Correction: A Bayesian belief data mining approach applied to rice and shrimp aquaculture.

[This corrects the article DOI: 10.1371/journal.pone.0262402.].

Health and wellbeing of staff working at higher education institutions globally during the post-COVID-19 pandemic period: evidence from a cross-sectional study.

BACKGROUND: The ongoing global crisis of Higher Education (HE) institutions during the post-COVID-19 pandemic period has increased the likelihood of enduring psychological stressors for staff. This study aimed to identify factors associated with job insecurity, burnout, psychological distress and coping amongst staff working at HE institutions globally. METHODS: An anonymous cross-sectional study was conducted in 2023 with staff at HE institutions across 16 countries. Job insecurity was measured using the Job Insecurity Scale (JIS), burnout using the Perceived Burnout measure question, psychological distress using the Kessler Psychological Distress Scale (K10), and coping using the Brief Resilient Coping Scale. Multivariable logistic regression with a stepwise variable selection method was used to identify associations. RESULTS: A total of 2,353 staff participated; the mean age (± SD) was 43(± 10) years and 61% were females. Most staff (85%) did not feel job insecurity, one-third (29%) perceived burnout in their jobs, more than two-thirds (73%) experienced moderate to very high levels of psychological distress, and more than half (58%) exhibited medium to high resilient coping. Perceived job insecurity was associated with staff working part-time [Adjusted Odds Ratio 1.53 (95% Confidence Intervals 1.15-2.02)], having an academic appointment [2.45 (1.78-3.27)], having multiple co-morbidities [1.86 (1.41-2.48)], perceived burnout [1.99 (1.54-2.56)] and moderate to very high level of psychological distress [1.68 (1.18-2.39)]. Perceived burnout was associated with being female [1.35 (1.12-1.63)], having multiple co-morbidities [1.53 (1.20-1.97)], perceived job insecurity [1.99 (1.55-2.57)], and moderate to very high levels of psychological distress [3.23 (2.42-4.30)]. Staff with multiple co-morbidities [1.46 (1.11-1.92)], mental health issues [2.73 (1.79-4.15)], perceived job insecurity [1.61 (1.13-2.30)], and perceived burnout [3.22 (2.41-4.31)] were associated with moderate to very high levels of psychological distress. Staff who perceived their mental health as good to excellent [3.36 (2.69-4.19)] were more likely to have medium to high resilient coping. CONCLUSIONS: Factors identified in this study should be considered in reviewing and updating current support strategies for staff at HE institutions across all countries to reduce stress and burnout and improve wellbeing.

Hyperpolarized 13C and 31P MRS detects differences in cardiac energetics, metabolism, and function in obesity, and responses following treatment.

Obesity is associated with important changes in cardiac energetics and function, and an increased risk of adverse cardiovascular outcomes. Multi-nuclear MRS and MRI techniques have the potential to provide a comprehensive non-invasive assessment of cardiac metabolic perturbation in obesity. A rat model of obesity was created by high-fat diet feeding. This model was characterized using in vivo hyperpolarized [1-13C]pyruvate and [2-13C]pyruvate MRS, echocardiography and perfused heart 31P MRS. Two groups of obese rats were subsequently treated with either caloric restriction or the glucagon-like peptide-1 analogue/agonist liraglutide, prior to reassessment. The model recapitulated cardiovascular consequences of human obesity, including mild left ventricular hypertrophy, and diastolic, but not systolic, dysfunction. Hyperpolarized 13C and 31P MRS demonstrated that obesity was associated with reduced myocardial pyruvate dehydrogenase flux, altered cardiac tricarboxylic acid (TCA) cycle metabolism, and impaired myocardial energetic status (lower phosphocreatine to adenosine triphosphate ratio and impaired cardiac ΔG~ATP). Both caloric restriction and liraglutide treatment were associated with normalization of metabolic changes, alongside improvement in cardiac diastolic function. In this model of obesity, hyperpolarized 13C and 31P MRS demonstrated abnormalities in cardiac metabolism at multiple levels, including myocardial substrate selection, TCA cycle, and high-energy phosphorus metabolism. Metabolic changes were linked with impairment of diastolic function and were reversed in concert following either caloric restriction or liraglutide treatment. With hyperpolarized 13C and 31P techniques now available for human use, the findings support a role for multi-nuclear MRS in the development of new therapies for obesity.

