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Abstract Retinal pigment epithelial (RPE) cells are exclusive to the retina, critically multifunctional in maintaining the visual functions and health of photoreceptors and the retina. Despite their vital functions throughout lifetime, RPE cells lack regenerative capacity, rendering them vulnerable which can lead to degenerative retinal diseases. With advancements in stem cell technology enabling the differentiation of functional cells from pluripotent stem cells and leveraging the robust autocrine and paracrine functions of RPE cells, extracellular vesicles (EVs) secreted by RPE cells hold significant therapeutic potential in supplementing RPE cell activity. While previous research has primarily focused on the trophic factors secreted by RPE cells, there is a lack of studies investigating miRNA, which serves as a master regulator of gene expression. Profiling and defining the functional role of miRNA contained within RPE‐secreted EVs is critical as it constitutes a necessary step in identifying the optimal phenotype of the EV‐secreting cell and understanding the biological cargo of EVs to develop EV‐based therapeutics. In this study, we present a comprehensive profile of miRNA in small extracellular vesicles (sEVs) secreted during RPE maturation following differentiation from human embryonic stem cells (hESCs); early‐stage hESC‐RPE (20–21 days in culture), mid‐stage hESC‐RPE (30–31 days in culture) and late‐stage hESC‐RPE (60–61 days in culture). This exploration is essential for ongoing efforts to develop and optimize EV‐based intraocular therapeutics utilizing RPE‐secreted EVs, which may significantly impact the function of dysfunctional RPE cells in retinal diseases.

Abstract Purpose Prostate MRI is established for the investigation of patients presenting with suspected early prostate cancer. Outcomes are dependent on both image quality and interpretation. This study assessed the impact of an educational intervention on participants’ theoretical knowledge of the technique. Methods Eighty-one clinicians from two centers with varying experience in prostate MRI participated. Baseline knowledge was assessed with 10 written and image-based multiple-choice questions (MCQs) prior to a course including didactic lectures and hands-on interactive workshops on prostate MRI interpretation. Post-course, participants completed a second 10-question MCQ test, matched by format, themes, and difficulty, to assess for any improvement in knowledge and performance. Results were assessed using the Wilcoxon rank sum test, and the Wilcoxon signed-rank test for paired data. Results Thirty-nine participants, including 25/49 (51.0%) and 14/32 (43.8%) at each center completed both assessments, with their results used for subsequent evaluation. Overall, there was a significant improvement from pre- (4.92 ± 2.41) to post-course scores (6.77 ± 1.46), p 500 MRIs reported) experience (6.83 ± 2.48 to 7.67 ± 0.82, p = 0.339). Conclusions A dedicated prostate MRI teaching course combining didactic lectures and hands-on workshops significantly improved short-term theoretical knowledge of the technique for clinicians with differing levels of experience. Critical relevance statement A dedicated teaching course significantly improved theoretical knowledge of the technique particularly for clinicians with less reporting experience and a lower baseline knowledge. The multiple-choice questions format mapped improved performance and may be considered as part of future MRI certification initiatives. Key points • Prostate MRI knowledge is important for image interpretation and optimizing acquisition sequences. • A dedicated teaching course significantly improved theoretical knowledge of the technique. • Improved performance was more apparent in clinicians with less reporting experience and a lower baseline knowledge. Graphical Abstract

Background: Mutations in MECP2 predominantly cause Rett syndrome and can be modeled in vitro using human stem cell–derived neurons. Patients with Rett syndrome have signs of cortical hyperexcitability, such as seizures. Human stem cell–derived MECP2 null excitatory neurons have smaller soma size and reduced synaptic connectivity but are also hyperexcitable due to higher input resistance. Paradoxically, networks of MECP2 null neurons show a decrease in the frequency of network bursts consistent with a hypoconnectivity phenotype. Here, we examine this issue. Methods: We reanalyzed multielectrode array data from 3 isogenic MECP2 cell line pairs recorded over 6 weeks (n = 144). We used a custom burst detection algorithm to analyze network events and isolated a phenomenon that we termed reverberating super bursts (RSBs). To probe potential mechanisms of RSBs, we conducted pharmacological manipulations using bicuculline, EGTA-AM, and DMSO on 1 cell line (n = 34). Results: RSBs, often misidentified as single long-duration bursts, consisted of a large-amplitude initial burst followed by several high-frequency, low-amplitude minibursts. Our analysis revealed that MECP2 null networks exhibited increased frequency of RSBs, which produced increased bursts compared with isogenic controls. Bicuculline or DMSO treatment did not affect RSBs. EGTA-AM selectively eliminated RSBs and rescued network burst dynamics. Conclusions: During early development, MECP2 null neurons are hyperexcitable and produce hyperexcitable networks. This may predispose them to the emergence of hypersynchronic states that potentially translate into seizures. Network hyperexcitability depends on asynchronous neurotransmitter release that is likely driven by presynaptic Ca2+ and can be rescued by EGTA-AM to restore typical network dynamics.

