bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining measures of emergency care access in low-income and middle-income countries: a scoping review
Authors: Hirner Sarah , Dhakal Jyotshila , Broccoli Morgan Carol , Ross Madeline , Calvello Hynes Emilie J , Bills Corey B 
Published: April 2023

BackgroundOver 50% of annual deaths in low-income and middle-income countries (LMICs) could be averted through access to high-quality emergency care.ObjectivesWe performed a scoping review of the literature that described at least one measure of emergency care access in LMICs in order to understand relevant barriers to emergency care systems.Eligibility criteriaEnglish language studies published between 1 January 1990 and 30 December 2020, with one or more discrete measure(s) of access to emergency health services in LMICs described.Source of evidencePubMed, Embase, Web of Science, CINAHL and the grey literature.Charting methodsA structured data extraction tool was used to identify and classify the number of ‘unique’ measures, and the number of times each unique measure was studied in the literature (‘total’ measures). Measures of access were categorised by access type, defined by Thomas and Penchansky, with further categorisation according to the ‘Three Delay’ model of seeking, reaching and receiving care, and the WHO’s Emergency Care Systems Framework (ECSF).ResultsA total of 3103 articles were screened. 75 met full study inclusion. Articles were uniformly descriptive (n=75, 100%). 137 discrete measures of access were reported. Unique measures of accommodation (n=42, 30.7%) and availability (n=40, 29.2%) were most common. Measures of seeking, reaching and receiving care were 22 (16.0%), 46 (33.6%) and 69 (50.4%), respectively. According to the ECSF slightly more measures focused on prehospital care—inclusive of care at the scene and through transport to a facility (n=76, 55.4%) as compared with facility-based care (n=57, 41.6%).ConclusionsNumerous measures of emergency care access are described in the literature, but many measures are overaddressed. Development of a core set of access measures with associated minimum standards are necessary to aid in ensuring universal access to high-quality emergency care in all settings.
Valsartan, Losartan and Irbesartan use in the USA, UK, Canada and Denmark after the nitrosamine recalls: a descriptive cohort study
Authors: Eworuke Efe , Shinde Mayura , Hou Laura , Paterson Michael J , Jensen Peter Bjødstrup , Maro Judith C , Rai Ashish , Scarnecchia Daniel , Pennap Dinci , Woronow Daniel , Ghosh Rebecca E , Welburn Stephen , Pottegard Anton , Platt Robert W , Lee Hana , Bradley Marie C 
Published: April 2023

ObjectivesTo examine valsartan, losartan and irbesartan usage and switching patterns in the USA, UK, Canada and Denmark before and after July 2018, when the first Angiotensin-Receptor-Blocker (ARB) (valsartan) was recalled.DesignRetrospective cohort study.SettingUSA, Canadian administrative healthcare data, Danish National Prescription Registry and UK primary care electronic health records.ParticipantsPatients aged 18 years and older between January 2014 and December 2020.InterventionValsartan, losartan and irbesartan.Main outcomeMonthly percentages of individual ARB episodes, new users and switches to another ARB, ACE inhibitors (ACEI) or calcium channel blockers containing products.ResultsWe identified 10.8, 3.2, 1.8 and 1.2 million ARB users in the USA, UK, Canada and Denmark, respectively. Overall proportions of valsartan, losartan and irbesartan use were 18.4%, 67.9% and 5.2% in the USA; 3.1%, 48.3% and 10.2% in the UK, 16.3%, 11.4% and 18.3% in Canada, 1%, 93.5% and 0.6% in Denmark. In July 2018, we observed an immediate steep decline in the proportion of valsartan use in the USA and Canada. A similar trend was observed in Denmark; however, the decline was only minimal. We observed no change in trends of ARB use in the UK. Accompanying the valsartan decline was an increase in switching to other ARBs in the USA, Canada and Denmark. There was a small increase in switching to ACEI relative to the valsartan-to-other-ARBs switch. We also observed increased switching from other affected ARBs, losartan and irbesartan, to other ARBs throughout 2019, in the USA and Canada, although the usage trends in the USA remained unchanged.ConclusionThe first recall notice for valsartan resulted in substantial decline in usage due to increased switching to other ARBs. Subsequent notices for losartan and irbesartan were also associated with increased switching around the time of the recall, however, overall usage trends remained unchanged.
Personalised recommendations for hospitalised patients with Acute Kidney Injury using a Kidney Action Team (KAT-AKI): protocol and early data of a randomised controlled trial
Authors: Aklilu Abinet Mathias , O’Connor Kyle D , Martin Melissa , Yamamoto Yu , Coronel-Moreno Claudia , Shvets Kristina , Jones Charles , Kadhim Bashar , Corona-Villalobos Celia P , Baker Megan L , Tan Jiawei , Freeman Natasha , Groener Marwin , Menez Steven , Brown Dannielle , Culli Samuel E , Lindsley John , Orias Marcelo , Parikh Chirag , Smith Abigail , Sundararajan Anusha , Wilson Francis P 
Published: April 2023

