bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new flavor of synthetic yeast communities sees the light
Authors: Rojas Vicente , Rivera Daniela , Ruiz Carlos , Larrondo Luis F. 
Published: February 2025

ABSTRACT

No organism is an island: organisms of varying taxonomic complexity, including genetic variants of a single species, can coexist in particular niches, cooperating for survival while simultaneously competing for environmental resources. In recent years, synthetic biology strategies have witnessed a surge of efforts focused on creating artificial microbial communities to tackle pressing questions about the complexity of natural systems and the interactions that underpin them. These engineered ecosystems depend on the number and nature of their members, allowing complex cell communication designs to recreate and create diverse interactions of interest. Due to its experimental simplicity, the budding yeast
Saccharomyces cerevisiae
has been harnessed to establish a mixture of varied cell populations with the potential to explore synthetic ecology, metabolic bioprocessing, biosensing, and pattern formation. Indeed, engineered yeast communities enable advanced molecule detection dynamics and logic operations. Here, we present a concise overview of the state-of-the-art, highlighting examples that exploit optogenetics to manipulate, through light stimulation, key yeast phenotypes at the community level, with unprecedented spatial and temporal regulation. Hence, we envision a bright future where the application of optogenetic approaches in synthetic communities (optoecology) illuminates the intricate dynamics of complex ecosystems and drives innovations in metabolic engineering strategies.
What are the lived healthcare experiences of patients with primary sclerosing cholangitis? A community-based qualitative interview study
Authors: Arndtz Katherine , Cameron Madeline , Hirschfield Gideon , Parry Jayne , Greenfield Sheila 
Published: February 2025

ObjectivesPrimary sclerosing cholangitis (PSC) is a rare chronic disease that presents challenges to both patients and clinicians. This study aimed to explore the experiences of patients with PSC regarding their disease and healthcare.DesignA series of semi-structured interviews was completed with patients with PSC, including questioning their experiences of living with PSC and its related healthcare.SettingParticipants were recruited from communities in England, Scotland and Wales, with advertisement via PSC Support (UK disease-specific charity support group).Participants18 patients aged between 21 and 72 years were interviewed; 10 were male (56%), and all were of Caucasian ethnicity. Inclusion criteria were as follows: adults, self-identifying as having a diagnosis of PSC, and currently under National Health Service treatment for this disease. Patients with a history of liver transplantation were excluded.ResultsParticipants confirmed the ongoing physical and psychological burden of PSC and its related healthcare. Living with PSC was described as a journey; the timeline of events was important to patients, with particular challenges identified along the way. These included difficulties in obtaining a diagnosis and accessing timely and knowledgeable medical care. Overcoming the unusual combination of uncertainties that PSC presents was of particular concern to participants; these differ from those observed in more common chronic diseases with established treatment pathways. Hidden complexities within chronic illness behaviour in PSC were described, including a noteworthy fragile doctor−patient relationship and dependence on the specialist. These produce additional challenges for the optimal clinical management of such patients by generalists and specialists.ConclusionsThis study complements the existing literature on the ongoing high burden of PSC, with added value from in-depth discussions with patients themselves. Priorities for further work have been identified, including the need for improved risk stratification tools to allow individualised management and prognostication, as well as improving access to knowledgeable care while maintaining a strong doctor–patient relationship.
Transcranial direct current stimulation combined with physical exercise in rotator cuff tendinopathy: a protocol for a blinded randomised controlled trial
Authors: Silva César Augusto Medeiros , Lima Vinicius Batista , Cosme Hannely Beatriz Menezes , Fonseca Romário Nóbrega Santos , Hazime Fuad Ahmad , da Silva Rodrigo Scattone , Freitas Rodrigo Pegado de Abreu , de Souza Clecio Gabriel 
Published: February 2025

