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Kok Yuen Ho,1 Kok Ann Gwee,2 Yew Kuang Cheng,3,4 Kam Hon Yoon,5 Hwan Tak Hee,6 Abdul Razakjr Omar7 1The Pain Clinic, Mt Alvernia Hospital, 2Stomach, Liver, and Bowel Centre, Gleneagles Hospital, 3Farrer Park Hospital, 4Yong Loo Lin School of Medicine, National University of Singapore, 5El Shaddai Arthritis and Rheumatism Specialist Medical Centre, 6Pinnacle Spine and Scoliosis Centre, Mt Elizabeth Medical Centre, 7Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore Abstract: COX2-selective and nonselective (ns) nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for chronic pain management. There are marked differences in the risk of adverse gastrointestinal (GI) and cardiovascular (CV) events among different NSAIDs. In 2017, publication of two randomized controlled trials and an individual patient-data meta-analysis provided robust data on the relative GI and CV tolerability profiles of currently available NSAIDs. The PRECISION study showed similar CV-event rates with celecoxib vs naproxen and ibuprofen, but GI tolerability was better for celecoxib. In the CONCERN study of high-GI-risk patients, celecoxib was associated with fewer adverse GI-tract events than naproxen. The meta-analysis showed no significant difference between celecoxib and ns-NSAIDs in the rate of acute myocardial infarction, and celecoxib was the only COX2-selective NSAID with a lower risk of adverse CV and GI events vs ns-NSAIDs. These data add to the body of knowledge about the relative tolerability of different NSAIDs and were used to propose an updated treatment algorithm. The decision about whether to use an NSAID and which one should be based on a patient’s risk of developing adverse GI and CV events. Lower- and upper-GI-tract events need to be considered. Celecoxib has a better lower-GI-tract tolerability profile than ns-NSAIDs plus a proton-pump inhibitor. In addition, the latest data suggest that long-term use of celecoxib 200 mg/day may be appropriate for patients at increased CV risk. Keywords: nonsteroidal anti-inflammatory drugs, chronic pain, COX2 inhibitors, cardiovascular risk, gastrointestinal risk

Azadeh Bahadoran,1,2 Mehdi Ebrahimi,3 Swee Keong Yeap,1 Nikoo Safi,1 Hassan Moeini,4 Mohd Hair-Bejo,1,5 Mohd Zobir Hussein,6 Abdul Rahman Omar1,5 1Institute of Bioscience, Universiti Putra Malaysia, UPM, Serdang, 2Department of Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, 3Department of Veterinary Preclinical Sciences, Universiti Putra Malaysia, UPM, Serdang, Malaysia; 4German Cancer Research Center, Heidelberg, Germany; 5Department of Veterinary Pathology and Microbiology, Universiti Putra Malaysia, UPM, 6Advanced Technology Institute, Universiti Putra Malaysia, UPM, Serdang, Malaysia Abstract: This study was aimed to evaluate the immunogenicity of recombinant plasmid deoxyribonucleic acid (DNA), pBud-H5-green fluorescent protein (GFP)-interferon-regulatory factor (IRF)3 following delivery using polyamidoamine (PAMAM) dendrimer and transactivator of transcription (TAT)-conjugated PAMAM dendrimer as well as the effect of IRF3 as the genetic adjuvant. BALB/c mice were vaccinated transdermally with pBud-H5-GFP, PAMAM/pBud-H5-GFP, TAT-PAMAM/pBud-H5-GFP, and TAT-PAMAM/pBud-H5-GFP-IRF3. The expression analysis of H5 gene from the blood by using quantitative real-time reverse transcriptase polymerase chain reaction confirmed the ability of PAMAM dendrimer as a carrier for gene delivery, as well as the ability of TAT peptide to enhance the delivery efficiency of PAMAM dendrimer. Mice immunized with modified PAMAM by TAT peptide showed higher hemagglutination inhibition titer, and larger CD3+/CD4+ T cells and CD3+/CD8+ T cells population, as well as the production of cytokines, namely, interferon (IFN)-γ, interleukin (IL)-2, IL-15, IL-12, IL-6, and tumor necrosis factor-α compared with those immunized with native PAMAM. These results suggest that the function of TAT peptide as a cell-penetrating peptide is able to enhance the gene delivery, which results in rapid distribution of H5 in the tissues of the immunized mice. Furthermore, pBud-H5-GFP co-expressing IRF3 as a genetic adjuvant demonstrated the highest hemagglutination inhibition titer besides larger CD3+/CD4+ and CD3+/CD8+ T cells population, and strong Th1-like cytokine responses among all the systems tested. In conclusion, TAT-PAMAM dendrimer-based delivery system with IRF3 as a genetic adjuvant is an attractive transdermal DNA vaccine delivery system utilized to evaluate the efficacy of the developed DNA vaccine in inducing protection during challenge with virulent H5N1 virus. Keywords: influenza virus, DNA vaccine, vaccine delivery, dendrimer, TAT peptide

Masoumeh Firouzamandi,1,2 Hassan Moeini,3 Seyed Davood Hosseini,4 Mohd Hair Bejo,1 Abdul Rahman Omar,1,3 Parvaneh Mehrbod,3 Mohamed E El Zowalaty,5 Thomas J Webster,6 Aini Ideris1,3 1Department of Veterinary Clinical Studies, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor, Malaysia; 2Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, Iran; 3Laboratory of Vaccine and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia; 4Razi Vaccine and Serum Research Institute, Arak, Iran; 5Biomedical Research Center, Vice President Office for Research, Qatar University, Doha, Qatar; 6Department of Chemical Engineering, Northeastern University, Boston, MA, USA Abstract: Plasmid DNA (pDNA)-based vaccines have emerged as effective subunit vaccines against viral and bacterial pathogens. In this study, a DNA vaccine, namely plasmid internal ribosome entry site-HN/F, was applied in ovo against Newcastle disease (ND). Vaccination was carried out using the DNA vaccine alone or as a mixture of the pDNA and dextran-spermine (D-SPM), a nanoparticle used for pDNA delivery. The results showed that in ovo vaccination with 40 µg pDNA/egg alone induced high levels of antibody titer (P0.05). Higher antibody titer was observed in the group immunized with 40 µg pDNA/egg at 4 weeks postvaccination. The findings also showed that vaccination with 40 µg pDNA/egg alone was able to confer protection against Newcastle disease virus strain NDIBS002 in two out of seven SPF chickens. Although the chickens produced antibody titers 3 weeks after in ovo vaccination, it was not sufficient to provide complete protection to the chickens from lethal viral challenge. In addition, vaccination with pDNA/D-SPM complex did not induce high antibody titer when compared with naked pDNA. Therefore, it was concluded that DNA vaccination with plasmid internal ribosome entry site-HN/F can be suitable for in ovo application against ND, whereas D-SPM is not recommended for in ovo gene delivery. Keywords: Newcastle disease, DNA vaccine, in ovo vaccination, Newcastle disease virus, dextran-spermine nanoparticle, hemagglutinin and fusion

