Cooperation in the Immune System Genetic studies of plant immunity have been tremendously influenced by Flor's gene-for-gene hypothesis, which posits that a single host resistance gene is matched by ...a single effector gene from a specific pathogen strain. Important goals for the future are, therefore, to better understand how the inherent trade-off between growth or fertility and immunity is managed in natural populations, to find out whether one can extrapolate from findings in A. thaliana to other species, and to test whether lessons from wild plants such as A. thaliana can be useful in crop breeding.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The mechanisms of action of and resistance to trastuzumab deruxtecan (T-DXd), an anti-HER2–drug conjugate for breast cancer treatment, remain unclear. The phase 2 DAISY trial evaluated the efficacy ...of T-DXd in patients with HER2-overexpressing ( n = 72, cohort 1), HER2-low ( n = 74, cohort 2) and HER2 non-expressing ( n = 40, cohort 3) metastatic breast cancer. In the full analysis set population ( n = 177), the confirmed objective response rate (primary endpoint) was 70.6% (95% confidence interval (CI) 58.3–81) in cohort 1, 37.5% (95% CI 26.4–49.7) in cohort 2 and 29.7% (95% CI 15.9–47) in cohort 3. The primary endpoint was met in cohorts 1 and 2. Secondary endpoints included safety. No new safety signals were observed. During treatment, HER2-expressing tumors ( n = 4) presented strong T-DXd staining. Conversely, HER2 immunohistochemistry 0 samples ( n = 3) presented no or very few T-DXd staining (Pearson correlation coefficient r = 0.75, P = 0.053). Among patients with HER2 immunohistochemistry 0 metastatic breast cancer, 5 of 14 (35.7%, 95% CI 12.8–64.9) with ERBB2 expression below the median presented a confirmed objective response as compared to 3 of 10 (30%, 95% CI 6.7–65.2) with ERBB2 expression above the median. Although HER2 expression is a determinant of T-DXd efficacy, our study suggests that additional mechanisms may also be involved. (ClinicalTrials.gov identifier NCT04132960 .)
Higher dietary fibre intakes are associated with a reduced risk of developing cardiovascular disease (CVD), and increasing intake has been shown to reduce blood pressure and other cardiometabolic ...risk factors. The extent to which dietary fibre can further reduce risk for those with CVD and treated with cardioprotective drugs has not been clearly established. We have examined the evidence for dietary fibre as adjunct therapy in those with CVD or hypertension.
Ovid MEDLINE, Embase, PubMed, and CENTRAL were searched to June 2021. Prospective observational studies reporting on fibre intakes and mortality in those with pre-existing CVD and controlled trials of increasing fibre intakes on cardiometabolic risk factors in those with CVD or hypertension were eligible. Outcomes were mortality (studies) and cardiometabolic risk factors (trials). Data synthesis was with random effects and dose response. Certainty of evidence was assessed using GRADE.
Three prospective studies including 7469 adults with CVD, and 12 trials of 878 adults with CVD or hypertension were identified. Moderate certainty evidence indicates reduced all-cause mortality (relative risk, RR0.75 (95% confidence interval, CI 0.58-0.97)) when comparing higher with lower fibre intakes. Low certainty evidence from trials of adults with cardiovascular disease indicates increasing fibre intakes reduced total (mean difference, MD - 0.42 mmol/L (95%CI - 0.78 to - 0.05) and low-density lipoprotein (LDL) cholesterol (MD - 0.47mmol/L (95%CI - 0.85 to - 0.10)). High certainty evidence from trials of adults with hypertension indicates increasing fibre intakes reduces systolic (MD 4.3 mmHg (95% CI 2.2 to 5.8)) and diastolic blood pressure (MD 3.1 mmHg (95% CI 1.7 to 4.4)). Moderate and low certainty evidence indicated improvements in fasting blood glucose (MD 0.48 mmol/L (- 0.91 to - 0.05)) and LDL cholesterol (MD 0.29 mmol/L (95% CI 0.17 to 0.40)). Benefits were observed irrespective of cardioprotective drug use.
These findings emphasise the likely benefits of promoting greater dietary fibre intakes for patients with CVD and hypertension. Further trials and cohort analyses in this area would increase confidence in these results.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
When independently evolved immune receptor variants meet in hybrid plants, they can activate immune signaling in the absence of non-self recognition. Such autoimmune risk alleles have recurrently ...evolved at the DANGEROUS MIX2 (DM2) nucleotide-binding domain and leucine-rich repeat (NLR)-encoding locus in A. thaliana. One of these activates signaling in the presence of a particular variant encoded at another NLR locus, DM1. We show that the risk variants of DM1 and DM2d NLRs signal through the same pathway that is activated when plant NLRs recognize non-self elicitors. This requires the P loops of each protein and Toll/interleukin-1 receptor (TIR)-domain-mediated heteromeric association of DM1 and DM2d. DM1 and DM2d each resides in a multimeric complex in the absence of signaling, with the DM1 complex shifting to higher molecular weight when heteromerizing DM2 variants are present. The activation of the DM1 complex appears to be sensitive to the conformation of the heteromerizing DM2 variant. Autoimmunity triggered by interaction of this NLR pair thus suggests that activity of heteromeric NLR signaling complexes depends on the sum of activation potentials of partner NLRs.
