bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomised, open-label, non-inferiority clinical trial on the efficacy and safety of a 7-day vs 14-day course of antibiotic treatment for uncomplicated enterococcal bacteraemia: the INTENSE trial protocol
Authors: Maldonado Natalia , Rosso-Fernández Clara M , Portillo-Calderón Inés , Borreguero Borreguero Irene , Tristán-Clavijo Enriqueta , Palacios-Baena Zaira R , Salamanca Elena , Fernández-Cuenca Felipe , De-Cueto Marina , Stolz-Larrieu Emilio , Rodriguez-Baño Jesús , López-Cortés Luis Eduardo 
Published: September 2023

IntroductionEnterococcusspp is responsible for 8%–15% of total bacteraemias with an associated global mortality around 23%–30%. Regarding the clinical management of enterococcal bacteraemia, the evidence on the duration of antibiotic treatment is scarce and the studies do not discriminate between complicated and uncomplicated bacteraemia.MethodsThe INTENSE study is a multicentre, open-label, randomised, pragmatic, phase-IV clinical trial to demonstrate the non-inferiority of a 7-day vs 14-day course for the treatment of uncomplicated enterococcal bacteraemia and incorporating the early switching to oral antibiotics when feasible. The primary efficacy endpoint is the clinical cure at day 30±2 after the end of the treatment. Secondary endpoints will include the rate of relapse or infective endocarditis, length of stay, duration of intravenous therapy,Clostridioides difficileinfection and the evaluation of the safety of both treatment arms through the recording and analysis of adverse events. For a 6% non-inferiority margin and considering a 5% withdrawal rate, 284 patients will be included.AnalysisThe difference in proportions with one-sided 95% CIs will be calculated for the clinical cure rate using the control group as reference. For secondary categorical endpoints, a similar analysis will be performed and Mann-Whitney U-test will be used to compare median values of quantitative variables. A superiority analysis applying the response adjusted for days of antibiotic risk will be performed if there were incidents in recruitment; will allow obtaining results with 194 patients recruited.Ethics and disseminationThe study has obtained the authorisation from the Spanish Regulatory Authority, the approval of the ethics committee and the agreement of the directors of each centre. Data will be published in peer-reviewed journals.Trial registration numberNCT05394298.
Spinal dural and epidural fistulas: role of cone beam CT in diagnosis and treatment
Authors: Shapiro Maksim , Nossek Erez , Sharashidze Vera , Tanaka Michihiro , Rutledge Caleb , Chung Charlotte , Khawaja Ayaz , Riina Howard , Nelson Peter Kim , Raz Eytan 
Published: September 2023

Understanding normal spinal arterial and venous anatomy, and spinal vascular disease, is impossible without flow-based methods. Development of practical spinal angiography led to site-specific categorization of spinal vascular conditions, defined by the ‘seat of disease’ in relation to the cord and its covers. This enabled identification of targets for highly successful surgical and endovascular treatments, and guided interpretation of later cross-sectional imaging.Spinal dural and epidural arteriovenous fistulas represent the most common types of spinal shunts. Although etiology is debated, anatomy provides excellent pathophysiologic correlation. A spectrum of fistulas, from foramen magnum to the sacrum, is now well-characterized.Most recently, use of cone beam CT angiography has yielded new insights into normal and pathologic anatomy, including venous outflow. It provides unrivaled visualization of the fistula and its relationship with spinal cord vessels, and is the first practical method to study normal and pathologic spinal veins in vivo—with multiple implications for both safety and efficacy of treatments. We advocate consistent use of cone beam CT imaging in modern spinal fistula evaluation.The role of open surgery is likely to remain undiminished, with increasing availability and use of hybrid operating rooms for practical intraoperative angiography enhancing safety and efficacy of complex surgery.
FGFR Inhibition: Understanding and Overcoming Resistance
Authors: Tripathi Abhishek , Li Daneng , Pal Sumanta K. 
Published: September 2023