The optimum setting of directional overcurrent relays (DOCRs) is required to avoid miscoordination and avail fast response. To fulfill these requirements, it is required to prefer optimization techniques and modifications in objective functions (OF). Many researchers have adopted soft computing techniques and suggested modifications in the objective function for problem formulation of overcurrent relay coordination. Though these modifications and suggestions attain an optimum value of relay parameters, unfortunately, some of them don't follow the fundamental requirements of overcurrent relay coordination. This paper reflects on such modified objective functions and conveys a proper approach. Further, the paper proposes a new objective function as per the overcurrent relay coordination criteria. The novelty of the paper is to modify the existing objective function as per overcurrent relays coordination criteria and to add a new term in it to avoid miscoordination. The proposed objective function (POF) is applied on two power system test networks and results reveal that it is efficient and accurate.

Abstract Background We aimed to prospectively compare the diagnostic performance of gadoxetic acid-enhanced MRI (EOB-MRI) and contrast-enhanced Computed Tomography (CECT) for hepatocellular carcinoma (HCC) detection and liver transplant (LT) eligibility assessment in cirrhotic patients with explant histopathology correlation. Methods In this prospective, single-institution ethics-approved study, 101 cirrhotic patients were enrolled consecutively from the pre-LT clinic with written informed consent. Patients underwent CECT and EOB-MRI alternately every 3 months until LT or study exclusion. Two blinded radiologists independently scored hepatic lesions on CECT and EOB-MRI utilizing the liver imaging reporting and data system (LI-RADS) version 2018. Liver explant histopathology was the reference standard. Pre-LT eligibility accuracies with EOB-MRI and CECT as per Milan criteria (MC) were assessed in reference to post-LT explant histopathology. Lesion-level and patient-level statistical analyses were performed. Results Sixty patients (49 men; age 33–72 years) underwent LT successfully. One hundred four non-treated HCC and 42 viable HCC in previously treated HCC were identified at explant histopathology. For LR-4/5 category lesions, EOB-MRI had a higher pooled sensitivity (86.7% versus 75.3%, p

In order to pave the way for a modernized electricity grid with distributed energy sources and storage, a direct energy transaction among peers in the local electricity market (LEM) is emerging. The design of the local energy market has frequently concentrated on its structures and technological problems, but little on how to increase the willingness of customers to participate by using a customer-centric approach. In this article, we provide consumer engagement strategies in LEM with a focus on maximizing financial return while exchanging energy with peers. The empirical investigation is subjected to two stages of optimization, the first of which has a goal of minimizing system costs and the second of which has a goal of maximizing consumer rewards. We present four methods for rewarding customers financially for taking part in LEM. Segmentation of customers is proposed to achieve the profit maximization goal. The system cost is calculated for two cases and cost saving is used to distribute among the market participants. The proposed LEM model results in 12.87% cost savings which is used to incentivize the active participants of the market. Thus policy makers can be recommended to integrate such market mechanisms to ensure a flexible and efficient market mechanism.

