| 1. |
- Ekman, Stefan, 1965-, et al.
(författare)
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Ramalina elegans återfunnen i Uppland
- 2015
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Ingår i: Lavbulletinen. - 1651-6435. ; 2014:2, s. 40-44
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 2. |
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| 3. |
- Badian, Reza A., et al.
(författare)
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Comparison of novel wide-field in vivo corneal confocal microscopy with skin biopsy for assessing peripheral neuropathy in type 2 diabetes
- 2023
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 72:7, s. 908-917
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Tidskriftsartikel (refereegranskat)abstract
- Diabetic peripheral neuropathy (DPN) is a serious complication of diabetes, where skin biopsy assessing intraepi-dermal nerve fiber density (IENFD) plays an important diagnostic role. In vivo confocal microscopy (IVCM) of the corneal subbasal nerve plexus has been proposed as a noninvasive diagnostic modality for DPN. Direct compari-sons of skin biopsy and IVCM in controlled cohorts are lacking, as IVCM relies on subjective selection of images depicting only 0.2% of the nerve plexus. We compared these diagnostic modalities in a fixed-age cohort of 41 participants with type 2 diabetes and 36 healthy participants using machine algorithms to create wide-field image mosaics and quantify nerves in an area 37 times the size of prior studies to avoid human bias. In the same partici-pants, and at the same time point, no correlation between IENFD and corneal nerve density was found. Corneal nerve density did not correlate with clinical measures of DPN, including neuropathy symptom and disability scores, nerve conduction studies, or quantitative sensory tests. Our findings indicate that corneal and intraepidermal nerves likely mirror different aspects of nerve degeneration, where only intraepidermal nerves appear to reflect the clinical status of DPN, suggesting that scrutiny is warranted concerning methodologies of studies using corneal nerves to assess DPN.
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| 4. |
- Dahlin, Lars B., et al.
(författare)
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Improved metabolic control using glucose monitoring systems leads to improvement in vibration perception thresholds in type 1 diabetes patients
- 2020
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 57:4, s. 433-438
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Few studies have examined how improved metabolic control might influence vibration perception thresholds (VPTs). The aim of this study was to evaluate if improved HbA1c can influence vibration thresholds in adults with type 1 diabetes (T1DM). Methods: VPTs were investigated at six frequencies (4–125 Hz) using VibroSense Meter in the sole of the foot at two occasions in 159 T1DM patients, at the heads of the first and fifth metatarsal bones, i.e. MTH1 and MTH5, respectively. The participants were divided into three groups: group A: HbA1c improved by more than 1 mmol/mol (n = 95), group B: HbA1c deteriorated by more than 1 mmol/mol (n = 48) and group C: HbA1c unchanged (± 1 mmol/mol) (n = 16) compared to baseline. Results: In group A, the mean z-score, reflecting the combined effect of all VPTs, improved being lower at the follow-up than at the baseline [0.2 (− 0.3 to 1.2) vs. −0.1 (− 0.7 to 0.8), p = 0.00002]. VPTs improved at 4 and 64 Hz at both MTH1 (metatarsal head 1) and MTH5. The VPTs at 125 Hz frequency improved at MTH5, but not at MTH1. No significant differences were seen in group B or group C. Conclusions: Lower HbA1c and lower VPTs in T1DM patients were associated with improved VPT, suggesting a reversible effect on nerve function by improved metabolic control.
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| 5. |
- Djureinovic, Dijana, et al.
(författare)
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Profiling cancer testis antigens in non-small-cell lung cancer
- 2016
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Ingår i: JCI INSIGHT. - : American Society for Clinical Investigation. - 2379-3708. ; 1:10
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Tidskriftsartikel (refereegranskat)abstract
- Cancer testis antigens (CTAs) are of clinical interest as biomarkers and present valuable targets for immunotherapy. To comprehensively characterize the CTA landscape of non-small-cell lung cancer (NSCLC), we compared RNAseq data from 199 NSCLC tissues to the normal transcriptome of 142 samples from 32 different normal organs. Of 232 CTAs currently annotated in the Caner Testis Database (CTdatabase), 96 were confirmed in NSCLC. To obtain an unbiased CTA profile of NSCLC, we applied stringent criteria on our RNAseq data set and defined 90 genes as CTAs, of which 55 genes were not annotated in the CTdatabase, thus representing potential new CTAs. Cluster analysis revealed that CTA expression is histology dependent and concurrent expression is common. IHC confirmed tissue-specific protein expression of selected new CTAs (TKTL1, TGIF2LX, VCX, and CXORF67). Furthermore, methylation was identified as a regulatory mechanism of CTA expression based on independent data from The Cancer Genome Atlas. The proposed prognostic impact of CTAs in lung cancer was not confirmed, neither in our RNAseq cohort nor in an independent meta-analysis of 1,117 NSCLC cases. In summary, we defined a set of 90 reliable CTAs, including information on protein expression, methylation, and survival association. The detailed RNAseq catalog can guide biomarker studies and efforts to identify targets for immunotherapeutic strategies.
