bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Enzymatic Burn Debridement: Results of the DETECT Multicenter Randomized Controlled Trial
Authors: Shoham Yaron , Rosenberg Lior , Hickerson William , Goverman Jeremy , Iyer Narayan , Barrera-Oro Julio , Lipovy Bretislav , Monstrey Stan , Blome-Eberwein Sigrid , Wibbenmeyer Lucy A , Scharpenberg Martin , Singer Adam J 
Published: September 2023

Abstract
Since 1970 surgeons have managed deep burns by surgical debridement and autografting. We tested the hypothesis that enzymatic debridement with NexoBrid would remove the eschar reducing surgery and achieve comparable long-term outcomes as standard of care (SOC). In this Phase 3 trial, we randomly assigned adults with deep burns (covering 3–30% of total body surface area [TBSA]) to NexoBrid, surgical or nonsurgical SOC, or placebo Gel Vehicle (GV) in a 3:3:1 ratio. The primary endpoint was complete eschar removal (ER) at the end of the debridement phase. Secondary outcomes were need for surgery, time to complete ER, and blood loss. Safety endpoints included wound closure and 12 and 24-months cosmesis on the Modified Vancouver Scar Scale. Patients were randomized to NexoBrid (n = 75), SOC (n = 75), and GV (n = 25). Complete ER was higher in the NexoBrid versus the GV group (93% vs 4%; P &lt; .001). Surgical excision was lower in the NexoBrid vs the SOC group (4% vs 72%; P &lt; .001). Median time to ER was 1.0 and 3.8 days for the NexoBrid and SOC respectively (P &lt; .001). ER blood loss was lower in the NexoBrid than the SOC group (14 ± 512 mL vs 814 ± 1020 mL, respectively; P &lt; .0001). MVSS scores at 12 and 24 months were noninferior in the NexoBrid versus SOC groups (3.7 ± 2.1 vs 5.0 ± 3.1 for the 12 months and 3.04 ± 2.2 vs 3.30 ± 2.76 for the 24 months). NexoBrid resulted in early complete ER in &gt;90% of burn patients, reduced surgery and blood loss. NexoBrid was safe and well tolerated without deleterious effects on wound closure and scarring.
Identification and Evaluation of Mobile Applications for Self-Management of Diet and Lifestyle for Patients with Inflammatory Bowel Disease
Authors: Gold Stephanie L , Chiew Brandon A , Rajagopalan Vidya , Lavallee Celeste M 
Published: September 2023

Abstract

Background
Mobile health applications (apps) providing diet and lifestyle self-management programs to patients with inflammatory bowel disease (IBD) are emerging. The objective of this study was to evaluate current apps available in the US and Canada based on app quality, perceived impact on diet and mental health and comprehensiveness to support self-management.

Methods
The Apple iOS and Google Play app stores were searched for terms related to IBD. Apps were included if they targeted diet and lifestyle behaviours for patients living with IBD and were available to the general public. Apps were excluded if they were not specific to IBD, not available in English, did not target diet or lifestyle therapy, were not available in the US and Canada, or did not offer stand-alone self-management programs. The Mobile App Rating Scale was used to assess mobile app quality.

Results
A total of 1,512 apps were identified through the app stores. Six apps met inclusion criteria. My IBD Care: Crohn’s and Colitis received the highest quality rating and LyfeMD received the highest overall app rating. Only these two apps provided behaviour tracking over time, and three (50 percent) apps provided good-quality information.

Conclusions
While many IBD-related apps exist, few support self-management of diet and lifestyle behaviours. The My IBD Care and LyfeMD apps had the highest ratings and can be used to track lifestyle behaviours. The effectiveness of these apps to improve behaviours, and subsequently impact the disease course and quality of life, should be explored in future studies.
FBBVA Lecture 2023. The Importance of Modeling Income Taxes over Time: U.S. Reforms and Outcomes
Authors: Borella Margherita , De Nardi Mariacristina , Pak Michael , Russo Nicolo , Yang Fang 
Published: September 2023

Abstract
The structure of taxes and their burden have undergone large and frequent changes over time. We provide a brief history of U.S. federal income tax reform since the 1960s, calculate effective federal income tax rates for each wave of the Panel Study of Income Dynamics, and discuss how effective taxation changed from 1969 to 2016. We show that most tax regimes are short-lived and that the variation in taxes over time and across groups is large. We also use an estimated dynamic model of couples and singles to show that the various tax regimes that we estimate imply very different labor market and saving behavior. These findings stress the importance of studying and modeling tax changes over time and across groups.
Education, Ontological Security, and Preserving Hope in Liminality: Learning from the Daily Strategies Exercised by Syrian Refugee Youth in Jordan
Authors: Salem Hiba 
Published: September 2023

