bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leveraging Tissue-Specific Enhancer–Target Gene Regulatory Networks Identifies Enhancer Somatic Mutations That Functionally Impact Lung Cancer
Authors: Hariprakash Judith Mary , Salviato Elisa , La Mastra Federica , Sebestyén Endre , Tagliaferri Ilario , Silva Raquel Sofia , Lucini Federica , Farina Lorenzo , Cinquanta Mario , Rancati Ilaria , Riboni Mirko , Minardi Simone Paolo , Roz Luca , Gorini Francesca , Lanzuolo Chiara , Casola Stefano , Ferrari Francesco 
Published: October 2023

Abstract

Enhancers are noncoding regulatory DNA regions that modulate the transcription of target genes, often over large distances along with the genomic sequence. Enhancer alterations have been associated with various pathological conditions, including cancer. However, the identification and characterization of somatic mutations in noncoding regulatory regions with a functional effect on tumorigenesis and prognosis remain a major challenge. Here, we present a strategy for detecting and characterizing enhancer mutations in a genome-wide analysis of patient cohorts, across three lung cancer subtypes. Lung tissue–specific enhancers were defined by integrating experimental data and public epigenomic profiles, and the genome-wide enhancer–target gene regulatory network of lung cells was constructed by integrating chromatin three-dimensional architecture data. Lung cancers possessed a similar mutation burden at tissue-specific enhancers and exons but with differences in their mutation signatures. Functionally relevant alterations were prioritized on the basis of the pathway-level integration of the effect of a mutation and the frequency of mutations on individual enhancers. The genes enriched for mutated enhancers converged on the regulation of key biological processes and pathways relevant to tumor biology. Recurrent mutations in individual enhancers also affected the expression of target genes, with potential relevance for patient prognosis. Together, these findings show that noncoding regulatory mutations have a potential relevance for cancer pathogenesis and can be exploited for patient classification.

Significance:
Mapping enhancer–target gene regulatory interactions and analyzing enhancer mutations at the level of their target genes and pathways reveal convergence of recurrent enhancer mutations on biological processes involved in tumorigenesis and prognosis.
Interactions between Gravity Waves and Cirrus Clouds: Asymptotic Modeling of Wave-Induced Ice Nucleation
Authors: Dolaptchiev Stamen I. , Spichtinger Peter , Baumgartner Manuel , Achatz Ulrich 
Published: October 2023

Abstract
We present an asymptotic approach for the systematic investigation of the effect of gravity waves (GWs) on ice clouds formed through homogeneous nucleation. In particular, we consider high- and midfrequency GWs in the tropopause region driving the formation of ice clouds, modeled with a double-moment bulk ice microphysics scheme. The asymptotic approach allows for identifying reduced equations for self-consistent description of the ice dynamics forced by GWs including the effects of diffusional growth and nucleation of ice crystals. Further, corresponding analytical solutions for a monochromatic GW are derived under a single-parcel approximation. The results provide a simple expression for the nucleated number of ice crystals in a nucleation event. It is demonstrated that the asymptotic solutions capture the dynamics of the full ice model and accurately predict the nucleated ice crystal number. The present approach is extended to allow for superposition of GWs, as well as for variable ice crystal mean mass in the deposition. Implications of the results for an improved representation of GW variability in cirrus parameterizations are discussed.
Challenges and Opportunities in Recruiting Research Participants Using Facebook: Lessons Learned from an Exemplar Study
Authors: Ashfield Sarah , Donelle Lorie , Smith Maxwell , Dubé Ève , Tryphonopoulos Panagiota 
Published: October 2023

