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The objective of this research is to identify the relationship between the neuropsychiatric symptoms (NPSs) of patients with major neurocognitive disorder (mNCD), their quality of life, illness intrusiveness and the caregiver’s burden. We assessed 131 patients with mNCD. Examination methods included WHO well-being index short version, illness intrusiveness rating scale, Alzheimer’s Disease Assessment Scale-Cog, Mini Mental State Examination and neuropsychiatric inventory. The results were analysed using standard statistical tests. In our sample, the prevalence of NPSs is 100%. A significant correlation (p < 0.0001) was observed with quality of life and illness intrusiveness. Additionally, a strong relationship was observed between NPSs and the caregiver’s burden (r = 0.9). The result is significantly twice as much stronger in comparison to the relationship between NPS and cognitive symptoms (r = 0.4). This is the first study in Hungary to assess the impact of NPS on the burden of relatives and quality of life. NPS had twice stronger impact on caregivers’ burden than cognitive decline. However, further studies are needed to assess the sub-syndromes in mNCD in relation to NPS.

Objectives Right ventricular (RV) failure with pulmonary hypertension (PH) is frequently encountered in patients with advanced left-sided heart disease (LHD). However, RV energetics in patients with postcapillary PH because of LHD has not been well studied. The authors investigated intraoperative RV energetics in patients with PH due to LHD based on pressure–volume curves with three-dimensional transesophageal echocardiography and pulmonary artery catheterization. Design Exploratory study. Setting National center. Participants Thirty-three patients who underwent cardiac surgery for LHD were enrolled. Ten patients had PH (mean pulmonary artery pressure ≥ 25 mmHg). Interventions None. Measurements and Main Results RV stroke work index (RVSWI) was calculated by integrating the area bounded by the pressure–volume curve. RV minute work index (RVMWI) was calculated as RVSWI × heart rate. Right ventriculo-arterial coupling was estimated as stroke volume divided by end-systolic volume (SV/ESV). The authors compared RV energetics between patients with and without PH because of LHD. RVSWI and RVMWI were significantly higher in patients with PH (690.7 mmHg·mL/m2 [601.6-737.1] v 440.9 mmHg·mL/m2 [330.8-585.3], p = 0.015, and 60,068 mmHg·mL/m2/min [35,547-68,741] v 26,351 mmHg·mL/m2/min [17,316-32,517], p = 0.011, respectively), although cardiac index was nearly identical. SV/ESV was significantly lower in patients with PH (0.520 [0.305-0.810] v 0.820 (0.650-1.090), p = 0.007). Conclusions Although cardiac index was similar, RVSWI and RVMWI were significantly higher and SV/ESV was significantly lower in patients with PH because of LHD, suggesting that patients with postcapillary PH have inefficient RV performance.

Objectives Assessment of viable tumor residue after definitive radiotherapy is essential in patients with nasopharyngeal carcinoma (NPC). This study aimed to investigate the use of Hopkins criteria on positron emission tomography/computed tomography (PET/CT) for posttreatment response evaluation and whether plasma Epstein‐Barr virus (EBV) DNA could bring additional value. Materials and methods NPC patients who underwent FDG‐PET/CT scan within 26 weeks after definitive radiotherapy were retrospectively reviewed. Residual disease was evaluated by Hopkins 5‐point score. Accuracy of Hopkins criteria before and after incorporating EBV DNA was calculated. Prognostic value for locoregional failure‐free survival (LRFFS) and disease‐free survival (DFS) was analyzed. Results One hundred and sixteen patients were evaluated. Median follow‐up time was 28.3 months (range 3.3‐92.0 months). Residual disease was found in 19 (16.4%) patients. Overall, Hopkins criteria had high specificity (86.6%; 95% CI, 78.2%‐92.7%) and negative prognostic value (NPV) (94.4%; 95% CI, 88.7%‐97.3%), while sensitivity and positive prognostic value (PPV) was 73.7% (95% CI, 48.8%‐90.9%), 51.9% (95% CI, 37.8%‐65.6%), respectively. Posttreatment plasma EBV DNA was not predictive of residual tumor (P = .272). PPV and accuracy were 50.0% (95% CI, 32.1%‐67.9%) and 83.0% (95% CI, 73.8%‐90.0%) after incorporating detectable EBV DNA into the scoring system. Positive PET/CT results were significantly correlated with inferior 3‐year LRFFS (95.7% vs 79.5%, P = .043) and 3‐year DFS (84.6% vs 54.4%, P = .028). Conclusions The Hopkins criteria demonstrated high NPV and specificity in posttreatment assessment, with the potential to be a reliable prognostic indicator for locoregional failure. Combining EBV DNA with PET/CT did not improve diagnostic accuracies. PET/CT should not be performed less than 12 weeks after treatment., Our study evaluated the Hopkins criteria and EBV DNA in the posttreatment assessment of nasopharyngeal carcinoma. Hopkins criteria showed high NPV and specificity. EBV DNA was not associated with residual disease, and combining EBV DNA with PET/CT did not improve diagnostic accuracies.

