bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detecting unexpected growths in health technologies expenditures: the case of MIPRES in Colombia
Authors: Espinosa Oscar , Bejarano Valeria , Sanabria Cristian , Rodríguez Jhonathan , Basto Sergio , Rodríguez-Lesmes Paul , Robayo Adriana 
Published: October 2023

AbstractWe developed an algorithm to explore unexpected growth in the usage and costs of health technologies. We exploit data from the expenditures on technologies funded by the Colombian government under the compulsory insurance system, where all prescriptions for technologies not included in an explicit list must be registered in a centralized information system, covering the period from 2017 to 2022. The algorithm consists of two steps: an outlier detection method based on the density of the expenditures for selecting a first set of technologies to consider (39 technologies out of 106,957), and two anomaly detection models for time series to determine which insurance companies, health providers, and regions have the most notorious increases. We have found that most medicines associated with atypical behavior and significant monetary growth could be linked to the use of recently introduced drugs in the market. These drugs have valid patents and very specific clinical indications, often involving high-cost pharmacological treatments. The most relevant case is the Burosumab, approved in 2018 to treat a rare genetic disorder affecting skeletal growth. Secondly, there is clear evidence of anomalous increasing trend evolutions in the identified enteral nutritional support supplements or Food for Special Medical Purposes. The health system did not purchase these products before July 2021, but in 2022 they represented more than 500,000 USD per month.
Contaminants from dredged sediments alter the transcriptome of Manila clam and induce shifts in microbiota composition
Authors: Bernardini Ilaria , Quagliariello Andrea , Peruzza Luca , Martino Maria Elena , Dalla Rovere Giulia , Iori Silvia , Asnicar Davide , Ciscato Maria , Fabrello Jacopo , Corami Fabiana , Cecchetto Martina , Giubilato Elisa , Carrer Claudio , Bettiol Cinzia , Semenzin Elena , Marcomini Antonio , Matozzo Valerio , Bargelloni Luca , Milan Massimo , Patarnello Tomaso 
Published: October 2023

Abstract
Background
The reuse of dredged sediments in ports and lagoons is a big issue as it should not affect the quality and the equilibrium of ecosystems. In the lagoon of Venice, sediment management is of crucial importance as sediments are often utilized to built-up structures necessary to limit erosion. However, the impact of sediment reuse on organisms inhabiting this delicate area is poorly known. The Manila clam is a filter-feeding species of high economic and ecological value for the Venice lagoon experiencing a drastic decline in the last decades. In order to define the molecular mechanisms behind sediment toxicity, we exposed clams to sediments sampled from different sites within one of the Venice lagoon navigable canals close to the industrial area. Moreover, we investigated the impacts of dredged sediments on clam’s microbial communities.

Results
Concentrations of the trace elements and organic chemicals showed increasing concentrations from the city of Venice to sites close to the industrial area of Porto Marghera, where PCDD/Fs and PCBs concentrations were up to 120 times higher than the southern lagoon. While bioaccumulation of organic contaminants of industrial origin reflected sediments’ chemical concentrations, metal bioaccumulation was not consistent with metal concentrations measured in sediments probably due to the activation of ABC transporters. At the transcriptional level, we found a persistent activation of the mTORC1 signalling pathway, which is central in the coordination of cellular responses to chemical stress. Microbiota characterization showed the over-representation of potential opportunistic pathogens following exposure to the most contaminated sediments, leading to host immune response activation. Despite the limited acquisition of new microbial species from sediments, the latter play an important role in shaping Manila clam microbial communities.