Histologic Findings of Sinusoidal Dilatation and Congestion in Liver Grafts Do Not Correlate with Hepatic Venous Anastomotic Gradients.

PURPOSE: Hepatic venous transplant anastomotic pressure gradient measurement and transjugular liver biopsy are commonly used in clinical decision-making in patients with suspected anastomotic hepatic venous outflow obstruction. This investigation aimed to determine if sinusoidal dilatation and congestion on histology are predictive of hepatic venous anastomotic outflow obstruction, and if it can help select patients for hepatic vein anastomosis stenting. MATERIALS AND METHODS: This is a single-center retrospective study of 166 transjugular liver biopsies in 139 patients obtained concurrently with transplant venous anastomotic pressure gradient measurement. Demographic characteristics, laboratory parameters, procedure and clinical data, and histology of time-zero allograft biopsies were analyzed. RESULTS: No relationship was found between transplant venous anastomotic pressure gradient and sinusoidal dilatation and congestion (P = 0.92). Logistic regression analysis for sinusoidal dilatation and congestion confirmed a significant relationship with reperfusion/preservation injury and/or necrosis of the allograft at time-zero biopsy (OR 6.6 [1.3-33.1], P = 0.02). CONCLUSION: There is no relationship between histologic sinusoidal dilatation and congestion and liver transplant hepatic vein anastomotic gradient. In this study group, sinusoidal dilatation and congestion is a nonspecific histopathologic finding that is not a reliable criterion to select patients for venous anastomosis stenting.

A Mitochondrial Basis for Heart Failure Progression.

In health, the human heart is able to match ATP supply and demand perfectly. It requires 6 kg of ATP per day to satisfy demands of external work (mechanical force generation) and internal work (ion movements and basal metabolism). The heart is able to link supply with demand via direct responses to ADP and AMP concentrations but calcium concentrations within myocytes play a key role, signalling both inotropy, chronotropy and matched increases in ATP production. Calcium/calmodulin-dependent protein kinase (CaMKII) is a key adapter to increased workload, facilitating a greater and more rapid calcium concentration change. In the failing heart, this is dysfunctional and ATP supply is impaired. This review aims to examine the mechanisms and pathologies that link increased energy demand to this disrupted situation. We examine the roles of calcium loading, oxidative stress, mitochondrial structural abnormalities and damage-associated molecular patterns.

Changes in the investigation and management of suspected myocardial infarction and injury during COVID-19: a multi-centre study using routinely collected healthcare data.

Objective: The COVID-19 pandemic was associated with a reduction in the incidence of myocardial infarction (MI) diagnosis, in part because patients were less likely to present to hospital. Whether changes in clinical decision making with respect to the investigation and management of patients with suspected MI also contributed to this phenomenon is unknown. Methods: Multicentre retrospective cohort study in three UK centres contributing data to the National Institute for Health Research Health Informatics Collaborative. Patients presenting to the Emergency Department (ED) of these centres between 1st January 2020 and 1st September 2020 were included. Three time epochs within this period were defined based on the course of the first wave of the COVID-19 pandemic: pre-pandemic (epoch 1), lockdown (epoch 2), post-lockdown (epoch 3). Results: During the study period, 10,670 unique patients attended the ED with chest pain or dyspnoea, of whom 6,928 were admitted. Despite fewer total ED attendances in epoch 2, patient presentations with dyspnoea were increased (p < 0.001), with greater likelihood of troponin testing in both chest pain (p = 0.001) and dyspnoea (p < 0.001). There was a dramatic reduction in elective and emergency cardiac procedures (both p < 0.001), and greater overall mortality of patients (p < 0.001), compared to the pre-pandemic period. Positive COVID-19 and/or troponin test results were associated with increased mortality (p < 0.001), though the temporal risk profile differed. Conclusions: The first wave of the COVID-19 pandemic was associated with significant changes not just in presentation, but also the investigation, management, and outcomes of patients presenting with suspected myocardial injury or MI.

