bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study protocol of the PRINCESS trial—PReoperative INtermittent fasting versus CarbohydratE loading to reduce inSulin resiStance versus standard of care in orthopaedic patients: a randomised controlled trial
Authors: Stobbe Ayla Y , de Klerk Eline S , van Wilpe Robert , Kievit Arthur J , Choi Kee Fong , Preckel Benedikt , Hollmann Markus W , Hermanides Jeroen , van Stijn Mireille F M , Hulst Abraham H 
Published: January 2025

IntroductionSurgical trauma induces a metabolic stress response, resulting in reduced insulin sensitivity and hyperglycaemia. Postoperative insulin resistance (IR) is associated with postoperative complications, and extended preoperative fasting may further aggravate the postoperative metabolic stress response. Nutritional strategies, such as carbohydrate loading (CHL), have been successfully used to attenuate postoperative IR. Recent evidence suggests that time-restricted feeding (TRF), a form of intermittent fasting, improves IR in the general population, even after a short period of TRF. We hypothesise that TRF, as well as CHL, improve postoperative IR.Methods and analysisThis open-label, single-centre, randomised controlled trial will compare the effect of short-term preoperative TRF, CHL and standard preoperative fasting on perioperative IR. A total of 75 orthopaedic patients presenting for elective intermediate to major surgery at a Dutch academic hospital will be randomly assigned to a control group (standard preoperative fasting), a TRF group or a CHL group. The primary outcome is postoperative IR, based on the updated homeostasis model assessment of IR, on the first day after surgery. Statistical analyses are performed using Student’s t-tests or Mann-Whitney U tests.Ethics and disseminationThe local medical ethics committee of the Amsterdam UMC, the Netherlands, approved the trial protocol in January 2023 (NL81556.018.22). No publication restrictions apply, and the results of the study will be disseminated through a peer-reviewed journal.Trial registration numberNCT05760339.
Socioeconomic position across the life course and falls among middle- and older-aged adults: protocol for a systematic review
Authors: Smit Frerik , van Zwieten Anita , Sherrington Catherine , Franco Marcia R , Cullati Stéphane , Blyth Fiona M , Khalatbari-Soltani Saman 
Published: January 2025

IntroductionIndividuals experiencing disadvantaged socioeconomic positions (SEPs) may be at increased risk of falls during middle and older age, and these impacts of socioeconomic factors may vary according to the duration, timing and sequencing of exposures across the life course. However, there has not been a recent systematic review of this evidence. This study, therefore, aims to synthesise existing knowledge on the association between SEP across the life course and falls within middle- and older-aged adults.Methods and analysisWe systematically searched for literature in three academic databases from database inception to 15 March 2024: MEDLINE (Ovid), Embase (Ovid) and PsycInfo (Ovid). The search strategy combined MeSH headings and search terms related to SEP, falls, middle- and older-aged adults and observational studies. Cohort, case-control and cross-sectional studies with mean or median participant age of >40 years, which report on the association between at least one socioeconomic indicator across the life course and one fall outcome and are published in peer-reviewed academic journals were included. No language or geographic restrictions were imposed. Titles and abstracts were screened by one reviewer with 20% of titles and abstracts also screened by a second reviewer. Two reviewers independently screened full texts. Data will be extracted using a standardised Excel template. Using a modified Quality in Prognosis Studies (QUIPS) tool, the risk of bias of included studies will be assessed by one reviewer with 20% of studies also independently appraised by a second reviewer. Meta-analyses will be conducted if sufficient homogeneity between studies permits. Otherwise, a narrative synthesis of results will be undertaken.Ethics and disseminationAs this is a review of published literature, no ethics approval is required. Findings will be disseminated through a journal article publication, conference presentations and plain-text summaries for public accessibility.PROSPERO registration numberCRD42024534813.
Machine-learning versus traditional methods for prediction of all-cause mortality after transcatheter aortic valve implantation: a systematic review and meta-analysis
Authors: Zaka Ammar , Mustafiz Cecil , Mutahar Daud , Sinhal Shreyans , Gorcilov James , Muston Benjamin , Evans Shaun , Gupta Aashray , Stretton Brandon , Kovoor Joshua , Mridha Naim , Sivagangabalan Gopal , Thiagalingam Aravinda , Ramponi Fabio , Chan Justin , Bennetts Jayme , Murdoch Dale J , Zaman Sarah , Chow Clara K , Jayasinghe Rohan , Kovoor Pramesh , Bacchi Stephen 
Published: January 2025