Summary:
Facchinetti and colleagues provide key insights into the evolution of resistance to fibroblast growth factor receptor (FGFR) inhibitors, including the development of kinase domain mutations and activation of the PI3K–AKT signaling axis. In a separate study, Subbiah and colleagues report extensive preclinical data and initial clinical data for RLY-4008, an FGFR2-selective inhibitor that is poised to minimize toxicity and overcome resistance through greater potency and selectivity.
See related article by Facchinetti et al., p. 1998 (5).
See related article by Subbiah et al., p. 2012 (7).
Different Home Blood Pressure Thresholds to Predict Perfect 24-Hour Ambulatory Blood Pressure Control in Treated Hypertension Based on an “All-in-One” Device
Authors: Kario Kazuomi , Tomitani Naoko , Hoshide Satoshi , Nishizawa Masafumi , Yoshida Tetsuro , Kabutoya Tomoyuki , Fujiwara Takeshi , Mizuno Hiroyuki , Okawara Yukie , Kanegae Hiroshi ,   on behalf of the HI-JAMP Study Group
Published: September 2023

BACKGROUND:
Home blood pressure (BP) is an important component of digital strategies for hypertension management. However, no studies have used the same device to investigate 24-hour BP control status in relation to different home BP control thresholds.

METHODS:
Participants in the general practitioner-based, multicenter HI-JAMP study (Home-Activity Information and Communication Technology-Based Japan Ambulatory Blood Pressure Monitoring Prospective) underwent office BP measurement, then 24-hour ambulatory BP monitoring, then home BP monitoring for 5 days. A validated all-in-one BP monitoring device was used to measure office, home, and ambulatory BP. Baseline data were used to investigate ambulatory BP control status in individuals with well-controlled home BP based on the different guideline thresholds (125/75 mm Hg, 130/80 mm Hg, and 135/85 mm Hg).

RESULTS:
Data from 2269 patients were analyzed. For individuals with well-controlled home BP <135/85 mm Hg (59.5% of the total population), the prevalence of uncontrolled 24-hour (≥130/80 mm Hg), daytime (≥135/85 mm Hg), and nighttime ambulatory BP (≥120/70 mm Hg) was 19.9%, 18.5%, and 33.6%, respectively. Corresponding prevalence rates in the 42.7% of participants with well-controlled home BP <130/80 mm Hg were 13.4%, 12.9%, and 26.0%, and when well-controlled home BP was strictly defined as <125/75 mm Hg (23.9% of the population), prevalence of rates of uncontrolled 24-hour, daytime, and nighttime ambulatory BP were 7.0%, 9.0%, and 15.3%, respectively.

CONCLUSIONS:
Home BP control status defined using different thresholds could predict 24-hour ambulatory BP control status in treated hypertension. One-third of individuals still had uncontrolled nocturnal hypertension when home BP was controlled to <135/85 mm Hg, but ambulatory BP was quite well controlled when home BP was <125/75 mm Hg.
Disrupted Lives: Caregivers' Experiences of In‐Hospital Cardiac Arrest Survivors' Recovery 5 Years Later
Authors: Harrod Molly , Hauschildt Katrina , Kamphuis Lee A. , Korpela Peggy R. , Rouse Marylena , Nallamothu Brahmajee K. , Iwashyna Theodore J. 
Published: September 2023

Background
Survivors of in‐hospital cardiac arrest (IHCA) experience ongoing physical and cognitive impairments, often requiring support from a caregiver at home afterwards. Caregivers are important in the survivor's recovery, yet there is little research specifically focused on their experiences once the survivor is discharged home. In this study, we highlight how caregivers for veteran IHCA survivors described and experienced their caregiver role, the strategies they used to fulfill their role, and the additional needs they still have years after the IHCA event.

