| 1. |
- Tabiri, S, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 2. |
- Bravo, L, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- de Rojas, I., et al.
(författare)
-
Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
|
|
| 6. |
|
|
| 7. |
- Zaborowski, AM, et al.
(författare)
-
Microsatellite instability in young patients with rectal cancer: molecular findings and treatment response
- 2022
-
Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 109:3, s. 251-255
-
Tidskriftsartikel (refereegranskat)abstract
- In this study of 400 patients with early-onset rectal cancer, 12.5 per cent demonstrated microsatellite instability (MSI). MSI was associated with a reduced likelihood of nodal positivity, an increased rate of pathological complete response, and improved disease-specific survival.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Amgad, M, et al.
(författare)
-
Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group
- 2020
-
Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 6:1, s. 16-
-
Tidskriftsartikel (refereegranskat)abstract
- Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring.
|
|
| 13. |
- Chatron, N., et al.
(författare)
-
Bi-allelic GAD1 variants cause a neonatal onset syndromic developmental and epileptic encephalopathy
- 2020
-
Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 143:5, s. 1447-1461
-
Tidskriftsartikel (refereegranskat)abstract
- Developmental and epileptic encephalopathies are a heterogeneous group of early-onset epilepsy syndromes dramatically impairing neurodevelopment. Modern genomic technologies have revealed a number of monogenic origins and opened the door to therapeutic hopes. Here we describe a new syndromic developmental and epileptic encephalopathy caused by bi-allelic loss-of-function variants in GAD1, as presented by 11 patients from six independent consanguineous families. Seizure onset occurred in the first 2 months of life in all patients. All 10 patients, from whom early disease history was available, presented with seizure onset in the first month of life, mainly consisting of epileptic spasms or myoclonic seizures. Early EEG showed suppression-burst or pattern of burst attenuation or hypsarrhythmia if only recorded in the post-neonatal period. Eight patients had joint contractures and/or pes equinovarus. Seven patients presented a cleft palate and two also had an omphalocele, reproducing the phenotype of the knockout Gad1(-/-) mouse model. Four patients died before 4 years of age. GAD1 encodes the glutamate decarboxylase enzyme GAD67, a critical actor of the c-aminobutyric acid (GABA) metabolism as it catalyses the decarboxylation of glutamic acid to form GABA. Our findings evoke a novel syndrome related to GAD67 deficiency, characterized by the unique association of developmental and epileptic encephalopathies, cleft palate, joint contractures and/or omphalocele.
|
|
| 14. |
- Gonzalez-Ericsson, Paula, et al.
(författare)
-
The path to a better biomarker: application of a risk management framework for the implementation of PD‐L1 and TILs as immuno‐oncology biomarkers into breast cancer clinical trials and daily practice
- 2020
-
Ingår i: Journal of Pathology. - : Wiley. - 1096-9896 .- 0022-3417. ; 250:5, s. 667-684
-
Forskningsöversikt (refereegranskat)abstract
- Immune checkpoint inhibitor therapies targeting PD‐1/PD‐L1 are now the standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD‐L1 expression on immune cells occupying ≥1% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab‐paclitaxel. However, concerns regarding variability between immunohistochemical PD‐L1 assay performance and inter‐reader reproducibility have been raised. High tumor‐infiltrating lymphocytes (TILs) have also been associated with response to PD‐1/PD‐L1 inhibitors in patients with breast cancer (BC). TILs can be easily assessed on hematoxylin and eosin–stained slides and have shown reliable inter‐reader reproducibility. As an established prognostic factor in early stage TNBC, TILs are soon anticipated to be reported in daily practice in many pathology laboratories worldwide. Because TILs and PD‐L1 are parts of an immunological spectrum in BC, we propose the systematic implementation of combined PD‐L1 and TIL analyses as a more comprehensive immuno‐oncological biomarker for patient selection for PD‐1/PD‐L1 inhibition‐based therapy in patients with BC. Although practical and regulatory considerations differ by jurisdiction, the pathology community has the responsibility to patients to implement assays that lead to optimal patient selection. We propose herewith a risk‐management framework that may help mitigate the risks of suboptimal patient selection for immuno‐therapeutic approaches in clinical trials and daily practice based on combined TILs/PD‐L1 assessment in BC.
|
|
| 15. |
- Jones, Benedict C, et al.
(författare)
-
To which world regions does the valence-dominance model of social perception apply?
- 2021
-
Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169
-
Tidskriftsartikel (refereegranskat)abstract
- Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Reulen, Raoul C, et al.
