358 results match your criteria: "Center for Clinical Research Dalarna - Uppsala university[Affiliation]"

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

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Associations between genetic variations in oxytocin pathway genes and hippocampal volume: Insights from the UK Biobank.

Cortex

December 2024

Department of Psychology, Stockholm University, Stockholm, Sweden; Stockholm University Brain Imaging Centre (SUBIC), Stockholm, Sweden; Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden. Electronic address:

The role of oxytocin-related genes in social-cognitive function has been previously established, but structural brain mechanisms underlying this link remain poorly understood. Utilizing a substantial dataset from the UK Biobank (N ≈ 30,000), this research determined associations between variations in ten single nucleotide polymorphisms (SNPs) within three oxytocin pathway genes (i.e.

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Schizophrenia (SCZ), bipolar (BD) and major depression disorder (MDD) are severe psychiatric disorders that are challenging to treat, often leading to treatment resistance (TR). It is crucial to develop effective methods to identify and treat patients at risk of TR at an early stage in a personalized manner, considering their biological basis, their clinical and psychosocial characteristics. Effective translation of theoretical knowledge into clinical practice is essential for achieving this goal.

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Article Synopsis
  • The study explored how levels of omega-3 and omega-6 polyunsaturated fatty acids (PUFA) in the blood affect the risk of developing allergic diseases, like rhinitis, from childhood through young adulthood.
  • The research involved 933 participants from the BAMSE cohort, analyzing PUFA levels at ages 8 and 16, and assessing their association with allergic reactions by age 24.
  • Findings indicated that higher levels of certain PUFA, particularly omega-3 and arachidonic acid, at age 8 were linked to lower risks of rhinitis and allergic sensitization; however, these relationships might be influenced by pre-existing conditions in childhood rather than new cases that develop later.
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  • The study investigates the effectiveness of a new implant called the DynamX bioadaptor compared to a traditional drug-eluting stent (DES) in improving outcomes for patients undergoing percutaneous coronary intervention (PCI) due to heart disease.
  • Conducted across 20 hospitals in Sweden, the study randomly assigned eligible patients aged 18-85 to receive either the bioadaptor or a zotarolimus-eluting DES, measuring outcomes such as target lesion failure after 12 months.
  • The primary goal is to ensure the new device is not worse than the DES by measuring specific heart-related adverse events and ensuring that the risk difference remains within a predefined limit, indicating safety and efficacy.
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The Expression of Vitamin D Receptor on Peripheral Blood Mononuclear Cells in Patients with Psoriasis.

Int J Mol Sci

October 2024

Department of Dermatology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden.

Vitamin D plays an important role in psoriasis, but its involvement in pathogenesis remains unclear. This study aimed to evaluate vitamin D receptor (VDR) expression on peripheral blood mononuclear cells (PBMCs) in patients with psoriasis and healthy controls and to study the effects of the Etanercept treatment on VDR expression on PBMCs in patients with psoriasis. Twenty patients with moderate to severe psoriasis received treatment with Etanercept for 24 weeks.

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Article Synopsis
  • Lipid content in nonobstructive coronary lesions can lead to poor clinical outcomes, particularly in relation to complications after stenting during percutaneous coronary intervention (PCI).
  • A study using near-infrared spectroscopy and intravascular ultrasound evaluated the relationship between lipid levels and major adverse cardiac events (MACE) in patients who underwent PCI for myocardial infarction.
  • Findings showed that high lipid levels and plaque burden at stent edges increased the risk of stent edge-related MACE, while pre- and post-PCI lipid content did not correlate with in-stent MACE.
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Long-Term Oxygen Therapy for 24 or 15 Hours per Day in Severe Hypoxemia.