Abstract
This article draws on a study with Syrian refugee youth and their teachers to examine how young people, holding liminal social and legal statuses in Jordan, manage uncertainty. Through an analysis of students' experiences, this article describes the varying strategies that they developed to protect their sense of hope across time by maintaining ontological security, or an understanding of self. These findings suggested that refugee youth, unable to navigate uncertainty through their educational spaces, explored alternative ways to actively build hope and sustain a sense of control in their lives. They nurtured hope by constructing a continuous narrative of their experiences, exploring their skills and potential, and forming attachments to ideas of place and possibility. Buildings on these findings, this article argues for the importance of integrating practices within education which respond to refugee youths’ needs to maintain ontological security and hope in the face of uncertainty.
Empirical bias-reducing adjustments to estimating functions
Authors: Kosmidis Ioannis , Lunardon Nicola 
Published: September 2023

AbstractWe develop a novel, general framework for reduced-bias M-estimation from asymptotically unbiased estimating functions. The framework relies on an empirical approximation of the bias by a function of derivatives of estimating function contributions. Reduced-bias M-estimation operates either implicitly, solving empirically adjusted estimating equations, or explicitly, subtracting the estimated bias from the original M-estimates, and applies to partially or fully specified models with likelihoods or surrogate objectives. Automatic differentiation can abstract away the algebra required to implement reduced-bias M-estimation. As a result, the bias-reduction methods, we introduce have broader applicability, straightforward implementation, and less algebraic or computational effort than other established bias-reduction methods that require resampling or expectations of products of log-likelihood derivatives. If M-estimation is by maximising an objective, then there always exists a bias-reducing penalised objective. That penalised objective relates to information criteria for model selection and can be enhanced with plug-in penalties to deliver reduced-bias M-estimates with extra properties, like finiteness for categorical data models. Inferential procedures and model selection procedures for M-estimators apply unaltered with the reduced-bias M-estimates. We demonstrate and assess the properties of reduced-bias M-estimation in well-used, prominent modelling settings of varying complexity.
COVID-19 Concerns, Information Needs, and Adverse Mental Health Outcomes among U.S. Soldiers
Authors: Quartana Phillip J , Beymer Matthew R , Gomez Stephanie A Q , Adler Amy B , Santo Theresa Jackson , Thomas Jeffrey L , Bell Amy Millikan 
Published: September 2023

ABSTRACT

Introduction
The coronavirus disease 2019 (COVID-19) pandemic disrupted U.S. Military operations and potentially compounded the risk for adverse mental health outcomes by layering unique occupational stress on top of general restrictions, fears, and concerns. The objective of the current study was to characterize the prevalence of COVID-19 concerns and information needs, demographic disparities in these outcomes, and the degree to which COVID-19 concerns and information needs were associated with heightened risk for adverse mental health outcomes among U.S. Army soldiers.

Materials and Methods
Command-directed anonymous surveys were administered electronically to U.S. soldiers assigned to one of three regional commands in the Northwest United States, Europe, and Asia-Pacific Region. Surveys were administered in May to June 2020 to complete (time 1: n = 21,294) and again in December 2020 to January 2021 (time 2: n = 10,861). Only active duty or active reservists/national guard were eligible to participate. Members from other branches of service were also not eligible.

Results
Highly prevalent COVID-19 concerns included the inability to spend time with friends/family, social activities, and changing rules, regulations, and guidance related to COVID-19. Some information needs were endorsed by one quarter or more soldiers at both time points, including stress management/coping, travel, how to protect oneself, and maintaining mission readiness. COVID-19 concerns and information needs were most prevalent among non-White soldiers. Concerns and information needs did not decline overall between the assessments. Finally, COVID-19 concerns were associated with greater risk of multiple adverse mental health outcomes at both time points.

