bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of combination therapies with BTK inhibitors and dasatinib to treat CNS-infiltrating E2A-PBX1+/preBCR+ ALL
Authors: Gentile Gaia , Poggio Teresa , Catalano Antonella , Voutilainen Minna , Lahnalampi Mari , Andrade-Martinez Marta , Ma Tobias , Sankowski Roman , Goncharenko Lina , Tholen Stefan , Han Kyuho , Morgens David W. , Prinz Marco , Lübbert Michael , Engel Sophia , Hartmann Tanja Nicole , Cario Gunnar , Schrappe Martin , Lenk Lennart , Stanulla Martin , Duyster Justus , Bronsert Peter , Bassik Michael C. , Cleary Michael L. , Schilling Oliver , Heinäniemi Merja , Duque-Afonso Jesús 
Published: April 2024

Abstract
The t(1;19) translocation, encoding the oncogenic fusion protein E2A (TCF3)-PBX1, is involved in acute lymphoblastic leukemia (ALL) and associated with a pre–B-cell receptor (preBCR+) phenotype. Relapse in patients with E2A-PBX1+ ALL frequently occurs in the central nervous system (CNS). Therefore, there is a medical need for the identification of CNS active regimens for the treatment of E2A-PBX1+/preBCR+ ALL. Using unbiased short hairpin RNA (shRNA) library screening approaches, we identified Bruton tyrosine kinase (BTK) as a key gene involved in both proliferation and dasatinib sensitivity of E2A-PBX1+/preBCR+ ALL. Depletion of BTK by shRNAs resulted in decreased proliferation of dasatinib-treated E2A-PBX1+/preBCR+ cells compared with control-transduced cells. Moreover, the combination of dasatinib with BTK inhibitors (BTKi; ibrutinib, acalabrutinib, or zanubrutinib) significantly decreased E2A-PBX1+/preBCR+ human and murine cell proliferation, reduced phospholipase C gamma 2 (PLCG2) and BTK phosphorylation and total protein levels and increased disease-free survival of mice in secondary transplantation assays, particularly reducing CNS-leukemic infiltration. Hence, dasatinib with ibrutinib reduced pPLCG2 and pBTK in primary ALL patient samples, including E2A-PBX1+ ALLs. In summary, genetic depletion and pharmacological inhibition of BTK increase dasatinib effects in human and mouse with E2A-PBX1+/preBCR+ ALL across most of performed assays, with the combination of dasatinib and BTKi proving effective in reducing CNS infiltration of E2A-PBX1+/preBCR+ ALL cells in vivo.
Myeloablative vs nonmyeloablative consolidation for primary central nervous system lymphoma: results of Alliance 51101
Authors: Batchelor Tracy T. , Giri Sharmila , Ruppert Amy S. , Geyer Susan M. , Smith Scott E. , Mohile Nimish , Swinnen Lode J. , Friedberg Jonathan W. , Kahl Brad S. , Bartlett Nancy L. , Hsi Eric D. , Cheson Bruce D. , Wagner-Johnston Nina , Nayak Lakshmi , Leonard John P. , Rubenstein James L. 
Published: April 2024

Abstract
Although it is evident that standard-dose whole-brain radiotherapy as consolidation is associated with significant neurotoxicity, the optimal consolidative strategy for primary central nervous system lymphoma (PCNSL) is not defined. We performed a randomized phase 2 clinical trial via the US Alliance cancer cooperative group to compare myeloablative consolidation supported by autologous stem cell transplantation with nonmyeloablative consolidation after induction therapy for PCNSL. To our knowledge, this is the first randomized trial to be initiated that eliminates whole-brain radiotherapy as a consolidative approach in newly diagnosed PCNSL. Patients aged 18 to 75 years were randomly assigned in a 1:1 manner to induction therapy (methotrexate, temozolomide, rituximab, and cytarabine) followed by consolidation with either thiotepa plus carmustine and autologous stem cell rescue vs induction followed by nonmyeloablative, infusional etoposide plus cytarabine. The primary end point was progression-free survival (PFS). A total of 113 patients were randomized, and 108 (54 in each arm) were evaluable. More patients in the nonmyeloablative arm experienced progressive disease or death during induction (28% vs 11%; P = .05). Thirty-six patients received autologous stem cell transplant, and 34 received nonmyeloablative consolidation. The estimated 2-year PFS was higher in the myeloablative vs nonmyeloablative arm (73% vs 51%; P = .02). However, a planned secondary analysis, landmarked at start of the consolidation, revealed that the estimated 2-year PFS in those who completed consolidation therapy was not significantly different between the arms (86% vs 71%; P = .21). Both consolidative strategies yielded encouraging efficacy and similar toxicity profiles. This trial was registered at www.clininicals.gov as #NCT01511562.
Resistance training's impact on blood biomarkers and cognitive function in older adults with low and high risk of mild cognitive impairment: a randomized controlled trial
Authors: Vints Wouter A. J. , Gökçe Evrim , Šeikinaitė Julija , Kušleikienė Simona , Česnaitienė Vida J. , Verbunt Jeanine , Levin Oron , Masiulis Nerijus 
Published: April 2024

