bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementing structured follow-up of neonatal and paediatric patients: an evaluation of three university hospital case studies using the functional resonance analysis method
Authors: Bos Véronique , Roorda Daniëlle , de Sonnaville Eleonore , van Boven Menne , Oosterlaan Jaap , van Goudoever Johannes , Klazinga Niek , Kringos Dionne 
Published: February 2022

Abstract
Background
In complex critical neonatal and paediatric clinical practice, little is known about long-term patient outcomes and what follow-up care is most valuable for patients. Emma Children’s Hospital, Amsterdam UMC (Netherlands), implemented a follow-up programme called Follow Me for neonatal and paediatric patient groups, to gain more insight into long-term outcomes and to use such outcomes to implement a learning cycle for clinical practice, improve follow-up care and facilitate research. Three departments initiated re-engineering and change processes. Each introduced multidisciplinary approaches to long-term follow-up, including regular standardised check-ups for defined age groups, based on medical indicators, developmental progress, and psychosocial outcomes in patients and their families. This research evaluates the implementation of the three follow-up programmes, comparing predefined procedures (work-as-imagined) with how the programmes were implemented in practice (work-as-done).

Methods
This study was conducted in 2019–2020 in the outpatient settings of the neonatal intensive care, paediatric intensive care and paediatric surgery departments of Emma Children’s Hospital. It focused on the organisational structure of the follow-up care. The functional resonance analysis method (FRAM) was applied, using documentary analysis, semi-structured interviews, observations and feedback sessions.

Results
One work-as-imagined model and four work-as-done models were described. The results showed vast data collection on medical, developmental and psychosocial indicators in all work-as-done models; however, process indicators for programme effectiveness and performance were missing. In practice there was a diverse allocation of roles and responsibilities and their interrelations to create a multidisciplinary team; there was no one-size-fits-all across the different departments. Although control and feedback loops for long-term outcomes were specified with respect to the follow-up groups within the programmes, they were found to overlap and misalign with other internal and external long-term outcome monitoring practices.

Conclusion
Implementing structured long-term follow-up may provide insights for improving daily practice and follow-up care, with the precondition of standardised measurements. Lessons learned from practice are (1) to address fragmentation in data collection and storage, (2) to incorporate the diverse ways to create a multidisciplinary team in practice, and (3) to include timely actionable indicators on programme effectiveness and performance, alongside medical, developmental and psychosocial indicators.
Treatment pathways and associated costs of metastatic colorectal cancer in Greece
Authors: Sougklakos Ioannis , Athanasiadis Elias , Boukovinas Ioannis , Karamouzis Michalis , Koutras Aggelos , Papakotoulas Paulos , Latsou Dimitra , Hatzikou Magda , Stamuli Eugena , Balasopoulos Athanasios , Sideris Aggelos 
Published: February 2022

Abstract
Objectives
Colorectal cancer (CRC) is the second leading cause of cancer in Europe, with 1.931.590 people newly diagnosed in 2020. The purpose of this study is the investigation of treatment options and healthcare resource metastatic CRC (mCRC) in Greece.

Methods
This study is based on the information collected in November 2020 by an expert panel comprising of 6 medical oncologists from major public and private centers around Greece. A 3-round survey was undertaken, according to Delphi method. The treatment phases studied were: pre-progression; disease progression and terminal care. Pharmaceutical costs and resource utilization data were considered from the perspective of the Greek National Services Organization (EOPYY). RESULTS: Experts agreed that the anticipated prevalence of RAS mutation in mCRC is 47% (30% RAS/BRAF WT Left, 17% RAS/BRAF WT Right); 8% BRAF while, MSI-H/dMMR are found in 5% of mCRC tumors. Based on mutational status, 74.8% of patients receive biological targeted therapies in combination with fluoropyrimidine/based combination chemotherapy, as 1st line treatment, and 25.2% combination chemotherapy alone. At 2nd line, 58.6% of patients receive biological targeted therapies in combination with chemotherapy, 25.4% immunotherapy, 11% combination chemotherapy and 5% biological targeted therapies. At 3rd line 56% of patients receive combination chemotherapy, 28% biological targeted therapies, 10% biological targeted therapies in combination with chemotherapy and 6% immunotherapy. The weighted annual cost (pharmaceuticals and resource use cost) in 1st line per mCRC patient was calculated at €28,407, in 2nd line €33,568, in 3rd line €25,550. The annual cost beyond 3rd line per patient regardless mutation was €19,501 per mCRC patient.