Background Facebook is a prominent social medial platform frequently used for business marketing. Researchers are starting to recognize the utility of this platform for developing research awareness, information dissemination, and more recently participant recruitment. Purpose This paper will provide an overview of methods used in Facebook recruitment through an exemplar study. It will highlight successes and challenges and provide insight into future opportunities for its’ use. Methods Two methods of Facebook recruitment are outlined in this paper: the use of Facebook groups and paid advertising. A step-by-step guide highlights how researchers can implement these specific methods of Facebook recruitment. Results Facebook was successfully utilized to recruit participants in the exemplar study. Recruitment was completed over a period of 82 days with a total cost of $157.09 Canadian dollars. Conclusion Facebook is a viable method of recruiting research participants. This method can be cost-effective, timely, and efficient in comparison to traditional research recruitment methods. However, one must balance the benefits and challenges of this type of recruitment.
The correlation between pregnancy, disease activity and adverse pregnancy outcomes in patients with systemic lupus erythematosus
Authors: Çetin Çiğdem , Saraç-Sivrikoz Tuğba , Ateş-Tıkız Müge , Zaralı Sibel , Ersoy Ayşenur , Yalçınkaya Yasemin , Gül Ahmet , İnanç Murat , Has Recep , Kalelioğlu İbrahim , Artım Esen Bahar 
Published: October 2023

Objective In this study, our pregnant systemic lupus erythematosus (SLE) cohort, which was under medical surveillance of both our Rheumatology and Obstetrics departments, was analyzed. We intended to determine the effects of pregnancy on disease activity and the correlation between disease flares and adverse pregnancy outcomes. Methods One hundred sixty eight pregnancy data involving 136 patients with SLE were examined. Cumulative clinical, laboratory, and serological parameters were described. Disease activity and flares were calculated using the systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) in the pre/postpartum periods and the SLEPDAI in the three trimesters of pregnancy. Patients with a SLEDAI-2K or SLEPDAI ≥ 4 were classified as “active.” Patients with lupus low disease activity state (LLDAS) during each of these periods were identified. Fetal/neonatal death, premature birth due to pre-eclampsia, eclampsia or hemolysis, elevated Liver enzymes (HELLP) syndrome, and neonates small for gestational age were determined as adverse pregnancy outcomes (APO). Results Out of 168 pregnancies, there were 60 (35.7%) pregnancies with flares covering the pregnancy and 6 months of postpartum period. The mean SLEDAI in the 6 months postpartum period was significantly higher compared to mean disease activity during pregnancy ( p < .05). Of all pregnancies, 132 (78.6%) were in LLDAS during pregnancy. Comparison of the frequency of severe postpartum flares in patients who were in LLDAS during pregnancy revealed a lower percentage of flares compared to those who were not in the LLDAS group (11 vs 29%, p < .05). APO was observed in 33.9% of 168 pregnancies. The mean SLEPDAI score was significantly higher in APO+ pregnancies than in APO− pregnancies (4.9 ± 6.1 vs 2.8 ± 4.9, p = .002). Comparison of SLICC damage score between APO – and + pregnancies revealed a significantly higher score in APO+ pregnancies (1.8 ± 2.1 vs 0.8 ± 1.3, p = .001). Conclusion Postpartum six-month period appears to have the highest risk for disease flares during SLE pregnancies. Disease activity during pregnancy increases the risk of APO. In order to achieve a positive pregnancy outcome and lower maternal morbidity, regular follow-up of patients is necessary.
Walled City of Lahore Authority: The Royal Trail Heritage Project
Authors: Waheed Zehra , Khan Noor Us Sabah 
Published: October 2023

This case is designed for MBA and undergraduate courses, aiming to emphasize the importance of stakeholder management in projects and familiarize participants with effective stakeholder management tools. The scenario revolves around a project involving community revitalization and historic preservation located in Lahore, Pakistan, known as the ‘City of Gardens’. The project area includes significant historical landmarks and charming, close-knit residential neighbourhoods where interconnected communities have lived for generations. The case unfolds through the perspective of Kamran Lashari, the protagonist, who inherits a challenging project burdened by a history of unsuccessful and possibly unmotivated predecessors. This project is facing a multitude of issues, spanning technical and managerial aspects. Its success is critical not only for its own sake but also because it sets the precedent for a series of ambitious community revitalization projects planned within the City of Gardens. Failure here could jeopardize future projects, strain relations with donors and permanently alienate the local community. The local community has harboured scepticism towards such endeavours, given their prior experiences with half-hearted attempts that brought inconvenience without any lasting benefits. These past efforts have left a bitter taste, making the community wary of new initiatives. Additionally, the project relies heavily on its partnership with the Aga Khan Trust for Culture, which provides invaluable technical support without substantial financial compensation. However, in Kamran Lashari’s inherited situation, this crucial partnership appears to be in shambles. In the classroom setting, students are encouraged to delve into a systematic analysis of the project’s extensive array of stakeholders, each with their own unique interests. This case provides an ideal backdrop for examining various stakeholder analysis frameworks, including the Warees Framework, Donaldson and Preston’s (1995) theory distinguishing between influencers and stakeholders based on power, legitimacy and urgency, as well as the power-support matrix. These frameworks offer valuable tools for dissecting and understanding the complex web of relationships and interests involved in this high-stakes project.
Buccal Fat Pad in Primary and Secondary Cleft Palate Repair: A Systematic Review of the Literature
Authors: Romero-Narvaez Carolina , Lin Lawrence O. , Kirschner Richard E. 
Published: October 2023