Abstract Objectives To compare the diagnostic performance of international hepatocellular carcinoma (HCC) guidelines with gadoxetic acid-enhanced MRI (EOB-MRI) and contrast-enhanced Computed tomography (CECT) and their impact on liver transplant (LT) allocation in cirrhotic patients with explant histopathology correlation. Methods In this prospective single-centre ethics-approved study, 101 cirrhotic patients were consecutively enrolled with informed consent from the pre-LT clinic. They underwent CECT and EOB-MRI alternately at three monthly intervals until LT or removal from LT list. Two abdominal radiologists, blinded to explant histopathology, independently recorded liver lesions visible on CECT and EOB-MRI. Imaging-based HCC scores were assigned to non-treated liver lesions utilizing Liver Imaging Reporting and Data System (LI-RADS), European Association for the Study of the Liver (EASL), Asian-Pacific Association for the Study of the Liver (APASL) and Korean Liver Cancer Association-National Cancer Center (KLCA) guidelines. Liver explant histopathology was the reference standard. Simulated LT eligibility was assessed as per Milan criteria (MC) in reference to explant histopathology. Results One hundred and three non-treated HCC and 12 non-HCC malignancy were identified at explant histopathology in 34 patients (29 men, 5 women, age 55–73 years). Higher HCC sensitivities of statistical significance were observed with EOB-MRI for LI-RADS 4 + 5, APASL and KLCA compared to LI-RADS 5 and EASL with greatest sensitivity obtained for LIRADS 4 + 5 lesions. HCC sensitivities by all guidelines with both EOB-MRI and CECT were significantly lower if all histopathology-detected HCCs were included in the analysis, compared to imaging-visible lesions only. A significantly greater variation in HCC sensitivity was noted across the guidelines with EOB-MRI compared to CECT. No significant differences in simulated LT eligibility based on MC were observed across the HCC scoring guidelines with EOB-MRI or CECT. Conclusion HCC sensitivities are variable depending on scoring guideline, lesion size and imaging modality utilised. Prior studies that included only lesions visible on pre-operative imaging overestimate the diagnostic performance of HCC scoring guidelines. Per-lesion differences in HCC diagnosis across these guidelines did not impact patient-level LT eligibility based on MC.

We present the case of a 23 year old male, marijuana smoker, who suffered acute anterior wall MI. OCT study revealed red thrombus with adequate minimum lumen area in LAD, which was managed with DAPT. Repeat OCT study revealed complete resolution of thrombus with underlying plaque erosion.

Abstract Objectives To evaluate gadoxetic acid-enhanced liver MRI (EOB-MRI) versus contrast-enhanced computed tomography (CECT) for preoperative detection of liver metastasis (LM) and reduction of open-close laparotomies for pancreatic ductal adenocarcinoma (PDAC). Methods Sixty-six patients with PDAC had undergone preoperative EOB-MRI and CECT. LM detection by EOB-MRI and CECT and their impact on surgical planning, open-close laparotomies were compared by clinical and radiology reports and retrospective analysis of imaging by two blinded independent readers. Histopathology or imaging follow-up was the reference standard. Statistical analysis was performed at patient and lesion levels with two-sided McNemar tests. Results EOB-MRI showed higher sensitivity versus CECT (71.7% [62.1-80.0] vs. 34% [25.0-43.8]; p = 0.009), comparable specificity (98.6%, [96.9-99.5] vs. 100%, [99.1-100], and higher AUROC (85.1%, [80.4-89.9] vs. 66.9%, [60.9-73.1]) for LM detection. An incremental 7.6% of patients were excluded from surgery with a potential reduction of up to 13.6% in futile open-close laparotomies due to LM detected on EOB-MRI only. Conclusions Preoperative EOB-MRI has superior diagnostic performance in detecting LM from PDAC. This better informs surgical eligibility with potential reduction of futile open-close laparotomies from attempted curative intent pancreatic cancer surgery.

Abstract Outpatient follow-up after hospital discharge improves continuity of care and reduces readmissions, but rates of follow-up remain low. It is not known whether electronic medical record (EMR)-based tools improve follow-up. The aim of this study was to determine if an EMR-based order to secure cardiology follow-up appointments at hospital discharge would improve follow-up rates and hospital readmission rates. A pre-post interventional study was conducted and evaluated 39,209 cardiovascular medicine discharges within an academic center between 2012 and 2017. Follow-up rates and readmission rates were compared during 2 years prior to EMR-order implementation (pre-order era 2012–2013, n = 12,852) and 4 years after implementation (EMR-order era 2014–2017, n = 26,357). The primary endpoint was 90-day cardiovascular follow-up rates within our health system. In the overall cohort, the mean age of patients was 69.3 years [SD 14.7] and 60.7% (n = 23,827) were male. In the pre-order era, 90-day follow-up was 56.7 ± 0.4% (7286 of 12,852) and increased to 67.9 ± 0.3% (17,888 of 26,357, P

The South African family physician (FP) is an expert generalist who has a number of roles to strengthen the district health system. A research study on FPs in district hospitals has previously demonstrated an impact; however, more evidence on impact in primary health care (PHC) is needed. By serving as a consultant for the PHC team, the FP may improve access to care, capacitate team members, enhance comprehensiveness of care, and improve coordination and continuity of care. This report narrates the story of how one of the FPs at a rural district hospital recorded his experience of being a consultant to the PHC team and was able to self-audit the experience. A self-designed audit tool analysed 1000 patient consultations with the FP and enabled a reflection on the coronavirus disease 2019 (COVID-19)-related changes to the consultant role. There was a clear need for FPs to consult patients with complex multi-morbidity and multifaceted psychosocial aspects to their illness, in consultation with their team members. Patients were referred to them by medical officers, other specialists, family medicine registrars, allied healthcare professionals and nurse practitioners. The FP’s ability to strengthen the PHC service outside the district hospital may be enhanced by creating more FP posts at a subdistrict level to support high-quality, team-based primary care in line with the PHC policy directions.

