| 1. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 2. |
- Broekman, Maarten J. E., et al.
(författare)
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Evaluating expert-based habitat suitability information of terrestrial mammals with GPS-tracking data
- 2022
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Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 31:8, s. 1526-1541
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Macroecological studies that require habitat suitability data for many species often derive this information from expert opinion. However, expert-based information is inherently subjective and thus prone to errors. The increasing availability of GPS tracking data offers opportunities to evaluate and supplement expert-based information with detailed empirical evidence. Here, we compared expert-based habitat suitability information from the International Union for Conservation of Nature (IUCN) with habitat suitability information derived from GPS-tracking data of 1,498 individuals from 49 mammal species.Location: Worldwide.Time period: 1998-2021.Major taxa studied: Forty-nine terrestrial mammal species.Methods: Using GPS data, we estimated two measures of habitat suitability for each individual animal: proportional habitat use (proportion of GPS locations within a habitat type), and selection ratio (habitat use relative to its availability). For each individual we then evaluated whether the GPS-based habitat suitability measures were in agreement with the IUCN data. To that end, we calculated the probability that the ranking of empirical habitat suitability measures was in agreement with IUCN's classification into suitable, marginal and unsuitable habitat types.Results: IUCN habitat suitability data were in accordance with the GPS data (> 95% probability of agreement) for 33 out of 49 species based on proportional habitat use estimates and for 25 out of 49 species based on selection ratios. In addition, 37 and 34 species had a > 50% probability of agreement based on proportional habitat use and selection ratios, respectively.Main conclusions: We show how GPS-tracking data can be used to evaluate IUCN habitat suitability data. Our findings indicate that for the majority of species included in this study, it is appropriate to use IUCN habitat suitability data in macroecological studies. Furthermore, we show that GPS-tracking data can be used to identify and prioritize species and habitat types for re-evaluation of IUCN habitat suitability data.
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| 3. |
- Fransson, Emma, et al.
(författare)
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Diagnostic Efficacy of Rectal Suction Biopsy with Regard to Weight in Children Investigated for Hirschsprung's Disease
- 2022
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Ingår i: Children. - : MDPI AG. - 2227-9067. ; 9:2, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIM: Diagnostic efficacy, defined as the percentage of rectal suction biopsy (RSB) specimens sufficient enough to determine the absence of ganglia cells in Hirschsprung's disease (HD) diagnosis, has been reported to be low, requiring repeated biopsies. The aim was to explore whether RSB diagnostic efficacy was influenced by the child's weight and to ascertain whether RSB efficacy differed between aganglionic and ganglionic tissue.MATERIALS AND METHODS: Efficacy analyses were conducted in a national HD-center's register on children 0-15 kg, examined between 2011-2019. First-time RSB diagnostic efficacy was correlated to the children's weight and final HD diagnosis.RESULTS: Among the 84 children who had first-time RSB, the overall diagnostic efficacy was 85% (71/84). The efficacy was higher among children weighing less than the identified cut-off of 9.0 kg (89% in 0-9.0 kg versus 62% in 9.01-15.0 kg, p = 0.026). Among children diagnosed with HD, 96% (26/27) weighed 0-9.0 kg. In this weight group, the diagnostic efficacy was lower in aganglionosis compared to ganglionosis (77%; 20/26 versus 96%; 43/45), p = 0.045).CONCLUSIONS: The RSB diagnostic efficacy was significantly higher in children weighing less than 9.0 kg and was less in aganglionic compared to ganglionic tissue. Therefore, weight can be useful to predict RSB diagnostic efficacy.
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| 4. |
- Fransson, Emma, et al.
