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Potentials recorded on the body surface from the heart are of a spatial and temporal function. The 12-lead electrocardiogram (ECG) provides a useful means of global temporal assessment; however, it yields limited spatial information due to the smoothing effect caused by the volume conductor. In an attempt to circumvent the smoothing problem, researchers have used the five-point method (FPM) to numerically estimate the analytical solution of the Laplacian with an array of monopolar electrodes. Researchers have also developed a bipolar concentric ring electrode system to estimate the analytical Laplacian, and others have used a quasi-bipolar electrode configuration. In a search to find an electrode configuration with a close approximation to the analytical Laplacian, development of a tri-polar concentric ring electrode based on the nine-point method (NPM) was conducted. A comparison of the NPM, FPM, and discrete form of the quasi-bipolar configuration was performed over a 400 x 400 mesh with 1/400 spacing by computer modeling. Different properties of bipolar, quasi-bipolar and tri-polar concentric ring electrodes were evaluated and compared, and verified with tank experiments. One-way analysis of variance (ANOVA) with post hoc t-test and Bonferroni corrections were performed to compare the performance of the various methods and electrode configurations. It was found that the tri-polar electrode has significantly improved accuracy and local sensitivity. This paper also discusses the development of an active sensor using the tri-polar electrode configuration. A 1-cm active Laplacian tri-polar sensor based on the NPM was tested and deemed feasible for acquiring Laplacian cardiac surface potentials.

Recent technological advancements have increased the efficacy of radiotherapy, leading to effective management of cancer patients with enhanced patient survival and improved quality of life. Several important developments like multileaf collimator, integration of imaging techniques like positron emission tomography (PET) and computed tomography (CT), involvement of advanced dose calculation algorithms, and delivery techniques have increased tumor dose distribution and decreased normal tissue toxicity. Three-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), stereotactic radiotherapy, image-guided radiotherapy (IGT), and particle therapy have facilitated the planning procedures, accurate tumor delineation, and dose estimation for effective personalized treatment. In this review, we present the technological advancements in various types of EBRT methods and discuss their clinical utility and associated limitations. We also reveal novel approaches of using biocompatible yttrium oxide scintillator-photosensitizer complex (YSM) that can generate X-ray induced cytotoxic reactive oxygen species, facilitating X-ray activated photodynamic therapy (XPDT (external beam) and/or iXPDT (internal X-ray source)) and azido-derivatives of 2-deoxy-D-glucose (2-DG) as agents for site-specific radiation-induced DNA damage.

The nutritional and economic potentials of livestock systems are compromised by the emergence and spread of antimicrobial resistance. A major driver of resistance is the misuse and abuse of antimicrobial drugs. The likelihood of misuse may be elevated in low- and middle-income countries where limited professional veterinary services and inadequately controlled access to drugs are assumed to promote non-prudent practices (e.g., self-administration of drugs). The extent of these practices, as well as the knowledge and attitudes motivating them, are largely unknown within most agricultural communities in low- and middle-income countries. The main objective of this study was to document dimensions of knowledge, attitudes and practices related to antimicrobial use and antimicrobial resistance in livestock systems and identify the livelihood factors associated with these dimensions. A mixed-methods ethnographic approach was used to survey households keeping layers in Ghana (N = 110) and Kenya (N = 76), pastoralists keeping cattle, sheep, and goats in Tanzania (N = 195), and broiler farmers in Zambia (N = 198), and Zimbabwe (N = 298). Across countries, we find that it is individuals who live or work at the farm who draw upon their knowledge and experiences to make decisions regarding antimicrobial use and related practices. Input from animal health professionals is rare and antimicrobials are sourced at local, privately owned agrovet drug shops. We also find that knowledge, attitudes, and particularly practices significantly varied across countries, with poultry farmers holding more knowledge, desirable attitudes, and prudent practices compared to pastoralist households. Multivariate models showed that variation in knowledge, attitudes and practices is related to several factors, including gender, disease dynamics on the farm, and source of animal health information. Study results emphasize that interventions to limit antimicrobial resistance should be founded upon a bottom-up understanding of antimicrobial use at the farm-level given limited input from animal health professionals and under-resourced regulatory capacities within most low- and middle-income countries. Establishing this bottom-up understanding across cultures and production systems will inform the development and implementation of the behavioral change interventions to combat antimicrobial resistance globally.