Background: Mild cognitive impairment (MCI) is a global-scale issue, due in large part to the rapidly growing elderly population. The main polyphenol contained in coffee beans, chlorogenic acid (CGA), improves attention in healthy individuals. The utility of CGAs for treating MCI, however, has not been evaluated. Objective: To determine the effects of continuous CGA intake on cognitive function, especially attention, in patients diagnosed with MCI. Methods: The study was a randomized controlled crossover trial including 34 patients with MCI. Participants were randomly divided into two groups: Those who first ingested a placebo beverage and those who first ingested an active beverage containing CGAs (553.6 mg/bottle) twice daily for 12 weeks. After a 4-week washout period, the subjects ingested the other beverage (i.e., placebo or active beverage) in the same manner. Endpoint measures included scores on the Japanese version of the Mini-Mental State Examination (MMSE), the Japanese version of the Alzheimer’s Disease Assessment Scale-cognitive component (ADAS-cog) testing overall cognitive function, and the Japanese version of the Trail Making Test (TMT-A, TMT-B) testing attention, along with the results of blood tests to evaluate safety. Results: In the TMT-B test, participants had a significantly reduced number of errors while ingesting the CGA beverage as compared with the placebo beverage (p

Updated therapeutic guidelines for inflammatory bowel disease call for effective disease assessment, early intervention, and personalized patient care using a treat-to-target (T2T) approach. The ongoing, intensive monitoring of a T2T strategy is best facilitated by a multidisciplinary team, but the increased demand on health care systems impedes implementation. Therefore, advanced practice providers have a growing role in bridging the gap between T2T recommendations and clinical practice. Advanced practice providers can effectively facilitate patient-care team communication, deliver patient education, perform in-clinic and remote monitoring of symptoms and treatment response, and assist patients with self-management.

BACKGROUND Melanoma is a highly malignant skin tumour, and is one of the most rapidly growing malignant tumors in recent years. According to statistics, the morbidity of cancer increases with age, accounting for 1.6% of new cancer cases and 0.6% of deaths worldwide. Melanoma has a serious impact on society and families, thus it is of great significance to find biological markers related to the diagnosis and treatment of melanoma. AIM To explore the expression and predictive value of mir-489 and mir-21 in melanoma metastasis. METHODS A total of 60 patients with malignant melanoma treated at our hospital from June 2017 to December 2018 were selected as a research group, while 40 healthy subjects were selected as a control group. qRT-PCR technique was used to detect miR-489 and miR-21 in serum of the two groups. ROC curve was drawn to evaluate the predictive value and diagnostic efficiency. Spearman test was used for correlation analysis. Logistic single- and multiple-factor analyses were performed to identify the risk factors related to melanoma metastasis. RESULTS The expression of miR-489 in the research group was significantly lower than that in the control group (P < 0.001). However, the expression of miR-21 in the research group was significantly higher than that in the control group (P < 0.001). The expression of miR-489 and miR-21 was related to TNM stage and metastasis (P < 0.001). In the diagnosis of melanoma patients, the sensitivity, specificity, and AUC of miR-489 alone were 75.56%, 80.00%, and 0.852, respectively. The sensitivity, specificity, and AUC of miR-21 alone were 77.78%, 82.22%, and 0.844, respectively. MiR-489 was negatively correlated with TNM stage of melanoma (r = -0.612, P < 0.001), while miR-21 was positively correlated with TNM stage (r = 0.609, P < 0.001). Logistic single- and multiple-factor regression analyses showed that TNM stage, miR-489, and mir-21 were independent risk factors for malignant melanoma metastasis. CONCLUSION MiR-489 and miR-21 may participate in the process of melanoma occurrence, development, and metastasis, and can be used as potential serum biomarkers for melanoma metastasis diagnosis and disease assessment.

This chapter describes technical considerations and current and future clinical applications of lesion detection using machine learning in the clinical setting. Lesion detection is central to neuroradiology and precedes all further processes which include but are not limited to lesion characterization, quantification, longitudinal disease assessment, prognosis, and prediction of treatment response. A number of machine learning algorithms focusing on lesion detection have been developed or are currently under development which may either support or extend the imaging process. Examples include machine learning applications in stroke, aneurysms, multiple sclerosis, neuro-oncology, neurodegeneration, and epilepsy.

Background: To characterize the course of Alzheimer’s disease (AD) over a longer time interval, we aimed to construct a disease course model for the entire span of the disease using two separate cohorts ranging from preclinical AD to AD dementia. Methods: We used longitudinal data from 127 participants with preclinical AD and 309 participants with mild cognitive impairments (MCI) due to AD from the Alzheimer’s Disease Neuroimaging Initiative. In order to develop a model of progression from preclinical AD to AD dementia, we estimated Alzheimer’s Disease Assessment Scale–Cognitive Subscale 13 (ADAS-cog 13) scores according to the follow-up time for each cohort, determined the time point at which the estimated scores of ADAS-cog 13 for the two cohorts first overlapped, and shifted the ADAS-cog 13 scores for the latter cohort at this time point to connect the two cohorts and to combine the data into a single unified progression course. Results: The estimated years for progression from the median ADAS-cog 13 score in the preclinical AD cohort (9.3 points) to the median ADAS-cog 13 score at the time of progression in the participants who progressed from preclinical AD to MCI due to AD (16.0 points) was 7.8 years. The estimated years for progression from preclinical AD to the median ADAS-cog 13 score at the time of progression in those who progressed from MCI to due AD to AD dementia (26.8 points) was 15.2 years. ADAS-cog 13 scores deteriorated most rapidly in female APOE ε4 carriers and most slowly in male APOE ε4 non-carriers ( p < 0.001). Conclusion: Our results suggest that disease progression modelling from preclinical AD to AD dementia may help clinicians to estimate where patients are in the disease course and provide information on variation in the disease course by sex and APOE ε4 status.