Abstract
Background
The aging brain exhibits a neuroinflammatory state, driven partly by peripheral pro-inflammatory stimuli, that accelerates cognitive deterioration. A growing body of evidence clearly indicates that physical exercise partly alleviates neuroinflammation and positively affects the aging process and cognition. In this randomized controlled trial, we aimed to observe the effect of 12 weeks of resistance training (RT) on peripheral biomarker levels, cognitive function changes and their interrelationship, and explore differences in those exercise-induced changes in older adults with high risk of mild cognitive impairment (MCI) compared to older adults with low risk of MCI.

Methods
Fifty-two participants ﻿(aged 60–85 years old, 28 female) were randomly allocated to a 12 week lower limb RT program consisting of two training sessions per week or waiting list control group. The Montreal Cognitive Assessment (MoCA) was used to stratify participants screened as high (< 26/30) or low risk (≥ 26/30) of MCI. We assessed serum Interleukin 6 (IL-6), Insulin-like Growth Factor-1 (IGF-1), and Kynurenine (KYN) levels. Cognitive measurement consisted of and four subtests of Automated Neuropsychological Assessment Metrics (ANAM), the two-choice reaction time, go/no-go, mathematical processing, and memory search test.

Results
Twelve weeks of RT improved Go/No-go test results in older adults with high MCI risk. RT did not significantly affect blood biomarkers. However, IGF-1 level increases were associated with improvements in response time on the mathematical processing test in the exercise group, and IL-6 level increases were associated with improvements in response time on the memory search test in the total group of participants. Finally, KYN levels significantly differed between older adults with low and high MCI risk but no significant associations with performance were found.

Conclusion
Our study results suggest a different effect of RT on inhibitory control between older adults with low compared to high MCI risk. IGF-1 may play a role in the mechanism behind the cognitive benefit of RT and KYN may be a surrogate biomarker for neurodegeneration and cognitive decline.
Carbon farming, overestimated negative emissions and the limits to emissions trading in land-use governance: the EU carbon removal certification proposal
Authors: Günther Philipp , Garske Beatrice , Heyl Katharine , Ekardt Felix 
Published: April 2024

AbstractThis article conducts a qualitative governance analysis of the European Commission’s 2022 proposal for a certification framework for carbon removals (CRCF). It highlights potential challenges and legal implications—with a specific focus on carbon farming. While the European Union (EU) acknowledges carbon farming as an important strategy to offset residual emissions, such carbon removal activities are prone to reversals and models often overestimate their sequestration potential. The CRCF aims to account for these issues, but the analysis shows that the proposal may, in part, undermine international climate and biodiversity goals set by the Paris Agreement and the Convention on Biological Diversity. Key concerns include its failure to consider the normative hierarchy between emission reductions and removals mandated by EU and international law, the introduction of a temporary removal crediting system, the extensive delegation of powers to the Commission, the possibility that it may incentivise shifting effects, and its lack of alignment with other EU environmental policies. Additionally, the CRCF’s failure to restrict the use of carbon credits after certification increases the risk of double claiming of removal activities—and the proposal may open the door for to future integration of carbon removals into the EU’s emission trading scheme, which should be avoided for various reasons. As an alternative, member states should consider targeted subsidy schemes and regulatory instruments to navigate these challenges in carbon farming effectively.
Long noncoding RNAs and mRNAs profiling in ovary during laying and broodiness in Taihe Black-Bone Silky Fowls (Gallus gallus Domesticus Brisson)
Authors: Tan Yuting , Huang Yunyan , Xu Chunhui , Huang Xuan , Li Shibao , Yin Zhaozheng 
Published: April 2024