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| 6. |
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| 7. |
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| 8. |
- Ekman, Linnéa, et al.
(författare)
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Diagnostic contribution of multi-frequency vibrometry to detection of peripheral neuropathy in type 1 diabetes mellitus compared with nerve conduction studies
- 2024
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Aim The aim was to assess the use of multi-frequency vibrometry (MFV) in detecting diabetic peripheral neuropathy (DPN) in type 1 diabetes in comparison to nerve conduction studies (NCS) and neurothesiometer (NT). Our objectives were to examine how VPTs correlated with NCS parameters, evaluate the efficacy of MFV in distinguishing DPN as well as to investigate whether MFV procedure could be based on fewer frequencies.Methods Adults with type 1 diabetes with previous MFV examinations were recruited at Skane University Hospital in Malmo, Sweden, between 2018 and 2020. Participants were examined regarding nerve function in the lower limbs through MFV, NT and NCS.Results A total of 66 participants (28 women and 38 men) with a median age of 50 (39 to 64) years were included in the study. Through NCS assessment, 33 participants (50%) were diagnosed with DPN. We found negative correlations between VPTs and all NCS parameters, where the strongest correlation was found between sural nerve amplitude and the 125 Hz frequency of MFV. A combination of four frequencies, two low (4 and 8 Hz) and two high (125 and 250 Hz), showed the highest classification efficacy (AUC 0.83, 95% CI 0.73-0.93).Conclusion We conclude that a strong correlation exists between the sural nerve amplitude and the VPTs at 125 Hz and that VPT testing with MFV can be focused on only four frequencies instead of seven, thus shortening test time, to distinguish DPN in the lower limb.
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| 9. |
- Ekman, Linnéa, et al.
(författare)
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Evaluation of small nerve fiber dysfunction in type 2 diabetes
- 2020
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 141:1, s. 38-46
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To assess potential correlations between intraepidermal nerve fiber densities (IENFD), graded with light microscopy, and clinical measures of peripheral neuropathy in elderly male subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes (T2DM), respectively. Materials and methods: IENFD was assessed in thin sections of skin biopsies from distal leg in 86 men (71-77 years); 24 NGT, 15 IGT, and 47 T2DM. Biopsies were immunohistochemically stained for protein gene product (PGP) 9.5, and intraepidermal nerve fibers (IENF) were quantified manually by light microscopy. IENFD was compared between groups with different glucose tolerance and related to neurophysiological tests, including nerve conduction study (NCS; sural and peroneal nerve), quantitative sensory testing (QST), and clinical examination (Total Neuropathy Score; Neuropathy Symptom Score and Neuropathy Disability Score). Results: Absent IENF was seen in subjects with T2DM (n = 10; 21%) and IGT (n = 1; 7%) but not in NGT. IENFD correlated weakly negatively with HbA1c (r = −.268, P =.013) and Total Neuropathy Score (r = −.219, P =.042). Positive correlations were found between IENFD and sural nerve amplitude (r =.371, P =.001) as well as conduction velocity of both the sural (r =.241, P =.029) and peroneal nerve (r =.258, P =.018). Proportions of abnormal sural nerve amplitude became significantly higher with decreasing IENFD. No correlation was found with QST. Inter-rater reliability of IENFD assessment was good (ICC = 0.887). Conclusions: Signs of neuropathy are becoming more prevalent with decreasing IENFD. IENFD can be meaningfully evaluated in thin histopathological sections using the presented technique to detect neuropathy.
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| 10. |
- Ekman, Linnéa, et al.
(författare)
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Examining practice effects in repeated measurements of vibration perception thresholds on finger pulps of healthy individuals – Is it possible to improve your results over a clinically relevant test interval?