(författare)
-
Risk Factors for Primary Bone Cancer After Childhood Cancer : A PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies Nested Case-Control Study
- 2023
-
Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 41:21, s. 3735-3746
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Radiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is uncertainty regarding the risks of bone tissue radiation doses below 10 Gy and the dose-response relationship for specific types of chemotherapy.METHODS: Twelve European countries contributed 228 cases and 228 matched controls to a nested case-control study within a cohort of 69,460 5-year survivors of childhood cancer. Odds ratios (ORs) of developing bone cancer for different levels of cumulative radiation exposure and cumulative doses of specific types of chemotherapy were calculated. Excess ORs were calculated to investigate the shape and extent of any dose-response relationship.RESULTS: The OR associated with bone tissue exposed to 1-4 Gy was 4.8-fold (95% CI, 1.2 to 19.6) and to 5-9 Gy was 9.6-fold (95% CI, 2.4 to 37.4) compared with unexposed bone tissue. The OR increased linearly with increasing dose of radiation ( P trend < .001) up to 78-fold (95% CI, 9.2 to 669.9) for doses of ≥40 Gy. For cumulative alkylating agent doses of 10,000-19,999 and ≥20,000 mg/m 2, the radiation-adjusted ORs were 7.1 (95% CI, 2.2 to 22.8) and 8.3 (95% CI, 2.8 to 24.4), respectively, with independent contributions from each of procarbazine, ifosfamide, and cyclophosphamide. Other cytotoxics were not associated with bone cancer. CONCLUSION: To our knowledge, we demonstrate-for the first time-that the risk of bone cancer is increased 5- to 10-fold after exposure of bone tissue to cumulative radiation doses of 1-9 Gy. Alkylating agents exceeding 10,000 mg/m 2 increase the risk 7- to 8-fold, particularly following procarbazine, ifosfamide, and cyclophosphamide. These substantially elevated risks should be used to develop/update clinical follow-up guidelines and survivorship care plans.
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
- Bateman, Daniel R., et al.
(författare)
-
Agitation and impulsivity in mid and late life as possible riskmarkers for incident dementia
- 2020
-
Ingår i: Alzheimer’s & Dementia. - : Elsevier. - 2352-8737. ; 6:1
-
Forskningsöversikt (refereegranskat)abstract
- To identify knowledge gaps regarding new-onset agitation and impulsivity prior to onsetof cognitive impairment or dementia the International Society to Advance Alzheimer’sResearch and Treatment Neuropsychiatric Syndromes (NPS) Professional InterestAreaconducted a scoping review. Extending a series of reviews exploring the pre-dementiarisk syndrome Mild Behavioral Impairment (MBI), we focused on late-onset agitationand impulsivity (the MBI impulse dyscontrol domain) and risk of incident cognitivedecline and dementia. This scoping review of agitation and impulsivity pre-dementiasyndromes summarizes the current biomedical literature in terms of epidemiology,diagnosis andmeasurement, neurobiology, neuroimaging, biomarkers, course and prognosis,treatment, and ongoing clinical trials. Validations for pre-dementia scales suchas the MBI Checklist, and incorporation into longitudinal and intervention trials, areneeded to better understand impulse dyscontrol as a risk factor for mild cognitiveimpairment and dementia.
|
|
| 25. |
|
|
| 26. |
- Heymer, Emma J., et al.
(författare)
-
Cumulative Absolute Risk of Subsequent Colorectal Cancer After Abdominopelvic Radiotherapy Among Childhood Cancer Survivors : A PanCareSurFup Study
- 2024
-
Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 42:3, s. 336-347
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE Childhood cancer survivors are at the risk of developing subsequent colorectal cancers (CRCs), but the absolute risks by treatment modality are uncertain. We quantified the absolute risks by radiotherapy treatment characteristics using clinically accessible data from a Pan-European wide case-control study nested within a large cohort of childhood cancer survivors: the PanCareSurFup Study. METHODS Odds ratios (ORs) from a case-control study comprising 143 CRC cases and 143 controls nested within a cohort of 69,460 survivors were calculated. These, together with standardized incidence ratios for CRC for this cohort and European general population CRC incidence rates and survivors' mortality rates, were used to estimate cumulative absolute risks (CARs) by attained age for different categories of radiation to the abdominopelvic area. RESULTS Overall, survivors treated with abdominopelvic radiotherapy treatment (ART) were three times more likely to develop a subsequent CRC than those who did not receive ART (OR, 3.1 [95% CI, 1.4 to 6.6]). For male survivors treated with ART, the CAR was 0.27% (95% CI, 0.17 to 0.59) by age 40 years, 1.08% (95% CI, 0.69 to 2.34) by age 50 years (0.27% expected in the general population), and 3.7% (95% CI, 2.36 to 7.80) by age 60 years (0.95% expected). For female survivors treated with ART, the CAR was 0.29% (95% CI, 0.18 to 0.62) by age 40 years, 1.03% (95% CI, 0.65 to 2.22) by age 50 years (0.27% expected), and 3.0% (95% CI, 1.91 to 6.37) by age 60 years (0.82% expected). CONCLUSION We demonstrated that by age 40 years survivors of childhood cancer treated with ART already have a similar risk of CRC as those age 50 years in the general population for whom population-based CRC screening begins in many countries. This information should be used in the development of survivorship guidelines for the risk stratification of survivors concerning CRC risk.