BackgroundAccurate mortality prediction following transcatheter aortic valve implantation (TAVI) is essential for mitigating risk, shared decision-making and periprocedural planning. Surgical risk models have demonstrated modest discriminative value for patients undergoing TAVI and are typically poorly calibrated, with incremental improvements seen in TAVI-specific models. Machine learning (ML) models offer an alternative risk stratification that may offer improved predictive accuracy.MethodsPubMed, EMBASE, Web of Science and Cochrane databases were searched until 16 December 2023 for studies comparing ML models with traditional statistical methods for event prediction after TAVI. The primary outcome was comparative discrimination measured by C-statistics with 95% CIs between ML models and traditional methods in estimating the risk of all-cause mortality at 30 days and 1 year.ResultsNine studies were included (29 608 patients). The summary C-statistic of the top performing ML models was 0.79 (95% CI 0.71 to 0.86), compared with traditional methods 0.68 (95% CI 0.61 to 0.76). The difference in C-statistic between all ML models and traditional methods was 0.11 (p<0.00001). Of the nine studies, two studies provided externally validated models and three studies reported calibration. Prediction Model Risk of Bias Assessment Tool tool demonstrated high risk of bias for all studies.ConclusionML models outperformed traditional risk scores in the discrimination of all-cause mortality following TAVI. While integration of ML algorithms into electronic healthcare systems may improve periprocedural risk stratification, immediate implementation in the clinical setting remains uncertain. Further research is required to overcome methodological and validation limitations.
Persistently different patterns of patient’s global assessment of health in rheumatoid arthritis are associated with pain and impaired function more than with inflammation: an inception cohort study over 15 years
Authors: Bala Valentina , Hafström Ingiäld , Svensson Björn , Ajeganova Sofia 
Published: January 2025

ObjectiveTo assess patient’s self-reported global assessment of health (PGA) in relation to inflammation, pain and disability in patients with rheumatoid arthritis (RA).MethodsData were obtained from the Better Anti-Rheumatic PharmacOTherapy early RA cohort, in which patients were scheduled for follow-up of 15 years. Longitudinal PGA trajectories were identified using hierarchical agglomerative clustering procedure with Wards methods, based on PGA assessments during the first 2 years. Multivariate linear regression and mixed models were used to evaluate associations between PGA, inflammation, pain and disability.ResultsTotally 2238 patients were included in 1991–2006. Three PGA trajectories were identified, low, medium and high, including 34%, 48% and 18% of the patients, respectively. The similar PGA patterns were shown for the inclusion periods before and after 1999. The patients in the low PGA group were less often women, had lower body mass index, lower levels of inflammatory variables, visual analogue scale (VAS) pain and Health Assessment Questionnaire (HAQ) scores at baseline than patients in the higher PGA groups. After adjustments, smoking and antibodies to cyclic citrullinated peptide status differentiated between being in low and high PGA groups. During the first year, all PGA groups showed improved outcomes, most pronounced in low PGA group. Fewer patients in high PGA group achieved remission, independent of remission criteria used. The outcomes were consistently different between the PGA groups from 6 months and onwards. The PGA levels from baseline over 15 years were best explained by VAS pain, followed by HAQ score, Disease Activity Score on 28 joints-3 and tender joint count, adjusted R2up to 77%, 41%, 27% and 26%, respectively.ConclusionPersistently higher PGA levels in RA were mostly related to pain and disability.
Switching to biological DMARDs versus cycling among JAK inhibitors in patients with rheumatoid arthritis and with inadequate response to JAK inhibitors: from FIRST registry
Authors: Miyazaki Yusuke , Nakayamada Shingo , Tanaka Hiroaki , Hanami Kentaro , Fukuyo Shunsuke , Kubo Satoshi , Yamaguchi Ayako , Miyagawa Ippei , Satoh-Kanda Yurie , Todoroki Yasuyuki , Inoue Yoshino , Ueno Masanobu , Tanaka Yoshiya 
Published: January 2025