- 2019
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:12
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Tidskriftsartikel (refereegranskat)abstract
- Aims To investigate practice effects in a test-retest situation, where vibration perception thresholds (VPT) were measured in healthy subjects using a multi-frequency test method. Methods In eight consecutive tests, VPTs were tested in the pulps of the index and little fingers at seven frequencies (8, 16, 32, 64, 125, 250 and 500 Hz). Subjects were twenty healthy adults aged 26 to 65 years (mean 46.0 ± 11.1 years; 10 male and 10 female). The subjects were examined at six tests with intervals of one month (mean 33 ± 6; time 0 to month 5) and at two additional tests with prolonged intervals (month 12 and 18). Linear mixed model analysis was performed to investigate differences over the subsequent test occasions. To examine where potential practice effects occurred, a pairwise comparison with Bonferroni correction was made. Results Small decreases in VPTs were found in 8 out of the 14 frequencies (index finger: 8, 16, 32, 250 and 500 Hz; little finger: 16, 250 and 500 Hz) within the test period from time 0 to month 5. In tests at 12 and 18 months, VPTs were increased compared to month 5, but lowered in comparison with time 0. Hence, minor significant decreases were found in three frequencies for the index finger (125, 250 and 500 Hz) and one frequency for the little finger (250 Hz) when examining VPTs with prolonged time intervals. Conclusions When evaluating vibration perception thresholds in a clinically relevant time period of once or twice a year, no consideration of practice effects is necessary when interpreting the results.
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| 11. |
- Ekman, Linnea, et al.
(författare)
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Normative values of the vibration perception thresholds at finger pulps and metatarsal heads in healthy adults
- 2021
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:4 April
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Tidskriftsartikel (refereegranskat)abstract
- Aims To establish normative values of vibration perception thresholds (VPTs), using multi-frequency vibrometry at finger pulps and at metatarsal heads of the foot in healthy adults. We also aimed to investigate factors that could potentially affect VPTs such as age, sex, height, weight, foot- or handedness and skin temperature. Methods VPTs were examined in 924 healthy and randomly selected subjects in the southern Sweden (mean 46 years; 628 women and 296 men). Inclusion criterias were adult subjects (>18 years) in considerable health without diabetes mellitus or other nerve affecting disorders. VPTs were measured at the finger pulps of index and little finger, as well as the first and fifth metatarsal heads of the foot, through multi-frequency vibrometry using the VibroSense Meter® I device. Patient characteristics were recorded and skin temperature was measured before assessment of VPTs. Results We present normative values of VPTs for a large population of both male and female subjects in various ages. VPTs detoriated as age increased (0.09-0.59 dB per year; p<0.001), i.e. progressing with normal aging. Increasing skin temperature affected VPTs in finger pulps, but not at metatarsal heads, with -0.2 to -1.6 dB, i.e. vibration perception improved with higher temperatures. Height was only found to affect the VPTs of metatarsal heads (250 Hz: 0.42 dB per cm). Sex, weight and handedness did not affect the VPTs. Conclusion We investigated the normative values of VPTs and presented affecting factors as age, skin temperature and height. With these results, VPT testing through multi-frequency vibrometry is enabled to be used in a clinical practice as a diagnostic tool when investigating neuropathy and other neurological disorders.
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| 12. |
- Ekman, Linnéa, et al.
(författare)
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Temporal trend of small nerve fibre degeneration in people with and without type 2 diabetes mellitus
- 2022
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Ingår i: Diabetic Medicine. - : John Wiley & Sons. - 0742-3071 .- 1464-5491. ; 39:3
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Tidskriftsartikel (refereegranskat)abstract
- Aims: We investigated the long-term temporal trend of intraepidermal nerve fibre density (IENFD) and the association between changes in IENFD and metabolic factors in individuals with and without type 2 diabetes. Methods: A total of 66 participants were enrolled in this longitudinal population-based study, at baseline consisting of 35 individuals (median 61 years) without diabetes and 31 individuals with type 2 diabetes mellitus. Participants underwent clinical and electrophysiological examinations, as well as a skin biopsy both at baseline and at the follow-up visit (mean 8.1 ± 0.5 years). IENFD was assessed in thin sections of 5 μm, stained with the protein gene product 9.5-antibody and compared between the groups. Results: IENFD decreased during the period in both groups, with a greater decline in the group without diabetes than in type 2 diabetes (−2.3 and −0.6 fibres/mm respectively; p < 0.001). While IENFD at baseline was significantly reduced in type 2 diabetes relative to people without (p < 0.001), no difference in IENFD was found between groups at the follow-up (p = 0.183). Linear mixed model analysis indicated that age, weight and HbA1c were associated with decrease in IENFD in the total population (p < 0.007). IENFD also decreased with increasing age and weight, but not with HbA1c, in the separate groups (p < 0.049). Conclusions: Despite lower IENFD levels at baseline in type 2 diabetes, IENFD was equal between the groups at follow-up. A decrease in IENFD is to a limited extent affected by body weight, and HbA1c, but age seems to be the long-term determinant of IENFD in an elderly population.
