bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does offering small financial incentives to smokers at the time of being wait-listed for surgery increase smoking cessation by the day of surgery? A randomised feasibility trial
Authors: Webb Ashley , Coward Lisa , Yousef Michael , Karamesinis Alexandra , Leong Samuel 
Published: December 2023

ObjectiveThis study aims to assess whether offering small financial incentives to smokers on elective surgery wait-lists is feasible and increases quitting before surgery.DesignRandomised controlled trial, prospective, double-blinded.SettingSingle-centre, Australian metropolitan public hospital.Participants620 adult smokers (≥10 cigarettes per day) were randomised on being wait-listed for elective surgery and 404 underwent operations (28 January 2021–31 July 2022) at the hospital (65.2%) by trial’s end.InterventionIntervention participants were offered at wait-listing an $A70 supermarket voucher for verified abstinence on the day of surgery, provided they registered an intention to quit before surgery. Registrants intending to quit were also referred to Quitline. Neither intervention was offered to control participants (usual care). Smokers wait-listed from 17 May 2021 were offered an increased incentive of $A140.Main outcome measuresPrimary outcome, quitting at least 24 hours before surgery, verified by exhaled carbon monoxide testing. Feasibility outcomes were the proportion taking up offers, ease of patient contact and disputes about quit status.ResultsOf 620 randomised participants (control 312, intervention 308), 404 had surgery at the hospital during the trial (control 214, intervention 190), which was lower than expected (for COVID-19 reasons). Offering $A70 resulted in 21.9% registering to quit, increasing to 32.6% with $A140. Telephone calls were the most effective means to gain registrations. The proportion of intervention group patients verified quit at least 24 hours before surgery was similar to controls (9.5% vs 8.9%, OR 1.1, 95% CI 0.5 to 2.2). Quitline contact was higher in the intervention group (13.2% vs 2.3%, OR 6.3, 95% CI 2.3 to 21.6). Disputes over test results did not occur, but 17.4% of intervention participants claiming quit failed verification.ConclusionA single offer of financial rewards for perioperative cessation was feasible, without achieving clinically important quit differences.Trial registration numberACTRN12620000130965.
RevealingRB1loss in an emerging entity: report of two cases of PRRX1-rearranged mesenchymal tumours
Authors: Cordier Fleur , Fadaei Sharareh , Ferdinande Liesbeth , Dochy Frederick , Vanwalleghem Lieve , Van Den Bossche Karolien , Loontiens Siebe , Van der Meulen Joni , Van Roy Nadine , Van Dorpe Jo , Creytens David 
Published: December 2023

AimsPRRX1-rearranged mesenchymal tumours are a recently identified and rare subgroup of soft tissue neoplasms with distinct morphological features and genetic alterations. This study aims to further investigate the immunohistochemical profile and underlying genetic alterations in these tumours in order to get more insight on their underlying biology and the unique profile of these tumours.MethodsTwo new molecular confirmed cases ofPRRX1-rearranged mesenchymal tumours were thoroughly studied with immunohistochemical stainings (RB1, CD34, ALK and pan-TRK), fluorescence in situ hybridisation (FISH)RB1/13q12and RNA-based next-generation sequencing.ResultsBoth cases exhibited typical morphological and molecular features, confirming the diagnosis ofPRRX1-rearranged mesenchymal tumours. Immunohistochemistry revealed RB1 loss in both cases, which was subsequently confirmed through FISH analysis. Additionally, one case showed focal positivity for CD34, ALK and pan-TRK on immunohistochemistry.ConclusionsWe identified loss ofRB1in two cases of PRRX1-rearranged mesenchymal tumours. This could suggest a potential association withRB1-deficient soft tissue tumours, although further research is necessary. Furthermore, the finding of focal positivity for CD34, ALK and pan-TRK on immunohistochemistry enriches the immunohistochemical profile of these tumours.
Screening instruments for early identification of unmet palliative care needs: a systematic review and meta-analysis
Authors: Xie Zhishan , Ding Jinfeng , Jiao Jingjing , Tang Siyuan , Huang Chongmei 
Published: December 2023

