| 1. |
- Huvila, J., et al.
(författare)
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Combined ASRGL1 and p53 immunohistochemistry as an independent predictor of survival in endometrioid endometrial carcinoma
- 2018
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Ingår i: Gynecologic Oncology. - : Academic Press Inc.. - 0090-8258 .- 1095-6859. ; 149:1, s. 173-180
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Tidskriftsartikel (refereegranskat)abstract
- Objective: In clinical practise, prognostication of endometrial cancer is based on clinicopathological risk factors. The use of immunohistochemistry-based markers as prognostic tools is generally not recommended and a systematic analysis of their utility as a panel is lacking. We evaluated whether an immunohistochemical marker panel could reliably assess endometrioid endometrial cancer (EEC) outcome independent of clinicopathological information. Methods: A cohort of 306 EEC specimens was profiled using tissue microarray (TMA). Cost- and time-efficient immunohistochemical analysis of well-established tissue biomarkers (ER, PR, HER2, Ki-67, MLH1 and p53) and two new biomarkers (L1CAM and ASRGL1) was carried out. Statistical modelling with embedded variable selection was applied on the staining results to identify minimal prognostic panels with maximal prognostic accuracy without compromising generalizability. Results: A panel including p53 and ASRGL1 immunohistochemistry was identified as the most accurate predictor of relapse-free and disease-specific survival. Within this panel, patients were allocated into high- (5.9%), intermediate- (29.5%) and low- (64.6%) risk groups where high-risk patients had a 30-fold risk (P < 0.001) of dying of EEC compared to the low-risk group. Conclusions: P53 and ASRGL1 immunoprofiling stratifies EEC patients into three risk groups with significantly different outcomes. This simple and easily applicable panel could provide a useful tool in EEC risk stratification and guiding the allocation of treatment modalities.
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| 2. |
- Li, Xiangyu, et al.
(författare)
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Classification of clear cell renal cell carcinoma based on PKM alternative splicing
- 2020
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Ingår i: Heliyon. - : Elsevier BV. - 2405-8440. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- Clear cell renal cell carcinoma (ccRCC) accounts for 70-80% of kidney cancer diagnoses and displays high molecular and histologic heterogeneity. Hence, it is necessary to reveal the underlying molecular mechanisms involved in progression of ccRCC to better stratify the patients and design effective treatment strategies. Here, we analyzed the survival outcome of ccRCC patients as a consequence of the differential expression of four transcript isoforms of the pyruvate kinase muscle type (PKM). We first extracted a classification biomarker consisting of eight gene pairs whose within-sample relative expression orderings (REOs) could be used to robustly classify the patients into two groups with distinct molecular characteristics and survival outcomes. Next, we validated our findings in a validation cohort and an independent Japanese ccRCC cohort. We finally performed drug repositioning analysis based on transcriptomic expression profiles of drug-perturbed cancer cell lines and proposed that paracetamol, nizatidine, dimethadione and conessine can be repurposed to treat the patients in one of the subtype of ccRCC whereas chenodeoxycholic acid, fenoterol and hexylcaine can be repurposed to treat the patients in the other subtype.
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| 3. |
- Li, Yanhong, et al.
(författare)
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Urinary aquaporin-2 excretion during ibuprofen or indomethacin treatment in preterm infants with patent ductus arteriosus
- 2011
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Ingår i: Acta Paediatrica. - : Wiley-Blackwell. - 0803-5253 .- 1651-2227. ; 100:1, s. 59-66
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Water channel AQP2 is the target for vasopressin (AVP) and a major determinant of urinary concentrating capacity. In mature kidneys, prostaglandins counteract the effect of AVP on AQP2 expression at functional sites. We investigated whether disturbances in water homeostasis in infants with patent ductus arteriosus (PDA) treated with prostaglandin inhibitors can be attributed to activation of AQP2. Methods: In 53 infants with symptomatic PDA (gestational age 24-33 weeks), 30 receiving ibuprofen and 23 indomethacin starting at 2-15 days of life, clinical and biochemical data were collected before treatment and after each dose of the drugs. Urinary AQP2 was determined by dot immunoblotting. Results: Urinary AQP2 level and osmolality were decreased in both groups. Urinary osmolality was overall low and correlated inversely with fluid uptake. In ibuprofen group, there was no correlation of AQP2 level with urinary osmolality. Conclusion: There was no AQP2 upregulation in the infants. The low urinary osmolality and dissociation between urinary osmolality and urinary AQP2 level indicate that the fluid retention sometimes observed in PDA infants treated with prostaglandin inhibitors is not caused by increased levels of functional AQP2. Thus, knowledge about the renal physiology of the adult cannot always be transferred to the infant kidney.
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| 4. |
- Hadimeri, Ursula, et al.
