bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting clinical events characterizing the progression of amyotrophic lateral sclerosis via machine learning approaches using routine visits data: a feasibility study
Authors: Guazzo Alessandro , Atzeni Michele , Idi Elena , Trescato Isotta , Tavazzi Erica , Longato Enrico , Manera Umberto , Chió Adriano , Gromicho Marta , Alves Inês , de Carvalho Mamede , Vettoretti Martina , Di Camillo Barbara 
Published: October 2024

Abstract
Background
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that results in death within a short time span (3-5 years). One of the major challenges in treating ALS is its highly heterogeneous disease progression and the lack of effective prognostic tools to forecast it. The main aim of this study was, then, to test the feasibility of predicting relevant clinical outcomes that characterize the progression of ALS with a two-year prediction horizon via artificial intelligence techniques using routine visits data.

Methods
Three classification problems were considered: predicting death (binary problem), predicting death or percutaneous endoscopic gastrostomy (PEG) (multiclass problem), and predicting death or non-invasive ventilation (NIV) (multiclass problem). Two supervised learning models, a logistic regression (LR) and a deep learning multilayer perceptron (MLP), were trained ensuring technical robustness and reproducibility. Moreover, to provide insights into model explainability and result interpretability, model coefficients for LR and Shapley values for both LR and MLP were considered to characterize the relationship between each variable and the outcome.

Results
On the one hand, predicting death was successful as both models yielded F1 scores and accuracy well above 0.7. The model explainability analysis performed for this outcome allowed for the understanding of how different methodological approaches consider the input variables when performing the prediction. On the other hand, predicting death alongside PEG or NIV proved to be much more challenging (F1 scores and accuracy in the 0.4-0.6 interval).

Conclusions
In conclusion, predicting death due to ALS proved to be feasible. However, predicting PEG or NIV in a multiclass fashion proved to be unfeasible with these data, regardless of the complexity of the methodological approach. The observed results suggest a potential ceiling on the amount of information extractable from the database, e.g., due to the intrinsic difficulty of the prediction tasks at hand, or to the absence of crucial predictors that are, however, not currently collected during routine practice.
Co-designing a blueprint for spreading person-centered, Whole Health care to HIV specialty care settings: a mixed methods protocol
Authors: Rupcic Sonia , Tam Ming Z. , DeLaughter Kathryn L. , Gifford Allen L. , Barker Anna M. , Bokhour Barbara G. , Xu Chris , Dryden Eileen , Anderson Ekaterina , Jasuja Guneet K. , Boudreau Jacqueline , Douglas Jamie H. , Hyde Justeen , Mozer Reagan , Zeliadt Steven B. , Fix Gemmae M. 
Published: October 2024

Abstract
Background
Since 2013, the Veterans Health Administration (VHA) has advanced a person-centered, Whole Health (WH) System of Care, a shift from a disease-oriented system to one that prioritizes “what matters most” to patients in their lives. Whole Health is predicated on patient-provider interactions marked by a multi-level understanding of health and trusted relationships that promote well-being. Presently, WH implementation has been focused largely in primary care settings, yet the goal is to effect a system-wide transformation of care so that Veterans receive WH across VHA clinical settings, including specialty care. This sort of system-wide cultural transformation is difficult to implement.

Methods
This three-aim mixed methods study will result in a co-designed implementation blueprint for spreading WH from primary to specialty care settings. Taking HIV specialty care as an illustrative case- because of its diverse models of relationships to primary care - to explore how to spread WH through specialty care settings. We will use the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework to organize quantitative and qualitative data and identify key determinants of WH receipt among Veterans living with HIV. Through a co-design process, we develop an adaptable implementation blueprint that identifies and matches implementation strategies to different HIV specialty care configurations.