BackgroundThe early detection of individuals who require palliative care is essential for the timely initiation of palliative care services. This systematic review and meta-analysis aimed to (1) Identify the screening instruments used by health professionals to promote early identification of patients who may benefit from palliative care; and (2) Assess the psychometric properties and clinical performance of the instruments.MethodsA comprehensive literature search was conducted in PubMed, Embase, CINAHL, Scopus, CNKI and Wanfang from inception to May 2023. We used the COnsensus-based Standards for the Selection of Health Measurement INstruments to assess the methodological quality of the development process for the instruments. The clinical performance of the instruments was assessed by narrative summary or meta-analysis. Subgroup analyses were conducted where necessary. The quality of included studies was assessed using the Newcastle-Ottawa Scale and the Cochrane Collaboration’s risk of bias assessment tool.ResultsWe included 31 studies that involved seven instruments. Thirteen studies reported the development and validation process of these instruments and 18 studies related to assessment of clinical performance of these instruments. The content validity of the instruments was doubtful or inadequate because of very low to moderate quality evidence. The pooled sensitivity (Se) ranged from 60.0% to 73.8%, with high heterogeneity (I2 of 88.15% to 99.36%). The pooled specificity (Sp) ranges from 70.4% to 90.2%, with high heterogeneity (I2 of 96.81% to 99.94%). The Supportive and Palliative Care Indicators Tool (SPICT) had better performance in hospitals than in general practice settings (Se=79.8% vs 45.3%, p=0.004; Sp=59.1% vs 97.0%, p=0.000).ConclusionThe clinical performance of existing instruments in identifying patients with palliative care needs early ranged from poor to reasonable. The SPICT is used most commonly, has better clinical performance than other instruments but performs better in hospital settings than in general practice settings.
Mortality rate and palliative sedation in an acute palliative care unit
Authors: Mercadante Sebastiano , Lo Cascio Alessio , Casuccio Alessandra 
Published: December 2023

AimTo assess the mortality rate and the use of palliative sedation (PS) in an advanced long-standing acute palliative care unit (APCU)MethodsThe charts of patients who died and eventually received PS, consecutively admitted to the APCU for 4 years, were reviewed. Patients’ characteristics and symptom intensity were recorded at admission, 3 days before death and the day before death (T0, T-3, T-end, respectively). For patients who were administered midazolam for PS, initial and final doses of drugs, as well as duration of PS until death, were recorded.ResultsOne hundred and forty-eight patients died in APCU (8.9%), and 45 of them (30.4%) received PS. Younger patients and those reporting high levels of dyspnoea at T-3 and T-end were more likely to be sedated (p=0.002, p=0.013 and 0.002, respectively). The mean duration of PS was 27.47 hours. Mean initial and final doses of midazolam were 35.45 mg/day (SD 19.7) and 45.57 mg/day (SD 20.6), respectively (p=0.001).ConclusionMortality rate in APCU was very low. As a percentage of the number of deaths, PS rate was similar to that reported in other settings. PS does not seem to accelerate impending death.
Synrift and post-rift thermal evolution of rifted margins: a re-evaluation of classic models of extension
Authors: Pérez-Gussinyé Marta , Xin Yanfang , Cunha Tiago , Ram Raghu , Andrés-Martínez Miguel , Dong Dongdong , García-Pintado Javier 
Published: December 2023

Abstract

The thermal evolution of continental rifted margins is key to understanding margin subsidence and hydrocarbon prospectivity. Observed heat-flow values, however, do not always comply with classic rifting models. Here, we use 2D numerical models to investigate the relationship between rifting, sedimentation and thermal history of margins. We find that during the synrift, the basement heat-flow and temperature are not only controlled by extension factor, but also by synrift sediment thickness and the evolution of deformation. As this progressively focuses oceanward, the proximal sectors thermally relax, while the distal sectors experience peak temperatures. In the post-rift, the lithosphere under the hyperextended margins does not return to its original state, at least for
c.
100 Myr after break-up. Instead, it mimics that of the adjacent oceanic plate, which is thinner than the original continental plate. This results in heat-flow increasing oceanward at post-rift stages, when classic rifting theory predicts complete thermal relaxation. Our models also predict slightly increased heat-flows in the adjacent oceanic crust, potentially extending hydrocarbon plays into distal margins and oceanic crust, previously discarded as immature. Finally, our models indicate that commonly used temperature approximations to calculate heat-flow during rifting may strongly differ from those occurring in nature.
ApHMM: Accelerating Profile Hidden Markov Models for Fast and Energy-efficient Genome Analysis
Authors: Firtina Can , Pillai Kamlesh , Kalsi Gurpreet S. , Suresh Bharathwaj , Cali Damla Senol , Kim Jeremie S. , Shahroodi Taha , Cavlak Meryem Banu , Lindegger Joël , Alser Mohammed , Luna Juan Gómez , Subramoney Sreenivas , Mutlu Onur 
Published: December 2023

