bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of the estimand framework in the analysis of patient-reported outcomes in single-arm trials: a case study in oncology
Authors: Thomassen Doranne , Roychoudhury Satrajit , Amdal Cecilie Delphin , Reynders Dries , Musoro Jammbe Z. , Sauerbrei Willi , Goetghebeur Els , le Cessie Saskia ,   SISAQOL-IMI Work Package 3, Kamalakar Rajesh , Sail Kavita , Basch Ethan , Reijneveld Jaap , Keating Karen , Su Yun , Alanya Ahu , Rumpold Gerhard , Sasseville Maxime , Black Jennifer , Molenberghs Geert , Rantell Khadija , Schlichting Michael , Regnault Antoine , Ness David , ten Seldam Silene , Reksten Tove Ragna , Schiel Anja , Falk Ragnhild Sorum , Campbell Alicyn , Cappelleri Joseph C. , Russell-Smith Alexander , Calvert Melanie , Cruz Rivera Samantha , Aiyegbusi Olalekan Lee , Liu Limin , Van Lancker Kelly , Rutherford Claudia , Bhatnagar Vishal , Chen Ting-Yu , Fiero Mallorie , Kluetz Paul 
Published: November 2024

Abstract
Background
Patient-reported outcomes (PROs) play an increasing role in the evaluation of oncology treatments. At the same time, single-arm trials are commonly included in regulatory approval submissions. Because of the high risk of biases, results from single-arm trials require careful interpretation. This benefits from a clearly defined estimand, or target of estimation. In this case study, we demonstrated how the ICH E9 (R1) estimand framework can be implemented in SATs with PRO endpoints.

Methods
For the global quality of life outcome in a real single-arm lung cancer trial, a range of possible estimands was defined. We focused on the choice of the variable of interest and strategies to deal with intercurrent events (death, treatment discontinuation and disease progression). Statistical methods were described for each estimand and the corresponding results on the trial data were shown.

Results
Each intercurrent event handling strategy resulted in its own estimated mean global quality of life over time, with a specific interpretation, suitable for a corresponding clinical research aim. In the setting of this case study, a ‘while alive’ strategy for death and a ‘treatment policy’ strategy for non-terminal intercurrent events were deemed aligned with a descriptive research aim to inform clinicians and patients about expected quality of life after the start of treatment.

Conclusions
The results show that decisions made in the estimand framework are not trivial. Trial results and their interpretation strongly depend on the chosen estimand. The estimand framework provides a structure to match a research question with a clear target of estimation, supporting specific clinical decisions. Adherence to this framework can help improve the quality of data collection, analysis and reporting of PROs in SATs, impacting decision making in clinical practice.
Exercise-based telerehabilitation in chronic low back pain – a scoping review
Authors: Sivertsson Jenny , Sernert Ninni , Åhlund Kristina 
Published: November 2024

Abstract
Background
Low back pain is a major global health problem. Physiotherapy involving exercises is considered first-line treatment. In recent years digital tools including telerehabilitation have increased, but the interventions are diverse. The aim of this study was to map how telerehabilitation approaches are used in studies evaluating exercise-based rehabilitation in patients with chronic low back pain.

Methods
A systematic literature search was conducted in PubMed, Cinahl and Cochrane Central between January 2017 and January 2024 for original studies on adults, 18 years or older, with chronic low back pain who received exercise-based telerehabilitation.

Results
The database search resulted in 1019 articles. Out of 37 full texts that were screened 28 articles were included in the analysis. The included studies showed a wide variation regarding technological solutions, interventions and outcome measures. The exercise-based telerehabilitation was usually delivered asynchronously via a smartphone application. The most common clinical outcome measure was pain and disability/physical function. Telerehabilitation compared to conventional exercise therapy showed similar clinical improvements.

Conclusions
This scoping review confirms the heterogeneity within this research area but also contributes by mapping and demonstrating some knowledge gaps in the literature. Further research focusing on synchronous and group interventions are needed. The new technologies described in the included studies provide added value through functional improvements and task redesign.

Trial registration
OSF https//doi.org/10.17605/OSF.IO/EMKCG.
Regenerative endodontic therapy in immature teeth using photobiomodulation and photodynamic therapy; a histomorphological study in canine model
Authors: Fouad Eman M. , Fawzy Mervat I. , Saafan Ali M. , Elhousiny Maha A. 
Published: November 2024

Abstract
Background
Regenerative endodontic therapy (RET) is still coming up short to demonstrate histological evidence for true regeneration with clinically feasible protocol of cell homing in single visit approach.

