bluuebunny/crossref_metadata_2025_split huggingface dataset:
Construction and evaluation of a novel prognostic risk model of aging-related genes in bladder cancer
Authors: Wang Delin , Ning Hao , Wu Haihu , Song Yufeng , Chu Yaru , Liu Feifan , Zhao Zhenlin , Wu Fei , Lyu Jiaju 
Published: July 2023

Abstract

Background
Bladder cancer (BLCA) is the most common malignancy of the urinary system. Muscle-invasive bladder cancer (MIBC), which constitutes approximately 25% of all BLCA cases, is characterized by frequent recurrence and early onset of metastasis. Bladder cancer most commonly occurs in elderly patients and is significantly associated with aging. However, the prognostic value of age-related genes in BLCA, especially in MIBC, remains unclear.

Materials and methods
Training and testing sets were obtained from The Cancer Genome Atlas BLCA project. Differentially expressed genes between BLCA and normal samples intersected with human aging-related genes. Univariate Cox regression and least absolute shrinkage and selection operator regression analyses were used to identify prognostic aging-related signatures, followed by the construction of a risk score model and nomogram. Kaplan-Meier and receiver operating characteristic analyses were conducted to assess the predictive power. An independent BLCA cohort of 165 samples was included for external validation. The CIBERSORT algorithm was used to explore the characteristics of the immune microenvironment.

Results
Seven genes (IGF1, NGF, GCLM, PYCR1, EFEMP1, APOC3, and IFNB1) were identified by Cox and least absolute shrinkage and selection operator analyses. After combining the gene signature with the clinical parameters of patients with BLCA, a risk-prognosis model and nomogram were constructed and validated with the testing set. Bladder cancer cases with high 7-gene signature scores (high-risk group) and low scores (low-risk group) showed distinct prognoses. Furthermore, 7 types of immune cells were significantly altered between the low- and high-risk groups.

Conclusions
Collectively, our data provide a 7-gene signature that serves as a potential biomarker for BLCA, especially MIBC. Moreover, this 7-gene signature highlights the role of the tumor immune microenvironment in prognosis and thus might be related to the response to anti-programmed cell death protein 1–based immunotherapy.
Adherence and related cardiovascular outcomes to single pill vs. separate pill administration of antihypertensive triple-combination therapy
Authors: Rea Federico , Morabito Gabriella , Savaré Laura , Pathak Atul , Corrao Giovanni , Mancia Giuseppe 
Published: July 2023

Objective:
To compare adherence to antihypertensive treatment between patients prescribed a three-drug single-pill combination (SPC) of perindopril/amlodipine/indapamide (P/A/I) vs. the combination of an angiotensin-converting enzyme inhibitor (ACEI), a calcium-channel blocker (CCB), and a diuretic (D) as a two-drug SPC plus a third drug given separately.

Methods:
Using the healthcare utilization database of the Lombardy Region (Italy), the 28 210 patients, aged at least 40 years, who were prescribed P/A/I SPC during 2015–2018 were identified and the date of the first prescription was defined as the index date. For each patient prescribed the SPC, a comparator who started ACEI/CCB/D treatment as a two-pill combination was considered. Adherence to the triple combination was assessed over the year after the index date as the proportion of the follow-up days covered by prescription (PDC). Patients who had a PDC >75% were defined as highly adherent to drug therapy. Log-binomial regression models were fitted to estimate the risk ratio of treatment adherence in relation to the drug treatment strategy.

Results:
About 59 and 25% of SPC and two-pill combination users showed high adherence, respectively. Compared with patients under a three-drug two-pill combination, those who were treated with the three-drug SPC had a higher propensity to be highly adherent to the triple combination (2.38, 95% confidence interval: 2.32–2.44). This was the case regardless of the sex, age, comorbidities, and number of co-treatments.

Conclusions:
In a real-life setting, patients under three-drug SPC exhibited more frequently a high adherence to antihypertensive treatment than those prescribed a three-drug two-pill combination.
Assessment of cardiovascular disease risk: a 2023 update
Authors: Goldsborough Earl , Tasdighi Erfan , Blaha Michael J 
Published: July 2023

Purpose of review
The aim of this study was to highlight the current best practice for atherosclerotic cardiovascular disease (CVD) risk evaluation, including selective use of adjunctive tools for risk stratification [e.g. coronary artery calcium (CAC) scoring] and risk enhancement [e.g. lipoprotein(a) [Lp(a)], polygenic risk scoring (PRS)].