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| 13. |
- Frostadottir, Drifa, et al.
(författare)
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Cold sensitivity and its association to functional disability following a major nerve trunk injury in the upper extremity-A national registry-based study.
- 2022
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:7
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To investigate self-reported cold sensitivity and functional disability after a repaired major nerve trunk injury in the upper extremity.METHODS: We identified 735 individuals with a major nerve trunk injury in the upper extremity, surgically treated with direct nerve repair or reconstructed with nerve autografts, in the Swedish national quality registry for hand surgery (HAKIR). Patient-reported symptoms, including cold sensitivity, and perceived disability were collected using two questionnaires (HQ-8 and QuickDASH) preoperatively, and at three and 12 months postoperatively.RESULTS: We included 281 individuals, who had responded the questionnaires, where 197 (70%) were men (median age 34 [interquartile range 25-52] years) and 84 (30%) were women (median age 41 [25-55]). Cold sensitivity (scored 0-100) was the most prominent symptom 12 months postoperatively after an injured and repaired/reconstructed median (p<0.001) or ulnar (p<0.001) nerve, while individuals with a radial nerve injury showed milder symptoms. Concomitant injuries did not affect cold sensitivity scores. Individuals with ulnar nerve injuries scored higher in stiffness (p = 0.019), weakness (p<0.001) and ability to perform daily activities (p = 0.003) at 12 months postoperatively than median nerve injuries. Individuals with a median, ulnar or radial nerve injury with severe (>70) cold sensitivity had 25, 37 and 30 points higher QuickDASH scores, respectively (p<0.001), at 12 months postoperatively than individuals with mild (<30) cold sensitivity. There were no differences in QuickDASH score or cold sensitivity score at 12 months postoperatively between direct nerve repair or nerve reconstruction with nerve autografts. Neither age, nor sex, affected QuickDASH score at 12 months postoperatively.CONCLUSION: Cold sensitivity after surgery for a major nerve trunk injury in the upper extremity can be substantial with impaired ability to perform daily activities, where an ulnar nerve injury may have a worse outcome.
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| 14. |
- Frostadottir, Drifa, et al.
(författare)
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Cold sensitivity, functional disability and predicting factors after a repaired digital nerve injury
- 2022
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- To investigate self-reported cold sensitivity and functional disability after a repaired digital nerve injury. We identified 3204 individuals operated with digital nerve repair in the Swedish national quality registry for hand surgery (HAKIR). Patient-reported symptoms, including cold sensitivity and perceived disability, were examined using two questionnaires (HQ-8 and QuickDASH), three and 12 months postoperatively. Patients with diabetes (n = 48; 3%) were identified in the Swedish National Diabetes Register (NDR). Cold sensitivity (scored 0–100) was the most prominent symptom among 1553 included individuals (998 men, 555 women; median age 41 [IQR 27–54] years). In the regression analysis, flexor tendon injury, hand fracture and injury to multiple structures predicted worsened cold sensitivity (6.9, 15.5 and 25.0 points; p = 0.005, 0.046 and < 0.001) at 12 months. Individuals with moderate (30–70) and severe (> 70) cold sensitivity had higher QuickDASH scores at three and 12 months postoperatively than individuals with mild cold sensitivity (6.0 and 5.5; 19.8 and 21.0 points; p = 0.001). Flexor tendon injury, injuries to multiple structures and diabetes had significant effect on QuickDASH scores at three, but not at 12, months postoperatively. Cold sensitivity is common after a digital nerve repair and impacts self-reported disability. A concomitant injury, particularly multiple injuries, predicts postoperative cold sensitivity.