ObjectivesThis study aimed to identify characteristics of patients with rheumatoid arthritis (RA) with an inadequate response to Janus kinase inhibitors (JAKi-IR) and evaluate the efficacy and safety of subsequent treatments.MethodsThis study included 434 patients with RA who started JAKi treatment. JAKi-IR patients were those who switched to another drug due to inadequate response or did not reach low disease activity within 26 weeks of beginning JAKi. The efficacy and safety of switched biological disease-modifying anti-rheumatic drugs (bDMARDs) or cycled targeted synthetic disease-modifying anti-rheumatic drugs were analysed 26 weeks after switching treatment in JAKi-IR patients.ResultsPatients with JAKi-IR RA accounted for 31.8% (n=138/434). Multiple logistic regression identified factors contributing to JAKi-IR, such as the prior use of multiple ineffective bDMARDs and suboptimal JAKi dosing. There were no differences in patient background when comparing patients with RA with JAKi-IR who cycled to another JAKi (n=31) versus those who switched to bDMARDs (n=45). Among those cycling to another JAKi, the Clinical Disease Activity Index (CDAI) scores improved by week 26, with higher remission rates, while retention and adverse events remained similar. Trajectory analysis identified three CDAI response patterns, with the ‘treatment response’ group showing rapid and sustained improvement when cycling to another JAKi. Multiple logistic regression in this group identified another JAKi cycle as the critical factor for the treatment response.ConclusionsCycling JAKis is more effective than switching to bDMARDs in JAKi-IR RA, with no differences in safety or retention. This study suggests that cycling to another JAKi may be appropriate for patients with RA with JAKi-IR.
Massless limit and conformal soft limit for celestial massive amplitudes
Authors: Fan Wei 
Published: January 2025

Abstract
In celestial holography, the massive and massless scalars in 4d space-time are represented by the Fourier transform of the bulk-to-boundary propagators and the Mellin transform of plane waves respectively. Recently, the 3pt celestial amplitude of one massive scalar and two massless scalars was discussed in arXiv:2312.08597. In this paper, we compute the 3pt celestial amplitude of two massive scalars and one massless scalar. Then we take the massless limit

$$m\rightarrow 0$$

m
→
0

for one of the massive scalars, during which process the gamma function

$$\Gamma (1-\Delta )$$

Γ
(
1
-
Δ
)

appears. By requiring the resulting amplitude to be well-defined, that is it goes to the 3pt amplitude of arXiv:2312.08597, the scaling dimension of this massive scalar has to be conformally soft

$$\Delta \rightarrow 1$$

Δ
→
1

. The pole

$$1/(1-\Delta )$$

1
/
(
1
-
Δ
)

coming from

$$\Gamma (1-\Delta )$$

Γ
(
1
-
Δ
)

is crucial for this massless limit. Without it the resulting amplitude would be zero. This can be compared with the conformal soft limit in celestial gluon amplitudes, where a singularity

$$1/(\Delta -1)$$

1
/
(
Δ
-
1
)

arises and the leading contribution comes from the soft energy

$$\omega \rightarrow 0$$

ω
→
0

. The phase factors in the massless limit of massive conformal primary wave functions, discussed in arXiv:1705.01027, plays an import and consistent role in the celestial massive amplitudes. Furthermore, the subleading orders

$$m^{2n}$$

m

2
n

can also contribute poles when the scaling dimension is analytically continued to

$$\Delta =1-n$$

Δ
=
1
-
n

or

$$\Delta = 2$$

Δ
=
2

, and we find that this consistent massless limit only exists for dimensions belonging to the generalized conformal primary operators

$$\Delta \in 2-{\mathbb {Z}}_{\geqslant 0}$$

Δ
∈
2
-

Z

⩾
0

of massless bosons.
Defining quantum games
Authors: Piispanen Laura , Pfaffhauser Marcel , Wootton James , Togelius Julian , Kultima Annakaisa 
Published: January 2025