The effect of sodium-glucose cotransporter-2 inhibitors on inflammatory biomarkers: A meta-analysis of randomized controlled trials.

AIMS: To conduct a meta-analysis of randomized controlled trials (RCTs) to assess the effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on inflammatory biomarkers. METHODS: Medline, Embase and the Cochrane Library were searched for RCTs investigating the effect of SGLT2 inhibitors on inflammatory biomarkers, adipokine profiles and insulin sensitivity. RESULTS: Thirty-eight RCTs were included (14 967 participants, 63.3% male, mean age 62 ± 8.6 years) with a median (interquartile range) follow-up of 16 (12-24) weeks. Meta-analysis showed that SGLT2 inhibitors significantly improved adiponectin, interleukin-6, tumour necrosis factor receptor-1 (vs. placebo alone: standardized mean difference [SMD] 0.34 [95% confidence interval {CI} 0.23, 0.45], mean difference [MD] -0.85 pg/mL [95% CI -1.32, -0.38], SMD -0.13 [95% CI -0.20, -0.06], respectively), leptin and homeostatic model assessment of insulin resistance index (vs. CONTROL: SMD -0.20 [95% CI -0.33, -0.07], MD -0.83 [95% CI -1.32, -0.33], respectively). There were no significant changes in C-reactive protein (CRP), tumour necrosis factor-α, plasminogen activator inhibitor-1, fibroblast growth factor-21 or monocyte chemoattractant protein-1. CONCLUSIONS: Our analysis shows that SGLT2 inhibitors likely improve adipokine biomarkers and insulin sensitivity, but there is little evidence that SGLT2 inhibitors improve other inflammatory biomarkers including CRP.

Image-Guided Transbronchial Pulmonary Cryoablation with a Flexible Cryoprobe in Swine: Performance and Radiology-Pathology Correlation.

PURPOSE: To evaluate the performance of a prototype flexible transbronchial cryoprobe compared with that of percutaneous transthoracic cryoablation and to define cone-beam computed tomography (CT) imaging and pathology cryolesion features in an in vivo swine model. MATERIALS AND METHODS: Transbronchial cryoablation was performed with a prototype flexible cryoprobe (3 central and 3 peripheral lung ablations in 3 swine) and compared with transthoracic cryoablation performed with a commercially available rigid cryoprobe (2 peripheral lung ablations in 1 swine). Procedural time and cryoablation success rates for endobronchial navigation and cryoneedle deployment were measured. Intraoperative cone-beam CT imaging features of cryolesions were characterized and correlated with gross pathology and hematoxylin and eosin-stained sections of the explanted cryolesions. RESULTS: The flexible cryoprobe was successfully navigated and delivered to each target through a steerable guiding sheath (6/6). At 4 minutes after ablation, 5 of 6 transbronchial and 2 of 2 transthoracic cryolesions were visible on cone-beam CT. The volumes on cone-beam CT images were 55.5 cm3 (SE ± 8.0) for central transbronchial ablations (n = 2), 72.5 cm3 (SE ± 8.1) for peripheral transbronchial ablations (n = 3), and 79.5 cm3 (SE ±11.6) for peripheral transthoracic ablations (n = 2). Pneumothorax developed in 1 animal after transbronchial ablation and during ablation in the transthoracic cryoablation. Images of cryoablation zones on cone-beam CT correlated well with the matched gross pathology and histopathology sections of the cryolesions. CONCLUSIONS: Transbronchial cryoablation with a flexible cryoprobe, delivered through a steerable guiding sheath, is feasible. Transbronchial cryoablation zones are imageable with cone-beam CT, with gross pathology and histopathology similar to those of transthoracic cryoablation.