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•Two unlinked plant NLRs physically interact to trigger autoimmunity•The N-terminal TIR domains mediate heteromeric NLR association•NLR multimerization is not sufficient for signaling
Mismatched combinations of plant immune proteins can trigger autoimmunity in hybrids. Tran, Chung et al. report that a pair of NLR immune receptor variants, encoded by unlinked loci, triggers autoimmunity through heteromeric association. Signaling activity of the NLR complex depends on the sum of activation potentials of individual partner NLRs.
Abstract
Aims
This research aimed to assess the rate and reliability of routine nurse‐completed malnutrition screening and report the prevalence of malnutrition risk on admission to Christchurch ...Hospital.
Methods
Student dietitians administered the Malnutrition Screening Tool to patients in three speciality wards within 48 h of admission. Student dietitians' Malnutrition Screening Tool scores were compared against documented nurse‐completed Malnutrition Screening Tool scores. Data were analysed using descriptive statistics, Fisher's exact test, and Cohen's kappa tests (interrater reliability
ⱪ
). A
p
‐value <0.05 was considered statistically significant.
Results
Student dietitians, using the Malnutrition Screening Tool, screened 360 (96%) of 377 eligible patients while nurses screened 332 (88%) patients. Student dietitians and nurses screened 119 patients (33%) and 63 patients (18%) respectively at risk of malnutrition. There was fair agreement (
ⱪ
= 0.311) in Malnutrition Screening Tool total scores between nurses and student dietitians. There was a significant difference in the proportion of patients screened at risk of malnutrition between nurses and student dietitians (
p
< 0.0001).
Conclusion
Malnutrition risk remains high in acute care settings. Nurses were less likely to screen patients as at risk of malnutrition than student dietitians. Regular support and training in using Malnutrition Screening Tool may help improve the rate and reliability of routine malnutrition screening.
Background
Numerous inclusion and exclusion criteria are involved in phase III moderate to severe psoriasis trials investigating the safety and efficacy of biologics. This questions the ...generalization of results.
Methods
In this cohort study, we applied inclusion/exclusion criteria for phase III trials from original protocols (adalimumab – REVEAL, ustekinumab – PHOENIX, brodalumab – AMAGINE, secukinumab FIXTURE) to all patients enrolled in the PsoBioTeq prospective registry who received a biological agent for the first time between July 2012 and November 2017. We then compared the efficacy, drug survival and occurrence of adverse events between patients who satisfied/did not satisfy the eligibility criteria for these phase III trials.
Results
A total of 1267 patients were enrolled, of whom 993 (78.4%) were not eligible for at least one RCT (randomized controlled trial) and 251 (19.1%) did not meet the PASI/PGA severity requirements. Apart from disease severity, the most frequent criteria resulting in exclusion were as follows: non‐plaque psoriasis (12.6%), significant cardiac disease (8.4%), significant liver disease (7.3%), elevated liver enzymes (4.9–9.6%) and personal history of diabetes (9.2%). There was no difference in drug survival between the two groups. The incidence ratio of adverse events was significantly lower in eligible versus non‐eligible patients 0.78 (95% CI 0.62–0.97) (P = 0.03).
Conclusion
The majority of patients treated with biologics in the PsoBioTeq real‐life registry would not have been eligible for phase III moderate to severe psoriasis trials. Patients not eligible for psoriasis phase III clinical trials have a higher incidence of adverse events.
Through the lens of evolution, climate change is an agent of natural selection that forces populations to change and adapt, or face extinction. However, current assessments of the risk of ...biodiversity associated with climate change
do not typically take into account how natural selection influences populations differently depending on their genetic makeup
. Here we make use of the extensive genome information that is available for Arabidopsis thaliana and measure how manipulation of the amount of rainfall affected the fitness of 517 natural Arabidopsis lines that were grown in Spain and Germany. This allowed us to directly infer selection along the genome
. Natural selection was particularly strong in the hot-dry location in Spain, where 63% of lines were killed and where natural selection substantially changed the frequency of approximately 5% of all genome-wide variants. A significant portion of this climate-driven natural selection of variants was predictable from signatures of local adaptation (R
= 29-52%), as genetic variants that were found in geographical areas with climates more similar to the experimental sites were positively selected. Field-validated predictions across the species range indicated that Mediterranean and western Siberian populations-at the edges of the environmental limits of this species-currently experience the strongest climate-driven selection. With more frequent droughts and rising temperatures in Europe
, we forecast an increase in directional natural selection moving northwards from the southern end of Europe, putting many native A. thaliana populations at evolutionary risk.
