SwePub - search: WFRF:(Fransson Fredrik)

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1.	Al-Husseini, Ali, et al. (author) Long-term postural control in elite athletes following mild traumatic brain injury 2022 In: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 13 Journal article (peer-reviewed)abstract Background: Traumas to the head and neck are common in sports and often affects otherwise healthy young individuals. Sports-related concussions (SRC), defined as a mild traumatic brain injury (mTBI), may inflict persistent neck and shoulder pain, and headache, but also more complex symptoms, such as imbalance, dizziness, and visual disturbances. These more complex symptoms are difficult to identify with standard health care diagnostic procedures.Objective: To investigate postural control in a group of former elite athletes with persistent post-concussive symptoms (PPCS) at least 6 months after the incident.Method: Postural control was examined using posturography during quiet stance and randomized balance perturbations with eyes open and eyes closed. Randomized balance perturbations were used to examine motor learning through sensorimotor adaptation. Force platform recordings were converted to reflect the energy used to maintain balance and spectrally categorized into total energy used, energy used for smooth corrective changes of posture (i.e., <0.1 Hz), and energy used for fast corrective movements to maintain balance (i.e., >0.1 Hz).Results: The mTBI group included 20 (13 males, mean age 26.6 years) elite athletes with PPCS and the control group included 12 athletes (9 males, mean age 26.4 years) with no history of SRC. The mTBI group used significantly more energy during balance perturbations than controls: +143% total energy, p = 0.004; +122% low frequency energy, p = 0.007; and +162% high frequency energy, p = 0.004. The mTBI subjects also adapted less to the balance perturbations than controls in total (18% mTBI vs. 37% controls, p = 0.042), low frequency (24% mTBI vs. 42% controls, p = 0.046), and high frequency (6% mTBI vs. 28% controls, p = 0.040). The mTBI subjects used significantly more energy during quiet stance than controls: +128% total energy, p = 0.034; +136% low-frequency energy, p = 0.048; and +109% high-frequency energy, p = 0.015.Conclusion: Athletes with previous mTBI and PPCS used more energy to stand compared to controls during balance perturbations and quiet stance and had diminished sensorimotor adaptation. Sports-related concussions are able to affect postural control and motor learning.
2.	Altuntas Vural, Ceren, 1980, et al. (author) Life after use: circular supply chains for second-life of electric vehicle batteries 2024 In: Production Planning and Control. - 0953-7287 .- 1366-5871. ; In Press Journal article (peer-reviewed)abstract Despite the increasing interest in second-life of electric vehicle batteries, the characteristics of supply chains to support such products are yet to be developed. The purpose of this paper is to investigate the key supply chain characteristics required to effectively accommodate circular models for second-life electric vehicle batteries. Through a longitudinal case study, we map possible application areas and customer segments, necessary key activities, and potential actors that might emerge in future supply chains for these products. The findings are discussed in relation to product-oriented, use-oriented, and result-oriented circular models. The suggested circular models and their comparisons provide insights into how different supply chain dimensions are configured for different circular business models, and the advantages, disadvantages, and prerequisites associated by each model.
3.	Bostanci, Nagihan, et al. (author) Dysbiosis of the Human Oral Microbiome During the Menstrual Cycle and Vulnerability to the External Exposures of Smoking and Dietary Sugar. 2021 In: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media SA. - 2235-2988. ; 11 Journal article (peer-reviewed)abstract Physiological hormonal fluctuations exert endogenous pressures on the structure and function of the human microbiome. As such, the menstrual cycle may selectively disrupt the homeostasis of the resident oral microbiome, thus compromising oral health. Hence, the aim of the present study was to structurally and functionally profile the salivary microbiome of 103 women in reproductive age with regular menstrual cycle, while evaluating the modifying influences of hormonal contraceptives, sex hormones, diet, and smoking. Whole saliva was sampled during the menstrual, follicular, and luteal phases (n = 309) of the cycle, and the participants reported questionnaire-based data concerning their life habits and oral or systemic health. No significant differences in alpha-diversity or phase-specific clustering of the overall microbiome were observed. Nevertheless, the salivary abundances of genera Campylobacter, Haemophilus, Prevotella, and Oribacterium varied throughout the cycle, and a higher species-richness was observed during the luteal phase. While the overall community structure maintained relatively intact, its functional properties were drastically affected. In particular, 11 functional modules were differentially abundant throughout the menstrual cycle, including pentose phosphate metabolism, and biosynthesis of cobalamin and neurotransmitter gamma-aminobutyric acid. The menstrual cycle phase, but not oral contraceptive usage, was accountable for greater variations in the metabolic pathways of the salivary microbiome. Further co-risk factor analysis demonstrated that Prevotella and Veillonella were increased in current smokers, whereas high dietary sugar consumption modified the richness and diversity of the microbiome during the cycle. This is the first large study to systematically address dysbiotic variations of the oral microbiome during the course of menstrual cycle, and document the additive effect of smoking and sugar consumption as environmental risk factors. It reveals the structural resilience and functional adaptability of the oral microbiome to the endogenous hormonal pressures of the menstrual cycle, while revealing its vulnerability to the exogenous exposures of diet and smoking.
4.	Brorsson, Joakim, 1988, et al. (author) Efficient Calculation of the Lattice Thermal Conductivity by Atomistic Simulations with Ab Initio Accuracy 2022 In: Advanced Theory and Simulations. - : Wiley. - 2513-0390. ; 5:2 Journal article (peer-reviewed)abstract High-order force constant expansions can provide accurate representations of the potential energy surface relevant to vibrational motion. They can be efficiently parametrized using quantum mechanical calculations and subsequently sampled at a fraction of the cost of the underlying reference calculations. Here, force constant expansions are combined via the hiphive package with GPU-accelerated molecular dynamics simulations via the GPUMD package to obtain an accurate, transferable, and efficient approach for sampling the dynamical properties of materials. The performance of this methodology is demonstrated by applying it both to materials with very low thermal conductivity (Ba8Ga16Ge30, SnSe) and a material with a relatively high lattice thermal conductivity (monolayer-MoS2). These cases cover both situations with weak (monolayer-MoS2, SnSe) and strong (Ba8Ga16Ge30) pho renormalization. The simulations also enable to access complementary information such as the spectral thermal conductivity, which allows to discriminate the contribution by different phonon modes while accounting for scattering to all orders. The software packages described here are made available to the scientific community as free and open-source software in order to encourage the more widespread use of these techniques as well as their evolution through continuous and collaborative development.