Recent findings
New studies have evaluated the efficacy of various risk assessment tools. These studies demonstrate the role of Lp(a) as a risk-enhancing factor ready for more widespread use. CAC is the gold standard method of assessing subclinical atherosclerosis, enabling true risk stratification of patients, and informing net benefit assessment for initiating or titrating lipid-lowering therapy (LLT).

Summary
Lp(a) concentration and CAC scoring, apart from the traditional risk factors, add the most value to the current CVD risk assessment approaches of all available tools, especially in terms of guiding LLT. In addition to new integrative tools such as the MESA CHD Risk Score and Coronary Age calculator, the future of risk assessment may include PRS and more advanced imaging techniques for atherosclerosis burden. Soon, polygenic risk scoring may be used to identify the age at which to begin CAC scoring, with CAC scores guiding preventive strategies.
Outcomes of People of Color in an Efficacy Trial of Cognitive-Behavioral Treatments for Anxiety, Depression, and Related Disorders
Authors: Cardona Nicole D. , Ametaj Amantia A. , Cassiello-Robbins Clair , Tirpak Julianne Wilner , Olesnycky Olenka , Sauer-Zavala Shannon , Farchione Todd J. , Barlow David H. 
Published: July 2023

Abstract
Although evidence-based psychological treatments such as cognitive behavioral therapy (CBT) have strong empirical support for reducing anxiety and depression symptoms, CBT outcome research often does not report race and ethnicity variables, or assess how well CBT works for people from historically excluded racial and ethnic groups. This study presents post hoc analyses comparing treatment retention and symptom outcomes for participants of color (n = 43) and White participants (n = 136) from a randomized controlled efficacy trial of CBT. χ2 tests and one-way ANCOVA showed no observable differences between the two samples on attrition or on clinician-rated measures of anxiety and depression at posttreatment and follow-up. Moderate to large within-group effect sizes on anxiety and depression were found for Black, Latinx, and Asian American participants at almost all time points. These preliminary findings suggest that CBT for anxiety and comorbid depression may be efficacious for Black, Asian American, and Latinx individuals.
Acute shortening and angulation for complex open fractures: an updated perspective
Authors: Pierrie Sarah N. , Beltran Michael J. 
Published: July 2023

Summary:Reestablishing an intact, healthy soft tissue envelope is a critical step in managing lower extremity injuries, particularly high-grade open tibia fractures. Acute shortening and angulation can be used independently or together to address complex soft tissue injuries, particularly when bone loss is present. These techniques facilitate management of difficult wounds and can be combined with local soft tissue rearrangement or pedicled flaps as needed, avoiding the need for free tissue transfer. After angular deformity correction, adjacent bone loss can be addressed with bone grafting or distraction histogenesis. This article discusses the indications for, surgical technique for, and limitations of acute shortening and angulation for management of open lower extremity fractures.
Reducing Intraoperative Hypothermia in Infants from the Neonatal Intensive Care Unit
Authors: Studer Abbey , Fleming Barbara , Jones Roderick C. , Rosenblatt Audrey , Sohn Lisa , Ivey Megan , Reynolds Marleta , Falciglia Gustave H. 
Published: July 2023

Introduction:
Infants from the neonatal intensive care unit (NICU) undergoing surgery in the operating room (OR) are at greater risk for hypothermia during surgery than afterward due to environmental heat loss, anesthesia, and inconsistent temperature monitoring. A multidisciplinary team aimed to reduce hypothermia (<36.1 °C) for infants at a level IV NICU at the beginning of the operation (first OR temperature) or at any time during the operation (lowest OR temperature) by 25%.

Methods:
The team followed preoperative, intraoperative (first, lowest, and last OR), and postoperative temperatures. It sought to reduce intraoperative hypothermia using the “Model for Improvement” by standardizing temperature monitoring, transport, and OR warming, including raising ambient OR temperatures to 74°F. Temperature monitoring was continuous, secure, and automated. The balancing metric was postoperative hyperthermia (>38 °C).