IntroductionPain is one of the primary symptoms affecting individuals with rotator cuff tendinopathy. Physical exercise serves as the main approach for managing this condition, aiming to restore movement patterns, optimise scapular kinematics and improve strength and local muscular endurance. Pain neuromodulation techniques, such as transcranial direct current stimulation (tDCS), may offer complementary non-pharmacological options for pain relief by promoting central modulation and altering cortical excitability.Methods and analysisThis protocol outlines a randomised, blinded clinical trial. Participants will be randomly allocated to two groups: G1 (active tDCS combined with progressive exercise) and G2 (sham tDCS combined with progressive exercise). The protocol will span 4 weeks, with two sessions per week. Pain intensity, measured using the numerical pain scale, will serve as the primary outcome. Secondary outcomes will include physical function, range of motion, global perception of change and treatment adherence.Ethics and disseminationThis protocol was approved by the Ethics Committee Health Sciences College of Trairi, Federal University of Rio Grande do Norte (number: 6.821.408). Followed the Declaration of Helsinki recommendations for research with human beings. The results will be published later in peer-reviewed journals and scientific events.Trial registration numberThe Brazilian Registry of Clinical Trials (RBR-59xmv6s); Results.
Nutritional interventions to prevent and reduce overweight and obesity during postacute stroke rehabilitation: a scoping review protocol
Authors: Nørtoft Mette , Sørensen Dorthe , Aadal Lena 
Published: February 2025

IntroductionIndividuals with stroke are at risk of long-term overweight and obesity due to biopsychosocial factors. Being overweight and obese is associated with an increased risk of numerous chronic conditions, including recurrent stroke. Unfortunately, recommendations for nutritional interventions vary. The objective of this scoping review is to identify and map the body of literature on professional nutritional interventions aimed at preventing or reducing overweight and obesity during postacute stroke rehabilitation.Methods and analysisThe review follows the Joanna Briggs Institute methodology for scoping reviews. A three-step librarian-assisted search strategy will be conducted using the bibliographic databases MEDLINE (PubMed), Embase, CINAHL and Web of Science. Indexed and grey literature in English and Scandinavian languages, from January 2010 to the present, will be considered for inclusion. The scoping review will include materials such as research articles, methodological papers and clinical guidelines that report on nutritional interventions aimed at preventing or reducing overweight and obesity among individuals with stroke (aged ≥18 years) from admission to rehabilitation hospitals. We will map and identify any kind of nutritional intervention in rehabilitation hospitals, nursing homes or their own environments in high-income countries. Two independent reviewers will conduct an iterative process for screening the identified literature, paper selection and data extraction. Disagreements will be resolved through discussion or with an additional reviewer. A data extraction form will be used to guide the data extraction.Ethics and disseminationThis review will involve the collection and analysis of secondary sources that have been published and/or are publicly available. Therefore, ethical approval is not required. The results will be published in an international peer-reviewed journal, presented at scientific conferences and disseminated through digital science communication platforms.Trial registration numberThe protocol is registered in the Open Science Framework:https://osf.io/ga63n/view_only=ee07beace7bb48d6b9c82cbf79cf2e95.
Results of a modified Delphi consensus on the optimal testing pathway for oesophago-gastric cancer care in the UK
Authors: Rodriguez-Justo Manuel , Mansoor Wasat , Bird Thomas , Eatock Martin , Starling Naureen , Taniere Philippe 
Published: February 2025

ObjectiveTo develop expert consensus on the optimal testing pathway for oesophago-gastric (OG) cancer care.Methods and analysisThe process followed a modified Delphi methodology to develop consensus on the optimal testing pathway for OG cancer care. In November 2023, a review of available literature on the topic of OG cancer was conducted. The results of this review informed a steering group discussion on the barriers and opportunities within the OG testing pathway. Six domains of focus were agreed on and used to develop. 36 agreed statements were developed into a Likert survey, which was distributed by a third party (M3 Global Research). Completed surveys were analysed to produce an arithmetic agreement score for each statement. The results were then reviewed by the steering group to agree on any recommendations and conclusions.ResultsA total of 50 responses were received from consultant oncologists (n=25), pathologists (n=15), specialist oncology pharmacists (n=5) and specialist oncology nurses (n=5). Consensus was achieved in 35/36 statements (97%). The steering group agreed on a commentary on the results and a series of recommendations for best-practice testing in OG cancer. Given the level of agreement and that the stopping criteria were met, it was decided not to undertake further Delphi rounds.ConclusionThe recommendations support the use of a reflex testing approach for human epidermal growth factor receptor 2, programmed death ligand 1 and microsatellite instability high/mismatch repair deficiency in patients diagnosed with OG cancer who are suitable for treatment with targeted therapy.
Global, regional and national burden of asthma attributable to NO2from 1990 to 2021: an analysis from the Global Burden of Disease Study 2021
Authors: Li Jingli , Zhang Chunyi , Qin E , Sun Jian , Liu Lingjing , Pu Guimei 
Published: February 2025