Conclusions
mCRC is a societal challenge for healthcare systems as the treatment is more prolonged but expand patients’ survival. Thus, reimbursement decisions should be based not just on the cost of the treatment, but on the magnitude of the benefit of its treatment on patients’ survival and quality of life.
Primary antiphospholipid syndrome in pediatrics: beyond thrombosis. Report of 32 cases and review of the evidence
Authors: Torres-Jimenez Alfonso-Ragnar , Ramirez-Nova Virginia , Cespedes-Cruz Adriana Ivonne , Sanchez-Jara Berenice , Velazquez-Cruz Alejandra , Bekker-Méndez Vilma Carolina , Guerra-Castillo Francisco Xavier 
Published: February 2022

Abstract
Objective
Describe the frequency of thrombotic and non-thrombotic clinical manifestations, laboratory, treatment and prognosis in patients with pediatric primary antiphospholipid syndrome.

Material and methods
A retrospective study was carried out in patients with a diagnosis of primary antiphospholipid antibody syndrome, under 16 years of age, under follow-up by the pediatric rheumatology service of the General Hospital, National Medical Center, La Raza, from January 2013 to December 2020. The antiphospholipid syndrome was defined when it met the laboratory criteria of the Sidney criteria and the presence of thrombosis or non-criteria manifestations of the disease (hematological, neurological, cutaneous, renal, cardiac or pulmonary). Demographic, clinical, laboratory, treatment, and prognosis data were collected.

Results
We report 32 patients, 21 female (65%) and 11 male (35%), mean age 11.75 years, evolution time 16 weeks. Thrombosis 9 patients (28%), 1 arterial and 8 venous. Non-thrombotic manifestations; Hematologic: thrombocytopenia 22 patients (69%), autoimmune hemolytic anemia 13 (40%), Fisher-Evans syndrome 6 (19%), lupus anticoagulant with hypoprothrombinemia syndrome 2 (6%). Dermatological: livedo reticularis 20 (62%), skin ulcers 2 (6%), Raynaud's phenomenon 8 (25%). Neurological: epilepsy 1 (3%), migraine 3 (9%), chorea 1 (3%) and cognitive impairment 3 (9%). Renal in 4 (13%). Laboratory: prolonged aPTT 30 (93%), lupus anticoagulant 32 (100%), positive IgG anticardiolipin 20 (62%), positive IgM anticardiolipin 19 (60%). AntiB2GPI was performed in only 3 patients, being positive in all. Treatment: anticoagulation in patients with thrombosis, antiplatelet in 23 (72%), steroid 30 (94%), immunosuppressant 30 (94%) and rituximab 4 (12.5%). No deaths were reported.

Conclusions
The clinical characteristics of patients with pediatric primary antiphospholipid syndrome differ from those presented in adults, since non-thrombotic manifestations are more frequent in children, for which classification criteria that include these manifestations are necessary for a better characterization of the disease in pediatric population.
Exploring the intersection of adverse childhood experiences, pediatric chronic pain, and rheumatic disease
Authors: Sonagra Maitry , Jones Jeremy , McGill Mackenzie , Gmuca Sabrina 
Published: February 2022

Abstract
Background
While the general relationship between ACEs and the development of chronic pain has become increasingly clear, how ACEs may shape a child’s clinical presentation with regards to chronic pain has yet to be fully expounded. We aimed to determine the association between ACEs and clinical manifestations of pediatric chronic pain and explore the interaction of ACEs and pediatric rheumatic disease among youth with chronic pain on health-related outcomes.

