Tumour-associated macrophages (TAMs) have been associated with survival in classic Hodgkin lymphoma (cHL) and other lymphoma types. The maturation and differentiation of tissue macrophages depends ...upon interactions between colony-stimulating factor 1 receptor (CSF1R) and its ligands. There remains, however, a lack of consistent information on CSF1R expression in TAMs. A new monoclonal antibody, FER216, was generated to investigate CSF1R protein distribution in formalin fixed tissue samples from 24 reactive lymphoid tissues and 187 different lymphoma types. We also analysed the distribution of CSF1R+, CD68+ and CD163+ macrophages by double immunostaining, and studied the relationship between CSF1R expression and survival in an independent series of 249 cHL patients. CSF1R+ TAMs were less frequent in B-cell lymphocytic leukaemia and lymphoblastic B-cell lymphoma than in diffuse large B-cell lymphoma, peripheral T-cell lymphoma, angioimmunoblastic T-cell lymphoma and cHL. HRS cells in cHL and, with the exception of three cases of anaplastic large cell lymphoma, the neoplastic cells in NHLs, lacked detectable CSF1R protein. A CSF1R+ enriched microenvironment in cHL was associated with shorter survival in an independent series of 249 cHL patients. CSF1R pathway activation was evident in the cHL and inactivation of this pathway could be a potential therapeutic target in cHL cases.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Infectious bursal disease virus (IBDV), a member of the Birnaviridae family, is a major avian pathogen responsible for an immunosuppressive disease affecting juvenile chickens. The IBDV genome is ...formed by two dsRNA segments. The largest one harbors two partially overlapping open reading frames encoding a non-structural polypeptide, known as VP5, and a large polyprotein, respectively. VP5 is non-essential for virus replication. However, it plays a major role in IBDV pathogenesis. VP5 accumulates at the plasma membrane (PM) of IBDV-infected cells. We have analyzed the mechanism underlying the VP5 PM targeting. Updated topological prediction algorithm servers fail to identify a transmembrane domain within the VP5 sequence. However, the VP5 polycationic C-terminal region, harboring three closely spaced patches formed by two or three consecutive basic amino acid residues (lysine or arginine), might account for its PM tropism. We have found that mutations, either C-terminal VP5 deletions or replacement of basic amino acids by alanine residues, that reduce the electropositive charge of the VP5 C-terminus abolish PM targeting. Lipid overlay assays performed with an affinity-purified Flag-tagged VP5 (FVP5) protein version show that this polypeptide binds several phosphoinositides (PIP), exhibiting a clear preference for monophosphate species. Experiments performed with FVP5 mutant proteins lacking the polycationic domain demonstrate that this region is essential for PIP binding. Data gathered with IBDV mutants expressing C-terminal deleted VP5 polypeptides generated by reverse genetics demonstrate that the VP5-PIP binding domain is required both for its PM targeting in infected cells, and for efficient virus dissemination. Data presented here lead us to hypothesize that IBDV might use a non-lytic VP5-dependent cell-to-cell spreading mechanism.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The acquisition, processing, and interpretation of thermal images from unmanned aerial vehicles (UAVs) is becoming a useful source of information for agronomic applications because of the higher ...temporal and spatial resolution of these products compared with those obtained from satellites. However, due to the low load capacity of the UAV they need to mount light, uncooled thermal cameras, where the microbolometer is not stabilized to a constant temperature. This makes the camera precision low for many applications. Additionally, the low contrast of the thermal images makes the photogrammetry process inaccurate, which result in large errors in the generation of orthoimages. In this research, we propose the use of new calibration algorithms, based on neural networks, which consider the sensor temperature and the digital response of the microbolometer as input data. In addition, we evaluate the use of the Wallis filter for improving the quality of the photogrammetry process using structure from motion software. With the proposed calibration algorithm, the measurement accuracy increased from 3.55 °C with the original camera configuration to 1.37 °C. The implementation of the Wallis filter increases the number of tie-point from 58,000 to 110,000 and decreases the total positing error from 7.1 m to 1.3 m.