IntroductionAlthough studies have examined the utility of clinical decision support tools in improving acute kidney injury (AKI) outcomes, no study has evaluated the effect of real-time, personalised AKI recommendations. This study aims to assess the impact of individualised AKI-specific recommendations delivered by trained clinicians and pharmacists immediately after AKI detection in hospitalised patients.Methods and analysisKAT-AKI is a multicentre randomised investigator-blinded trial being conducted across eight hospitals at two major US hospital systems planning to enrol 4000 patients over 3 years (between 1 November 2021 and 1 November 2024). A real-time electronic AKI alert system informs a dedicated team composed of a physician and pharmacist who independently review the chart in real time, screen for eligibility and provide combined recommendations across the following domains: diagnostics, volume, potassium, acid–base and medications. Recommendations are delivered to the primary team in the alert arm or logged for future analysis in the usual care arm. The planned primary outcome is a composite of AKI progression, dialysis and mortality within 14 days from randomisation. A key secondary outcome is the percentage of recommendations implemented by the primary team within 24 hours from randomisation. The study has enrolled 500 individuals over 8.5 months. Two-thirds were on a medical floor at the time of the alert and 17.8% were in an intensive care unit. Virtually all participants were recommended for at least one diagnostic intervention. More than half (51.6%) had recommendations to discontinue or dose-adjust a medication. The median time from AKI alert to randomisation was 28 (IQR 15.8–51.5) min.Ethics and disseminationThe study was approved by the ethics committee of each study site (Yale University and Johns Hopkins institutional review board (IRB) and a central IRB (BRANY, Biomedical Research Alliance of New York). We are committed to open dissemination of the data through clinicaltrials.gov and sharing of data on an open repository as well as publication in a peer-reviewed journal on completion.Trial registration numberNCT04040296.
Comparing relationships between single types of adverse childhood experiences and health-related outcomes: a combined primary data study of eight cross-sectional surveys in England and Wales
Authors: Bellis Mark A , Hughes Karen , Cresswell Katie , Ford Kat 
Published: April 2023

ObjectivesAdverse childhood experiences (ACEs) show strong cumulative associations with ill-health across the life course. Harms can arise even in those exposed to a single ACE type but few studies examine such exposure. For individuals experiencing a single ACE type, we examine which ACEs are most strongly related to different health harms.DesignSecondary analysis of combined data from eight cross-sectional general population ACE surveys.SettingHouseholds in England and Wales.Participants20 556 residents aged 18–69 years.MeasuresTen self-reported outcomes were examined: smoking, cannabis use, binge drinking, obesity, sexually transmitted infection, teenage pregnancy, mental well-being, violence perpetration, violence victimisation and incarceration. Adjusted ORs and percentage changes in outcomes were calculated for each type of ACE exposure.ResultsSignificance and magnitude of associations between each ACE and outcome varied. Binge drinking was associated with childhood verbal abuse (VA), parental separation (PS) and household alcohol problem (AP), while obesity was linked to sexual abuse (SA) and household mental illness. SA also showed the biggest increase in cannabis use (25.5% vs 10.8%, no ACEs). Household AP was the ACE most strongly associated with violence and incarceration. PS was associated with teenage pregnancy (9.1% vs 3.7%, no ACEs) and 5 other outcomes. VA was associated with 7 of the 10 outcomes examined.ConclusionExposure to a single ACE increases risks of poorer outcomes across health-harming behaviours, sexual health, mental well-being and criminal domains. Toxic stress can arise from ACEs such as physical and SA but other more prevalent ACEs (eg, VA, PS) may also contribute substantively to poorer life course health.
End of life in haematology: quality of life predictors – retrospective cohort study
Authors: Korsos Victoria , Ali Alla'a , Malagon Talia , Khosrow-Khavar Farzin , Thomas Doneal , Sirhan Shireen , Davison Kelly , Assouline Sarit , Cassis Chantal 
Published: April 2023

