bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine-learning based prediction of appendicitis for patients presenting with acute abdominal pain at the emergency department
Authors: Schipper Anoeska , Belgers Peter , O’Connor Rory , Jie Kim Ellis , Dooijes Robin , Bosma Joeran Sander , Kurstjens Steef , Kusters Ron , van Ginneken Bram , Rutten Matthieu 
Published: December 2024

Abstract
Background
Acute abdominal pain (AAP) constitutes 5–10% of all emergency department (ED) visits, with appendicitis being a prevalent AAP etiology often necessitating surgical intervention. The variability in AAP symptoms and causes, combined with the challenge of identifying appendicitis, complicate timely intervention. To estimate the risk of appendicitis, scoring systems such as the Alvarado score have been developed. However, diagnostic errors and delays remain common. Although various machine learning (ML) models have been proposed to enhance appendicitis detection, none have been seamlessly integrated into the ED workflows for AAP or are specifically designed to diagnose appendicitis as early as possible within the clinical decision-making process. To mimic daily clinical practice, this proof-of-concept study aims to develop ML models that support decision-making using comprehensive clinical data up to key decision points in the ED workflow to detect appendicitis in patients presenting with AAP.

Methods
Data from the Dutch triage system at the ED, vital signs, complete medical history and physical examination findings and routine laboratory test results were retrospectively extracted from 350 AAP patients presenting to the ED of a Dutch teaching hospital from 2016 to 2023. Two eXtreme Gradient Boosting ML models were developed to differentiate cases with appendicitis from other AAP causes: one model used all data up to and including physical examination, and the other was extended with routine laboratory test results. The performance of both models was evaluated on a validation set (n = 68) and compared to the Alvarado scoring system as well as three ED physicians in a reader study.

Results
The ML models achieved AUROCs of 0.919 without laboratory test results and 0.923 with the addition of laboratory test results. The Alvarado scoring system attained an AUROC of 0.824. ED physicians achieved AUROCs of 0.894, 0.826, and 0.791 without laboratory test results, increasing to AUROCs of 0.923, 0.892, and 0.859 with laboratory test results.

Conclusions
Both ML models demonstrated comparable high accuracy in predicting appendicitis in patients with AAP, outperforming the Alvarado scoring system. The ML models matched or surpassed ED physician performance in detecting appendicitis, with the largest potential performance gain observed in absence of laboratory test results. Integration could assist ED physicians in early and accurate diagnosis of appendicitis.

Graphical abstract
Risk of infection and conversion time from external to definitive fixation in open tibial fracture
Authors: Aljuhani Wazzan S. , Alshabi Yasir A. , Alanazi Abdullah M. , Alothri Meshal A. , Almutairi Saleh A. , Aljaafri Ziad A. , Alzahrani Abdullah M. 
Published: December 2024

Abstract

Background
An open fracture of the tibia is one of the most common and dangerous type of open fractures. In the management of these injuries, the primary focus is on reducing the infection rate, as this is crucial for achieving the best clinical outcomes. This study aims to explore how provisional external fixation duration influences the rates of infection and union in open tibial shaft fractures.

Methods
A retrospective study with a total of 55 patients who received temporary external fixation. Groups A (less than 12 days), B (12–24), C (25–36), and D (more than 36) were the four groups into which they were split according to the conversion time.

Results
12.8%, 18.2%, 50%, and 100% of the infections were found in Groups A, B, C, and D, respectively. Significant (P < 0.05) differences were found throughout the four groups. The conversion time from external to definitive fixation was found to have a relationship with the occurrence of an infection (P = 0.004). A higher prevalence of infection was observed over time. However, no association was observed between infection and antibiotic duration or initial debridement time (P = 0.689 and P = 0.963, respectively).