N Engl J Med

September 2024

From Respiratory Medicine, Allergology, and Palliative Medicine, Department of Clinical Sciences in Lund, Faculty of Medicine, Lund University, Lund (M.E., F.B.), the Department of Medicine, Blekinge Hospital, Karlskrona (M.E.), the COPD Center, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg (A.A.), and the Department of Respiratory Medicine and Allergology, Sahlgrenska University Hospital (S.P.), Gothenburg, Karlstad County Hospital, Karlstad (T.K.), Northern Älvsborg County Hospital, Trollhättan (B.P.), Linköping University Hospital, Linköping (O.K.), Falun Hospital, Falun (P.S.), the Department of Respiratory Medicine and Allergology, Faculty of Medicine, Karolinska University Hospital (M.R.), and Karolinska University Hospital Huddinge (R.H.), Stockholm, the Department of Medical Sciences, Respiratory, Allergy, and Sleep Research, Uppsala University (A.P., E.L., C.J.), and the Uppsala Clinical Research Center (N.H.), Uppsala, the Center for Research and Development, Gävle Hospital, Gävle (A.P.), the Department of Public Health and Clinical Medicine, Umeå University, Umeå (A.B.), Sundsvall-Härnösand County Hospital, Sundsvall (B.S.), and the Department of Respiratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro (J.S.) - all in Sweden; the Institute for Breathing and Sleep and the Department of Respiratory and Sleep Medicine, Austin Health, Melbourne, VIC (C.F.M.), and the Graduate School of Medicine, Faculty of Science, Medicine, and Health, University of Wollongong, Wollongong, NSW (D.C.C.) - both in Australia.

Background: Long-term oxygen supplementation for at least 15 hours per day prolongs survival among patients with severe hypoxemia. On the basis of a nonrandomized comparison, long-term oxygen therapy has been recommended to be used for 24 hours per day, a more burdensome regimen.

Methods: To test the hypothesis that long-term oxygen therapy used for 24 hours per day does not result in a lower risk of hospitalization or death at 1 year than therapy for 15 hours per day, we conducted a multicenter, registry-based, randomized, controlled trial involving patients who were starting oxygen therapy for chronic, severe hypoxemia at rest.

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Background And Aims: The optimal antithrombotic therapy in patients with device-detected atrial fibrillation (DDAF) is unknown. Concomitant vascular disease can modify the benefits and risks of anticoagulation.

Methods: These pre-specified analyses of the NOAH-AFNET 6 (n = 2534 patients) and ARTESiA (n = 4012 patients) trials compared anticoagulation with no anticoagulation in patients with DDAF with or without vascular disease, defined as prior stroke/transient ischaemic attack, coronary or peripheral artery disease.

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Oxytocin pathway gene variation and corticostriatal resting-state functional connectivity.

Compr Psychoneuroendocrinol

November 2024

Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, BMC, Husargatan 3, 75124, Uppsala, Sweden.

Genetic variations in single nucleotide polymorphisms (SNPs) within oxytocin pathway genes have been linked to social behavior and neurodevelopmental conditions. However, the neurobiological mechanisms underlying these associations remain elusive. In this study, we investigated the relationship between variations of 10 SNPs in oxytocin pathway genes and resting-state functional connectivity among 55 independent components using a large sample from the UK Biobank (N ≈ 30,000).

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Vitamin D plays a role in inflammatory skin disease, but the exact mechanisms and the clinical significance remain unclear. According to the free hormone hypothesis, it is the free concentration of 25-hydroxy vitamin D (25(OH)D) that is biologically active. Vitamin D-binding protein (DBP) acts as the major transporter of vitamin D in the circulation, and DBP concentration defines the free 25(OH)D levels.

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The most widely used conditioning regimens in autologous haematopoietic stem cell transplantation (ASCT) for multiple sclerosis (MS) are BEAM with anti-thymocyte globulin (ATG) and high-dose cyclophosphamide with ATG (Cy/ATG). In this retrospective study, we compare efficacy and safety of these regimens when used for relapsing-remitting MS. We assessed 231 patients treated in Sweden before January 1, 2020.

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Treatment regimens for post-kala-azar dermal leishmaniasis (PKDL) are usually extrapolated from those for visceral leishmaniasis (VL), but drug pharmacokinetics (PK) can differ due to disease-specific variations in absorption, distribution, and elimination. This study characterized PK differences in paromomycin and miltefosine between 109 PKDL and 264 VL patients from Eastern Africa. VL patients showed 0.

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Unveiling the therapeutic potential of Taxifolin in Cancer: From molecular mechanisms to immune modulation and synergistic combinations.