ObjectivesHaematology patients are more likely to receive high intensity care near end of life (EOL) than patients with solid malignancy. Previous authors have suggested indicators of quality EOL for haematology patients, based on a solid oncology model. We conducted a retrospective chart review with the objectives of (1) determining our performance on these quality EOL indicators, (2) describing the timing of level of intervention (LOI) discussion and palliative care (PC) consultation prior to death and (3) evaluating whether goals of therapy (GOT), PC consultation and earlier LOI discussion are predictors of quality EOL.MethodsWe identified patients who died from haematological malignancies between April 2014 and March 2016 (n=319) at four participating McGill University hospitals and performed retrospective chart reviews.ResultsWe found that 17% of patients were administered chemotherapy less than 14 days prior to death, 20% of patients were admitted to intensive care, 14% were intubated and 5% were resuscitated less than 30 days prior to death, 18% of patients received blood transfusion less than 7 days prior to death and 67% of patients died in an acute care setting. LOI discussion and PC consultation occurred a median of 22 days (IQR 7–103) and 9 days (IQR 3–19) before death. Patients with non-curative GOT, PC consultation or discussed LOI were significantly less likely to have high intensity EOL outcomes.ConclusionsIn this study, we demonstrate that LOI discussions, PC consults and physician established GOT are associated with quality EOL outcomes for patients with haematological malignancies.
Single-Cell Spatial Analysis Identifies Regulators of Brain Tumor–Initiating Cells
Authors: Mirzaei Reza , D'Mello Charlotte , Liu Marina , Nikolic Ana , Kumar Mehul , Visser Frank , Bose Pinaki , Gallo Marco , Yong V. Wee 
Published: April 2023

Abstract

Glioblastomas (GBM) are aggressive brain tumors with extensive intratumoral heterogeneity that contributes to treatment resistance. Spatial characterization of GBMs could provide insights into the role of the brain tumor microenvironment in regulating intratumoral heterogeneity. Here, we performed spatial transcriptomic and single-cell analyses of the mouse and human GBM microenvironment to dissect the impact of distinct anatomical regions of brains on GBM. In a syngeneic GBM mouse model, spatial transcriptomics revealed that numerous extracellular matrix (ECM) molecules, including biglycan, were elevated in areas infiltrated with brain tumor–initiating cells (BTIC). Single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin using sequencing showed that ECM molecules were differentially expressed by GBM cells based on their differentiation and cellular programming phenotypes. Exogeneous biglycan or overexpression of biglycan resulted in a higher proliferation rate of BTICs, which was associated mechanistically with low-density lipoprotein receptor-related protein 6 (LRP6) binding and activation of the Wnt/β-catenin pathway. Biglycan-overexpressing BTICs developed into larger tumors and displayed mesenchymal phenotypes when implanted intracranially in mice. This study points to the spatial heterogeneity of ECM molecules in GBM and suggests that the biglycan–LRP6 axis could be a therapeutic target to curb tumor growth.

Significance:
Characterization of the spatial heterogeneity of glioblastoma identifies regulators of brain tumor–initiating cells and tumor growth that could serve as candidates for therapeutic interventions to improve the prognosis of patients.
Li–Fraumeni Syndrome–Associated Dimer-Forming Mutant p53 Promotes Transactivation-Independent Mitochondrial Cell Death
Authors: Choe Joshua H. , Kawase Tatsuya , Xu An , Guzman Asja , Obradovic Aleksandar Z. , Low-Calle Ana Maria , Alaghebandan Bita , Raghavan Ananya , Long Kaitlin , Hwang Paul M. , Schiffman Joshua D. , Zhu Yan , Zhao Ruiying , Lee Dung-Fang , Katz Chen , Prives Carol 
Published: April 2023