Aim
The aim of the present study is to evaluate the regenerative potential of photobiomodulation (PBM) on RET in immature roots when photodynamic therapy (PDT) protocol is implemented for root canal disinfection in canine model.

Materials and methods
Seventy-two root canals were recruited, with sixty assigned to experimental groups and twelve to positive and negative controls. Following the induction of pulp necrosis and apical periodontitis, the roots were divided into two experimental groups: Group I received RET followed by PBM (seven sessions with an 808 nm diode laser at 300 mW for 90 s), and Group II received RET without PBM. Follow-ups were conducted at 1, 2, and 3 months (subgroups A, B, and C respectively). Qualitative and quantitative assessment was carried out histologically. All data were statistically analyzed with the Mann-Whitney U test and Bonferroni’s adjustment, as well as Chi square test.

Results
The newly formed hard tissue highly resembled true dentine where the dentinal tubules looked well organized lined by poly layers palisading pattern of rounded odontoblast-like cells with cytoplasmic processes extending through the predentine layer. GI exhibited statistically significantly higher scores of vital tissue infiltration and hard tissue deposition in subgroups A and B (P ≤ 0.05). The inflammatory cells scores were significantly lower in GI than in GII at all time intervals. However, no significance could be detected regarding apical closure.

Conclusion
The disinfection protocol of PDT and subsequent irradiation with low power laser in PBM protocol pose a promising potential for regenerative endodontics in immature teeth.
Effect of saliva on accuracy of digital dental implant transfer using two different materials of intraoral scan bodies with different exposed lengths
Authors: Tawfik Mohamed Hesham Ahmed , EL Torky Ibrahim Ramadan , El Sheikh Mohamed Maamoun 
Published: November 2024

Abstract
Background
The accuracy of digital implant transfer is currently under investigation in relation to the effect of saliva, scan body material, and exposed length.

Methods
Six completely edentulous casts with four implant fixtures were fabricated. The four implant fixtures in each cast were placed below the crest of the ridge of the casts by 1.5 mm. The four implant fixtures were alternately attached to four implant scan bodies (PEEK) Group (I) and (TITANIUM) Group (II). For each cast, two flexible polyurethane layers with varying thicknesses were fabricated and molded on the six 3D printed identical casts after the placement of the implant fixtures in each cast for the soft tissue moulage in the cast. The six casts were alternately covered with a 2 mm and 4 mm thick layer. The six reference casts were recorded using a coordinate measurement machine (CMM) and subsequently scanned with an Intraoral scanner (MEDIT I 700). The scanning was conducted under both dry and wet conditions, with artificial saliva applied. The scanning platform consisted of two transparent acrylic boxes, and the process followed standardized scanning conditions using a digital lux meter (n = 48). The mean difference and standard deviation values (± SD) between the implant scan bodies measured on the reference and experimental scans were calculated using the inspection software program (Medit design). Data were fed to the computer and analyzed using IBM SPSS software package version 20.0. (Armonk, NY: IBM Corp). The Kolmogorov-Smirnov test and Shapiro-Wilk test were used to verify the normality of distribution. Quantitative data mean and standard deviation. The significance of the obtained results was determined at the 5% level. The student t-test for normally distributed quantitative variables was used to compare the two groups studied.

Results
Statistically significant differences in wettability condition discrepancies were found between groups (I) and (II) (p < 0.05). In addition, there were statistically significant differences in intraoral scan body (ISB) length between the two groups (p < 0.05). Regarding the intraoral scan body material, statistically significant differences were found between the two groups (p < 0.05).