Discussion
This study will co-design a flexible implementation blueprint for spreading WH from VHA primary care throughout HIV specialty care settings. This protocol contributes to the science of end-user engagement while also answering calls for greater transparency in how implementation strategies are identified, tailored, and spread.
The use of outcome data from quality registries to learn and improve; a Dutch nationwide quantitative analysis in five disease areas
Authors: Slingerland Stacey R. , Moers Lise A. M. , Medendorp Niki M. , van der Nat Paul B. , Derks Lineke , Timmermans Marijke J. C. , de Keizer Nicolette , ten Dam Marc , Denissen Geke , van Veghel Dennis 
Published: October 2024

AbstractBackgroundClinical quality registries (CQR) aid in measuring, collecting and monitoring outcome data but it is still unknown how these data are used by hospitals to improve the quality of care. This study assessed the current state of outcome-based quality improvement in the Netherlands in 2022 based on data from multiple disease areas and CQRs; cardiothoracic surgery (Netherlands Heart Registration [NHR]), cardiology (NHR), nephrology, (Nefrovision), intensive care (National Intensive Care Evaluation [NICE]), and orthopaedic surgery (Dutch Arthroplasty Register [LROI]).Methods & resultsThe Health Outcomes Management Evaluation (HOME) model was used to assess the current state of outcome-based quality improvement. A questionnaire with 36 questions was sent to healthcare departments of the six disease areas in participating hospitals within five quality registrations in the Netherlands. In total, 124 responses were received; 20 within cardiology, 12 within cardiothoracic surgery, 30 within nephrology, 35 within intensive care and 27 within orthopaedic surgery. Results showed outcome measures were actively used to improve the quality of care, several improvement initiatives were implemented, but outcomes were not always monitored regularly. Results differed between hospitals, but differences were limited between disease areas.ConclusionThe current state of outcome-based quality improvement in all five disease areas is that outcome measures were consequently employed and used on a frequent basis aiming to achieve quality improvement in healthcare. Results can be improved by structurally embedding the entire improvement cycle into the organisation.
Future health technology trends, policy, and governance perspective: the Turkish case
Authors: Kambur Elif Sena , Yıldırım Hasan Hüseyin 
Published: October 2024

Abstract
Background
Advanced health technologies that emerge with the development of technology have an impact on health systems. This study aimed to determine the effects of these technologies on Türkiye’s health system and present policy recommendations to reshape Türkiye’s health system and policies accordingly.

Methods
Interviews were conducted with senior managers, bureaucrats, policy-makers and decision-makers from seven different institutions on the subject. Content analysis was performed on the data obtained and evaluative categories were established.

Results
It was concluded that these technologies would not have a positive impact on two identified themes, a negative impact on seven themes and a predominant impact on five themes in Türkiye.

Conclusions
To adapt to the new health ecosystem in Türkiye, it is recommended to increase digital literacy, conduct economic evaluations of technologies, promote domestic production, ensure up-to-date follow-up, collaborate with the engineering field, enhance health technology evaluation practices, improve access to technologies and ensure that the infrastructures of health institutions are compatible with technologies. Various policy suggestions have been presented for the development of Türkiye’s health system.
Successful control of an environmental reservoir of NDM-producing Klebsiella pneumoniae associated with nosocomial transmissions in a low-incidence setting
Authors: Moulin Estelle , Filippidis Paraskevas , Paire-Ficout Corinne Aymon , Blanc Dominique S. , Grandbastien Bruno , Senn Laurence 
Published: October 2024

Abstract
Background
The hospital wastewater system has been reported as a source of nosocomial acquisition of carbapenemase producing Enterobacteriaceae (CPE) in various settings. Cleaning and disinfection protocols or replacement of contaminated equipment often fail to eradicate these environmental reservoirs, which can lead to long-term transmission of CPE. We report a successful multimodal approach to control a New Delhi metallo-beta-lactamase positive Klebsiella pneumoniae (NDM-KP) nosocomial outbreak implicating contamination of sink traps in a low-incidence setting.

Methods
Following the incidental identification of NDM-KP in a urine culture of an inpatient, we performed an epidemiological investigation, including patient and environmental CPE screening, and whole genome sequencing (WGS) of strains. We also implemented multimodal infection prevention and control (IPC) measures, namely the isolation of cases, waterless patient care, replacement of contaminated P-traps and connecting pieces, and bleach and steam disinfection of sinks for 6 months, followed by patient and environmental screenings for eradication.

