bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-inflammatory effects of cyclodextrin nanoparticles enable macrophage repolarization and reduce inflammation
Authors: Brettner Felix E. B. , Gier Stefanie , Haessler Annika , Schreiner Jonas , Vogel-Kindgen Sarah , Windbergs Maike 
Published: December 2024

AbstractInflammation plays a critical role in the pathophysiology of many diseases, and dysregulation of the involved signaling cascades often culminates in uncontrollable disease progression and, ultimately, chronic manifestation. Addressing these disorders requires balancing inflammation control while preserving essential immune functions. Cyclodextrins (CDs), particularly β-CD, have gained attention as biocompatible biomaterials with intrinsic anti-inflammatory properties, and chemical modification of their backbone offers a promising strategy to enhance their physicochemical properties, adaptability, and therapeutic potential. This study evaluated and characterized the immunomodulatory effects of amphiphilic CD derivatives, which self-assemble into nanoparticles, compared to soluble parent β-CD. In a human macrophage model, CD nanoparticles demonstrated superior anti-inflammatory activity, with derivative-specific effects tied to their physicochemical properties, surpassing the soluble β-CD control. Alongside the downregulation of key pro-inflammatory markers, significant reductions in inflammasome activation and changes in lipid profiles were observed. The findings of this study underscore the potential of cyclodextrin-based nanoparticles as versatile biomaterials for treating the complex pathophysiology of various acute and chronic inflammation-associated disorders.
Built-in selection or confounder bias? Dynamic Landmarking in matched propensity score analyses
Authors: Strobel Alexandra , Wienke Andreas , Gummert Jan , Bleiziffer Sabine , Kuss Oliver 
Published: December 2024

Abstract
Background
Propensity score matching has become a popular method for estimating causal treatment effects in non-randomized studies. However, for time-to-event outcomes, the estimation of hazard ratios based on propensity scores can be challenging if omitted or unobserved covariates are present. Not accounting for such covariates could lead to treatment estimates, differing from the estimate of interest. However, researchers often do not know whether (and, if so, which) covariates will cause this divergence.

Methods
To address this issue, we extended a previously described method, Dynamic Landmarking, which was originally developed for randomized trials. The method is based on successively deletion of sorted observations and gradually fitting univariable Cox models. In addition, the balance of observed, but omitted covariates can be measured by the sum of squared z-differences.

Results
By simulation we show, that Dynamic Landmarking provides a good visual tool for detecting and distinguishing treatment effect estimates underlying built-in selection or confounding bias. We illustrate the approach with a data set from cardiac surgery and provide some recommendations on how to use and interpret Dynamic Landmarking in propensity score matched studies.

Conclusion
Dynamic Landmarking is a useful post-hoc diagnosis tool for visualizing whether an estimated hazard ratio could be distorted by confounding or built-in selection bias.
The analysis and reporting of multiple outcomes in mental health trials: a methodological systematic review
Authors: Stringer Dominic , Payne Mollie , Carter Ben , Emsley Richard 
Published: December 2024

Abstract
Background
The choice of a single primary outcome in randomised trials can be difficult, especially in mental health where interventions may be complex and target several outcomes simultaneously. We carried out a systematic review to assess the quality of the analysis and reporting of multiple outcomes in mental health RCTs, comparing approaches with current CONSORT and other regulatory guidance.

Methods
The review included all late-stage mental health trials published between 1st January 2019 to 31st December 2020 in 9 leading medical and mental health journals. Pilot and feasibility trials, non-randomised trials, and early phase trials were excluded. The total number of primary, secondary and other outcomes was recorded, as was any strategy used to incorporate multiple primary outcomes in the primary analysis.

Results
There were 147 included mental health trials. Most trials (101/147) followed CONSORT guidance by specifying a single primary outcome with other outcomes defined as secondary and analysed in separate statistical analyses, although a minority (10/147) did not specify any outcomes as primary. Where multiple primary outcomes were specified (33/147), most (26/33) did not correct for multiplicity, contradicting regulatory guidance. The median number of clinical outcomes reported across studies was 8 (IQR 5–11 ).

