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Aims: People with a learning disability are at increased risk of becoming homeless, but little is known about how learning disability is viewed by people accessing homeless services. This study aimed to obtain the views of people experiencing homelessness about learning disability, in the context of a project that was exploring how to increase identification of learning disability. Methods: A qualitative approach was used, and 19 adults were interviewed who were receiving support from homeless services in the North-East of England. Information from the interviews was analysed using thematic analysis. Results: Four themes were identified relating to understanding of learning disability, the role of identification, day-to-day challenges, and experiences of services. Conclusion: There is a need to: promote better understanding of learning disability; for early identification processes that involve the person in a meaningful way; and the provision of support that is non-stigmatising, practical and which addresses health concerns.

Cryogenic electron microscopy (cryo-EM) is a pivotal technique for imaging macromolecular structures. However, despite extensive processing of large image sets collected in cryo-EM experiments to amplify the signal-to-noise ratio, the reconstructed 3D protein-density maps are often limited in quality due to residual noise, which in turn affects the accuracy of the macromolecular representation. Here, crefDenoiser is introduced, a denoising neural network model designed to enhance the signal in 3D cryo-EM maps produced with standard processing pipelines. The crefDenoiser model is trained without the need for `clean' ground-truth target maps. Instead, a custom dataset is employed, composed of real noisy protein half-maps sourced from the Electron Microscopy Data Bank repository. Competing with the current state-of-the-art, crefDenoiser is designed to optimize for the theoretical noise-free map during self-supervised training. We demonstrate that our model successfully amplifies the signal across a wide variety of protein maps, outperforming a classic map denoiser and following a network-based sharpening model. Without biasing the map, the proposed denoising method leads to improved visibility of protein structural features, including protein domains, secondary structure elements and modest high-resolution feature restoration.

BackgroundThere is no neoadjuvant immunotherapy for early-stage oral cancer patients. We report a single-arm, open-label, pilot clinical trial assessing the efficacy and safety of topical toll-like receptor-7 (TLR-7) agonist, imiquimod, utilized in a neoadjuvant setting in early-stage oral squamous cell carcinoma (OSCC).MethodsThe primary endpoint is reduction in tumor cell counts assessed by quantitative multiplex immunofluorescence and the immune-related pathologic response. The secondary endpoint is safety.Results60% of patients experienced a 50% reduction or greater in tumor cell count post-treatment (95% CI = 32% to 84%). Similarly, 60% of patients had immune-related major pathologic response (irMPR) with two complete pathologic responses, and 40% had partial response (PR) with the percent residual viable tumor ranging from 25% to 65%. An increase in functional helper and cytotoxic T-cells significantly contributed to a reduction in tumor (R=0.54 and 0.55, respectively). The treatment was well tolerated with the application site mucositis being the most common adverse event (grades 1-3), and no grade 4 life-threatening event. The median follow-up time was 17 months (95% CI = 16 months - not reached), and one-year recurrence-free survival was 93% of evaluable patients.ConclusionNeoadjuvant imiquimod immunotherapy could be safe and promising regimen for early-stage oral cancer.Trial registrationClinicalTrials.gov, Identifier NCT04883645.

Interest among consumers in the availability of organically produced fruits and vegetables is increasing. Seafood demand is increasingly being met by fish raised using aquaculture methods that provide fish excretory products that can meet organic standards for nutrient sources for organic vegetables. We conducted an experiment in a glass greenhouse to evaluate fish biosolids as a substrate amendment for organic tomato transplant production. We compared the fish biosolids treatment to several different organic fertilizers, along with a commonly used inorganic slow-release fertilizer (Osmocote). All treatments used a target N concentration of 400 mg/L incorporated into the substrate and we also included fish biosolids treatments of 200 and 800 mg N/L. Plant performance was monitored for 4 weeks starting with commercially available 2-week-old seedlings. The results showed that the 800 mg N/L fish biosolids treatment compared very favorably with the conventional Osmocote treatment at the conclusion of the trial. The 800 mg N/L fish biosolids treatment exceeded the Osmocote treatment for chlorophyll content and for leaf number for the first 3 weeks of the 4-week trial. Grower management protocols could further improve seedling performance by providing additional top dressings of fish biosolids or fish effluent waters as plants age.