Abstract

Cancer-relevant mutations in the oligomerization domain (OD) of the p53 tumor suppressor protein, unlike those in the DNA binding domain, have not been well elucidated. Here, we characterized the germline OD mutant p53(A347D), which occurs in cancer-prone Li–Fraumeni syndrome (LFS) patients. Unlike wild-type p53, mutant p53(A347D) cannot form tetramers and exists as a hyperstable dimeric protein. Further, p53(A347D) cannot bind or transactivate the majority of canonical p53 target genes. Isogenic cell lines harboring either p53(A347D) or no p53 yield comparable tumorigenic properties, yet p53(A347D) displays remarkable neomorphic activities. Cells bearing p53(A347D) possess a distinct transcriptional profile and undergo metabolic reprogramming. Further, p53(A347D) induces striking mitochondrial network aberration and associates with mitochondria to drive apoptotic cell death upon topoisomerase II inhibition in the absence of transcription. Thus, dimer-forming p53 demonstrates both loss-of-function (LOF) and gain-of-function (GOF) properties compared with the wild-type form of the protein.

Significance:
A mutant p53 (A347D), which can only form dimers, is associated with increased cancer susceptibility in LFS individuals. We found that this mutant wields a double-edged sword, driving tumorigenesis through LOF while gaining enhanced apoptogenic activity as a new GOF, thereby yielding a potential vulnerability to select therapeutic approaches.
See related commentary by Stieg et al., p. 1046.
See related article by Gencel-Augusto et al., p. 1230.
This article is highlighted in the In This Issue feature, p. 1027
Opportunities for Achieving the Cancer Moonshot Goal of a 50% Reduction in Cancer Mortality by 2047
Authors: Shiels Meredith S. , Lipkowitz Stanley , Campos Nicole G. , Schiffman Mark , Schiller John T. , Freedman Neal D. , Berrington de González Amy 
Published: April 2023

Abstract

On February 2, 2022, President Biden and First Lady Dr. Biden reignited the Cancer Moonshot, setting a new goal to reduce age-standardized cancer mortality rates by at least 50% over the next 25 years in the United States. We estimated trends in U.S. cancer mortality during 2000 to 2019 for all cancers and the six leading types (lung, colorectum, pancreas, breast, prostate, liver). Cancer death rates overall declined by 1.4% per year from 2000 to 2015, accelerating to 2.3% per year during 2016 to 2019, driven by strong declines in lung cancer mortality (−4.7%/year, 2014 to 2019). Recent declines in colorectal (−2.0%/year, 2010–2019) and breast cancer death rates (−1.2%/year, 2013–2019) also contributed. However, trends for other cancer types were less promising. To achieve the Moonshot goal, progress against lung, colorectal, and breast cancer deaths needs to be maintained and/or accelerated, and new strategies for prostate, liver, pancreatic, and other cancers are needed. We reviewed opportunities to prevent, detect, and treat these common cancers that could further reduce population-level cancer death rates and also reduce disparities.

Significance:
We reviewed opportunities to prevent, detect, and treat common cancers, and show that to achieve the Moonshot goal, progress against lung, colorectal, and breast cancer deaths needs to be maintained and/or accelerated, and new strategies for prostate, liver, pancreatic, and other cancers are needed.
See related commentary by Bertagnolli et al., p. 1049.
This article is highlighted in the In This Issue feature, p. 1027
Identificaton and Diversity of Endophytic Fungi Associated with The Seagrasses of Cebu, Central Philippines
Authors: Kinamot Venus , Monotilla Alvin 
Published: April 2023

Endophytic fungi were poorly documented in the marine environment, especially in seagrasses regardless of their importance as sources of novel metabolites. In the Philippines, studies are dearth despite having large areas of seagrass meadows. Thus, this study was conducted to isolate and identify endophytic fungi associated with common seagrasses: Enhalus acoroides, Cymodocea serrulata, and Thalassia hemprichii from the Philippines by morphologic and molecular methods. Seven species were identified in this study: Aspergillus tamarii, A. ochraceopetaliformis, A. sydowii, Penicillium citrinum, Xylaria sp., Beauveria bassiana, and Eutypella sp. Morphologically, Aspergillus spp. had septate hyphae, biseriate conidiophore, and smooth to rough globose conidia. Penicillium had a green colony, biverticillate conidiophore, and smooth, globose conidia. Beauveria bassiana had white to cream colonies with irregular edges and a powdery appearance. The conidiogenous cells had zigzag rachis in which a chain of conidia emerged. Eutypella sp. had white, filariform, and plumose colony. Xylaria sp. had a white colony with conspicuous radial lines and a plumose margin. Phylogenetic analysis using 80 ITS rDNA sequences by neighbor-joining revealed the clustering of our isolates with the closest match taxa in the same clade with 100% bootstrap value. The estimate of evolutionary divergence between our isolates and their closest match taxa by pairwise distance showed no nucleotide base substitution suggesting high sequence identity between sequences. The most diverse endophyte is Aspergillus as it is ubiquitously adapted to the marine environment. To our knowledge, this is the first report of these species colonizing the seagrasses from the Philippines.
Aspectos radiológicos do baço intrapancreático
Authors: Lima Luara Araújo Rodrigues , Gomes Raissa Fernanda Maciel , Sousa André Luca Araujo de , Pinto Antonione Santos Bezerra , Costa Vanessa da Conceição Soares , Oliveira Leonam Costa 
Published: April 2023

