bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does destination make a difference? Outcomes after a policy change affecting cutoff times for prehospital transport
Authors: Renaud Elizabeth , Cummings Olivia , Vanover Melissa , Tanzer Joshua Ray , McCarthy Andrew 
Published: January 2024

BACKGROUND
Facilitating primary triage and care at pediatric trauma centers (PTCs) can improve outcomes for children after trauma. However, scene location and regional emergency medical services regulations may result in initial evaluation occurring at nonpediatric facilities with later transportation to PTCs for definitive care. In this study, we assessed the results of a change in transport time cutoff from 30 to 45 minutes on pediatric patient outcomes.

METHODS
After institutional review board approval, the Pediatric Trauma Database at a level 1 PTC was queried for patients seen before (January 1, 2015, to December 31, 2017) and after (January 1, 2018, to December 31, 2020) the implementation of a policy increasing transport cutoff time from 30 to 45 minutes. Patient outcomes were compared by transport status and Injury Severity Score (ISS) using generalized linear regression analysis.

RESULTS
A total of 505 patients were seen before policy changes, and 413 patients, after policy changes. Both groups had similar numbers of severely injured patients (ISS, ≥15; pre, 64 [13%]; post, 61 [15%]). Average transport time increased after change (pre, 20 minutes [95% confidence interval, 18–22 minutes]; post, 29 minutes [95% confidence interval, 26–33 minutes]; p = 0.0252), consistent with policy compliance. The proportion of transferred patients did not change after policy implementation (p = 0.5856), and the complications among all patients with an ISS of ≥15 did not significantly decrease (pre, 75%; post, 65.6%). However, those patients with an ISS of ≥15 admitted directly from the scene had a lower frequency of complications after the policy changes (pre, 76%; post, 59%; p = 0.0319), and in the postperiod, transferred patients with an ISS of ≥15 had a higher complication rate than those admitted directly from the scene (p < 0.0001).

CONCLUSION
Direct scene admission to a PTC is associated with a lower complication profile for patients with higher ISS. Methods to ensure adherence to cutoff thresholds for emergency medical services transport may have a positive benefit on patient outcomes.

LEVEL OF EVIDENCE
Prognostic and Epidemiological; Level IV.
Clinical Research in Renal Transplantation: A Bibliometric Perspective on a Half-century of Innovation and Progress
Authors: Jiang Decan , Mantas Anna , Studier-Fischer Alexander , Fuchs Juri , Uluk Deniz , Loos Martin , Mieth Markus , Zeier Martin , Husen Peri , Golriz Mohammad , Kahlert Christoph , Ryschich Eduard , Mehrabi Arianeb , Pratschke Johann , Michalski Christoph W. , Czigany Zoltan 
Published: January 2024

Background.
Groundbreaking biomedical research has transformed renal transplantation (RT) into a widespread clinical procedure that represents the mainstay of treatment for end-stage kidney failure today. Here, we aimed to provide a comprehensive bibliometric perspective on the last half-century of innovation in clinical RT.

Methods.
The Web of Science Core Collection was used for a comprehensive screening yielding 123 303 research items during a 50-y period (January 1973–October 2022). The final data set of the 200 most-cited articles was selected on the basis of a citation-based strategy aiming to minimize bias.

Results.
Studies on clinical and immunological outcomes (n = 63 and 48), registry-based epi research (n = 38), and randomized controlled trials (n = 35) dominated the data set. Lead US authors have signed 110 of 200 articles. The overall level of evidence was high, with 84% of level1 and -2 reports. Highest numbers of these articles were published in New England Journal of Medicine, Transplantation, and American Journal of Transplantation. Increasing trend was observed in the number of female authors in the postmillennial era (26% versus 7%).

Conclusions.
This study highlights important trends in RT research of the past half-century. This bibliometric perspective identifies the most intensively researched areas and shift of research interests over time; however, it also describes important imbalances in distribution of academic prolificacy based on topic, geographical aspects, and gender.
Potential and Uncertainties of RejectClass in Acute Kidney Graft Dysfunction: An Independent Validation Study
Authors: von Samson-Himmelstjerna Friedrich A. , Kakavand Nassim , Gleske Charlotte , Schraml Florian , Basta Agathe A. , Braunisch Matthias C. , Bräsen Jan H. , Schmitz Jessica , Kraus Daniel , Weinmann-Menke Julia , Zacharias Helena U. , Vaulet Thibaut , Naesens Maarten , Krautter Markus , Schwenger Vedat , Esser Grit , Kolbrink Benedikt , Amann Kerstin , Holzmann-Littig Christopher , Echterdiek Fabian , Kunzendorf Ulrich , Renders Lutz , Schulte Kevin , Heemann Uwe ,   on behalf of the TRABIO study group
Published: January 2024

Background.
Kidney graft rejections are classified based on the Banff classification. The RejectClass algorithm, initially derived from a cohort comprising mostly protocol biopsies, identifies data-driven phenotypes of acute rejection and chronic pathology using Banff lesion scores. It also provides composite scores for inflammation activity and chronicity. This study independently evaluates the performance of RejectClass in a cohort consisting entirely of indication biopsies.

