bluuebunny/crossref_metadata_2025_split huggingface dataset:
What implementation strategies and outcome measures are used to transform healthcare organizations into learning health systems? A mixed-methods review protocol
Authors: Somerville Mari , Cassidy Christine , Curran Janet , Rothfus Melissa , Sinclair Doug , Elliott Rose Annette 
Published: September 2022

Abstract
Background
A learning health system (LHS) framework provides an opportunity for health system restructuring to provide value-based healthcare. However, there is little evidence showing how to effectively implement a LHS in practice.

Objective
A mixed-methods review is proposed to identify and synthesize the existing evidence on effective implementation strategies and outcomes of LHS in an international context.

Methods
A mixed-methods systematic review will be conducted following methodological guidance from Joanna Briggs Institute (JBI) and PRISMA reporting guidelines. Six databases (CINAHL, Embase, MEDLINE, PAIS, Scopus and Nursing & Allied Health Database) will be searched for terms related to LHS, implementation and evaluation measures. Three reviewers will independently screen the titles, abstracts and full texts of retrieved articles. Studies will be included if they report on the implementation of a LHS in any healthcare setting. Qualitative, quantitative or mixed-methods study designs will be considered for inclusion. No restrictions will be placed on language or date of publication. Grey literature will be considered for inclusion but reviews and protocol papers will be excluded. Data will be extracted from included studies using a standardized extraction form. One reviewer will extract all data and a second will verify. Critical appraisal of all included studies will be conducted by two reviewers. A convergent integration approach to data synthesis will be used, where qualitative and quantitative data will be synthesized separately and then integrated to present overarching findings. Data will be presented in tables and narratively.

Conclusion
This review will address a gap in the literature related to implementation of LHS. The findings from this review will provide researchers with a better understanding of how to design and implement LHS interventions. This systematic review was registered in PROSPERO (CRD42022293348).
Costs and cost-effectiveness of HIV counselling and testing modalities in Southern Mozambique
Authors: Choo Jun Hao , Lopez-Varela Elisa , Fuente-Soro Laura , Augusto Orvalho , Sacoor Charfudin , Nhacolo Ariel , Wei Stanley , Naniche Denise , Thomas Ranjeeta , Sicuri Elisa 
Published: September 2022

Abstract
Objective
Despite the high HIV associated burden, Mozambique lacks data on HIV counselling and testing (HCT) costs. To help guide national HIV/AIDS programs, we estimated the cost per test for voluntary counselling and testing (VCT) from the patient’s perspective and the costs per person tested and per HIV-positive individual linked to care to the healthcare provider for VCT, provider-initiated counselling and testing (PICT) and home-based testing (HBT). We also assessed the cost-effectiveness of these strategies for linking patients to care.

Methods
Data from a cohort study conducted in the Manhiça District were used to derive costs and linkage-to-care outcomes of the three HCT strategies. A decision tree was used to model HCT costs according to the likelihood of HCT linking individuals to care and to obtain the incremental cost-effectiveness ratios (ICERs) of PICT and HBT with VCT as the comparator. Sensitivity analyses were performed to assess robustness of base-case findings.

Findings
Based on costs and valuations in 2015, average and median VCT costs to the patient per individual tested were US$1.34 and US$1.08, respectively. Costs per individual tested were greatest for HBT (US$11.07), followed by VCT (US$7.79), and PICT (US$7.14). The costs per HIV-positive individual linked to care followed a similar trend. PICT was not cost-effective in comparison with VCT at a willingness-to-accept threshold of US$4.53, but only marginally given a corresponding base-case ICER of US$4.15, while HBT was dominated, with higher costs and lower impact than VCT. Base-case results for the comparison between PICT and VCT presented great uncertainty, whereas findings for HBT were robust.