ObjectivesThis study aims to systematically assess the global, regional, and national burden of asthma attributable to nitrogen dioxide (NO₂) pollution.Design and settingAnalysis of population-level data from 1990 to 2021 obtained from the Global Burden of Disease Study 2021, covering 204 countries and territories.ParticipantsParticipants included patients with asthma attributable to NO₂ pollution.Main outcomes and measuresAsthma-related disability-adjusted life-years (DALYs) and age-standardised DALY rates (ASDR) attributable to NO₂ pollution across 204 countries and territories. The estimated annual percentage change (EAPC) was used to assess temporal trends to identify regions with increasing or decreasing asthma burdens.ResultsIn 2021, NO₂ pollution contributed to approximately 176.73 thousand DALYs globally, with an ASDR of 2.48 per 100 000 population (95% uncertainty interval (UI) −2.26 to 10.30). The global ASDR declined significantly from 1990 to 2021, with an EAPC of −1.93% (95% CI −2.14% to −1.72%). High-income North America had the highest ASDR (10.74 per 100 000; 95% UI 10.12 to 46.56), while Australasia experienced the most significant reduction in ASDR over the study period (EAPC −3.92%; 95% CI −4.46% to −3.37%). In contrast, Oceania and Southeast Asia showed increasing trends in asthma burden, with EAPCs of 2.33% (95% CI 1.57% to 3.10%) and 1.14% (95% CI 0.81% to 1.47%), respectively. The 5–9 age group carried the highest asthma burden, reflecting the vulnerability of younger children to NO₂ exposure. A positive correlation between ASDR and sociodemographic index (SDI) was observed (R=0.637, p<0.001), indicating a greater asthma burden in higher SDI regions.ConclusionThe findings highlight significant regional and demographic disparities in asthma burden attributable to NO₂ pollution. Tailored public health strategies are needed to address the rising burden in vulnerable regions. Future research should focus on identifying effective interventions to reduce NO₂ exposure and improve asthma outcomes, especially in rapidly developing areas.
Tumor mutational burden and survival on immune checkpoint inhibition in >8000 patients across 24 cancer types
Authors: Gandara David R , Agarwal Neeraj , Gupta Shilpa , Klempner Samuel J , Andrews Miles C , Mahipal Amit , Subbiah Vivek , Eskander Ramez N , Carbone David P , Riess Jonathan W , Sammons Sarah , Snider Jeremy , Bouzit Lilia , Cho-Phan Cheryl , Price Megan , Li Gerald , Quintanilha Julia C F , Huang Richard Sheng Poe , Ross Jeffrey S , Fabrizio David , Oxnard Geoffrey R , Graf Ryon P 
Published: February 2025

BackgroundThere is uncertainty around clinical applicability of tumor mutational burden (TMB) across cancer types, in part because of inconsistency between TMB measurements from different platforms. The KEYNOTE 158 trial supported United States Food and Drug Administration (FDA) approval of the Foundation Medicine test (FoundationOneCDx) at TMB≥10 mut/Mb as a companion diagnostic (CDx) for single-agent pembrolizumab in second+line. Using a large real-world dataset with validated survival endpoint data, we evaluated clinical validity of TMB measurement by the test in over 8000 patients across 24 cancer types who received single-agent immune checkpoint inhibitor (ICI).MethodsPatients with advanced-stage cancers from 24 cancer types treated with single-agent anti-PD(L)1 therapy in standard-of-care settings were included. Deidentified data from electronic health records from approximately 280 cancer treatment facilities were captured into a clinico-genomic database. This study used the TMB algorithm from the FDA-approved test supporting solid tumor CDx and composite mortality variable validated against the national death index: real-world overall survival (rwOS). Following a prespecified analysis plan, rwOS by TMB level was assessed using Cox PH models adjusted for Eastern Cooperative Oncology Group performance status, prior treatment, microsatellite instability, sex, age, opioid rx pretherapy, and socioeconomic assessment.Results8440 patients met inclusion criteria. Adjusting for aforementioned factors, increasing TMB was significantly associated with rwOS across tumor types; HRs (95% CIs) relative to TMB<5: TMB 5 to <10: 0.95 (0.89 to 1.02), TMB 10 to <20: 0.79 (0.73 to 0.85), TMB≥20: 0.52 (0.47 to 0.58). For individual cancer types with prespecified statistical power, adjusted rwOS comparing TMB≥10 vs TMB<10 significantly favored TMB≥10 in 9 of 10 cancer types. In microsatellite stable subcohorts (except colorectal cancer), TMB≥10 remained associated with enriched ICI benefit. Exploratory assessments of patients receiving ICI+chemotherapy (n=4369) observed more favorable rwOS only in TMB≥20.ConclusionsAcross >8000 patients treated with single-agent ICI, and within individual cancer types with sufficient power, elevated TMB based on the FDA-approved CDx was associated with more favorable rwOS compared with similar patients with lower TMB levels. This biomarker deserves further clinical investigation to potentially guide the use of immunotherapy in expanded clinical contexts.
Evaluation of VLA-4 (integrin α4β1) as a shared target for radiopharmaceutical therapy across solid tumors
Authors: Reyes-González Jeyshka M. , Rajkumar Harikrishnan , Lee Woonghee , Baidoo Kwamena E. , Edinger Robert S. , Diehl George , Nambiar Divya , Okada Reona , Edmondson Elijah F. , Fayn Stanley , Buckley John , Jaswal Ambika P. , Cortez Angel , Marsh Ian R. , Josefsson Anders , Kohanbash Gary , Nedrow Jessie R. , Anderson Carolyn J. , Escorcia Freddy E. , Nguyen Rosa , Patel Ravi B. 
Published: February 2025