The inverse sum indeg index of a connected graph G is defined as the sum of the ratio for all edges uv in the edge set of G, where denotes the degree of a point u. Recently, Pattabiraman [] has obtained bounds for the inverse sum indeg index of graphs. The upper and lower bounds obtained in terms of harmonic index and second Zagreb index are prone to some error. In this note we correct these errors by establishing the proper bounds in terms of harmonic index and second Zagreb index.

Microbial communities are catalysts that drive the operation of microbial fuel cells (MFCs). In this study, the use of a defined co-culture of Escherichia coli and Pseudomonas aeruginosa towards improved power generation in MFCs is described. The co-culture has been initially evaluated for substrate consumption, biofilm formation and microbial electron transfer activity. The co-culture gave an enhanced power density of 190.44 mW m−2, while E. coli and P. aeruginosa as pure cultures generated lesser power densities of 139.24 and 158.76 mW m−2 respectively. The photosynthetic alga Chlorella vulgaris was then inoculated in the cathode chamber. Co-cultures in the presence of C. vulgaris improved the mean power density from 175 mW m−2 to 248 mW m−2, a 41.7% rise. A synergistic effect was observed when the co-cultures were coupled with C. vulgaris. Combining co-cultures with photosynthetic MFCs offers a lot of promise in studying mechanisms and expanding the nature of applications.

This paper introduces a new protection system for solar photovoltaic generator (SPVG)-connected networks. The system is a combination of voltage-restrained overcurrent relays (VROCRs) and directional overcurrent relays (DOCRs). The DOCRs are implemented to sense high fault current on the grid side, and VROCRs are deployed to sense low fault current supplied by the SPVG. Furthermore, a novel challenge for the optimal coordination of DOCRs-DOCRs and DOCRs-VROCRs is formulated. Due to the inclusion of additional constraints of VROCR, the relay coordination problem becomes more complicated. To solve this complex problem, a hybrid Harmony Search Algorithm-Bollinger Bands (HSA-BB) method is proposed. Also, the lower and upper bands in BB are dynamically adjusted with the generation number to assist the HSA in the exploration and exploitation stages. The proposed method is implemented on three different SPVG-connected networks. To exhibit the effectiveness of the proposed method, the obtained results are compared with the genetic algorithm (GA), particle swarm optimization (PSO), cuckoo search algorithm (CSA), HSA and hybrid GA-nonlinear programming (GA-NLP) method. Also, the superiority of the proposed method is evaluated using descriptive and nonparametric statistical tests.

Stribeck curves have long been used for understanding the lubricating behaviour of oils and greases, and in the recent years for applications ranging from ball point inks to synovial fluids. In the current work, an attempt is made to show as to what one can read from Stribeck curves of food samples such as chocolate spread, sauce etc. Additionally, the effect of saliva – human and artificial – on the frictional behaviour has also been studied. The tests were carried out on an MCR Tribometer with a ball-on-three-pin configuration. Polydimethylsiloxane and glass were used to simulate soft contact conditions that exist in the human mouth. Results from the tribological tests are plotted in the form of extended Stribeck curves, wherein, the friction coefficient is plotted as a function of rotational speed. Since the tribometer is capable of speeds as low as a few nanometres per second, it is also possible to observe the build-up of static friction and its transition into the kinetic regime of friction. Results indicate that certain aspects of the Stribeck curve can offer an insight into the correlation between the frictional behaviour of food to their sensory feel.

Parasites causing malaria need to migrate in order to penetrate tissue barriers and enter host cells. Here we show that the actin filament-binding protein coronin regulates gliding motility in Plasmodium berghei sporozoites, the highly motile forms of a rodent malaria-causing parasite transmitted by mosquitoes. Parasites lacking coronin show motility defects that impair colonization of the mosquito salivary glands but not migration in the skin, yet result in decreased transmission efficiency. In non-motile sporozoites low calcium concentrations mediate actin-independent coronin localization to the periphery. Engagement of extracellular ligands triggers an intracellular calcium release followed by the actin-dependent relocalization of coronin to the rear and initiation of motility. Mutational analysis and imaging suggest that coronin organizes actin filaments for productive motility. Using coronin-mCherry as a marker for the presence of actin filaments we found that protein kinase A contributes to actin filament disassembly. We finally speculate that calcium and cAMP-mediated signaling regulate a switch from rapid parasite motility to host cell invasion by differentially influencing actin dynamics.