Chean Yeah Yong,1 Swee Keong Yeap,2 Kok Lian Ho,3 Abdul Rahman Omar,2,4 Wen Siang Tan1,2 1Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, 2Institute of Bioscience, 3Department of Pathology, Faculty of Medicine and Health Sciences, 4Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor, Malaysia Abstract: Influenza A virus poses a major threat to human health, causing outbreaks from time to time. Currently available vaccines employ inactivated viruses of different strains to provide protection against influenza virus infection. However, high mutation rates of influenza virus hemagglutinin (H) and neuraminidase (N) glycoproteins give rise to vaccine escape mutants. Thus, an effective vaccine providing protection against all strains of influenza virus would be a valuable asset. The ectodomain of matrix 2 protein (M2e) was found to be highly conserved despite mutations of the H and N glycoproteins. Hence, one to five copies of M2e were fused to the carboxyl-terminal end of the recombinant nodavirus capsid protein derived from Macrobrachium rosenbergii. The chimeric proteins harboring up to five copies of M2e formed nanosized virus-like particles approximately 30 nm in diameter, which could be purified easily by immobilized metal affinity chromatography. BALB/c mice immunized subcutaneously with these chimeric proteins developed antibodies specifically against M2e, and the titer was proportional to the copy numbers of M2e displayed on the nodavirus capsid nanoparticles. The fusion proteins also induced a type 1 T helper immune response. Collectively, M2e displayed on the nodavirus capsid nanoparticles could provide an alternative solution to a possible influenza pandemic in the future. Keywords: matrix 2 ectodomain, nodavirus capsid, virus-like particle, fusion protein, subunit vaccine, immunogenicity

Nadiah Abu,1,2 Nurul Elyani Mohamed,2 Swee Keong Yeap,3 Kian Lam Lim,4 M Nadeem Akhtar,5 Aimi Jamil Zulfadli,3 Beh Boon Kee,2 Mohd Puad Abdullah,2 Abdul Rahman Omar,3 Noorjahan Banu Alitheen2 1Bright Sparks Unit, Universiti Malaya, Kuala Lumpur, Malaysia; 2Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, 3Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor Darul Ehsan, Malaysia; 4Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Lot PT, Jalan Sungai Long, Bandar Sungai Long, Cheras, Selangor, Malaysia; 5Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang, Lebuhraya Tun Razak, Kuantan Pahang, Malaysia Abstract: Flavokawain B (FKB) is a naturally occurring chalcone that can be isolated through the root extracts of the kava-kava plant (Piper methysticum). It can also be synthesized chemically to increase the yield. This compound is a promising candidate as a biological agent, as it is reported to be involved in a wide range of biological activities. Furthermore, FKB was reported to have antitumorigenic effects in several cancer cell lines in vitro. However, the in vivo antitumor effects of FKB have not been reported on yet. Breast cancer is one of the major causes of cancer-related deaths in the world today. Any potential treatment should not only impede the growth of the tumor, but also modulate the immune system efficiently and inhibit the formation of secondary tumors. As presented in our study, FKB induced apoptosis in 4T1 tumors in vivo, as evidenced by the terminal deoxynucleotidyl transferase dUTP nick end labeling and hematoxylin and eosin staining of the tumor. FKB also regulated the immune system by increasing both helper and cytolytic T-cell and natural killer cell populations. In addition, FKB also enhanced the levels of interleukin 2 and interferon gamma but suppressed interleukin 1B. Apart from that, FKB was also found to inhibit metastasis, as evaluated by clonogenic assay, bone marrow smearing assay, real-time polymerase chain reaction, western blot, and proteome profiler analysis. All in all, FKB may serve as a promising anticancer agent, especially in treating breast cancer. Keywords: flavokawain B, kava-kava, 4T1, cancer, metastasis

Seyed Davoud Jazayeri,1 Aini Ideris,1,2 Kamyar Shameli,3 Hassan Moeini,1 Abdul Rahman Omar1,21Institute of Bioscience, 2Faculty of Veterinary Medicine, 3Faculty of Science, Universiti Putra Malaysia, Serdang, Selangor, MalaysiaAbstract: In order to develop a systemically administered safe and effective nonviral gene delivery system against avian influenza virus (AIV) that induced cytokine expression, the hemagglutinin (H5) gene of AIV, A/Ck/Malaysia/5858/04 (H5N1) and green fluorescent protein were cloned into a coexpression vector pIRES (pIREGFP-H5) and formulated using green synthesis of silver nanoparticles (AgNPs) with poly(ethylene glycol) and transfected into primary duodenal cells taken from 18-day-old specific-pathogen-free chick embryos. The AgNPs were prepared using moderated temperature and characterized for particle size, surface charge, ultraviolet-visible spectra, DNA loading, and stability. AgNPs and AgNP-pIREGFP-H5 were prepared in the size range of 13.9 nm and 25 nm with a positive charge of +78 ± 0.6 mV and +40 ± 6.2 mV, respectively. AgNPs with a positive surface charge could encapsulate pIREGFP-H5 efficiently. The ultraviolet-visible spectra for AgNP-pIREGFP-H5 treated with DNase I showed that the AgNPs were able to encapsulate pIREGFP-H5 efficiently. Polymerase chain reaction showed that AgNP-pIREGFP-H5 entered into primary duodenal cells rapidly, as early as one hour after transfection. Green fluorescent protein expression was observed after 36 hours, peaked at 48 hours, and remained stable for up to 60 hours. In addition, green fluorescent protein expression generally increased with increasing DNA concentration and time. Cells were transfected using Lipocurax in vitro transfection reagent as a positive control. A multiplex quantitative mRNA gene expression assay in the transfected primary duodenal cells via the transfection reagent and AgNPs with pIREGFP-H5 revealed expression of interleukin (IL)-18, IL-15, and IL-12β.Keywords: silver nanoparticles, avian influenza, hemagglutinin, transfection, primary cells