Acute calculus cholecystitis is a very common disease with several area of uncertainty. The World Society of Emergency Surgery developed extensive guidelines in order to cover grey areas. The diagnostic criteria, the antimicrobial therapy, the evaluation of associated common bile duct stones, the identification of “high risk” patients, the surgical timing, the type of surgery, and the alternatives to surgery are discussed. Moreover the algorithm is proposed: as soon as diagnosis is made and after the evaluation of choledocholitiasis risk, laparoscopic cholecystectomy should be offered to all patients exception of those with high risk of morbidity or mortality. These Guidelines must be considered as an adjunctive tool for decision but they are not substitute of the clinical judgement for the individual patient.

Background The Global Program for the Elimination of Lymphatic Filariasis (GPELF) started operation in 2000 and aimed at eliminating the disease by the year 2020, following 5–6 rounds of effective annual Mass Drug Administration (MDA). The MDA programme took off in Ghana in 2001 and has interrupted transmission in many areas while it has persisted in some areas after 10 or more rounds of MDA. This study was to appreciate community members’ perspectives on MDA after over 15 years of implementation. Findings will inform strategies to mobilise community members to participate fully in MDA to enhance the disease elimination process. Methods This was a qualitative study, employing key-informant in-depth-interviews. Respondents were selected based on their recognition by community members as opinion leaders and persons who were knowledgeable about the topic of interest in the community. A snowball sampling technique was used to select respondents. Results Respondents were well informed about the MDA with most of them saying, it has been implemented for over 12 years. They were aware that the MDA was for the treatment/control of LF (elephantiasis). It came to light that MDA compliance was affected by five related barriers. These are; Medication, Personal, Health system, Disease and Social structure related barriers. Adverse effects of the drugs and the fact that many people perceived that they were not susceptibility to the infection have grossly affected the ingestion of the drugs. Conclusion There is a need for community mobilization and promotional activities to explain the expected adverse reactions associated with the drugs to the people. Also the importance of why every qualified person in the community must comply with MDA must be emphasized.

Metabolic dysfunction‐associated steatohepatitis‐driven hepatocellular carcinoma (MASH‐HCC) is a global clinical challenge for which there is a limited understanding of disease pathogenesis and a subsequent lack of therapeutic interventions. We previously identified that tumor necrosis factor‐alpha (TNF‐α) upregulated apoptosis antagonizing transcription factor (AATF) in MASH. Here, we investigated the effect of TNF‐α converting enzyme (TACE) inhibition as a promising targeted therapy against AATF‐mediated steatohepatitis to hepatocarcinogenesis. A preclinical murine model that recapitulates human MASH‐HCC was used in the study. C57Bl/6 mice were fed with chow diet normal water (CD) or western diet sugar water (WD) along with a low dose of carbon tetrachloride (CCl4; 0.2 μL·g−1, weekly) for 24 weeks. TACE activity, TNF‐α levels, and AATF expression were measured. The mice were treated with the TACE inhibitor Marimastat for 12 weeks, followed by analyses of liver injury, fibrosis, inflammation, and oncogenic signaling. In vitro experiments using stable clones of AATF control and AATF knockdown were also conducted. We found that AATF expression was upregulated in WD/CCl4 mice, which developed severe MASH at 12 weeks and advanced fibrosis with HCC at 24 weeks. WD/CCl4 mice showed increased TACE activity with reduced hepatic expression of sirtuin 1 (Sirt1) and tissue inhibitor of metalloproteinase 3 (Timp3). The involvement of the SIRT1/TIMP3/TACE axis was confirmed by the release of TNF‐α, which upregulated AATF, a key molecular driver of MASH‐HCC. Interestingly, TACE inhibition by Marimastat reduced liver injury, dyslipidemia, AATF expression, and oncogenic signaling, effectively preventing hepatocarcinogenesis. Furthermore, Marimastat inhibited the activation of JNK, ERK1/2, and AKT, which are key regulators of tumorigenesis in WD/CCl4 mice and in AATF control cells, but had no effect on AATF knockdown cells. This study shows that TACE inhibition prevents AATF‐mediated inflammation, fibrosis, and oncogenesis in MASH‐HCC, offering a potential target for therapeutic intervention. The SIRT1/TIMP3/TACE axis is involved in the release of TNF‐α, which upregulates AATF, a key molecular driver of MASH‐HCC. This study shows that inhibition of TNF‐α converting enzyme (TACE) by Marimastat reduces liver injury, dyslipidemia, AATF expression, and oncogenic signaling, effectively preventing hepatocarcinogenesis. Thus, TACE inhibition represents a promising targeted therapy against AATF‐mediated steatohepatitis and hepatocarcinogenesis.