Methods.
We retrospectively applied RejectClass to 441 patients from the German TRABIO (TRAnsplant BIOpsies) cohort who had received indication biopsies. The primary endpoint was death-censored graft failure during 2 y of follow-up.

Results.
The application of RejectClass to our cohort demonstrated moderately comparable phenotypic features with the derivation cohort, and most clusters indicated an elevated risk of graft loss. However, the reproduction of all phenotypes and the associated risks of graft failure, as depicted in the original studies, was not fully accomplished. In contrast, adjusted Cox proportional hazards analyses substantiated that both the inflammation score and the chronicity score are independently associated with graft loss, exhibiting hazard ratios of 1.7 (95% confidence interval, 1.2-2.3; P = 0.002) and 2.2 (95% confidence interval, 1.8-2.6; P < 0.001), respectively, per 0.25-point increment (scale: 0.0–1.0).

Conclusions.
The composite inflammation and chronicity scores may already have direct utility in quantitatively assessing the disease stage. Further refinement and validation of RejectClass clusters are necessary to achieve more reliable and accurate phenotyping of rejection.
Metformin mitigates insulin signaling variations induced by COVID-19 vaccine boosters in type 2 diabetes
Authors: Zhai Lixiang , Zhuang Min , Wong Hoi Ki , Lin Chengyuan , Zhang Jialing , Bao Gengyu , Zhang Yijing , Xu Shujun , Luo Jingyuan , Yuan Shuofeng , Wong Hoi Leong Xavier , Bian Zhao-xiang 
Published: January 2024

AbstractDiabetes is associated with an increased risk of Coronavirus disease 2019 (COVID-19) vulnerability and mortality. COVID-19 vaccines significantly reduce the risks of serious COVID-19 outcomes, but the impact of COVID-19 vaccines including their effectiveness and adverse effects in patients with diabetes are not well known yet. Here, we showed that 61.1% patients with type 2 diabetes, but not healthy controls, exhibited aggravated insulin resistance towards the booster shots of the COVID-19 vaccine. Furthermore, we showed that COVID-19 vaccination once a week also impaired insulin sensitivity in healthy mice after four weeks. We further showed that metformin, a common anti-diabetic medication, improved the impaired insulin signaling induced by COVID-19 vaccination in mice. This study suggests clinical implications for the close monitoring of glycemic control in diabetic patients after receiving COVID-19 vaccines and indicates the beneficial action of metformin in counteracting insulin signaling variations induced by COVID-19 vaccination in diabetic patients.
First-episode mild depression in young adults is a pre-proatherogenic condition even in the absence of subclinical metabolic syndrome: lowered lecithin-cholesterol acyltransferase as a key factor
Authors: Maes Michael , Vasupanrajit Asara , Jirakran Ketsupar , Zhou Bo , Tunvirachaisakul Chavit , Almulla Abbas F. 
Published: January 2024