Conclusions
Sediment management in the Venice lagoon will increase in the next years to maintain and create new canals as well as to allow the operation of the new mobile gates at the three Venice lagoon inlets. Our data reveal important transcriptional and microbial changes of Manila clams after exposure to sediments, therefore reuse of dredged sediments represents a potential risk for the conservation of this species and possibly for other organisms inhabiting the Venice lagoon.
Mechanical thrombectomy in intermediate- and high-risk acute pulmonary embolism: hemodynamic outcomes at three months
Authors: Lauder Lucas , Pérez Navarro Patricia , Götzinger Felix , Ewen Sebastian , Al Ghorani Hussam , Haring Bernhard , Lepper Philipp M. , Kulenthiran Saarraaken , Böhm Michael , Link Andreas , Scheller Bruno , Mahfoud Felix 
Published: October 2023

Abstract
Background
Mechanical thrombectomy has been shown to reduce thrombus burden and pulmonary artery pressure (PAP) and to improve right ventricular (RV) function in patients with high-risk or intermediate-high-risk pulmonary embolism (PE). As hemodynamic data after mechanical thrombectomy for PE are scarce, we aimed to assess the hemodynamic effects of mechanical thrombectomy in acute PE with right heart overload.

Methods
In this prospective, open-label study, patients with acute symptomatic, computed tomography-documented PE with signs of right heart overload underwent mechanical thrombectomy using the FlowTriever System. Right heart catheterization was performed immediately before and after thrombectomy and after three months. Transthoracic echocardiography was performed before thrombectomy, discharge, and at three months. This analysis was done after 20 patients completed three months of follow-up.

Results
Twenty-nine patients (34% female) underwent mechanical thrombectomy, of which 20 completed three months follow-up with right heart catheterization. Most patients were at high (17%) or intermediate-high (76%) risk and had bilateral PE (79%). Before thrombectomy, systolic PAP (sPAP) was severely elevated (mean 51.3 ± 11.6 mmHg). Mean sPAP dropped by -15.0 mmHg (95% confidence interval [CI]: -18.9 to -11.0; p < 0.001) immediately after the procedure and continued to decrease from post-thrombectomy to three months (-6.4 mmHg, 95% CI: -10-0 to -2.9; p = 0.002). RV/left ventricular (LV) ratio immediately reduced within two days by -0.37 (95% CI: -0.47 to -0.27; p < 0.001). The proportion of patients with a tricuspid annular plane systolic excursion (TAPSE)/sPAP ratio < 0.31 mm/mmHg decreased from 28% at baseline to 0% before discharge and at three months (p = 0.007). There were no procedure-related major adverse events.

Conclusions
Mechanical thrombectomy for acute PE was safe and immediately reduced PAP and improved right heart function. The reduction in PAP was maintained at three months follow-up.
Circular RNA P4HB promotes glycolysis and tumor progression by binding with PKM2 in lung adenocarcinoma
Authors: Li Haoran , Guo Haifa , Huang Qi , Wang Shaodong , Li Xiao , Qiu Mantang 
Published: October 2023

Abstract
Background
Emerging evidence indicates that circular RNAs (circRNAs) play vital roles in tumor progression, including lung adenocarcinomas (LUAD). However, the mechanisms by which circRNAs promote the progression of LUAD still require further investigation.

Methods
Quantitative real-time PCR was performed to detect the expression of circP4HB in LUAD tissues and cells. Then, Kaplan–Meier analysis was used to determine the prognostic value of circP4HB expression. We employed RNA pull-down, RNA immunoprecipitation, mass spectrometry, cells fraction, glucose consumption, lactate production, pyruvate kinase M2 (PKM2) activity, and macrophage polarization assays to uncover the underlying mechanisms of circP4HB in LUAD.

Results
We found that circP4HB is upregulated in LUAD tissues and correlated with advanced TNM stages and lymph node metastasis. LUAD patients with high circP4HB expression had poor prognoses. Functionally, circP4HB promoted LUAD progression in vivo and in vitro. Upregulated circP4HB increased glucose consumption, lactate production and accelerated aerobic glycolysis in LUAD cells. Mechanically, circP4HB mainly accumulated in the cytoplasm of LUAD cells and bound with PKM2 and subsequently upregulating PKM2 enzymatic activity by increasing its tetramer formation. Additionally, circP4HB promoted M2 macrophage phenotype shift via targeting PKM2. Finally, rescue assays further confirmed that circP4HB could promote LUAD cell progression through its interaction with PKM2.

Conclusion
These results demonstrate that circP4HB could promote LUAD progression, indicating circP4HB might be a potential therapeutic target of LUAD.

