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Screening genotypes based on grain yield stability in different ecological zones is a prerequisite for developing a widely adapted genotype. For this purpose, 16 chickpea desi genotypes' evaluation through cooperative yield trial commenced during 2019-2020 at nine diversified locations across Punjab, Pakistan. Data underwent genotype by environment interaction (G × E) and mega environment analysis. Genotype plus genotype × environment (GGE) biplot view for yield depicted that G-4 (CH-21/13) was the ideal and superior genotype for stability and yield potential. GGE biplot 'what-won-where' for yield formed an irregular polygon showing interconnection among G-3 (CH-2016), G-4 (CH-21/13), G-8 (D-17003), G-11(D-17019), G-13 (TG-1427), G-14 (TG-1430), and G-16 (TG-1510), indicating these genotypes were comparatively more stable. Graphical representation of the mega environment analysis illustrated that E-1 (Pulses Research Institute, AARI, Faisalabad, Pakistan) was ideal and most discriminating for genotype screening. Results also revealed that the first mega environment's construction included the grouping of E-1 (Pulses Research Institute, AARI, Faisalabad, Pakistan), E-2 (Nuclear Institute for Agriculture and Biology, Faisalabad, Pakistan), E-3 (Gram Breeding Research Station, Kallurkot, Pakistan), and E-4 (Gram Breeding Research Station, Kallurkot, Barani, Pakistan), with G-4 (CH-21/13) as the winning genotype. Biplot also depicted that G-3 (CH-2016) was best in the second mega environment made by E-6 (Regional Agricultural Research Institute, Pakistan), and G-8 (D-17003) was a winner in E-4 (Gram Breeding Research Station, Kallurkot, Barani, Pakistan). Combined analysis showed that G-4 (CH-21/13), G-8 (D-17003), and G-13 (TG-1427) were the most stable and high-yielding; therefore, these genotypes may considerably be widely adaptive across environments. [ABSTRACT FROM AUTHOR]

Using diffusion tensor imaging (DTI), we assessed the extent to which fractional anisotropy values in the dorsal (i.e., arcuate fasciculus; AF) versus ventral (i.e., inferior fronto-occipital fasciculus; IFOF) distinction of structural white matter pathways associated with selected reading processes, could be replicated in skilled adult readers (N = 17) and extended to adults with reading impairments (N = 13). In addition to the AF and IFOF, motor-based tracts (i.e., posterior limb of the internal capsule (PLIC) and the frontal aslant tract (FAT)) were isolated to explore their role in reading performance. Several interesting relationships with reading performance emerged. First, orthographic awareness was related to the left IFOF in skilled readers, whereas orthographic awareness was related to left PLIC for impaired readers. Morphological awareness was related to left FAT for skilled readers, whereas morphological awareness was related to right AF, right IFOF and left PLIC for impaired readers. Overall, these findings support the notion that adult reading performance (both skilled and impaired) is related to the structural properties of the ventral white matter pathways. More consideration should be paid to motor pathways, particularly the PLIC, and their role in compensatory reading strategies in individuals with reading impairments.

Purpose: To shorten CEST acquisition time by leveraging Z-spectrum undersampling combined with deep learning for CEST map construction from undersampled Z-spectra., Methods: Fisher information gain analysis identified optimal frequency offsets (termed "Fisher offsets") for the multi-pool fitting model, maximizing information gain for the amplitude and the FWHM parameters. These offsets guided initial subsampling levels. A U-NET, trained on undersampled brain CEST images from 18 volunteers, produced CEST maps at 3 T with varied undersampling levels. Feasibility was first tested using retrospective undersampling at three levels, followed by prospective in vivo undersampling (15 of 53 offsets), reducing scan time significantly. Additionally, glioblastoma grade IV pathology was simulated to evaluate network performance in patient-like cases., Results: Traditional multi-pool models failed to quantify CEST maps from undersampled images (structural similarity index [SSIM] <0.2, peak SNR <20, Pearson r <0.1). Conversely, U-NET fitting successfully addressed undersampled data challenges. The study suggests CEST scan time reduction is feasible by undersampling 15, 25, or 35 of 53 Z-spectrum offsets. Prospective undersampling cut scan time by 3.5 times, with a maximum mean squared error of 4.4e-4, r = 0.82, and SSIM = 0.84, compared to the ground truth. The network also reliably predicted CEST values for simulated glioblastoma pathology., Conclusion: The U-NET architecture effectively quantifies CEST maps from undersampled Z-spectra at various undersampling levels., (© 2024 International Society for Magnetic Resonance in Medicine.)