Phytomedicine

October 2024

Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates; College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates. Electronic address:

Article Synopsis
  • - Taxifolin (TAX), a natural flavonoid found in medicinal plants, shows potential in cancer therapy by inhibiting tumor growth and enhancing the effectiveness of traditional chemotherapy through various biological mechanisms.
  • - The review analyzes TAX’s antitumor mechanisms, its synergistic effects with chemotherapeutic agents, and its ability to protect cells from chemotherapy-related toxicities, while also exploring its safety and pharmacokinetic challenges.
  • - Research indicates that TAX can block tumor cell proliferation and invasion by targeting specific pathways, and it also has a beneficial role in improving immune responses against tumors, potentially enhancing the effectiveness of immune therapies.
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Background: Modern drug-eluting stents have seen significant improvements, yet still create a rigid cage within the coronary artery. There is a 2% to 4% annual incidence of target lesion failure (TLF) beyond 1 year, and half of the patients experience angina after 5 years. The DynamX bioadaptor is a sirolimus-eluting, thin (71 µm) cobalt-chromium platform with helical strands that unlock and separate after in vivo degradation of the bioresorbable polymer coating.

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Problem: Preterm birth (PTB) is a leading cause of infant mortality and morbidity. The pathogenesis of PTB is complex and involves many factors, including socioeconomy, inflammation and infection. Asymmetric dimethylarginine, ADMA and symmetric dimethylarginine, SDMA are involved in labor as inhibitors of nitric oxide, a known relaxant of the uterine smooth muscles.

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Conjugated hyperbilirubinemia associated with accidental rifapentine overdose.

Int J Tuberc Lung Dis

July 2024

Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital and Trauma Center, University of California, San Francisco (UCSF), San Francisco, CA, USA.

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Background: Selenoprotein P (SELENOP) transports selenium to extrahepatic tissues and is a biomarker of selenium status. Low soil selenium leads to low dietary selenium intake. A consequence is an increased risk of cardiovascular disease.

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The presence of periodontal pathogens is associated with an increased prevalence of rheumatoid arthritis (RA). The systemic antibody response to epitopes of these bacteria is often used as a proxy to study correlations between bacteria and RA. The primary aim of the present study is to examine the correlation between the presence of (Aa) in the oral cavity and serum antibodies against the leukotoxin (LtxA) produced by this bacterium.

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Background: Motor neuron disease is a progressive, fatal neurodegenerative disease for which there is no cure. Acceptance and Commitment Therapy (ACT) is a psychological therapy incorporating acceptance, mindfulness, and behaviour change techniques. We aimed to evaluate the effectiveness of ACT plus usual care, compared with usual care alone, for improving quality of life in people with motor neuron disease.

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Introduction: Post-kala-azar dermal leishmaniasis (PKDL) arises as a dermal complication following a visceral leishmaniasis (VL) infection. Current treatment options for PKDL are unsatisfactory, and there is a knowledge gap regarding the distribution of antileishmanial compounds within human skin. The present study investigated the skin distribution of miltefosine in PKDL patients, with the aim to improve the understanding of the pharmacokinetics at the skin target site in PKDL.

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Background: Selenium-dependent deiodinases play a central role in thyroid hormone regulation and metabolism. In many European countries, insufficient selenium intake may consequently lead to adverse effects on thyroid function. In this randomised placebo-controlled double-blind study, we examined the effect of supplementation with selenium and coenzyme Q on thyroid hormonal status, cardiovascular (CV) mortality and health-related quality of life (Hr-QoL).

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Genome-wide association study identifies 30 obsessive-compulsive disorder associated loci.

medRxiv

March 2024

Department of Community Health and Epidemiology and Faculty of Computer Science, Dalhousie University, Halifax, NS, Canada.

Article Synopsis
  • Obsessive-compulsive disorder (OCD) affects about 1% of people and has a strong genetic component, but previous studies have not fully explained its genetic causes or biological mechanisms.
  • A large genome-wide association study (GWAS) analyzed data from over 53,000 OCD cases and over 2 million control participants, identifying 30 significant genetic markers related to OCD and suggesting a 6.7% heritability from SNPs.
  • The research also found 249 candidate risk genes linked to OCD, particularly in specific brain regions, and showed genetic correlations with various psychiatric disorders, laying the groundwork for further studies and potential treatments.
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  • The study investigates how pre-biologic biomarker levels, specifically immunoglobulin E (IgE), blood eosinophil count (BEC), and fractional exhaled nitric oxide (FeNO), influence asthma treatment outcomes when patients start biologic therapy.
  • Conducted across 23 countries with over 3750 patients, the research focused on changes in exacerbation rates, symptom control, and lung function about a year after starting treatment.
  • Results showed that higher levels of BEC and FeNO were linked to significant improvements in lung function for specific biologic therapies, while IgE was not a strong predictor of treatment effectiveness.
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