Conclusion
PICT and VCT are likely equally cost-effective in Manhiça. We recommend that VCT be offered as the predominant HCT strategy in Mozambique, but expansion of PICT could be considered in limited-resource areas. HBT without facilitated linkage or reduced costs is unlikely to be cost-effective.
Global research trends and foci of artificial intelligence-based tumor pathology: a scientometric study
Authors: Shen Zefeng , Hu Jintao , Wu Haiyang , Chen Zeshi , Wu Weixia , Lin Junyi , Xu Zixin , Kong Jianqiu , Lin Tianxin 
Published: September 2022

Abstract
Background
With the development of digital pathology and the renewal of deep learning algorithm, artificial intelligence (AI) is widely applied in tumor pathology. Previous researches have demonstrated that AI-based tumor pathology may help to solve the challenges faced by traditional pathology. This technology has attracted the attention of scholars in many fields and a large amount of articles have been published. This study mainly summarizes the knowledge structure of AI-based tumor pathology through bibliometric analysis, and discusses the potential research trends and foci.

Methods
Publications related to AI-based tumor pathology from 1999 to 2021 were selected from Web of Science Core Collection. VOSviewer and Citespace were mainly used to perform and visualize co-authorship, co-citation, and co-occurrence analysis of countries, institutions, authors, references and keywords in this field.

Results
A total of 2753 papers were included. The papers on AI-based tumor pathology research had been continuously increased since 1999. The United States made the largest contribution in this field, in terms of publications (1138, 41.34%), H-index (85) and total citations (35,539 times). We identified the most productive institution and author were Harvard Medical School and Madabhushi Anant, while Jemal Ahmedin was the most co-cited author. Scientific Reports was the most prominent journal and after analysis, Lecture Notes in Computer Science was the journal with highest total link strength. According to the result of references and keywords analysis, “breast cancer histopathology” “convolutional neural network” and “histopathological image” were identified as the major future research foci.

Conclusions
AI-based tumor pathology is in the stage of vigorous development and has a bright prospect. International transboundary cooperation among countries and institutions should be strengthened in the future. It is foreseeable that more research foci will be lied in the interpretability of deep learning-based model and the development of multi-modal fusion model.
The associations between plasma soluble Trem1 and neurological diseases: a Mendelian randomization study
Authors: Shi Xiaolei , Wei Tao , Hu Yachun , Wang Meng , Tang Yi 
Published: September 2022

Abstract
Background
Triggering receptor expressed on myeloid cell 1 (Trem1) is an important regulator of cellular inflammatory responses. Neuroinflammation is a common thread across various neurological diseases. Soluble Trem1 (sTrem1) in plasma is associated with the development of central nervous system disorders. However, the extent of any causative effects of plasma sTrem1 on the risk of these disorders is still unclear.

Method
Genetic variants for plasma sTrem1 levels were selected as instrumental variables. Summary-level statistics of neurological disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), epilepsy, cerebrovascular diseases, and migraine were collected from genome-wide association studies (GWASs). Whether plasma sTrem1 was causally associated with neurological disorders was assessed using a two-sample Mendelian randomization (MR) analysis, with false discovery rate (FDR)-adjusted methods applied.

Results
We inferred suggestive association of higher plasma sTrem1 with the risk of AD (odds ratio [OR] per one standard deviation [SD] increase = 1.064, 95% CI 1.012–1.119, P = 0.014, PFDR = 0.056). Moreover, there was significant association between plasma sTrem1 level and the risk of epilepsy (OR per one SD increase = 1.044, 95% CI 1.016–1.072, P = 0.002, PFDR = 0.032), with a modest statistical power of 41%. Null associations were found for plasma sTrem1 with other neurological diseases and their subtypes.

Conclusions
Taken together, this study indicates suggestive association between plasma sTrem1 and AD. Moreover, higher plasma sTrem1 was associated with the increased risk of epilepsy. The findings support the hypothesis that sTrem1 may be a vital element on the causal pathway to AD and epilepsy.
Seasonal epidemiological and clinical characteristics of pediatric patients with human parainfluenza virus infection by serotype: a retrospective study
Authors: Han Ji Yoon , Suh Woosuck , Han Seung Beom 
Published: September 2022

Abstract
Background
The development of the polymerase chain reaction (PCR) test promoted the evaluation of the epidemiological and clinical characteristics of human parainfluenza virus (HPIV) type 4, which has been rarely studied using conventional diagnostic methods. This study aimed to determine the seasonal epidemiological and clinical characteristics of all four HPIV serotypes (HPIV-1, HPIV-2, HPIV-3, and HPIV-4) during the era of PCR testing.