5.	Eriksson, Fredrik, 1992, et al. (author) Tuning the Through-Plane Lattice Thermal Conductivity in van der Waals Structures through Rotational (Dis)ordering 2023 In: ACS Nano. - 1936-086X .- 1936-0851. ; 17:24, s. 25565-25574 Journal article (peer-reviewed)abstract It has recently been demonstrated that MoS2 with irregular interlayer rotations can achieve an extreme anisotropy in the lattice thermal conductivity (LTC), which is, for example, of interest for applications in waste heat management in integrated circuits. Here, we show by atomic-scale simulations based on machine-learned potentials that this principle extends to other two-dimensional materials, including C and BN. In all three materials, introducing rotational disorder drives the through-plane LTC to the glass limit, while the in-plane LTC remains almost unchanged compared to those of the ideal bulk materials. We demonstrate that the ultralow through-plane LTC is connected to the collapse of their transverse acoustic modes in the through-plane direction. Furthermore, we find that the twist angle in periodic moiré structures representing rotational order provides an efficient means for tuning the through-plane LTC that operates for all chemistries considered here. The minimal through-plane LTC is obtained for angles between 1 and 4° depending on the material, with the biggest effect in MoS2. The angular dependence is correlated with the degree of stacking disorder in the materials, which in turn is connected to the slip surface. This provides a simple descriptor for predicting the optimal conditions at which the LTC is expected to become minimal.
6.	Fransson, Emma, PhD, 1973-, et al. (author) Cohort profile : the Swedish Maternal Microbiome project (SweMaMi) - assessing the dynamic associations between the microbiome and maternal and neonatal adverse events 2022 In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 12:10 Journal article (peer-reviewed)abstract Purpose The Swedish Maternal Microbiome (SweMaMi) project was initiated to better understand the dynamics of the microbiome in pregnancy, with longitudinal microbiome sampling, shotgun metagenomics, extensive questionnaires and health registry linkage. Participants Pregnant women were recruited before the 20th gestational week during 2017-2021 in Sweden. In total, 5439 pregnancies (5193 unique women) were included. For 3973 pregnancies (73%), samples were provided at baseline, and for 3141 (58%) at all three timepoints (second and third trimester and postpartum). In total, 38 591 maternal microbiome samples (vaginal, faecal and saliva) and 3109 infant faecal samples were collected. Questionnaires were used to collect information on general, reproductive and mental health, diet and lifestyle, complemented by linkage to the nationwide health registries, also used to follow up the health of the offspring (up to age 10). Findings to date The cohort is fairly representative for the total Swedish pregnant population (data from 2019), with 41% first-time mothers. Women with university level education, born in Sweden, with normal body mass index, not using tobacco-products and aged 30-34 years were slightly over-represented. Future plans The sample and data collection were finalised in November 2021. The next steps are the characterisation of the microbial DNA and linkage to the health and demographic information from the questionnaires and registries. The role of the microbiome on maternal and neonatal outcomes and early-childhood diseases will be explored (including preterm birth, miscarriage) and the role and interaction of other risk factors and confounders (including endometriosis, polycystic ovarian syndrome, diet, drug use). This is currently among the largest pregnancy cohorts in the world with longitudinal design and detailed and standardised microbiome sampling enabling follow-up of both mothers and children. The findings are expected to contribute greatly to the field of reproductive health focusing on pregnancy and neonatal outcomes.
7.	Fransson, Erik, 1990, et al. (author) Efficient construction of linear models in materials modeling and applications to force constant expansions 2020 In: npj Computational Materials. - : Springer Science and Business Media LLC. - 2057-3960. ; 6:1 Journal article (peer-reviewed)abstract Linear models, such as force constant (FC) and cluster expansions, play a key role in physics and materials science. While they can in principle be parametrized using regression and feature selection approaches, the convergence behavior of these techniques, in particular with respect to thermodynamic properties is not well understood. Here, we therefore analyze the efficacy and efficiency of several state-of-the-art regression and feature selection methods, in particular in the context of FC extraction and the prediction of different thermodynamic properties. Generic feature selection algorithms such as recursive feature elimination with ordinary least-squares (OLS), automatic relevance determination regression, and the adaptive least absolute shrinkage and selection operator can yield physically sound models for systems with a modest number of degrees of freedom. For large unit cells with low symmetry and/or high-order expansions they come, however, with a non-negligible computational cost that can be more than two orders of magnitude higher than that of OLS. In such cases, OLS with cutoff selection provides a viable route as demonstrated here for both second-order FCs in large low-symmetry unit cells and high-order FCs in low-symmetry systems. While regression techniques are thus very powerful, they require well-tuned protocols. Here, the present work establishes guidelines for the design of protocols that are readily usable, e.g., in high-throughput and materials discovery schemes. Since the underlying algorithms are not specific to FC construction, the general conclusions drawn here also have a bearing on the construction of other linear models in physics and materials science.
8.	Fransson, Erik, 1990, et al. (author) Limits of the phonon quasi-particle picture at the cubic-to-tetragonal phase transition in halide perovskites 2023 In: Communications Physics. - 2399-3650. ; 6:1 Journal article (peer-reviewed)abstract The soft modes associated with continuous-order phase transitions are associated with strong anharmonicity. This leads to the overdamped limit where the phonon quasi-particle picture can break down. However, this limit is commonly restricted to a narrow temperature range, making it difficult to observe its signature feature, namely the breakdown of the inverse relationship between the relaxation time and damping. Here we present a physically intuitive picture based on the relaxation times of the mode coordinate and its conjugate momentum, which at the instability approach infinity and the inverse damping factor, respectively. We demonstrate this behavior for the cubic-to-tetragonal phase transition of the inorganic halide perovskite CsPbBr3 via molecular dynamics simulations, and show that the overdamped region extends almost 200 K above the transition temperature. Further, we investigate how the dynamics of these soft phonon modes change when crossing the phase transition.
9.	Fransson, Göran, 1968-, et al. (author) Exploring how a digitally skilled teacher’s self-understanding influences his professional learning strategies. A research cooperation between a teacher and a researcher 2021 In: Teacher Development. - : Taylor & Francis. - 1366-4530 .- 1747-5120. ; 25:4, s. 432-448 Journal article (peer-reviewed)abstract The call for digitalisation in compulsory and upper secondary schools implies the need for teachers to pursue professional development. Here, teachers’ self-understanding may influence how they use, relate to and learn about digital technologies. The purpose of this article is to explore how a teacher’s self-understanding influences his professional development activities and, in turn, is influenced by his learning. In focus for this case study is one upper secondary school teacher’s endeavour to enact digital technologies and find suitable strategies for professional learning. This teacher and a researcher formed a reflective research partnership to explore how, and whether, the teacher’s self-understanding and professional learning strategies influenced each other. Reflective conversations, reflective writings and theoretical inputs facilitated the analysis.The findings show, for example, how his task perception changed over time from an emphasis on teaching to a greater emphasis on improvement, supporting colleagues in their learning and contributing to the professionalisation of the teaching community. This in turn influenced him adopting a self-directed informal learning strategy.