Abstract
Radiopharmaceutical therapy (RPT) is a promising approach to treating solid tumors, but therapeutic advances are impeded by the lack of broadly expressed targets and shared molecular vulnerability across different tumor types. We evaluate VLA-4 (integrin α4β1) as a potential target for RPT in solid tumors using radiolabeled copper-64 ([64Cu]Cu-) and copper-67 ([67Cu]Cu-CB-TE1A1P-PEG4-LLP2A) LLP2A, a peptidomimetic ligand of VLA-4, for preclinical imaging and RPT testing. Expression analysis of ITGA4, encoding the alpha 4 subunit of VLA-4, revealed overexpression in hematological malignancies and various solid tumors compared to healthy tissue. Flow cytometry showed medium to high VLA-4 expression in 77% of tested cancer cell lines. PET/CT imaging with [64Cu]Cu-LLP2A demonstrated tracer uptake in tumors and lymphoid tissues. In toxicity studies, [67Cu]Cu-LLP2A administered at 37-74 MBq was well-tolerated, causing only thymic atrophy without long-term hematological or tissue toxicity. Tumor dose response was observed in B16-F10 melanoma models. Using orthotopic syngeneic models (B16-F10, B78, 4T1, GL261, TH-MYCN, and E2A-PBX1) and human cancer models (SK-MEL-37, 143B, and IMR-5), we conducted PET/CT imaging and biodistribution studies, with selected models used for [64Cu]Cu-LLP2A dosimetry calculations. Given VLA-4's broad expression across cancer tissues, demonstrated on-target effects, acceptable toxicity profile, and favorable dosimetry in preclinical models, further investigation of [67Cu]Cu-LLP2A as an RPT agent is warranted.
Induced Cytokinesis Generates Highly Proliferative Mononuclear Cardiomyocytes at the Expense of Contractility
Authors: Lam Nicholas T. , Nguyen Ngoc Uyen Nhi , Elhelaly Waleed M. , Hsu Ching-Cheng , Menendez-Montes Ivan , Xiao Feng , Ali Shah R. , Vo Nelson , Briard Nathan , El-Feky Lobna , Omari Qamar M. , Cardoso Alisson C. , Liu Yan , Ahmed Mahmoud Salama , Li Shujuan , Thet Suwannee , Xing Chao , Zangi Lior , Sadek Hesham A. 
Published: February 2025

BACKGROUND:
Cytokinesis is the last step in the eukaryotic cell cycle, which physically separates a mitotic cell into 2 daughter cells. A few days after birth in mouse cardiomyocytes, DNA synthesis occurs without cytokinesis, leading to the majority of cardiomyocytes becoming binucleated instead of generating 2 daughter cells with 1 nucleus each. This results in cell cycle arrest of cardiomyocytes, and the mouse heart is no longer able to regenerate. A longstanding unanswered question is whether binucleation of cardiomyocytes is a result of cytokinesis failure.

METHODS:
To address this, we generated several transgenic mouse models to determine whether forced induction of cardiomyocyte cytokinesis generates mononucleated cardiomyocytes and restores the endogenous regenerative properties of the myocardium. We focused on 2 complementary regulators of cytokinesis: Plk1 (polo-like kinase 1) and Ect2 (epithelial cell-transformation sequence 2).