Methods
The medical records of hospitalized pediatric patients diagnosed with HPIV infections by a multiplex PCR test between 2015 and 2021 were retrospectively reviewed to determine the seasonal distributions of each HPIV serotype. For patients with a single HPIV infection, the clinical characteristics of each HPIV serotype were evaluated and compared with one another.

Results
Among the 514 cases of HPIV infection, HPIV-1, HPIV-2, HPIV-3, and HPIV-4 were identified in 27.2%, 11.9%, 42.6%, and 18.3% of cases, respectively. HPIV-3 was most prevalent in spring, and the other three serotypes were most prevalent in autumn. For patients with a single HPIV infection, those infected by HPIV-1 and HPIV-3 were younger than those infected by HPIV-2 and HPIV-4 (P < 0.001). Croup and lower respiratory tract infection (LRI) were most frequently diagnosed in patients infected by HPIV-1 (P < 0.001) and HPIV-4 (P = 0.002), respectively. During 2020–2021, HPIV-3 was most prevalent in autumn and caused fewer LRIs (P = 0.009) and more seizures (P < 0.001) than during 2015–2019.

Conclusions
Each HPIV serotype exhibited a distinct seasonal predominance, and some differences in the clinical characteristics of the HPIV serotypes were observed. HPIV-4 acted as an important cause of LRI. Considering the recent changes in the epidemiological and clinical characteristics of HPIV-3, more time-series analyses should be conducted.
Understanding the socioeconomic costs of dystrophic epidermolysis bullosa in Europe: a costing and health-related quality of life study
Authors: Angelis A. , Mellerio J. E. , Kanavos P. 
Published: September 2022

Abstract
Background
Dystrophic epidermolysis bullosa (EB) is a family of rare genetic dermatological conditions. Recent evidence indicated that in addition to its detrimental implications on patient health-related quality of life (HRQoL), there are substantial socioeconomic cost implications, especially regarding direct non-medical costs. This study aims to understand the burden of dystrophic EB (DEB) in Europe, using a primary EB patient-level dataset.

Methods
A bottom-up, cross-sectional, study design was adopted for non-institutionalised patients diagnosed with EB who received outpatient care across EU5 countries: France, Germany, Italy, Spain, and the United Kingdom. A prevalence-based approach was used to estimate resource utilisation from a societal perspective, including direct (medical and non-medical) and indirect costs for patients and caregivers. Patient and caregiver outcomes were obtained using the EQ-5D questionnaire.

Results
A sample of 91 DEB patients was analysed. Overall, average EU5 annual cost per patient was estimated at €53,359, ranging from €18,783 (France) to €79,405 (Germany). Average EU5 annual direct medical costs were estimated at €8357 (15.7% of total), ranging from €5658 (France) to €12,576 (Germany); average direct non-medical costs were estimated at €41,353 (77.5% of total), ranging from €11,961 (France) to €57,000 (Germany); and average indirect costs were estimated at €3649 (6.8% of total), ranging from €1025 (Italy) to €9930 (United Kingdom). Costs varied across patients with different disability but also between children and adults. The mean EQ-5D index score for adult DEB patients ranged between 0.304 (United Kingdom) and 0.541 (Germany), with an EU5 average of 0.456, whereas the mean EQ-5D visual analogue scale score ranged between 47.5 (Germany) and 70.0 (France), with an EU5 average of 61.9. Limitations included potential patient selection bias, recall bias, and exclusion of bandaging and related costs.

Conclusions
The study revealed a substantial socioeconomic burden for DEB in Europe, attributable mostly to high direct non-medical costs, with the majority of patients requiring support from caregivers at home. Compared to the average economic burden of the overall EB patient population, costs for DEB patients are higher across all components of direct medical, direct non-medical and indirect costs.
A novel loss-of-function mutation of the voltage-gated potassium channel Kv10.2 involved in epilepsy and autism
Authors: Galán-Vidal Jesús , Socuéllamos Paula G. , Baena-Nuevo María , Contreras Lizbeth , González Teresa , Pérez-Poyato María S. , Valenzuela Carmen , González-Lamuño Domingo , Gandarillas Alberto 
Published: September 2022

Abstract
Background
Novel developmental mutations associated with disease are a continuous challenge in medicine. Clinical consequences caused by these mutations include neuron and cognitive alterations that can lead to epilepsy or autism spectrum disorders. Often, it is difficult to identify the physiological defects and the appropriate treatments.