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| 15. |
- Graham, Emelie Linnéa, 1989-
(författare)
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Insights into key processes governing atmospheric aerosol loadings and their interactions with clouds
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aerosol particles are ubiquitous in the atmosphere and an essential part of the atmospheric radiation balance regulating the Earth’s temperature. Aerosol-cloud interaction still remains the largest single uncertainty in future climate projections. In addition, aerosols are also responsible for air pollution, causing severe health effects. With various origins and short atmospheric lifetimes, aerosols are unevenly distributed in the atmosphere, making simulations of air pollution and future climate scenarios challenging. This thesis aims to improve the understanding of the physical and chemical processes that govern aerosol concentration in the atmosphere, using both field as well as laboratory experiments.Field measurements were performed at a remote station at Mt Åreskutan, central Sweden. Located at 1250 m a.s.l. the station is frequently covered by clouds, allowing for in-cloud measurements. Aerosol particle size distribution measurements revealed a shift towards smaller diameters in the ambient aerosol size distribution after the station had been within a cloud. This is a result of the larger (> 60 nm) particles being more effectively scavenged by clouds as compared with the smaller end of the size distribution. Chemical analysis revealed a similar composition of the cloud water as the particulate matter, suggesting that cloud droplet activation at Mt Åreskutan is primarily dependent on particle size, and the aerosol population to have been internally mixed. Similarly, measurement of hygroscopicity and volatility revealed similar water-solubility and evaporation behaviour for the ambient aerosols and cloud residuals, with the organic fraction representative of aged boreal secondary organic aerosol (SOA) and showing no signs of significant aqueous phase processing.The NArVE laboratory campaign took place in an atmospheric simulation chamber at Paul Scherrer Institute, Switzerland. The experiments traced nitrate-induced SOA formation and ageing of three biogenic precursors, namely α-pinene, isoprene, and β-caryophyllene, using mass spectrometric techniques and evaporation measurements. The volatility of α-pinene SOA from nitrate oxidation was found to be higher than the corresponding ozonolysis products. The nitrate oxidation of isoprene resulted in species with similar volatility to α-pinene, while the β-caryophyllene system produced lower volatility compounds then the other two precursors. Quantitative comparison of the volatility measurements to commonly-used theoretical parameterizations revealed the need for further studies of the impact of the nitrate functional group on molecular volatility. Dark ageing of α-pinene was found to mainly occur through particle phase oxidation forming less volatile species. During the photolysis related to sunrise the molecular composition changed towards more volatile species, while no significant evaporation could be observed for the α-pinene and isoprene systems.A common theme in all these studies was investigating the level of detail needed to theoretically describe the observations. We found that while simple approximations (such as internal mixing and size-independent chemical composition of the particles) are often sufficient to capture trends in atmospheric aerosol properties, more research on (1) the processes taking place on shorter time- and smaller size scales than investigated here and (2) the effects of nitrate group on molecular volatility are warranted.
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| 16. |
- Graham, Emelie Linnéa, et al.
(författare)
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Physical and chemical properties of aerosol particles and cloud residuals on Mt. angstrom reskutan in Central Sweden during summer 2014
- 2020
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Ingår i: Tellus. Series B, Chemical and physical meteorology. - : Stockholm University Press. - 0280-6509 .- 1600-0889. ; 72:1
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Tidskriftsartikel (refereegranskat)abstract
- The size distribution, volatility and hygroscopicity of ambient aerosols and cloud residuals were measured with a differential mobility particle sizer (DMPS) and a volatility-hygroscopicity tandem differential mobility analyser (VHTDMA) coupled to a counterflow virtual impactor (CVI) inlet during the Cloud and Aerosol Experiment at Are (CAEsAR) campaign at Mt. Areskutan during summer 2014. The chemical composition of particulate matter (PM) and cloud water were analysed offline using thermo-optical OC/EC analysis and ion chromatography. The importance of aerosol particle size for cloud droplet activation and subsequent particle scavenging was clearly visible in the measured size distributions. Cloud residuals were shifted towards larger sizes compared to ambient aerosol, and the cloud events were followed by a size distribution dominated by smaller particles. Organics dominated both PM (62% organic mass fraction) and cloud water (63% organic mass fraction) composition. The volatility and hygroscopicity of the ambient aerosols were representative of homogeneous aged aerosol with contributions from biogenic secondary organics, with median volume fraction remaining (VFR) of 0.04-0.05, and median hygroscopicity parameter kappa of 0.16-0.24 for 100-300 nm particles. The corresponding VFR and kappa for the cloud residuals were 0.03-0.04 and 0.18-0.20. The chemical composition, hygroscopicity and volatility measurements thus showed no major differences between the ambient aerosol particles and cloud residuals. The VFR and kappa values predicted based on the chemical composition measurements agreed well with the VHTDMA measurements, indicating the bulk chemical composition to be a reasonable approximation throughout the size distribution. There were indications, however, of some more subtle changes in time scales not achievable by the offline chemical analysis applied here. Further, online observations of aerosol and cloud residual chemical composition are therefore warranted.