Abstract
In this research article, we survey existing quantum physics-related games and, based on this survey, propose a definition for the concept of quantum games. We define a quantum game as any type of rule-based game that either employs the principles of quantum physics or references quantum phenomena or the theory of quantum physics through any of three proposed dimensions: the perceivable dimension of quantum physics, the dimension of quantum technologies, and the dimension of scientific purposes, such as citizen science or education. We also discuss the concept of quantum computer games, which are games on quantum computers, as well as definitions for the concept of science games. Various games explore quantum physics and quantum computing through digital, analogue, and hybrid means, with various incentives driving their development. As interest in games as educational tools for supporting quantum literacy grows, understanding the diverse landscape of quantum games becomes increasingly important. We propose that the three dimensions of quantum games identified in this article be used for designing, analysing, and defining the phenomenon of quantum games.
A Multipotent PROX1+ Tumor Stem/Progenitor Cell Population Emerges During Intestinal Tumorigenesis and Mediates Radioresistance in Colorectal Cancer
Authors: Kallio Pauliina , Bessone Cinzia , Seyednasrollah Fatemeh , Brodkin Jefim , Lassila Marika , Högström Jenny , González-Loyola Alejandra , Petrova Tatiana V. , Haglund Caj , Alitalo Kari 
Published: January 2025

Abstract
Colorectal carcinoma (CRC) progression is associated with an increase in PROX1+ tumor cells, which exhibit features of CRC stem cells and contribute to metastasis. Here, we aimed to provide a better understanding to the function of PROX1+ cells in CRC, investigating their progeny and their role in therapy resistance. PROX1+ cells in intestinal adenomas of ApcMin/+ mice expressed intestinal epithelial and CRC stem cell markers, and cells with high PROX1 expression could both self-renew tumor stem/progenitor cells and contribute to differentiated tumor cells. Most PROX1-lineage traced tumor cells were stem/progenitor cells, which can supply cells to multiple intestinal tumor cell lineages, whereas most lineage-traced LGR5+ tumor cells were enterocytes, indicating that PROX1+ and LGR5+ tumor stem cells have distinct differentiation programs. Although the PROX1+ tumor cells proliferated slower than PROX1- cells, irradiation increased the proportion of PROX1+ cells in human CRC cell lines, patient-derived organoids, and tumor xenografts. Furthermore, transcripts related to DNA damage repair (DDR) were enriched in PROX1+ vs. PROX1- cells in adenomas and in CRC tumor cells from patients. Experiments with PROX1 silencing and overexpression indicated that PROX1 expression enhances CRC cell colony formation following irradiation. PROX1 interacted with DDR proteins, including components of non-homologous end-joining (NHEJ) and base excision repair, and inhibition of NHEJ repair led to a decreased proportion of PROX1+ cells following irradiation. In conclusion, PROX1+ cells are irradiation-resistant tumor stem/progenitor cells capable of self-renewal and differentiation. DDR inhibitors could represent a strategy to target the treatment-resistant PROX1+ tumor stem cells.
Comparison of Lean, Obese, and Weight Loss Models Reveals TREM2 Deficiency Attenuates Breast Cancer Growth Uniquely in Lean Mice and Alters Clonal T Cell Populations
Authors: Pierro Elysa W. , Cottam Matthew A. , An Hanbing , Lehmann Brian D. , Pietenpol Jennifer A. , Wellen Kathryn E. , Makowski Liza , Rathmell Jeffrey C. , Fingleton Barbara , Hasty Alyssa H. 
Published: January 2025

Abstract
Obesity is an established risk factor for breast cancer development and poor prognosis. The adipose environment surrounding breast tumors, which is inflamed in obesity, has been implicated in tumor progression, and TREM2, a transmembrane receptor expressed on macrophages in adipose tissue and tumors, is an emerging therapeutic target for cancer. A better understanding of the mechanisms for the obesity-breast cancer association and the potential benefits of weight loss could help inform treatment strategies. Here, we utilized lean, obese, and weight loss mouse models to examine the impacts of TREM2 deficiency (Trem2+/+ and Trem2-/-) on postmenopausal breast cancer depending on weight history conditions. Trem2 deficiency constrained tumor growth in lean, but not obese or weight loss, mice. Single-cell RNA sequencing, in conjunction with VDJ sequencing of tumor and tumor-adjacent mammary adipose tissue (mATTum-adj) immune cells, revealed differences in the immune landscapes across the different models. Tumors of lean Trem2-/- mice exhibited a shift in clonal CD8+ T cells from an exhausted to an effector memory state, accompanied increased clonality of CD4+ Th1 cells, that was not observed in any other diet-genotype group. Notably, identical T cell clonotypes were identified in the tumor and mATTum-adj of the same mouse. Finally, anti-PD-1 therapy restricted tumor growth in lean and weight loss, but not obese, mice. These findings indicate that weight history could impact the efficacy of TREM2 inhibition in postmenopausal breast cancer. The reported immunological interactions between tumors and the surrounding adipose tissue highlight significant differences under obese and weight loss conditions.
Beliefs About the Speaker’s Reasoning Ability Influence Pragmatic Interpretation: Children and Adults as Speakers
Authors: Mayn Alexandra , Loy Jia E. , Demberg Vera 
Published: January 2025