(författare)
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Systematic orientation of fresh rectal suction biopsies improves histopathological diagnostics in hirschsprung’s disease – a method description and preliminary report
- 2023
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Ingår i: BMC Pediatrics. - 1471-2431. ; 23
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Tidskriftsartikel (refereegranskat)abstract
- Background: Optimizing rectal suction biopsy (RSB) diagnostics in Hirschsprung’s disease (HD) may shorten diagnostic time and prevent need for repeated biopsies. Aim: To explore whether systematic orientation of fresh RSB specimens increased biopsy quality, diagnostic times, diagnostic efficacy, and histopathologic workload, and to explore these outcome measures for aganglionic specimens. Materials/Methods: This was an observational case-control study conducted at a national referral center for HD on data collected from the local HD-diagnostic register. From 2019 each fresh RSB was oriented by the collector in a notch in a foam cushion, placed in a separate cassette, and sent in formalin for pathological analysis. Outcome measures of oriented RSB samples collected 2019–2021 were compared to those of non-oriented RSB samples collected 2015–2018. Staining/immunohistochemistry consisted of hematoxylin eosin, S-100 and calretinin. Results: 78 children with 81 RSBs and 242 biopsy analyzes were included. The frequency of high-quality RSB specimens was higher in oriented: 40% (42/106) versus non-oriented 25% (34/136) (p = 0.018), the diagnostic turnaround time was shorter: 2 days (1–5) versus 3 days (2–8) (p = 0.015), and the number of additional sectioning/leveling/re-orientation per biopsy was lower: 7 (3–26) versus 16 (7–72) (p = 0.011). Specifically for aganglionic specimens, the frequency of high-quality biopsies was generally higher in oriented than in non-oriented RSB specimens: 47% (28/59) versus 14% (7/50) (p < 0.001); the diagnostic efficacy was higher 95% (19/20) versus 60% (9/15) (p = 0.027) and the diagnostic turnaround time shorter: 2 days (2–3) versus 3 days (2–8) (p = 0.036). Conclusions: Systematic orientation of fresh RSB specimens improves HD diagnostics. Improvement was consistent in aganglionic specimens.
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| 5. |
- Graneli, Christina, et al.
(författare)
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Histopathological dimensions differ between aganglionic and ganglionic bowel wall in children with Hirschsprung’s disease
- 2022
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the validation of new imaging technology for children with Hirschsprung’s disease (HSCR), basic anatomical parameters of the bowel wall must be established specifically for this patient group. Aim: To explore differences in histoanatomical layers of bowel wall, comparing ganglionic and aganglionic bowel walls, and to examine if the bowel wall thickness is linked to patient weight. Methods: This was an observational study of bowel specimens from children weighing 0–10 kg, operated on consecutively during 2018–2020. Ganglionic and aganglionic bowel walls were measured in digitalized microscopy images from 10 sites per trans-sectional specimen and compared regarding the thickness of their histoanatomical layers. Results: Bowel walls were measured in 21 children. Full bowel wall thickness did not differ between aganglionic and ganglionic bowel (2.20 vs 2.04; p = 0.802) while weight at surgery correlated positively with both ganglionic and aganglionic bowel wall thickness (r = 0.688 and 0.849, respectively), and age at surgery with ganglionic bowel wall thickness (r = 0.517). In aganglionic segments, the muscularis externa layer was thicker compared to that in ganglionosis (0.45 vs 0.31 mm, p = 0.012) whereas the muscularis interna was thinner (0.45 vs 0.62 mm, p < 0.001). A diagnostic index was identified whereby a lower ratio of muscularis interna/externa thickness followed by a thinner muscularis interna differed between aganglionic and ganglionic bowel in all specimens. Conclusion: Thicknesses of the bowel wall’s muscle layers differ between aganglionic and ganglionic bowel walls in children with HSCR. These findings support a diagnostic index that could be validated for transfer to instant diagnostic imaging techniques.
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| 6. |
- Granéli, Christina, et al.
(författare)
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Ultra high frequency ultrasonography to distinguish ganglionic from aganglionic bowel wall in Hirschsprung disease : A first report
- 2021
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Ingår i: Journal of Pediatric Surgery. - : Elsevier BV. - 0022-3468. ; 56:12, s. 2281-2285
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Tidskriftsartikel (refereegranskat)abstract
- Background/Purpose: In Hirschsprung disease (HD) surgery, confirming ganglionic bowel is essential. A faster diagnostic method than the current frozen biopsy is desirable. This study investigated whether aganglionic and ganglionic intestinal wall can be distinguished from each other by ultra high frequency ultrasound (UHF ultrasound). Methods: In an HD center during 2019, intestinal walls of recto-sigmoid specimens from HD patients were examined ex vivo with a 70 MHz UHF ultrasound transducer. Data from four sites were described. Histopathologic analysis was compared to the ultrasonography outcome at each site. Each patient's specimen served as its own control. Results: 11 resected recto-sigmoid specimens (median 20 cm long [range 6.5–33]) with transition zones of 5 cm (2–11 cm) were taken from children aged 22 days (13–48) weighing 3668 g (3500–5508); 44 key sites were analyzed. There was full concordance for 42/44 (95%) key sites and 10 of 11 (91%) specimens. The specimen with discordance of two key sites contained a segment of aganglionosis (3 cm) and a transition zone (1 cm): the site discordance was limited to the transition zone ends. Conclusions: This first report on UHF ultrasound in recto-sigmoid HD shows promising results in identifying aganglionosis, transition zones and ganglionic bowel. Further in vivo studies are required.