The purpose of the study was to examine the occurrence of metritis on reproduction of beef cows. A total of 2,962 cows were examined, and samples were collected from those displaying clinical ...symptoms of bovine metritis for bacterial analysis. Bacterial species identification was performed using culture and PCR techniques. The findings revealed that bovine metritis affected 5.5% of the reproductive cow population with the presence of Streptococcus spp., Staphylococcus aureus, Escherichia coli, and Salmonella spp. at the rates of 87.7%, 61.1%, 59.9% and 17.3%, respectively. The results also demonstrated that Streptococcus spp. was the most prevalent group, while Salmonella spp. had the lowest prevalence across different breeds and litters. However, in the Limousin crossbred cows, the infection rate of E. coli surpassed that of the other bacteria and a significantly higher infection rate for E. coli was observed in litter 4 and litter ≥6 compared to the others. The disk diffusion method was utilized to assess antibiotic resistance patterns of the isolated bacteria. Among the bacteria, marbofloxacin exhibited the lowest prevalence of antibiotic resistance (16.9%), while doxycycline had the highest prevalence (82.2%). All cows recovered from the disease within 3-5 days of treatment, and all of them resumed estrus in the subsequent reproductive cycle. The pregnancy rate ranged from 66.7% to 80.0% for the first insemination in the next reproductive cycle.
The extremes of lighting (e.g. too much or too little light) usually cause many troubles for machine and human vision. Many recent works have mainly focused on under-exposure cases where images are ...often captured in low-light conditions (e.g. nighttime) and achieved promising results for enhancing the quality of images. However, they are inferior to handling images under over-exposure. To mitigate this limitation, we propose a novel unsupervised enhancement framework which is robust against various lighting conditions while does not require any well-exposed images to serve as the ground-truths. Our main concept is to construct pseudo-ground-truth images synthesized from multiple source images that simulate all potential exposure scenarios to train the enhancement network. Our extensive experiments show that the proposed approach consistently outperforms the current state-of-the-art unsupervised counterparts in several public datasets in terms of both quantitative metrics and qualitative results. Our code is available at https://github.com/VinAIResearch/PSENet-Image-Enhancement.
Objectives
Chest CT has been widely used to screen and to evaluate the severity of COVID-19 disease in the early stages of infection without severe acute respiratory syndrome, but no prospective data ...are available to study the relationship between extent of lung damage and short-term mortality. The objective was to evaluate association between standardized simple visual lung damage CT score (vldCTs) at admission, which does not require any software, and 30-day mortality.
Methods
In a single-center prospective cohort of COVID-19 patients included during 4 weeks, the presence and extent of ground glass opacities(GGO), consolidation opacities, or both of them were visually assessed in each of the 5 lung lobes (score from 0 to 4 per lobe depending on the percentage and out of 20 per patient = vldCTs) after the first chest CT performed to detect COVID-19 pneumonia.
Results
Among 210 confirmed COVID-19 patients, the number of survivors and non-survivors was 162 (77%) and 48 (23%), respectively at 30 days. vldCTs was significantly higher in non-survivors, and the AUC of vldCTs to distinguish survivors and non-survivors was 0.72 (95%CI 0.628–0.807,
p
< 0.001); the best cut-off vldCTs value was 7. During follow-up, significant differences in discharges and 30-day mortality were observed between patients with vldCTs ≥ 7 versus vldCTs < 7: (98 85.2% vs 49 51.6%;
p
< 0.001 and 36 37.9% vs 12 12.4%;
p
< 0.001, respectively. The 30-day mortality increased if vldCTs ≥ 7 (HR, 3.16 (1.50–6.43);
p
= 0.001), independent of age, respiratory rate and oxygen saturation levels, and comorbidities at admission.
Conclusions
By using chest CT in COVID-19 patients, extensive lung damage can be visually assessed with a score related to 30-day mortality independent of conventional risk factors of the disease.
Key Points
• In non-selected COVID-19 patients included prospectively during 4 weeks, the extent of ground glass opacities(GGO) and consolidation opacities evaluated by a simple visual score was related to 30-day mortality independent of age, respiratory rate, oxygen saturation levels, comorbidities, and hs-troponin I level at admission.
• This severity score should be incorporated into risk stratification algorithms and in structured chest CT reports requiring a standardized reading by radiologists in case of COVID-19.
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