Conclusions
COVID-19 concerns and information needs were prevalent and showed little evidence of decrement over the course of the first 6 months of the pandemic. COVID-19 concerns were consistently associated with adverse mental health outcomes. These data highlight two targets and potential demographic subgroups such that local leadership and Army medicine and public health enterprises can be better prepared to monitor and address to maintain force health and readiness in the face of possible future biomedical threats.
Outcome of Laparoscopic Versus Open Appendectomy for Acute Appendicitis—Results of a Propensity Score Matching Analysis of 542 Patients and Consequences for the Military Surgeon
Authors: Beltzer Christian , Haas Frank , Jahn Lena-Sofia , Bellmann Valerie , Strohäker Jens , Willms Arnulf , Schmidt Roland 
Published: September 2023

ABSTRACT

Introduction
Appendectomy is the treatment of choice for acute appendicitis. The procedure can be performed open or laparoscopically. However, laparoscopy is not available on military missions abroad. It is unclear whether treatment outcomes differ between the two surgical approaches.

Materials and Methods
Treatment data of all patients undergoing open and laparoscopic appendectomies in the German Armed Forces Hospital of Ulm from 2013 to 2017 were collected retrospectively. A propensity score matching analysis was performed to minimize the influence of potential confounders and to assess the influence of surgical approach on outcome (reoperations, superficial and deep surgical infections, length of postoperative ileus, need for intravenous analgesics, and operative time).

Results
A total of 542 patients with complete datasets were included in the propensity score matching analysis, among these 64 with open and 478 laparoscopic procedures. There were no statistically significant differences between open and laparoscopic surgeries with respect to all outcome variables, with the exception of a 25-minute prolonged operative time for the open approach.

Conclusions
Open appendectomy can be considered equivalent in outcome to the laparoscopic procedure and thus can be performed on military missions abroad without compromising outcome. Military surgeons must continue to be trained and confident in open appendectomy.
Prevalence and Correlates of Cannabis Use among U.S. Veterans during the Second Wave of the COVID-19 Pandemic
Authors: Manzo Laura L , Sarkar Sayantani , Nicholson Nicholas R , Sanft Tara , Poghosyan Hermine 
Published: September 2023

ABSTRACT

Introduction
Military veterans are at increased risk of substance use disorders. Limited research is available about veterans’ cannabis use (CU) during the coronavirus disease 2019 (COVID-19) pandemic. This study estimated the prevalence of past 30-day CU, investigated individual-level correlates of past 30-day CU, and evaluated the reasons (medical, recreational, or both) of past 30-day CU among U.S. Veterans during the second wave of the COVID-19 pandemic.

Materials and Methods
We used population-based, cross-sectional data from the 2021 Behavioral Risk Factor Surveillance System Survey Marijuana Use model. The sample included nationally representative military veterans aged 18+ years (n = 11,167). The outcome was past 30-day CU. Individual-level demographic, socioeconomic, behavioral, and clinical correlates were examined. Analyses were weighted to account for the survey’s complex design with results generalizable to nearly 2.9 million veterans. We conducted weighted descriptive statistics, prevalence estimates, and multivariable logistic regression analyses.

Results
Out of 2.9 million veterans, 11.1% self-reported as non-Hispanic Black, 3.7% Hispanic, and 79.1% non-Hispanic White; 88.5% were men, and 72.8% were aged 50+ years. About 14.6% were current tobacco smokers, 4.7% were current e-cigarette users, 12.5% were binge alcohol drinkers, and 43.4% had three or more comorbid conditions. Overall, 8.5% reported CU in the past 30 days, of which 30.4% used it for medical reasons and 25.8% used it for nonmedical reasons. The prevalence of past 30-day CU decreased with age, education, and income level. Compared to their counterparts, the odds of past 30-day CU were greater among men, those living in urban areas, those with frequent mental distress, infrequent physical distress, and those who had at least one comorbid condition. Non-Hispanic Black veterans had 89% increased odds of past 30-day CU (adjusted odds ratio [AOR] =1.89, 95% confidence interval [CI], 1.19-3.0) compared with non-Hispanic White veterans. Current tobacco smokers had 3.54 (95% CI, 2.40-5.24) and former smokers had 1.78 (95% CI, 1.28-2.47) times higher odds of reporting past 30-day CU than never smokers. Current e-cigarette use (AOR = 3.37, 95% CI, 2.20-5.16) and binge drinking (AOR = 3.18, 95% CI, 2.29-4.41) were also statistically significantly associated with increased odds of past 30-day CU compared to no e-cigarette use and no binge drinking.