10.	Fransson, Helena, et al. (author) EndoReCo banar väg för ökad kunskap och akademisk meritering 2022 In: Tandläkartidningen. - : Sveriges tandläkarförbund. - 0039-6982. ; 114:12, s. 46-52 Journal article (peer-reviewed)abstract För att minska kunskapsluckorna inom odontologin krävs samarbete mellan lärosätena. Det ger även möjlighet till akademisk meritering, vilket är angeläget då antalet seniora forskare med behörighet för forskningshandledning i Sverige är färre än någonsin. EndoReCo (Endodontic Research Collaboration) är ett skandinaviskt forskningsnätverk i endodonti som kan ta del av just dessa fördelar.
11.	Fransson, Marcus, et al. (author) Svår traumatisk hjärnskada 2020 In: Läkartidningen. - Stockholm, Sweden : Sveriges Läkarförbund. - 0023-7205 .- 1652-7518. ; 117 Journal article (peer-reviewed)abstract De flesta är ense om att:handläggning ska sträva efter att nå normala fysiologiska förhållandentidig administrering av tranexamsyra minskar mortalitetensteroider och hypotermibehandling inte har en roll ihandläggningeneffekten av blodförtunnande behandling ska reverseras.Åsikterna går isär vad gäller:val mellan hyperton koksaltlösning och mannitol vidförhöjt intrakraniellt tryckval av bedömningsskala för medvetandegrad.
12.	Fransson, Per-Anders, et al. (author) Deep Brain Stimulation in the Subthalamic Nuclei Alters Postural Alignment and Adaptation in Parkinson’s Disease 2021 In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:12 Journal article (peer-reviewed)abstract Parkinson’s disease (PD) can produce postural abnormalities of the standing body position such as kyphosis. We investigated the effects of PD, deep brain stimulation (DBS) in the subthalamic nucleus (STN), vision and adaptation on body position in a well-defined group of patients with PD in quiet standing and during balance perturbations. Ten patients with PD and 25 young and 17 old control participants were recruited. Body position was measured with 3D motion tracking of the ankle, knee, hip, shoulder and head. By taking the ankle as reference, we mapped the position of the joints during quiet standing and balance perturbations through repeated calf muscle vibration. We did this to explore the effect of PD, DBS in the STN, and vision on the motor learning process of adaptation in response to the repeated stimulus. We found that patients with PD adopt a different body position with DBS ON vs. DBS OFF, to young and old controls, and with eyes open vs. eyes closed. There was an altered body position in PD with greater flexion of the head, shoulder and knee (p≤0.042) and a posterior position of the hip with DBS OFF (p≤0.014). With DBS ON, body position was brought more in line with the position taken by control participants but there was still evidence of greater flexion at the head, shoulder and knee. The amplitude of movement during the vibration period decreased in controls at all measured sites with eyes open and closed (except at the head in old controls with eyes open) showing adaptation which contrasted the weaker adaptive responses in patients with PD. Our findings suggest that alterations of posture and greater forward leaning with repeated calf vibration, are independent from reduced movement amplitude changes. DBS in the STN can significantly improve body position in PD although the effects are not completely reversed. Patients with PD maintain adaptive capabilities by leaning further forward and reducing movement amplitude despite their kyphotic posture.
13.	Fransson, Per-Anders, et al. (author) Deep brain stimulation in the subthalamic nuclei alters postural alignment and adaptation in Parkinson's disease 2021 In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:12 Journal article (peer-reviewed)abstract Parkinson's disease (PD) can produce postural abnormalities of the standing body position such as kyphosis. We investigated the effects of PD, deep brain stimulation (DBS) in the subthalamic nucleus (STN), vision and adaptation on body position in a well-defined group of patients with PD in quiet standing and during balance perturbations. Ten patients with PD and 25 young and 17 old control participants were recruited. Body position was measured with 3D motion tracking of the ankle, knee, hip, shoulder and head. By taking the ankle as reference, we mapped the position of the joints during quiet standing and balance perturbations through repeated calf muscle vibration. We did this to explore the effect of PD, DBS in the STN, and vision on the motor learning process of adaptation in response to the repeated stimulus. We found that patients with PD adopt a different body position with DBS ON vs. DBS OFF, to young and old controls, and with eyes open vs. eyes closed. There was an altered body position in PD with greater flexion of the head, shoulder and knee (p≤0.042) and a posterior position of the hip with DBS OFF (p≤0.014). With DBS ON, body position was brought more in line with the position taken by control participants but there was still evidence of greater flexion at the head, shoulder and knee. The amplitude of movement during the vibration period decreased in controls at all measured sites with eyes open and closed (except at the head in old controls with eyes open) showing adaptation which contrasted the weaker adaptive responses in patients with PD. Our findings suggest that alterations of posture and greater forward leaning with repeated calf vibration, are independent from reduced movement amplitude changes. DBS in the STN can significantly improve body position in PD although the effects are not completely reversed. Patients with PD maintain adaptive capabilities by leaning further forward and reducing movement amplitude despite their kyphotic posture.
14.	Fransson, Per-Anders, et al. (author) Exploring the Effects of Deep Brain Stimulation and Vision on Tremor in Parkinson's Disease : Benefits from Objective Methods 2020 In: Journal of NeuroEngineering and Rehabilitation. - : Springer Science and Business Media LLC. - 1743-0003. ; 17:1 Journal article (peer-reviewed)abstract BACKGROUND: Tremor is a cardinal symptom of Parkinson's disease (PD) that may cause severe disability. As such, objective methods to determine the exact characteristics of the tremor may improve the evaluation of therapy. This methodology study aims to validate the utility of two objective technical methods of recording Parkinsonian tremor and evaluate their ability to determine the effects of Deep Brain Stimulation (DBS) of the subthalamic nucleus and of vision.METHODS: We studied 10 patients with idiopathic PD, who were responsive to L-Dopa and had more than 1 year use of bilateral subthalamic nucleus stimulation. The patients did not have to display visible tremor to be included in the study. Tremor was recorded with two objective methods, a force platform and a 3 dimensional (3D) motion capture system that tracked movements in four key proximal sections of the body (knee, hip, shoulder and head). They were assessed after an overnight withdrawal of anti-PD medications with DBS ON and OFF and with eyes open and closed during unperturbed and perturbed stance with randomized calf vibration, using a randomized test order design.RESULTS: Tremor was detected with the Unified Parkinson's Disease Rating Scale (UPDRS) in 6 of 10 patients but only distally (hands and feet) with DBS OFF. With the force platform and the 3D motion capture system, tremor was detected in 6 of 10 and 7 of 10 patients respectively, mostly in DBS OFF but also with DBS ON in some patients. The 3D motion capture system revealed that more than one body section was usually affected by tremor and that the tremor amplitude was non-uniform, but the frequency almost identical, across sites. DBS reduced tremor amplitude non-uniformly across the body. Visual input mostly reduced tremor amplitude with DBS ON.CONCLUSIONS: Technical recording methods offer objective and sensitive detection of tremor that provide detailed characteristics such as peak amplitude, frequency and distribution pattern, and thus, provide information that can guide the optimization of treatments. Both methods detected the effects of DBS and visual input but the 3D motion system was more versatile in that it could detail the presence and properties of tremor at individual body sections.