Conclusions
Results of this study demonstrate that the likelihood of infection increases when the change from external fixation to definitive internal fixation is delayed. Therefore, it is important to convert to definitive internal fixation immediately when the local and general conditions are favorable for doing so.
Application of four pricing models for orphan medicines: a case study for lumasiran
Authors: Rosenberg Noa , Manders Evert , van den Berg Sibren , Deesker Lisa J. , Garrelfs Sander F. , de Visser Saco J. , Groothoff Jaap W. , Hollak Carla E. M. 
Published: December 2024

Abstract
Background
The combination of high prices and uncertain effectiveness is a growing challenge in the field of orphan medicines, hampering health technology assessments. Hence, new methods for establishing price benchmarks might be necessary to support reimbursement negotiations. In this study, we applied several pricing models containing cost-based elements to the case of lumasiran for treating primary hyperoxaluria type 1.

Methods
Price ranges were calculated by estimating minimum and maximum scenarios for four pricing models: Novel Cancer Pricing Model (NCP-model), AIM Model for Innovative Medicines (AIM-model), Discounted Cash Flow model (DCF-model), and the Real-Option Rate Of Return model (ROROR-model). Data was gathered from disease registries, scientific literature, Security and Exchange Committee filings, and expert opinion. A sensitivity analysis was performed to assess the parameters with the largest influence.

Results
Outcomes resulting from the NCP-model ranged between €87,000 and €224,000 per patient per year, between €33,000 and €340,000 for the AIM-model, between €182,000 and €748,000 for the DCF-model, and between €81,000 and €273,000 for the ROROR-model.

Conclusion
Outcomes of the four pricing models show wide and heterogeneous price ranges. The DCF-model might be most compatible with the case of lumasiran, due to inclusion of parameters for prevalence, incidence, prescription restrictions and cost of capital. The minimum DCF price could serve as a starting point for pricing and reimbursement negotiations. Uncertainties can be solved by more transparency on input variables.
Association of preconception premenstrual disorders with perinatal depression: an analysis of the perinatal clinical database of a single Japanese institution
Authors: Ohsuga Takuma , Egawa Miho , Tsuyuki Kaori , Ueda Akihiko , Komatsu Maya , Chigusa Yoshitsugu , Mogami Haruta , Mandai Masaki 
Published: December 2024

Abstract
Background
Recent studies have identified premenstrual disorders (PMDs) as a risk factor for postpartum depression. However, routine screening for preconception PMDs is not yet common in Japan. This study investigated the association between preconception PMDs and perinatal depression in a single tertiary care setting.

Methods
We analyzed data from pregnant women who gave birth at Kyoto University Hospital between April 2020 and October 2023. The Premenstrual Symptoms Screening Tool was administered at the first postconception visit to retrospectively assess PMD status before the current pregnancy. The Edinburgh Postnatal Depression Scale (EPDS) was administered during pregnancy and one month postpartum as a prospective measure of perinatal depression. EPDS cutoff values were set at 12/13 during pregnancy and 8/9 at one month postpartum.

Results
Of the 781 women analyzed, 53 had preconception PMD. Univariate and multivariate logistic regression analyses revealed that preconception PMD was associated with an EPDS score of ≥ 13 during pregnancy, with a crude odds ratio (OR) of 5.78 (95% confidence interval [CI]: 2.70–11.75) and an adjusted OR of 3.71 (95% CI: 1.54–8.35). For an EPDS score of ≥ 9 at 1 month postpartum, the crude OR was 3.36 (95% CI: 1.79–6.12) and the adjusted OR was 2.16 (95% CI: 1.04–4.35).

Conclusions
Our findings indicate that preconception PMDs are a significant risk factor for both depression during pregnancy and postpartum depression. These results support the implementation of preconception PMD screening during antenatal checkups as a preventive measure and to identify women in need of early mental health care.
Decision-making for childhood vaccination in crisis settings: a survey of practice & barriers
Authors: Light Page M. , Singh Neha S. , Alhaffar Mervat , Allison Lauren E. , Mounier-Jack Sandra , Ratnayake Ruwan , Checchi Francesco , Abdelmagid Nada 
Published: December 2024

Abstract
Background
Children, particularly those who have received no routine vaccinations (zero-dose children), are at high risk of vaccine-preventable diseases in humanitarian crisis settings. However, the decision-making processes underlying vaccine intervention design and delivery in such settings are poorly understood. The present study investigated the decision-making practices of organisations involved in childhood vaccination in humanitarian crisis settings globally via an online survey.

