Miracle-dz/UniFAR-FTUs huggingface dataset:
Innovative application of postbiotics, parabiotics and encapsulated Lactobacillus plantarum RM1 and Lactobacillus paracasei KC39 for detoxification of aflatoxin M1 in milk powder

Abstract This study aimed to evaluate aflatoxin M1 (AFM1) level in milk powder and infant milk formulae, in addition to applying innovative methods for AFM1 & AFB1 detoxification. Fifty random samples of milk powder and infant formulae (25 of each) were collected from the Egyptian markets for assessing AFM1 level using ELISA technique. Bioactive components comprising cell free supernatants (postbiotic), acid-dead cells (parabiotic) and the encapsulated-cells of Lactobacillus plantarum RM1 and Lactobacillus paracasei KC39 were evaluated for their antifungal activity against toxigenic mold strains and their impact on AFB1 and AFM1 reduction in reconstituted milk powder. AFM1 concentration in unpacked milk powder was higher than that of packed samples and infant formulae, although these differences were not significant (P > 0.05). About 96.0, 29.4 and 25.0% of the tested infant formulae, unpacked, and packed milk powder were unacceptable in terms of the AFM1 limit defined by Egyptian and European standards, while all samples were in accordance with the USA/FDA standard. All tested mycotoxigenic strains were sensitive to the different treatments of the probiotics with the highest sensitivity regarding Fusarium strain with L. paracasei KC39 compared to other genera. The degradation ratios of AFM1 using the bioactives of the L. paracasei KC39 were higher than that of L. plantarum RM1 bioactives. Additionally, KC39 parabiotic manifested the best AFB1 reduction (60.56%). In conclusion, the positive and highly significant relationship (P < 0.05) between these effective biocompounds mirrors their major detoxification role which gives a safe solution for AFs contamination issues in milk and milk products.
Individual participant data meta‐analysis versus aggregate data meta‐analysis: A case study in eczema and food allergy prevention

Meta‐analysis traditionally uses aggregate data from published reports. Individual Participant Data (IPD) meta‐analysis, which obtains and synthesizes participant‐level data, is potentially more informative, but resource‐intensive. The impact on the findings of meta‐analyses using IPD in comparison with aggregate data has rarely been formally evaluated.
An orthogonal IL-2 and IL-2Rβ system drives persistence and activation of CAR T cells and clearance of bulky lymphoma

Description Orthogonal IL-2 improves CAR T cell–mediated antitumor efficacy by selectively and controllably expanding and activating CAR T cells in vivo. An orthogonal approach to cancer Interleukin-2 (IL-2) is an important cytokine for T cell activation and has been considered as a treatment for cancer. However, systemic administration of IL-2 often leads to severe toxicity. To address this, Zhang et al. and Aspuria et al. engineered T cells to express an IL-2 receptor β (IL-2Rβ) that can only be activated by a modified, orthogonal IL-2. Orthogonal IL-2Rβ was introduced to CAR T cells targeting CD19, and the CAR T cells were transferred to mice bearing leukemias or lymphomas. Administration of orthogonal IL-2 to CAR T cell recipients drove activation, expansion, and antitumor efficacy of CAR T cells in both preclinical models with limited systemic toxicity. Thus, orthogonal cytokine-receptor pairs may offer a safer approach to enhance adoptive cell therapy. Chimeric antigen receptor (CAR) T cells induce durable responses in patients with refractory hematological tumors. However, low CAR T cell activity, poor engraftment, or short in-patient persistence can lead to tumor progression or relapse. Furthermore, excessive CAR T cell expansion and activation can result in life-threatening cytokine release syndrome (CRS). Thus, in-patient control of the CAR T cell population is essential. Interleukin-2 (IL-2) is a critical cytokine for T cell proliferation and effector function, but its clinical use is limited by immune-mediated toxicity. Here, we report on an orthogonal IL-2 receptor and ligand system that enables specific in vivo control of CAR T cell expansion and activation, wherein an orthogonal human IL-2 (STK-009) selectively pairs with an orthogonal human IL-2Rβ (hoRb) expressed on CAR T cells. STK-009 expands hoRb-expressing CAR T cells in the presence and absence of tumor antigen and maintains the presence of stem cell memory T cells (TSCM) and effector T cells. In preclinical models of human CAR-refractory lymphoma, STK-009 treatment resulted in systemic and intratumoral expansion and activation of hoRb-expressing anti–CD19-CD28ζ CAR T cells (SYNCAR). The orthogonal IL-2 receptor/ligand system delivers complete responses in large subcutaneous lymphomas, even with substantially reduced CAR T cell doses, by selectively expanding and activating CAR T cells in vivo. STK-009 withdrawal allowed normal CAR T cell contraction, thereby limiting CRS induced by tumor antigen–specific T cell activation. These data suggest that the orthogonal IL-2 receptor/ligand system provides the in vivo control necessary to maximize efficacy of CAR T therapies.
Exercise-Based Interventions Aimed at Improving Balance in Children with Autism Spectrum Disorder: A Meta-Analysis