15.	Hellgren, Rikard, 1988-, et al. (author) Measurement of ice pressure on a concrete dam with a prototype ice load panel 2020 In: Cold Regions Science and Technology. - : Elsevier. - 0165-232X .- 1872-7441. ; 170 Journal article (peer-reviewed)abstract This paper presents the development and installation of a prototype ice load panel and measurements of ice load from February 2016 to February 2018 at the Rätan hydropower dam in Sweden. The design of the 1 × 3 m2 panel enables direct measurement of ice pressure on the concrete surface is based on previous experience from similar measurements with sea ice. Important features of the design are sufficient height and width to reduce scale effects and to cover the ice thickness and variations in water level. The Rätan dam was chosen based on several criteria so that the ice load is considered to be reasonably idealized against the dam structure.For the three winters 2016, 2016/2017, 2017/2018, the maximum ice load recorded was 161 kN/m, 164 kN/m and 61 kN/m respectively. There were significant daily fluctuations during the cold winter months, and the daily peak ice loads showed a visual correlation with the daily average temperature and with the daily pattern of operation of the power station with its corresponding water level variations.
16.	Holmsten, Karin, et al. (author) Treatment Patterns and Efficacy of Chemotherapy After Pembrolizumab in Advanced Urothelial Cancer-a Real-World Study in the pre-Antibody-Drug Conjugate Era 2023 In: Clinical Genitourinary Cancer. - : Elsevier. - 1558-7673 .- 1938-0682. ; 21:6, s. E438-E448 Journal article (peer-reviewed)abstract This retrospective real-world study shows that vinflunine and platinum-combinations were the most common regimens after previous pembrolizumab in patients with metastatic urothelial cancer (mUC). The median progression-free and overall survival were 3.3 and 7.7 months respectively. Conventional chemotherapy after immunotherapy may remain to be a late-stage treatment option for selected patients in the era of targeted precision medicine of mUC. Background: Immune checkpoint inhibitors (ICIs) have been established as a routine treatment in patients with metastatic urothelial cancer (mUC). However, there has been no standard of care after progression on ICIs. We investigated real-world treatment patterns and efficacy of chemotherapy (CHT) after pembrolizumab, in the era before introduction of maintenance avelumab and antibody-drug conjugates (ADC). Patients and Methods: An observational, retrospective study was conducted at twelve Nordic centers. Patients with mUC were treated according to investigator s ' choice of CHT after pembrolizumab. Primary endpoint was overall response (ORR) and disease control rate (DCR); secondary endpoints were progression-free (PFS) and overall survival (OS). Results: In total, 102 patients were included whereof 23 patients received CHT after pembrolizumab as second line treatment (subcohort A) and 79 patients in third line (subcohort B). Platinum-gemcitabine combinations were the most common regimens in subcohort A, and vinflunine in subcohort B. The ORR and DCR were 36% and 47%, respectively. Presence of liver metastases was independently associated with lower ORR and DCR. The PFS and OS were 3.3 months and 7.7 months, respectively. Eastern Cooperative Oncology Group Performance Status (ECOG PS) and number of previous cycles of pembrolizumab were found to be independent prognostic factors associated with OS. Conclusion: In a real-world setting, CHT showed clinically
17.	Hugerth, Luisa W, et al. (author) Assessment of In Vitro and In Silico Protocols for Sequence-Based Characterization of the Human Vaginal Microbiome 2020 In: mSphere. - : American Society for Microbiology. - 2379-5042. ; 5:6 Journal article (peer-reviewed)abstract The vaginal microbiome has been connected to a wide range of health outcomes. This has led to a thriving research environment but also to the use of conflicting methodologies to study its microbial composition. Here, we systematically assessed best practices for the sequencing-based characterization of the human vaginal microbiome. As far as 16S rRNA gene sequencing is concerned, the V1-V3 region performed best in silico, but limitations of current sequencing technologies meant that the V3-V4 region performed equally well. Both approaches presented very good agreement with qPCR quantification of key taxa, provided that an appropriate bioinformatic pipeline was used. Shotgun metagenomic sequencing presents an interesting alternative to 16S rRNA gene amplification and sequencing but requires deeper sequencing and more bioinformatic expertise and infrastructure. We assessed different tools for the removal of host reads and the taxonomic annotation of metagenomic reads, including a new, easy-to-build and -use reference database of vaginal taxa. This curated database performed as well as the best-performing previously published strategies. Despite the many advantages of shotgun sequencing, none of the shotgun approaches assessed here agreed with the qPCR data as well as the 16S rRNA gene sequencing.IMPORTANCE The vaginal microbiome has been connected to various aspects of host health, including susceptibility to sexually transmitted infections as well as gynecological cancers and pregnancy outcomes. This has led to a thriving research environment but also to conflicting available methodologies, including many studies that do not report their molecular biological and bioinformatic methods in sufficient detail to be considered reproducible. This can lead to conflicting messages and delay progress from descriptive to intervention studies. By systematically assessing best practices for the characterization of the human vaginal microbiome, this study will enable past studies to be assessed more critically and assist future studies in the selection of appropriate methods for their specific research questions.
18.	Kastrati, Gránit, et al. (author) Genetic Influence on Nociceptive Processing in the Human Brain : A Twin Study 2022 In: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 32:2, s. 266-274 Journal article (peer-reviewed)abstract Nociceptive processing in the human brain is complex and involves several brain structures and varies across individuals. Determining the structures that contribute to interindividual differences in nociceptive processing is likely to improve our understanding of why some individuals feel more pain than others. Here, we found specific parts of the cerebral response to nociception that are under genetic influence by employing a classic twin-design. We found genetic influences on nociceptive processing in the midcingulate cortex and bilateral posterior insula. In addition to brain activations, we found genetic contributions to large-scale functional connectivity (FC) during nociceptive processing. We conclude that additive genetics influence specific brain regions involved in nociceptive processing. The genetic influence on FC during nociceptive processing is not limited to core nociceptive brain regions, such as the dorsal posterior insula and somatosensory areas, but also involves cognitive and affective brain circuitry. These findings improve our understanding of human pain perception and increases chances to find new treatments for clinical pain.