Profile hidden Markov models (pHMMs) are widely employed in various bioinformatics applications to identify similarities between biological sequences, such as DNA or protein sequences. In pHMMs, sequences are represented as graph structures, where states and edges capture modifications (i.e., insertions, deletions, and substitutions) by assigning probabilities to them. These probabilities are subsequently used to compute the similarity score between a sequence and a pHMM graph. The Baum-Welch algorithm, a prevalent and highly accurate method, utilizes these probabilities to optimize and compute similarity scores. Accurate computation of these probabilities is essential for the correct identification of sequence similarities. However, the Baum-Welch algorithm is computationally intensive, and existing solutions offer either software-only or hardware-only approaches with fixed pHMM designs. When we analyze state-of-the-art works, we identify an urgent need for a flexible, high-performance, and energy-efficient hardware-software co-design to address the major inefficiencies in the Baum-Welch algorithm for pHMMs.We introduceApHMM, thefirstflexible acceleration framework designed to significantly reduce both computational and energy overheads associated with the Baum-Welch algorithm for pHMMs. ApHMM employs hardware-software co-design to tackle the major inefficiencies in the Baum-Welch algorithm by (1) designing flexible hardware to accommodate various pHMM designs, (2) exploiting predictable data dependency patterns through on-chip memory with memoization techniques, (3) rapidly filtering out unnecessary computations using a hardware-based filter, and (4) minimizing redundant computations.ApHMM achieves substantial speedups of 15.55×–260.03×, 1.83×–5.34×, and 27.97× when compared to CPU, GPU, and FPGA implementations of the Baum-Welch algorithm, respectively. ApHMM outperforms state-of-the-art CPU implementations in three key bioinformatics applications: (1) error correction, (2) protein family search, and (3) multiple sequence alignment, by 1.29×–59.94×, 1.03×–1.75×, and 1.03×–1.95×, respectively, while improving their energy efficiency by 64.24×–115.46×, 1.75×, and 1.96×.
FGFR1 Signaling Facilitates Obesity-Driven Pulmonary Outgrowth in Metastatic Breast Cancer
Authors: Kulkoyluoglu Cotul Eylem , Safdar Muhammad Hassan , Paez Sebastian Juan , Kulkarni Aneesha , Ayers Mitchell G. , Lin Hang , Xianyu Zilin , Teegarden Dorothy , Hursting Stephen D. , Wendt Michael K. 
Published: December 2023

Abstract

Survival of dormant, disseminated breast cancer cells contributes to tumor relapse and metastasis. Women with a body mass index greater than 35 have an increased risk of developing metastatic recurrence. Herein, we investigated the effect of diet-induced obesity (DIO) on primary tumor growth and metastatic progression using both metastatic and systemically dormant mouse models of breast cancer. This approach led to increased PT growth and pulmonary metastasis. We developed a novel protocol to induce obesity in Balb/c mice by combining dietary and hormonal interventions with a thermoneutral housing strategy. In contrast to standard housing conditions, ovariectomized Balb/c mice fed a high-fat diet under thermoneutral conditions became obese over a period of 10 weeks, resulting in a 250% gain in fat mass. Obese mice injected with the D2.OR model developed macroscopic pulmonary nodules compared with the dormant phenotype of these cells in mice fed a control diet. Analysis of the serum from obese Balb/c mice revealed increased levels of FGF2 as compared with lean mice. We demonstrate that serum from obese animals, exogenous FGF stimulation, or constitutive stimulation through autocrine and paracrine FGF2 is sufficient to break dormancy and drive pulmonary outgrowth. Blockade of FGFR signaling or specific depletion of FGFR1 prevented obesity-associated outgrowth of the D2.OR model.

Implications:
Overall, this study developed a novel DIO model that allowed for demonstration of FGF2:FGFR1 signaling as a key molecular mechanism connecting obesity to breakage of systemic tumor dormancy and metastatic progression.
Breast Cancer Polygenic-Risk Score Influence on Risk-Reducing Endocrine Therapy Use: Genetic Risk Estimate (GENRE) Trial 1-Year and 2-Year Follow-Up
Authors: Stan Daniela L. , Kim Julian O. , Schaid Daniel J. , Carlson Erin E. , Kim Christina A. , Sinnwell Jason P. , Couch Fergus J. , Vachon Celine M. , Cooke Andrew L. , Goldenberg Benjamin A. , Pruthi Sandhya 
Published: December 2023