AbstractBackgroundMajor depression is classified into distinct subtypes: simple (SDMD) and major dysmood disorder (MDMD). MDMD patients exhibit elevated atherogenicity and decreased reverse cholesterol transport (RCT). However, comprehensive data regarding lipid metabolism is absent in first episode (FE)-SDMD.ObjectivesIn this case-control study, plasma lipid levels, lecithin-cholesterol acyltransferase (LCAT), free cholesterol, ApoA1, ApoB, and ApoE are compared between academic students with first episode SDMD (FE-SDMD) (n=44) or SDMD (n=64) and control students (n=44), after excluding those with metabolic syndrome (MetS).ResultsLCAT is decreased, and free cholesterol and ApoE increased in subjects with SDMD and FE-SDMD as compared with controls. There were no significant alterations in high-density lipoprotein cholesterol (HDLc), apolipoprotein (Apo)A1, RCT, ApoB and triglycerides in SDMD. LCAT, free cholesterol and atherogenicity indices are significantly associated with suicidal behaviors and the SDMD phenome. The effects of LCAT on those phenome features is completely mediated by free cholesterol and brooding. SDMD and FE-SDMD patients without signs of subclinical MetS show lowered LCAT and increased free cholesterol as compared with normal controls. There are significant interactions between the SDMD and FE-SDMD diagnosis and subclinical MetS, which result in decreased HDLc and RCT, and an increased ApoB/ApoA ratio.DiscussionFE-SDMD and SDMD are pre-proatherogenic states, because of decreased LCAT, and increased free cholesterol and ApoE, and their intersections with subclinical MetS. These aberrations may drive atherogenicity, and activation of peripheral and central oxidative, neuro-immune, and degenerative pathways. Individuals with FE-SDMD should be screened for increased atherogenicity risk by measuring LCAT, free cholesterol and ApoE.
Disentangling the relationship between cancer mortality and COVID-19 in the US
Authors: Hansen Chelsea L. , Viboud Cécile , Simonsen Lone 
Published: January 2024

AbstractSeveral countries have reported that deaths with a primary code of cancer did not rise during COVID-19 pandemic waves compared to baseline pre-pandemic levels. This is in apparent conflict with findings from cohort studies where cancer has been identified as a risk factor for COVID-19 mortality. Here we further elucidate the relationship between cancer mortality and COVID-19 on a population level in the US by testing the impact of death certificate coding changes during the pandemic and leveraging heterogeneity in pandemic intensity across US states. We computed excess mortality from weekly deaths during 2014-2020 nationally and for three states with distinct COVID-19 wave timing (NY, TX, and CA). We compared pandemic-related mortality patterns from underlying and multiple cause (MC) death data for six types of cancer and compared to that seen for chronic conditions such as diabetes and Alzheimer’s. Any death certificate coding changes should be eliminated by study of MC data.Nationally in 2020, we found only modest excess MC cancer mortality (∼13,600 deaths), representing a 3% elevation over baseline level. Mortality elevation was measurably higher for less deadly cancers (breast, colorectal, and hematologic, 2-7%) than cancers with a poor 5-year survival (lung and pancreatic, 0-1%). In comparison, there was substantial elevation in MC deaths from diabetes (37%) and Alzheimer’s (19%). Homing in on the intense spring 2020 COVID-19 wave in NY, mortality elevation was 1-16% for different types of cancer and 128% and 49% for diabetes and Alzheimer’s, respectively. To investigate the peculiar absence of excess mortality on deadly cancers, we implemented a demographic model and simulated the expected covid-related mortality using COVID-19 attack rates, life expectancy, population size and mean age for each chronic condition. This model indicates that these factors largely explain the considerable differences in observed excess mortality between these chronic conditions during the COVID-19 pandemic, even if cancer had increased the relative risk of mortality by a factor of 2 or 5.In conclusion, we found limited elevation in cancer mortality during COVID-19 waves, even after considering MC mortality, and this was especially pronounced for the deadliest cancers. Our demographic model predicted low expected excess mortality in populations living with certain types of cancer, even if cancer is a risk factor for COVID-19 fatality, due to competing mortality risk. We also find a moderate increase in excess mortality from hematological cancers, aligned with other types of observational studies. While our study concentrates on the immediate consequences of the COVID-19 pandemic on cancer mortality in 2020, further research should consider excess mortality in the complete pandemic period. Also, a study of the delayed impact of the pandemic on cancer mortality due to delayed diagnosis and treatment during the pandemic period is warranted.
Higher long-term visit-to-visit blood pressure variability is associated with severe cerebral small vessel disease in the general population
Authors: Zhao Xinyu , Ying Hui , Li Jing , Shi Xianquan , Chen Shuohua , Lv Han , Wu Shouling , Wang Zhenchang 
Published: January 2024