Methods and Results
Between March and July 2019, semistructured telephone interviews were conducted with 12 caregivers for veteran IHCA survivors. Interviews were transcribed, and content analysis was performed. Patterns within the data were further analyzed and grouped into themes. A predominant theme of “disruption” was identified across 3 different domains including the following: (1) disruption in caregiver's life, (2) disruption in caregiver–patient relationship, and (3) disruption in caregiver's well‐being. Disruption was associated with both positive and negative caregiver experiences. Strategies caregivers used and resources they felt would have helped them adjust to their caregiver role were also identified.

Conclusions
Caregivers for veteran IHCA survivors experienced a disruption in many facets of their lives. Caregivers felt the veterans' IHCA impacted various aspects of their lives, and they continued to need additional support in order to care for the IHCA survivor and themselves. Although some were able to procure coping strategies, such as counseling and engaging in stress‐relieving activities, most indicated additional help and resources were still needed.
Large-Eddy Simulations of the Tropical Cyclone Boundary Layer at Landfall in an Idealized Urban Environment
Authors: Rozoff Christopher M. , Nolan David S. , Bryan George H. , Hendricks Eric A. , Knievel Jason C. 
Published: September 2023

Abstract
Populated urban areas along many coastal regions are vulnerable to landfalling tropical cyclones (TCs). To the detriment of surface parameterizations in mesoscale models, the complexities of turbulence at high TC wind speeds in urban canopies are presently poorly understood. Thus, this study explores the impacts of urban morphology on TC-strength winds and boundary layer turbulence in landfalling TCs. To better quantify how urban structures interact with TC winds, large-eddy simulations (LESs) are conducted with the Cloud Model 1 (CM1). This implementation of CM1 includes immersed boundary conditions (IBCs) to represent buildings and eddy recycling to maintain realistic turbulent flow perturbations. Within the IBCs, an idealized coastal city with varying scales is introduced. TC winds impinge perpendicularly to the urbanized coastline. Numerical experiments show that buildings generate distinct, intricate flow patterns that vary significantly as the city structure is varied. Urban IBCs produce much stronger turbulent kinetic energy than is produced by conventional surface parameterizations. Strong effective eddy viscosity due to resolved eddy mixing is displayed in the wake of buildings within the urban canopy, while deep and enhanced effective eddy viscosity is present downstream. Such effects are not seen in a comparison LES using a simple surface parameterization with high roughness values. Wind tunneling effects in streamwise canyons enhance pedestrian-level winds well beyond what is possible without buildings. In the arena of regional mesoscale modeling, this type of LES framework with IBCs can be used to improve parameters in surface and boundary layer schemes to more accurately represent the drag coefficient and the eddy viscosity in landfalling TC boundary layers.

Significance Statement
This is among the first large-eddy simulation model studies to examine the impacts of tropical cyclone–like winds around explicitly resolved buildings. This work is a step forward in bridging the gap between engineering studies that use computational fluid dynamics models or laboratory experiments for flow through cities and mesoscale model simulations of landfalling tropical cyclones that use surface parameterizations specialized for urban land use.
What Controls the Entrainment Rate of Dry Buoyant Thermals with Varying Initial Aspect Ratio?
Authors: Morrison Hugh , Jeevanjee Nadir , Lecoanet Daniel , Peters John M. 
Published: September 2023

Abstract
This study uses theory and numerical simulations to analyze the nondimensional spreading rate α (change in radius with height) of buoyant thermals as they rise and entrain surrounding environmental fluid. A focus is on how α varies with initial thermal aspect ratio Ar, defined as height divided by width of the initial buoyancy perturbation. An analytic equation for thermal ascent rate wt that depends on α is derived from the thermal-volume-averaged momentum budget equation. The thermal top height when wt is maximum, defining a critical height zc, is inversely proportional to α. The height zc also corresponds to the thermal top height when buoyant fluid along the thermal’s vertical axis is fully replaced by entrained nonbuoyant environmental fluid rising from below the thermal. The time scale for this process is controlled by the vertical velocity of parcels rising upward through the thermal’s core. This parcel vertical velocity is approximated from Hill’s analytic spherical vortex, yielding an analytic inverse relation between α and Ar. Physically, this α–Ar relation is connected to changes in circulation as Ar is modified. Numerical simulations of thermals with Ar varied from 0.5 to 2 give α values close to the analytic theoretical relation, with a factor of ∼3 decrease in α as Ar is increased from 0.5 to 2. The theory also explains why α of initially spherical thermals from past laboratory and modeling studies is about 0.15. Overall, this study provides a theoretical underpinning for understanding the entrainment behavior of thermals, relevant to buoyantly driven atmospheric flows.