Abstract
Background
Broodiness significantly impacts poultry egg production, particularly notable in specific breeds such as the black-boned Silky, characterized by pronounced broodiness. An understanding of the alterations in ovarian signaling is essential for elucidating the mechanisms that influence broodiness. However, comparative research on the characteristics of long non-coding RNAs (lncRNAs) in the ovaries of broody chickens (BC) and high egg-laying chickens (GC) remains scant. In this investigation, we employed RNA sequencing to assess the ovarian transcriptomes, which include both lncRNAs and mRNAs, in eight Taihe Black-Bone Silky Fowls (TBsf), categorized into broody and high egg-laying groups. This study aims to provide a clearer understanding of the genetic underpinnings associated with broodiness and egg production.

Results
We have identified a total of 16,444 mRNAs and 18,756 lncRNAs, of which 349 mRNAs and 651 lncRNAs exhibited significantly different expression (DE) between the BC and GC groups. Furthermore, we have identified the cis-regulated and trans-regulated target genes of differentially abundant lncRNA transcripts and have constructed an lncRNA-mRNA trans-regulated interaction network linked to ovarian follicle development. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analyses have revealed that DE mRNAs and the target genes of DE lncRNAs are associated with pathways including neuroactive ligand-receptor interaction, CCR6 chemokine receptor binding, G-protein coupled receptor binding, cytokine-cytokine receptor interaction, and ECM-receptor interaction.

Conclusion
Our research presents a comprehensive compilation of lncRNAs and mRNAs linked to ovarian development. Additionally, it establishes a predictive interaction network involving differentially abundant lncRNAs and differentially expressed genes (DEGs) within TBsf. This significantly contributes to our understanding of the intricate interactions between lncRNAs and genes governing brooding behavior.
Fall risk factors among poly-medicated older Lebanese patients in primary care settings: a secondary cross-sectional analysis of the “MGPIDP-L project”
Authors: Khatib Sarah El , Malham Carmela Bou , Andrieu Sandrine , Strumia Mathilde , Cestac Philippe , Salameh Pascale 
Published: April 2024

Abstract
Background
Falling is a major concern for the health of older adults and significantly affects their quality of life. Identifying the various risk factors and the differences between older patients can be challenging. The objective of this study was to identify the risk factors for falls among polymedicated community-dwelling older Lebanese patients following a medication review.

Methods
In this analytical cross-sectional study, we examined the risk factors for falls in 850 patients aged ≥ 65 years who were taking ≥ 5 medications daily. The study involved conducting a medication review over the course of a year in primary care settings and using multivariate logistic regression analysis to analyze the data.

Results
Our results showed that 106 (19.5%) of the 850 included patients had fallen at least once in the three months prior to the medication review. Loss of appetite and functional dependence were identified as the most significant predictors of falls ORa = 3.020, CI [2.074–4.397] and ORa = 2.877, CI [1.787–4.632], respectively. Other risk factors for falls included drowsiness ORa = 2.172, CI [1.499–3.145], and the use of beta-blockers ORa = 1.943, CI [1.339–2.820].

Conclusion
Our study highlights the importance of addressing multiple risk factors for falls among Lebanese older adults and emphasizes the need for customized interventions and ongoing monitoring to prevent falls and improve health outcomes. This study sheds light on a critical issue in the Lebanese older population and provides valuable insight into the complex nature of falls among poly-medicated Lebanese community-dwelling older adults.

Trial registration
2021REC-001- INSPECT -09–04.
First-in-human study of GFH018, a small molecule inhibitor of transforming growth factor-β receptor I inhibitor, in patients with advanced solid tumors
Authors: Guo Ye , Wang Zishu , Zhou Huan , Pan Hongming , Han Weidong , Deng Yanhong , Li Qun , Xue Junli , Ge Xiaoxiao , Wang Shuang , Wang Jing , Zhang Yue , Zhao Congqiao , Zhu Huaqiang , Wang Yu , Shen Haige , Liu Dong , Li Jin 
Published: April 2024

Abstract
Background
Transforming growth factor-β (TGF-β) is a cytokine with multiple functions, including cell growth regulation, extracellular matrix production, angiogenesis homeostasis adjustment and et al. TGF-β pathway activation promotes tumor metastasis/progression and mediates epithelial-mesenchymal transmission suppressing immunosurveillance in advanced tumors. GFH018, a small molecule inhibitor blocking TGF-β signal transduction, inhibits the progression and/or metastasis of advanced cancers. This first-in-human study evaluated the safety, tolerability, pharmacokinetics (PK), and efficacy of GFH018 monotherapy in patients with advanced solid tumors.