Baço – acessório localizado dentro do parênquima pancreático – é uma anomalia congênita do tecido esplênico, com características morfológicas e histológicas semelhante ao baço normal apresentado, geralmente, na cauda do pâncreas. O baço acessório intrapancreático (BAI) trata-se, sobretudo, de uma lesão benigna, usualmente assintomática e encontrada incidentalmente em estudos de imagem, mas que suscitam frequentemente uma preocupação de malignidade e podem ser radiologicamente indistinguíveis de tumores neuroendócrinos, tumores pancreáticos e adenocarcinomas. O presente estudo visa, portanto, relatar um caso de baço acessório intrapancreático através da tomografia computadorizada (TC) e ressonância magnética (RM), além de correlacionar os achados radiográficos do relato de caso com outros métodos radiológicos encontrados na revisão de literatura. As informações contidas foram obtidas por meio de revisão do prontuário, entrevista com o paciente, registro fotográfico dos métodos diagnósticos em geral e dados laboratoriais, aos quais o paciente foi submetido. Nesse contexto, o relato de caso é de um homem com história prévia de carcinoma de células renais que, após realização de nefrectomia total à esquerda e de linfonodos retroperitoneais, constatou no seguimento de seus exames de controle pós-operatório uma imagem nodular na cauda pancreática sugestiva de metástase, mas que, através do estudo tomográfico e de RM, foi possível realizar o correto diagnóstico, tratando-se apenas de uma afecção benigna assintomática e de intervenção conservadora descrita como BAI.
Interpersonal violence in a city of Paraná: a study about the epidemiological profile of victims and characterization of dental trauma
Authors: Sato Cindy Maki , Pinto Paulo Henrique Viana , Costa Larissa Barros , Silva Ricardo Henrique Alves da 
Published: April 2023

The socioeconomic context and population vulnerability are directly associated with violence in the country. In Brazil, the Criminal Code provides the illicit act and punishes the aggressor who offends the physical aggression from a person. Interpersonal violence is an illegal act and is associated with the vulnerability of victims. Therefore, the study of the epidemiological profile of victims of interpersonal violence is needed to alert the population about their susceptibility. The present study aimed to design the epidemiological profile of victims of bodily injury from interpersonal violence in the region of Maringá, in the state of Paraná, and to study the characterization of dental injuries in terms of permanent weakness and deformity. Four thousand nine hundred sixty-two reports performed between 2018 and 2020 were analyzed using descriptive statistics. Data collected included: sex, age, marital status, the region affected by the bodily injury, type of dental trauma, and responses to “weakness” or/and “permanent deformity”. During the period studied, there was a prevalence of female victims (57.8%), white skin color (80.2%), aged between 21 and 30 years (24.9%), single (54.9%), and the most affected region was the upper limbs (32.1%). Regarding bodily injuries with dental involvement, 67 cases were reported, male victims were prevalent (60.3%), and dental fracture was highlighted with 54.4% of examined injuries. The implementation of the Forensic Dentistry Centre took place in August 2019 at the Medico-Legal Institute of Maringá. Also, with the interruption of expert activities in 2020 - due to the COVID-19 pandemic – relevant outcomes regarding permanent weakness were

observed. The epidemiological profile of victims is characterized by the female sex, white skin color, the age group from 21 to 30 years old, and singles. Regarding dental trauma, male victims, and dental fractures were prevalent. Furthermore, there was an increase in the classification of "permanent weakness", as well as a slight increase in cases of "further assessment required" for permanent deformity.