(författare)
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Fistula diameter correlates with echocardiographic characteristics in stable hemodialysis patients
- 2015
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Ingår i: NEPHROLOGY @ POINT OF CARE. - : Wichtig Publishing. - 2059-3007. ; 1:1, s. E44-E48
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Tidskriftsartikel (refereegranskat)abstract
- Aims and background: Left ventricular hypertrophy (LVH) is a common finding in hemodialysis patients. The aim of the present study was to investigate if the diameter of the distal radiocephalic fistula could influence left ventricular variables in stable hemodialysis patients.Methods: Nineteen patients were investigated. Measurements of the diameter of the arteriovenous (AV) fistula were performed in 4 different locations. The patients were investigated using M-mode recordings and measurements in the 2D image. Doppler ultrasound was also performed. Transonic measurements were performed after ultrasound investigation.Results: Fistula mean and maximal diameter correlated with left ventricular characteristics. Fistula flow correlated neither with the left ventricular characteristics nor with fistula diameters.Conclusions: The maximal diameter of the distal AV fistula seems to be a sensitive marker of LVH in stable hemodialysis patients.
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| 5. |
- Glimelius, Bengt, et al.
(författare)
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U-CAN : a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.
- 2018
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 57:2, s. 187-194
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Tidskriftsartikel (refereegranskat)abstract
- Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.
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| 6. |
- Hayashi, Shirley Yumi, et al.
(författare)
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Left ventricular mechanical dyssynchrony in patients with different stages of chronic kidney disease and the effects of hemodialysis
- 2013
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Ingår i: Hemodialysis International. - : Wiley-Blackwell. - 1492-7535 .- 1542-4758. ; 17:3, s. 346-358
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Tidskriftsartikel (refereegranskat)abstract
- Left ventricular (LV) dyssynchrony is a known cause of mortality in patients with heart failure and may possibly play a similar role in patients with chronic kidney disease (CKD) in whom sudden death is one of the most common and as yet not fully explained cause of death. LV synchronicity and its relationship with increased volume load and various biomarkers was analyzed in 145 patients including 53 patients with CKD stages 3 and 4 and in 92 CKD stage 5 patients undergoing hemodialysis (HD) or peritoneal dialysis (PD) using color tissue Doppler imaging and tissue synchronization imaging. The HD patients were evaluated both before and after a single HD session. LV dyssynchrony was defined as a regional difference in time to peak systolic myocardial velocity, between 12 LV segments>105milliseconds. LV dyssynchrony was present in 54% of the patients with no difference between CKD 3 and 4 (58%), HD (48%), and PD (51%). LV dyssynchrony was independently associated with LV mass index and increased estimation of LV end-diastolic pressure. A single HD session resulted in significant changes in LV synchronicity variableswith improvement in 50% of the patientsespecially in patients with higher myocardial systolic velocities and lower LV mass index. Abnormalities in LV synchronicity are highly prevalent in CKD patients already prior to dialysis treatment and are associated with LV hypertrophy, LV dysfunction and load conditions, underlining the importance of volume status for LV synchronicity in CKD patients.
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| 7. |
- Liu, Hanxiao, et al.
(författare)
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Rollout approach to sensor scheduling for remote state estimation under integrity attack
- 2022
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Ingår i: Automatica. - : Elsevier BV. - 0005-1098 .- 1873-2836. ; 144
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Tidskriftsartikel (refereegranskat)abstract
- We consider the sensor scheduling problem for remote state estimation under integrity attacks. We seek to optimize a trade-off between the energy consumption of communications and the state estimation error covariance when the acknowledgment (ACK) information, sent by the remote estimator to the local sensor, is compromised. The sensor scheduling problem is formulated as an infinite horizon discounted optimal control problem with infinite states. We first analyze the underlying Markov decision process (MDP) and show that the optimal scheduling without ACK attack is of the threshold type. Thus, we can simplify the problem by replacing the original state space with a finite state space. For the simplified MDP, when the ACK is under attack, the problem is modeled as a partially observable Markov decision process (POMDP). We analyze the induced MDP that uses a belief vector as its state for the POMDP. We investigate the properties of the exact optimal solution via contractive models and show that the threshold type of solution for the POMDP cannot be readily obtained. A suboptimal solution is then obtained via a rollout approach, which is a prominent class of reinforcement learning (RL) methods based on approximation in value space. We present two variants of rollout and provide performance bounds of those variants. Finally, numerical examples are used to demonstrate the effectiveness of the proposed rollout methods by comparing them with a finite history window approach that is widely used in RL for POMDP.
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| 8. |
- Vieux, Rachel, et al.
(författare)
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The renal adverse effects of ibuprofen are not mediated by AQP2 water channels
- 2010
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Ingår i: Pediatric nephrology (Berlin, West). - : Springer Science and Business Media LLC. - 0931-041X .- 1432-198X. ; 25:7, s. 1277-1284
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to determine (1) whether ibuprofen treatment in very preterm infants causes an increase in the renal water channel aquaporin-2 (AQP2) activity in the collecting duct via prostaglandin synthesis inhibition and (2) whether AQP2 activity remains disturbed long after ibuprofen treatment has ended. This was a prospective study involving premature infants with a gestation age of 27-31 weeks who received treatment between December 2005 and August 2006 in a tertiary Neonatal Intensive Care Unit. Each ibuprofen-treated infant was matched to two controls. Renal glomerular and tubular function were evaluated weekly for 1 month, and urinary AQP2 was measured by immuno-dotting. In total, 166 longitudinal samples were analyzed in 36 infants. Median [interquartile range] gestational age and birthweight were 28 [27.0-29.5] weeks and 1160 [1041-1242] g, respectively. Perinatal factors were similar in both groups. Urine output was significantly decreased in the ibuprofen-treated infants during the treatment. The urinary AQP2 level decreased significantly from day 2 to day 7 in both groups and was similar thereafter for the first month of life in ibuprofen-treated and control groups. Based on our results, we conclude that ibuprofen-induced oligo-anuria is not associated with a change in AQP2 activity and that ibuprofen does not affect AQP2 activity during the first month of life in very preterm neonates.