|
|
| 27. |
- Heymer, Emma J., et al.
(författare)
-
Risk of subsequent gliomas and meningiomas among 69,460 5-year survivors of childhood and adolescent cancer in Europe : the PanCareSurFup study
- 2024
-
Ingår i: British Journal of Cancer. - 0007-0920. ; 130:6, s. 976-986
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Childhood cancer survivors are at risk of subsequent gliomas and meningiomas, but the risks beyond age 40 years are uncertain. We quantified these risks in the largest ever cohort. Methods: Using data from 69,460 5-year childhood cancer survivors (diagnosed 1940–2008), across Europe, standardized incidence ratios (SIRs) and cumulative incidence were calculated. Results: In total, 279 glioma and 761 meningioma were identified. CNS tumour (SIR: 16.2, 95% CI: 13.7, 19.2) and leukaemia (SIR: 11.2, 95% CI: 8.8, 14.2) survivors were at greatest risk of glioma. The SIR for CNS tumour survivors was still 4.3-fold after age 50 (95% CI: 1.9, 9.6), and for leukaemia survivors still 10.2-fold after age 40 (95% CI: 4.9, 21.4). Following cranial radiotherapy (CRT), the cumulative incidence of a glioma in CNS tumour survivors was 2.7%, 3.7% and 5.0% by ages 40, 50 and 60, respectively, whilst for leukaemia this was 1.2% and 1.7% by ages 40 and 50. The cumulative incidence of a meningioma after CRT in CNS tumour survivors doubled from 5.9% to 12.5% between ages 40 and 60, and in leukaemia survivors increased from 5.8% to 10.2% between ages 40 and 50. Discussion: Clinicians following up survivors should be aware that the substantial risks of meningioma and glioma following CRT are sustained beyond age 40 and be vigilant for symptoms.
|
|
| 28. |
- Kok, Ellen M., et al.
(författare)
-
The effects of gaze-display feedback on medical students’ self-monitoring and learning in radiology
- 2024
-
Ingår i: Advances in Health Sciences Education. - 1382-4996.
-
Tidskriftsartikel (refereegranskat)abstract
- Self-monitoring is essential for effectively regulating learning, but difficult in visual diagnostic tasks such as radiograph interpretation. Eye-tracking technology can visualize viewing behavior in gaze displays, thereby providing information about visual search and decision-making. We hypothesized that individually adaptive gaze-display feedback improves posttest performance and self-monitoring of medical students who learn to detect nodules in radiographs. We investigated the effects of: (1) Search displays, showing which part of the image was searched by the participant; and (2) Decision displays, showing which parts of the image received prolonged attention in 78 medical students. After a pretest and instruction, participants practiced identifying nodules in 16 cases under search-display, decision-display, or no feedback conditions (n = 26 per condition). A 10-case posttest, without feedback, was administered to assess learning outcomes. After each case, participants provided self-monitoring and confidence judgments. Afterward, participants reported on self-efficacy, perceived competence, feedback use, and perceived usefulness of the feedback. Bayesian analyses showed no benefits of gaze displays for post-test performance, monitoring accuracy (absolute difference between participants’ estimated and their actual test performance), completeness of viewing behavior, self-efficacy, and perceived competence. Participants receiving search-displays reported greater feedback utilization than participants receiving decision-displays, and also found the feedback more useful when the gaze data displayed was precise and accurate. As the completeness of search was not related to posttest performance, search displays might not have been sufficiently informative to improve self-monitoring. Information from decision displays was rarely used to inform self-monitoring. Further research should address if and when gaze displays can support learning.
|
|
| 29. |
- Kok, Gautam, et al.