Conclusions
Most trials are correctly following CONSORT guidance. However, there was little consideration given to multiplicity or correlation between outcomes even where multiple primary outcomes were stated. Trials should correct for multiplicity when multiple primary outcomes are specified or describe some other strategy to address the multiplicity. Overall, very few mental health trials are taking advantage of multiple outcome strategies in the primary analysis, especially more complex strategies such as multivariate modelling. More work is required to show these exist, aid interpretation, increase efficiency and are easily implemented.

Registration
Our systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 11th January 2023 (CRD42023382274).
Influence of an enhanced recovery programme on clinical outcomes and health-related quality of life after pancreaticoduodenectomy ad modum Whipple – an explorative and comparative single-centre study
Authors: Andersson Thomas , Engström My , Wennerblom Johanna , Gyllensten Hanna , Bjerså Kristofer 
Published: December 2024

Abstract
Background
The introduction of enhanced recovery programmes (ERP) in pancreatic surgery has significantly improved clinical outcomes by decreasing the length of hospital stay, cost and complications without increasing readmissions and reoperations. To complement evidence on these outcomes, there is a need to explore patients’ perspectives of a structured ERP. Therefore, this study aimed to explore the health-related quality of life (HRQoL) of patients before and after implementing ERP in pancreaticoduodenectomy ad modum Whipple (PD) at a regional surgical centre.

Method
This was an explorative and comparative single-centre study in Sweden. A prospective cohort receiving ERP was included between October 2019 and December 2022 (n = 73) and was compared with a retrospective pre-ERP cohort between October 2011 and December 2013 (n = 65). EQ-5D, the European Organization for Research and Treatment of Cancer (EORCT) Quality of Life Questionnaire Cancer 30 items (QOL-C30), and EORCT Quality of Life Questionnaire pancreatic cancer module (QOL-PAN26) were collected preoperatively and at three and six months postoperatively. Demographic and clinical variables were collected from patient charts. Complications were expressed using the Clavien-Dindo Classification and the Comprehensive Complications Index (CCI).

Results
There were no significant differences in general health, cancer- or disease-specific HRQoL between the pre-ERP and ERP cohorts. Length of stay was significantly shorter in the ERP cohort (16 vs. 11 days; p < 0.001). There was no significant difference in CCI.

Conclusion
No significant differences were found in the HRQoL of patients who participated in an ERP compared to those who did not. However, a significant decrease in LoS was found when ERP was applied.

Trial registration
Not applicable.
Prognostic factors in patients with gastrointestinal perforation under the acute care surgery model : a retrospective cohort study
Authors: Sung Kiyoung , Hwang Sanguk , Lee Jaeheon , Cho Jinbeom 
Published: December 2024

Abstract
Background
Gastrointestinal perforation (GIP) is a life-threatening condition that necessitates immediate surgical intervention. This study aims to identify prognostic factors in patients with GIP treated within a standardized acute care surgery (ACS) framework.

Materials and methods
This single center retrospective cohort study analyzed patients diagnosed with GIP who underwent emergent surgery and were admitted to the intensive care unit between January 2013 and March 2023.

Results
Among 354 patients, the mortality was 11%, and 38% of survivors experienced significant complications (Clavien-Dindo class III or higher). Independent prognostic factors for mortality included initial sequential organ failure assessment (SOFA) scores (at the time of admission or ACS activation), postoperative SOFA (p-SOFA) scores, and postoperative body temperatures. For morbidity, independent predictors were the extent of peritonitis, the open surgery, postoperative albumin levels, and p-SOFA scores. These factors showed significant predictive accuracy for patient outcomes, as evidenced by the area under the receiver operating characteristic curve. The Random Forest model identified p-SOFA scores and postoperative albumin levels as the most significant predictors for both survival and complications, with feature importances of 40.46% and 36.61% for survival, and 39.97% and 37.28% for complications, respectively. Postoperative body temperature also played a moderately important role, contributing 14.63% to mortality and 15.9% to morbidity predictions. Patients with a p-SOFA score ≥ 7, postoperative albumin ≤ 2, and body temperature ≤ 36 °C, as well as those with a p-SOFA score ≥ 10, albumin ≤ 2.9, and body temperature ≤ 36 °C, had a 100% mortality rate. These factors are critical indicators for predicting patient outcomes.