Results
We have isolated and cultured primary cells from the skin of a patient with combined epilepsy and autism syndrome. A mutation in the potassium channel protein Kv10.2 was identified. We have characterised the alteration of the mutant channel and found that it causes loss of function (LOF). Primary cells from the skin displayed a very striking growth defect and increased differentiation. In vitro treatment with various carbonic anhydrase inhibitors with various degrees of specificity for potassium channels, (Brinzolamide, Acetazolamide, Retigabine) restored the activation capacity of the mutated channel. Interestingly, the drugs also recovered in vitro the expansion capacity of the mutated skin cells. Furthermore, treatment with Acetazolamide clearly improved the patient regarding epilepsy and cognitive skills. When the treatment was temporarily halted the syndrome worsened again.

Conclusions
By in vitro studying primary cells from the patient and the activation capacity of the mutated protein, we could first, find a readout for the cellular defects and second, test pharmaceutical treatments that proved to be beneficial. The results show the involvement of a novel LOF mutation of a Potassium channel in autism syndrome with epilepsy and the great potential of in vitro cultures of primary cells in personalised medicine of rare diseases.
Behçet’s disease in Wales: an epidemiological description of national surveillance data
Authors: Ashman Annie , Tucker David , Williams Ceri , Davies Llion 
Published: September 2022

Abstract
Objectives
Behçet’s disease is a rare, chronic, incurable, multisystemic disease. It causes significant morbidity, with patients experiencing symptoms including mucous membrane ulcers, and joint pain and swelling. It is an important cause of avoidable blindness due to ocular involvement. The aetiology is unknown. The aims were to identify population prevalence of Behçet’s disease in Wales in comparison to other endemic and non-endemic regions, and provide an epidemiological profile of a case series of adult patients. This is the first analysis of data from the Adult Rare Diseases Surveillance Registry for Wales, established in 2020 as part of the COVID-19 pandemic response.

Results
Between 1995 and 2020, 347 adults and 5 children were recorded in Wales with a diagnosis of Behçet’s disease. Population prevalence was calculated as 11.1 per 100,000 population. Of the adult cases, 76.9% were female, and 6.6% died before the end of the study period. When comparing genders, there were no statistically significant differences in age at diagnosis, mortality or socioeconomic status. There was no evidence that the age at which cases were diagnosed had changed over time. Survival analyses showed no significant differences in durations of survival between genders or individuals residing in different WIMD 2019 quintiles. Age at diagnosis was the only factor significantly and independently associated with poorer durations of survival (p < 0.001).
Methylation-based markers of aging and lifestyle-related factors and risk of breast cancer: a pooled analysis of four prospective studies
Authors: Dugué Pierre-Antoine , Bodelon Clara , Chung Felicia F. , Brewer Hannah R. , Ambatipudi Srikant , Sampson Joshua N. , Cuenin Cyrille , Chajès Veronique , Romieu Isabelle , Fiorito Giovanni , Sacerdote Carlotta , Krogh Vittorio , Panico Salvatore , Tumino Rosario , Vineis Paolo , Polidoro Silvia , Baglietto Laura , English Dallas , Severi Gianluca , Giles Graham G. , Milne Roger L. , Herceg Zdenko , Garcia-Closas Montserrat , Flanagan James M. , Southey Melissa C. 
Published: September 2022

Abstract
Background
DNA methylation in blood may reflect adverse exposures accumulated over the lifetime and could therefore provide potential improvements in the prediction of cancer risk. A substantial body of research has shown associations between epigenetic aging and risk of disease, including cancer. Here we aimed to study epigenetic measures of aging and lifestyle-related factors in association with risk of breast cancer.