Background: Pancreatic cancer remains a lethal malignancy with a 5-year survival rate below 6% and about 500,000 deaths annually worldwide. Pancreatic adenocarcinoma, the most prevalent form, is commonly associated with diabetes, chronic pancreatitis, obesity, and smoking, mainly affecting individuals aged 60 to 80 years. This systematic review aims to evaluate the efficacy of immunotherapeutic approaches in the treatment of pancreatic cancer., Methods: A systematic search was conducted to identify clinical trials (Phases I-III) assessing immunotherapy in pancreatic cancer in PubMed/Medline, CINAHL, Scopus, and Web of Science, adhering to PRISMA Statement 2020 guidelines. The final search was completed on May 25, 2024. Ongoing trials were sourced from ClinicalTrials.gov and the World Health Organization's International Clinical Trials Registry Platform (ICTRP). Keywords such as "pancreatic," "immunotherapy," "cancer," and "clinical trial" were used across databases. Gray literature was excluded., Results: Phase I trials, involving 337 patients, reported a median overall survival (OS) of 13.6 months (IQR: 5-62.5 months) and a median progression-free survival (PFS) of 5.1 months (IQR: 1.9-11.7 months). Phase II/III trials pooled in a total of 1463 participants had a median OS of 12.2 months (IQR: 2.5-35.55 months) and a median PFS of 8.8 months (IQR: 1.4-33.51 months)., Conclusions: Immunotherapy shows potential for extending survival among pancreatic cancer patients, though results vary. The immunosuppressive nature of the tumor microenvironment and diverse patient responses underline the need for further research to optimize these therapeutic strategies., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Goal attainment scaling (GAS), an established individualized, patient-centred outcome measure, is used to capture the patient's voice. Although first introduced ~60 years ago, there are few published guidelines for implementing GAS, and almost none for its use when caregivers GAS is implemented with caregiver input. We conducted a systematic review of studies that implemented GAS with caregiver input; and examined variations in GAS implementation, analysis, and reporting., Methods: Literature was retrieved from Medline, Embase, Cochrane, PsycInfo and CINAHL databases. We included randomized controlled trials (published between 1968 and November 2022) that used GAS as an outcome measure and involved caregiver input during goal setting., Results: Of the 2610 studies imported for screening, 21 met the inclusion criteria. Most studies employed GAS as a primary outcome. The majority (76%) had children as study participants. The most common disorders represented were cerebral palsy, developmental disorders, and dementia/Alzheimer's disease. The traditional five-point GAS scale, with levels from -2 to +2, was most often implemented, with -1 level typically being the baseline. However, most studies omitted essential GAS details from their reports including the number of goals set, number of attainment levels and whether any training was given to GAS facilitators., Conclusions: GAS with caregiver input has been used in a limited number of randomized controlled trials, primarily in pediatric patients and adults with dementia. There is a variability in GAS implementation and many crucial details related to the specifics of GAS implementation are omitted from reports, which may limit reproducibility. Here we propose catalog that may be utilized when reporting research results pertaining to GAS with caregivers to enhance the application of this patient-centered outcome measure., (© 2024. The Author(s).)