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| 17. |
- Grinberg, Marianna, et al.
(författare)
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Reaching the limits of prognostication in non-small cell lung cancer : an optimized biomarker panel fails to outperform clinical parameters.
- 2017
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Ingår i: Modern Pathology. - : Elsevier BV. - 0893-3952 .- 1530-0285. ; 30:7, s. 964-977
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Tidskriftsartikel (refereegranskat)abstract
- Numerous protein biomarkers have been analyzed to improve prognostication in non-small cell lung cancer, but have not yet demonstrated sufficient value to be introduced into clinical practice. Here, we aimed to develop and validate a prognostic model for surgically resected non-small cell lung cancer. A biomarker panel was selected based on (1) prognostic association in published literature, (2) prognostic association in gene expression data sets, (3) availability of reliable antibodies, and (4) representation of diverse biological processes. The five selected proteins (MKI67, EZH2, SLC2A1, CADM1, and NKX2-1 alias TTF1) were analyzed by immunohistochemistry on tissue microarrays including tissue from 326 non-small cell lung cancer patients. One score was obtained for each tumor and each protein. The scores were combined, with or without the inclusion of clinical parameters, and the best prognostic model was defined according to the corresponding concordance index (C-index). The best-performing model was subsequently validated in an independent cohort consisting of tissue from 345 non-small cell lung cancer patients. The model based only on protein expression did not perform better compared to clinicopathological parameters, whereas combining protein expression with clinicopathological data resulted in a slightly better prognostic performance (C-index: all non-small cell lung cancer 0.63 vs 0.64; adenocarcinoma: 0.66 vs 0.70, squamous cell carcinoma: 0.57 vs 0.56). However, this modest effect did not translate into a significantly improved accuracy of survival prediction. The combination of a prognostic biomarker panel with clinicopathological parameters did not improve survival prediction in non-small cell lung cancer, questioning the potential of immunohistochemistry-based assessment of protein biomarkers for prognostication in clinical practice.Modern Pathology advance online publication, 10 March 2017; doi:10.1038/modpathol.2017.14.
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| 18. |
- Huusko, Linnea L., et al.
(författare)
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Climate sensitivity indices and their relation with projected temperature change in CMIP6 models
- 2021
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Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 16:6
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Tidskriftsartikel (refereegranskat)abstract
- Equilibrium climate sensitivity (ECS) and transient climate response (TCR) are both measures of the sensitivity of the climate system to external forcing, in terms of temperature response to CO2 doubling. Here it is shown that, of the two, TCR in current-generation coupled climate models is better correlated with the model projected temperature change from the pre-industrial state, not only on decadal time scales but throughout much of the 21st century. For strong mitigation scenarios the difference persists until the end of the century. Historical forcing on the other hand has a significant degree of predictive power of past temperature evolution in the models, but is not relevant to the magnitude of temperature change in their future projections. Regional analysis shows a superior predictive power of ECS over TCR during the latter half of the 21st century in areas with slow warming, illustrating that although TCR is a better predictor of warming on a global scale, it does not capture delayed regional feedbacks, or pattern effects. The transient warming at CO2 quadrupling (T140) is found to be correlated with global mean temperature anomaly for a longer time than TCR, and it also better describes the pattern of regional temperature anomaly at the end of the century. Over the 20th century, there is a weak correlation between total forcing and ECS, contributing to, but not determining, the model agreement with observed warming. ECS and aerosol forcing in the models are not correlated.
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| 19. |
- Ising, Erik, et al.