BACKGROUND Food insecurity and housing instability, both social determinants of health (SDoH), disproportionately affect economically unstable, under-resourced US communities in which children with sickle cell disease (SCD) live. Association between these SDoH markers and dietary quality among children with SCD is unknown. PROCEDURES We assessed a cross-sectional sample of dyadic parent-child patients and young adult patients up to age 21 from one pediatric SCD center. Food insecurity, housing instability, and dietary quality were measured using validated US instruments and a food frequency questionnaire. Better dietary quality was defined using US dietary guidelines. Multivariate regression assessed for associations among dietary quality and food insecurity with or without (±) housing instability and housing instability alone. RESULTS Of 100 enrolled participants, 53% were Black and 43% Hispanic; mean age 10.6 ± 5.6 years. Overall, 70% reported less than or equal to one economic instability: 40% housing instability alone and 30% both food insecurity and housing instability. Eighty percent received more than or equal to one federal food assistance benefit. Compared to no economic instability, food insecurity ± housing instability was significantly associated with higher intake of higher dairy and pizza, while housing instability alone was significantly associated with higher dairy intake. Food insecurity ± housing instability was significantly associated with lower intake of whole grains compared to housing instability alone. CONCLUSIONS Our sample reported high frequencies of both food insecurity and housing instability; having more than or equal to one SDoH was associated with elements of poorer diet quality. Screening families of children with SCD for food insecurity and housing instability may identify those with potential nutrition-related social needs.

This study aimed to develop a warning system platform for coffee rust incidence fifteen days in advance, as well as validating and regionalizing multiple linear regression models based on meteorological variables. The models developed by Pinto were validated in five counties. Experiments were set up in a randomized block design with five treatments and five replications. The experimental plot had six lines with 20 central plants of useful area. Assessments of coffee rust incidence were carried out fortnightly. The data collected from automatic stations were adjusted in new multiple linear regression models (MLRM) for five counties. Meteorological variables were lagged concerning disease assessment dates. After the adjustments, two models were selected and calculated for five counties, later there was an expansion to include ten more counties and 35 properties to validate these models. The result showed that the adjusted models of 15–30 days before rust incidence for Carmo do Rio Claro and Nova Resende counties were promising. These models were the best at forecasting disease 15 days in advance. With these models and the geoinformation systems, the warning platform and interface will be improved in the coffee grower region of the south and savannas of the Minas Gerais State, Brazil.

Background: Urdbean leaf crinkle disease (ULCD) is one of the most devastating biotic stress factors which is responsible for drastic yield loss in urdbean [Vigna mungo (L.) Hepper]. The etiology of ULCD is still unknown and there are conflicting reports on its transmission through seed, insect vectors, grafting and infected sap. Methods: Per cent seed transmission of ULCD had been studied during kharif, rabi and summer during the year 2019-2020 under natural and insect proof conditions. The effect on yield and seed quality parameters due to ULCD infection was studied. Urdbean cultivar VBN 8 was used in the present study. Result: The per cent seed transmission of ULCD was recorded ranging from 52.88 to 71.64% under natural conditions. In the insect proof glasshouse condition, the seed transmission was 83.62%. All the yield and seed quality parameters were adversely affected upon ULCD infection. The reduction in yield was recorded as 64.36% over the uninfected healthy plants. In ULCD infected seeds, the germination was reduced (84%) as compared to healthy seeds (92%).

Wheat (Triticum aestivum L.) yields are commonly affected by foliar infection by fungal pathogens. Of these, three wheat leaf blotch fungal diseases, septoria nodorum blotch (SNB), tan spot (TS) and septoria tritici blotch (STB), caused by Parastagonospora nodorum (Pn), Pyrenophora tritici-repentis (Ptr) and Zymoseptoria tritici (Zt), respectively, induce major yield losses. Infection results in necrotic areas on the leaf, and it is often difficult to determine the underlying causative pathogen from visible symptoms alone, especially in mixed infections. Here, a regional survey of 330 wheat samples collected across three seasons (years 2015–2017) from four north-west European countries was undertaken. Using quantitative polymerase chain reaction (qPCR) assays specific for each pathogen, as well as disease assessment of leaf materials, distinct regional differences were identified. Two-thirds (65%) of all samples harbored at least two of the three pathogens. Norway had high SNB abundance, but also showed mixed infections of SNB, TS and STB. In Germany, TS was prevalent, with STB also common. Danish samples commonly possessed all three pathogens, with STB prevalent, followed by TS and SNB. The UK had a major prevalence of STB with minimal occurrence of TS and SNB. Across all samples, qPCR identified Zt, Pn and Ptr in 90%, 54% and 57% of samples, respectively. For each pathogen, average disease levels via visual assessment showed modest positive correlation with fungal DNA concentrations (R2 = 0.13–0.32). Overall, our study highlights that the occurrence of mixed infection is common and widespread, with important implications for wheat disease management and breeding strategies.