AbstractBackgroundLong-term blood pressure (BP) variability is related to several diseases, but its impact on cerebral small vessel disease (cSVD) is uncertain. The study explored the relationship between BP variability, total cSVD burden, and its typical features.MethodThe study involved 1284 participants from the Kailuan cohort. From 2006 to 2022, systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) variability were calculated as low, middle, or high. Magnetic resonance imaging was used to identify white matter hyperintensities (WMH), lacunae (LA), cerebral microbleeds (CMBs), and visible perivascular spaces (PVS). The burden of cSVD was defined as non, mild, moderate, or severe. Logistic regression was used to estimate the odds ratio (OR) and confidence interval (CI).ResultsHigh SBP variability was associated with moderate cSVD burden (OR=1.89, 95% CI: 1.09-3.29) and PVS (OR= 1.62, 95%CI: 1.10-2.39). The DBP was associated with LA (OR=1.74, 95%CI: 1.06-2.84). The PP showed obvious risk effects on moderate/severe cSVD burden (OR= 1.99, 95%CI: 1.17-3.41; OR=2.49, 1.34-4.63). These associations were modified by age and hypertension status. In the young adults (age<60 years old), only high PP variability associated with severe cSVD burden (OR=3.33, 95%CI: 1.31-8.44), LA (OR=3.02, 95%CI: 1.31-6.93), and PVS (OR=1.86, 95%CI: 1.20-2.88). The risk effect of SBP and PP variability on cSVD burden was only significant in the participants with hypertension.ConclusionHigh long-term BP variability, especially in combination with hypertension, is a risk factor for total cSVD burden, LA, and PVS. it is crucial to pay attention to PP variability in young adults.
Evaluation of the Effects of Oxidative Stress and Biomarkers of Inflammation in Cardiomyopathy Sufferers
Authors: Tiwari Shivam , Shankar Om , Singh Royana , Yadav Ajay Kumar , Maurya Anil Kumar , Choudhary Umesh 
Published: January 2024

ABSTRACTIntroductionCardiovascular disease can develop and worsen as a result of inflammation and oxidative stress. The current research looked into the relationship between oxidative damage and biomarkers of inflammation in individuals with cardiomyopathy.MethodsParticular kits for ELISA were used to measure the serum concentrations of CRP, TNF-α, IL-6, and NT-proBNP. These specific ELISA kits are based on sandwich enzyme immunoassay techniques whose results are quantitative. The accuracy of the tests was established by comparing them to control sera that were included in the kits and had known quantities of the analytes.ResultsWhen compared to individuals without cardiomyopathy (control group), we found that cardiomyopathy patients had significantly higher blood C-reactive protein concentrations (P =<0.0001). When compared between control case and cardiomyopathy patients, then find that cardiomyopathy patients had significantly higher concentrations of tumour necrosis factor-alpha (TNF-alpha) (P =<0.0001). TNF-α associated favourably with malondialdehyde (P =<0.0001, r =0.4524) and glutathione peroxidase (GPX) (P =<0.0001, r =0.8311) in Cardiomyopathy patients. Interleukin-6 was not significantly linked with GPX (P =0.0001, r =-0.1194) in cardiomyopathy patients. In those with cardiomyopathy, there was a strong association (P=<0.0001, r=0.4826) between malondialdehyde and NT-proBNP. Furthermore, we observed that the activity of glutathione peroxidase (GPX) exhibited a significant connection with NT-proBNP (P =<0.0001, r = 0.6084) in all cardiomyopathy patients.ConclusionsIn cardiomyopathy patients, but not in normal cases, there is a correlation between inflammatory and oxidative stress indicators. These findings imply intricate cross-talk between the two cellular processes in late-stage cardiomyopathy.
A Human Factors Approach to Childhood Pneumonia A qualitative study in Malawian primary care
Authors: Mbakaya Balwani , Chisale Master R.O. , Wu Tsung-Shu Joseph , Ledwidge Mark T , Nyambalo Billy , Watson Chris , Gallagher Joe 
Published: January 2024

AbstractIntroductionPneumonia is one of the major causes of childhood mortality worldwide. Most of these deaths are readily preventable or treatable with proven cost effective interventions. The aim of this study is to investigate the assessment and management of childhood pneumonia in primary care in Malawi.MethodsSemi-structured interviews were used to elicit accounts of the assessment, treatment and referral process as experienced by staff and caregivers in 10 health facilities in Northern Malawi. Staff members dealing with assessment of children under-five years of age (Doctors, Clinical Officers, Medical Assistants, Nurses, Nurse Midwife Technicians, Student Nurses and Health Surveillance Assistants) were included. It also involved policy makers from the area and caregivers of children presenting with pneumonia. Data was analysed using thematic analysis following the SEIPS 101 tools (task sequence, use of technology and tools, and work system barriers and facilitators).Results43 interviews were undertaken. A process map of the flow of patients with pneumonia was created, showing the tasks undertaken and the interactions between staff and patients. In their interviews caregivers identified a number of barriers to appropriate care including insufficient education for caregivers on the management of sick children and distance to healthcare availability. Staff identified several organisational elements that served as barriers to the implementation of care. They included workload, lack of resources such as medications and batteries, uncertainty regarding markers of severity and need to give all antibiotics. The health passport system and effective teamwork and community were highlighted as being important facilitators.ConclusionThis study provides information on the challenges and issues involved in managing childhood pneumonia in primary care in Malawi. These barriers included a lack of resources, staff and caregiver education and heavy workload. The ability to identify severe illness accurately and identify those who do not require antibiotics were highlighted as issues for health workers.
Gene dysregulation among virally suppressed people living with HIV links to non-AIDS defining cancer pathways
Authors: Quach Bryan C. , Earley Eric , Zhou Linran , Willis Caryn , Marks Jesse A. , Stratford Jeran K. , Fang Fang , Bierut Laura J. , Milloy M-J S. , Hayashi Kanna , DeBeck Kora , Hancock Dana B. , Xu Ke , Aouizerat Bradley E. , Johnson Eric O. 
Published: January 2024