Results
Between February and May 2022, five NDM-KP cases were identified in an eight-bed neurosurgical intermediate care unit. Among the eight sink traps of the unit, three were positive for NDM-KP. Patient and environmental isolates belonged to multilocus sequence typing ST-268. All isolate genomes were genetically very similar suggesting cross-transmission and a potential role of the environment as the source of transmissions. Following the introduction of combined IPC measures, no new case was subsequently detected and sink traps remained negative for NDM-KP within 6 months after the intervention.

Conclusion
The implementation of multimodal IPC measures, including waterless patient care combined with the replacement and disinfection of P-traps and connecting pieces, was successful in the control of NDM-KP after eight months. In a low-incidence setting, this approach has made it possible to pursue the objective of zero transmission of carbapenemase-producing Enterobacteriaceae (CPE).
A tumorigenicity evaluation platform for cell therapies based on brain organoids
Authors: Xue Jun , Chu Youjun , Huang Yanwang , Chen Ming , Sun Meng , Fan Zhiqin , Wu Yonghe , Chen Liang 
Published: October 2024

Abstract
Background
Tumorigenicity represents a critical challenge in stem cell-based therapies requiring rigorous monitoring. Conventional approaches for tumorigenicity evaluation are based on animal models and have numerous limitations. Brain organoids, which recapitulate the structural and functional complexity of the human brain, have been widely used in neuroscience research. However, the capacity of brain organoids for tumorigenicity evaluation needs to be further elucidated.

Methods
A cerebral organoid model produced from human pluripotent stem cells (hPSCs) was employed. Meanwhile, to enhance the detection sensitivity for potential tumorigenic cells, we created a glioblastoma-like organoid (GBM organoid) model from TP53−/−/PTEN−/− hPSCs to provide a tumor microenvironment for injected cells. Midbrain dopamine (mDA) cells from human embryonic stem cells were utilized as a cell therapy product. mDA cells, hPSCs, mDA cells spiked with hPSCs, and immature mDA cells were then injected into the brain organoids and NOD SCID mice. The injected cells within the brain organoids were characterized, and compared with those injected in vivo to evaluate the capability of the brain organoids for tumorigenicity evaluation. Single-cell RNA sequencing was performed to identify the differential gene expression between the cerebral organoids and the GBM organoids.

Results
Both cerebral organoids and GBM organoids supported maturation of the injected mDA cells. The hPSCs and immature mDA cells injected in the GBM organoids showed a significantly higher proliferative capacity than those injected in the cerebral organoids and in NOD SCID mice. Furthermore, the spiked hPSCs were detectable in both the cerebral organoids and the GBM organoids. Notably, the GBM organoids demonstrated a superior capacity to enhance proliferation and pluripotency of spiked hPSCs compared to the cerebral organoids and the mouse model. Kyoto Encyclopedia of Genes and Genomes analysis revealed upregulation of tumor-related metabolic pathways and cytokines in the GBM organoids, suggesting that these factors underlie the high detection sensitivity for tumorigenicity evaluation.

Conclusions
Our findings suggest that brain organoids could represent a novel and effective platform for evaluating the tumorigenic risk in stem cell-based therapies. Notably, the GBM organoids offer a superior platform that could complement or potentially replace traditional animal-based models for tumorigenicity evaluation.
NF1 expression profiling in IDH-wildtype glioblastoma: genomic associations and survival outcomes
Authors: Chang Michael , Sherief Mohamed , Ioannou Maria , Chinnasamy Viveka , Chen Lucy , Frost Michael , Mattson-Hoss Michelle , Sarnoff Herb , Kamson David O. , Holdhoff Matthias , Mukherjee Debraj , Bettegowda Chetan , Rincon-Torroella Jordina , Croog Victoria , Huang Peng , Rodriguez Fausto J. , Lucas Calixto-Hope G. , Schreck Karisa C. 
Published: October 2024

Abstract
Background
NF1 inactivation is associated with sensitivity to MEK inhibitor targeted therapy in low-grade and some high-grade gliomas. NF1 loss may also be a harbinger of exploitable vulnerabilities in IDH-wildtype glioblastoma (GBM). Accurate and consistent detection of NF1 loss, however, is fraught given the large gene size, challenges with complete coverage and variant calling upon sequencing, and mechanisms of mRNA and protein regulation that result in early degradation in the absence of genomic alterations. Here, we seek to perform a composite analysis for NF1 loss accounting for genomic alterations and protein expression via immunohistochemistry. We also characterize the landscape of NF1 alterations in GBM.