Methods
We conducted a cross-sectional cohort study of patients aged ≤18 years with chronic pain seen in a pediatric rheumatology amplified pain clinic between August 2018 and July 2020. We stratified subjects into three groups: no ACEs, one ACE, and ≥ 2 ACEs. We assessed clinical signs and symptoms associated with the presence of ACEs using Chi-square or Wilcoxon-rank test. The association between ACEs as well as other variables of interest with functional impairment was tested using simple and multivariable linear regression.

Results
Of the 412 patients included, more than 75% of patients reported at least one ACE. Most frequent included history of mental illness in a first degree relative (56%) and parental divorce or separation (20%). Those with ≥2 ACEs had more somatic symptoms, worse functional disability, and a higher proportion of mental health conditions. There appeared to be a dose dependent interaction between ACEs and functional disability from co-morbid rheumatologic disease. In multivariable regression, higher verbal pain score, symptom severity score (SSS), and presence of autonomic changes were associated with estimated average increase in FDI score (β = 1.05, 1.95 and 4.76 respectively; all p < 0.01).

Conclusion
Children with chronic pain and/or rheumatologic diseases who are exposed to ACEs are at increased risk of greater symptomatology, functional disability, and somatization of symptoms. Our findings indicate an ongoing need for systemic evaluation of ACEs in children with chronic pain and/or rheumatic disease and incorporation of trauma-based care.
Higher levels of neurofilament light chain and total tau in CSF are associated with negative outcome after shunt surgery in patients with normal pressure hydrocephalus
Authors: Braun Madelene , Bjurnemark Caroline , Seo Woosung , Freyhult Eva , Nyholm Dag , Niemelä Valter , Blennow Kaj , Zetterberg Henrik , Fällmar David , Kultima Kim , Virhammar Johan 
Published: February 2022

Abstract
Background
Lumbar punctures are a common examination in the work-up of patients with idiopathic normal pressure hydrocephalus (iNPH) and cerebrospinal fluid (CSF) biomarkers should therefore be available for use in selection of shunt candidates. The aim of this study was to investigate if CSF biomarkers are associated with outcome after shunt surgery alone or in combination with comorbidity and imaging markers, and investigate associations between CSF biomarkers and symptoms.

Methods
Preoperative CSF biomarkers were analyzed in 455 patients operated with shunt surgery for iNPH at a single center during 2011–2018. Symptoms before and 12 months after shunt surgery were graded with the Swedish iNPH scale. Neurofilament light chain protein (NfL), total tau (T-tau), phosphorylated tau (P-tau) and amyloid beta1-42 (Aβ1-42) CSF levels were measured. Evans’ index and disproportionately enlarged subarachnoid space hydrocephalus were measured on preoperative CT-scans. Preoperative evaluation and follow-up 12 months after shunt surgery were available in 376 patients.

Results
Higher levels of NfL and T-tau were associated with less improvement after shunt surgery (β = − 3.10, p = 0.016 and β = − 2.45, p = 0.012, respectively). Patients whose symptoms deteriorated after shunt surgery had higher preoperative levels of NfL (1250 ng/L [IQR:1020–2220] vs. 1020 [770–1649], p < 0.001) and T-tau (221 ng/L [IQR: 159–346] vs. 190 [135–261], p = 0.0039) than patients with postoperative improvement on the iNPH scale. Among the patients who improved ≥ 5 levels on the iNPH scale (55%), NfL was abnormal in 22%, T-tau in 14%, P-tau in 6% and Aβ1-42 in 45%, compared with normal reference limits. The inclusion of CSF biomarkers, imaging markers and comorbidity in multivariate predictive Orthogonal Projections to Latent Structures (OPLS) models to did not improve predictability in outcome after shunt surgery.

