jingyu , Fu Wentao , Zhao Hong , Pierce William F. , Chang Elaine , Dinin Jeannette , Fiero Mallorie H. , Rahman Nam Atiqur , Tang Shenghui , Pazdur Richard , Kluetz Paul G. , Amiri-Kordestani Laleh , Suzman Daniel L. 
Published: September 2024

Abstract
On December 15, 2023, the FDA granted traditional approval to enfortumab vedotin-ejfv plus pembrolizumab (EV + Pembro) for patients with locally advanced or metastatic urothelial carcinoma (la/mUC). Substantial evidence of effectiveness was obtained from EV-302/KEYNOTE-A39 (NCT04223856), an open-label, randomized trial evaluating EV + Pembro versus cisplatin or carboplatin plus gemcitabine (Plat + Gem) in patients with previously untreated la/mUC. A total of 886 patients were randomized (1:1) to receive EV 1.25 mg/kg intravenously on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity plus Pembro 200 mg intravenously on day 1 of each 21-day cycle for up to 35 cycles or Plat + Gem for up to 6 cycles. Dual primary endpoints were progression-free survival determined by blinded independent central review and overall survival. The median progression-free survival was 12.5 months [95% confidence interval (CI), 10.4–16.6] in the EV + Pembro arm and 6.3 months (95% CI, 6.2–6.5) in the Plat + Gem arm [HR, 0.450 (95% CI, 0.377–0.538); P value &lt; 0.0001]. The median overall survival was 31.5 months (95% CI, 25.4–not estimable) in the EV + Pembro arm and 16.1 months (95% CI, 13.9–18.3) in the Plat + Gem arm [HR, 0.468 (95% CI, 0.376–0.582); P value &lt; 0.0001]. The safety profile of EV + Pembro was similar to that observed in EV-103/KEYNOTE-869 in cisplatin-ineligible patients with la/mUC. This article summarizes the data and the FDA thought process supporting traditional approval of EV + Pembro, as well as additional exploratory analyses conducted by the FDA.
Risk of Stroke or Systemic Embolism According to Baseline Frequency and Duration of Subclinical Atrial Fibrillation: Insights From the ARTESiA Trial
Authors: McIntyre William F. , Benz Alexander P. , Healey Jeff S. , Connolly Stuart J. , Yang Mu , Lee Shun Fu , Field Thalia S. , Alings Marco , Benezet-Mazuecos J. , Boriani Giuseppe , Nielsen J. Cosedis , Gold Michael R. , Pergolini Francesco , Glotzer Taya V. , Granger Christopher B. , Lopes Renato D. 
Published: September 2024

BACKGROUND:
In the ARTESiA trial (Apixaban for the Reduction of Thromboembolism in Patients With Device-Detected Subclinical Atrial Fibrillation), apixaban, compared with aspirin, reduced stroke or systemic embolism in patients with device-detected subclinical atrial fibrillation (SCAF). Clinical guidelines recommend considering SCAF episode duration when deciding whether to prescribe oral anticoagulation for this population.

METHODS:

We performed a retrospective cohort study in ARTESiA. Using Cox regression adjusted for CHA
2
DS
2
-VASc score and treatment allocation (apixaban or aspirin), we assessed frequency of SCAF episodes and duration of the longest SCAF episode in the 6 months before randomization as predictors of stroke risk and of apixaban treatment effect.

RESULTS:

Among 3986 patients with complete baseline SCAF data, 703 (17.6%) had no SCAF episode ≥6 minutes in the 6 months before enrollment. Among 3283 patients (82.4%) with ≥1 episode of SCAF ≥6 minutes in the 6 months before enrollment, 2542 (77.4%) had up to 5 episodes, and 741 (22.6%) had ≥6 episodes. The longest episode lasted <1 hour in 1030 patients (31.4%), 1 to <6 hours in 1421 patients (43.3%), and >6 hours in 832 patients (25.3%). Higher baseline SCAF frequency was not associated with increased risk of stroke or systemic embolism: 1.1% for 1 to 5 episodes versus 1.2%/patient-year for ≥6 episodes (adjusted hazard ratio, 0.89 [95% CI, 0.59–1.34]). In an exploratory analysis, patients with previous SCAF but no episode ≥6 minutes in the 6 months before enrollment had a lower risk of stroke or systemic embolism than patients with at least one episode during that period (0.5% versus 1.1%/patient-year; adjusted hazard ratio, 0.48 [95% CI, 0.27–0.85]). The frequency of SCAF did not modify the reduction in stroke or systemic embolism with apixaban (
P
interaction
=0.1). The duration of the longest SCAF episode in the 6 months before enrollment was not associated with the risk of stroke or systemic embolism during follow-up (<1 hour: 1.0%/patient-year [reference]; 1–6 hours: 1.2%/patient-year [adjusted hazard ratio, 1.27 (95% CI, 0.85–1.90)]; >6 hours: 1.0%/patient-year [adjusted hazard ratio, 1.02 (95% CI, 0.63–1.66)]). SCAF duration did not modify the reduction in stroke or systemic embolism with apixaban (
P
trend
=0.1).