Abstract
The cooperative principle states that communicators expect each other to be cooperative and adhere to rational conversational principles. Do listeners keep track of the reasoning sophistication of the speaker and incorporate it into the inferences they derive? In two experiments, we asked participants to interpret ambiguous messages in the reference game paradigm, which they were told were sent either by another adult or by a 4-year-old child. We found an effect of speaker identity: if sent by an adult, an ambiguous message was much more likely to be interpreted as an implicature, while if sent by a child, it was a lot more likely to be interpreted literally. We also observed substantial individual variability, which points to different beliefs and strategies among our participants. We discuss how these speaker effects can be modeled in the Rational Speech Act framework.
“Groupitizing”: A Visuo-Spatial and Arithmetic Phenomenon
Authors: Maldonado Moscoso Paula A. , Anobile Giovanni , Maduli Giuseppe , Arrighi Roberto , Castaldi Elisa 
Published: January 2025

Abstract
When objects are grouped in space, humans can estimate numerosity more precisely than when they are randomly scattered. This phenomenon, called groupitizing, is thought to arise from the interplay of two components: the subitizing system which identifies both the number of subgroups and of items within each group, and the possibility to perform basic arithmetic operations on the subitized groups. Here we directly investigate the relative role of these two components in groupitizing via an interference (dual task) paradigm. Participants were required to estimate numerosities of grouped and ungrouped arrays while their attentional resources were fully available (single task) or while performing concurrent tasks loading auditory or visuo-spatial attention (both known to interfere with the subitizing process) as well as while performing arithmetic calculation. The attentional cost of performing any concurrent task was overall higher for grouped than ungrouped stimuli, supporting the idea that groupitizing relies on the recruitment of more than one attention-dependent mechanism. However, depriving visuo-spatial attention and preventing participants from performing calculations caused the strongest decrement in sensory precision for grouped numerosities indicating that these attentional components play a major role in groupitizing. These results are in line with the existence of an estimation mechanism that might operate across all numerical ranges, supplemented by attentional mechanisms (subitizing). This study shows that this attentional-demanding mechanism can be activated also when processing numerosities outside of the subitizing regime (n &gt; 4), provided that grouping cues are available and, in concert with calculation abilities, gives rise to the groupitizing phenomenon.
On the Perception of Moral Standing to Blame
Authors: Ghezae Isaias , Yang Fan , Yu Hongbo 
Published: January 2025

Abstract
Is everyone equally justified in blaming another’s moral transgression? Across five studies (four pre-registered; total N = 1,316 American participants), we investigated the perception of moral standing to blame—the appropriateness and legitimacy for someone to blame a moral wrongdoing. We propose and provide evidence for a moral commitment hypothesis—a blamer is perceived to have low moral standing to blame a moral transgressor if the blamer demonstrates weak commitment to that moral rule. As hypothesized, we found that when blamers did not have the chance or relevant experience to demonstrate good commitment to a moral rule, participants generally believed that they had high moral standing to blame. However, when a blamer demonstrated bad commitment to a moral rule in their past behaviors, participants consistently granted the blamer low moral standing to blame. Low moral standing to blame was generally associated with perceiving the blame to be less effective and less likely to be accepted. Moreover, indirectly demonstrating moral commitment, such as acknowledging one’s past wrongdoing and feeling/expressing guilt, modestly restored moral standing to blame. Our studies demonstrate moral commitment as a key mechanism for determining moral standing to blame and emphasize the importance of considering a blamer’s moral standing as a crucial factor in fully understanding the psychology of blame.