Conclusions
Higher levels of T-tau and NfL were associated with a less favorable response to shunt surgery, suggesting a more active neurodegeneration in this group of patients. However, CSF levels of these biomarkers can be elevated also in patients who respond to shunt surgery. Thus, none of these CSF biomarkers, alone or used in combination, are suitable for excluding patients from surgery.
Development of digital diagnostic templates by cluster analysis based on 2249 lateral cephalograms of Chinese Han population
Authors: Su Hong , Lu Wenhsuan , Deng Jingjing , Chen Gui , Jiang Ruoping , Wei Yan , Zhang Xiaoyun , Xu Tianmin , Han Bing 
Published: February 2022

Abstract
Background
To establish the digital diagnostic templates by cluster analysis based on a set of cephalometric films and evaluate the outcome of the different treatment methods in the patients affiliated to the same cephalometric morphology template (CMT). These templates could be used for the automatic diagnosis of dentofacial deformities and prediction of treatment outcomes in the future.

Methods
In this study, we assessed the coordinates of 60 different landmarks on the cephalograms of 2249 patients (14.35 ± 4.99 years, range from 7 to 62) with dentofacial deformities. The cephalometric data were subjected to dentist for clustering without a priori pattern definitions to generate biologically informative CMTs. Three templates were selected to evaluate the treatment outcome of patients affiliated to the same CMT.

Results
The cluster analysis yielded 21 distinct groups. The total discriminant accuracy was 89.1%, while the cross-validation accuracy was 85.0%, showing that the clusters were robust. All CMTs were automatically created and drawn using a computer, based on the average coordinates of each cluster. Individuals affiliated to the same CMT showed similar dentofacial features. We also evaluated differences in the outcomes of patients affiliated to the same CMT.

Conclusions
Our results demonstrated the utility of clustering methods for grouping dentofacial deformities with similar dentofacial features. Clustering methods can be used to evaluate the differences in the outcomes of patients affiliated to the same CMT, which has good clinical application value.
An updated view on the centrosome as a cell cycle regulator
Authors: Lin Muyang , Xie Shuang Shuang , Chan Kuan Yoow 
Published: February 2022

AbstractThe centrosome is a multifunctional organelle that is known primarily for its microtubule organising function. Centrosomal defects caused by changes in centrosomal structure or number have been associated with human diseases ranging from congenital defects to cancer. We are only beginning to appreciate how the non-microtubule organising roles of the centrosome are related to these clinical conditions. In this review, we will discuss the historical evidence that led to the proposal that the centrosome participates in cell cycle regulation. We then summarize the body of work that describes the involvement of the mammalian centrosome in triggering cell cycle progression and checkpoint signalling. Then we will highlight work from the fission yeast model organism, revealing the molecular details that explain how the spindle pole body (SPB, the yeast functional equivalent of the centrosome), participates in these cell cycle transitions. Importantly, we will discuss some of the emerging questions from recent discoveries related to the role of the centrosome as a cell cycle regulator.
Clusters, lines and webs—so does my patient have psychosis? reflections on the use of psychiatric conceptual frameworks from a clinical vantage point
Authors: Kovacs Tibor Zoltan , Hill Reece William , Watson Stuart , Turkington Douglas 
Published: February 2022

AbstractMental health professionals working in hospitals or community clinics inevitably face the realisation that we possess imperfect conceptual means to understand mental disorders. In this paper the authors bring together ideas from the fields of Philosophy, Psychiatry, Cognitive Psychology and Linguistics to reflect on the ways we represent phenomena of high practical importance that we often take for granted, but are nevertheless difficult to define in ontological terms. The paper follows through the development of the concept of psychosis over the last two centuries in the interplay of three different conceptual orientations: the categorical, dimensional and network approaches. Each of these represent the available knowledge and dominant thinking styles of the era in which they emerged and take markedly different stances regarding the nature of mental phenomena. Without particular commitment to any ontological positions or models described, the authors invite the reader into a thinking process about the strengths and weaknesses of these models, and how they can be reconciled in multidisciplinary settings to benefit the process of patient care.
Development of models of care coordination for rare conditions: a qualitative study
Authors: Walton Holly , Simpson Amy , Ramsay Angus I. G. , Hunter Amy , Jones Jennifer , Ng Pei Li , Leeson-Beevers Kerry , Bloom Lara , Kai Joe , Kokocinska Maria , Sutcliffe Alastair G. , Morris Stephen , Fulop Naomi J. 
Published: February 2022