Methods
Individuals involved in the design or delivery of childhood vaccination programmes in humanitarian crisis settings were invited to fill out a self-administered online survey. Respondents were asked about factors influencing intervention design and vaccine delivery; use of technical guidance, specifically the WHO decision-making framework for vaccination in acute humanitarian emergencies (WHO Framework); and practices for reaching zero-dose children.

Results
Fourteen responses were received. Large international organisations and UN agencies were overrepresented in the sample. Technical guidance was considered of high importance when designing vaccine interventions. However, the WHO Framework is not available in relevant languages and has not been well-distributed to local and national actors. Awareness of initiatives to reach zero-dose children was high within our sample, though this may not accurately reflect global awareness. Security and resource availability were key barriers to vaccine delivery and reaching zero-dose children. Problems with vaccine access in our sample pertained primarily to issues with the procurement system rather than vaccine cost.

Conclusions
The WHO Framework should be provided in more languages, and vaccination actors at local and national level should be engaged to improve its practicality and increase awareness of its aims. In order to reach zero-dose children, vaccines must be made available for use in expanded age groups, which is sometimes not currently feasible within the Gavi/UNICEF procurement system. Clarifying this policy would allow relevant organisations to reach more zero-dose children. Additionally, security is a key barrier impeding vaccine delivery, including for zero-dose children. Safe operational space for humanitarian actors in conflict must be maintained and global conflict resolution mechanisms improved.
The extent of physical and psychological workplace violence experienced by prehospital personnel in Denmark: a survey
Authors: Schøsler Brit , Bang Frederik Stuhr , Mikkelsen Søren 
Published: December 2024

Abstract
Background
Workplace violence against healthcare workers has been a well-known problem for more than 40 years. This problem is also relevant for prehospital personnel who are at risk of physical and/or psychological violence during work. Violence and threats of violence can have physical and psychological consequences, including personal challenges in their everyday life, use of sick days, reports, and the need for professional help. Therefore, this study aimed to describe the extent of and subsequent reporting of physical and psychological workplace violence toward the prehospital healthcare workers in Denmark in a two-year period. Moreover, we wanted to elucidate any possible effect of workplace violence on the private and professional lives of the prehospital healthcare personnel.

Methods
A nation-wide survey where a validated anonymised questionnaire was directed to all of the approximately 4500 Danish prehospital healthcare workers.

Results
Out of 584 complete responses we found that 47.4% had experienced psychological violence on the job whereas 25.7% had experienced physical violence on the job within the past two years. The perpetrators were mainly patients or relatives of the patients. Physical violence was mostly reported as punching, pushing, and kicking, while psychological violence included threats of violence and other intimidation. After experiencing violence the respondents reported both physical and psychological harm, which for some prehospital healthcare workers had consequences for their professional and/or personal life. Furthermore, some prehospital healthcare workers reported that the violence had resulted in some patients receiving worse treatment afterwards. We found that violence was rarely reported to either employers or the police, because respondents believed the events were not important enough to merit reporting, or because a report was not considered to make any difference to the healthcare worker. The survey demonstrates that, as a minimum, at least one healthcare worker in 30 and one healthcare worker in 16 has been exposed to episodes of violence and threats of violence within the last two years.

Conclusion
We suggest that the prehospital organisations emphasise reporting future episodes of physical and/or psychological violence. Knowing the extent of the problem is a prerequisite for addressing, debriefing, and/or other psychological follow-up.

Trial registration
N/A.
Efficacy of azithromycin combined with compounded atovaquone in treating babesiosis in giant pandas
Authors: Ma Rui , Yue Chanjuan , Gu Jiang , Wu Wei , Hou Rong , Huang Wenjun , Li Bi , Xue Fei , Huang Chong , Bi Wenlei , Liu Jiabin , Yu Xiang , Li Zusheng , Yang Wanjing , Fu Mingxia , Yang Hong , Qi Dunwu 
Published: December 2024

Abstract
Background
Babesia is a tick-borne protozoan blood parasite that can cause hemolytic anemia, thrombocytopenia, lethargy and splenomegaly in giant pandas.