Conclusions
CU is prevalent among veterans, and certain subgroups are at higher risk of CU. Thus, identifying high-risk subgroups of veterans and adequately educating them about CU’s benefits, risks, and safety is crucial.
Limiting Exposure to Scattered Radiation From a CT System Installed in a Two-Sided Deployable ISO-Shelter
Authors: Tucker Jonathan E , Wirt Michael D 
Published: September 2023

ABSTRACT

Introduction
Diagnostic radiology in the deployed military environment (in-theater diagnostic radiology) was greatly improved in the early 1990s with the addition of CT systems installed in military-grade one-sided expandable ISO-shelters. These shelters were provided with limited radiation shielding by several flexible lead curtains covering only a small portion of the shelter walls, necessitating placement of deployed CT systems at substantial distances from the field medical facility to limit exposures to personnel from secondary radiation. The newest generation deployable CT system is housed in a two-sided ISO-shelter with radiation shielding applied to the shelter walls. To ensure compliance with military and national standards for protection against ionizing radiation, we developed a simple method to calculate safe distances based on workload, frequencies of the various CT exams performed, and occupancy of controlled and uncontrolled areas.

Materials and Methods
Calculation of radiation air kerma rates outside a two-sided CT ISO-shelter was developed using guidance from the National Council on Radiation Protection and Measurements Report No. 147. The simplified formula included measured radiation transmission factors for the ISO-shelter wall and installed shielding, occupancy factors, fraction of all CT exams that covered the chest, abdomen, and/or pelvis, total number of CT exams per week, and shielding design goals for controlled and uncontrolled areas. The formula was modified subsequently to account for whole-body CT exams expected during armed conflict.

Results
Calculated safe distances revealed that the shielded two-sided CT ISO-shelter can be positioned much closer to the surgical shelters of the field medical unit than the previously unshielded one-sided CT ISO-shelter. Tables of safe distances for controlled and uncontrolled areas for the two medical support environments of disaster relief/peacekeeping and combat are provided. For example, for a controlled area at 100% occupancy when 300 CT exams per week are performed and 50% of those exams are of the chest, abdomen, and/or pelvis, the safe distance between the nearest surgical shelter and the shielded CT ISO-shelter is 2.1 m. By comparison, the safe distance for an unshielded CT ISO-shelter is 8.5 m under the same conditions. For lower occupancy factors and lower weekly workload, safe distances from the nearest surgical shelter are often negligible.

Conclusions
The shielding in the new deployable CT ISO-shelter substantially reduces the distance between it and the surgical shelters of the field medical unit necessary to ensure radiation safety. Safe distances depend on several factors including workload, types and frequencies of CT exams, occupancy factors, and classification of the area around the ISO-shelter, i.e., controlled and uncontrolled.
Simultaneous quantification of Gadoxetic acid and Cisplatin in hepatocellular carcinomas using laser ablation–inductively coupled plasma–mass spectrometry
Authors: Kronenberg Katharina , Werner Julia , Bohrer Peter , Steiger Katja , Buchholz Rebecca , von Bremen-Kühne Maximilian , Elinkmann Matthias , Paprottka Philipp M , Braren Rickmer F , Lohöfer Fabian K , Karst Uwe 
Published: September 2023

Abstract
The gadolinium-based contrast agent Gadoxetic acid and the platinum-based antitumor agent Cisplatin were quantitatively imaged in liver and liver cancer (hepatocellular carcinoma, HCC) tissue of rats by means of laser ablation–inductively coupled plasma–mass spectrometry. HCC bearing rats simultaneously received a tail vein injection of the hepatocyte-specific magnetic resonance imaging contrast agent Gadoxetic acid and a transarterial injection of Cisplatin 15 min before sacrifice and liver removal. Resecting HCC with adjacent liver tissue allows the comparison of Gd, Pt, and endogenous elements like Fe, Cu, and Zn in the various tissue types. Region of interest analysis reveals lower concentrations of Gd in HCC and higher Gd content in the adjacent liver, fitting the selective uptake of Gadoxetic acid into hepatocytes. Furthermore, two malignancy grades and their possible impact on the Gadoxetic acid and Cisplatin uptake are compared. For this, four high grade (G3) and two moderate grade (G2) HCCs were analysed, including a control sample each. Gd concentrations were lower in HCC irrespective of the grade of dedifferentiation (G2, G3) compared to adjacent liver. Despite local arterial Cisplatin injection, concentrations of Pt were similar or also reduced in HCC compared to liver tissue. In addition, endogenous Fe, Cu, and Zn were quantified. While Zn was homogenously distributed, higher Fe concentrations were determined in liver tissue compared to HCC. Hotspots of Cu suggest a deregulated copper homeostasis in certain liver lesions. The Gd and Fe distributions are compared in detail with cellular alterations examined by hematoxylin and eosin staining.
PRO-DRUG NANOPARTICLES AS SYNERGISTIC DRUG COMBINATION CARRIERS FOR IDH1-WT GLIOBLASTOMA
Authors: Cavanagh Robert , Baquain Saif , Oz Umut Can , Sikder Amrita , ElSherbeny Amr , Alexander Cameron , Scherman Oren , Rahman Ruman 
Published: September 2023