Results:
Over 4 years, there were 1235 operations: 455 in the baseline and 780 in the intervention period. The percentage of infants experiencing hypothermia upon OR arrival and at any point during the operation decreased from 48.7% to 6.4% and 67.5% to 37.4%, respectively. Upon return to the NICU, the percentage of infants experiencing postoperative hypothermia decreased from 5.8% to 2.1%, while postoperative hyperthermia increased from 0.8% to 2.6%.

Conclusions:
Intraoperative hypothermia is more prevalent than postoperative hypothermia. Standardizing temperature monitoring, transport, and OR warming reduces both; however, further reduction requires a better understanding of how and when risk factors contribute to hypothermia to avoid further increasing hyperthermia. Continuous, secure, and automated data collection improved temperature management by enhancing situational awareness and facilitating data analysis.
Feeding Outcomes After Mandibular Distraction for Airway Obstruction in Infants
Authors: Yi Amber , Brand William T. , Black Jonathan S. 
Published: July 2023

Robin sequence is a congenital issue resulting in airway obstruction, difficulty feeding, and failure to thrive. Mandibular Distraction Osteogenesis is used to improve airway obstruction in these patients, but little data exists characterizing feeding outcomes following surgery. This study aims to evaluate feeding outcomes and weight gain following mandibular distraction for airway correction in infants. A single-center retrospective chart review was conducted, and patients under 12 months old who underwent mandibular distraction between December 2015 and July 2021 were included in the study. The presence of cleft palate, distance of distraction, and polysomnography results were recorded. The primary outcomes were the length of distraction, need for nasogastric tube or G-tube at discharge, time lapsed to achieve full oral feeds, and weight gain (kilogram). Ten patients met the criteria. Of those 10 patients, 4 were syndromic, 7 had a cleft palate, and 4 had a congenital cardiac diagnosis. The average length of stay postsurgery was 28 days. Eight patients achieved full oral feeds in an average of 65.6 days. Five patients required nasogastric tube or G-tube at discharge, with 3 of these patients later transitioning to full oral feeds. All patients gained weight 3 months postsurgery with an average of 0.521 kg/mo. Patients who achieved full oral feeds gained an average of 0.549 kg/mo. Patients with supplementation gained an average of 0.454 kg/mo. All patients demonstrated improvement in airway obstruction with an average postoperative apnea hypopnea index of 1.64. Further investigation is necessary to identify challenges seen in feeding after mandibular distraction osteogenesis and improve care.
Quantifying Cell-State Densities in Single-Cell Phenotypic Landscapes using Mellon
Authors: Otto Dominik , Jordan Cailin , Dury Brennan , Dien Christine , Setty Manu 
Published: July 2023

AbstractCell-state density characterizes the distribution of cells along phenotypic landscapes and is crucial for unraveling the mechanisms that drive cellular differentiation, regeneration, and disease. Here, we present Mellon, a novel computational algorithm for high-resolution estimation of cell-state densities from single-cell data. We demonstrate Mellon’s efficacy by dissecting the density landscape of various differentiating systems, revealing a consistent pattern of high-density regions corresponding to major cell types intertwined with low-density, rare transitory states. Utilizing hematopoietic stem cell fate specification to B-cells as a case study, we present evidence implicating enhancer priming and the activation of master regulators in the emergence of these transitory states. Mellon offers the flexibility to perform temporal interpolation of time-series data, providing a detailed view of cell-state dynamics during the inherently continuous developmental processes. Scalable and adaptable, Mellon facilitates density estimation across various single-cell data modalities, scaling linearly with the number of cells. Our work underscores the importance of cell-state density in understanding the differentiation processes, and the potential of Mellon to provide new insights into the regulatory mechanisms guiding cellular fate decisions.
Diurnal variation of brain activity in the human suprachiasmatic nucleus
Authors: Oka Satoshi , Ogawa Akitoshi , Osada Takahiro , Tanaka Masaki , Nakajima Koji , Kamagata Koji , Aoki Shigeki , Oshima Yasushi , Tanaka Sakae , Kirino Eiji , Nakamura Takahiro J. , Konishi Seiki 
Published: July 2023