(författare)
-
Treatment of ARS deficiencies with specific amino acids
- 2021
-
Ingår i: Genetics in Medicine. - : Elsevier BV. - 1098-3600. ; 23:11, s. 2202-2207
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Recessive cytosolic aminoacyl-tRNA synthetase (ARS) deficiencies are severe multiorgan diseases, with limited treatment options. By loading transfer RNAs (tRNAs) with their cognate amino acids, ARS are essential for protein translation. However, it remains unknown why ARS deficiencies lead to specific symptoms, especially early life and during infections. We set out to increase pathophysiological insight and improve therapeutic possibilities. Methods: In fibroblasts from patients with isoleucyl-RS (IARS), leucyl-RS (LARS), phenylalanyl-RS-beta-subunit (FARSB), and seryl-RS (SARS) deficiencies, we investigated aminoacylation activity, thermostability, and sensitivity to ARS-specific amino acid concentrations, and developed personalized treatments. Results: Aminoacylation activity was reduced in all patients, and further diminished at 38.5/40 °C (PLARS and PFARSB), consistent with infectious deteriorations. With lower cognate amino acid concentrations, patient fibroblast growth was severely affected. To prevent local and/or temporal deficiencies, we treated patients with corresponding amino acids (follow-up: 1/2–2 2/3rd years), and intensified treatment during infections. All patients showed beneficial treatment effects, most strikingly in growth (without tube feeding), head circumference, development, coping with infections, and oxygen dependency. Conclusion: For these four ARS deficiencies, we observed a common disease mechanism of episodic insufficient aminoacylation to meet translational demands and illustrate the power of amino acid supplementation for the expanding ARS patient group. Moreover, we provide a strategy for personalized preclinical functional evaluation.
|
|
| 30. |
|
|
| 31. |
- Rodriguez, Sébastien, et al.
(författare)
-
Science goals and new mission concepts for future exploration of Titan's atmosphere, geology and habitability : titan POlar scout/orbitEr and in situ lake lander and DrONe explorer (POSEIDON)
- 2022
-
Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 54:2-3, s. 911-973
-
Tidskriftsartikel (refereegranskat)abstract
- In response to ESA’s “Voyage 2050” announcement of opportunity, we propose an ambitious L-class mission to explore one of the most exciting bodies in the Solar System, Saturn’s largest moon Titan. Titan, a “world with two oceans”, is an organic-rich body with interior-surface-atmosphere interactions that are comparable in complexity to the Earth. Titan is also one of the few places in the Solar System with habitability potential. Titan’s remarkable nature was only partly revealed by the Cassini-Huygens mission and still holds mysteries requiring a complete exploration using a variety of vehicles and instruments. The proposed mission concept POSEIDON (Titan POlar Scout/orbitEr and In situ lake lander DrONe explorer) would perform joint orbital and in situ investigations of Titan. It is designed to build on and exceed the scope and scientific/technological accomplishments of Cassini-Huygens, exploring Titan in ways that were not previously possible, in particular through full close-up and in situ coverage over long periods of time. In the proposed mission architecture, POSEIDON consists of two major elements: a spacecraft with a large set of instruments that would orbit Titan, preferably in a low-eccentricity polar orbit, and a suite of in situ investigation components, i.e. a lake lander, a “heavy” drone (possibly amphibious) and/or a fleet of mini-drones, dedicated to the exploration of the polar regions. The ideal arrival time at Titan would be slightly before the next northern Spring equinox (2039), as equinoxes are the most active periods to monitor still largely unknown atmospheric and surface seasonal changes. The exploration of Titan’s northern latitudes with an orbiter and in situ element(s) would be highly complementary in terms of timing (with possible mission timing overlap), locations, and science goals with the upcoming NASA New Frontiers Dragonfly mission that will provide in situ exploration of Titan’s equatorial regions, in the mid-2030s.
|
|
| 32. |
- Sartelli, Massimo, et al.
(författare)
-
Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action
- 2023
-
Ingår i: WORLD JOURNAL OF EMERGENCY SURGERY. - 1749-7922. ; 18:1
-
Forskningsöversikt (refereegranskat)abstract
- Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or "golden rules," for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice.
|
|
| 33. |
|
|
| 34. |
- Simoes, JP, et al.
(författare)
-
Multidisciplinary Tinnitus Research: Challenges and Future Directions From the Perspective of Early Stage Researchers
- 2021
-
Ingår i: Frontiers in aging neuroscience. - : Frontiers Media SA. - 1663-4365. ; 13, s. 647285-
-
Tidskriftsartikel (refereegranskat)abstract
- Tinnitus can be a burdensome condition on both individual and societal levels. Many aspects of this condition remain elusive, including its underlying mechanisms, ultimately hindering the development of a cure. Interdisciplinary approaches are required to overcome long-established research challenges. This review summarizes current knowledge in various tinnitus-relevant research fields including tinnitus generating mechanisms, heterogeneity, epidemiology, assessment, and treatment development, in an effort to highlight the main challenges and provide suggestions for future research to overcome them. Four common themes across different areas were identified as future research direction: (1) Further establishment of multicenter and multidisciplinary collaborations; (2) Systematic reviews and syntheses of existing knowledge; (3) Standardization of research methods including tinnitus assessment, data acquisition, and data analysis protocols; (4) The design of studies with large sample sizes and the creation of large tinnitus-specific databases that would allow in-depth exploration of tinnitus heterogeneity.
|
|
| 35. |
- Van Bockstal, MR, et al.