The effect of sodium-glucose co-transporter 2 inhibitors on outcomes after cardiac resynchronization therapy.

AIMS: The trials upon which recommendations for the use of cardiac resynchronization therapy (CRT) in heart failure used optimal medical therapy (OMT) before sodium-glucose co-transporter 2 inhibitors (SGLT2i). Moreover, the SGLT2i heart failure trials included only a small proportion of participants with CRT, and therefore, it remains uncertain whether SGLT2i should be considered part of OMT prior to CRT. METHODS AND RESULTS: We compared electrocardiogram (ECG) and echocardiographic responses to CRT as well as hospitalization and mortality rates in consecutive patients undergoing implantation at a large tertiary centre between January 2019 to June 2022 with and without SGLT2i treatment. Three hundred seventy-four participants were included aged 74.0 ± 11.5 years (mean ± standard deviation), with a left ventricular ejection fraction (LVEF) of 31.8 ± 9.9% and QRS duration of 161 ± 29 ms. The majority had non-ischaemic cardiomyopathy (58%) and were in NYHA Class II/III (83.6%). These characteristics were similar between patients with (n = 66) and without (n = 308) prior SGLT2i treatment. Both groups demonstrated similar evidence of response to CRT in terms of QRS duration shortening, and improvements in LVEF, left ventricular end-diastolic inner-dimension (LVIDd) and diastolic function (E/A and e/e'). While there was no difference in rates of hospitalization (for heart failure or overall), mortality was significantly lower in patients treated with SGLT2i compared with those who were not (6.5 vs. 16.6%, P = 0.049). CONCLUSIONS: We observed an improvement in mortality in patients undergoing CRT prescribed SGLT2i compared with those not prescribed SGLT2i, despite similar degrees of reverse remodelling. The authors recommend starting SGLT2i prior to CRT implantation, where it does not delay implantation.

The Relationship Between Early Term Birth and the Risk of Later Childhood Mental Disorders Within a Pregnancy Cohort.

This study examines whether gestational age, birth weight, and early term birth is associated with childhood mental disorders in 342 pregnant women recruited at less than 20 weeks gestation and were then followed up until 4 years postpartum, including 93 children born at early term. Women were assessed at recruitment using the Structured Clinical Interview for DSM. At 4 years of age their children were assessed using the Preschool Age Psychiatric Assessment (PAPA) and the Child Behavior Checklist (CBCL). This study found earlier birth predicted an increased risk for anxiety disorders and demonstrated a significant interaction between gestational age and lower birthweight. The risk for ADHD increased with lower gestational age independent of birthweight. In contrast, gestational age was not associated with Oppositional Defiant Disorder, Conduct Disorder, internalizing or externalizing symptoms. These findings highlight the important differences in the association of early term birth and vulnerability for specific mental disorders.

Abscopal downstaging of intermediate stage hepatocellular via combination cryoablation and immunotherapy with complete pathologic response.

The abscopal effect is a rare phenomenon characterized by disease regression in distant sites after tumoral locoregional therapy. Locoregional therapy, such as cryoablation, can induce an antitumor immunological response, potentially improving outcomes in cancer patients receiving immunotherapy. This report describes a patient with multifocal hepatocellular carcinoma who progressed through multiple locoregional therapies, was initially unresponsive to immunotherapy, and later achieved rapid and sustained disease regression with a combination cryoablation and immunotherapy. A 5-year sustained complete tumor response successfully bridged to liver transplantation.

Use of Resonant Acoustic Mixing Technology for Ultra-Low-Dose Blending in a Single-Step Mixing Process.