Methods
We evaluated the efficacy and safety profile of a therapeutic regimen combining atovaquone and zithromycin in the context of babesiosis in giant pandas that have been naturally infected. The examined pandas underwent clinical and laboratory analyses, including hematology, biochemistry and thyroid hormone profiles. Upon diagnosis, the giant pandas were administered a compounded treatment consisting of atovaquone oral suspension (15 mg/kg, PO, q8 h), azithromycin tablets (10 mg/kg, PO, q24 h) and Enteral Nutritional Suspension (TPF) as a fat-rich supplement (0.5 ml/kg, PO, q8 h) for a 10-day period.

Results
The combination treatment increased the red blood cell count, hemoglobin levels and hematocrit in the pandas within a short period, while also reducing parasite levels below the PCR detection threshold.

Conclusions
Our study suggested that atovaquone and azithromycin combination therapy is highly effective for emergency treatment of Babesia sp. infection in giant pandas.

Graphical Abstract
Overwintering of Usutu virus in mosquitoes, The Netherlands
Authors: Koenraadt C. J. M. , Münger E. , Schrama M. J. J. , Spitzen J. , Altundag S. , Sikkema R. S. , Munnink B. B. Oude , Koopmans M. P. G. , Blom R. 
Published: December 2024

AbstractAnalyses of mosquito-borne virus outbreaks have revealed the presence of similar virus strains over several years. However, it remains unclear how mosquito-borne viruses can persist over winter, when conditions are generally unfavorable for virus circulation. One potential route for virus persistence is via diapausing mosquitoes. We therefore studied whether Usutu virus (USUV), West Nile virus (WNV) and/or Sindbis virus (SINV) can be identified in diapausing mosquitoes in The Netherlands. Mosquito collections were carried out in November 2022 in hibernacula located in two areas with previously observed WNV and/or USUV activity. A total of 4857 mosquitoes, belonging to four species (groups) (Culex pipiens/torrentium, Culiseta annulata, Anopheles maculipennis s.l. and Culex territans), were collected. WNV-, USUV- and SINV-screening using a multiplex real-time RT-PCR assay was carried out on mono-specific mosquito pools. One Culex pipiens/torrentium pool tested positive for USUV RNA. Whole genome sequencing and subsequent phylogenetic analysis revealed that the virus belongs to USUV lineage Africa 3 and clusters with other USUV sequences derived from The Netherlands in 2022. This finding confirms our hypothesis of the potential of local overwintering of USUV in diapausing mosquitoes in The Netherlands.
Graphical Abstract
High leptin levels in blood are associated with chronic widespread pain in rheumatoid arthritis
Authors: Aronsson M. , Bergman S. , Lindqvist E. , Andersson M. L. E. 
Published: December 2024

Abstract
Background
High body mass index (BMI) has been shown to have an association with chronic widespread pain (CWP), both in Rheumatoid arthritis (RA) and in other pain conditions such as fibromyalgia. Research on the adipose tissue and it’s adipokines, for example the well described leptin, is emerging. The objective of this study was to determine if there is an association between leptin levels in blood and CWP in patients with RA.

Methods
In this cross-sectional study 334 patients with RA filled in a questionnaire including a pain mannequin and questions on weight, length and waist circumference. Data from the pain mannequin was used to calculate CWP. The subjects also submitted blood samples to a biobank that were used for this study to determine leptin levels using an ELISA-method.

Results
Patients fulfilling the 2019 criteria for CWP in this study had significantly higher leptin levels, waist circumferences and BMI. There was a significant association between leptin levels and CWP, odds ratio (OR) 1.014 (95% confidence interval (CI) 1.007–1.020), p < 0.001. The association remained after adjusting for BMI, gender and age OR 1.008 (95% CI 1.000-1.017), p 0.046. When leptin was divided into quartile groups a trend could be observed where higher leptin values gave higher OR for CWP.

Conclusions
This study showed an increased occurrence of CWP in RA-patients with high leptin levels. The association between leptin and CWP remained after adjusting for gender, age and BMI or waist circumference. This suggests that not just production of leptin in the adipose tissue, but also other factors such as leptin resistance may play a role. The association between leptin and CWP was strongest in the patients with the highest leptin levels.