Fatemeh Abedini,1 Hossein Hosseinkhani,2 Maznah Ismail,1,3 Abraham J Domb,4 Abdul Rahman Omar,1,5 Pei Pei Chong,1,2 Po-Da Hong,3 Dah-Shyong Yu,6 Ira-Yudovin Farber41Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, Selangor, 2Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan, 3Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia, 4Institute of Drug Research, The Center for Nanoscience and Nanotechnology, School of Pharmacy-Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel, 5Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor, Malaysia, 6Nanomedicine Research Center, National Defense Medical Center, Taipei, TaiwanPurpose: The failure of colorectal cancer treatments is partly due to overexpression of CXCR4 by tumor cells, which plays a critical role in cell metastasis. Moreover, serum alkaline phosphatase (ALP) levels are frequently elevated in patients with metastatic colorectal cancer. A polysaccharide, dextran, was chosen as the vector of siRNA. Spermine was conjugated to oxidized dextran by reductive amination process to obtain cationized dextran, so-called dextran-spermine, in order to prepare CXCR4-siRNAs/dextran-spermine nanoparticles. The fabricated nanoparticles were used in order to investigate whether downregulation of CXCR4 expression could affect serum ALP in mouse models of colorectal cancer.Methods: Colorectal cancer was established in BALB/C mice following injection of mouse colon carcinoma cells CT.26WT through the tail vein. CXCR4 siRNA for two sites of the target gene was administered following injection of naked siRNA or siRNA encapsulated into nanoparticles.Results: In vivo animal data revealed that CXCR4 silencing by dextran-spermine nanoparticles significantly downregulated CXCR4 expression compared with naked CXCR4 siRNA. Furthermore, there was correlation between CXCR4 expression and serum ALP.Conclusion: CXCR4 siRNA/dextran-spermine nanoparticles appear to be highly effective, and may be suitable for further in vivo applications. Further research evaluation will be needed to determine the effect of CXCR4 silencing on serum ALP levels, which may be a useful marker to predict liver metastasis in colorectal cancer.Keywords: nanoparticles, cationized dextran, colorectal cancer, serum ALP enzyme, CXCR4, siRNA

Fatemeh Abedini1, Maznah Ismail1,4, Hossein Hosseinkhani2, Tengku Azmi Tengku Ibrahim1,3, Abdul Rahman Omar1,3, Pei Pei Chong4, Mohd Hair Bejo3, Abraham J Domb51Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, Selangor Darul Ehsan, Malaysia; 2Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan; 3Faculty of Veterinary Medicine, 4Faculty of Medicine and Health Science, Universiti Putra Malaysia, Selangor Darul Ehsan, Malaysia; 5Department of Medicinal Chemistry and Natural Products, School of Pharmacy, Hebrew University-Hadassah Medical School, Jerusalem, IsraelAbstract: Liver metastasis is the main cause of mortality related to colorectal cancer. CXCR4 is necessary for the outgrowth of colon cancer micrometastases. In oncology, it has been demonstrated that several human tumors release lactate dehydrogenase (LDH) into the circulation. CXCR4 gene expression and serum LDH levels are often increased in patients with colorectal cancer. Despite technological advances in cancer therapy, five-year overall survival is still around 50%. Therefore, better treatment needs to be developed. RNA interference (RNAi) is a modern and powerful tool for inhibition of gene expression. However, the rate-limiting step in this technology is effective delivery of RNAi agents. We have investigated a novel strategy of CXCR4 siRNA therapy and its effect on serum LDH levels in a BALB/C mouse model of colorectal cancer metastasis to the liver. Hepatic metastasis was established by injecting a CT26.WT mouse colon carcinoma cell line via the tail vein. Our results demonstrated that CXCR4 siRNA/dextran-spermine nanoparticles achieved high silencing efficiency with low toxicity. Favorable localization of the nanoparticles was confirmed with CXCR4 gene expression in the liver, that was correlated with serum LDH levels. More research will be needed to determine the effect of CXCR4 silencing on serum LDH levels, which may be a useful marker for predicting liver metastasis in colorectal cancer.Keywords: colorectal cancer, CXCR4 siRNA, serum LDH, liver, dextran-spermine

PurposeTo describe the earliest features of ABCA4-associated retinopathy.DesignCase series.ParticipantsChildren with a clinical and molecular diagnosis of ABCA4-associated retinopathy without evidence of macular atrophy.MethodsThe retinal phenotype was characterized by color fundus photography, OCT, fundus autofluorescence (FAF) imaging, electroretinography, and in 2 patients, adaptive optics scanning laser ophthalmoscopy (AOSLO). Sequencing of the ABCA4 gene was performed in all patients.Main outcome measuresVisual acuity, OCT, FAF, electroretinography, and AOSLO results.ResultsEight children with ABCA4-associated retinopathy without macular atrophy were identified. Biallelic variants in ABCA4 were identified in all patients. Four children were asymptomatic, and 4 reported loss of VA. Patients were young (median age, 8.5 years; interquartile range, 6.8 years) with good visual acuity (median, 0.155 logarithm of the minimum angle of resolution [logMAR]; interquartile range, 0.29 logMAR). At presentation, the macula appeared normal (n = 3), had a subtly altered foveal reflex (n = 4), or demonstrated manifest fine yellow dots (n = 1). Fundus autofluorescence identified hyperautofluorescent dots in the central macula in 3 patients, 2 of whom showed a normal fundus appearance. Only 1 child had widespread hyperautofluorescent retinal flecks at presentation. OCT imaging identified hyperreflectivity at the base of the outer nuclear layer in all 8 patients. Where loss of outer nuclear volume was evident, this appeared to occur preferentially at a perifoveal locus. Longitudinal split-detector AOSLO imaging in 2 individuals confirmed that the greatest change in cone spacing occurred in the perifoveal, and not foveolar, photoreceptors. Electroretinography showed a reduced B-wave-to-A-wave ratio in 3 of 5 patients tested; in 2 children, recordings clearly showed electronegative results.ConclusionsIn childhood-onset ABCA4-associated retinopathy, the earliest stages of macular atrophy involve the parafovea and spare the foveola. In some cases, these changes are predated by tiny, foveal, yellow, hyperautofluorescent dots. Hyperreflectivity at the base of the outer nuclear layer, previously described as thickening of the external limiting membrane, is likely to represent a structural change at the level of the foveal cone nuclei. Electroretinography suggests that the initial site of retinal dysfunction may occur after phototransduction.

To date, over 150 disease-associated variants in CRB1 have been described, resulting in a range of retinal disease phenotypes including Leber congenital amaurosis and retinitis pigmentosa. Despite this, no genotype-phenotype correlations are currently recognised. We performed a retrospective review of electronic patient records to identify patients with macular dystrophy due to bi-allelic variants in CRB1. In total, seven unrelated individuals were identified. The median age at presentation was 21 years, with a median acuity of 0.55 decimalised Snellen units (IQR = 0.43). The follow-up period ranged from 0 to 19 years (median = 2.0 years), with a median final decimalised Snellen acuity of 0.65 (IQR = 0.70). Fundoscopy revealed only a subtly altered foveal reflex, which evolved into a bull's-eye pattern of outer retinal atrophy. Optical coherence tomography identified structural changes-intraretinal cysts in the early stages of disease, and later outer retinal atrophy. Genetic testing revealed that one rare allele (c.498_506del, p.(Ile167_Gly169del)) was present in all patients, with one patient being homozygous for the variant and six being heterozygous. In trans with this, one variant recurred twice (p.(Cys896Ter)), while the four remaining alleles were each observed once (p.(Pro1381Thr), p.(Ser478ProfsTer24), p.(Cys195Phe) and p.(Arg764Cys)). These findings show that the rare CRB1 variant, c.498_506del, is strongly associated with localised retinal dysfunction. The clinical findings are much milder than those observed with bi-allelic, loss-of-function variants in CRB1, suggesting this in-frame deletion acts as a hypomorphic allele. This is the most prevalent disease-causing CRB1 variant identified in the non-Asian population to date.