Methods
We assembled a single-institution, retrospective cohort of 542 IDH-wildtype GBM with somatic next generation sequencing to investigate the frequency and nature of detected NF1 alterations. We selected 69 GBMs from which to build a tissue microarray (TMA) of 44 NF1-wildtype and 25 NF1-mutant cases. We performed NF1 immunohistochemistry using two different NF1 antibodies (NFC, Sigma-Aldrich; and iNF-07E, iNFixion Bioscience) and correlated results with clinical, genomic, and other immunohistochemical features.

Results
In our retrospective cohort, we identified 88 IDH-wildtype GBM with NF1 alterations (16%). NF1 alterations were mutually exclusive with EGFR and MDM2 alterations (p-adj < 0.001, 0.05, respectively), but co-occurred with PIK3R1 alterations (Log2(OR) = − 1.6, p-adj = 0.03). Of the 63 scorable sporadic GBMs in the TMA, 14 harbored NF1 inactivating alterations and of those, 12 (86%) demonstrated minimal NF1 immunoreactivity by NFC antibody, compared to 8 (57%) by iNF-07E antibody. Among the 42 scorable NF1-wildtype GBM in the TMA, NF1 immunostaining was minimal in 18 (43%) by NFC antibody compared to 4 (10%) by iNF-07E antibody, potentially reflecting false positives or differential protein regulation. Minimal immunoreactivity by NFC antibody was associated with decreased median overall survival (8.5 vs. 16.4 months, p = 0.011). Cox proportional hazards model correcting for prognostic variables in this subset revealed HR 3.23 (95% CI 1.29–8.06, p = 0.01) associated with decreased NF1 expression by IHC.

Conclusion
NF1 immunostaining may serve as a sensitive surrogate marker of NF1 genomic inactivation and a valuable extension to next-generation sequencing for defining NF1 status. Minimal NF1 immunoreactivity is a poor prognostic marker, even in IDH-wildtype glioblastoma without apparent NF1 genomic alterations, but the underlying molecular mechanism requires further investigation.
Effects of climate change on open air heritage: a review and the situation in the region of Mediterranean
Authors: Nastou Marina Panagiota P. , Zerefos Stelios C. 
Published: October 2024

Abstract
This paper collects research information and registered data regarding the relationship between climate change and heritage, aiming to present a comprehensive state of studies and research on the subject. This relationship between these two cores is basically the main subject of this research, as well as the discovery of the areas with little information. Nowadays, there is a remarkable increase in the concern of the damage of cultural heritage and the research of methods and means of protection and of interpretation of its value. In the meanwhile, climate change is the other pillar of this paper, with evident damage, eminent jeopardy and accumulative downgrade of heritage assets. The aforementioned facts create a threatening background for the safeguarding of cultural and natural heritage and the transmission to the next generations. In general, stakeholders should focus on the mitigation of the human causes of climate change and the necessary adaptation to the climatic conditions for heritage protection. Through the collection of data, this paper presents the region of Mediterranean, as it has a strategic geographic location and the climatic conditions have already shown notable deviations. The presented information relates to the indices and measurements of the effects of climate change and the overall assessment of the risks of heritage, the irreversible impairment, the most common cultural aspects of the studies and the urgent need of protection. The scope of these data is the design of the appropriate management plan, taking into account the unique identity of each piece of heritage and its environment. To sum up, the kinds of heritage incorporated into the environment structuring a completed landscape with immediate exposure to the conditions, seem to lack the essential research for their preservation. For this reason, the adequate management of cultural and natural heritage in jeopardy, such as the cases in the Mediterranean region, require multidisciplinary assessment for heritage management.
Spatiotemporal distribution of toponymic cultural heritage in Jiangsu Province and its historical and geographical influencing factors
Authors: Jiao Min , Lu Lu 
Published: October 2024