Objective To review the evidence supporting the use of buccal fat pad (BFP) in primary and secondary cleft palate repair and its short- and long- term clinical outcomes. Design Systematic review conducted by 2 independent reviewers following PRISMA guidelines. Setting: None Participants Articles were identified from three databases (Pubmed/Medline, Embase and Web of Science). Search terms included “cleft palate”, “palatoplasty”, “palate repair”, “buccal fat pad”. Interventions Use of BFP in primary and secondary cleft palatoplasty. Main Outcome Measures Primary outcomes were immediate postoperative complications, postoperative fistula, and maxillary growth. Secondary outcomes were palatal length, speech, and donor site morbidity. Results Ninety-one reports were retrieved after excluding duplicates. Twenty-three studies were included (13 case series and 10 comparative studies). Overall level of evidence was low. Randomized and non-randomized studies had a high risk of bias. In primary palatoplasty, BFP was more frequently used filling lateral relaxing incisions(57.4%), or in the hard-soft palate junction and covering mucosal defects(30.1%). In these patients, post operative fistula incidence was 2.8%. Two studies found wider transverse maxillary dimensions after BFP use. No higher incidence of bleeding, infection, dehiscence, or flap necrosis was reported. In secondary palatoplasty, no recurrent fistulas were reported for patients undergoing BFP for fistula repair. Conclusions BFP appears to be associated with a favorable impact in fistula prevention and management, as well as in transverse maxillary growth. However, there is a high heterogeneity among studies, high risk of bias and overall low quality of evidence. More high-quality research with long-term follow-up is warranted.
Optimization of safflower oil-based polyester biocomposite reinforced with diatomite: An response surface methodology approach and assessment of artificial neural network findings
Authors: Dağ Mustafa 
Published: October 2023

In this investigation, the examination revolves around the characterization of diatomite-enhanced modified safflower oil (MSO)-derived polyester biocomposites. The primary objective is to explore the feasibility of these biocomposites as a substitute for petrochemical-based unsaturated polyester (UP) materials, with the overarching goal of enhancing their economic sustainability. Experimental data analysis employed Response Surface Methodology (RSM) and Artificial Neural Network (ANN), uncovering the optimal composition for the polyester biocomposite to be 6.7 wt.% MSO and 4.5 wt.% diatomite. During the RSM analysis, it was noted that the response parameters exhibited quadratic p-values, specifically, for density ( p < .0001), thermal conductivity ( p < .0001), and Shore D hardness ( p < .0003). However, higher ratios of MSO lead to decreased hardness and increased curing time. SEM images reveal a detrimental impact on the surface morphology of the polyester biocomposite when the diatomite content reaches 8 wt.%. Additionally, Fourier Transform Infrared Spectroscopy (FTIR) and Thermogravimetric Analysis (TGA) offer valuable insights into the chemical bond structure and thermal behavior of the biocomposite, respectively. The Cure Index (CI) value for the diatomite-enhanced composite was determined to be 0.925, indicating a favorable contribution to the polyester curing process. The study finds that diatomite contributes to a linear change in the thermal conductivity coefficient, making the biocomposite suitable for use in the insulation industry. Overall, the study suggests that diatomite reinforced MSO-based polyester biocomposites have the potential as an alternative to petrochemical unsaturated polyester.
Delay to Surgical Treatment in Geriatric Hip Fracture Patients
Authors: Joseph Elias G. , Serotte Jordan , Haider Mohammad N. , Pavlesen Sonja , Anders Mark 
Published: October 2023