Abstract Background The aim of this quality improvement (QI) project was to increase Colorectal Cancer (CRC) screening in patients ages 50–75 years from a baseline of 27–40% within 12 months in a primary care clinic in limited resource communities. Methods The multidisciplinary QI-team applied the Plan-Do-Study-Act method and developed stakeholder analysis, an Ishikawa fish bone diagram, a process flow map, and a driver diagram. Major barriers to suboptimal CRC screening included limited health literacy, language preferences, absence of stool test options, and knowledge gaps among patients and providers. The outcome measure was CRC screening rates, while stool test and colonoscopy completion rates served as process measures. Major interventions included the use of a patient-navigator, leveraging digital health technology to create a novel CRC screening data dashboard, educating patients and providers, patient centered-shared decision making, and creating messages and educational videos in patient’s preferred languages. We used monthly run charts and statistical process control charts (SPC) for data analysis. Results We observed a sustainable, steady increase in CRC screening rates from baseline rates of 27.0–40.0% (n = 1304/3271) during the study period and 45.6% (n = 1493/3,271) six months post-study, with median rates of 34.0% in the run chart and mean rates of 43.0% in the SPC chart. Furthermore, we observed an increase in colonoscopy completion rates during the study and six months post-study to 65.0% (n = 411/631) and 72.9% (n = 461/631) respectively, from a baseline rate of 25.0%, with a median of 63.0% in the monthly run chart. Conclusion The increase in CRC screening rates highlights the effectiveness of addressing barriers such as health literacy, language preferences, and knowledge gaps. This underscores the value of a multifaceted approach and the role of a patient navigator in enhancing preventive, patient-centered care. This project focused on population health and addressing social determinants of health to overcome disparities and improve CRC screening in a primary care setting. Continued emphasis on these strategies is likely to further advance colorectal cancer screening efforts.

Abstract While ventricular shunts are the main treatment for adult hydrocephalus, shunt malfunction remains a common problem that can be challenging to diagnose. Computer vision-derived algorithms present a potential solution. We designed a feasibility study to see if such an algorithm could automatically predict ventriculomegaly indicative of shunt failure in a real-life adult hydrocephalus population. We retrospectively identified a consecutive series of adult shunted hydrocephalus patients over an eight-year period. Associated computed tomography scans were extracted and each scan was reviewed by two investigators. A machine learning algorithm was trained to identify the lateral and third ventricles, and then applied to test scans. Results were compared to human performance using Sørensen–Dice coefficients, calculated total ventricular volumes, and ventriculomegaly as documented in the electronic medical record. 5610 axial images from 191 patients were included for final analysis, with 52 segments (13.6% of total data) reserved for testing. Algorithmic performance on the test group averaged a Dice score of 0.809 ± 0.094. Calculated total ventricular volumes did not differ significantly between computer-derived volumes and volumes marked by either the first reviewer or second reviewer (p > 0.05). Algorithm detection of ventriculomegaly was correct in all test cases and this correlated with correct prediction of need for shunt revision in 92.3% of test cases. Though development challenges remain, it is feasible to create automated algorithms that detect ventriculomegaly in adult hydrocephalus shunt malfunction with high reliability and accuracy.

Abstract Background Ewing sarcoma (ES) is the second most common primary malignant bone tumor in children and adolescents. Despite more intensive chemotherapy regimens and improved local control therapy, there is still a considerable rate of recurrent/progressive disease. Methods A retrospective study of 50 relapsed/progressive ES patients who were treated at the National Cancer Institute (NCI), Cairo University, during the period from 1st of January 2008 to the end of December 2018, to assess different prognostic variables and disease outcomes. Results Out of fifty eligible cases, 32 patients (64%) had disease recurrence, and 18 (36%) developed disease progression on treatment. The median follow-up period was 7.4 months. The median overall survival (OS) was 7.5 months, and the cumulative OS was 64% at 6 months and 32.6% at 1 year. The cumulative event-free survival (EFS) was 41.3% at 6 months and 22.3% at 1 year. Patients with disease recurrence had better OS and EFS than patients with disease progression (p = 0.019). Patients who underwent local control at relapse/progression had a significantly better outcome than patients who received chemotherapy only (p 2 years from initial diagnosis was the only independent predictor of better survival outcome. Conclusions Patients with relapsing/progressive ES portended a poor outcome, with disease progression on treatment faring worse than relapse. Better outcome was observed in patients who experienced recurrence > 2 years after diagnosis, patients with disease recurrence rather than disease progression on treatment, and patients who underwent local control along with intensive chemotherapy.

In this report, spiritual health is conceived as well-being in the relationship that the individual has with himself, with nature, with others and with God, a subject that has increasingly occupied the interest of researchers and educators during the last three decades. This research has estimated the validity and reliability of the Spiritual Well-being Scale, Romanian children’s version. The instrument consists of 27 statements to assess spiritual well-being in children and adolescents, on a five-point Likert scale. For content validity, six experts participated evaluating the clarity and relevance of the statements. For construct validity, 503 students from primary and middle school level attending Romanian schools from different regions participated. An exploratory factor analysis was performed using the principal axis method, with an oblimin rotation. It is concluded that the resulting instrument has the appropriate psychometric properties and can be useful for the assessment of the spiritual wellbeing of minors in clinical and educational contexts.

Objetivo: caracterizar o perfil epidemiológico dos casos e óbitos da hanseníase em Mato Grosso - Brasil, no período de 2011 a 2020. Método: estudo observacional, de base populacional, de todos os casos e óbitos notificados por hanseníase no período de 2011 a 2020. A posteriori, foi realizado os paramentos dos indivíduos notificados, estimando-se a tendência por meio da regressão de Prais-Winsten. Resultados: nos anos de estudo foram registrados 37.623 casos novos, taxa média de 114,7/100 mil habitantes com maiores taxas de incidência nos casos multibacilares e no sexo masculino, assim como na proporção de óbitos (58%; 88,2%) respectivamente. Quanto à tendência, foi crescente ao longo dos anos e no sexo feminino. Conclusão: os resultados sugerem que há um perfil de casos mais incidentes, possíveis áreas com disseminação da doença e atraso do diagnóstico, ressaltando a necessidade da utilização dos indicadores como forma de monitorar a endemia, fortalecendo a atenção e vigilância integral à hanseníase.