Methods
This phase I, open-label, multicenter study used a modified 3+3 dose escalation and expansion design. Adult patients with advanced solid tumors failing the standard of care were enrolled. Starting at 5 mg, eight dose levels up to 85 mg were evaluated. Patients received GFH018 BID (14d-on/14d-off) starting on the 4th day after a single dose on cycle 1, day 1. Subsequent cycles were defined as 28 days. The study also explored the safety of 85 mg BID 7d-on/7d-off. Adverse events were graded using NCI criteria for adverse events (NCI-CTCAE v5.0). PK was analyzed using a noncompartmental method. Efficacy was evaluated using RECIST 1.1. Blood samples were collected for biomarker analysis.

Results
Fifty patients were enrolled and received at least one dose of GFH018. No dose-limiting toxicity occurred, and the maximum tolerated dose was not reached. Forty-three patients (86.0%) had at least one treatment-related adverse event (TRAE), and three patients (6.0%) had ≥ G3 TRAEs. The most common TRAEs (any grade/grade ≥3) were AST increased (18%/0%), proteinuria (14%/2%), anemia (14%/2%), and ALT increased (12%/0%). No significant cardiotoxicity or bleeding was observed. GFH018 PK was linear and dose-independent, with a mean half-life of 2.25–8.60 h from 5 – 85 mg. Nine patients (18.0%) achieved stable disease, and one patient with thymic carcinoma achieved tumor shrinkage, with the maximum target lesion decreased by 18.4%. Serum TGF-β1 levels were not associated with clinical responses. The comprehensive recommended dose for Phase II was defined as 85 mg BID 14d-on/14d-off.

Conclusions
GFH018 monotherapy presented a favorable safety profile without cardiac toxicity or bleeding. Modest efficacy warrants further studies, including combination strategies.

Trial registration
ClinicalTrial. gov (https://www.clinicaltrials.gov/), NCT05051241. Registered on 2021-09-02.
Comparative visual outcomes of the first versus second eye following small-incision lenticule extraction (SMILE)
Authors: Li Anzhen , Yang Xiaowei , Wang Wei , Huang Wenbin , Ding Hui , Nie Ke , Zhong Tan , Hu Shisi , Yang Zhenduo , Zhong Xingwu 
Published: April 2024

Abstract
Background
This study aimed to compare the visual outcomes of the first operated eyes with those of the second operated eyes following small-incision lenticule extraction (SMILE).

Methods
A total of 202 patients (404 eyes) underwent SMILE using the tear film mark centration method for myopia and myopic astigmatism correction. Baseline characteristics, objective optical quality, decentered displacement, induced corneal aberrations, and modulation transfer function (MTF) values were assessed. Linear regression analyzed the relationship between decentration and visual quality parameters, including corneal aberrations and MTF values.

Results
No significant difference was observed in objective visual quality, efficacy, and safety indexes between the two groups (all P > 0.05). The average decentered displacement for the first and second surgical eyes was 0.278 ± 0.17 mm and 0.315 ± 0.15 mm, respectively (P = 0.002). The horizontal coma in the first surgical eyes were notably lower than in the second (P = 0.000). MTF values at spatial frequencies of 5, 10, 15, and 20 cycles/degree (c/d) were higher in the first surgical eyes compared to the second (all P < 0.05). Linear regression indicated that high-order aberrations (HOAs), root mean square (RMS) coma, spherical aberration, horizontal coma, vertical coma, and eccentric displacement were all linearly correlated. Furthermore, MTF values exhibited a linear relationship with eccentric displacement across these spatial frequencies.