Objective: Lupus nephritis (LN) is one of the most severe manifestations of SLE; however, we know little about the lived experience of LN. This research investigates patient experiences and perspectives of (1) LN diagnosis; (2) living with LN; and (3) LN healthcare and treatment., Methods: Patients aged ≥18 years with biopsy-proven pure or mixed International Society of Nephrology/Renal Pathology Society class III, IV or V LN were purposefully recruited from a Canadian lupus cohort to participate in semistructured in-depth interviews., Results: Thirty patients with LN completed the interviews. The mean (SD) age was 42.1 (16.4) years, and 86.7% were female. Participants described challenges seeking, receiving and adjusting to a LN diagnosis, and some reported that their diagnosis process took weeks to years. While 16 participants were provided resources by healthcare providers to help them through the process of diagnosis, the need for accessible LN-specific information at diagnosis was highlighted (n=18). Participants also described the unpredictability of living with LN, particularly related to impacts on physical and mental health, relationships, leisure activities, employment and education, and family planning. While most (n=26) participants reported a positive impression of their care, the side effects of LN medications and the need to increase patient and societal awareness/understanding of LN were highlighted in the context of healthcare and treatment., Conclusions: The unpredictability of living with LN, the heavy treatment burden and a lack of patient/societal awareness substantially affect the lived experience of LN. These findings will inform the development of LN-specific patient resources to increase understanding of LN and improve well-being for patients., Competing Interests: Competing interests: FSC and SJE have no conflicts of interest to disclose. MRWB has received consulting fees from AbbVie, AstraZeneca, Janssen, GSK and Sanofi-Genzyme. KC has received consulting fees from Novartis and speaker fees from Alexion. SG and AB are employees of GSK. AB also holds stock/shares in GSK. AEC has received grant/research support from GSK, and consulting fees from AstraZeneca, Bristol Myers Squibb and GSK., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To model the referral, diagnostic and treatment pathway for cardiovascular disease (CVD) in the English National Health Service (NHS) to provide commissioners and managers with a methodology to optimise patient flow and reduce waiting lists., Study Design: A systems dynamics approach modelling the CVD healthcare system in England. The model is designed to capture current and predict future states of waiting lists., Setting: Routinely collected, publicly available data streams of primary and secondary care, sourced from NHS Digital, NHS England, the Office of National Statistics and StatsWales., Data Collection and Extraction Methods: The data used to train and validate the model were routinely collected and publicly available data. It was extracted and implemented in the model using the PySD package in python., Results: NHS cardiovascular waiting lists in England have increased by over 40% compared with pre- COVID-19 levels. The rise in waiting lists was primarily due to restrictions in referrals from primary care, creating a bottleneck postpandemic. Predictive models show increasing point capacities within the system may paradoxically worsen downstream flow. While there is no simple rate-limiting step, the intervention that would most improve patient flow would be to increase consultant outpatient appointments., Conclusions: The increase in NHS CVD waiting lists in England can be captured using a systems dynamics approach, as can the future state of waiting lists in the presence of further shocks/interventions. It is important for those planning services to use such a systems-oriented approach because the feed-forward and feedback nature of patient flow through referral, diagnostics and treatment leads to counterintuitive effects of interventions designed to reduce waiting lists., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Competing Interests: There are no conflicts of interest.

Results: While the inferior longitudinal fasciculus was more strongly related to spelling behaviour in skilled adults, the uncinate fasciculus was more strongly related to spelling behaviour in impaired adults. We found strong left lateralization of the arcuate fasciculus and inferior longitudinal fasciculus in both groups. However, lateralization of the inferior frontal occipital fasciculus was more strongly related to spelling response time behaviour in skilled adults, whereas lateralization of the uncinate fasciculus was more strongly related to spelling accuracy behaviour in the impaired adults., Conclusion: This study provides some useful information for understanding the underlying white matter pathways that support spelling in skilled and impaired adults and underscore the advantage of adopting multiple spelling tasks and outcomes (i.e., response time and accuracy) to better characterize brain-behaviour relationships in skilled and impaired adults.