Emerging infectious diseases may become serious threats to wildlife, a prominent example being the white-nose disease (WND). In case of WND, the cold-loving fungus Pseudogymnoascus destructans colonizes bats during hibernation, invades the skin and has already lead to the death of millions of bats in North America. P. destructans most likely originated from Europe, where it also causes lesions but without associated mortalities. However, it is still unclear how European bats cope with the fungus. Hence, it is important to have tools that precisely characterise disease progression. Because hibernation is a physiological state during which bats are vulnerable to disturbance, in-situ assessments of the clinical status should be carried out minimal-invasively to avoid detrimental impacts on bats. However, currently available disease assessment methods require handling/touching bats and are therefore invasive: i) UV-light trans-illumination of wing membranes to detect lesions and ii) a qPCR-based quantification of fungal material from wing membrane swabs. Since P. destructans (‘Pd') becomes visible on all furless skin with distinct distribution patterns, we investigated the use of visible symptoms to assess levels of infections without handling/touching bats. We introduce a technique which we termed ‘Visual Pd-score’ (a visual classification scheme), which can be applied without disturbing the animals. To assess its reliability, we used P. destructans infected greater mouse-eared bats (Myotis myotis) to compare the novel method with the two existing golden-standard techniques. Our results show that infection levels obtained from all three techniques are correlated. Importantly, the information carried by the Visual Pd-score is most similar to a composite index combining the information from the qPCR-based and UV-light quantification methods. We conclude that the Visual Pd-score represents a promising index to better characterise disease severity as it is simultaneously representative for fungal colonization and wing damage. We discuss advantages and disadvantages of the applied techniques and conclude that the Visual Pd-score is particularly useful for routine hibernacula counts or large-scale P. destructans-surveillance. In combination with the lesion detection technique the new method is also applicable to immunological studies where both fungal colonization and associated damage have to be investigated, while qPCRs from swabs of all body parts are especially useful if it is necessary to detect cryptic infections, e.g. during the early hibernation period.

Cassava production and productivity in Eastern, Central, and Southern Africa are ravaged by cassava brown streak disease (CBSD), causing yield losses of up to 100% when susceptible varieties are grown. Efforts to develop CBSD-resistant clones are underway. However, the methods for screening CBSD resistance currently vary between breeders and pathologists, with the limited empirical data to support their choices. In this study, we used the empirical CBSD foliar and root necrosis data from two breeding populations, termed cycle zero (C0) and cycle one (C1), to assess and compare the effectiveness of the CBSD screening methods of breeders vs. pathologists. On the one hand, the estimates of broad-sense heritability (H2) for the CBSD root necrosis assessment of breeder ranged from 0.15 to 0.87, while for the assessment method of pathologists, H2 varied from 0.00 to 0.71 in C0 clones. On the other hand, the marker-based heritability estimates (h2) for C0 ranged from 0.00 to 0.70 for the assessment method of breeders and from 0.00 to 0.63 for the assessment method of pathologists. For cycle one (C1) population, where both foliar and root necrosis data were analyzed for clones assessed at clonal evaluation trials (CETs) and advanced yield trials (AYTs), H2 varied from 0.10 to 0.59 for the assessment method of breeders, while the H2 values ranged from 0.09 to 0.35 for the CBSD computation method of pathologists. In general, higher correlations were recorded for foliar severity from the assessment method of breeders (r = 0.4, p ≤ 0.01 for CBSD3s and r = 0.37, p ≤ 0.01 for CBSD6s) in C1 clones evaluated at both clonal and advanced breeding stages than from the approach of pathologists. Ranking of top 10 C1 clones by their indexed best linear unbiased predictors (BLUPs) for CBSD foliar and root necrosis showed four overlapping clones between clonal and advanced selection stages for the method of breeders; meanwhile, only a clone featured in both clonal and advanced selection stages from the CBSD assessment method of pathologists. Overall, the CBSD assessment method of breeders was more effective than the assessment method of pathologists, and thus, it justifies its continued use in CBSD resistance breeding.