Conclusion
It is crucial to establish a system that ensures rapid preoperative work-up, accurate surgical intervention, and evidence-based postoperative critical care. Implementing such a system and assessing patient outcomes after surgery using the identified factors could provide a more detailed evaluation.
Laparoscopic-assisted versus ultrasound-guided transversus abdominis plane block for laparoscopic cholecystectomy: a systematic review and meta-analysis
Authors: Ghani Sundus Abdul , Hussain Hassan Ul , Wahid Maryam Abdul , Majeed Neha , Burney Sheeba , Tanveer Areesha , Asghar Muhammad Sohaib 
Published: December 2024

Abstract
Background
Laparoscopic-assisted (LTAP) and ultrasound-guided (UTAP) transversus abdominis plane (TAP) blocks are widely used for postoperative analgesia in laparoscopic cholecystectomy (LC), yet their comparative effectiveness remains unclear. The aim of this meta-analysis was to systematically evaluate and compare postoperative outcomes of LTAP and UTAP in LC.

Materials and methodology
A comprehensive literature search of five electronic databases was conducted from the inception of the paper till 2 June 2024 following PRISMA guidelines. Eligibility criteria included: (a) randomized controlled trials (RCTs); (b) adult patients (≥ 18 years) undergoing elective LC; (c) intervention group undergoing LTAP; (d) control group receiving UTAP; (e) outcomes: postoperative pain intensity using VAS score; time to first analgesic need; postoperative morphine consumption; postoperative nausea vomiting (PONV); time to first bowel evacuation; time to first flatus. Mendeley Desktop 1.19.8 was used for article retrieval and for the removal of duplicates. Risk of bias was assessed using the Cochrane Risk of Bias Tool, and statistical analysis was performed using Review Manager, applying a random-effects model. Forest plots represented combined effects of Risk Ratios (RRs) for dichotomous outcomes and weighted mean differences (WMDs) for continuous outcomes with a 95% confidence interval (CI). P-value ≤ 0.05 was considered statistically significant and Higgin’s I² test was employed to assess heterogeneity.

Results
Seven RCTs in total involving 603 patients were included in the analysis, with 236 patients in the LTAP group and 232 in the UTAP group. No statistically significant differences observed between LTAP and UTAP in postoperative pain intensity at 6, 12, and 24 h, time to first analgesic need, postoperative morphine consumption, PONV, time to first stools, and time to first flatus, initially. Sensitivity analysis revealed a significant reduction in 6-hour postoperative pain in the LTAP group (WMD = 0.39; 95% CI = 0.10,0.67; P = 0.008; I² = 0%), but no significant differences were found in later time points (12 h: WMD = 0.12; 95% CI = -0.17,0.40; P = 0.42; I² = 0%; 24 h: WMD = -0.04; 95% CI = -0.26, 0.18; P = 0.73; I² = 5%) or in other outcomes. Moderate levels of heterogeneity and an overall low risk of bias in quality assessment were observed among the studies.