Background: Although morbidity and mortality from COVID-19 have been widely reported, the indirect effects of the pandemic beyond 2020 on other major diseases and health service activity have not been well described., Methods and Results: Analyses used national administrative electronic hospital records in England, Scotland, and Wales for 2016-21. Admissions and procedures during the pandemic (2020-21) related to six major cardiovascular conditions [acute coronary syndrome (ACS), heart failure (HF), stroke/transient ischaemic attack (TIA), peripheral arterial disease (PAD), aortic aneurysm (AA), and venous thromboembolism(VTE)] were compared with the annual average in the pre-pandemic period (2016-19). Differences were assessed by time period and urgency of care.In 2020, there were 31 064 (-6%) fewer hospital admissions [14 506 (-4%) fewer emergencies, 16 560 (-23%) fewer elective admissions] compared with 2016-19 for the six major cardiovascular diseases (CVDs) combined. The proportional reduction in admissions was similar in all three countries. Overall, hospital admissions returned to pre-pandemic levels in 2021. Elective admissions remained substantially below expected levels for almost all conditions in all three countries [-10 996 (-15%) fewer admissions]. However, these reductions were offset by higher than expected total emergency admissions [+25 878 (+6%) higher admissions], notably for HF and stroke in England, and for VTE in all three countries. Analyses for procedures showed similar temporal variations to admissions., Conclusion: The present study highlights increasing emergency cardiovascular admissions during the pandemic, in the context of a substantial and sustained reduction in elective admissions and procedures. This is likely to increase further the demands on cardiovascular services over the coming years., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Pancreatic cancer (PC) carries a high risk of venous thromboembolism (VTE). Several risk assessment models (RAMs) predict benefit of thromboprophylaxis in solid tumors; however, none are verified in metastatic pancreatic cancer (mPC)., Methods: A retrospective mPC cohort treated at an academic cancer center from 2010 to 2016 was investigated for VTE incidence (VTEmets). Multivariable regression analysis was used to assess multiple VTE risk factors. Overall survival (OS) was compared between mPC groups with and without VTE. Survival was analyzed using Kaplan-Meier survival plots and Cox proportional hazards regressions., Results: 400 mPC patients (median age 66; 52% males) were included. 87% had performance status of ECOG 0-1; 70% had advanced stage at PC diagnosis. Incidence of VTEmets was 17.5%; median time of occurrence 3.48 months after mPC diagnosis. Survival analysis started at median VTE occurrence. Median OS was 10.5 months in VTEmets vs. 13.4 in non-VTE group. Only advanced stage (OR 3.7, p = .001) correlated with increased VTE risk., Conclusions: The results suggest mPC carries a significant VTE burden. VTE predicts poor outcomes from the point of median VTE occurrence. Advanced stage disease is the strongest risk factor. Future studies are needed to define risk stratification, survival benefit, and choice of thromboprophylaxis., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Due to lower intensity of infection and greater intervals from last exposure, parasitologic detection methods for schistosomiasis are poorly sensitive in non-endemic areas, challenging accurate diagnosis., Methods: We evaluated parasitologic versus indirect detection methods for schistosomiasis. We included specimens submitted for Schistosoma serology, and stool for ova and parasite microscopy. Three real-time PCR assays targeting Schistosoma mansoni and S. haematobium were performed. Primary outcome measures were sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), where both microscopy and serology were the composite reference standard against serum PCR., Results: Of 8168 serum specimens submitted for Schistosoma serology, 638 (7.8%) were reactive and 6705 (82.1%) were non-reactive. Of 156,771 stool specimens submitted for ova and parasite testing, 46 (0.03%) were positive for eggs of S. mansoni . Four (0.5%) urine specimens were positive for eggs of S. haematobium . Combined serum PCRs targeting S. mansoni had a sensitivity and specificity of 27.8% (95% CI = 18.3-39.1%) and 100% (95% CI = 83.9-100%), respectively, with PPV of 100% (95% CI = 100%) and NPV of 26.9% (95% CI = 24.3-29.7%). The one serum sample positive for S. haematobium was also detectable by our S. haematobium PCR. No cross-reactivity was observed for all three PCR assays., Conclusions: Although serology is highly sensitive, parasitologic tests signify active infection, but are limited by low population-level sensitivity, particularly in non-endemic settings. Although serum PCR offered no performance advantage over stool microscopy, its role in diagnostic parasitology should be pursued due to its high-throughput and operator-independent nature., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2023.)