BackgroundPD-1 and PD-L1 inhibitors have emerged as promising treatments for patients with head and neck squamous cell carcinoma (HNSCC).MethodsSystematic review and meta-analysis of PD-1 and PD-L1 inhibitors in HNSCC. Outcomes: median overall survival (mOS), median progression-free survival (mPFS), Response Evaluation Criteria in Solid Tumors (RECIST) and treatment-related adverse events (TRAEs).ResultsEleven trials reported data on 1088 patients (mean age: 59.9 years, range: 18-90). The total mOS was 7.97 months (range: 6.0-16.5). Mean mPFS for all studies was 2.84 months (range: 1.9-6.5). PD-1 inhibitors had a lower rate of RECIST Progressive Disease than PD-L1 inhibitors (42.61%, 95% confidence interval [CI]: 36.29-49.06 vs. 56.79%, 95% CI: 49.18-64.19, P

Background: We explored the accuracy of using the learning disability screening questionnaire (LDSQ) in services for people experiencing homelessness in the United Kingdom. Method: We examined the concordance between the LDSQ outcomes and assessments of intellectual disability. Seventy adults experiencing homelessness completed the LDSQ. Staff completed the LDSQ and a measure of adaptive functioning for 38 of this group. Nine participants received an intellectual assessment. Results: Sensitivity and specificity for the LDSQ when completed by staff was 83% and 96% respectively and 50% and 92% when completed by the individual. Seven people had intellectual and adaptive functioning in the intellectual disability range. Conclusion: The results suggest that the LDSQ would be an appropriate and beneficial screening tool to use within services for people experiencing homelessness. More accurate results would be likely if it were completed by staff.

PurposePatients with resected, local-regionally advanced, head and neck squamous cell carcinoma (HNSCC) have a one-year disease-free survival (DFS) rate of 65%-69% despite adjuvant (chemo)radiotherapy. Neoadjuvant PD-1 immune-checkpoint blockade (ICB) has demonstrated clinical activity, but biomarkers of response and effect on survival remain unclear.Patients and methodsEligible patients had resectable squamous cell carcinoma of the oral cavity, larynx, hypopharynx, or oropharynx (p16-negative) and clinical stage T3-T4 and/or two or more nodal metastases or clinical extracapsular nodal extension (ENE). Patients received neoadjuvant pembrolizumab 200 mg 1-3 weeks prior to surgery, were stratified by absence (intermediate-risk) or presence (high-risk) of positive margins and/or ENE, and received adjuvant radiotherapy (60-66 Gy) and concurrent pembrolizumab (every 3 weeks × 6 doses). Patients with high-risk HNSCC also received weekly, concurrent cisplatin (40 mg/m2). Primary outcome was one-year DFS. Secondary endpoints were one-year overall survival (OS) and pathologic response (PR). Safety was evaluated with CTCAE v5.0.ResultsFrom February 2016 to October 2020, 92 patients enrolled. The median age was 59 years (range, 27-80), 30% were female, 86% had stage T3-T4, and 69% had ≥N2. At a median follow-up of 28 months, one-year DFS was 97% (95% CI, 71%-90%) in the intermediate-risk group and 66% (95% CI, 55%-84%) in the high-risk group. Patients with a PR had significantly improved one-year DFS relative to patients without response (93% vs. 72%, hazard ratio 0.29; 95% CI, 11%-77%). No new safety signals were identified.ConclusionsNeoadjuvant and adjuvant pembrolizumab increased one-year DFS rate in intermediate-risk, but not high-risk, HNSCC relative to historical control. PR to neoadjuvant ICB is a promising surrogate for DFS.

Proper crop management requires rapid detection methods for abiotic and biotic stresses to ensure plant health and yield. Hemp (Cannabis sativa L.) is an emerging economically and environmentally sustainable crop capable of yielding high biomass. Nitrogen deficiency significantly reduces hemp plant growth, affecting photosynthetic capacity and ultimately decreasing yield. When symptoms of nitrogen deficiency are visible to humans, there is often already lost yield. A real-time, non-destructive detection method, such as Raman spectroscopy, is therefore critical to identify nitrogen deficiency in living hemp plant tissue for fast, precise crop remediation. A two-part experiment was conducted to investigate portable Raman spectroscopy as a viable hemp nitrogen deficiency detection method and to compare the technique’s predictive ability against a handheld SPAD (chlorophyll index) meter. Raman spectra and SPAD readings were used to train separate nitrogen deficiency discrimination models. Raman scans displayed characteristic spectral markers indicative of nitrogen deficiency corresponding to vibrational modes of carotenoids, essential pigments for photosynthesis. The Raman-based model consistently predicted nitrogen deficiency in hemp prior to the onset of visible stress symptoms across both experiments, while SPAD only differentiated nitrogen deficiency in the second experiment when the stress was more pronounced. Our findings add to the repertoire of plant stresses that hand-held Raman spectroscopy can detect by demonstrating the ability to provide assessments of nitrogen deficiency. This method can be implemented at the point of cultivation, allowing for timely interventions and efficient resource use.