AbstractThe suprachiasmatic nucleus (SCN) is the central clock for circadian rhythms. Animal studies have revealed daily rhythms in the neuronal activity in the SCN. However, the circadian activity of the human SCN has remained elusive. In this study, to reveal the diurnal variation of the SCN activity in humans, the SCN was localized, and its activity was investigated using perfusion imaging. We scanned each participant four times a day, every six hours, and higher activity was observed at noon while lower activity was recorded in the early morning. The SCN activity was then measured every thirty minutes for six hours from midnight to dawn and showed a decreasing trend and was comparable with the rodent SCN activity after switching off the lights. These results suggest that the diurnal variation of the human SCN follows the zeitgeber cycles of mammals and is modulated by physical lights rather than the local time.
Signatures of Jamming in the Cellular Potts Model
Authors: Devanny Alexander J. , Lee Daniel J. , Kampman Lucas , Kaufman Laura J. 
Published: July 2023

AbstractWe explore the jamming transition in the Cellular Potts Model (CPM) as a function of confinement, cell adhesion, and cell shape. To accurately characterize jamming, we compare Potts simulations of unconfined single cells, cellular aggregates, and confluent monolayers as a function of cell adhesion energies and target cell shape. We consider metrics that may identify signatures of the jamming transition, including diffusion coefficients, anomalous diffusion exponents, cell shape, cell-cell rearrangements, and velocity correlations. We find that the onset of jamming coincides with an abrupt drop in cell mobility, rapid transition to sub-diffusive behavior, and cessation of rearrangements between neighboring cells that is unique to confluent monolayers. Velocity correlations reveal collective migration as a natural consequence of high energy barriers to neighbor rearrangements for certain cell types. Cell shapes across the jamming transition in the Potts model are found to be generally consistent with predictions of vertex-type simulations and trends from experiment. Finally, we demonstrate that changes in cell shape can fluidize cellular monolayers at cellular interaction energies where jamming otherwise occurs.
The Impact of AI-Based Modeling on the Accuracy of Protein Assembly Prediction: Insights from CASP15
Authors: Ozden Burcu , Kryshtafovych Andriy , Karaca Ezgi 
Published: July 2023

ABSTRACTIn CASP15, 87 predictors submitted around 11,000 models on 41 assembly targets. The community demonstrated exceptional performance in overall fold and interface contact prediction, achieving an impressive success rate of 90% (compared to 31% in CASP14). This remarkable accomplishment is largely due to the incorporation of DeepMind’s AF2-Multimer approach into custom-built prediction pipelines. To evaluate the added value of participating methods, we compared the community models to the baseline AF2-Multimer predictor. In over 1/3 of cases the community models were superior to the baseline predictor. The main reasons for this improved performance were the use of custom-built multiple sequence alignments, optimized AF2-Multimer sampling, and the manual assembly of AF2-Multimer-built subcomplexes. The best three groups, in order, are Zheng, Venclovas and Wallner. Zheng and Venclovas reached a 73.2% success rate over all (41) cases, while Wallner attained 69.4% success rate over 36 cases. Nonetheless, challenges remain in predicting structures with weak evolutionary signals, such as nanobody-antigen, antibody-antigen, and viral complexes. Expectedly, modeling large complexes remains also challenging due to their high memory compute demands.In addition to the assembly category, we assessed the accuracy of modeling interdomain interfaces in the tertiary structure prediction targets. Models on seven targets featuring 17 unique interfaces were analyzed. Best predictors achieved the 76.5% success rate, with the UM-TBM group being the leader. In the interdomain category, we observed that the predictors faced challenges, as in the case of the assembly category, when the evolutionary signal for a given domain pair was weak or the structure was large. Overall, CASP15 witnessed unprecedented improvement in interface modeling, reflecting the AI revolution seen in CASP14.
Pathogenic aggregates alter actin organization and cellular viscosity resulting in stalled clathrin mediated endocytosis
Authors: Singh Surya Bansi , Rajput Shatruhan Singh , Sharma Aditya , Ananthanarayanan Vaishnavi , Nandi Amitabha , Patil Shivprasad , Majumdar Amitabha , Subramanyam Deepa 
Published: July 2023