PURPOSE: To evaluate the use of resonant acoustic mixing (RAM) technology for homogenous blending of a morphologically challenging model API in low-dose concentrations (<0.1% w/w), and assess the potential for blend uniformity (BU) optimization. METHODS: Caffeine (CAF) mixing was carried out using a LabRAM I benchtop mixer. Uniformity was assessed under a range of mixing conditions and sample preparation procedures in order to optimize system performance. The capacity for microscale mixing was evaluated from final parameters for 0.05% and 0.0125% CAF blends. RESULTS: Upon optimization, RAM was able to accurately prepare homogeneous mixtures of <0.1% CAF in dilutions of up to 1 part per 8,000. Results from a 0.05% blend targeting 125 µg CAF dosage amounts revealed an AV score of 8.8 while a 0.0125% w/w blend accurately prepared 25 µg of CAF with 99.3% accuracy (98.7% label claim) and AV of 10.1. Microscale mixing in the 0.05% w/w blend was confirmed from plots of BU data against sample size demonstrating a slope of 0.05 within the range of 250-10 mg sample (125-5 µg CAF). L1 BU criteria only failed at the level of 2 µg CAF, despite target precision to 26 nanograms (98.7% label claim). CONCLUSIONS: This study presents the first instance of a homogenously mixed <0.1% (w/w) blend using RAM technology and demonstrate the suitability for reproducible dosing of single-digit microgram drug amounts. Uniformity is documented for API amounts 60x smaller than a recent report has shown and 10,000x smaller than achieved previously with CAF.

GLI1+ perivascular, renal, progenitor cells: The likely source of spontaneous neoplasia that created the AGMK1-9T7 cell line.

The AGMK1-9T7 cell line has been used to study neoplasia in tissue culture. By passage in cell culture, these cells evolved to become tumorigenic and metastatic in immunodeficient mice at passage 40. Of the 20 x 106 kidney cells originally plated, less than 2% formed the colonies that evolved to create this cell line. These cells could be the progeny of some type of kidney progenitor cells. To characterize these cells, we documented their renal lineage by their expression of PAX-2 and MIOX, detected by indirect immunofluorescence. These cells assessed by flow-cytometry expressed high levels of CD44, CD73, CD105, Sca-1, and GLI1 across all passages tested; these markers have been reported to be expressed by renal progenitor cells. The expression of GLI1 was confirmed by immunofluorescence and western blot analysis. Cells from passages 13 to 23 possessed the ability to differentiate into adipocytes, osteoblasts, and chondrocytes; after passage 23, their ability to form these cell types was lost. These data indicate that the cells that formed the AGMK1-9T7 cell line were GLI1+ perivascular, kidney, progenitor cells.

Immune Effects of Cryoablation in Woodchuck Hepatocellular Carcinoma.

Objectives: Local and systemic immune responses evoked by locoregional therapies such as cryoablation are incompletely understood. The aim of this study was to characterize cryoablation-related immune response and the capacity of immune drugs to augment immunity upon cryoablation for the treatment of hepatocellular carcinoma (HCC) using a woodchuck hepatocellular carcinoma model. Materials and Methods: Twelve woodchucks chronically infected with woodchuck hepatitis virus and with hepatocellular carcinoma underwent imaging with contrast-enhanced CT. Partial cryoablation of tumors in three woodchucks was performed. Fourteen days after cryoablation, liver tissues were harvested and stained with H&E and TUNEL, and immune infiltrates were quantified. Peripheral blood mononuclear cells (PBMC) were collected from ablated and nonablated woodchucks, labeled with carboxyfluorescein succinimidyl ester (CFSE) and cultured with immune-modulating drugs, including a small PD-L1 antagonist molecule (BMS-202) and three TLR7/8 agonists (DSR 6434, GS-9620, gardiquimod). After incubation, cell replication and immune cell populations were analyzed by flow cytometry. Results: Local immune response in tumors was characterized by an increased number of CD3+ T lymphocytes and natural killer cells in the cryolesion margin compared to other tumor regions. T regulatory cells were found in higher numbers in distant tumors within the liver compared to untreated or control tumors. Cryoablation also augmented the systemic immune response as demonstrated by higher numbers of PBMC responses upon immune drug stimulation in the cryoablation group. Conclusions: Partial cryoablation augmented immune effects in both treated and remote untreated tumor microenvironments, as well as systemically, in woodchucks with HCC. Characterization of these mechanisms may enhance development of novel drug-device combinations for treatment of HCC.