Graphical Abstract
Peer-led safer supply and opioid agonist treatment medication distribution: a case study from rural British Columbia
Authors: Scow Marnie , McDougall Jenny , Slaunwhite Amanda , Palis Heather 
Published: October 2023

Abstract
Background
British Columbia (BC) has been facing a public health emergency of overdose since 2016, with rural regions of the province facing the highest rates of death. Peers (in this case, people with lived experience of substance use) are known to be effective patient navigators in health systems and can play a role in connecting patients to care and reducing overdose risk.

Case presentation
We outline a peer-led program focused on opioid agonist treatment and prescribed safe supply medication delivery that began in March 2020 at a clinic in rural BC. The peer takes an Indigenous harm reduction approach and is focused on meeting the needs of the whole person. The peer has regular contact with approximately 50 clients and navigates medication delivery and appointments for approximately 10–15 people each day. Clients have been retained on the medication, and experienced improvement in other outcomes, including securing housing, employment and managing acute and chronic health conditions. The peer has established contact with clients since March 2020 to support engagement with health care and continuity of medication access. This program highlights the importance and value of peer-led work and need for further investments in peer-led programs to respond to the unregulated drug poisoning crisis.

Conclusions
This peer-led intervention is a promising approach to engaging people who remain disconnected from health services in care in a rural community. This model could be adapted to other settings to support patient contact with the health system and medication access and continuity, with the ultimate goal of reducing overdose risk.
Academic contributions to the development of evidence and policy systems: an EPPI Centre collective autoethnography
Authors: Oliver Sandy , Dickson Kelly , Bangpan Mukdarut 
Published: October 2023

Abstract
Background
Evidence for policy systems emerging around the world combine the fields of research synthesis, evidence-informed policy and public engagement with research. We conducted this retrospective collective autoethnography to understand the role of academics in developing such systems.

Methods
We constructed a timeline of EPPI Centre work and associated events since 1990. We employed: Transition Theory to reveal emerging and influential innovations; and Transformative Social Innovation theory to track their increasing depth, reach and embeddedness in research and policy organisations.

Findings
The EPPI Centre, alongside other small research units, collaborated with national and international organisations at the research-policy interface to incubate, spread and embed new ways of working with evidence and policy. Sustainable change arising from research-policy interactions was less about uptake and embedding of innovations, but more about co-developing and tailoring innovations with organisations to suit their missions and structures for creating new knowledge or using knowledge for decisions. Both spreading and embedding innovation relied on mutual learning that both accommodated and challenged established assumptions and values of collaborating organisations as they adapted to closer ways of working. The incubation, spread and embedding of innovations have been iterative, with new ways of working inspiring further innovation as they spread and embedded. Institutionalising evidence for policy required change in both institutions generating evidence and institutions developing policy.

Conclusions
Key mechanisms for academic contributions to advancing evidence for policy were: contract research focusing attention at the research-policy interface; a willingness to work in unfamiliar fields; inclusive ways of working to move from conflict to consensus; and incentives and opportunities for reflection and consolidating learning.
Cost-effectiveness analysis of surgical proximal femur fracture prevention in elderly: a Markov cohort simulation model
Authors: Alnemer Momin S. , Kotliar Konstantin E. , Neuhaus Valentin , Pape Hans-Christoph , Ciritsis Bernhard D. 
Published: October 2023

Abstract
Background
Hip fractures are a common and costly health problem, resulting in significant morbidity and mortality, as well as high costs for healthcare systems, especially for the elderly. Implementing surgical preventive strategies has the potential to improve the quality of life and reduce the burden on healthcare resources, particularly in the long term. However, there are currently limited guidelines for standardizing hip fracture prophylaxis practices.

Methods
This study used a cost-effectiveness analysis with a finite-state Markov model and cohort simulation to evaluate the primary and secondary surgical prevention of hip fractures in the elderly. Patients aged 60 to 90 years were simulated in two different models (A and B) to assess prevention at different levels. Model A assumed prophylaxis was performed during the fracture operation on the contralateral side, while Model B included individuals with high fracture risk factors. Costs were obtained from the Centers for Medicare & Medicaid Services, and transition probabilities and health state utilities were derived from available literature. The baseline assumption was a 10% reduction in fracture risk after prophylaxis. A sensitivity analysis was also conducted to assess the reliability and variability of the results.