Lymphoma patients with persistent disease undergoing autologous transplantation have a very poor prognosis in the rituximab era. The addition of radioimmunotherapy to the conditioning regimen may ...improve the outcome for these patients. In a prospective, phase 2 study, we evaluated the safety and efficacy of the addition of (90)Y-ibritumomab tiuxetan to the conditioning chemotherapy in patients with refractory diffuse large B-cell lymphoma. Thirty patients with induction failure (primary refractory; n=18) or refractory to salvage immunochemotherapy at relapse (n=12) were included in the study. The median age of the patients was 53 years (range, 25-67). All patients were given (90)Y-ibritumomab tiuxetan at a fixed dose of 0.4 mCi/kg (maximum dose 32 mCi) 14 days prior to the preparative chemotherapy regimen. Histological examination showed that 22 patients had de novo diffuse large B-cell lymphoma and eight had transformed diffuse large B-cell lymphoma. All patients had persistent disease at the time of transplantation, with 25 patients considered to be chemorefractory. The median time to neutrophil recovery (>500 white blood cells/μL) was 11 days (range, 9-21), while the median time to platelet recovery (>20,000 platelets/μL) was 13 days (range, 11-35). The overall response rate at day +100 was 70% (95% CI, 53.6-86.4) with 60% (95% CI, 42.5-77.5) of patients obtaining a complete response. After a median follow-up of 31 months for alive patients (range, 16-54), the estimated 3-year overall and progression-free survival rates are 63% (95% CI, 48-82) and 61% (95% CI, 45-80), respectively. We conclude that autologous transplantation with conditioning including (90)Y-ibritumomab tiuxetan is safe and results in a very high response rate with promising survival in this group of patients with refractory diffuse large B-cell lymphoma with a very poor prognosis. Study registered at European Union Drug Regulating Authorities Clinical Trials (EudraCT) N. 2007-003198-22.
Left ventricular noncompaction (LVNC) is a heterogeneous entity with uncertain prognosis.
This study sought to develop and validate a prediction model of major adverse cardiovascular events (MACE) ...and to identify LVNC cases without events during long-term follow-up.
This is a retrospective longitudinal multicenter cohort study of consecutive patients fulfilling LVNC criteria by echocardiography or cardiovascular magnetic resonance. MACE were defined as heart failure (HF), ventricular arrhythmias (VAs), systemic embolisms, or all-cause mortality.
A total of 585 patients were included (45 ± 20 years of age, 57% male). LV ejection fraction (LVEF) was 48% ± 17%, and 18% presented late gadolinium enhancement (LGE). After a median follow-up of 5.1 years, MACE occurred in 223 (38%) patients: HF in 110 (19%), VAs in 87 (15%), systemic embolisms in 18 (3%), and 34 (6%) died. LVEF was the main variable independently associated with MACE (P < 0.05). LGE was associated with HF and VAs in patients with LVEF >35% (P < 0.05). A prediction model of MACE was developed using Cox regression, composed by age, sex, electrocardiography, cardiovascular risk factors, LVEF, and family aggregation. C-index was 0.72 (95% confidence interval: 0.67-0.75) in the derivation cohort and 0.72 (95% confidence interval: 0.71-0.73) in an external validation cohort. Patients with no electrocardiogram abnormalities, LVEF ≥50%, no LGE, and negative family screening presented no MACE at follow-up.
LVNC is associated with an increased risk of heart failure and ventricular arrhythmias. LVEF is the variable most strongly associated with MACE; however, LGE confers additional risk in patients without severe systolic dysfunction. A risk prediction model is developed and validated to guide management.
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Physical restraints are associated with severe side effects and suffering. A comprehensive, person-centered, methodology was implemented in 41 Spanish nursing homes to safely eliminate restraints.