Trial registration
This study is a cross-sectional study without intervention and the cohort used was initiated prior to the implementation of mandatory registration requirements, therefore it is not registered.
Readiness to implement contingency management to promote PrEP initiation and adherence among people who inject drugs: results from a multi-site implementation survey
Authors: Pickering Eleanor , Viera Adam , Sung Minhee L. , Davidson Daniel , Bailey Genie , Buchelli Marianne , Jenkins Mark , Kolakowski Jennifer , Maier Leah , Edelman E. Jennifer , Rash Carla J. 
Published: December 2024

Abstract
Background
Contingency management (CM), an incentive-based intervention to encourage target behaviors, effectively promotes medication adherence. However, efforts to extend CM to HIV pre-exposure prophylaxis (PrEP) have been lacking. As part of a randomized clinical trial to promote HIV Prevention among people who inject drugs (PWID), we examined the readiness of staff in community-based organizations serving PWID to implement CM for PrEP uptake and adherence in this population.

Methods
From April to August 2022, we conducted a survey of staff from four community-based organizations providing HIV testing, harm reduction, and outreach services in the northeastern United States. We assessed knowledge and attitudes regarding PrEP for PWID on five-point Likert scales (e.g., Poor to Excellent, Not at all to Extremely). Using a modified version of the Contingency Management Beliefs Questionnaire, we assessed the degree to which attitudes about CM for HIV prevention influenced interest in its adoption on a scale from “1-No influence at all” to “5-Very strong influence”. We explored endorsement patterns, along with average values of individual items and subscale scores.

Results
Among 271 staff invitations, 123 (45.4%) responded. The majority (88.6%) of respondents reported prior PrEP awareness, with a mean self-rated knowledge of 2.98 out of 5 (SD = 1.1). Attitudes towards PrEP, including its relevance to and importance for clients (both means = 4.3), efficacy (mean = 4.5), and safety (mean = 4.2), were positive. Items related to practicality and confidence in providing PrEP-related care had relatively lower ratings. Respondents endorsed influential generalized (mean = 2.1) and training-related (mean = 2.5) CM implementation barriers less frequently than positive attitudes towards CM (mean = 3.6). Staff favored adding CM to existing services (mean = 3.8), and highly endorsed it as “useful for targeting HIV prevention with PrEP” (mean = 3.7).

Conclusions
Respondents generally supported the use of CM to promote HIV prevention among PWID and favored adding it to their existing services. Though respondents understood the value of both PrEP and CM to support HIV prevention activities, findings corroborate research citing relative lack of knowledge and confidence regarding PrEP management among clients, potentially detracting from implementation readiness.

Trial Registration Number
NCT04738825.
Decoding burn trauma: biomarkers for early diagnosis of burn-induced pathologies
Authors: Khalaf Fadi , Touma Daniella , Pappas Alexandra , Hatim Lareina , Wojtowicz-Piotrowski Stephanie , Jeschke Marc G. 
Published: December 2024

AbstractBurn injuries represent a significant global challenge due to their multifaceted nature, characterized by a complex cascade of metabolic and immune dysfunction that can result in severe complications. If not identified and managed promptly, these complications can escalate, often leading to fatal outcomes. This underscores the critical importance of timely and precise diagnosis. Fortunately, biomarkers for burn-induced pathologies and outcomes have emerged as powerful diagnostic and prognostic tools. These biomarkers enable early diagnosis and intervention, facilitate risk assessment, support patient-specific treatment, monitoring of disease progression, and therapeutic efficacy, ultimately contributing to improved patient outcomes. However, while previous studies have provided valuable biomarkers for the detection of burn-induced pathologies, many of these were constrained by the techniques and sample sizes available at the time, which can limit the generalizability of the findings. This review highlights numerous biomarkers studied in the literature to date, underscoring the need to replicate these findings in more diverse and representative populations. It also emphasizes the importance of advancing research efforts to develop more efficient, accurate, and cost-effective approaches for integrating biomarkers into clinical practice.