19.	Kim, Shi En, et al. (author) Extremely anisotropic van der Waals thermal conductors 2021 In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 597:7878, s. 660-665 Journal article (peer-reviewed)abstract The densification of integrated circuits requires thermal management strategies and high thermal conductivity materials1–3. Recent innovations include the development of materials with thermal conduction anisotropy, which can remove hotspots along the fast-axis direction and provide thermal insulation along the slow axis4,5. However, most artificially engineered thermal conductors have anisotropy ratios much smaller than those seen in naturally anisotropic materials. Here we report extremely anisotropic thermal conductors based on large-area van der Waals thin films with random interlayer rotations, which produce a room-temperature thermal anisotropy ratio close to 900 in MoS2, one of the highest ever reported. This is enabled by the interlayer rotations that impede the through-plane thermal transport, while the long-range intralayer crystallinity maintains high in-plane thermal conductivity. We measure ultralow thermal conductivities in the through-plane direction for MoS2 (57 ± 3 mW m−1 K−1) and WS2 (41 ± 3 mW m−1 K−1) films, and we quantitatively explain these values using molecular dynamics simulations that reveal one-dimensional glass-like thermal transport. Conversely, the in-plane thermal conductivity in these MoS2 films is close to the single-crystal value. Covering nanofabricated gold electrodes with our anisotropic films prevents overheating of the electrodes and blocks heat from reaching the device surface. Our work establishes interlayer rotation in crystalline layered materials as a new degree of freedom for engineering-directed heat transport in solid-state systems.
20.	Krog, Maria Christine, et al. (author) The microbiome in reproductive health: protocol for a systems biology approach using a prospective, observational study design 2022 In: Human Reproduction Open. - : Oxford University Press (OUP). - 2399-3529. ; 2022:2 Journal article (peer-reviewed)abstract STUDY QUESTIONWhat is the microbiome profile across different body sites in relation to the normal menstrual cycle (with and without hormonal contraception), recurrent pregnancy loss (RPL) (before and during pregnancy, pregnancy loss or birth) and endometriosis (before, during and after surgery)? How do these profiles interact with genetics, environmental exposures, immunological and endocrine biomarkers?WHAT IS KNOWN ALREADYThe microbiome is a key factor influencing human health and disease in areas as diverse as immune functioning, gastrointestinal disease and mental and metabolic disorders. There is mounting evidence to suggest that the reproductive microbiome may be influential in general and reproductive health, fertility and pregnancy outcomes.STUDY DESIGN, SIZE, DURATIONThis is a prospective, longitudinal, observational study using a systems biology approach in three cohorts totalling 920 participants. Since microbiome profiles by shot-gun sequencing have never been investigated in healthy controls during varying phases of the menstrual cycle, patients with RPL and patients with endometriosis, no formal sample size calculation can be performed. The study period is from 2017 to 2024 and allows for longitudinal profiling of study participants to enable deeper understanding of the role of the microbiome and of host–microbe interactions in reproductive health.PARTICIPANTS/MATERIALS, SETTING, METHODSParticipants in each cohort are as follows: Part 1 MiMens—150 healthy women with or without hormonal contraception; Part 2 MiRPL—200 couples with RPL, 50 healthy couples with prior uncomplicated pregnancy and 150 newborns; Part 3 MiEndo—120 patients with endometriosis requiring surgery with or without hormonal treatment. Microbiome profiles from saliva, faeces, rectal mucosa, vaginal fluid and endometrium will be studied, as well as the Omics profile, endocrine disrupting chemicals and endocrine and immune factors in blood, hair, saliva and urine. Pregnancy loss products, seminal microbiome, HLA types, endometriotic tissue and genetic risk and comprehensive questionnaire data will also be studied, where appropriate. Correlations with mental and physical health will be evaluated.
21.	Lindgren, Eric, 1997, et al. (author) calorine: A Python package for constructing and sampling neuroevolution potential models 2024 In: Journal of Open Source Software. - 2475-9066. ; 9:95, s. 6264-6264 Journal article (peer-reviewed)abstract Molecular dynamics (MD) simulations are a key tool in computational chemistry, physics, and materials science, aiding the understanding of microscopic processes but also guiding the development of novel materials. A MD simulation requires a model for the interatomic interactions. To this end, one traditionally often uses empirical interatomic potentials or force fields, which are fast but inaccurate, or ab-initio methods based on electronic structure theory such as density functional theory, which are accurate but computationally very expensive (Müser et al., 2023). Machine-learned interatomic potentials (MLIPs) have in recent years emerged as an alternative to these approaches, combining the speed of heuristic force fields with the accuracy of ab-initio techniques (Unke et al., 2021). Neuroevolution potentials (NEPs), implemented in the GPUMD package, in particular, are a highly accurate and efficient class of MLIPs (Fan et al., 2021, 2022; Fan, 2022). NEP models have already been used to study a variety of properties in a range of materials, with recent examples including radiation damage in tungsten (Liu et al., 2023), phase transitions (Fransson, Wiktor, et al., 2023) and dynamics of halide perovskites (Fransson, Rosander, et al., 2023) as well as thermal transport in two-dimensional materials (Sha et al., 2023). Here, we present calorine, a Python package that simplifies the construction, analysis and use of NEP models via GPUMD.
22.	Mota De Almeida, Fernando, et al. (author) Periradicular surgery: A longitudinal registry study of 10-year outcomes and factors predictive of post-surgical extraction 2023 In: International endodontic journal. - : John Wiley & Sons. - 0143-2885 .- 1365-2591. ; 56:10, s. 1212-1221 Journal article (peer-reviewed)abstract AimThis historical prospective cohort study of the adult population of Sweden is based on data from a national registry: the primary aim was to evaluate the long-term survival of teeth after periradicular surgery. A secondary aim was to identify factors predictive of extraction within 10 years of registration of periradicular surgery. MethodologyThe cohort consisted of all individuals who had undergone periradicular surgery to treat apical periodontitis, as reported to the Swedish Social Insurance Agency (SSIA) in 2009. The cohort was followed until 31 December 2020. Subsequent registrations of extractions were collected for Kaplan-Meier survival analyses and survival tables. The patients' sex, age, dental service provider and tooth group were also retrieved from SSIA. Only one tooth per individual was included in the analyses. Multivariable regression analysis was used and p < .05 was considered statistically significant. The reporting guidelines STROBE and PROBE were followed. ResultsAfter data cleaning, and exclusion of 157 teeth, 5622 teeth/individuals remained for analysis. The mean age of the individuals at the time of the periradicular surgery was 60.5 years (range 20-97, standard deviation 13.31); 55% were women. At the end of the follow-up, that is, up to 12 years, a total of 34.1% of the teeth had been reported as extracted. The multivariate logistic regression analysis, based on follow-up data at 10 years after registration of the periradicular surgery, included 5548 teeth, of which 1461 (26.3%) had been extracted. Significant associations between the independent variables tooth group and dental care setting (both p < .001) and the dependent variable extraction were found. The highest odds ratio (OR) for extraction applied to tooth group: compared to maxillary incisors and canines, mandibular molars were at greatest risk of extraction (OR 2.429, confidence interval 1.975-2.987, p < .001). ConclusionsAfter periradicular surgery in predominantly elderly people in Sweden, approximately three-quarters of the teeth are retained over a 10-year period. The type of tooth is associated with extraction: mandibular molars are at greater risk of extraction than maxillary incisors and canines.