Background Hip fractures in the geriatric population are frequently encountered. There is increasing focus on minimizing the delay to surgery in these patients. This study was designed to evaluate factors responsible for a delay to surgery in a geriatric hip fracture population and how time to surgery affects mortality. Methods A retrospective cohort of patients sustaining low energy geriatric hip fractures in either an American College of Surgeons (ACS) verified Level 1 trauma center or a local university affiliated community teaching hospital were reviewed. The following variables were evaluated as independent risk factors for delay to surgery: demographic data, surgical details, use of cardiology resources, treatment center, and comorbidities. As a secondary objective, the effect of time to surgery on 1 year mortality was analyzed. Results 1157 patients met inclusion criteria. The following factors increased the risk of delay to surgery greater than 48 hours: male sex, treatment in a community hospital (versus trauma center), older age, multiple comorbidities (eg, cardiovascular-related conditions or other fractures), cardiology consultation, and an American Society of Anesthesiologists physical status score of 3 or 4. Cardiology consultation was the strongest independent predictor of risk for delay to surgery of >48 hours (odds ratio, 6.68; 95% confidence interval, 4.40 to 10.14; P < .001). The 1-year mortality of patients did not differ when surgical treatment occurred before 48 hours or after 48 hours (Log-rank test P = .109). Conclusion The presence of cardiovascular comorbidities and cardiology consultations can delay surgical treatments for hip fractures in patients greater than 65 years old, but the delay did not influence 1-year all-cause mortality. Level of Evidence Level IV.
Are Autonomous Vehicles Really “Autonomous?”: The Importance of Human Factors in AV Safety
Authors: Valdovinos Samantha , Barbrack Claire , Podest Nicole 
Published: October 2023

Autonomous vehicles are automobiles that require no human intervention, but they still require user awareness. They are not yet fully developed, and their goal is to be completely autonomous. Despite having stricter safety standards than traditional vehicles, they are not yet safe enough. So, what is “safe enough?” Before going into depth about changes that should be made to enhance safety culture, a detailed explanation of the current information on autonomous vehicles will set up the improvements to follow: (1) the definition of autonomous vehicles (background), (2) the problem, (3) current state of autonomous vehicles and (4) future actions to take. Through extensive research, autonomous vehicles have been found to lack clear expectations from the user and efficacy from the existing safety regulations, which leads the research of this paper towards the next steps for an appropriate safety culture.
Racial and ethnic differences in clinical outcomes among patients with multiple myeloma treated with CAR T-cell therapy
Authors: Peres Lauren C. , Oswald Laura B. , Dillard Christen M. , De Avila Gabriel , Nishihori Taiga , Blue Brandon J. , Freeman Ciara L. , Locke Frederick L. , Alsina Melissa , Castaneda Puglianini Omar , Shune Leyla , Sborov Douglas W. , Wagner Charlotte , Dima Danai , Hashmi Hamza , Davis James A. , Kocoglu Mehmet H. , Badros Ashraf Z. , Atrash Shebli , Simmons Gary , Kalariya Nilesh , Ferreri Christopher , Anderson Larry D. , Afrough Aimaz , Kaur Gurbakhash , Lin Yi , Liu Lawrence , Nadeem Omar , Voorhees Peter , Khouri Jack , McGuirk Joseph , Sidana Surbhi , Hansen Doris K. , Patel Krina 
Published: October 2023