Reading and spelling skills are important to communicate in today's literate society, however, the underlying processes of spelling skills are under-researched compared to reading skills. Our goals were to (a) study how the component skills of phonological, orthographic and morphological awareness are different in adults with and without reading difficulties, and (b) characterize the relationship between the component skills and reading and spelling performance in both skilled and poor readers. Participants (N = 37, N = 15 with reading impairments and N = 22 skilled readers) took part in the study where they completed several literacy-based measures. We performed a series of mixed ANOVAs to study the between-group differences in performance and the relationship between different literacy outcomes, respectively. We found evidence for poor phonological and morphological awareness in the poor readers compared to the skilled readers. We also found differential relationships between the component skills and reading and spelling behavior. Specifically, sound awareness was significantly related to reading and spelling measures in the skilled readers, whereas morphological and sound awareness played an important role in the same skills in the poor readers. We discuss these findings in the context of potential remediation strategies for adults with persistent literacy impairments., (© 2023 The Authors. Dyslexia published by John Wiley & Sons Ltd.)

Purpose: To develop a novel 3D abdominal CEST MRI technique at 3 T using MR multitasking, which enables entire-liver coverage with free-breathing acquisition., Methods: k-Space data were continuously acquired with repetitive steady-state CEST (ss-CEST) modules. The stack-of-stars acquisition pattern was used for k-space sampling. MR multitasking was used to reconstruct motion-resolved 3D CEST images of 53 frequency offsets with entire-liver coverage and 2.0 × 2.0 × 6.0 mm 3 spatial resolution. The total scan time was 9 min. The sensitivity of amide proton transfer (APT)-CEST (magnetization transfer asymmetry [MTR asym ] at 3.5 ppm) and glycogen CEST (glycoCEST) (mean MTR asym around 1.0 ppm) signals generated with the proposed method were tested with fasting experiments., Results: Both APT-CEST and glycoCEST signals showed high sensitivity between post-fasting and post-meal acquisitions. APT-CEST and glycoCEST MTRasym signals from post-mean scans were significantly increased (APT-CEST: -0.019 ± 0.017 in post-fasting scans, 0.014 ± 0.021 in post-meal scans, p < 0.01; glycoCEST: 0.003 ± 0.009 in post-fasting scans, 0.027 ± 0.021 in post-meal scans, p < 0.01)., Conclusion: The proposed 3D abdominal steady-state CEST method using MR multitasking can generate CEST images of the entire liver during free breathing., (© 2022 International Society for Magnetic Resonance in Medicine.)

Objectives: To provide estimates for how different treatment pathways for the management of severe aortic stenosis (AS) may affect National Health Service (NHS) England waiting list duration and associated mortality., Design: We constructed a mathematical model of the excess waiting list and found the closed-form analytic solution to that model. From published data, we calculated estimates for how the strategies listed under Interventions may affect the time to clear the backlog of patients waiting for treatment and the associated waiting list mortality., Setting: The NHS in England., Participants: Estimated patients with AS in England., Interventions: (1) Increasing the capacity for the treatment of severe AS, (2) converting proportions of cases from surgery to transcatheter aortic valve implantation and (3) a combination of these two., Results: In a capacitated system, clearing the backlog by returning to pre-COVID-19 capacity is not possible. A conversion rate of 50% would clear the backlog within 666 (533-848) days with 1419 (597-2189) deaths while waiting during this time. A 20% capacity increase would require 535 (434-666) days, with an associated mortality of 1172 (466-1859). A combination of converting 40% cases and increasing capacity by 20% would clear the backlog within a year (343 (281-410) days) with 784 (292-1324) deaths while awaiting treatment., Conclusion: A strategy change to the management of severe AS is required to reduce the NHS backlog and waiting list deaths during the post-COVID-19 'recovery' period. However, plausible adaptations will still incur a substantial wait to treatment and many hundreds dying while waiting., Competing Interests: Competing interests: BG acknowledges grants not related to this project from the David Telling Charitable Trust, and the Biotechnology and Biological Sciences Research Council, he additionally declared Associate Editorship of Anesthesia Journal, and being the chair DMSC for the COPIA Trial. All other authors confirm that they have no competing interests to declare., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Purpose: To perform fast 3D steady-state CEST (ss-CEST) imaging using MR Multitasking., Methods: A continuous acquisition sequence with repetitive ss-CEST modules was developed. Each ss-CEST module contains a single-lobe Gaussian saturation pulse, followed by a spoiler gradient and eight FLASH readouts (one "training line" + seven "imaging lines"). Three-dimensional Cartesian encoding was used for k-space acquisition. Reconstructed CEST images were quantified with four-pool Lorentzian fitting., Results: Steady-state CEST with whole-brain coverage was performed in 5.6 s per saturation frequency offset at the spatial resolution of 1.7 × 1.7 × 3.0 mm 3 . The total scan time was 5.5 min for 55 different frequency offsets. Quantitative CEST maps from multipool fitting showed consistent image quality across the volume., Conclusion: Three-dimensional ss-CEST with whole-brain coverage can be done at 3 T within 5.5 min using MR Multitasking., (© 2021 International Society for Magnetic Resonance in Medicine.)