Background: Measurable residual disease (MRD) by multiparameter flow cytometry (MFC) is highly prognostic for relapse and overall survival (OS) in patients (pts) with acute lymphoblastic leukemia (ALL). However, many pts with apparent "MRD negativity" by MFC still relapse. These relapses are likely due to residual leukemia that is present below the level of detection of MFC (generally ~1x10-4). In light of the limitations of conventional MRD assays, we sought to evaluate the clinical impact of a highly sensitive next-generation sequencing (NGS)-based MRD assay that is capable of detecting residual leukemia at a level of 1x10-6. Methods: We performed a retrospective study of 67 pts with previously untreated Philadelphia chromosome-negative ALL who received frontline therapy between 2/2012 and 7/2018 with a hyper-CVAD-based regimen (n=44) or a lower-intensity hyper-CVD-based regimen (n=23), which was usually combined with inotuzumab ozogamicin, and achieved complete remission (CR). Pts were selected for this study based on availability of banked samples at baseline and at sequential remission time points up to 4.5 months after start of therapy. Six-color MFC was performed as standard of care with an analytic sensitivity of 0.01% (1x10-4). Pretreatment genomic DNA derived from bone marrow was evaluated using a quantitative NGS MRD assay (Adaptive Biotechnologies Co., Seattle, WA) to identify dominant rearrangements within the B-cell receptor (IgH [VDJ and DJ], IgK and IgL). High throughput NGS of remission samples was subsequently performed to assess the target clonal rearrangements at an established analytic sensitivity of 0.0001% (1x10-6). Results: The baseline characteristics of the study population are shown in Table 1. Twenty pts (30%) underwent allogeneic stem cell transplant (alloSCT) in first remission. In the entire cohort, 14 pts relapsed (21%), including 2 with CNS-only relapses. The median duration of follow-up for the entire cohort was 51 months. Among the 109 remission samples, 84 were MRD-negative (MRDneg), 24 were MRD-positive (MRDpos), and 1 was indeterminate by MFC (Figure 1). All 24 MRDpos samples by MFC were also MRDpos by NGS. Among the 84 MRDneg samples by MFC, 32 (38%) were MRDpos by NGS. For these discordant cases, the median level of MRD by NGS was below the expected level of detection by MFC (median 0.002% [range 0.00002%-1.15%]). At the time of CR, 44/67 pts (66%), achieved MRDneg by MFC and 14/38 (37%) achieved MRDneg by NGS. The rates of MRDneg by MFC in pts treated with hyper-CVAD or hyper-CVD regimens were 61% and 74%, respectively, and by NGS were 32% and 46%, respectively. Achieving MRDneg by NGS at the time of CR better predicted the likelihood of durable remission than did achieving MRDneg by MFC. The 5-year cumulative incidence of relapse (CIR) of the 44 pts who achieved MRDneg by MFC and of 14 pts who achieved MRDneg by NGS was 27% and 8%, respectively. Only 1 out of 14 pts who achieved MRDneg by NGS at the time of CR subsequently relapsed. In contrast, MRD status by NGS did not predict for relapse when evaluated at post-CR time points. Among pts treated with a more intensive hyper-CVAD regimen, achievement of MRDneg by NGS at CR provided additional prognostic information compared to MRD status by MFC at the same time point and identified pts with an excellent long-term outcome. The 5-year OS rate for pts who achieved MRDneg by NGS at CR was 100% vs. 55% for those who were MRDpos by NGS (Figure 2A; P Conclusion: Early assessment of MRD using an ultrasensitive NGS assay can identify pts with ALL who have a very low risk of relapse and excellent long-term survival. Prospective studies are warranted to assess whether de-intensification of therapy is feasible for this favorable-risk group of pts who rapidly achieve MRDneg remission. Disclosures Short: Amgen: Honoraria; Astellas: Research Funding; AstraZeneca: Consultancy; Takeda Oncology: Consultancy, Honoraria, Research Funding. Kantarjian:Takeda: Honoraria; Amgen: Honoraria, Research Funding; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Cyclacel: Research Funding; Pfizer: Honoraria, Research Funding; Agios: Honoraria, Research Funding; Novartis: Research Funding; Immunogen: Research Funding; AbbVie: Honoraria, Research Funding; BMS: Research Funding; Ariad: Research Funding; Jazz Pharma: Research Funding; Daiichi-Sankyo: Research Funding; Astex: Research Funding. Konopleva:F. Hoffmann La-Roche: Consultancy, Research Funding; Eli Lilly: Research Funding; Cellectis: Research Funding; Calithera: Research Funding; Rafael Pharmaceutical: Research Funding; Amgen: Consultancy; Sanofi: Research Funding; Stemline Therapeutics: Consultancy, Research Funding; Ablynx: Research Funding; Agios: Research Funding; AbbVie: Consultancy, Research Funding; Ascentage: Research Funding; AstraZeneca: Research Funding; Forty-Seven: Consultancy, Research Funding; Reata Pharmaceutical Inc.;: Patents & Royalties: patents and royalties with patent US 7,795,305 B2 on CDDO-compounds and combination therapies, licensed to Reata Pharmaceutical; Kisoji: Consultancy; Genentech: Consultancy, Research Funding. Jain:Cellectis: Research Funding; BMS: Research Funding; BeiGene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Fate Therapeutics: Research Funding; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Aprea Therapeutics: Research Funding; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; ADC Therapeutics: Research Funding; TG Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Precision Bioscienes: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kebriaei:Kite: Other: Served on advisory board; Amgen: Other: Research Support; Ziopharm: Other: Research Support; Pfizer: Other: Served on advisory board; Novartis: Other: Served on advisory board; Jazz: Consultancy. Yilmaz:Pfizer: Research Funding; Daicho Sankyo: Research Funding; Pint Pharma: Honoraria. Issa:Celegene: Research Funding; Syndax: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees. Ravandi:BMS: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria, Research Funding; Xencor: Consultancy, Honoraria, Research Funding; Macrogenics: Research Funding; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Orsenix: Consultancy, Honoraria, Research Funding. Jabbour:Amgen: Other: Advisory role, Research Funding; Adaptive Biotechnologies: Other: Advisory role, Research Funding; BMS: Other: Advisory role, Research Funding; Genentech: Other: Advisory role, Research Funding; AbbVie: Other: Advisory role, Research Funding; Takeda: Other: Advisory role, Research Funding; Pfizer: Other: Advisory role, Research Funding.

This protocol describes the inoculation preparation, bioassay and disease assessment of Ascochyta rabiei isolates on a differential set of chickpea host genotypes.