Methods
Using data from four prospective case–control studies nested in three cohorts of European ancestry participants, including a total of 1,655 breast cancer cases, we calculated three methylation-based measures of lifestyle factors (body mass index [BMI], tobacco smoking and alcohol consumption) and seven measures of epigenetic aging (Horvath-based, Hannum-based, PhenoAge and GrimAge). All measures were regression-adjusted for their respective risk factors and expressed per standard deviation (SD). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional or unconditional logistic regression and pooled using fixed-effects meta-analysis. Subgroup analyses were conducted by age at blood draw, time from blood sample to diagnosis, oestrogen receptor-positivity status and tumour stage.

Results
None of the measures of epigenetic aging were associated with risk of breast cancer in the pooled analysis: Horvath ‘age acceleration’ (AA): OR per SD = 1.02, 95%CI: 0.95–1.10; AA-Hannum: OR = 1.03, 95%CI:0.95–1.12; PhenoAge: OR = 1.01, 95%CI: 0.94–1.09 and GrimAge: OR = 1.03, 95%CI: 0.94–1.12, in models adjusting for white blood cell proportions, body mass index, smoking and alcohol consumption. The BMI-adjusted predictor of BMI was associated with breast cancer risk, OR per SD = 1.09, 95%CI: 1.01–1.17. The results for the alcohol and smoking methylation-based predictors were consistent with a null association. Risk did not appear to substantially vary by age at blood draw, time to diagnosis or tumour characteristics.

Conclusion
We found no evidence that methylation-based measures of aging, smoking or alcohol consumption were associated with risk of breast cancer. A methylation-based marker of BMI was associated with risk and may provide insights into the underlying associations between BMI and breast cancer.
The current status and future prospects for molecular imaging-guided precision surgery
Authors: Boekestijn Imke , van Oosterom Matthias N. , Dell’Oglio Paolo , van Velden Floris H. P. , Pool Martin , Maurer Tobias , Rietbergen Daphne D. D. , Buckle Tessa , van Leeuwen Fijs W. B. 
Published: September 2022

AbstractMolecular imaging technologies are increasingly used to diagnose, monitor, and guide treatment of i.e., cancer. In this review, the current status and future prospects of the use of molecular imaging as an instrument to help realize precision surgery is addressed with focus on the main components that form the conceptual basis of intraoperative molecular imaging. Paramount for successful interventions is the relevance and accessibility of surgical targets. In addition, selection of the correct combination of imaging agents and modalities is critical to visualize both microscopic and bulk disease sites with high affinity and specificity. In this context developments within engineering/imaging physics continue to drive the growth of image-guided surgery. Particularly important herein is enhancement of sensitivity through improved contrast and spatial resolution, features that are critical if sites of cancer involvement are not to be overlooked during surgery. By facilitating the connection between surgical planning and surgical execution, digital surgery technologies such as computer-aided visualization nicely complement these technologies. The complexity of image guidance, combined with the plurality of technologies that are becoming available, also drives the need for evaluation mechanisms that can objectively score the impact that technologies exert on the performance of healthcare professionals and outcome improvement for patients.
CSF rhinorrhea: non-contrast CT, contrast-enhanced CT cisternography or combined?
Authors: Hablas Lina Tarek , Ammar Alshimaa Magdy , Elnagar Rehab Mohamed 
Published: September 2022

Abstract
Background
Radiologic diagnosis of CSF leaks is challenging. We evaluated the diagnostic value of non-contrast CT and contrast-enhanced CT cisternography in identifying the presence of CSF rhinorrhea and site of leak as well as comparing them to surgical data and/or clinical follow-up.

Results
Fifty patients (20 males and 30 females) were included in our study with age ranging from 19 to 67 years. 76% of cases had spontaneous CSF rhinorrhea. Cribriform plate defect was the most common site of CSF leak, accounting for about 50% of cases. The highest sensitivity, specificity, PPV and NPV for diagnosis of CSF rhinorrhea were observed with the combined NCCT and CECTC with values 87%, 100%, 100% and 67%, respectively.

Conclusion
Accurate surgical planning and successful dural repair requires accurate localization of the dural and osseous defects. CT cisternography which already involves pre-cisternography non-contrast images holds great sensitivity in detection of the exact defect site together with confirmation of the CSF leak.