Quantitative analysis of dynamic contrast-enhanced cardiovascular MRI (cMRI) datasets enables the assessment of myocardial blood flow (MBF) for objective evaluation of ischemic heart disease in patients with suspected coronary artery disease. State-of-the-art MBF quantification techniques use constrained deconvolution and are highly sensitive to noise and motion-induced errors, which can lead to unreliable outcomes in the setting of high-resolution MBF mapping. To overcome these limitations, recent iterative approaches incorporate spatial-smoothness constraints to tackle pixel-wise MBF mapping. However, such iterative methods require a computational time of up to 30 minutes per acquired myocardial slice, which is a major practical limitation. Furthermore, they cannot enforce robustness to residual nonrigid motion which can occur in clinical stress/rest studies of patients with arrhythmia. We present a non-iterative patch-wise deep learning approach for pixel-wise MBF quantification wherein local spatio-temporal features are learned from a large dataset of myocardial patches acquired in clinical stress/rest cMRI studies. Our approach is scanner-independent, computationally efficient, robust to noise, and has the unique feature of robustness to motion-induced errors. Numerical and experimental results obtained using real patient data demonstrate the effectiveness of our approach.Clinical Relevance- The proposed patch-wise deep learning approach significantly improves the reliability of high-resolution myocardial blood flow quantification in cMRI by improving its robustness to noise and nonrigid myocardial motion and is up to 300-fold faster than state-of-the-art iterative approaches.

Purpose: Genetic testing results are currently obtained approximately 1 year after referral to a medical genetics team for autosomal dominant polycystic kidney disease (ADPKD). We evaluated a mainstream genetic testing (MGT) pathway whereby the nephrology team provided pre-test counseling and selection of patients with suspected ADPKD for genetic testing prior to direct patient interaction by a medical geneticist., Sources of Information: A multidisciplinary team of nephrologists, genetic counselors, and medical geneticists developed an MGT pathway for ADPKD using current testing criteria for adult patient with suspected ADPKD and literature from MGT in oncology., Methods: An MGT pathway was assessed using a prospective cohort and compared to a retrospective cohort of 56 patients with ADPKD who received genetic testing using the standard, traditional pathway prior to implementing the MGT for ADPKD. The mainstream pathway was evaluated using time to diagnosis, diagnostic yield, and a patient survey to assess patient perceptions of the MGT pathway., Key Findings: We assessed 26 patients with ADPKD using the MGT and 18 underwent genetic testing with return of results. Of them, 52 patients had data available for analysis in the traditional control cohort. The time for return of results using our MGT pathway was significantly shorter with a median time to results of 6 months compared to 12 months for the traditional pathway. We identified causative variants in 61% of patients, variants of uncertain significance in 28%, and 10% had negative testing which is in line with expectations from the literature. The patient surveys showed high satisfaction rates with the MGT pathway., Limitations: This report is an evaluation of a new genetic testing pathway restricted to a single, publicly funded health care center. The MGT pathway involved a prospective collection of a limited number of patients with ADPKD with comparison to a retrospective cohort of patients with ADPKD evaluated by standard testing., Implications: A MGT pathway using clearly defined criteria and commercially available gene panels for ADPKD can be successfully implemented in a publicly funded health care system to reduce the time required to obtain genetic results., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)