Objective: To characterize the epidemiological profile of leprosy cases and deaths in Mato Grosso - Brazil, from 2011 to 2020. Method: A population-based observational study of all leprosy cases and deaths reported between 2011 and 2020. Subsequently, the reported individuals were matched, and the trend was estimated using the Prais-Winsten regression. Results: 37,623 new cases were registered in the study years, with an average rate of 114.7/100,000 inhabitants, with higher incidence rates in multibacillary cases and males, and in the proportion of deaths (58%; 88.2%), respectively. As for the trend, it has increased over the years and among women. Conclusion: The results suggest a profile of more incident cases, possible areas with the spread of the disease, and delayed diagnosis, highlighting the need to use indicators to monitor the endemic and strengthen comprehensive care and surveillance of leprosy.

Objetivo: Caracterizar el perfil epidemiológico de los casos y muertes por lepra en Mato Grosso - Brasil, de 2011 a 2020. Método: estudio observacional basado en la población de todos los casos y muertes por lepra notificados entre 2011 y 2020. Posteriormente, se emparejaron los individuos declarados y se estimó la tendencia mediante la regresión de Prais-Winsten. Resultados: Se registraron 37.623 nuevos casos en los años de estudio, una tasa media de 114,7/100.000 habitantes, con tasas de incidencia más elevadas en los casos multibacilares y en los varones, así como en la proporción de muertes (58%; 88,2% respectivamente). En cuanto a la tendencia, ha aumentado con los años y en el sexo femenino. Conclusión: Los resultados sugieren que existe un perfil de más casos incidentes, posibles zonas de propagación de la enfermedad y un retraso en el diagnóstico, lo que pone de manifiesto la necesidad de utilizar indicadores como forma de seguimiento de la endemia, de reforzar la atención integral y la vigilancia de la lepra.

Abstract The management of perioperative acute myocardial infarction (AMI) following oncologic neurosurgery requires balancing competing risks of myocardial ischemia and postoperative bleeding. There are limited human data to establish the safest timing of antiplatelet or anticoagulation therapy following neurosurgical procedures. For patients with malignancy experiencing AMI in the acute postoperative period, staged percutaneous coronary intervention (PCI) with upfront coronary aspiration thrombectomy followed by delayed completion PCI may offer an opportunity for myocardial salvage while minimizing postoperative bleeding risks. CYP2C19 genotyping and platelet aggregation studies can help confirm adequate platelet inhibition once antiplatelet therapy is resumed.

This paper is an in-depth study that starts from a preliminary one, where we surveyed 141 ranchers from the town of Coto-Coto in Peru to obtain as much information as possible about the relationship between two economic variables, Activity Cost and Financial Management. Furthermore, we study the correlation of the first one of them with three other economic variables. To do this, we process the survey data using logical operators with the support of the plithogenic statistics theory. These results given in the form of plithogenic values are logically aggregated and were converted to crisp values and studied through the use of statistical tools, specifically Kendall's Tau b. The study of economic variables within the field of cattle farming is of great importance because it allows us to improve the productivity of this economic sector, which is also part of the most accepted human diet worldwide. A substantial advantage in the use of plithogeny is that linguistic values that are more natural for livestock farmers were processed, in addition, uncertainty and indeterminacy were taken into account by the use of neutrosophic numbers.

Activity Cost and Financial Management are two variables of vital importance in livestock production. This paper aims to measure the relationship existing between these two variables within the production of beef cattle in the Coto-Coto Chilca Livestock Fair in Peru. To do this, we selected 141 ranchers from the area to give their opinions regarding the behavior of these two variables. The data were represented with the help of an Indeterminate Likert Scale, to capture the uncertainty and indeterminacy of the respondents' opinion. Survey results were compared for the two variables using a measure of neutrosophic similarities. Neutrosophic similarities are used to measure the degree of similarity between two neutrosophic sets measured in certain aspects.

This paper presents Pose Calibrated Feature Aggregation Network (PCFAN), an architecture for set/video face recognition. Using stacked attention blocks and a multi-modal architecture, it automatically assigns adaptive weights to every instance in the set, based on both the recognition embeddings and the associated face metadata. It uses these weights to produce a single, compact feature vector for the set. The model automatically learns to advocate for features from images with more favourable qualities and poses, which inherently hold more information. Our block can be inserted on top of any standard recognition model for set prediction and improved performance, particularly in unconstrained scenarios where subject pose and image quality vary considerably between frames. We test our approach on three challenging video face-recognition datasets, IJB-A, IJB-B, and YTF, and report state-of-the-art results. Moreover, a comparison with top aggregation methods as our baselines demonstrates that PCFAN is the superior approach.

Multi-label zero-shot learning expands upon the traditional single-label zero-shot learning paradigm by addressing the challenge of accurately classifying images containing multiple unseen classes, which are not part of the training data. Current techniques rely on attention mechanisms to tackle the complexities of multi-label zero-shot learning (ZSL) and generalized zero-shot learning (GZSL). However, the generation of features, especially within the context of a generative approach, remains an unexplored area. In this paper, we propose a generative approach that leverages the capabilities of Conditional Variational Autoencoder (CVAE) and Conditional Generative Adversarial Network (CGAN) to enhance the quality of generative data for both multi-label ZSL and GZSL. Additionally, we introduce a novel “Regressor” as a supplementary tool to improve the reconstruction of visual features. This Regressor operates in conjunction with a “cycle-consistency loss” to ensure that the generated features preserve the key qualities of the original features even after undergoing transformations. To gauge the efficacy of our proposed approach, we conducted comprehensive experiments on two widely recognized benchmark datasets: NUS-WIDE and MS COCO. Our evaluation spanned both multi-label ZSL and GZSL scenarios. Notably, our approach yielded significant enhancements in mean Average Precision (mAP) for both datasets. Specifically, we observed a 0.2% increase in performance on the NUS-WIDE dataset and a notable 2.6% improvement on the MS COCO dataset in the context of Multi-label ZSL. The results clearly demonstrate that our generative approach outperforms existing methods on these widely-recognized datasets.