23.	Patel, Mitesh, et al. (author) Effects of Deep Brain Stimulation on Postural Control in Parkinson's Disease 2020 In: Computers in Biology and Medicine. - : Elsevier BV. - 0010-4825. ; 122 Journal article (peer-reviewed)abstract The standard approach to the evaluation of tremor in medical practice is subjective scoring. The objective of this study was to show that signal processing of physiological data, that are known to be altered by tremor in Parkinson's disease (PD), can quantify the postural dynamics and the effects of DBS. We measured postural control and its capacity to adapt to balance perturbations with a force platform and perturbed balance by altering visual feedback and using pseudo-random binary sequence perturbations (PRBS) of different durations. Our signal processing involved converting the postural control data into spectral power with Fast-Fourier Transformation across a wide bandwidth and then subdividing this into three bands (0–4 Hz, 4–7 Hz and 7–25 Hz). We quantified the amount of power in each bandwidth. From 25 eligible participants, 10 PD participants (9 males, mean age 63.8 years) fulfilled the inclusion criteria; idiopathic PD responsive to L-Dopa; >1 year use of bilateral STN stimulation. Seventeen controls (9 males, mean age 71.2 years) were studied for comparison. Participants with PD were assessed after overnight withdrawal of anti-PD medications. Postural control was measured with a force platform during quiet stance (35 s) and during PRBS calf muscle vibration that perturbed stance (200 s). Tests were performed with eyes open and eyes closed and with DBS ON and DBS OFF. The balance perturbation period was divided into five sequential 35-s periods to assess the subject's ability to address postural imbalance using adaptation. The signal processing analyses revealed that DBS did not significantly change the dynamics of postural control in the 0–4 Hz spectral power but the device reduced the use of spectral power >4 Hz; a finding that was present in both anteroposterior and lateral directions, during vibration, and more so in eyes open tests. Visual feedback, which usually improves postural stability, was less effective in participants with PD with DBS OFF across all postural sway frequencies during quiet stance and during balance perturbations. The expected adaptation of postural control was found in healthy participants between the first and last balance perturbation period. However, adaptation was almost abolished across all spectral frequencies in both the anteroposterior and lateral directions, with both eyes open and eyes closed and DBS ON and OFF in participants with PD. To conclude, this study revealed that DBS altered the spectral frequency dynamics of postural control in participants through a reduction of the power used >4 Hz. Moreover, DBS tended to increase the stabilizing effect of vision across all spectral bands. However, the signal processing analyses also revealed that DBS was not able to restore adaptive motor control abilities in PD.
24.	Patel, Mitesh, et al. (author) Spectral Analysis of Body Movement during Deep Brain Stimulation in Parkinson's Disease 2021 In: Gait and Posture. - : Elsevier BV. - 0966-6362. ; 86, s. 217-225 Journal article (peer-reviewed)abstract Background: The characteristics of Parkinson's disease (PD) include postural instability and resting tremor. However, reductions of tremor amplitude do not always improve postural stability. Research question: What is the effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on spectral analysis of body movement in patients with PD when tested without anti-PD medication? The effect of visual cues was also studied. Methods: Ten patients with PD (mean age 64.3 years, range 59−69 years) and 17 control participants (mean age 71.2 years, range 65–79 years) were recruited. Spectral power following a period of quiet stance (35 s) was analysed in three different spectral power bands (0−4 Hz, 4−7 Hz and 7−25 Hz). Motion markers were secured to the head, shoulder, hip, and knee, which recorded movements in two directions, the anteroposterior and lateral. Results: DBS STN significantly changed the spectral distribution pattern across the body in the anteroposterior (p = 0.029) and lateral directions (p ≤ 0.003). DBS predominantly reduced spectral power at the head (p ≤ 0.037) and shoulder (p ≤ 0.031) in the lateral direction. The spectral power of the lower and upper body in patients with PD, with DBS ON, were more similar to the control group, than to DBS OFF. Visual cues mainly reduced spectral power in the anteroposterior direction at the shoulder (p ≤ 0.041) in controls and in patients with PD with DBS ON. Significance: There is an altered postural strategy in patients with PD with DBS ON as shown by an altered spectral power distribution pattern across body segments and a reduction of spectral power in the lateral direction at the head and shoulder. A reduction of spectral power in controls and in patients with PD with DBS ON suggests that visual cues are able to reduce spectral power to some extent, but not with DBS OFF where postural sway and power are larger.
25.	Patel, Mitesh, et al. (author) Strategic Alterations of Posture are Delayed in Parkinson's Disease Patients during Deep Brain Stimulation 2021 In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1 Journal article (peer-reviewed)abstract Parkinson's disease (PD) is characterized by rigidity, akinesia, postural instability and tremor. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces tremor but the effects on postural instability are inconsistent. Another component of postural control is the postural strategy, traditionally referred to as the ankle or hip strategy, which is determined by the coupling between the joint motions of the body. We aimed to determine whether DBS STN and vision (eyes open vs. eyes closed) affect the postural strategy in PD in quiet stance or during balance perturbations. Linear motion was recorded from the knee, hip, shoulder and head in 10 patients with idiopathic PD with DBS STN (after withdrawal of other anti-PD medication), 25 younger adult controls and 17 older adult controls. Correlation analyses were performed on anterior-posterior linear motion data to determine the coupling between the four positions measured. All participants were asked to stand for a 30 s period of quiet stance and a 200 s period of calf vibration. The 200 s vibration period was subdivided into four 50 s periods to study adaptation between the first vibration period (30-80 s) and the last vibration period (180-230 s). Movement was recorded in patients with PD with DBS ON and DBS OFF, and all participants were investigated with eyes closed and eyes open. DBS settings were randomized and double-blindly programmed. Patients with PD had greater coupling of the body compared to old and young controls during balance perturbations (p ≤ 0.046). Controls adopted a strategy with greater flexibility, particularly using the knee as a point of pivot, whereas patients with PD adopted an ankle strategy, i.e., they used the ankle as the point of pivot. There was higher flexibility in patients with PD with DBS ON and eyes open compared to DBS OFF and eyes closed (p ≤ 0.011). During balance perturbations, controls quickly adopted a new strategy that they retained throughout the test, but patients with PD were slower to adapt. Patients with PD further increased the coupling between segmental movement during balance perturbations with DBS ON but retained a high level of coupling with DBS OFF throughout balance perturbations. The ankle strategy during balance perturbations in patients with PD was most evident with DBS OFF and eyes closed. The increased coupling with balance perturbations implies a mechanism to reduce complexity at a cost of exerting more energy. Strategic alterations of posture were altered by DBS in patients with PD and were delayed. Our findings therefore show that DBS does not fully compensate for disease-related effects on posture.