Conclusions
The presence of saliva significantly affects the accuracy of the digital implant transfer. Additionally, using a longer intraoral scan body improves the accuracy of digital implant impressions. The titanium scan body had a greater level of precision on the implant impression scan.
The potential for attractive toxic sugar baits to complement core malaria interventions strategies: the need for more evidence
Authors: Zembere Kennedy 
Published: November 2024

AbstractDespite its success, the increased use of insecticide-treated nets (ITNs) and indoor residual spraying (IRS) has contributed to the development of insecticide resistance in malaria vectors and shifts in biting patterns of the primary malaria vectors. The limitations portrayed by ITNs and IRS suggest that their use alone will not reduce malaria to elimination levels as the remaining untargeted vectors continue to sustain residual malaria transmission (RMT). RMT is a big challenge to malaria elimination because even at 100% ITN and IRS coverage, malaria transmission persists as outdoor vectors avoid or reduce contact with such interventions. With the recent increase in the outdoor biting Anopheles arabiensis (hard to control using routine tools), in most African countries, including Malawi, novel tools such as the attractive toxic sugar baits (ATSBs), targeting outdoor biting vectors in addition to controlling indoor vectors are greatly needed to complement current tools, and could facilitate sustainable malaria control. The ATSB is one potential tool that has been tested in different settings with promising results, and more trials are ongoing in other African countries. ATSBs have been attributed to reductions of mosquito densities and malaria incidence with over 80% and 50%, respectively, and there is hope that by 2025, ATSBs would be considered for the World Health Organization prequalification listing as a complementary tool for mosquito control. This article highlights evidence that ATSBs can advance malaria elimination by complementing indoor-based tools. However, for effective control programmes and elimination campaigns, the use of ATSBs alone might not be adequate, and this article recommends the combined use of ATSBs with either IRS or ITNs.
Dendritic cells under the control of the preimplantation embryo secretome: an in vitro study
Authors: Kyvelidou Christiana , Haselrieder Sofia , von Gierke Maria , Gostner Johanna M. , Biasio Wolfgang , Wirleitner Barbara , Heufler Christine , Toth Bettina , Hofer-Tollinger Susanne 
Published: November 2024

Abstract
Objective
To study the crosstalk between maternal immune cells and the developing embryo by investigating the immunogenic properties of human blastocyst spent media (SM) on dendritic cells.

Methods
In this prospective multicenter experimental study, human preimplantation embryo spent media were collected after blastocyst formation, grouped based on successful or unsuccessful implantation, and analyzed by protein array or used to stimulate monocyte derived dendritic cells (moDC). The immunomodulatory properties of SM on moDC were investigated by analyzing changes in phenotype, cytokine secretion, indoleamine 2,3-dioxygenase (IDO) activity, and ability to activate T cells.

Results
A plethora of cytokines and growth factors secreted from preimplantation embryos was detected. Exposure to embryo SM altered the phenotype of moDC in a manner dependent on the implantation outcome. Specifically, SM from non-implanted embryos increased the expression of co-stimulatory molecules and activation markers on moDC. Furthermore, SM treated dendritic cells secreted low levels of cytokines and growth factors and were able to stimulate naïve T cells. Activation of IDO was decreased in moDC after stimulation with SM.

Conclusions
Our findings show that human preimplantation embryos secrete an abundance of molecules with the ability to significantly affect and even regulate immune cells in their environment.
Effects of sodium-glucose cotransporter-2 inhibitors on chronic kidney disease progression: a multi-state survival model
Authors: Tansawet Amarit , Looareesuwan Panu , Teza Htun , Boongird Sarinya , McKay Gareth J. , Attia John , Pattanaprateep Oraluck , Thakkinstian Ammarin 
Published: November 2024

Abstract
Background
Current guidelines recommend good glycemic control in patients with type 2 diabetes (T2D) to limit the progression of associated complications with combination therapies. This study aimed to compare the rate of chronic kidney disease (CKD) progression between patients who did or did not receive sodium-glucose cotransporter-2 inhibitors (SGLT2i) using a multistate model with two intermediate states (i.e., CKD stage 4 (CKD4) and 5 (CKD5)) and one absorbing state (i.e., death).

Methods
Data from patients with T2D and CKD stage 3 (CKD3) were retrieved for analysis. Patients treated with SGLT2i were matched 1:2 by prescription date with non-SGLT2i patients. The multistate model was constructed from Cox survival regression models specific to each transition stage. Cumulative failure and transition probabilities were estimated from bootstrapping.

Results
Data from 6582 patients (2194 and 4388 patients in the SGLT2i and non-SGLT2i groups, respectively) were analyzed. At 10-year follow-up, patients in the SGLT2i group were more likely to remain at CKD3 compared to the non-SGLT2i group: 82.3% (95% CI 79.9%, 84.6%) vs 60.4% (57.6%, 63.4%). Transition probabilities to CKD4, CKD5, and death were lower in the SGLT2i group than non-SGLT2i group: 11.3% (9.5%, 13.3%) vs 19.8% (17.4%, 22.2%), 2.4% (1.5%, 3.4%) vs 7.4% (5.8%, 9.0%), and 4.1% (2.9%, 5.3%) vs 12.4% (10.3%, 14.6%), respectively.