Crouch gait, also referred to as flexed knee gait, is an abnormal walking pattern, characterized by an excessive flexion of the knee, and sometimes also with anomalous flexion in the hip and/or the ankle, during the stance phase of gait. Due to the fact that the amount of clinical data related to crouch gait are scarce, it is difficult to find studies addressing this problem from a data-based perspective. Consequently, in this paper we propose a gait recognition strategy using synthetic data that have been obtained using a polynomial based-generator. Furthermore, though this study, we consider datasets that correspond to different levels of crouch gait severity. The classification of the elements of the datasets into the different levels of abnormality is achieved by using different algorithms like k-nearest neighbors (KNN) and Naive Bayes (NB), among others. On the other hand, to evaluate the classification performance we consider different metrics, including accuracy (Acc) and F measure (FM). The obtained results show that the proposed strategy is able to recognize crouch gait with an accuracy of more than 92%. Thus, it is our belief that this recognition strategy may be useful during the diagnosis phase of crouch gait disease. Finally, the crouch gait recognition approach introduced here may be extended to identify other gait abnormalities.

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P

The use of DC microgrids (DC-µGs) offers a variety of environmental benefits; albeit, a successful implementation depends on the implementation of an Energy Management System (EMS). An EMS is broadly implemented with a hierarchical and centralized structure, where the communications layer presents as a key element of the system to achieve a successful operation. Additionally, the relatively low cost of wireless communication technologies and the advantages offered by remote monitoring have promoted the inclusion of the Internet of Things (IoT) and Wireless Sensor and Actuator Network (WSAN) technologies in the energy sector. In this article is presented the development of an IoT EMS based on a WSAN (IoT-EMS-WSAN) for the management of a DC-µG. The proposed EMS is composed of a WiFi-based WSAN that is interconnected to a DC-µG, a cloud server, and a User Web App. The proposed system was compared to a conventional EMS with a high latency wired communication layer. In comparison to the conventional EMS, the IoT-EMS-WSAN increased the updating time from 100 ms to 1200 ms; also, the bus of the DC-µG maintained its stability even though its variations increased; finally, the DC bus responded to an energy-outage scenario with a recovery time of 1 s instead of 150 ms, as seen with the conventional EMS. Despite the reduced latency, the developed IoT-EMS-WSAN was demonstrated to be a reliable tool for the management, monitoring, and remote controlling of a DC-µG.

The symptoms of multiple sclerosis (MS) are determined by the location of demyelinating lesions in the white matter of the brain and spinal cord. Currently, magnetic resonance imaging (MRI) is the most common tool used for diagnosing MS, understanding the course of the disease, and analyzing the effects of treatments. However, undesirable components may appear during the generation of MRI scans, such as noise or intensity variations. Mathematical morphology (MM) is a powerful image analysis technique that helps to filter the image and extract relevant structures. Granulometry is an image measurement tool for measuring MM that determines the size distribution of objects in an image without explicitly segmenting each object. While several methods have been proposed for the automatic segmentation of MS lesions in MRI scans, in some cases, only simple data preprocessing, such as image resizing to standardize the input dimensions, has been performed before the algorithm training. Therefore, this paper proposes an MRI preprocessing algorithm capable of performing elementary morphological transformations in brain images of MS patients and healthy individuals in order to delete undesirable components and extract the relevant structures such as MS lesions. Also, the algorithm computes the granulometry in MRI scans to describe the size qualities of lesions. Using this algorithm, we trained two artificial neural networks (ANNs) to predict MS diagnoses. By computing the differences in granulometry measurements between an image with MS lesions and a reference image (without lesions), we determined the size characterization of the lesions. Then, the ANNs were evaluated with the validation set, and the performance results (test accuracy = 0.9753; cross-entropy loss = 0.0247) show that the proposed algorithm can support specialists in making decisions to diagnose MS and estimating the disease progress based on granulometry values.

(1) Background: Saudi Arabia (SA) is a country with a low incidence of gastric cancer (GC). In this study, we sought to assess the epidemiology of GC, its clinicopathological profiles, and its association with risk factors as well as to identify premalignant gastric lesions (PGL) and examine neoplastic progression. (2) Methods: This five-year prospective study screened for GC and PGL in asymptomatic Saudi patients, aged 45–75 years (n = 35,640) and living in Al Kharj, Riyadh province in central SA. Those who were positive in a high-sensitivity guaiac fecal occult blood test (HSgFOBT+) and had negative results in colonoscopy offered to undergo upper GI endoscopy (n = 1242). Factors associated with GC were examined. (3) Results: The five-year participation rate was 87% (1080/1242). The incidence rate of GC was 26.9 new cases per 100,000 population per year (9.6 new cases per year/total population at risk—35,640), and it was 8.9 cases per 1000 persons per year among the 1080 subjects with HSgFOBT+ and negative colonoscopy results. The five-year mortality rate was 67% among patients with GC (n = 48), 3.0% among participants in the gastric screening program (n = 1080) and 0.09% among the original population participating in the colorectal screening program (n = 35,640). Intestinal-type adenocarcinoma was the most frequent type (77%), with the tumor most commonly located in the antrum (41%). Overall, 334 participants had PGL, and seven of them (2.1%) showed neoplastic progression to GC during the follow-up. Factors associated with GC were age, Helicobacter pylori (HP) infection, obesity (body mass index BMI > 30), smoking, a diet of salty preserved foods, low income and a family history of GC. (4) Conclusions: The incidence of GC is low in central SA, but screening for PGL and GC among patients with HSgFOBT+ and negative colonoscopy may prevent or result in the early treatment of GC. HP eradication, normal body weight, not smoking and adhering to a healthy diet can reduce the risk of GC. The resulting data provide important input for the improvement of national guidelines.

Primary hepatic neuroendocrine carcinomas (PHNECs) are extremely rare, with only about 90 cases having been reported in the English-language literature. Among all neuroendocrine neoplasms, primary hepatic neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) are extremely rare, accounting for 0.3% of NETs and 0.28–0.46% of malignant liver tumors. Additionally, primary hepatic NECs occur infrequently. The clinical diagnosis of primary hepatic NEC remains challenging because of its rarity and the lack of information about its characteristic appearance on images. Consequently, pathological examination through the performance of a preoperative liver tumor biopsy is essential for diagnosis. Due to the lack of availability of substantial high-quality data, there is no standard therapy for primary hepatic NEC. We present the first case of PHNEC metastasized to the mesentery reported in the English-language literature.