(författare)
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Vibrotactile sense might improve over time in paediatric subjects with type 1 diabetes - a mid-term follow-up using multifrequency vibrometry
- 2022
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Ingår i: Acta Pædiatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 111:2, s. 411-417
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Tidskriftsartikel (refereegranskat)abstract
- AimImpaired vibrotactile sense, mirroring diabetic peripheral neuropathy, is present among children and adolescents with type 1 diabetes. This study aims to re-examine the vibrotactile sense of paediatric type 1 diabetes subjects in order to evaluate any alterations in the vibrotactile sense over time.MethodsA VibroSense Meter I device was used to determine the vibrotactile perception thresholds (VPTs) for seven frequencies from the pulp of index and little fingers and for five frequencies from metatarsal heads one and five on the sole of the foot, of 37 children and adolescents with type 1 diabetes, previously examined in a larger cohort. Subjects were followed up after a median time of 30 months. Z-scores of VPTs were calculated using previously collected normative data.ResultsVPTs improved over time at low frequencies (especially 16 Hz) on the foot, while not being statistically significant different on the rest of the frequencies, either on hand or foot. VPTs were not correlated to HbA1c.ConclusionA mid-term follow-up of vibrotactile sense in paediatric subjects with type 1 diabetes shows a conceivable normalization of previously impaired vibrotactile sense on some frequencies on the foot, indicating that vibrotactile sense might fluctuate over time.
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| 20. |
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| 21. |
- Lindholm, Eero, et al.
(författare)
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Diabetic Neuropathy assessed with Multifrequency Vibrometry Develops Earlier than Nephropathy but Later than Retinopathy
- 2023
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Ingår i: Experimental and Clinical Endocrinology & Diabetes. - : Georg Thieme Verlag KG. - 1439-3646 .- 0947-7349. ; 131:4, s. 187-193
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diabetes is associated with systemic complications. Prevalence of diabetic nephropathy, and retinopathy, in type 1 diabetes is declining but it is not known if this is true also for diabetic neuropathy.Aim: To investigate the relationship between large fiber diabetic neuropathy and other diabetic complications.Materials and methods: Neuropathy, defined here as large fiber neuropathy, was assessed by measuring vibration perception thresholds at four different frequencies on the sole of the foot using a standard VibroSense Meter and/or neuropathic symptoms, in 599 type 1 diabetic individuals. Retinopathy status was graded using the International Clinical Disease Severity Scale. Grade of albuminuria and previous history of any macrovascular complications, were registered.Results: Diabetic individuals without retinopathy had similar vibration thresholds as age- and gender-matched control persons without diabetes, whereas those without microalbuminuria had higher thresholds than controls. Two persons out of 599 (0.3%) had microalbuminuria, but not retinopathy or neuropathy, and 12/134 (9%) without retinopathy had signs of neuropathy. Totally 119/536 (22%) of the patients without microalbuminuria had neuropathy. Vibration thresholds increased with rising severity of retinopathy and grade of albuminuria. In a multinomial logistic regression analysis, neuropathy was associated with retinopathy (OR 2.96 [1.35-6.49], p=0.007), nephropathy (OR 6.25 [3.21-12.15]; p=6.7x10-8) and macrovascular disease (OR 2.72 [1.50-4.93], p=0.001).Conclusions: Despite recent changes in the incidence of diabetic complications, the onset of large fiber neuropathy follows that of retinopathy but precedes the onset of nephropathy in type 1 diabetes.
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| 22. |
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| 23. |
- Rao, Shuan, et al.
(författare)
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RANK rewires energy homeostasis in lung cancer cells and drives primary lung cancer
- 2017
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Ingår i: Genes & Development. - : Cold Spring Harbor Laboratory. - 0890-9369 .- 1549-5477. ; 31:20, s. 2099-2112
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Tidskriftsartikel (refereegranskat)abstract
- Lung cancer is the leading cause of cancer deaths. Besides smoking, epidemiological studies have linked female sex hormones to lung cancer in women; however, the underlying mechanisms remain unclear. Here we report that the receptor activator of nuclear factor-kB (RANK), the key regulator of osteoclastogenesis, is frequently expressed in primary lung tumors, an active RANK pathway correlates with decreased survival, and pharmacologic RANK inhibition reduces tumor growth in patient-derived lung cancer xenografts. Clonal genetic inactivation of KRas(G12D) in mouse lung epithelial cells markedly impairs the progression of KRas(G12D)-driven lung cancer, resulting in a significant survival advantage. Mechanistically, RANK rewires energy homeostasis in human and murine lung cancer cells and promotes expansion of lung cancer stem-like cells, which is blocked by inhibiting mitochondrial respiration. Our data also indicate survival differences in KRas(G12D)-driven lung cancer between male and female mice, and we show that female sex hormones can promote lung cancer progression via the RANK pathway. These data uncover a direct role for RANK in lung cancer and may explain why female sex hormones accelerate lung cancer development. Inhibition of RANK using the approved drug denosumab may be a therapeutic drug candidate for primary lung cancer.