Conclusion
SGLT2i may delay the decline in renal function and slow CKD progression compared to standard care without SGLT2i.
Bromodomain proteins as potential therapeutic targets for B-cell non-Hodgkin lymphoma
Authors: Zou Dan , Feng Sitong , Hu Bowen , Guo Mengya , Lv Yan , Ma Rong , Du Yuxin , Feng Jifeng 
Published: November 2024

Abstract
Background
B-cell non-Hodgkin lymphoma (B-NHL) is the most common type of lymphoma and is significantly heterogeneous among various subtypes. Despite of considerable advancements in treatment strategies for B-NHL, the prognosis of relapsed/refractory patients remains poor.

Main text
It has been indicated that epigenetic dysregulation is critically associated with the pathogenesis of most hematological malignancies, resulting in the clinical targeting of epigenetic modifications. Bromodomain (BRD) proteins are essential epigenetic regulators which contain eight subfamilies, including BRD and extra-terminal domain (BET) family, histone acetyltransferases (HATs) and HAT-related proteins, transcriptional coactivators, transcriptional mediators, methyltransferases, helicases, ATP-dependent chromatin-remodeling complexes, and nuclear-scaffolding proteins. Most pre-clinical and clinical studies on B-NHL have focused predominantly on the BET family and the use of BET inhibitors as mono-treatment or co-treatment with other anti-tumor drugs. Furthermore, preclinical models of B-NHL have revealed that BET degraders are more active than BET inhibitors. Moreover, with the development of BET inhibitors and degraders, non-BET BRD protein inhibitors have also been designed and have shown antitumor activities in B-NHL preclinical models. This review summarized the mechanism of BRD proteins and the recent progress of BRD protein-related drugs in B-NHL. This study aimed to collect the most recent evidences and summarize possibility on whether BRD proteins can serve as therapeutic targets for B-NHL.

Conclusion
In summary, BRD proteins are critical epigenetic regulatory factors and may be potential therapeutic targets for B-NHL.
High flow nasal cannula and low level continuous positive airway pressure have different physiological effects during de novo acute hypoxemic respiratory failure
Authors: Tuffet Samuel , Boujelben Mohamed Ahmed , Haudebourg Anne-Fleur , Maraffi Tommaso , Perier François , Labedade Pascale , Moncomble Elsa , Gendreau Ségolène , Lacheny Matthieu , Vivier Emmanuel , Mekontso-Dessap Armand , Carteaux Guillaume 
Published: November 2024

Abstract
Background
Large tidal volumes during de novo acute hypoxemic respiratory failure (AHRF) may promote patient self-inflicted lung injury. Tidal volume assessment under high flow nasal cannula (HFNC) is not routinely feasible at the bedside. Our objective was to determine whether tidal volume during low-level continuous positive airway pressure (CPAP) could predict tidal volume during HFNC and to compare the physiological effects of HFNC and low-level CPAP.

Methods
Prospective, single-center study including 29 de novo AHRF patients treated with HFNC (50 to 60 L.min− 1). Patients were monitored using electrical impedance tomography during HFNC then CPAP at 4 cmH2O. Tidal volume during HFNC was calculated based on tidal impedance variation. The ability of tidal volume under low-level CPAP to predict tidal volume under HFNC was explored using Bland-Altman analysis. CPAP and HFNC were compared in terms of tidal volume, minute ventilation, respiratory comfort, dyspnea, oxygenation, ventilation distribution, end-expiratory lung volume, thoraco-abdominal asynchrony and recruitment.