Abstract
As a typical intangible cultural heritage, Toponymic Cultural Heritage (TCH) is rich in geographic information and semantic and physical connotations. In the context of the heritage conservation era, it is highly important to study the spatiotemporal distribution characteristics of toponymic cultural heritage and explore its historical and geographic influencing factors on the sustainable conservation and development of toponymic cultural heritage. However, most existing studies focus on the toponym cultural landscape, and less attention has been given to TCH. Therefore, on the basis of the data of 357 provincial TCH items in Jiangsu Province, this study investigated the spatiotemporal distribution characteristics and historical–geographical influencing factors of the TCH by using geospatial analysis methods, such as the average nearest neighbor, tyson polygon, kernel density estimation, standard deviational ellipse, and superposition coupling analysis, and proposed several strategies for adaptive reuse of TCH. The results show that (1) the TCHs of Jiangsu Province have a spatial distribution characteristic of "sparse in the north, scattered in the middle and dense in the south" and form a high-density agglomeration around the southern part of Jiangsu Province. In the distribution of cultural districts, the Jinling cultural district, the Wu cultural district, and the Huaiyang cultural district have the largest number of TCHs. (2) From the Pre-Qin period to the Ming and Qing Dynasties, TCHs, such as Nanjing, Yangzhou, Zhenjiang, Changzhou, and Suzhou, tended to merge in the southern part of Jiangsu. (3) In terms of type, the roads, streets and alleys of TCHs are the richest, and all types of TCHs are spatially clustered in the southern part of Jiangsu Province, which has a high level of urbanization, industrialization, and a superior geographic environment. (4) TCHs have spatial tendencies toward low altitudes and hydrophilicity, and relatively favorable natural geographical conditions provide a high-quality environment for TCHs in southern Jiangsu Province. Influenced by historical, humanistic, and geographical factors, TCH is unevenly developed spatially. As a historical population concentration area, an important political, economic, and cultural core area, and a center of gravity for cultural development, more TCH resources have survived in the southern part of Jiangsu Province. This study provides a new perspective for interpreting and recognizing TCH as a special intangible cultural heritage and can provide a reference for the sustainable conservation and development of TCH.
Height status matters for risk of mortality in critically ill children
Authors: Nosaka Nobuyuki , Anzai Tatsuhiko , Wakabayashi Kenji 
Published: October 2024

Abstract
Background
Anthropometric measurements are crucial in pediatric critical care, but the impact of height on ICU outcomes is underexplored despite a substantial number of short-for-age children in ICUs. Previous studies suggest that short stature increases the risk of poor clinical outcomes. This study examines the relationship between short stature and ICU outcomes.

Methods
We conducted a retrospective cohort study using a Japanese nationwide database (the Japanese Intensive Care Patient Database; JIPAD), which included pediatric patients under 16 years admitted to ICUs from April 2015 to March 2020. Height standard deviation scores (SD scores) were calculated based on age and sex. Short-stature patients were defined as height SD score <  − 2. The primary outcome was all-cause ICU mortality, and the secondary outcome was the length of stay in ICU.

Results
Out of 6,377 pediatric patients, 27.2% were classified as having short stature. The ICU mortality rate was significantly higher in the short-stature group compared to the normal-height group (3.6% vs. 1.4%, p < 0.01). Multivariable logistic regression showed that short stature was independently associated with increased ICU mortality (OR = 2.73, 95% CI 1.81–4.11). Additionally, the Fine–Gray subdistribution hazards model indicated that short stature was associated with a lower chance of ICU discharge for each additional day (HR 0.85, 95% CI 0.81–0.90, p < 0.01).

Conclusions
Short stature is a significant risk factor for increased ICU mortality and prolonged ICU stay in critically ill children. Height should be considered in risk assessments and management strategies in pediatric intensive care to improve outcomes.