Significance Statement
Thermals, which are coherent, quasi-spherical regions of upward-moving buoyant fluid, are a key feature of many convective atmospheric flows. The purpose of this study is to characterize how thermals entrain surrounding fluid and spread out as they rise. We use theory and numerical modeling to explain why entrainment rate decreases with an increase in the initial thermal aspect ratio—the ratio of height to width. This work also explains why the nondimensional spreading rate (change in thermal radius with height) of initially spherical thermals from past laboratory and numerical modeling studies is about 0.15. Overall, this work provides a framework for conceptualizing the entrainment behavior of thermals and thus improved understanding of vertical transport in convective atmospheric flows.
Revisiting the Global Energy Budget Dynamics with a Multivariate Earth Energy Balance Model to Account for the Warming Pattern Effect
Authors: Meyssignac Benoit , Guillaume-Castel Robin , Roca Rémy 
Published: September 2023

Abstract
Climate feedbacks are sensitive to the geographical distribution of sea surface temperature (SST). This sensitivity, called the pattern effect, affects the amplitude of the Earth radiative response to anomalies in global mean surface temperature (GMST) and thus is essential in shaping the global energy budget dynamics. Zero-dimensional energy balance models (EBMs) are the simplest representation of the global energy budget dynamics. Many only depend on GMST anomalies and cannot account for the pattern effect explicitly. In EBMs, the pattern effect leads to apparent variations of the global climate feedback parameter λ. Assuming a variable λ in EBMs enables them to more accurately reproduce AOGCM simulations of the GMST anomalies but it leads to variations in λ of >+15%. These large variations mean λ is not a constant and the Taylor expansion underpinning EBMs’ formulation does not hold, casting doubts on the physical grounding of such EBMs. Here we propose a new EBM based on a multivariate linear Earth radiative response, which depends on both the GMST and the surface warming pattern. The resulting multilinear EBM accurately reproduces AOGCM simulations of anomalies in Earth radiative response and GMST under abrupt 4xCO2 forcing. When interpreted in terms of variable λ, the multivariate EBM leads to small variations in λ that are physically consistent with the underpinning Taylor expansion. We analyze with the multivariate framework the variations of the planetary heat uptake N as a function of the GMST and the pattern of warming through a 3D generalization of the Gregory plot. We show that the apparent nonlinear behavior of the radiative response of the Earth against GMST seen in classical monovariate EBMs (and in classical Gregory plots) can actually be explained by a bilinear dependance of the radiative response of the Earth on the GMST and the pattern of warming. The multivariate EBM further provides an explicit dependence of the global energy budget on the pattern of warming and on the climate state. It has important consequences on the expression of the climate sensitivity.
Disparities in Clinical Trial Enrollment and Reporting in Rectal Cancer: A Systematic Review and Demographic Comparison to the National Cancer Database
Authors: Sawaf Tuleen , Gudipudi Rachana , Ofshteyn Asya , Sarode Anuja L. , Bingmer Katherine , Bliggenstorfer Jonathan , Stein Sharon L. , Steinhagen Emily ,   on behalf of UH-RISES (University Hospitals Research in Surgical Outcomes and Effectiveness Center)
Published: September 2023