Abstract
Introduction
Improving care coordination for people with rare conditions may help to reduce burden on patients and carers and improve the care that patients receive. We recently developed a taxonomy of different ways of coordinating care for rare conditions. It is not yet known which models of care coordination are appropriate in different situations. This study aimed to: (1) explore what types of care coordination may be appropriate in different situations, and (2) use these findings to develop hypothetical models of care coordination for rare conditions.

Methods
To explore appropriateness of different types of care coordination, we conducted interviews (n = 30), four focus groups (n = 22) and two workshops (n = 27) with patients, carers, healthcare professionals, commissioners, and charity representatives. Participants were asked about preferences, benefits and challenges, and the factors influencing coordination. Thematic analysis was used to develop hypothetical models of care coordination. Models were refined following feedback from workshop participants.

Results
Stakeholders prefer models of care that: are nationally centralised or a hybrid of national and local care, involve professionals collaborating to deliver care, have clear roles and responsibilities outlined (including administrative, coordinator, clinical and charity roles), provide access to records and offer flexible appointments (in terms of timing and mode). Many factors influenced coordination, including those relating to the patient (e.g., condition complexity, patient’s location and ability to coordinate their own care), the healthcare professional (e.g., knowledge and time), the healthcare environment (e.g., resources) and societal factors (e.g., availability of funding). We developed and refined ten illustrative hypothetical models of care coordination for rare conditions.

Conclusion
Findings underline that different models of care coordination may be appropriate in different situations. It is possible to develop models of care coordination which are tailored to the individual in context. Findings may be used to facilitate planning around which models of care coordination may be appropriate in different services or circumstances. Findings may also be used by key stakeholders (e.g. patient organisations, clinicians and service planners) as a decision-making tool.
Clinical measurement of cellular DNA damage hypersensitivity in patients with DNA repair defects
Authors: Hammarsten Ola , Lyytikäinen Anna , Thunström Sofia , Ek Torben , Fasth Anders , Ekwall Olov , Cajander Sara , Borgström Emilie Wahren , Smith C. I. Edvard , Johansson Pegah 
Published: February 2022

Abstract
Background
DNA repair deficiency disorders are rare inherited diseases arising from pathogenic (disease-causing) variants in genes involved in DNA repair. There are no standardized diagnostic assays for the investigation of pathological significance of unknown variants in DNA repair genes. We hypothesized that our assays for measuring in vitro patient blood cell hypersensitivity to DNA-damaging agents can be used to establish the pathological significance of unknown variants in DNA repair genes. Six patients with variants in the DNA repair genes PRKDC (two siblings), DCLRE1C (two siblings), NBN, and MSH6 were included. Here, we used the cell division assay (CDA) and the γ-H2AX assay, which were both developed and clinically validated by us, to measure patient cell hypersensitivity in response to ionizing radiation, mitomycin C, cytarabine and doxorubicin.

Results
Radiation hypersensitivity was detected in the two patients with variants in the PRKDC gene (p < 0.0001 for both at 3.5 Gy), and the two patients with DCLRE1C variants (p < 0.0001 at 3.5 Gy for sibling 1 and p < 0.0001 at 1 Gy for sibling 2). The cells from the patients with the PRKDC variant were also deficient in removing γ-H2AX (p < 0.001). The cells from the patient with variants in the NBN gene were hypersensitive to mitomycin C (p = 0.0008) and deficient in both induction and removal of γ-H2AX in response to radiation.

Conclusions
The combination of the CDA and the γ-H2AX assay is useful in investigating the significance of unknown variants in some DNA repair genes.