Abstract

Refinement of breast cancer risk estimates with a polygenic-risk score (PRS) may improve uptake of risk-reducing endocrine therapy (ET). A previous clinical trial assessed the influence of adding a PRS to traditional risk estimates on ET use. We stratified participants according to PRS-refined breast cancer risk and evaluated ET use and ET-related quality of life (QOL) at 1-year (previously reported) and 2-year follow-ups. Of 151 participants, 58 (38.4%) initiated ET, and 22 (14.6%) discontinued ET by 2 years; 42 (27.8%) and 36 (23.8%) participants were using ET at 1- and 2-year follow-ups, respectively. At the 2-year follow-up, 39% of participants with a lifetime breast cancer risk of 40.1% to 100.0%, 18% with a 20.1% to 40.0% risk, and 16% with a 0.0% to 20.0% risk were taking ET (overall P = 0.01). Moreover, 40% of participants whose breast cancer risk increased by 10% or greater with addition of the PRS to a traditional breast cancer-risk model were taking ET versus 0% whose risk decreased by 10% or greater (P = 0.004). QOL was similar for participants taking or not taking ET at 1- and 2-year follow-ups, although most who discontinued ET did so because of adverse effects. However, these QOL results may have been skewed by the long interval between QOL surveys and lack of baseline QOL data. PRS-informed breast cancer prevention counseling has a lasting, but waning, effect over time. Additional follow-up studies are needed to address the effect of PRS on ET adherence, ET-related QOL, supplemental breast cancer screening, and other risk-reducing behaviors.

Prevention Relevance:
Risk-reducing medications for breast cancer are considerably underused. Informing women at risk with precise and individualized risk assessment tools may substantially affect the incidence of breast cancer. In our study, a risk assessment tool (IBIS-polygenic-risk score) yielded promising results, with 39% of women at highest risk starting preventive medication.
Blood Monocyte Phenotype Is A Marker of Cardiovascular Risk in Type 2 Diabetes
Authors: Julla Jean-Baptiste , Girard Diane , Diedisheim Marc , Saulnier Pierre-Jean , Tran Vuong Bao , Blériot Camille , Carcarino Elena , De Keizer Joe , Orliaguet Lucie , Nemazanyy Ivan , Potier Charline , Khider Kennan , Tonui Dorothy Chepngenoh , Ejlalmanesh Tina , Ballaire Raphaelle , Mambu Mambueni Hendrick , Germain Stéphane , Gaborit Bénédicte , Vidal-Trécan Tiphaine , Riveline Jean-Pierre , Garchon Henri-Jean , Fenaille François , Lemoine Sophie , Carlier Aurélie , Castelli Florence , Potier Louis , Masson David , Roussel Ronan , Vandiedonck Claire , Hadjadj Samy , Alzaid Fawaz , Gautier Jean-François , Venteclef Nicolas 
Published: December 2023

BACKGROUND:
Diabetes is a major risk factor for atherosclerotic cardiovascular diseases with a 2-fold higher risk of cardiovascular events in people with diabetes compared with those without. Circulating monocytes are inflammatory effector cells involved in both type 2 diabetes (T2D) and atherogenesis.

METHODS:
We investigated the relationship between circulating monocytes and cardiovascular risk progression in people with T2D, using phenotypic, transcriptomic, and metabolomic analyses. cardiovascular risk progression was estimated with coronary artery calcium score in a cohort of 672 people with T2D.

RESULTS:
Coronary artery calcium score was positively correlated with blood monocyte count and frequency of the classical monocyte subtype. Unsupervised k-means clustering based on monocyte subtype profiles revealed 3 main endotypes of people with T2D at varying risk of cardiovascular events. These observations were confirmed in a validation cohort of 279 T2D participants. The predictive association between monocyte count and major adverse cardiovascular events was validated through an independent prospective cohort of 757 patients with T2D. Integration of monocyte transcriptome analyses and plasma metabolomes showed a disruption of mitochondrial pathways (tricarboxylic acid cycle, oxidative phosphorylation pathway) that underlined a proatherogenic phenotype.

CONCLUSIONS:
In this study, we provide evidence that frequency and monocyte phenotypic profile are closely linked to cardiovascular risk in patients with T2D. The assessment of monocyte frequency and count is a valuable predictive marker for risk of cardiovascular events in patients with T2D.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04353869
INO80-Dependent Remodeling of Transcriptional Regulatory Network Underlies the Progression of Heart Failure
Authors: Ren Zongna , Zhao Wanqing , Li Dandan , Yu Peng , Mao Lin , Zhao Quanyi , Yao Luyan , Zhang Xuelin , Liu Yandan , Zhou Bingying , Wang Li 
Published: December 2023

BACKGROUND:
Progressive remodeling of cardiac gene expression underlies decline in cardiac function, eventually leading to heart failure. However, the major determinants of transcriptional network switching from normal to failed hearts remain to be determined.