AbstractCombination antiretroviral therapy (ART) has changed the landscape of the HIV epidemic by providing an effective means for viral suppression to people living with HIV (PLWH). Understanding living with HIV as a chronic disease requires an improved understanding of how HIV and/or ART impacts susceptibility to and development of co-occurring conditions. Genome-wide gene expression (transcriptome) differences provide a key view into biological dysregulation associated with living with HIV. Here we present the first whole blood transcriptome-wide study comparing gene expression profiles between virally suppressed PLWH and HIV negative individuals (N=555). We identify 566 genes and 5 immune cell types with differential proportions by HIV status, which were significantly enriched for immune function and cancer pathways. Leveraging quantitative trait loci (QTL) for these HIV status-associated genes, partitioned heritability, and colocalization analyses, we observed limited genetic drivers of these relationships. Our findings suggest that gene dysregulation does not return to a pre-infection state for virally suppressed PLWH, and that persistent gene dysregulation is broadly associated with immune function and cancer pathways, highlighting potential biological drivers for these causes of excess mortality and targets for pharmacological preventative treatment among PLWH.
Neonatal Respiratory Morbidity among Late Preterm Births by Planned Mode of Delivery and Gestational Age
Authors: Clapp Mark A. , Li Siguo , Cohen Jessica L. , Gyamfi-Bannerman Cynthia , Knudsen Amy B. , Lorch Scott A , Thaweethai Tanayott , Wright Jason D. , Kaimal Anjali J. , Melamed Alexander 
Published: January 2024

AbstractObjectiveTo estimate the effect of late preterm antenatal steroids on the absolute risk of respiratory morbidity among subgroups of patients based on the planned mode of delivery and gestational age at presentation.MethodsThis was a secondary analysis of the Antenatal Late Preterm Steroid (ALPS) Trial, a multicenter trial originally conducted within the NICHD’s MFMU network of individuals with singleton gestations and without pre-existing diabetes who were at high risk for late preterm delivery (34-36 weeks of gestation). We fit binomial regression models to estimate the absolute risk of respiratory morbidity, with and without steroid administration, by gestational age and planned mode of delivery at the time of presentation. We assumed a homogenous effect of steroids on the log-odds scale, as was reported in the ALPS trial. The primary outcome was neonatal respiratory morbidity, as defined in the ALPS TrialResultsThe analysis included 2,825 patients at risk for late preterm birth. The risk of respiratory morbidity varied significantly by planned mode of delivery (adjusted risk ratio (aRR) 1.90 (95% confidence interval (CI) 1.55, 2.33) for cesarean compared to vaginal delivery) and day of gestation at presentation (aRR 0.92 (95% CI 0.90, 0.94)). For those planning a cesarean delivery and presenting in the 34th week of gestation, the risk of neonatal respiratory morbidity was 39.4% (95% CI 30.8, 47.9%) without steroids and 32.0% (95% CI 24.6, 39.4%) with steroids. In contrast, for patients presenting in the 36th week and planning a vaginal delivery, the risk of neonatal respiratory morbidity was 6.9% (95% CI 5.6, 8.6%) without steroids and 5.6% (95% 4.2, 7.0%) with steroids.ConclusionThe absolute risk of neonatal respiratory morbidity among patients at risk for late preterm delivery varies considerably by gestational age at presentation and planned mode of delivery. As only communicating the relative risk reduction of antenatal steroids for respiratory morbidity may lead to an inaccurate perception of benefit, individualized estimates of absolute risk expected with and without treatment may inform shared decision-making.