(författare)
-
Interobserver Agreement of PD-L1/SP142 Immunohistochemistry and Tumor-Infiltrating Lymphocytes (TILs) in Distant Metastases of Triple-Negative Breast Cancer: A Proof-of-Concept Study. A Report on Behalf of the International Immuno-Oncology Biomarker Working Group
- 2021
-
Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:19
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with advanced triple-negative breast cancer (TNBC) benefit from treatment with atezolizumab, provided that the tumor contains ≥1% of PD-L1/SP142-positive immune cells. Numbers of tumor-infiltrating lymphocytes (TILs) vary strongly according to the anatomic localization of TNBC metastases. We investigated inter-pathologist agreement in the assessment of PD-L1/SP142 immunohistochemistry and TILs. Ten pathologists evaluated PD-L1/SP142 expression in a proficiency test comprising 28 primary TNBCs, as well as PD-L1/SP142 expression and levels of TILs in 49 distant TNBC metastases with various localizations. Interobserver agreement for PD-L1 status (positive vs. negative) was high in the proficiency test: the corresponding scores as percentages showed good agreement with the consensus diagnosis. In TNBC metastases, there was substantial variability in PD-L1 status at the individual patient level. For one in five patients, the chance of treatment was essentially random, with half of the pathologists designating them as positive and half negative. Assessment of PD-L1/SP142 and TILs as percentages in TNBC metastases showed poor and moderate agreement, respectively. Additional training for metastatic TNBC is required to enhance interobserver agreement. Such training, focusing on metastatic specimens, seems worthwhile, since the same pathologists obtained high percentages of concordance (ranging from 93% to 100%) on the PD-L1 status of primary TNBCs.
|
|
| 36. |
|
|
| 37. |
- Williams, JC, et al.
(författare)
-
Urine and stone analysis for the investigation of the renal stone former: a consensus conference
- 2021
-
Ingår i: Urolithiasis. - : Springer Science and Business Media LLC. - 2194-7236 .- 2194-7228. ; 49:1, s. 1-16
-
Tidskriftsartikel (refereegranskat)abstract
- The Consensus Group deliberated on a number of questions concerning urine and stone analysis over a period of months, and then met to develop consensus. The Group concluded that analyses of urine and stones should be routine in the diagnosis and treatment of urinary stone diseases. At present, the 24-h urine is the most useful type of urine collection, and accepted methods for analysis are described. Patient education is also important for obtaining a proper urine sample. Graphical methods for reporting urine analysis results can be helpful both for the physician and for educating the patient as to proper dietary changes that could be beneficial. Proper analysis of stones is also essential for diagnosis and management of patients. The Consensus Group also agreed that research has shown that evaluation of urinary crystals could be very valuable, but the Group also recognizes that existing methods for assessment of crystalluria do not allow this to be part of stone treatment in many places.
|
|
| 38. |
- Zhang, H. B., et al.
(författare)
-
Snow cover persistence reverses the altitudinal patterns of warming above and below 5000 m on the Tibetan Plateau
- 2022
-
Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697. ; 803
-
Tidskriftsartikel (refereegranskat)abstract
- The Tibetan Plateau (TP) is a global warming hotspot, however, the warming status at high elevation (>5000 m) is poorly understood due to very sparse observations. Here we analyze spatial patterns in TP warming rates based on a novel near-surface air temperature dataset of 1980-2014 recently developed by ingesting high-elevation observations and downscaled reanalysis datasets. We show that the high snow cover persistence at high elevation reduces strengthening of positive feedbacks responsible for elevation dependent warming at low-middle elevations, leading to reversed altitudinal patterns of TP warming above and below 5000 m. An important negative feedback is induced by the presence of snow and glaciers at elevations above 5000 m, due to their "buffer-ing" effects by consuming or reflecting energy that would be used for warming in the absence of snow or ice. A further decrease in snow cover and glacier extent at high elevations may thus amplify the warming on the TP. (c) 2021 Elsevier B.V. All rights reserved.
|
|