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| 7. |
- Hawez, Tebin, et al.
(författare)
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Ultra-High Frequency Ultrasound Imaging of Bowel Wall in Hirschsprung’s Disease—Correlation and Agreement Analyses of Histoanatomy
- 2023
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Ingår i: Diagnostics. - 2075-4418. ; 13:8
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Tidskriftsartikel (refereegranskat)abstract
- Hirschsprung’s disease (HD) is characterized by aganglionosis in the bowel wall, requiring resection. Ultra-high frequency ultrasound (UHFUS) imaging of the bowel wall has been suggested to be an instantaneous method of deciding resection length. The aim of this study was to validate UHFUS imaging of the bowel wall in children with HD by exploring the correlation and systematic differences between UHFUS and histopathology. Resected fresh bowel specimens of children 0–1 years old, operated on for rectosigmoid aganglionosis at a national HD center 2018–2021, were examined ex vivo with UHFUS center frequency 50 MHz. Aganglionosis and ganglionosis were confirmed by histopathological staining and immunohistochemistry. Histoanatomical layers of bowel wall in histopathological and UHFUS images, respectively, were outlined using MATLAB programs. Both histopathological and UHFUS images were available for 19 aganglionic and 18 ganglionic specimens. The thickness of muscularis interna correlated positively between histopathology and UHFUS in both aganglionosis (R = 0.651, p = 0.003) and ganglionosis (R = 0.534, p = 0.023). The muscularis interna was systematically thicker in histopathology than in UHFUS images in both aganglionosis (0.499 vs. 0.309 mm; p < 0.001) and ganglionosis (0.644 versus 0.556 mm; p = 0.003). Significant correlations and systematic differences between histopathological and UHFUS images support the hypothesis that UHFUS reproduces the histoanatomy of the bowel wall in HD accurately.
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| 8. |
- Mishra, A., et al.
(författare)
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Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
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Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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| 9. |
- Tzelves, Lazaros, et al.
(författare)
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Artificial intelligence supporting cancer patients across Europe - The ASCAPE project
- 2022
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 17:4
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Breast and prostate cancer survivors can experience impaired quality of life (QoL) in several QoL domains. The current strategy to support cancer survivors with impaired QoL is suboptimal, leading to unmet patient needs. ASCAPE aims to provide personalized- and artificial intelligence (AI)-based predictions for QoL issues in breast- and prostate cancer patients as well as to suggest potential interventions to their physicians to offer a more modern and holistic approach on cancer rehabilitation.METHODS AND ANALYSES: An AI-based platform aiming to predict QoL issues and suggest appropriate interventions to clinicians will be built based on patient data gathered through medical records, questionnaires, apps, and wearables. This platform will be prospectively evaluated through a longitudinal study where breast and prostate cancer survivors from four different study sites across the Europe will be enrolled. The evaluation of the AI-based follow-up strategy through the ASCAPE platform will be based on patients' experience, engagement, and potential improvement in QoL during the study as well as on clinicians' view on how ASCAPE platform impacts their clinical practice and doctor-patient relationship, and their experience in using the platform.ETHICS AND DISSEMINATION: ASCAPE is the first research project that will prospectively investigate an AI-based approach for an individualized follow-up strategy for patients with breast- or prostate cancer focusing on patients' QoL issues. ASCAPE represents a paradigm shift both in terms of a more individualized approach for follow-up based on QoL issues, which is an unmet need for cancer survivors, and in terms of how to use Big Data in cancer care through democratizing the knowledge and the access to AI and Big Data related innovations.TRIAL REGISTRATION: Trial Registration on clinicaltrials.gov: NCT04879563.
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