Abstract
Idecabtagene vicleucel (ide-cel) was the first chimeric antigen receptor T-cell therapy to gain US Food and Drug Administration approval for patients with relapsed/refractory multiple myeloma (RRMM). The clinical outcomes of standard of care (SOC) ide-cel in racially and ethnically diverse populations have been understudied. This study pooled data from 207 patients with RRMM (28% patients of racial and ethnic minority groups) treated with SOC ide-cel across 11 institutions to examine racial and ethnic differences in the incidence of toxicities and adverse events, response to ide-cel, and survival. This study included 22 (11%) Hispanic, 36 (17%) non-Hispanic Black, and 149 (72%) non-Hispanic White patients with RRMM. Compared with Hispanic and non-Hispanic White patients, non-Hispanic Black patients had higher median levels of C-reactive protein (1.0, 0.8, and 3.5 mg/dL, respectively; P = .02) and baseline ferritin (362.0 vs 307.0 vs 680.5, respectively; P = .08) and were more likely to develop cytokine release syndrome (77%, 85%, and 97%, respectively; P = .04). Although best overall response rate was lower among Hispanic patients (59%) than among non-Hispanic Black (86%) and White patients (86%; P = .01), there were no racial and ethnic differences in progression-free or overall survival. We provide, to our knowledge, the first and largest investigation of clinical outcomes of SOC ide-cel by race and ethnicity. Despite differences in safety and response to ide-cel, our findings encourage the use of ide-cel in all patients with RRMM. These findings should be confirmed in larger samples of diverse patients with RRMM, with longer follow-up time.
Pulmonary radioaerosol mucociliary clearance assessment: searching for genotype-specific differences and potential as an outcome measure in primary ciliary dyskinesia
Authors: Marthin June K. , Holgersen Mathias G. , Nielsen Kim G. , Mortensen Jann 
Published: October 2023

BackgroundPulmonary radioaerosol mucociliary clearance (PRMC) is a reliable method for assessingin vivowhole lung mucociliary clearance and has been used at the Danish PCD Centre as a supplementary diagnostic test for primary ciliary dyskinesia (PCD) for more than two decades. This study aimed to investigate genotype-specific differences in PRMC measures and evaluate its potential as an outcome parameter.Material and methodsThe study was based on a retrospective analysis of PRMC tests performed over a 24-year period (1999–2022) in individuals referred for PCD work-up and included patients with genetically confirmed PCD and non-PCD controls. Patients inhaled nebulised technetium-albumin-colloid before static and dynamic imaging was obtained. Three parameters were evaluated: 1-h lung retention (LR1), tracheobronchial velocity (TBV) and cough clearance.ResultsThe study included 69 patients from the Danish PCD cohort, representing 26 different PCD genotypes. Mucociliary clearance by PRMC was consistently absent in most PCD patients, regardless of genotype. However, a single patient with aCCDC103mutation, preserved ciliary function and normal nasal nitric oxide levels exhibited normal LR1 and low TBV values. Voluntary cough significantly improved clearance, with a median improvement of 11% (interquartile range 4–24%).ConclusionAbsent mucociliary clearance by PRMC should be expected in PCD regardless of genotype but residual ciliary function could result in measurable PRMC. This indicates a potential for PRMC to detect improvements in ciliary function if this can be restored. Addressing involuntary cough and peripheral deposition of radioaerosol is important if PRMC is to be used as an outcome measure in future clinical PCD trials.
New Technology of Multidirectional Loading Rotary Extrusion
Authors: Zhang Zhimin , Xue Yong , Zhang Xing , Dong Beibei , Cheng Mei , Chen Zhe 
Published: October 2023

AbstractTo satisfy the requirements for the precise formation of large-scale high-performance lightweight components with inner ring reinforcement, a new multidirectional loading rotary extrusion forming technology is developed to match the linear motion with the rotary motion and actively increases the strong shear force. Its principle is that the radial force and rotating torque increase when the blank is axially extruded and loaded. Through the synergistic action of axial, radial, and rotating motions, the orderly flow of metal is controlled, and the cumulative severe plastic deformation (SPD) of an “uplift-trowel” micro-area is generated. Consequently, materials are uniformly strengthened and toughened. Simultaneously, through the continuous deformation of a punch “ellipse-circle,” a high reinforcement component is grown on the cylinder wall to achieve the high-quality formation of cylindrical parts or the inner-ring-reinforcement components. Additionally, the effective strain increases with rotation speed, and the maximum intensity on the basal plane decreases as the number of revolutions increase. The punch structure also affects the axial extrusion loading and equivalent plastic strain. Thus, the proposed technology enriches the plastic forming theory and widens the application field of plastic forming. Furthermore, the formed large-scale high-performance inner-ring-stiffened magnesium components have been successfully verified in aerospace equipment, thereby solving the problems of integral forming and severe deformation strengthening and toughening. The developed technology has good prospects for mass production and application.