One of the many challenges in running a business is cost accounting. While there are many different costing methods, there is still a need to create new ones. The aim of this article is to develop a new method of cost calculation, which is adapted to modern conditions related to the adaptation of products to the needs of customers. This article presents an original method of determining production costs, which is based on the labor consumption of products. This method is a combination and development of known methods; however, by applying more precise accounting bases, it leads to more precise results. The developed method of cost calculation, thanks to its universality, can be used in most enterprises.

Abstract Vegetation indices (VIs) are produced as a combination of different reflectance bands that are captured by multispectral images (MSIs). These indices, such as normalized difference vegetation index (NDVI), are reported to be proxy indicators of photosynthetic activity, plant canopy biomass, and leaf area index. To determine the utility of using VI derived from MSI to model plant growth, random regression (RR) models with linear splines and different orders of Legendre polynomials were applied to data collected (years 2019 and 2020) as part of the Genome‐to‐Fields initiative. Growth curves of maize (Zea mays L.) hybrids were modeled using both NDVI and cumulative NDVI (cNDVI) phenotypes. Due to the difference in MSI recording dates, and sparse overlap in hybrids between years, all the analyses were nested within a year. Results indicate that RR models using Legendre polynomials provide a robust and scalable method for modeling growth curves using phenotypes extracted from MSI; however, RR models using linear splines showed inconsistent convergence. Growth curves estimated using NDVI and cNDVI showed low‐to‐moderate heritability (0.11–0.44) and a range of genetic correlations (−0.15 to 0.97) with grain yield. This study demonstrates the utility of MSI for modeling genetic growth trends, with the best modeling results obtained when using Legendre polynomials and cNDVI.

The cuticle, a hydrophobic layer of cutin and waxes synthesized by plant epidermal cells, is the major barrier to water loss when stomata are closed at night and under water-limited conditions. Elucidating the genetic architecture of natural variation for leaf cuticular conductance (g c) is important for identifying genes relevant to improving crop productivity in drought-prone environments. To this end, we conducted a genome-wide association study of g c of adult leaves in a maize inbred association panel that was evaluated in four environments (Maricopa, AZ, and San Diego, CA, in 2016 and 2017). Five genomic regions significantly associated with g c were resolved to seven plausible candidate genes (ISTL1, two SEC14 homologs, cyclase-associated protein, a CER7 homolog, GDSL lipase, and β-D-XYLOSIDASE 4). These candidates are potentially involved in cuticle biosynthesis, trafficking and deposition of cuticle lipids, cutin polymerization, and cell wall modification. Laser microdissection RNA sequencing revealed that all these candidate genes, with the exception of the CER7 homolog, were expressed in the zone of the expanding adult maize leaf where cuticle maturation occurs. With direct application to genetic improvement, moderately high average predictive abilities were observed for whole-genome prediction of g c in locations (0.46 and 0.45) and across all environments (0.52). The findings of this study provide novel insights into the genetic control of g c and have the potential to help breeders more effectively develop drought-tolerant maize for target environments.

Abstract Background PD‐1 and PD‐L1 inhibitors have emerged as promising treatments for patients with head and neck squamous cell carcinoma (HNSCC). Methods Systematic review and meta‐analysis of PD‐1 and PD‐L1 inhibitors in HNSCC. Outcomes: median overall survival (mOS), median progression‐free survival (mPFS), Response Evaluation Criteria in Solid Tumors (RECIST) and treatment‐related adverse events (TRAEs). Results Eleven trials reported data on 1088 patients (mean age: 59.9 years, range: 18–90). The total mOS was 7.97 months (range: 6.0–16.5). Mean mPFS for all studies was 2.84 months (range: 1.9–6.5). PD‐1 inhibitors had a lower rate of RECIST Progressive Disease than PD‐L1 inhibitors (42.61%, 95% confidence interval [CI]: 36.29–49.06 vs. 56.79%, 95% CI: 49.18–64.19, P

Abstract Some machine learning applications do not allow for data augmentation or are applied to modalities where the augmentation is difficult to define. Our study aimed to develop a new method in semi-supervised learning (SSL) applicable to various modalities of data (images, sound, text), especially when augmentation is hard or impossible to define, i.e., medical images. Assuming that all samples, labeled and unlabeled, come from the same data distribution, we can say that labeled and unlabeled data sets used in the semi-supervised learning tasks are similar. Based on this observation, the data embeddings created by the classifier should also be similar for both sets. In our method, finding these embeddings is achieved based on two models—classifier and an auxiliary discriminator model, inspired by the Generative Adversarial Network (GAN) learning process. The classifier is trained to build embeddings for labeled and unlabeled datasets to cheat discriminator, which recognizes whether the embedding comes from a labeled or unlabeled dataset. The method was named the DGSSC from Discriminator Guided Semi-Supervised Classifier. The experimental research aimed evaluation of the proposed method on the classification task in combination with the teacher-student approach and comparison with other SSL methods. In most experiments, training the networks with the DGSSC method improves accuracy with the teacher-student approach. It does not deteriorate the accuracy of any experiment.