26.	Sjögren, Julia, et al. (author) Reduced Vestibulo-Ocular Reflex During Fast Head Rotation in Complete Darkness 2023 In: Perceptual and Motor Skills. - 0031-5125. Journal article (peer-reviewed)abstract The human vestibulo-ocular reflex (VOR) leads to maintenance of the acuity of an image on the retina and contributes to the perception of orientation during high acceleration head movements. Our objective was to determine whether vision affects the horizontal VOR by assessing and comparing the performance at the boundaries of contribution of: (a) unrestricted visual information and (b) no visual information. Understanding how the VOR performs under both lighted and unlighted conditions is of paramount importance to avoiding falls, perhaps particularly among the elderly. We tested 23 participants (M age = 35.3 years, standard error of mean (SEM) = 2.0 years). The participants were tested with the video Head Impulse Test (vHIT), EyeSeeCam from Interacoustics™, which assesses whether VOR is of the expected angular velocity compared to head movement angular velocity. The vHIT tests were performed under two conditions: (a) in a well-lit room and (b) in complete darkness. The VOR was analyzed by evaluating the gain (quotient between eye and head angular velocity) at 40, 60 and 80 ms time stamps after the start of head movement. Additionally, we calculated the approximate linear gain between 0-100 ms through regression. The gain decreased significantly faster across time stamps in complete darkness (p < .001), by 10% in darkness compared with a 2% decrease in light. In complete darkness, the VOR gain gradually declined, reaching a marked reduction at 80 ms by 10% (p < .001), at which the head velocities were 150°/second or faster. The approximate linear gain value was not significantly different in complete darkness and in light. These findings suggest that information from the visual system can modulate the high velocity VOR. Subsequently, fast head turns might cause postural imbalance and momentary disorientation in poor light in people with reduced sensory discrimination or motor control, like the elderly.
27.	Sjögren, Julia, et al. (author) Short-Latency Covert Saccades - The Explanation for Good Dynamic Visual Performance After Unilateral Vestibular Loss? 2021 In: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 12 Journal article (peer-reviewed)abstract Background: Functional head impulse test (fHIT) tests the ability of the vestibulo-ocular reflex (VOR) to allow visual perception during head movements. Our previous study showed that active head movements to the side with a vestibular lesion generated a dynamic visual performance that were as good as during movements to the intact side. Objective: To examine the differences in eye position during the head impulse test when performed with active and passive head movements, in order to better understand the role of the different saccade properties in improving visual performance. Method: We recruited 8 subjects with complete unilateral vestibular loss (4 men and 4 women, mean age 47 years) and tested them with video Head Impulse Test (vHIT) and Functional Head Impulse Test (fHIT) during passive and active movements while looking at a target. We assessed the mean absolute position error of the eye during different time frames of the head movement, the peak latency and the peak velocity of the first saccade, as well as the visual performance during the head movement. Results: Active head impulses to the lesioned side generated dynamic visual performances that were as good as when testing the intact side. Active head impulses resulted in smaller position errors during the visual perception task (p = 0.006) compared to passive head-impulses and the position error during the visual perception time frame correlated with shorter latencies of the first saccade (p < 0.001). Conclusion: Actively generated head impulses toward the side with a complete vestibular loss resulted in a position error within or close to the margin necessary to obtain visual perception for a brief period of time in patients with chronic unilateral vestibular loss. This seems to be attributed to the appearance of short-latency covert saccades, which position the eyes in a more favorable position during head movements.
28.	Sterpu, Irene, et al. (author) No evidence for a placental microbiome in human pregnancies at term 2021 In: American Journal of Obstetrics and Gynecology. - : Elsevier. - 0002-9378 .- 1097-6868. ; 224:3, s. 296.e1-296.e23 Journal article (peer-reviewed)abstract Background: The placenta plays an important role in the modulation of pregnancy immunity; however, there is no consensus regarding the existence of a placental microbiome in healthy full-term pregnancies.Objective: This study aimed to investigate the existence and origin of a placental microbiome.Study Design: A cross-sectional study comparing samples (3 layers of placental tissue, amniotic fluid, vernix caseosa, and saliva, vaginal, and rectal samples) from 2 groups of full-term births: 50 women not in labor with elective cesarean deliveries and 26 with vaginal deliveries. The comparisons were performed using polymerase chain reaction amplification and DNA sequencing techniques and bacterial culture experiments.Result: There were no significant differences regarding background characteristics between women who delivered by elective cesarean and those who delivered vaginally. Quantitative measurements of bacterial content in all 3 placental layers (quantitative polymerase chain reaction of the 16S ribosomal RNA gene) did not show any significant difference among any of the sample types and the negative controls. Here, 16S ribosomal RNA gene sequencing of the maternal side of the placenta could not differentiate between bacteria in the placental tissue and contamination of the laboratory reagents with bacterial DNA. Probe-specific quantitative polymerase chain reaction for bacterial taxa suspected to be present in the placenta could not detect any statistically significant difference between the 2 groups. In bacterial cultures, substantially more bacteria were observed in the placenta layers from vaginal deliveries than those from cesarean deliveries. In addition, 16S ribosomal RNA gene sequencing of bacterial colonies revealed that most of the bacteria that grew on the plates were genera typically found in human skin; moreover, it revealed that placentas delivered vaginally contained a high prevalence of common vaginal bacteria. Bacterial growth inhibition experiments indicated that placental tissue may facilitate the inhibition of bacterial growth.Conclusion: We found no evidence to support the existence of a placental microbiome in our study of 76 term pregnancies, which used polymerase chain reaction amplification and sequencing techniques and bacterial culture experiments. Incidental findings of bacterial species could be due to contamination or to low-grade bacterial presence in some locations; such bacteria do not represent a placental microbiome per se.
29.	Tesi, Bianca, et al. (author) Diagnostic yield and clinical impact of germline sequencing in children with CNS and extracranial solid tumors : a nationwide, prospective Swedish study 2024 In: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 39 Journal article (peer-reviewed)abstract BackgroundChildhood cancer predisposition (ChiCaP) syndromes are increasingly recognized as contributing factors to childhood cancer development. Yet, due to variable availability of germline testing, many children with ChiCaP might go undetected today. We report results from the nationwide and prospective ChiCaP study that investigated diagnostic yield and clinical impact of integrating germline whole-genome sequencing (gWGS) with tumor sequencing and systematic phenotyping in children with solid tumors.MethodsgWGS was performed in 309 children at diagnosis of CNS (n = 123, 40%) or extracranial (n = 186, 60%) solid tumors and analyzed for disease-causing variants in 189 known cancer predisposing genes. Tumor sequencing data were available for 74% (227/309) of patients. In addition, a standardized clinical assessment for underlying predisposition was performed in 95% (293/309) of patients.FindingsThe prevalence of ChiCaP diagnoses was 11% (35/309), of which 69% (24/35) were unknown at inclusion (diagnostic yield 8%, 24/298). A second-hit and/or relevant mutational signature was observed in 19/21 (90%) tumors with informative data. ChiCaP diagnoses were more prevalent among patients with retinoblastomas (50%, 6/12) and high-grade astrocytomas (37%, 6/16), and in those with non-cancer related features (23%, 20/88), and ≥2 positive ChiCaP criteria (28%, 22/79). ChiCaP diagnoses were autosomal dominant in 80% (28/35) of patients, yet confirmed de novo in 64% (18/28). The 35 ChiCaP findings resulted in tailored surveillance (86%, 30/35) and treatment recommendations (31%, 11/35).InterpretationOverall, our results demonstrate that systematic phenotyping, combined with genomics-based diagnostics of ChiCaP in children with solid tumors is feasible in large-scale clinical practice and critically guides personalized care in a sizable proportion of patients.