A secondary daily persistent headache from onset with underlying nutcracker physiology and spinal epidural venous congestion: case series with lumbar vein embolization as a therapeutic approach.

The authors have published on a unique subset of patients whose headaches worsened in the Trendelenburg position and who on time-resolved MR angiography demonstrated left renal vein compression (nutcracker physiology) with retrograde left second lumbar vein (L2LV) flow and regional spinal epidural venous plexus (EVP) congestion. We hypothesized that the spinal EVP congestion subsequently causes a secondary congestion of the cerebral venous system, which then leads to an elevation of CSF pressure above that individuals CSF pressure set point. This results in a daily headache from onset. Thus, eliminating the spinal EVP could conceivably improve or eliminate the manifested headache syndrome. We now present a case series of four patients with long-term follow-up utilizing lumbar vein coil embolization as a new therapeutic approach. In each patient, the MR angiography findings were verified by catheter-based venography. Treatment consisted of endovascular embolization of the second lumbar vein. Four patients have had coil embolization of which three are 1 year or longer from their procedure while one is 10 months posttreatment. All patients were women. Duration of daily headache prior to embolization ranged from 4 to 8 years. Post-embolization: Three patients are either headache free or 90-95% improved with substantial pain free time. There were no procedure-related complications. Our results suggest that embolization of L2LV in a specific patient population with nutcracker physiology may substantially improve head pain issues. This is a minimally invasive outpatient technique with no apparent side effects.

Evaluating the sensitivity of newborn rats and newborn hamsters to oncogenic DNA.

To evaluate the risk of residual cellular DNA in vaccines manufactured in tumorigenic cell lines, we have been establishing in vivo assays to quantify the oncogenic activity of DNA. We had generated three oncogene-expression plasmids: pMSV-T24-H-ras, which expresses activated H-ras; pMSV-c-myc, which expresses c-myc; and pMSV-T24-H-ras/MSV-c-myc, which expresses both oncogenes. Tumors were induced in mice by pMSV-T24-H-ras plus pMSV-c-myc or by pMSV-T24-H-ras/MSV-c-myc. Because newborn hamsters and newborn rats have been recommended for oncogenicity testing of the DNA from tumorigenic mammalian cell-substrates used for vaccine production, we evaluated their sensitivity. Newborn hamsters and rats were inoculated with different doses of pMSV-T24-H-ras/MSV-c-myc to determine their sensitivity to tumor induction and with the single-oncogene-expression plasmids to determine whether single oncogenes could induce tumors. Newborn rats were more sensitive than newborn hamsters, and activated H-ras but not c-myc induced tumors in newborns of both rodent species. DNA from four cell lines established from tumors induced by pMSV-T24-H-ras/MSV-c-myc was inoculated into newborn rats. Because no tumors were induced by this cellular DNA, which should be optimal as it contains both oncogenes linked and present in several copies, we conclude that available in vivo models are not sensitive enough to detect the oncogenicity of cellular DNA.

Deepfake detection with and without content warnings.

The rapid advancement of 'deepfake' video technology-which uses deep learning artificial intelligence algorithms to create fake videos that look real-has given urgency to the question of how policymakers and technology companies should moderate inauthentic content. We conduct an experiment to measure people's alertness to and ability to detect a high-quality deepfake among a set of videos. First, we find that in a natural setting with no content warnings, individuals who are exposed to a deepfake video of neutral content are no more likely to detect anything out of the ordinary (32.9%) compared to a control group who viewed only authentic videos (34.1%). Second, we find that when individuals are given a warning that at least one video in a set of five is a deepfake, only 21.6% of respondents correctly identify the deepfake as the only inauthentic video, while the remainder erroneously select at least one genuine video as a deepfake.