Interest among consumers in the availability of organically produced fruits and vegetables is increasing. Seafood demand is increasingly being met by fish raised using aquaculture methods that provide fish excretory products that can meet organic standards for nutrient sources for organic vegetables. We conducted an experiment in a glass greenhouse to evaluate fish biosolids as a substrate amendment for organic tomato transplant production. We compared the fish biosolids treatment to several different organic fertilizers, along with a commonly used inorganic slow-release fertilizer (Osmocote). All treatments used a target N concentration of 400 mg/L incorporated into the substrate and we also included fish biosolids treatments of 200 and 800 mg N/L. Plant performance was monitored for 4 weeks starting with commercially available 2-week-old seedlings. The results showed that the 800 mg N/L fish biosolids treatment compared very favorably with the conventional Osmocote treatment at the conclusion of the trial. The 800 mg N/L fish biosolids treatment exceeded the Osmocote treatment for chlorophyll content and for leaf number for the first 3 weeks of the 4-week trial. Grower management protocols could further improve seedling performance by providing additional top dressings of fish biosolids or fish effluent waters as plants age. [ABSTRACT FROM AUTHOR]

Why you should read this article: • To recognise that people with intellectual disabilities are over-represented in homeless populations, but services may not recognise their intellectual disabilities • To read about the short-term impact of screening with the Learning Disability Screening Questionnaire (LDSQ) on people known to a homeless service • To be aware that use of the LDSQ to identify people with intellectual disabilities in homeless services may lead to positive healthcare outcomes, such as annual health checks. Background: Research suggests that people with intellectual disabilities are over-represented in homeless populations, but services may not recognise their intellectual disability. Aim: To explore the short-term impact of screening with the Learning Disability Screening Questionnaire (LDSQ) on seven people known to a homeless service in England. These participants had been found to have intellectual and adaptive functioning in the intellectual disability range in a larger study of the use of the LDSQ in homeless services. Method: The LDSQ impact questionnaire was used to evaluate participants’ views on the benefits and drawbacks of screening with the LDSQ. Changes in participants’ health status were also explored. Findings: There appeared to be many benefits of using the LDSQ and few drawbacks. Six of the seven participants had been placed on the GP learning disability register following participation in the larger study, of whom four had received an annual health check and two had received new treatment. Conclusion: Using the LDSQ in a homeless service appears to be beneficial for people with intellectual disabilities who are homeless and can lead to positive healthcare outcomes. [ABSTRACT FROM AUTHOR]

Aims: People with a learning disability are at increased risk of becoming homeless, but little is known about how learning disability is viewed by people accessing homeless services. This study aimed to obtain the views of people experiencing homelessness about learning disability, in the context of a project that was exploring how to increase identification of learning disability. Methods: A qualitative approach was used, and 19 adults were interviewed who were receiving support from homeless services in the North-East of England. Information from the interviews was analysed using thematic analysis. Results: Four themes were identified relating to understanding of learning disability, the role of identification, day-to-day challenges, and experiences of services. Conclusion: There is a need to: promote better understanding of learning disability; for early identification processes that involve the person in a meaningful way; and the provision of support that is non-stigmatising, practical and which addresses health concerns. [ABSTRACT FROM AUTHOR]