CONCLUSIONS:
In ARTESiA, baseline SCAF frequency and longest episode duration were not associated with risk of stroke or systemic embolism and did not modify the effect of apixaban on reduction of stroke or systemic embolism.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01938248.
SEEP: Training Dynamics Grounds Latent Representation Search for Mitigating Backdoor Poisoning Attacks
Authors: He Xuanli , Xu Qiongkai , Wang Jun , Rubinstein Benjamin I. P. , Cohn Trevor 
Published: September 2024

Abstract
Modern NLP models are often trained on public datasets drawn from diverse sources, rendering them vulnerable to data poisoning attacks. These attacks can manipulate the model’s behavior in ways engineered by the attacker. One such tactic involves the implantation of backdoors, achieved by poisoning specific training instances with a textual trigger and a target class label. Several strategies have been proposed to mitigate the risks associated with backdoor attacks by identifying and removing suspected poisoned examples. However, we observe that these strategies fail to offer effective protection against several advanced backdoor attacks. To remedy this deficiency, we propose a novel defensive mechanism that first exploits training dynamics to identify poisoned samples with high precision, followed by a label propagation step to improve recall and thus remove the majority of poisoned instances. Compared with recent advanced defense methods, our method considerably reduces the success rates of several backdoor attacks while maintaining high classification accuracy on clean test sets.
Do LLMs Exhibit Human-like Response Biases? A Case Study in Survey Design
Authors: Tjuatja Lindia , Chen Valerie , Wu Tongshuang , Talwalkwar Ameet , Neubig Graham 
Published: September 2024

Abstract
One widely cited barrier to the adoption of LLMs as proxies for humans in subjective tasks is their sensitivity to prompt wording—but interestingly, humans also display sensitivities to instruction changes in the form of response biases. We investigate the extent to which LLMs reflect human response biases, if at all. We look to survey design, where human response biases caused by changes in the wordings of “prompts” have been extensively explored in social psychology literature. Drawing from these works, we design a dataset and framework to evaluate whether LLMs exhibit human-like response biases in survey questionnaires. Our comprehensive evaluation of nine models shows that popular open and commercial LLMs generally fail to reflect human-like behavior, particularly in models that have undergone RLHF. Furthermore, even if a model shows a significant change in the same direction as humans, we find that they are sensitive to perturbations that do not elicit significant changes in humans. These results highlight the pitfalls of using LLMs as human proxies, and underscore the need for finer-grained characterizations of model behavior.1
The Establishment of Science-Policy Interfaces for the Global Plastics Treaty: Reflections on Small Island Developing States’ Perspectives
Authors: Stöfen-O’Brien Aleke , Graham Roxanne 
Published: September 2024

Abstract
On 2 March 2022, the United Nations Environment Assembly of the United Nations Environment Programme (UNEP) requested the Executive Director of UNEP to convene an international negotiating committee (INC) charged with moving towards the negotiation of an international legally binding instrument on plastics by 2024. Due to the complex environmental, societal, and human health impacts of plastic pollution, the work undertaken ought to consider the best available science, traditional knowledge, and local knowledge systems in the context of scientific and socioeconomic assessments. This article explores the importance of specifically considering the challenges faced by small island developing States in the development of a Science-Policy Interface (SPI) as is envisaged by the INC. It is argued that in the creation of a global SPI on plastic pollution, a vision for the co-creation and co-design of traditional and local stakeholders’ knowledge must be integrated from the beginning.