Los nuevos enfoques pedagógicos invitan al profesorado a desarrollar prácticas de colaboración que influyan en el aprendizaje profundo del estudiantado. En dicho contexto, este artículo tiene como objetivo describir el proceso de resignificación de estudiantes y profesorado sobre la cultura de evaluación y aprendizaje desde el enfoque de la pedagogía de proyectos. El diseño de esta investigación educativa se enmarca en un estudio de caso con metodología cualitativa. Las personas participantes fueron seleccionadas de forma intencionada y corresponden a nueve docentes de aula y 144 estudiantes que cursaban quinto y sexto grado de educación primaria en un centro escolar de la comuna de Temuco, región de La Araucanía, Chile. ​​Para la recolección de información se utilizaron las técnicas de observación participante y grupos de discusión con el propósito de ahondar en el análisis de sus experiencias de resignificación desde el enfoque de la teoría fundamentada. Los hallazgos evidencian que el desarrollo de la metodología de proyectos contribuye a favorecer el rol protagónico del estudiantado durante el proceso pedagógico al involucrarse de manera activa en la evaluación de su aprendizaje. Se puede concluir que la integración de metodologías innovadoras resulta desafiante y se traduce en una oportunidad para el desarrollo profesional docente, en tanto les permite posicionarse como co-aprendices en el proyecto de aprendizaje. Se recomienda abordar la pedagogía de proyectos para propiciar la resignificación de la cultura de evaluación y aprendizaje de manera que se resguarde su sentido formador, democrático y situado en la escuela.

Abstract Background T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy with few accepted prognostic factors that limit the efficiency of therapy. The aim of the current study was to assess the clinical and laboratory features of T-cell receptor (TCR) aberrations and early T-cell precursor (ETP) subtype as well as their outcome to therapy. Methods Sixty-three newly diagnosed pediatric T-ALL patients were assessed for the ETP status using immunophenotyping. Screening of TCRA/D aberrations was done by fluorescent in situ hybridization (FISH). The data were correlated to the patients’ clinical features, response to treatment, and survival rates. Results Seven patients (11%) had ETP-ALL. The ETP-ALL patients were older (P = 0.013), presented with lower white blood cell (WBC) count (P = 0.001) and lower percentage of peripheral blood (PB) blast cells (P = 0.037), more likely to have hyperdiploid karyotype (P = 0.009), and had been associated with TCRA/D gene amplification (P = 0.014) compared to other T-ALL patients. Of note, the same associations had been significantly observed in patients with TCRA/D gene amplification. Patients with TCRA/D amplification frequently coincided with TCRβ aberrations (P = 0.025). TCR-β aberrations were significantly associated with negative MRD at the end of induction compared to TCR-β-negative patients. There was a nonsignificant trend of ETP-positive cases to have lower overall survival (OS) (P = 0.06). Patients with TCR aberrations had no significant differences regarding disease-free survival (DFS) or OS rates compared to those with normal TCR. Conclusion ETP-ALL patients tend to have increased mortalities. There was no significant impact of TCR aberrations on the survival rates of the patients.

El objetivo de esta investigación es construir y validar una escala de medición que aborda cuatro dimensiones del aspecto interno de la Responsabilidad Social Empresarial en las relaciones obrero-patronales que son: discriminación, equidad de género, acoso laboral y políticas de recursos humanos. Para el diseño de la escala se realizó una revisión de la literatura científica sobre la dimensión interna de la RSE. Participó una muestra de 167 empleados de pequeñas y medianas empresas (Pymes). Se utilizó un proceso de validez cuantitativo basado en el análisis factorial. La escala quedó integrada por 30 ítems. Se realizó el análisis factorial con rotación varimax y presentó una adecuación muestral KMO de .861. Se encontró que los resultados son significativos y que con los cuatro factores se explica un 62.731% de la varianza total. El alfa de Cronbach fue igual a .910. El instrumento desarrollado permitirá a las Pymes realizar una autoevaluación, que les permita identificar elementos para establecer mejoras en su responsabilidad social empresarial interna.

Abstract Fatty acid amide hydrolase (FAAH) is a widely conserved amidase in eukaryotes, perhaps best known for inactivating N-acylethanolamine lipid mediators. However, FAAH enzymes hydrolyze a wide range of acylamide substrates. Analysis of FAAHs from multiple angiosperm species revealed two conserved phylogenetic groups that differed in key conserved residues in the substrate binding pocket. While the foundation group of plant FAAHs, designated FAAH1, has been studied at the structural and functional level in Arabidopsis thaliana, nothing is known about FAAH2 members. Here, we combined computational and biochemical approaches to compare the structural and enzymatic properties of two FAAH isoforms in the legume Medicago truncatula designated MtFAAH1 and MtFAAH2a. Differences in structural and physicochemical properties of the substrate binding pockets, predicted from homology modeling, molecular docking, and molecular dynamic simulation experiments, suggested that these two FAAH isoforms would exhibit differences in their amidohydrolase activity profiles. Indeed, kinetic studies of purified, recombinant MtFAAHs indicated a reciprocal preference for acylamide substrates with MtFAAH1 more efficiently utilizing long-chain acylamides, and MtFAAH2a more efficiently hydrolyzing short-chain and aromatic acylamides. This first report of the enzymatic behavior of two phylogenetically distinct plant FAAHs will provide a foundation for further investigations regarding FAAH isoforms in legumes and other plant species.

Background: Human beings consume different chemical forms of iodine in their diet. These are transported by different mechanisms in the cell. The forms of iodine can be part of thyroid hormones, bind to lipids, be an antioxidant, or be an oxidant, depending on their chemical form. The excessive consumption of iodine has been associated with pancreatic damage and diabetes mellitus type 2, but the association between disease and the chemical form consumed in the diet is unknown. This research analyzes the effect of excessive iodine consumption as Lugol (molecular iodine/potassium iodide solution) and iodate on parameters of pancreatic function, thyroid and lipid profiles, antioxidant and oxidant status, the expression of IR/Akt/P-Akt/GLUT4, and transcription factors PPAR-γ and CEBP-β. Methods: Three groups of Wistar rats were treated with 300 μg/L of iodine in drinking water: (1) control, (2) KIO3, and (3) Lugol. Results: Lugol and KIO3 consumption increased total iodine levels. Only KIO3 increased TSH levels. Both induced high serum glucose levels and increased oxidative stress and pancreatic alpha-amylase activity. Insulin levels and antioxidant status decreased significantly. PPAR-γ and C/EBP-β mRNA expression increased. Conclusion: The pancreatic damage, hypertriglyceridemia, and oxidative stress were independent of the chemical form of iodine consumed. These effects depended on PPAR-γ, C/EBP-β, GLUT-4, and IR.

El presente estudio cuantificó los niveles de Dietilestilbestrol (DES), zeranol y acetato de trembolona por ensayo inmunoenzimático en muestras pechugas de pollo comerciales de origen nacional e importado. Se utilizaron 72 muestras de pechuga de pollo de origen nacional e importado, y se detectó la presencia de zeranol y trembolona en las muestras de origen nacional e importadas; el compuesto DES no fue detectado en ninguna de las muestras evaluadas. Las concentraciones de zeranol entre la carne de origen nacional e importando se encontraron por debajo de las normas mexicanas sin embargo no mostraron diferencias estadísticas entre ellos. La presencia de acetato de trembolona se encontró por debajo de los límites permitidos por las normas mexicanas. Los resultados sugieren que es necesario regular continuamente las prácticas de las granjas de producción avícola ya que el uso excesivo de estos compuestos puede ser riesgoso para la salud del consumidor.