Results
Under HFNC, patients had a tidal volume of 6.6 (5.9–8.7) mL.kg− 1 PBW. 20 (69%) patients exhibited a tidal volume between 4 and 8 mL.kg− 1 PBW, while in 5 (17%) patients it exceeded 9 mL.kg− 1 PBW. Tidal volume under CPAP was higher (9.4 (8.3–11) mL.kg− 1 PBW, p < 0.001). Tidal volumes under CPAP and under HFNC were modestly correlated (Spearman r = 0.50, p = 0.005). Bland-Altman analysis showed a bias of 2.4 mL.kg− 1, with limits of agreement ranging from − 1.1 mL.kg− 1to 5.9 mL.kg− 1. Nevertheless, a larger (> 11.5 mL.kg− 1 PBW ) tidal volume under low-level CPAP predicted a larger (> 9 mL.kg− 1 PBW ) tidal volume under HFNC with 80% sensitivity and 96% specificity. Low-level CPAP was associated with increased minute ventilation, end-expiratory lung volume, and oxygenation as compared to HFNC. It decreased signs of respiratory distress in the most severe patients but was associated with lower comfort compared to HFNC.

Conclusion
Among ICU patients with de novo AHRF, tidal volume under HFNC was mostly protective. Tidal volume during CPAP at 4 cmH2O did not predict tidal volume during HFNC. Such low-level CPAP was associated with increased tidal volume, minute ventilation, end-expiratory volume, and oxygenation.

Trial registration
ClinicalTrials.gov ID NCT03919331. Registration date: 2019-03-26.
From fixing to connecting: parents’ experiences supporting adult children with eating disorders
Authors: Geller J. , Fernandes A. , Marshall S. , Srikameswaran S. 
Published: November 2024

Abstract
Background
Unlike evidence-based guidelines that exist for families of youth with eating disorders, little is known about the optimal role for families of adult patients. Given issues of patient autonomy and confidentiality, it is common for family members to report high levels of distress, confusion about how to offer support, and feelings of exclusion. Nevertheless, interactions with parents play a critical role in the recovery process. The purpose of this research was to increase understanding of support experiences of parents of adult children while identifying what they believe to be the most beneficial forms of support.

Methods
Sixteen parents of adults who were either recovered or actively engaged in intensive eating disorders treatment participated in semi-structured interviews. Participants were asked to describe the nature of their relationship, beliefs about their child’s support needs, and factors that challenged or facilitated their capacity to offer what they deemed as optimal support.

Results
In the context of receiving support and practicing self-care, parents’ aspiration shifted from fixing the eating disorder to prioritizing a relational goal of unrelenting connection with their child. Achieving this involved three key skills: managing reactions and expectations, learning boundaries, and practicing validation.

Conclusions
This research highlights the ongoing challenges faced by parents, indicating that interventions aimed at supporting their own well-being and fostering connection with their child may be of benefit.
Treatment utilization among people with drug use disorders in prison: a national longitudinal cohort study
Authors: Lokdam Nicoline Toresen , Stavseth Marianne Riksheim , Skjaervø Ingeborg , Bukten Anne 
Published: November 2024

Abstract
Background
Drug use disorders are highly prevalent among people in prison. Nevertheless, treatment coverage for individuals with drug use disorders in prison remains understudied and unknown. The aim of this study was to estimate treatment coverage among a sample of people with harmful and likely drug dependence before entering prison and to investigate the factors associated with treatment utilization.

Methods
This was a longitudinal cohort study using baseline survey data linked to registry data on imprisonment and treatment utilization. The study is based on the Norwegian Offender Mental Health and Addiction (NorMA) cohort (n = 733) recruited in 2013–2014 from 57 Norwegian prisons. At baseline, participants reported drug use the year before imprisonment, using the Drug Use Disorder Identification Test (DUDIT). The outcome of interest was DUD treatment, defined as at least one DUD treatment episode from the specialized health services during baseline imprisonment.

Results
40% of the sample had DUDIT scores that indicated likely drug dependence (≥ 25) and a need for treatment. Among this group, 64% received DUD treatment while imprisoned. Longer imprisonment (> 12 months; aOR = 8.87, p < 0.001), Nordic country of birth (aOR = 2.85, p = 0.003), daily/almost daily injecting drug use (aOR = 2.58, p < 0.001) and polydrug use (aOR = 2.19, p = 0.002) were positively associated with treatment utilization in prison.

Conclusions
Most people with likely drug dependence before entering prison in Norway received DUD treatment during their time in prison. More severe drug use (Injecting drug use and polydrug use), longer imprisonments and being born in the Nordics were positively associated with treatment utilization. People in prison must have access to adequate treatment during imprisonment, and further studies should investigate the possible individual or structural barriers resulting in treatment gaps, especially for people who are foreign born and people with short sentences.