Conclusions
There was no discernible difference in visual acuity, efficacy, or safety between the two operated eyes. Nonetheless, the first operated eyes exhibited reduced decentered displacement and demonstrated superior outcomes in terms of horizontal coma and MTF values compared to the second operated eyes following SMILE. The variations in visual quality parameters were linearly correlated with decentered displacement.
Implementation of COVID-19 vaccination services in prison in six European countries: translating emergency intervention into routine life-course vaccination
Authors: Mazzilli Sara , Cocco Nicola , Petri Davide , Moazen Babak , Rosello Alicia , D’Arcy Jemima , Plugge Emma , Baglietto Laura , Murauer Eva , Stöver Heino , Trattonikolas Tassos , Stylianou Iakovos , Doltu Svetlana , Busmachiu Vladislav , Mavrou Josefina , Yiasemi Ioanna , Barbiros Irina , da Costa Filipa Alves , Meroueh Fadi , Ranieri Roberto , Tavoschi Lara 
Published: April 2024

Abstract
Background
Evidence has shown that the risk of transmission of SARS-CoV-2 is much higher in prisons than in the community. The release of the COVID-19 vaccine and the recommendation by WHO to include prisons among priority settings have led to the inclusion of prisons in national COVID-19 vaccination strategies. Evidence on prison health and healthcare services provision is limited and often focuses on a single country or institution due to the multiple challenges of conducting research in prison settings. The present study was done in the framework of the EU-founded project RISE-Vac. It aimed to analyse the best practices and challenges applied in implementing COVID-19 universal vaccination services during the pandemic to support future expansion of routine life course vaccination services for people living in prison (PLP).

Methods
Two online cross-sectional surveys were designed and piloted: survey1 on prison characteristics and (non-COVID-19) immunisation practices; survey2 on the implementation and coverage of COVID-19 vaccination with open-ended questions for thematic analysis. Each RISE-Vac project partner distributed the questionnaire to one or two prisons in their country. Answers were collected from eight European prisons’ directors or medical directors between November 2021-May 2022.

Results
According to our findings, the implementation modalities of COVID-19 vaccination services in the surveyed prisons were effective in improving PLP vaccination coverage. Strategies for optimal management of the vaccination campaign included: periodic time slot for PLP vaccination; new staff recruitment and task shifting; distribution of informational material both to PLP and prison staff. Key challenges included continuity of care after release, immunisation information system, and vaccine hesitancy.

Conclusions
To the best of our knowledge, this is the first study describing the implementation of COVID-19 vaccination services in European prisons, suggesting that the expansion of vaccination provision in prison is possible. There is no unique solution that will fit every country but commonalities likely to be important in the design and implementation of future vaccination campaigns targeting PLP emerged. Increased availability of vaccination services in prison is not only possible, but feasible and highly desirable, and can contribute to the reduction of health inequalities.
Evidence-based interventions for identifying candidate quality indicators to assess quality of care in diabetic foot clinics: a scoping review
Authors: Lusendi Flora Mbela , Vanherwegen An-Sofie , Doggen Kris , Nobels Frank , Matricali Giovanni Arnoldo 
Published: April 2024

Abstract
Background
Foot ulcers in people with diabetes are a serious complication requiring a complex management and have a high societal impact. Quality monitoring systems to optimize diabetic foot care exist, but a formal and more evidence-based approach to develop quality indicators (QIs) is lacking. We aimed to identify a set of candidate indicators for diabetic foot care by adopting an evidence-based methodology.

Methods
A systematic search was conducted across four academic databases: PubMed, Embase CINAHL and Cochrane Library. Studies that reported evidence-based interventions related to organization or delivery of diabetic foot care were searched. Data from the eligible studies were summarized and used to formulate process and structure indicators. The evidence for each candidate QI was described in a methodical and transparent manner. The review process was reported according to the “Preferred Reported Items for Systematic reviews and Meta-Analysis” (PRISMA) statements and its extension for scoping reviews.

Results
In total, 981 full-text articles were screened, and 322 clinical studies were used to formulate 42 candidate QIs.

Conclusions
An evidence-based approach could be used to select candidate indicators for diabetic foot ulcer care, relating to the following domains: wound healing interventions, peripheral artery disease, offloading, secondary prevention, and interventions related to organization of care. In a further step, the feasibility of the identified set of indicators will be assessed by a multidisciplinary panel of diabetic foot care stakeholders.