Abstract

AIMS
Synergistic combinations of doxorubicin and gemcitabine have been assessed for post-surgical treatment of IDH1 wild-type glioblastoma (GBM). As a complementary drug carrier, hyperbranched and micellar nanoparticles are being investigated to enable enhanced drug loading and sustained drug release.

METHOD
2D and 3D spheroid in vitro models have been generated from patient-derived glioblastoma cells resected from tumour core and invasive margin. Drug combinations were screened using synergy quantification from the Chou and Talalay method and synergy mechanisms investigated using measures of caspase 3/6-mediated apoptosis and γH2AX-mediated DNA damage. Polymeric nanoparticles (PEG-PCL) loaded with Cy5 were tested for internalisation and subsequent endocytosis pathway determination. Both single drug and drug combinations are currently being incorporated into PEG-PCL nanoparticles for in vitro assessment of biocompatibility, cellular uptake and cytotoxicity.

RESULTS
Data demonstrate synergism with doxorubicin and gemcitabine combinations is obtained in a molar ratio de- pendent manner. Consistent with this, enhanced apoptosis and DNA damage is observed in a synergistic manner. PEG-PCL nanoparticles demonstrate effcient cellular uptake and are internalised via dynamin-dependent caveolae and clathrin endocytotic pathways. Interestingly, nanoparticle internalisation is substantially in- creased (approx. 50%) in invasive GBM cells relative to proliferative core cells.

CONCLUSIONS
Doxorubicin and gemcitabine has been identified as a synergistic drug combination with the potential for sustained drug release when combined with PEG-PCL nanoparticle formulations. Together, the data has provided a platform of knowledge that will enable translation to pre-clinical in vivo models.
BULK RNA-SEQ DECONVOLUTION OF IMAGE-LOCALIZED HIGGRADE GLIOMA BIOPSIES REVEALS MEANINGFUL CELLULAR STATES
Authors: Curtin Lee , Bond Kamila , Velez Sebastian , Hawkins-Daarud Andrea , Urcuyo Javier C , De Leon Gustavo , Langworthy Jazlynn , Sereduk Christopher , Singleton Kyle W , Jackson Pamela R , Krishna Chandan , Zimmerman Richard S , Patra Devi P , Bendok Bernard R , Smith Kris A , Nakaji Peter , Donev Kliment , Baxter Leslie C , Mrugala Maciej M , Al-Dalahmah Osama , Hu Leland S , Tran Nhan L , Canoll Peter , Swanson Kristin R 
Published: September 2023

Abstract

AIMS
High-grade glioma continues to have dismal survival with current standard-of-care treatment, owing in part to its intra- and inter-patient heterogeneity. Typical diagnostic biopsies are taken from the dense tumor core to determine the presence of abnormal cells and the status of a few key genes (e.g. IDH1, MGMT). However, the tumor core is typically resected, leaving behind possibly genetically, transcriptomically and/or phenotypically distinct invasive margins that repopulate the disease. As these remaining populations are the ones ultimately being treated, it is important to know their compositional differences from the tumor core. We aim to identify the phenotypic niches defined by the relative composition of key cellular populations and understand their variation amongst patients.

METHOD
We have established an image-localized research biopsy study, that samples from both the invasive margin and tumor core. From this protocol, we currently have 202 samples from 58 patients with available bulk RNA-Seq, collected between Mayo Clinic and Barrow Neurological Institute. Using a single-cell reference dataset from our collaborators at Columbia University, we used CIBERSORTx, a deconvolution method, to predict relative abundances of 7 normal, 6 glioma, and 5 immune cell states for each sample.

RESULTS
We find that these cell state abundances connect to patient survival and show regional differences. For example, proneural glioma states were higher in invasive regions, whereas proliferative and mesenchymal states were higher in the tumor core.

CONCLUSIONS
Our analysis demonstrates a need to characterize the residual tissue following glioma resection to better understand the recurrent disease.