This study explores the performance of a solar chimney for enhancing passive ventilation and thermal comfort in the northeast of Colombia. A theoretical model and a quasi-steady computational fluid dynamics model were employed to analyse the airflow generated by the solar chimney and optimize its design. Then, the computational fluid dynamics model was used to investigate thermal comfort in the test section. The numerical model results were validated against a scaled experimental test bench. Results evidenced that solar chimneys could improve the indoor environment in the northeast of Colombia. A chimney with a length of 4 m and an angle of inclination of 55°, connected to a single room of 27 cubic meters in Bucaramanga, could improve natural ventilation and provide thermal comfort during January, March, April, August, November, and December as per the guidelines set in ASHRAE Standard 55. During the other months, it could provide partial comfort during specific hours, with being September the most critical month. This study provides valuable insights for future research dealing with the development of sustainable low-income homes in this Colombian region.

México ocupa el 10mo lugar en exportación de miel. A nivel nacional Tabasco se encuentra rezagado en el 25vo lugar como productor. En México, la apicultura se realiza principalmente con abejas africanizadas, el comportamiento altamente defensivo y la varroosis, son los principales factores que frenan su desarrollo. El objetivo fue seleccionar abejas progenitoras en diferentes agroecosistemas del estado. Se evaluaron 165 colonias, en apiarios comerciales localizados en Comalcalco, Cárdenas y Paraíso Tabasco. Se estableció un índice de selección (10 puntos) mediante ponderaciones de: Producción de miel (PM=5), mansedumbre (M=2), comportamiento higiénico (CH=1.5), acicalamiento (AC=1.5), infestación de varroa en abejas adultas (IVAA=0.5) e infestación de varroa en cría operculada (IVCO=0.5). Con los datos transformados, se realizaron análisis de varianza, pruebas de medias y correlaciones de Pearson. Se encontró baja IVAA e IVCO (4.73±2.91% y 4.12±2.46%). Buen comportamiento de AC (24.53±11.67%), nivel medio de CH (89.82±8.20%), nivel medio de M (3.38±0.73) y nivel medio de PM=36.08±5.15 kg Colonia-1. Se encontró baja correlación entre M y PM (r=0.292, p=0.000), sugiriendo que abejas con mayor mansedumbre, tienden a ser más productivas. Muy baja correlación de PM con IVAA (r=-0.120, p=0.126) y con IVCO (r=-0.145, p=0.063), indicando que ambos parámetros impactan negativamente la producción. Muy bajas correlaciones positivas con CH (r=0.130, p=0.097) y AC (r =0.091, p=0.242), indicando que buen nivel de CH y AC impactan favorablemente la producción. Se seleccionaron 19 colonias con mayores puntos ponderados, con las cuales se reproducirán abejas reinas y zánganos con fines de mejoramiento genético en los diferentes agroecosistemas

Oncolytic viral (OV) therapies are promising novel treatment modalities for cancers refractory to conventional treatment, such as glioblastoma, within the central nervous system (CNS). Although OVs have received regulatory approval for use in the CNS, efficacy is hampered by obstacles related to delivery, under-/over-active immune responses, and the “immune-cold” nature of most CNS malignancies. SUMO, the Small Ubiquitin-like Modifier, is a family of proteins that serve as a high-level regulator of a large variety of key physiologic processes including the host immune response. The SUMO pathway has also been implicated in the pathogenesis of both wild-type viruses and CNS malignancies. As such, the intersection of OV biology with the SUMO pathway makes SUMOtherapeutics particularly interesting as adjuvant therapies for the enhancement of OV efficacy alone and in concert with other immunotherapeutic agents. Accordingly, the authors herein provide: 1) an overview of the SUMO pathway and its role in CNS malignancies; 2) describe the current state of CNS-targeted OVs; and 3) describe the interplay between the SUMO pathway and the viral lifecycle and host immune response.

Background: The Al-Kharj colorectal cancer (CRC) screening program was implemented for five years (2017-2022) in a central urban area of Riyadh Province, Saudi Arabia, to assess the participation and impact of the program in average-risk individuals. Methods: The high sensitivity-guaiac based-fecal occult blood test (HSgFOBT) was used as a first-line investigation to identify asymptomatic patients, aged 45–75 years, requiring CRC screening using colonoscopy. The program was run in three tertiary hospitals in the area. Results: The five-year participation rate was 73% (35,640/48,897). The average age was 53 years (range 45–75), 49% were female (17,464/35,640), all were asymptomatic, and 77% had adequate bowel preparation. The HSgFOBT (+) rate was 6.3% (n = 2245), and 76% (n = 1701) of these underwent colonoscopy. The prevalence of findings were as follows: CRC, 4.8% (81/1701); advanced adenoma, 9.5% (162/1701); adenoma, 15.9% (270/1701); non-adenomatous polyps, 7.9% (135/1701); and no polyps or tumors, 25.4% (432/1701). Among participants aged 45–50 years, early onset-CRC had female predominance, while those ≥50 years with late onset-CRC were predominantly male. CRC was more prevalent in the left colon (P < 0.005). Conclusions: Approximately one-third of the participants diagnosed with CRC had early-onset CRC. Screening participation was desirable for the defined target population. Public education is necessary along with expanded colonoscopy resources to continue further citizen participation.

Abstract Increasing the intensity of tumor treating fields (TTF) within a tumor bed improves clinical efficacy, but reaching sufficiently high field intensities to achieve growth arrest remains challenging due in part to the insulating nature of the cranium. Using MRI-derived finite element models (FEMs) and simulations, we optimized an exhaustive set of intracranial electrode locations to obtain maximum TTF intensities in three clinically challenging high-grade glioma (HGG) cases (i.e., thalamic, left temporal, brainstem). Electric field strengths were converted into therapeutic enhancement ratios (TER) to evaluate the predicted impact of stimulation on tumor growth. Concurrently, conventional transcranial configurations were simulated/optimized for comparison. Optimized intracranial TTF were able to achieve field strengths that have previously been shown capable of inducing complete growth arrest, in 98–100% of the tumor volumes using only 0.54–0.64 A current. The reconceptualization of TTF as a targeted, intracranial therapy has the potential to provide a meaningful survival benefit to patients with HGG and other brain tumors, including those in surgically challenging, deep, or anatomically eloquent locations which may preclude surgical resection. Accordingly, such an approach may ultimately represent a paradigm shift in the use of TTFs for the treatment of brain cancer.