Background Cancer care guidelines based on clinical trial data in homogenous populations may not be applicable to all rectal cancer patients. The aim of this study was to evaluate whether patients enrolled in rectal cancer clinical trials (CTs) are representative of United States (U.S.) rectal cancer patients. Methods Prospective rectal cancer CTs from 2010 to 2019 in the United States were systematically reviewed. In trials with multiple arms reporting separate demographic variables, each arm was considered a separate CT group in the analysis. Demographic variables considered in the analysis were age, sex, race/ethnicity, facility location throughout the United States, rural vs urban geography, and facility type. Participant demographics from trial and the National Cancer Database (NCDB) participants were compared using chi-squared goodness of fit and one-sample t-test where applicable. Results Of 50 CT groups identified, 42 (82%) studies reported mean or median age. Trial participants were younger compared to NCDB patients ( P < .001 all studies). All but three trials had fewer female patients than NCDB (48.2% female, P < .001). Less than half the CT groups reported on race or ethnicity. Eighteen out of 22 trials (82%) had a smaller percentage of Black patients and 4 out of 8 (50%) trials had fewer Hispanic or Spanish origin patients than the NCDB. No CTs reported comorbidities, socioeconomic factors, or education. CT primary sites were largely at academic centers and in urban areas. Conclusion The present study supports the need for improved demographic representation and transparency in rectal cancer clinical trials.
Panicum miliaceum L. and Bone Healing Properties in Rat Model of Femur Fracture by Activating Phosphate Stimulating Macrophages via BMP2 and RANK Signaling Pathway
Authors: Zhang Yubing , Wang Qiu , Pan Hansong , Xu Hongye , Deng Wei , Sun Xiaohai 
Published: September 2023

Objectives The aim of this study was to investigate the effect of Panicum miliaceum involved in the repair of femur bone fracture in rats. Materials and Methods In this study, 40 Wistar rats in five groups were studied as healthy, rats with lesion induced by surgery in femur (FX), FX rats treated with P. miliaceum extract (FX +100 and 200 P. miliaceum) and FX rats treated with Osteocare syrup (FX + OC). After 40 days, the serum levels of blood calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP) along with activity of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) enzymes, and nitric oxide (NO) level were measured. The serum level of cytokines (IL-6, C-reactive protein [CRP], IL-10, IL-1β, and tumor necrosis factor-α [TNF-α]) was also measured by ELISA. The expression of OPG, RANK, RANKL, and BMP-2 genes and proteins were evaluated by real-time PCR and Western blotting techniques, respectively. Results The results showed that P. miliaceum was able to decrease the activity of ALP enzyme in addition to increasing serum Ca and P levels and GPx, SOD, and CAT activity. P. miliaceum reduces serum IL-6, IL-1β, and TNF-α, and NO levels. Also, the extract of this plant could increase the expression of OPG/RANK/BMP-2 pathway genes and proteins. Conclusion P. miliaceum can be used as a prodrug in traditional medicine to repair bone fractures and osteoporosis.
Development of Emotional Intelligence During an Adventure and Experiential-Based Learning Course
Authors: Silver Adam I. , Marshall Rob , Huston Dave , Gentry Greg 
Published: September 2023

Background The United States Air Force Academy's Center for Character and Leadership Development developed the ‘Adventure and Experiential Based Learning’ (AEBL) course—a new experiential education summer course intended to develop interpersonal leadership skills in 1,100 sophomore cadets. Purpose Improving cadet emotional intelligence (EI) is of particular focus due to its value in leader effectiveness. Methodology/Approach Rather than rely upon the more common military pedagogy of lecture-based learning or a military handbook that prescribes exactly what participant success looks like, the aim of the course examined in this study was to improve participant EI via a combination of experiential education methods including interactive classwork, challenge course experimentation, and a capstone 28-h adventure comprised of uncertainty and stressful team dynamics. To measure the effect the experiential education curriculum had on participant EI, the Workgroup Emotional Intelligence Profile (WEIP) was used in a pre/postsurvey method. Findings/Conclusion The results indicated a significant increase in EI among AEBL participants as measured by the WEIP. Implications Outdoor experiences like the one described in this article may be an effective way to train EI skills.