...Data were collected in 2 waves: September 2011 (at the beginning of the intervention, n = 4361) and September 2014 (n = 5051). Use of 10 different types of physical restraints was recorded, as well as frequency of psychotropic medication prescription, falls, and mortality.
Mean age was 83.4 (SD 8.5) and 63.5% of the residents had dementia. Frequency (95% confidence interval) of people having at least 1 restraint was reduced from 18.1% (17.0–19.3) to 1.6% (1.3–2.0). Use of benzodiazepines was also reduced, with no significant changes in other psychotropic medications and mortality. The rate of total falls increased from 13.1% (12.1–14.1) to 16.1% (15.1–17.1), with no significant increase in injurious falls.
Physical restraints can almost completely be eliminated with reasonable levels of safety.
Dengue has emerged as an unprecedented epidemic in Peru, and it is anticipated that this issue will escalate further owing to climate change. This study aimed to determine the risk factors associated ...with death from dengue in patients treated at Hospital II in Pucallpa, Peru. This retrospective cohort study collected information from the medical records of patients with a diagnosis of dengue treated at Hospital II Pucallpa-Peru between January 2019 and March 2023. The primary outcome was death, and the secondary outcome was death, development of severe dengue, or Intensive Care Unit (ICU) admission. Cox regression models were used to determine risk factors. The clinical records of 152 patients were evaluated, with a median age of 27.5 years (interquartile range, 11-45). Among all patients, 29 (19.1%) developed severe dengue, 31 (20.4%) were admitted to the ICU, and 13 (8.6%) died during follow-up. In the survival analysis, bilirubin >1.2 mg/dL was associated with a higher risk of death aHR: 11.38 (95% CI: 1.2 106.8). Additionally, factors associated with poor prognosis included having 1 to 3 comorbidities aRR: 1.92 (1.2 to 3.2), AST greater than or equal to251 U/L aRR: 6.79 (2.2 to 21.4), history of previous dengue aRR: 1.84 (1.0 to 3.3), and fibrinogen greater than or equal to400 mg/dL aRR: 2.23 (1.2 to 4.1). Elevated bilirubin was associated with death from dengue, whereas an increase in comorbidities and a history of previous dengue were related to a poor prognosis of the disease. Early identification of severe dengue would be more feasible with improved access to laboratory testing, particularly in tropical areas with a high dengue incidence.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Canistel (Pouteria campechiana (Kunth) Baehni; yellow sapote, canistel) is an edible fruit that is native to Mexico; the tree is used as an ornamental and medicinal plant. Descriptive studies were ...carried out with the objective of characterizing the morphology of the fruit and leaves of trees located in different regions of Mexico to select outstanding specimens for large scale reproduction. The selection of trees was carried out in three geographically neighboring areas, where visible differences have been observed in fruit morphology: size, shape, color, number of seeds, and leaf shape. Semi-ripe fruit were collected from each area, weight and measurements were noted, seeds were extracted, and a data matrix was obtained: (fruit weight (grams), fruit polar diameter (centimeters), fruit equatorial diameter (centimeters), pulp weight (grams), number of seeds, seed weight (grams), seed polar diameter (centimeters), seed equatorial diameter (centimeters), and total soluble solids (SST)). Leaves were collected at the mature stage, and an image analysis was carried out to evaluate morphometric parameters: area, perimeter, major diameter, minor diameter, circularity, solidity, and angle. An analysis of variance was performed to find significant differences in the fruit data and a principal component analysis was performed with the leaf data. In Zone 2, the fruit had three seeds, the highest weight in all the zones sampled (180 to 330 g), and the greatest amount of pulp (198.88 g); they were subglobose in shape, and 33% soluble solids. There were eight months to harvest in Zone 1 and nine months in Zone 3. The main variables in the principal component analysis were leaf area, perimeter, and minor diameter; 84.6% of the variability represented by the first three components is sufficient to explain the difference between the leaves of the three zones. This data can be used to assess the propagation of canistel in areas with favorable climatic conditions for fruiting in tropical and subtropical regions.
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