Video is an increasingly important resource in higher education. A key limitation of lecture video is that it is fundamentally a sequential information stream. Quickly accessing the content aligned with specific learning objectives in a video recording of a classroom lecture is challenging. Recent research has enabled automatic reorganization of a lecture video into segments discussing different subtopics. This paper explores AI generation of visual and textual summaries of lecture video segments to improve navigation. A visual summary consists of a subset of images in the video segment that are considered the most unique and important by image analysis. A textual summary consists of a set of keywords selected from the screen text in the video segment by analyzing several factors including frequency, font size, time on screen, and existence in domain and language dictionaries. Evaluation was performed against keywords and summary images selected by human experts with the following results for the most relevant formulations. AI driven keyword selection yielded an F-1 score of 0.63 versus 0.26 for keywords sampled randomly from valid keyword candidates. AI driven visual summary yielded an F-1 score of 0.70 versus 0.59 for K-medoid clustering that is often employed for similar tasks. Surveys showed that 79% (72%) of the users agreed that a visual (textual) summary made a lecture video more useful. This framework is implemented in Videopoints, a real-world lecture video portal available to educational institutions.

Tomi Pastinen and colleagues report a genome-wide analysis of allelic expression variation in lymphoblastoid cell lines from HapMap individuals. Cis -acting variants altering gene expression are a source of phenotypic differences. The cis -acting components of expression variation can be identified through the mapping of differences in allelic expression (AE), which is the measure of relative expression between two allelic transcripts. We generated a map of AE associated SNPs using quantitative measurements of AE on Illumina Human1M BeadChips. In 53 lymphoblastoid cell lines derived from donors of European descent, we identified common cis variants affecting 30% (2935/9751) of the measured RefSeq transcripts at 0.001 permutation significance. The pervasive influence of cis -regulatory variants, which explain 50% of population variation in AE, extend to full-length transcripts and their isoforms as well as to unannotated transcripts. These strong effects facilitate fine mapping of cis -regulatory SNPs, as demonstrated by dissection of heritable control of transcripts in the systemic lupus erythematosus–associated C8orf13 - BLK region in chromosome 8. The dense collection of associations will facilitate large-scale isolation of cis -regulatory SNPs.

Microscopic review of tissue sections is of foundational importance in pathology, yet the traditional chemistry-based histology laboratory methods are labour intensive, tissue destructive, poorly scalable to the evolving needs of precision medicine and cause delays in patient diagnosis and treatment. Recent AI-based techniques offer promise in upending histology workflow; one such method developed by PictorLabs can generate near-instantaneous diagnostic images via a machine learning algorithm. Here, we demonstrate the utility of virtual staining in a blinded, wash-out controlled study of 16 cases of lymph node excisional biopsies, including a spectrum of diagnoses from reactive to lymphoma and compare the diagnostic performance of virtual and chemical H&Es across a range of stain quality, image quality, morphometric assessment and diagnostic interpretation parameters as well as proposed follow-up immunostains. Our results show non-inferior performance of virtual H&E stains across all parameters, including an improved stain quality pass rate (92% vs 79% for virtual vs chemical stains, respectively) and an equivalent rate of binary diagnostic concordance (90% vs 92%). More detailed adjudicated reviews of differential diagnoses and proposed IHC panels showed no major discordances. Virtual H&Es appear fit for purpose and non-inferior to chemical H&Es in diagnostic assessment of clinical lymph node samples, in a limited pilot study.

Objectives: Characterization of the epidemiology and cost of lawn-mower injuries is potentially useful to inform injury prevention and health policy efforts. We examined the incidence, distribution, types and severity, and emergency department (ED) and hospitalization charges of lawn-mower injuries among all age groups across the United States. Methods: This retrospective, cross-sectional study used nationally representative, population-based (all-payer) data from the US Nationwide Emergency Department Sample for lawn-mower–related ED visits and hospitalizations from January 1, 2006, through December 31, 2013. Lawn-mower injuries were identified by using International Classification of Diseases, Ninth Revision, Clinical Modification code E920 (accidents caused by a powered lawn mower). We analyzed data on demographic characteristics, age, geographic distribution, type of injury, injury severity, and hospital charges. Results: We calculated a weighted estimate of 51 151 lawn-mower injuries during the 8-year study period. The most common types of injuries were lacerations (n = 23 907, 46.7%), fractures (n = 11 433, 22.4%), and amputations (n = 11 013, 21.5%). The most common injury locations were wrist or hand (n = 33 477, 65.4%) and foot or toe (n = 10 122, 19.8%). Mean ED charges were $2482 per patient, and mean inpatient charges were $36 987 per patient. The most common procedures performed were wound irrigation or debridement (n = 1436, 29.9%) and amputation (n = 1230, 25.6%). Conclusions: Lawn-mower injuries occurred at a constant rate during the study period. Changes to nationwide industry safety standards are needed to reduce the frequency and severity of these preventable injuries.