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| 24. |
- Tsakonas, Georgios, et al.
(författare)
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c-MET as a biomarker in patients with surgically resected non-small cell lung cancer
- 2019
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Ingår i: Lung Cancer. - : Elsevier. - 0169-5002 .- 1872-8332. ; 133, s. 69-74
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Tidskriftsartikel (refereegranskat)abstract
- Background: c-MET protein overexpression has been proposed as a biomarker in non-small cell lung cancer (NSCLC), albeit its role in the clinical setting has not been firmly established yet. Patients and methods: We designed a retrospective cohort study, consisting of 725 patients with surgically removed NSCLC. Immunohistochemistry (IHC) was conducted in tissue microarrays (TMA) from lung tumors and healthy tissue. IHC staining was quantified using H-scores (range 0-300). Association between c-MET H-score and overall survival (OS) as well as progression-free survival (PFS) was explored. Results: c-MET H-score >= 20 had a significant positive impact on OS in the multivariate analysis in the whole study population, HR = 0.79 (95%CI: 0.64 - 0.97). The prognostic effect of c-MET H-score >= 20 was even stronger in patients who received adjuvant treatment with a HR = 0.61 (95% CI: 0.40 - 0.93). In the subgroup of adenocarcinoma and squamous cell carcinoma patients with stage IIA-IIIB disease, the prognostic impact of c-MET was significant in the univariate analysis (HR = 0.60, 95% CI: 0.43 - 0.83). Conclusion: c-MET H-score >= 20 is a positive prognostic biomarker for OS in early stage NSCLC. This benefit seems to be strongly correlated to adjuvant chemotherapy, therefore rendering c-MET H-score >= 20 a possible predictive biomarker for platinum-based adjuvant chemotherapy in early stage NSCLC.
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| 25. |
- Yu, Hui, et al.
(författare)
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Programmed Cell Death Ligand 1 Expression in Resected Non-Small Cell Lung Cancer
- 2021
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Ingår i: Clinical Lung Cancer. - : Elsevier. - 1525-7304 .- 1938-0690. ; 22:4, s. 555-562
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recently, anti-programmed cell death 1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) immunotherapies have yielded promising outcomes for patients with advanced non-small cell lung cancer (NSCLC) and led to great interest in applying these agents to treat resectable early-stage NSCLC. The objective of our study was to evaluate PD-L1 protein expression in resectable early-stage NSCLC specimens from a large Northern European cohort, examine the relationship to clinical characteristics, and demonstrate the prognostic role in resected NSCLC.Material and Methods: A large cohort of 875 NSCLC tumors consisted of 337 patients from Sweden and 538 patients from Norway was studied. All the patients had undergone pulmonary resection, and most patients had had early-stage NSCLC. PD-L1 protein expression was assessed by immunohistochemistry using the Dako PD-L1 22C3 pharmDx kit. The tumor proportion score for PD-L1 protein expression was compared with comprehensive demographic and clinicopathologic data.Results: The overall prevalence of PD-L1 protein expression in the resectable NSCLC cohort was 9.5% at a tumor proportion score cutoff of ≥ 50%. Stage I NSCLC had lower PD-L1 expression compared with that of the other stages (P = .0012). PD-L1 expression correlated with wild-type EGFR gene expression (P = .0156) and mutated KRAS gene expression (P = .0004). No significant association was found between PD-L1 expression and mortality after multivariable adjustment for clinical characteristics, although the survival curves showed PD-L1 expression significantly correlated with a poor prognosis in the total NSCLC cohort and in the adenocarcinoma subgroup.Conclusion: PD-L1 expression in the present large cohort of resectable NSCLC was relatively low compared with data from clinical trials of advanced NSCLC. PD-L1 expression correlated positively with tumor stage, wild-type EGFR, and KRAS mutation. PD-L1 expression was not found as an independent prognostic factor in the present study. These findings could be important in the future when evaluating the role of anti-PD-1/PD-L1 immunotherapy in the setting of neoadjuvant or adjuvant trials for early-stage resectable NSCLC.
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