Background and study aims Endoscopic ultrasound (EUS) may be a useful modality for disease assessment and risk stratification in ulcerative colitis. We assessed the reliability of a newly developed EUS index of inflammation called the EUS-Ulcerative Colitis (EUS-UC) score. Patients and methods The EUS-UC score components include total wall thickness, hyperemia, and depth of inflammation (DOI). Three blinded expert endosonographers assessed EUS videos of 58 patients with UC in triplicate. Intra- and inter-rater reliability of the hyperemia and DOI component scores were estimated using intra-class correlation coefficients (ICCs). Total wall thickness reliability estimates could not be assessed in this study. The ICCs were compared to the original indices from which they were derived. Results For hyperemia, the inter-class ICC was “moderate” at 0.556 (95 % CI = 0.434–0.651) and the intra class ICC was “almost perfect” at 0.884 (95 % CI = 0.835–0.920). The newly defined hyperemia score performed better than the original index from which is was derived. The DOI inter-class ICC was “fair” at 0.335 (95 % CI = 0.201–0.464), and the intra-class ICC was “substantial” at 0.732 (95 % CI = 0.642–0.802). The DOI reliability estimates were similar to the original index from which it was derived. Conclusions The hyperemia component of the EUS-UC score performed significantly better than the original index from which it was derived, but the reliability of the DOI component was suboptimal. Intra-class correlation was excellent for both components. The EUS-UC score is a promising instrument for assessment of UC and further validation is required.

Arguably, the most important advances in modern clinical care have arisen not through the development of new drugs but instead through a recognition that the Gestalt approach to disease assessment is simply not adequate when it comes to selecting and assessing response to therapy. Accurate and regular assessment with an appropriate measurement instrument gives the clinician and patient reliable information to track disease trajectory and make treatment decisions. Achieving consensus on a single disease-specific instrument has considerable advantages, facilitating adoption of international treatment guidelines, and interpretation of data from trials, cohorts, and registries to make translation into routine care seamless1. In the context of rheumatoid arthritis (RA), the 28-joint count Disease Activity Score (DAS28) has been widely adopted as the most frequently used generally continuous measure of activity. The DAS28 has established cutpoints for high, moderate, and low disease activity and remission. The term near remission is increasingly preferred because it better differentiates those with some residual disease from those in true remission. Clinicians are used to the measure and what the numbers mean clinically, and this has allowed a smooth translation of research findings into clinical practice, including the implementation of treat to target and adoption of clinical guidelines. It has been harder to achieve this consensus in the field of psoriatic arthritis (PsA), with no current agreement on the most appropriate instrument to adopt. Why is this the case, and what are the key barriers2? The greatest challenge in the adoption of a composite measure for routine care in PsA has been philosophical: should we incorporate multiple domains of disease into a single measure to identify the totality of disease, or should we focus on 1 domain at a time for accurate assessment and to avoid diluting responsiveness? PsA may manifest in a variety … Address correspondence to W. Tillett, Royal National Hospital for Rheumatic Diseases, Upper Borough Walls, Bath BA1 1RL, UK. E-mail: w.tillett{at}nhs.net

The objective of this study is to evaluate the effects of physical therapy on the cognitive and functional capacity of patients with Alzheimer’s Disease (AD). This is a systematic review of randomized or quasi-randomized clinical trials, using the descriptors: AD, dementia and physical therapy. Two studies were included with a total of 207 participants. In study 1, no statistically significant difference was found on the mini-mental state examination (MMSE) (MD 0.0, 95%CI −5.76 to 5.76), neuropsychiatric inventory (MD −4.50, 95%CI −21.24 to 12.24) and Pfeffer instrumental activities questionnaire (MD 0.0 95%CI −6.48 to 6.48). In study 2, there was no statistically significant difference on the MMSE (MD −1.60, 95% CI −3.57 to 0.37), clock-drawing test (MD −0.20, 95%CI −0.61 to 0.21) and Alzheimer’s Disease Assessment Scale - cognitive subscale (MD 1.0, 95%CI −2.21 to 4.21) after 12 months. There was no consistent evidence on the effectiveness of physiotherapeutic intervention in improving cognitive function and functional capacity of patients with AD. More studies should be conducted for better evidence. RESUMO O objetivo do estudo é avaliar os efeitos da fisioterapia na capacidade cognitiva e funcional de pacientes com doença de Alzheimer (DA). Trata-se de revisão sistemática de ensaios clínicos randomizados ou quasi-randomizados utilizando os descritores: DA, demência e fisioterapia. Dois estudos foram incluídos, com um total de 207 participantes. No Estudo 1, não houve diferença estatisticamente significativa no miniexame do estado mental (MEEM) (MD 0,0, IC 95% 5,76−5,76), inventário neuropsiquiátrico (MD −4,50, IC 95% 12,24−21,24) e questionário de atividades instrumentais Pfeffer (MD 0,0 IC 95% −6,48 a 6,48). No Estudo 2, não houve diferença estatisticamente significativa no MEEM (MD −1,60, IC 95% −3,57 a 0,37), teste do desenho do relógio (MD −0,20, IC95% −0,61 a 0,21) e escala de avaliação da doença de Alzheimer - subitem cognição (MD 1,0, IC95% −2,21 a 4,21) após 12 meses. Não houve evidência consistente da eficácia da intervenção fisioterapêutica na melhora da função cognitiva e capacidade funcional na DA. Recomenda-se a produção de mais estudos para encontrar possíveis evidências. RESUMEN El presente estudio tiene como objetivo evaluar los efectos de la fisioterapia en la capacidad cognitiva y funcional de pacientes con enfermedad de Alzheimer (EA). Se trata de una revisión sistemática de ensayos clínicos aleatorizados o casi-aleatorizados, en que se utilizó los descriptores: EA, demencia y fisioterapia. Se incluyeron dos estudios, con un total de 207 participantes. En el Estudio 1, no hubo diferencias estadísticamente significativas en el Miniexamen del estado mental (MEEM) (MD 0,0, IC 95%: 5,6 -5,76), en el inventario neuropsiquiátrico (MD -4,50, IC 95%: 12,24 -21,24) y en el cuestionario de actividades instrumentales de Pfeffer (MD: 0,0 IC 95% IC: -6,48 a 6,48). En el Estudio 2, no hubo diferencias estadísticamente significativas en el MEEM (MD −1,60, IC 95% −3,57 a 0,37), el test de diseño del reloj (MD −0,20, IC 95% −0,61 a 0,21) y la escala de evaluación de la enfermedad de Alzheimer: subítem de cognición (MD 1,0, IC 95% −2,21 a 4,21) tras 12 meses. No hubo evidencia consistente de la eficacia de la intervención fisioterapéutica en la mejora de la función cognitiva y de la capacidad funcional en la EA. Se recomienda realizar estudios adicionales para encontrar posibles evidencias.