Results
With a 10% fracture risk reduction, model A costs between $8,850 and $46,940 per quality-adjusted life-year ($/QALY). Additionally, it proved most cost-effective in the age range between 61 and 81 years. The sensitivity analysis established that a reduction of ≥ 2.8% is needed for prophylaxis to be definitely cost-effective. The cost-effectiveness at the secondary prevention level was most sensitive to the cost of the contralateral side’s prophylaxis, the patient’s age, and fracture treatment cost. For high-risk patients with no fracture history, the cost-effectiveness of a preventive strategy depends on their risk profile. In the baseline analysis, the incremental cost-effectiveness ratio at the primary prevention level varied between $11,000/QALY and $74,000/QALY, which is below the defined willingness to pay threshold.

Conclusion
Due to the high cost of hip fracture treatment and its increased morbidity, surgical prophylaxis strategies have demonstrated that they can significantly relieve the healthcare system. Various key assumptions facilitated the modeling, allowing for adequate room for uncertainty. Further research is needed to evaluate health-state-associated risks.
Potential determinants of antibody responses after vaccination against SARS-CoV-2 in older persons: the Doetinchem Cohort Study
Authors: Kuijpers Yunus , Picavet H. Susan J. , de Rond Lia , de Zeeuw-Brouwer Mary-lène , Rutkens Ryanne , Gijsbers Esther , Slits Irene , Engelfriet Peter , Buisman Anne-Marie , Verschuren W. M. Monique 
Published: October 2023

Abstract
Background
Immune responses to vaccination vary widely between individuals. The aim of this study was to identify health-related variables potentially underlying the antibody responses to SARS-CoV-2 vaccination in older persons. We recruited participants in the long-running Doetinchem Cohort Study (DCS) who underwent vaccination as part of the national COVID-19 program, and measured antibody concentrations to SARS-CoV-2 Spike protein (S1) and Nucleoprotein (N) at baseline (T0), and a month after both the first vaccination (T1), and the second vaccination (T2). Associations between the antibody concentrations and demographic variables, including age, sex, socio-economic status (SES), comorbidities (cardiovascular diseases and immune mediated diseases), various health parameters (cardiometabolic markers, inflammation markers, kidney- and lung function) and a composite measure of frailty (‘frailty index’, ranging from 0 to 1) were tested using multivariate models.

Results
We included 1457 persons aged 50 to 92 years old. Of these persons 1257 were infection naïve after their primary vaccination series. The majority (N = 954) of these individuals were vaccinated with two doses of BNT162b2 (Pfizer) and their data were used for further analysis. A higher frailty index was associated with lower anti-S1 antibody responses at T1 and T2 for both men (RT1 = -0.095, PT1 = 0.05; RT2 = -0.11, PT2 = 0.02) and women (RT1 = -0.24, PT1 < 0.01; RT2 = -0.15, PT2 < 0.01). After correcting for age and sex the frailty index was also associated with the relative increase in anti-S1 IgG concentrations between the two vaccinations (β = 1.6, P < 0.01). Within the construct of frailty, history of a cardiac catheterization, diabetes, gastrointestinal disease, a cognitive speed in the lowest decile of the population distribution, and impaired lung function were associated with lower antibody responses after both vaccinations.

Conclusions
Components of frailty play a key role in the primary vaccination response to the BNT162b2 vaccine within an ageing population. Older persons with various comorbidities have a lowered immune response after their first vaccination, and while frail and sick older persons see a stronger increase after their second vaccination compared to healthy people, they still have a lower antibody response after their second vaccination.
Dehydroepiandrosterone-induced polycystic ovary syndrome mouse model requires continous treatments to maintain reproductive phenotypes
Authors: Wu Haowen , Zhao Bining , Yao Qiyang , Kang Jihong 
Published: October 2023

Abstract
Background
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy associated with infertility and metabolic disorder in women of reproductive age. Animal models have been developed and used as tools to unravel the pathogenesis of PCOS, among which most postnatal models employ continuing experimental manipulations. However, the persistence and stability of these animals after modeling is unknown. Dehydroepiandrosterone (DHEA)-induced PCOS mouse model is commonly used in PCOS studies. Thus the aim of the present study was to investigate the reproductive features of DHEA-induced PCOS mice fed a normal chow or an high-fat diet (HFD) with treatment withdrawal or consecutive treatments after PCOS mouse models were established.