30.	Tesi, Bianca, et al. (author) Diagnostic yield and clinical impact of germline sequencing in children with CNS and extracranial solid tumors : a nationwide, prospective Swedish study 2024 In: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 39 Journal article (peer-reviewed)abstract Background: Childhood cancer predisposition (ChiCaP) syndromes are increasingly recognized as contributing factors to childhood cancer development. Yet, due to variable availability of germline testing, many children with ChiCaP might go undetected today. We report results from the nationwide and prospective ChiCaP study that investigated diagnostic yield and clinical impact of integrating germline whole-genome sequencing (gWGS) with tumor sequencing and systematic phenotyping in children with solid tumors.Methods: gWGS was performed in 309 children at diagnosis of CNS (n = 123, 40%) or extracranial (n = 186, 60%) solid tumors and analyzed for disease-causing variants in 189 known cancer predisposing genes. Tumor sequencing data were available for 74% (227/309) of patients. In addition, a standardized clinical assessment for underlying predisposition was performed in 95% (293/309) of patients.Findings: The prevalence of ChiCaP diagnoses was 11% (35/309), of which 69% (24/35) were unknown at inclusion (diagnostic yield 8%, 24/298). A second-hit and/or relevant mutational signature was observed in 19/21 (90%) tumors with informative data. ChiCaP diagnoses were more prevalent among patients with retinoblastomas (50%, 6/12) and high-grade astrocytomas (37%, 6/16), and in those with non-cancer related features (23%, 20/88), and ≥2 positive ChiCaP criteria (28%, 22/79). ChiCaP diagnoses were autosomal dominant in 80% (28/35) of patients, yet confirmed de novo in 64% (18/28). The 35 ChiCaP findings resulted in tailored surveillance (86%, 30/35) and treatment recommendations (31%, 11/35).Interpretation: Overall, our results demonstrate that systematic phenotyping, combined with genomics-based diagnostics of ChiCaP in children with solid tumors is feasible in large-scale clinical practice and critically guides personalized care in a sizable proportion of patients.Funding: The study was supported by the Swedish Childhood Cancer Fund and the Ministry of Health and Social Affairs.
31.	Wadensten, Elisabeth, et al. (author) Diagnostic Yield From a Nationwide Implementation of Precision Medicine for all Children With Cancer. 2023 In: JCO precision oncology. - : American Society of Clinical Oncology. - 2473-4284. ; 7 Journal article (peer-reviewed)abstract Several studies have indicated that broad genomic characterization of childhood cancer provides diagnostically and/or therapeutically relevant information in selected high-risk cases. However, the extent to which such characterization offers clinically actionable data in a prospective broadly inclusive setting remains largely unexplored.We implemented prospective whole-genome sequencing (WGS) of tumor and germline, complemented by whole-transcriptome sequencing (RNA-Seq) for all children diagnosed with a primary or relapsed solid malignancy in Sweden. Multidisciplinary molecular tumor boards were set up to integrate genomic data in the clinical decision process along with a medicolegal framework enabling secondary use of sequencing data for research purposes.During the study's first 14 months, 118 solid tumors from 117 patients were subjected to WGS, with complementary RNA-Seq for fusion gene detection in 52 tumors. There was no significant geographic bias in patient enrollment, and the included tumor types reflected the annual national incidence of pediatric solid tumor types. Of the 112 tumors with somatic mutations, 106 (95%) exhibited alterations with a clear clinical correlation. In 46 of 118 tumors (39%), sequencing only corroborated histopathological diagnoses, while in 59 cases (50%), it contributed to additional subclassification or detection of prognostic markers. Potential treatment targets were found in 31 patients (26%), most commonly ALK mutations/fusions (n = 4), RAS/RAF/MEK/ERK pathway mutations (n = 14), FGFR1 mutations/fusions (n = 5), IDH1 mutations (n = 2), and NTRK2 gene fusions (n = 2). In one patient, the tumor diagnosis was revised based on sequencing. Clinically relevant germline variants were detected in 8 of 94 patients (8.5%).Up-front, large-scale genomic characterization of pediatric solid malignancies provides diagnostically valuable data in the majority of patients also in a largely unselected cohort.
32.	Wadensten, Elisabeth, et al. (author) Diagnostic Yield From a Nationwide Implementation of Precision Medicine for all Children With Cancer 2023 In: JCO Precision Oncology. - : American Society of Clinical Oncology. - 2473-4284. ; :7 Journal article (peer-reviewed)abstract Purpose: Several studies have indicated that broad genomic characterization of childhood cancer provides diagnostically and/or therapeutically relevant information in selected high-risk cases. However, the extent to which such characterization offers clinically actionable data in a prospective broadly inclusive setting remains largely unexplored.Methods: We implemented prospective whole-genome sequencing (WGS) of tumor and germline, complemented by whole-transcriptome sequencing (RNA-Seq) for all children diagnosed with a primary or relapsed solid malignancy in Sweden. Multidisciplinary molecular tumor boards were set up to integrate genomic data in the clinical decision process along with a medicolegal framework enabling secondary use of sequencing data for research purposes.Results: During the study's first 14 months, 118 solid tumors from 117 patients were subjected to WGS, with complementary RNA-Seq for fusion gene detection in 52 tumors. There was no significant geographic bias in patient enrollment, and the included tumor types reflected the annual national incidence of pediatric solid tumor types. Of the 112 tumors with somatic mutations, 106 (95%) exhibited alterations with a clear clinical correlation. In 46 of 118 tumors (39%), sequencing only corroborated histopathological diagnoses, while in 59 cases (50%), it contributed to additional subclassification or detection of prognostic markers. Potential treatment targets were found in 31 patients (26%), most commonly ALK mutations/fusions (n = 4), RAS/RAF/MEK/ERK pathway mutations (n = 14), FGFR1 mutations/fusions (n = 5), IDH1 mutations (n = 2), and NTRK2 gene fusions (n = 2). In one patient, the tumor diagnosis was revised based on sequencing. Clinically relevant germline variants were detected in 8 of 94 patients (8.5%).Conclusion: Up-front, large-scale genomic characterization of pediatric solid malignancies provides diagnostically valuable data in the majority of patients also in a largely unselected cohort.

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