Sickle cell disease is a hemoglobinopathy that results in paroxysmal arteriolar occlusion and tissue infarction that can manifest in a plurality of tissues. Rarely, these infarcted crises manifest in the bony orbit. Orbital infarction usually presents with acute onset of periorbital tenderness, swelling, erythema, and pain. Soft tissue swelling can result in proptosis and attenuation of extraocular movements. Expedient diagnosis of sickle cell orbital infarction is crucial because this is a potentially sight-threatening entity. Diagnosis can be delayed since the presentation has physical and radiographic findings mimicking various infectious and traumatic processes. We describe a patient who presented with sickle cell orbital crisis without pain. This case highlights the importance of maintaining a high index of suspicion in patients with known sickle cell disease or of African descent born outside the United States in a region where screening for hemoglobinopathy is not routine, even when the presentation is not classic.

PurposeTo investigate the socioeconomic effect on pediatric ophthalmologists (POs) of the first year of the COVID-19 pandemic and to assess the association of practice type with financial impact.MethodsAn email follow-up survey of all AAPOS active members (POs) in April 2021, was used in conjunction with two prior surveys. The majority of US states were represented, and respondents were categorized as academic/university (AU), hospital employee (H), or one of three types of private practice: multispecialty ophthalmology practice (MSP), pediatric ophthalmology/strabismus group (PG), or solo practice (SP).ResultsThe cumulative results during this one-year period revealed 1,533,203 examinations not performed, of which 498,291 were Medicaid. Over 65,000 surgeries were not performed. The average salary loss per PO was $57,188. The total loss of revenue for the pediatric ophthalmology sector was over $303,788,000. Practice groups making at least 75% of their prior year revenue were as follows: H, 81%; AU, 64%; MSP, 52%; PG, 50%; SP, 40%. Salary reduction in each group was as follows: H, 4.2%; AU, 15.4%; MSP, 17.2%; PG, 23.1%; SP, 40.9%. The average loss per practice was $290,151. More than 95% of private practice POs received funds from the Paycheck Protection Program.ConclusionsAt the one-year mark of the pandemic, patient care had been severely disrupted, with subsequent financial consequences. Private practice providers (and especially solo practices) were disproportionally negatively affected.

Standardized terminology is critical to providing consistent reports to referring clinicians. This lexicon aims to provide a reference for terminology frequently used in rectal cancer and reflects the consensus of the Society of Abdominal Radiology Disease Focused Panel in Rectal cancer. This lexicon divided the terms into the following categories: primary tumor staging, nodal staging, treatment response, anal canal anatomy, general anatomy, and treatments.

Retinal pigment epithelial (RPE) cells are exclusive to the retina, critically multifunctional in maintaining the visual functions and health of photoreceptors and the retina. Despite their vital functions throughout lifetime, RPE cells lack regenerative capacity, rendering them vulnerable which can lead to degenerative retinal diseases. With advancements in stem cell technology enabling the differentiation of functional cells from pluripotent stem cells and leveraging the robust autocrine and paracrine functions of RPE cells, extracellular vesicles (EVs) secreted by RPE cells hold significant therapeutic potential in supplementing RPE cell activity. While previous research has primarily focused on the trophic factors secreted by RPE cells, there is a lack of studies investigating miRNA, which serves as a master regulator of gene expression. Profiling and defining the functional role of miRNA contained within RPE‐secreted EVs is critical as it constitutes a necessary step in identifying the optimal phenotype of the EV‐secreting cell and understanding the biological cargo of EVs to develop EV‐based therapeutics. In this study, we present a comprehensive profile of miRNA in small extracellular vesicles (sEVs) secreted during RPE maturation following differentiation from human embryonic stem cells (hESCs); early‐stage hESC‐RPE (20–21 days in culture), mid‐stage hESC‐RPE (30–31 days in culture) and late‐stage hESC‐RPE (60–61 days in culture). This exploration is essential for ongoing efforts to develop and optimize EV‐based intraocular therapeutics utilizing RPE‐secreted EVs, which may significantly impact the function of dysfunctional RPE cells in retinal diseases. [ABSTRACT FROM AUTHOR]