Proper crop management requires rapid detection methods for abiotic and biotic stresses to ensure plant health and yield. Hemp (Cannabis sativa L.) is an emerging economically and environmentally sustainable crop capable of yielding high biomass. Nitrogen deficiency significantly reduces hemp plant growth, affecting photosynthetic capacity and ultimately decreasing yield. When symptoms of nitrogen deficiency are visible to humans, there is often already lost yield. A real-time, non-destructive detection method, such as Raman spectroscopy, is therefore critical to identify nitrogen deficiency in living hemp plant tissue for fast, precise crop remediation. A two-part experiment was conducted to investigate portable Raman spectroscopy as a viable hemp nitrogen deficiency detection method and to compare the technique's predictive ability against a handheld SPAD (chlorophyll index) meter. Raman spectra and SPAD readings were used to train separate nitrogen deficiency discrimination models. Raman scans displayed characteristic spectral markers indicative of nitrogen deficiency corresponding to vibrational modes of carotenoids, essential pigments for photosynthesis. The Raman-based model consistently predicted nitrogen deficiency in hemp prior to the onset of visible stress symptoms across both experiments, while SPAD only differentiated nitrogen deficiency in the second experiment when the stress was more pronounced. Our findings add to the repertoire of plant stresses that hand-held Raman spectroscopy can detect by demonstrating the ability to provide assessments of nitrogen deficiency. This method can be implemented at the point of cultivation, allowing for timely interventions and efficient resource use. [ABSTRACT FROM AUTHOR]

Abstract Background Neuroinflammation may contribute to the pathogenesis of Huntington’s disease, given evidence of activated microglia and elevated levels of inflammatory molecules in disease gene carriers, even those many years from symptom onset. We have shown previously that monocytes from Huntington’s disease patients are hyper-reactive to stimulation in a manner dependent on their autonomous expression of the disease-causing mutant HTT protein. To date, however, whether human microglia are similarly hyper-responsive in a cell-autonomous manner has not been determined. Methods Microglial-like cells were derived from human pluripotent stem cells (PSCs) expressing mutant HTT containing varying polyglutamine lengths. These included lines that are otherwise isogenic, such that any observed differences can be attributed with certainty to the disease mutation itself. Analyses by quantitative PCR and immunofluorescence microscopy respectively of key genes and protein markers were undertaken to determine whether Huntington’s disease PSCs differentiated normally to a microglial fate. The resultant cultures and their supernatants were then assessed by various biochemical assays and multiplex ELISAs for viability and responses to stimulation, including the release of pro-inflammatory cytokines and reactive oxygen species. Conditioned media were applied to PSC-derived striatal neurons, and vice versa, to determine the effects that the secretomes of each cell type might have on the other. Results Human PSCs generated microglia successfully irrespective of the expression of mutant HTT. These cells, however, were hyper-reactive to stimulation in the production of pro-inflammatory cytokines such as IL-6 and TNFα. They also released elevated levels of reactive oxygen species that have neurotoxic potential. Accompanying such phenotypes, human Huntington’s disease PSC-derived microglia showed increased levels of apoptosis and were more susceptible to exogenous stress. Such stress appeared to be induced by supernatants from human PSC-derived striatal neurons expressing mutant HTT with a long polyglutamine tract. Conclusions These studies show, for the first time, that human Huntington’s disease PSC-derived microglia are hyper-reactive due to their autonomous expression of mutant HTT. This provides a cellular basis for the contribution that neuroinflammation might make to Huntington’s disease pathogenesis.

Abstract Sweet corn (Zea mays L.) is consistently one of the most highly consumed vegetables in the United States, providing a valuable opportunity to increase nutrient intake through biofortification. Significant variation for carotenoid (provitamin A, lutein, zeaxanthin) and tocochromanol (vitamin E, antioxidants) levels is present in temperate sweet corn germplasm, yet previous genome‐wide association studies (GWAS) of these traits have been limited by low statistical power and mapping resolution. Here, we employed a high‐quality transcriptomic dataset collected from fresh sweet corn kernels to conduct transcriptome‐wide association studies (TWAS) and transcriptome prediction studies for 39 carotenoid and tocochromanol traits. In agreement with previous GWAS findings, TWAS detected significant associations for four causal genes, β‐carotene hydroxylase (crtRB1), lycopene epsilon cyclase (lcyE), γ‐tocopherol methyltransferase (vte4), and homogentisate geranylgeranyltransferase (hggt1) on a transcriptome‐wide level. Pathway‐level analysis revealed additional associations for deoxy‐xylulose synthase2 (dxs2), diphosphocytidyl methyl erythritol synthase2 (dmes2), cytidine methyl kinase1 (cmk1), and geranylgeranyl hydrogenase1 (ggh1), of which, dmes2, cmk1, and ggh1 have not previously been identified through maize association studies. Evaluation of prediction models incorporating genome‐wide markers and transcriptome‐wide abundances revealed a trait‐dependent benefit to the inclusion of both genomic and transcriptomic data over solely genomic data, but both transcriptome‐ and genome‐wide datasets outperformed a priori candidate gene‐targeted prediction models for most traits. Altogether, this study represents an important step toward understanding the role of regulatory variation in the accumulation of vitamins in fresh sweet corn kernels.