METHODS:
In this study, we integrated human samples, genetic mouse models, and genomic approaches, including bulk RNA sequencing, single-cell RNA sequencing, chromatin immunoprecipitation followed by high-throughput sequencing, and assay for transposase-accessible chromatin with high-throughput sequencing, to identify the role of chromatin remodeling complex INO80 in heart homeostasis and dysfunction.

RESULTS:

The INO80 chromatin remodeling complex was abundantly expressed in mature cardiomyocytes, and its expression further increased in mouse and human heart failure. Cardiomyocyte-specific overexpression of
Ino80
, its core catalytic subunit, induced heart failure within 4 days. Combining RNA sequencing, chromatin immunoprecipitation followed by high-throughput sequencing, and assay for transposase-accessible chromatin with high-throughput sequencing, we revealed INO80 overexpression-dependent reshaping of the nucleosomal landscape that remodeled a core set of transcription factors, most notably the MEF2 (Myocyte Enhancer Factor 2) family, whose target genes were closely associated with cardiac function. Conditional cardiomyocyte-specific deletion of
Ino80
in an established mouse model of heart failure demonstrated remarkable preservation of cardiac function.

CONCLUSIONS:
In summary, our findings shed light on the INO80-dependent remodeling of the chromatin landscape and transcriptional networks as a major mechanism underlying cardiac dysfunction in heart failure, and suggest INO80 as a potential preventative or interventional target.
Metabolic Communication by SGLT2 Inhibition
Authors: Billing Anja M. , Kim Young Chul , Gullaksen Søren , Schrage Benedikt , Raabe Janice , Hutzfeldt Arvid , Demir Fatih , Kovalenko Elina , Lassé Moritz , Dugourd Aurelien , Fallegger Robin , Klampe Birgit , Jaegers Johannes , Li Qing , Kravtsova Olha , Crespo-Masip Maria , Palermo Amelia , Fenton Robert A. , Hoxha Elion , Blankenberg Stefan , Kirchhof Paulus , Huber Tobias B. , Laugesen Esben , Zeller Tanja , Chrysopoulou Maria , Saez-Rodriguez Julio , Magnussen Christina , Eschenhagen Thomas , Staruschenko Alexander , Siuzdak Gary , Poulsen Per L. , Schwab Clarissa , Cuello Friederike , Vallon Volker , Rinschen Markus M. 
Published: December 2023

BACKGROUND:
SGLT2 (sodium-glucose cotransporter 2) inhibitors (SGLT2i) can protect the kidneys and heart, but the underlying mechanism remains poorly understood.

METHODS:
To gain insights on primary effects of SGLT2i that are not confounded by pathophysiologic processes or are secondary to improvement by SGLT2i, we performed an in-depth proteomics, phosphoproteomics, and metabolomics analysis by integrating signatures from multiple metabolic organs and body fluids after 1 week of SGLT2i treatment of nondiabetic as well as diabetic mice with early and uncomplicated hyperglycemia.

RESULTS:
Kidneys of nondiabetic mice reacted most strongly to SGLT2i in terms of proteomic reconfiguration, including evidence for less early proximal tubule glucotoxicity and a broad downregulation of the apical uptake transport machinery (including sodium, glucose, urate, purine bases, and amino acids), supported by mouse and human SGLT2 interactome studies. SGLT2i affected heart and liver signaling, but more reactive organs included the white adipose tissue, showing more lipolysis, and, particularly, the gut microbiome, with a lower relative abundance of bacteria taxa capable of fermenting phenylalanine and tryptophan to cardiovascular uremic toxins, resulting in lower plasma levels of these compounds (including p-cresol sulfate). SGLT2i was detectable in murine stool samples and its addition to human stool microbiota fermentation recapitulated some murine microbiome findings, suggesting direct inhibition of fermentation of aromatic amino acids and tryptophan. In mice lacking SGLT2 and in patients with decompensated heart failure or diabetes, the SGLT2i likewise reduced circulating p-cresol sulfate, and p-cresol impaired contractility and rhythm in human induced pluripotent stem cell–derived engineered heart tissue.

CONCLUSIONS:
SGLT2i reduced microbiome formation of uremic toxins such as p-cresol sulfate and thereby their body exposure and need for renal detoxification, which, combined with direct kidney effects of SGLT2i, including less proximal tubule glucotoxicity and a broad downregulation of apical transporters (including sodium, amino acid, and urate uptake), provides a metabolic foundation for kidney and cardiovascular protection.