Conclusion
Our meta-analysis indicated no clear advantage of LTAP over UTAP in managing postoperative pain and related outcomes in LC. Although LTAP may offer logistical benefits by reducing the need for equipment and personnel, further large-scale RCTs focusing on procedure-specific outcomes are needed to establish definitive conclusions.
The potential of AB-free kava in enabling tobacco cessation via management of abstinence-related stress and insomnia: study protocol for a randomized clinical trial
Authors: Xing Chengguo , Malaty John , Malham Melissa Bou , Orlando Frank A. , Lynch Allison , Huo Zhiguang , François Magda , Firpi-Morell Roberto , Fisher Carla L. , Christou Demetra D. , Salloum Ramzi G. 
Published: December 2024

Abstract
Background
As the primary cause of various preventable illnesses, smoking results in approximately five million premature deaths each year in the US and a multitude of adults living with serious illness. The majority of smokers know the health risks associated with smoking and intend to quit. However, quitting is very difficult partly because of insomnia and stress associated with it. Current tobacco cessation medications are not designed to address these problems, which may have contributed to their limited success in enabling cessation. Novel interventions are thus urgently needed to enhance success rates in tobacco cessation. Based on its historical usage and our preliminary data, kava is such a candidate. Kava, customarily enjoyed by South Pacific Islanders, is known for its relaxing effects, stress-relieving properties, and ability to enhance sleep. In the US, it is marketed and distributed as a dietary supplement due to its recognized calming properties. A pilot trial was performed among active smokers with a one-week ingestion of a kava supplement. The results for the first-time revealed kava’s potential in enabling tobacco cessation with effects on a panel of biological signatures. The primary goal of this trial is to replicate kava’s effects on the biological signatures of tobacco use, stress, and sleep in addition to its compliance and safety among those who smoke.

Methods
A double-blind randomized placebo controlled two-arm trial will enroll 76 smokers with intention to quit, who will consume AB-free kava at a dietary supplement dose or placebo, 3 times per day for 4 weeks with two follow-ups.

Discussion
The study will (1) monitor the adherence to and safety of AB-free kava consumption among smokers and evaluate changes in smoking habits, and (2) quantify a panel of non-invasive translatable biomarkers to objectively evaluate AB-free kava’s holistic effects on biological signatures associated with tobacco use, stress, and sleep. We hypothesize that AB-free kava is a novel and promising intervention to facilitate tobacco cessation via its holistic effects associated with managing stress and insomnia during abstinence. If the results from this study support our hypothesis, kava could emerge as an affordable and accessible dietary supplement candidate for tobacco cessation.

Trial Registration
registered on 04/14/2023 in ClinicalTrials.gov with the identifier NCT05814055.
The conflict between oral health and patient autonomy in dentistry: a scoping review
Authors: Kovács Szilárd Dávid , Irawan Anggi Septia , Zörgő Szilvia , Kovács József 
Published: December 2024

Abstract
Background
Respect for patient autonomy, the principle that patients are capable to make informed decisions about medical interventions, is fundamental in present-day medicine. However, if a patient’s request is medically not indicated, the practitioner faces an ethical dilemma represented by the conflict of the principles of patient autonomy, beneficence, and maleficence. Adjacent to topics such as medical assistance in dying and healthy limb amputation, this ethical dilemma also manifests in the care of the maxillofacial region (the oral cavity and its surroundings), an area crucial to esthetic appearance, but also to everyday functions including mastication, speech, and facial expression, all of which are related to well-being. Our aim was to explore the manifestations and resolutions of the conflict between oral health and patient autonomy in relevant literature in order to contribute to the discourse of ethical challenges concerning patient autonomy, beneficence, and nonmaleficence.

Methods
We screened all journal articles discussing the researched ethical dilemma obtained from three databases. Two researchers developed a hierarchical coding scheme, where the parent and grandparent codes were designated deductively as: Case (situations involving the researched ethical dilemma), Judgement (decisions made in the ethical dilemma), and Principle (ideas, rules, propositions explaining the judgements); child codes were developed inductively. After coding the sources, we utilized thematic analysis to construct code constellations.

Results
Most themes identified in our sources advocated for the practitioner to choose the alternative that benefits the patient from a medical perspective, although no theme excluded the consideration of patient autonomy. Instances where respect for patient autonomy was encouraged concerned oral preventive care or when the requested intervention was expected to have an insignificant impact on oral health.