AbstractProtein aggregation is a common underlying feature of neurodegenerative disorders. Cells expressing neurodegeneration–associated mutant proteins show altered uptake of ligands, suggestive of impaired endocytosis, in a manner as yet unknown. Using live cell imaging, we show that clathrin-mediated endocytosis (CME) is affected due to altered actin cytoskeletal organization in the presence of Huntingtin aggregates. Additionally, we find that cells containing Huntingtin aggregates are stiffer and less viscous than their wild-type counterparts due to altered actin conformation, and not merely due to the physical presence of aggregate(s). We further demonstrate that CME and cellular viscosity can be rescued by overexpressing Hip1, Arp2/3 or transient LatrunculinA treatment. Examination of other pathogenic aggregates revealed that only a subset of these display defective CME, along with altered actin organization and increased stiffness. Together, our results point to an intimate connection between functional CME, actin organization and cellular stiffness in the context of neurodegeneration.
Preclinical assessment of CAR-NK cell-mediated killing efficacy and pharmacokinetics in a rapid zebrafish xenograft model of metastatic breast cancer
Authors: Shankar Nivedha Murali , Montero Paola Ortiz , Kurzyukova Anastasia , Rackwitz Wiebke , Künzel Stephan R. , Wels Winfried S. , Tonn Torsten , Knopf Franziska , Eitler Jiri 
Published: July 2023

ABSTRACTNatural killer (NK) cells are attractive effectors for adoptive immunotherapy of cancer. Results from first-in-human studies using chimeric antigen receptor (CAR)-engineered primary NK cells and NK-92 cells are encouraging in terms of efficacy and safety. In order to further improve treatment strategies and to test the efficacy of CAR-NK cells in a personalized manner, preclinical screening assays using patient-derived tumor samples are needed. Zebrafish (Danio rerio) embryos and larvae represent an attractive xenograft model to study growth and dissemination of patient-derived tumor cells because of their superb live cell imaging properties. Injection into the organism’s circulation allows investigation of metastasis, cancer cell-to-immune cell-interactions and studies of the tumor cell response to anti-cancer drugs.Here, we established a zebrafish larval xenograft model to test the efficacy of CAR-NK cells against metastatic breast cancerin vivoby injecting metastatic breast cancer cells followed by CAR-NK cell injection into the Duct of Cuvier (DoC). We validated the functionality of the system with two different CAR-NK cell lines specific for PD-L1 and ErbB2 (PD-L1.CAR NK-92 and ErbB2.CAR NK- 92 cells) against the PD-L1-expressing MDA-MB-231 and ErbB2-expressing MDA-MB-453 breast cancer cell lines.Injected cancer cells were viable and populated peripheral regions of the larvae, including the caudal hematopoietic tissue (CHT), simulating homing of cancer cells to blood forming sites. CAR-NK cells injected 2.5 hours later migrated to the CHT and rapidly eliminated individual cancer cells throughout the organism. Confocal live-cell imaging demonstrated intravascular migration and real-time interaction of CAR-NK cells with MDA-MB-231 cells, explaining the rapid and effectivein vivocytotoxicity.Thus, our data suggest that zebrafish larvae can be used for rapid and cost-effectivein vivoassessment of CAR-NK cell potency and to predict patient response to therapy.
Reshaping water-related urban places with collaborative participation: a critical examination of the Kabataş waterfront
Authors: Cihan Yavuzcan Meryem Melis , Gür Elmira Ayşe 
Published: July 2023

PurposeThis study aims to draw a general framework for recreating water-related urban places. It discusses design criteria and processes that will strengthen people's and the city's relationship with the waterfront. It also explores the functional requirements of a participatory process to incorporate social and functional relations into place making.Design/methodology/approachThe study is based on a comprehensive case study of the Kabataş project process. Data collection methods include archive searches, questionnaires, interviews and analysis. The study analyses the architectural decisions, the role and perspectives of the key actors and the current dynamics that shape the process. It points out shortcomings and needs of communication and collaboration with different stakeholders, especially with the users.FindingsThe results show that political and power dynamics play an important role in shaping the process. Non-transparent processes increase the gap between the aspects of community and decision makers in current practices. Establishing holistic, waterfront-specific and collaborative approaches is a necessity. The results also show that the success of participation depends on procedural dynamics such as scope, method, timing, representativeness of the community, institutionalisation level, transparency and deliberation.Originality/valueDespite the intense interest in waterfront regeneration, few studies have focused on the potential of the participatory process. The study examines the intersections of waterfront design decisions and collaborative participation at various scales and emphasises the importance of local actors in the social production of space.