RESULTS:
We found that cardiomyocyte-specific transgenic overexpression of constitutively active Plk1(T210D) promotes mitosis and cytokinesis in adult hearts, whereas overexpression of Ect2 alone promotes only cytokinesis. Cardiomyocyte-specific overexpression of both Plk1(T210D) and Ect2 concomitantly (double transgenic) prevents binucleation of cardiomyocytes postnatally and results in widespread cardiomyocyte mitosis, cardiac enlargement, contractile failure, and death before 2 weeks of age. Similarly, doxycycline-inducible cardiomyocyte-specific overexpression of both proteins (inducible double transgenic) in the adult heart results in reversible widespread cardiomyocyte mitosis and contractile failure. Transient induction of both genes in adult mice improves left ventricular systolic function after myocardial infarction.

CONCLUSIONS:
These results collectively demonstrate that cytokinesis failure mediates cardiomyocyte multinucleation and cell cycle exit of postnatal cardiomyocytes, but may be a protective mechanism to preserve the contractile function of the myocardium.
«Есть всё-таки что-то эротическое в происходящем на границах нашей империи»: эссе-расследование одной крылатой фразы
Authors: Абашин Сергей 
Published: February 2025

Abstract
The article examines a quote from the diary of the Minister of Internal Affairs of the Russian Empire, Pyotr Valuev, dedicated to the events of the summer of 1865 in Central Asia. This quote, including the phrase “There is still something erotic in what is happening on the borders of our empire,” became popular both in various academic texts and in the media sphere and turned into an oft-repeated aphorism. Sergei Abashin restores the original quote and “unpacks” the historical context in which it appeared, as well as the author’s own intentions. The article shows how the mistake of scientists when publishing Valuev’s diaries and manipulations with the quote led to various interpretations of it, far from the meaning of the original statement. The article is written in the genre of an academic research essay.
Anticoagulation Monitoring Strategies During Extracorporeal Membrane Oxygenation (ECMO) Therapy – Differences Between Simultaneously Obtained Coagulation Tests: A Retrospective Single-Center Cohort Study
Authors: Reisinger Alexander C. , Schneider Nikolaus , Koellinger Marco , Hatzl Stefan , Hackl Gerald , Raggam Reinhard , von Lewinski Dirk , Posch Florian , Eller Philipp 
Published: February 2025

Introduction During extracorporeal membrane oxygenation (ECMO) systemic anticoagulation with unfractionated heparin (UFH) is standard-of-care. However, there is uncertainty regarding optimal anticoagulation monitoring strategies. Methods We retrospectively investigated venovenous and venoarterial ECMO patients at the medical ICUs at the Medical University of Graz, Austria. We analyzed the correlation and concordance of R-time in thromboelastography (TEG), activated partial thromboplastin time (aPTT), and anti-Xa activity. The proportion within target range, the association of coagulation parameters above or below target range (aPTT 54–72 s; equals 1.5–2× upper limit of normal (ULN), anti-Xa activity 0.2–0.5 U/mL, and R-time in assays without heparinase 675–900 s; equals 1.5–2× ULN) with mortality, bleeding events and thrombotic complications were investigated. Results We analyzed 671 clusters of simultaneously performed coagulation tests in 85 ECMO cases that fulfilled inclusion criteria. Median age of patients was 57 years and 32% were female. There were poor correlations between the three coagulation tests and the proportion of discordance was 46%. Within the target range were 21% of R-time, 15% of aPTT, and 44% of anti-Xa activity measurements. Singular and multiple bleeding events occurred in 25 and 32 patients, respectively. The most common bleeding locations were catheter and cannula insertion sites followed by pulmonary hemorrhage. In VA-ECMO, anti-Xa activity was associated (OR 1.03 [1.01–1.06], p = 0.005) and correlated with bleeding events (spearman rho 0.49, p = 0.002; point biserial 0.49, p = 0.001). aPTT level below target range was associated with reduced mortality (OR 0.98 [0.97–0.99], p = 0.024). Thrombotic events occurred in six patients with no association of coagulation tests. Conclusion There was a high rate of discordance and poor correlation between aPTT, anti-Xa activity and R-time in TEG in ECMO patients. We found high rates of bleeding events and in VA-ECMO an association with elevated anti-Xa activity levels.