Non-alcoholic fatty liver disease (NAFLD) is a risk factor for hepatic fibrosis and cirrhosis. Acoustic structure quantification (ASQ), based on statistical analysis of ultrasound echoes, is an emerging technique for hepatic steatosis diagnosis. A standardized measurement protocol for ASQ analysis was suggested previously; however, an optimal ultrasound scanning approach has not been concluded thus far. In this study, the suitability of scanning approaches for the ASQ-based evaluation of hepatic steatosis was investigated. Hepatic fat fractions (HFFs; liver segments VIII, III and VI) of 70 living liver donors were assessed with magnetic resonance spectroscopy. A clinical ultrasound machine equipped with a 3-MHz convex transducer was used to scan each participant using the intercostal, epigastric and subcostal planes to acquire raw data for estimating two ASQ parameters ( C m 2 and focal disturbance [FD] ratio) of segments VIII, III and VI, respectively. The parameters were plotted as functions of the HFF for calculating the values of the correlation coefficient (r) and probability value (p). The diagnostic performance of the parameters in discriminating between the normal and steatotic (≥5 and ≥10%) groups was also compared using receiver operating characteristic (ROC) curves. The C m 2 and FD ratio values measured using the epigastric and subcostal planes did not correlate with the severity of hepatic steatosis. However, intercostal imaging exhibited a higher correlation between the ASQ parameters and HFF (r = −0.64, p C m 2 and FD ratio in detecting hepatic steatosis using intercostal imaging was also satisfactory (areas under ROC curves >0.8). Intercostal imaging is an appropriate scanning approach for ASQ analysis of the liver.

Brown rust (caused by Puccinia melanocephala) and orange rust (caused by P. kuehnii) are two major diseases of sugarcane in Florida. To better understand the epidemiology of these two rusts, disease severity and weather variables were monitored for two seasons in cultivars CL90-4725 (susceptible to brown rust and resistant to orange rust) and CL85-1040 (susceptible to orange rust and resistant to brown rust). Brown rust was most severe during mid-May to mid-July, whereas orange rust severity peaked during two periods: mid-May to early August and then November to December. Overall, disease severity was higher for orange rust than for brown rust. Maximum disease severity was correlated with the number of hours at night with an average temperature of 20 to 22.2°C for brown rust one season and orange rust both seasons. Slightly higher correlation was obtained when relative humidity above 90% was included in the number of hours at night with an average temperature of 20 to 22.2°C for brown rust but not orange rust, suggesting that leaf wetness is not a limiting factor for either disease in Florida. Epidemics of brown rust began at lower night temperatures (16.7 to 22.2°C) in one season, but epidemics of orange rust lasted longer under higher temperatures. The correlation of rust severity on recently emerged leaves with conducive temperatures recorded in 10-, 20-, or 30-day windows starting 7 days before disease assessment suggested that earlier inoculum production is needed to create severe epidemics that result in yield loss.

Diabetes mellitus is common and complicates 2–5% of pregnancies in the UK, with an increasing prevalence of pre-existing diabetes mellitus in pregnancy. Hyperglycaemia directly correlates with adverse maternal and fetal outcomes, including congenital anomaly, miscarriage, pre-eclampsia, pre-term delivery, macrosomia, stillbirth and neonatal hypoglycaemia. Optimal glycaemic control before conception and during the antenatal period is paramount to reduce these risks. Pre-pregnancy preparation should focus on glycaemic control, medication review and end-organ disease assessment. All diabetic women of childbearing age not planning a pregnancy should be offered contraception. Antenatal care should focus on education from a multidisciplinary team. Women should understand the changes that occur in pregnancy and the need for more intense monitoring and tighter glycaemic control. Increased surveillance focuses on end-organ disease (retinal, renal), the development of pre-eclampsia and the presence of fetal complications. The postpartum period is valuable for reiterating the benefits of contraception and planning of future pregnancies. This article focuses on the management of pre-existing diabetes mellitus from pre-conception to the postpartum period.