Conclusions
Ethical conflicts concerning patient autonomy, beneficence, and nonmaleficence have a marked presence in oral care. These conflicts arise through the issue of body modification, evident in cosmetic dentistry and requests for tooth extraction. Our sources generally support the argumentation for beneficence, despite the rise of cosmetic procedures in dentistry.
Assessing the comparative effects of interventions in COPD: a tutorial on network meta-analysis for clinicians
Authors: Haeussler Katrin , Ismaila Afisi S. , Malmenäs Mia , Noorduyn Stephen G. , Green Nathan , Compton Chris , Thabane Lehana , Vogelmeier Claus F. , Halpin David M. G. 
Published: December 2024

AbstractTo optimize patient outcomes, healthcare decisions should be based on the most up-to-date high-quality evidence. Randomized controlled trials (RCTs) are vital for demonstrating the efficacy of interventions; however, information on how an intervention compares to already available treatments and/or fits into treatment algorithms is sometimes limited. Although different therapeutic classes are available for the treatment of chronic obstructive pulmonary disease (COPD), assessing the relative efficacy of these treatments is challenging. Synthesizing evidence from multiple RCTs via meta-analysis can help provide a comprehensive assessment of all available evidence and a “global summary” of findings. Pairwise meta-analysis is a well-established method that can be used if two treatments have previously been examined in head-to-head clinical trials. However, for some comparisons, no head-to-head studies are available, for example the efficacy of single-inhaler triple therapies for the treatment of COPD. In such cases, network meta-analysis (NMA) can be used, to indirectly compare treatments by assessing their effects relative to a common comparator using data from multiple studies. However, incorrect choice or application of methods can hinder interpretation of findings or lead to invalid summary estimates. As such, the use of the GRADE reporting framework is an essential step to assess the certainty of the evidence. With an increasing reliance on NMAs to inform clinical decisions, it is now particularly important that healthcare professionals understand the appropriate usage of different methods of NMA and critically appraise published evidence when informing their clinical decisions. This review provides an overview of NMA as a method for evidence synthesis within the field of COPD pharmacotherapy. We discuss key considerations when conducting an NMA and interpreting NMA outputs, and provide guidance on the most appropriate methodology for the data available and potential implications of the incorrect application of methods. We conclude with a simple illustrative example of NMA methodologies using simulated data, demonstrating that when applied correctly, the outcome of the analysis should be similar regardless of the methodology chosen.
Environmental constraints for improving motor flexibility during obstacle crossing in older adults
Authors: Suda Yuki , Higuchi Takahiro 
Published: December 2024

Abstract
Background
An age-related decline in motor flexibility, which is the ability to synergistically control the degrees of freedom of the body to ensure stable performance of a task, is a factor that contributes to falls. We investigated whether providing environmental constraints to increase the movement repertoire (i.e., the motor solution that works to achieve one’s goal), in combination with aiming at precise control of the performance, would be effective for improving motor flexibility, and whether the effect on the leading limb would extend to the trailing limb.

Methods
Fifteen older adults (75.1 ± 6.2 years and 14 younger adults (34.6 ± 5.0 years) performed under three walking conditions: walking normally and crossing the obstacle (normal), walking and crossing the obstacle with constraints of foot placement after stepping over it (constrained), and walking and crossing the obstacle with constraints as in the constrained condition, in addition to aiming for maintaining a constant clearance height at the moment of obstacle crossing (precision). An uncontrolled manifold analysis was used to quantify motor flexibility as the synergy index. The foot height at the moment of obstacle crossing was used as the performance variable and seven segmental angles were used as the elemental variables. A higher synergy index indicates greater motor flexibility.

Results
For the leading limb, the synergy index was significantly higher under the precision condition than those under the other conditions. This suggests that not only providing environmental constraints but also keeping constant the performance variable is critical to improving motor flexibility. Moreover, the effects of an increase in the synergy index in the leading limb extended to the trailing limb.

Conclusions
Providing environmental constraints to increase the movement repertoire while also aiming for precision in the performance variable was an effective method of improving motor flexibility during obstacle crossing for older adults.