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| 9. |
- Wollenhaupt, Julia, et al.
(författare)
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Pro-oxidative priming but maintained cardiac function in a broad spectrum of murine models of chronic kidney disease
- 2022
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Ingår i: Redox Biology. - : Elsevier BV. - 2213-2317. ; 56
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Patients with chronic kidney disease (CKD) have an increased risk of cardiovascular events and exhibit myocardial changes including left ventricular (LV) hypertrophy and fibrosis, overall referred to as 'uremic cardiomyopathy'. Although different CKD animal models have been studied for cardiac effects, lack of consistent reporting on cardiac function and pathology complicates clear comparison of these models. Therefore, this study aimed at a systematic and comprehensive comparison of cardiac function and cardiac pathophysiological characteristics in eight different CKD models and mouse strains, with a main focus on adenine-induced CKD. Methods and results: CKD of different severity and duration was induced by subtotal nephrectomy or adenine-rich diet in various strains (C57BL/6J, C57BL/6 N, hyperlipidemic C57BL/6J ApoE(-/-), 129/Sv), followed by the analysis of kidney function and morphology, blood pressure, cardiac function, cardiac hypertrophy, fibrosis, myocardial calcification and inflammation using functional, histological and molecular techniques, including cardiac gene expression profiling supplemented by oxidative stress analysis. Intriguingly, despite uremia of variable degree, neither cardiac dysfunction, hypertrophy nor interstitial fibrosis were observed. However, already moderate CKD altered cardiac oxidative stress responses and enhanced oxidative stress markers in each mouse strain, with cardiac RNA sequencing revealing activation of oxidative stress signaling as well as anti-inflammatory feedback responses. Conclusion: This study considerably expands the knowledge on strain-and protocol-specific differences in the field of cardiorenal research and reveals that several weeks of at least moderate experimental CKD increase oxidative stress responses in the heart in a broad spectrum of mouse models. However, this was insufficient to induce relevant systolic or diastolic dysfunction, suggesting that additional "hits " are required to induce uremic cardiomyopathy. Translational perspective: Patients with chronic kidney disease (CKD) have an increased risk of cardiovascular adverse events and exhibit myocardial changes, overall referred to as 'uremic cardiomyopathy'. We revealed that CKD increases cardiac oxidative stress responses in the heart. Nonetheless, several weeks of at least moderate experimental CKD do not necessarily trigger cardiac dysfunction and remodeling, suggesting that additional "hits " are required to induce uremic cardiomyopathy in the clinical setting. Whether the altered cardiac oxidative stress balance in CKD may increase the risk and extent of cardiovascular damage upon additional cardiovascular risk factors and/or events will be addressed in future studies.
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| 10. |
- Zelenina, Marina, et al.
(författare)
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Urinary aquaporin-2 excretion during early human development
- 2006
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Ingår i: Pediatric nephrology (Berlin, West). - : Springer Science and Business Media LLC. - 0931-041X .- 1432-198X. ; 21:7, s. 947-952
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Tidskriftsartikel (refereegranskat)abstract
- This study was undertaken to assess one of the determinants of kidney concentrating capacity, aquaporin-2 (AQP2), in order to understand the physiopathology of water balance in newborn babies. Urinary AQP2 excretion has been shown to be proportional to AQP2 level in the apical plasma membrane of the kidney collecting ducts and has been suggested as a marker of vasopressin (AVP) action. Urinary AQP2 excretion in the early postnatal period and at 3 weeks of age was measured in 123 neonates admitted during a 6-month period to the neonatal intensive care unit of the Children's Hospital of Toulouse, France. Clinical and biochemical data were collected for each child. During the first days after birth, higher urinary AQP2 was observed in boys than in girls (P=0.01) and positively correlated with urinary sodium/potassium (Na/K) ratio (r=0.33, P=0.01). When the babies had reached 3 weeks of age, urinary AQP2 was proportional to the gestational age at birth (r=0.33, P=0.0068) and daily weight gain (r=0.36, P=0.003). It did not correlate with urinary osmolality, which was overall very low in all babies. Urinary AQP2 was decreased in conditions of impaired renal function (r=-0.42, P=0.0005) and acidosis (P=0.03). Prenatal corticosteroid treatment had no significant impact on urinary AQP2 level. Our data show that urinary AQP2 correlates with the overall maturity of tubular function in human neonates. In babies at this early age, urinary AQP2 cannot serve as a direct marker of the renal action of AVP but reflects AQP2 expression level associated with different physiopathological conditions.
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