The fungus Sclerotinia sclerotiorum is the major pathogen affecting common beans yield worldwide and an adequate disease quantification is demanded in some trials. However, a set of standard area diagrams (SADs) to aid visual assessment of severity of white mold (SWM) is lacking. This study developed SADs consisting of eight color images of diseased leaflets with severity values that ranged from 0.4 to 53.7%. Twenty raters [10 experienced (ER) and 10 inexperienced (IR)] validated the SADs by assessing the same set of 50 images twice, the first without SADs and the second using it as an aid. The SADs significantly improved both accuracy and precision for IR as evidenced by increases from 0.86 to 0.98 in the coefficients of bias (Cb) from 0.93 to 0.98 in correlation coefficient (r) and from 0.86 to 0.96 in overall agreement [Lin's concordance correlation coefficients (ρc)] without and with SADs, respectively, whereas for ER only precision (r) was improved by SADs. The SWM estimates were also more reliable because inter-rater reliability (coefficient of determination, R2) was significantly increased for both ER and IR by using SADs. Therefore, the SADs presented is thought to be a valuable tool to provide accurate, precise and reliable estimates of the SWM on common bean leaflets in epidemiological studies, evaluation of disease control methods, assessment of aggressiveness of pathogen isolates, disease resistance and other types of surveys regarding the common beans-S. sclerotiorum interaction.

Ladakh region does not favour cultivation of crops due to the harsh physio-geographical conditions. In recent years, the protected cultivation has been used extensively to grow vegetable and fruit crops in this region. However, favourable climate for plant growth inside the poly house, also provide conducive environment for several plant pathogens. Thus, present study was undertaken to determine the disease incidence (DI) and disease severity (DS) in six different vegetable and fruit crops namely Cucumis sativus, Brassica oleracea var. botrytis, Capsicum annuum, Solanum lycopersicum, Luffa sp. and Fragaria spp. grown under protected cultivation in various areas of Ladakh. Results suggest that the DI for the studied crops did not show significant variation (F ≤ 2.7; p ≥ 0.15). Similarly, the DS among the study crops was also statistically indifferent among different protected cultivation sites studied in different areas of Ladakh region (p ≥ 0.08), except for Solanum lycopersicum (F = 6.1; p = 0.037). The highest DI recorded was 51.5 ± 5.5 in Solanum lycopersicum followed by 30.9 ± 5.2 in Brassica oleracea var. botrytis. Similarly, highest DS was 27.0 ± 3.1 observed in Solanum lycopersicum followed by 23.6 ± 4.8 in Brassica oleracea var. botrytis. The variation in DI and DS among the study crops was statistically significant (F ≥ 32.9; p

Glomerella leaf spot (GLS) causes severe necrotic leaf symptoms on Gala, the most cultivated apple cultivar in Brazil. To evaluate this disease, the standard area diagram set (SADs) developed on the state of Parana for a leaf severity level up to 30.93% has been used. However, in samples collected in the states of Santa Catarina and Rio Grande do Sul, disease symptoms reach 75% of severity. Therefore, the objective of this study was to develop and to validate new SADs that include higher GLS severity levels. The proposed SADs have 10 color images of diseased leaves with severity values ranging from 0.2 to 75%. These SADs were validated by 12 raters and have significantly improved the disease assessment. Therefore, it is believed that SADs developed in the present study will allow an adequate evaluation in regions or orchards where the disease is more severe.

One of the drawbacks of conducting research on Goss's bacterial wilt and leaf blight disease, caused by the bacterium Clavibacter nebraskensis (Cn) on corn (Zea mays L.), is the lack of standardized and validated inoculation and disease assessment methods. Here we report foliar and root inoculation techniques with a standardized scale for reliable assessment of symptoms to allow for disease assessment of the Goss's wilt disease on corn. The leaf inoculation method allowed for the application of equal amounts of inoculum, which ensured consistency in measurements and prevented inoculum run off from the inoculation site. The reliability of a leaf inoculation method based on either lesion length or disease severity, and root inoculation based on disease severity was validated statistically using two Cn isolates, Cmn14-5-1 and DOAB232, which possess high and low levels of aggressiveness, respectively. The leaf disease-severity and the lesion length methods for disease assessment clearly provided the most precise estimation of the level of aggressiveness of Cn isolates among the tested years (2015, 2016, and 2017 growing seasons). In addition, the disease severity based on the root inoculation method was validated, but the high variation among experimental runs within each year suggested that it might be the least reliable method for assessment of the disease severity. Our results indicated no significant trend in overall isolate aggressiveness over the years using the leaf inoculation method based on either lesion length or leaf disease-severity.

Alzheimer’s disease (AD) is the sixth leading cause of death in the United States and the most common neurodegenerative disease in adults over 65. Early-stage AD is often misinterpreted as normal cognitive aging because it may not cause adverse symptoms or visible behavioral changes for up to 20 years. Machine learning has been used to avoid misinterpretation of data and more accurately predict the onset of AD. This study aims to use the data typically available in a clinical setting to predict the onset of AD while maintaining a high level of accuracy. This study proposes a deep learning model that uses multimodal input data and performs multitask classification to predict AD diagnosis and scores of two commonly used cognitive assessments: Alzheimer’s Disease Assessment Scale (ADAS) and Mini-Mental State Examination (MMSE). The model was validated using the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset of 1737 patients. The current model achieved a greater accuracy in predicting AD diagnosis and a lower error in predicting ADAS and MMSE scores than existing state-of-the-art models. This model can be applied to the clinical setting so that accurate diagnosis can be achieved, and appropriate action can be taken. Future investigations could include using a convolutional neural network (CNN) to process data from clinical images directly or training and validating the model with other clinical datasets to further improve its accuracy.