Methods
Prepubertal C57BL/6 J mice (age 25 days) were injected (s.c.) daily with DHEA on a normal chow or a 60% HFD for 20 consecutive days to induce PCOS mouse models. Mice injected with the vehicle sesame oil were used as controls. After 20 days, mice were divided into 2 groups, namely “Continue dosing group” and “Stop dosing group”. The animals were consecutively treated with DHEA or DHEA + HFD, or housed without any treatment for 2 or 4 weeks. Estrous cycles were evaluated during this period. At the end of the experiment, serum testosterone (T) levels were measured and the morphology of ovaries was evaluated.

Results
The mice in Continue dosing groups maintained reproductive phenotypes of PCOS mouse models. In contrast, 2 or 4 weeks after PCOS models were established, the mice with treatment withdrawal in Stop dosing groups exhibited normal serum testosterone levels, regular estrous cycle, and relatively normal ovarian morphology. In addition, even with consecutive treatments, there was no marked difference in body weight between DHEA mice on the normal chow or an HFD in Continue dosing groups and the control animals 3 weeks after modeling.

Conclusions
After PCOS mice were induced with DHEA or DHEA + HFD, the mice still need consecutive treatments to maintain reproductive phenotypes to be regarded as PCOS mice that meet the diagnostic criteria of PCOS defined by the 2003 Rotterdam criteria.
Outcome of severely injured patients in a unique trauma system with 24/7 double trauma surgeon on-call service
Authors: van Wessem Karlijn J. P. , Leenen Luke P. H. , Houwert R. Marijn , Benders Kim E. M. , Simmermacher Roger K. J. , van Baal Mark C. P. M. , de Bruin Ivar G. J. M. , de Jong Mirjam B. , Nijs Stefaan J. B. , Hietbrink Falco 
Published: October 2023

Abstract
Background
The presence of in-house attending trauma surgeons has improved efficiency of processes in the treatment of polytrauma patients. However, literature remains equivocal regarding the influence of the presence of in-house attendings on mortality. In our hospital there is a double trauma surgeon on-call system. In this system an in-house trauma surgeon is 24/7 backed up by a second trauma surgeon to assist with urgent surgery or multiple casualties. The aim of this study was to evaluate outcome in severely injured patients in this unique trauma system.

Methods
From 2014 to 2021, a prospective population-based cohort consisting of consecutive polytrauma patients aged ≥ 15 years requiring both urgent surgery (≤ 24h) and admission to Intensive Care Unit (ICU) was investigated. Demographics, treatment, outcome parameters and pre- and in-hospital transfer times were analyzed.

Results
Three hundred thirteen patients with a median age of 44 years (71% male), and median Injury Severity Score (ISS) of 33 were included. Mortality rate was 19% (68% due to traumatic brain injury). All patients stayed ≤ 32 min in ED before transport to either CT or OR. Fifty-one percent of patients who needed damage control surgery (DCS) had a more deranged physiology, needed more blood products, were more quickly in OR with shorter time in OR, than patients with early definitive care (EDC). There was no difference in mortality rate between DCS and EDC patients. Fifty-six percent of patients had surgery during off-hours. There was no difference in outcome between patients who had surgery during daytime and during off-hours. Death could possibly have been prevented in 1 exsanguinating patient (1.7%).

Conclusion
In this cohort of severely injured patients in need of urgent surgery and ICU support it was demonstrated that surgical decision making was swift and accurate with low preventable death rates. 24/7 Physical presence of a dedicated trauma team has likely contributed to these good outcomes.