Children with Autism Spectrum Disorder (ASD) often have deficits in motor skills, especially balance. This article presents a meta-analytic review of 15 intervention studies that aimed to improve balance in children and adolescents with ASD. Across these studies, there were 195 participants with ASD for whom pre-intervention and post-intervention balance scores were available. We measured the standardized mean difference (Hedges’ g) between their pre-intervention and post-intervention balance scores and found a large, positive effect from these balance interventions (standardized mean difference—1.82 (95% CI [1.34, 2.29]). Various balance intervention procedures were shown to be very efficacious for children and adolescents with ASD. Clearly, balance is a motor skill that is very susceptible to intervention efforts. We also provided recommendations to researchers regarding what information to include when conducting intervention studies.
Impact of public-funded health insurances in India on health care utilisation and financial risk protection: a systematic review

Objective Universal Health Coverage aims to address the challenges posed by healthcare inequalities and inequities by increasing the accessibility and affordability of healthcare for the entire population. This review provides information related to impact of public-funded health insurance (PFHI) on financial risk protection and utilisation of healthcare. Design Systematic review. Data sources Medline (via PubMed, Web of Science), Scopus, Social Science Research Network and 3ie impact evaluation repository were searched from their inception until 15 July 2020, for English-language publications. Eligibility criteria Studies giving information about the different PFHI in India, irrespective of population groups (above 18 years), were included. Cross-sectional studies with comparison, impact evaluations, difference-in-difference design based on before and after implementation of the scheme, pre–post, experimental trials and quasi-randomised trials were eligible for inclusion. Data extraction and synthesis Data extraction was performed by three reviewers independently. Due to heterogeneity in population and study design, statistical pooling was not possible; therefore, narrative synthesis was performed. Outcomes Utilisation of healthcare, willingness-to-pay (WTP), out-of-pocket expenditure (including outpatient and inpatient), catastrophic health expenditure and impoverishment. Results The impact of PFHI on financial risk protection reports no conclusive evidence to suggest that the schemes had any impact on financial protection. The impact of PFHIs such as Rashtriya Swasthy Bima Yojana, Vajpayee Arogyashree and Pradhan Mantri Jan Arogya Yojana showed increased access and utilisation of healthcare services. There is a lack of evidence to conclude on WTP an additional amount to the existing monthly financial contribution. Conclusion Different central and state PFHIs increased the utilisation of healthcare services by the beneficiaries, but there was no conclusive evidence for reduction in financial risk protection of the beneficiaries. Registration Not registered.
Case Report: Genetic Alterations Associated with the Progression of Carotid Paraganglioma

Paragangliomas (PGLs) are rare neuroendocrine tumors that can develop from any paraganglion across the body. The carotid body is the most often location of PGLs in the head and neck region. Carotid PGLs (CPGLs) are characterized by predominantly non-aggressive behavior; however, all tumors have the potential to metastasize. To date, molecular mechanisms of paraganglioma progression remain elusive. We report a case of a 38-year-old woman with metastatic CPGL manifesting as a recurrent tumor with lymph node metastasis. The tumor was fast-growing and had a high Ki-67 proliferation index. Immunohistochemical (IHC) examination and whole-exome sequencing were performed for both recurrent tumor and metastasis. A germline pathogenic splice acceptor variant in the SDHB gene was found in the patient. Immunoreactivity of the SDHB subunit was weak diffuse in both samples, indicating deficiency of the succinate dehydrogenase. Moreover, the recurrent tumor exhibited loss of heterozygosity (LOH) at the SDHB locus, that is according to Knudson’s "two-hit" hypothesis of cancer causation. We also identified a rare somatic promotor mutation in the TERT gene associated with the tumor progression. Obtained results confirmed the indicative role of the germline SDHB mutation for metastatic CPGLs, as well as the potential prognostic value of the TERT promoter mutation.
MR diffusion and dynamic‐contrast enhanced imaging to distinguish meningioma, paraganglioma, and schwannoma in the cerebellopontine angle and jugular foramen

Differentiation of meningiomas, paragangliomas, and schwannomas in the cerebellopontine angle and jugular foramen remains challenging when conventional MRI findings are inconclusive. This study aimed to assess the clinical utility of diffusion‐weighted imaging (DWI) and dynamic contrast‐enhanced MRI (DCE‐MRI) findings for tumor type differentiation and to identify the most significant diagnostic parameters.
SARS-CoV-2 detection in multi-sample pools in a real pandemic scenario: A screening strategy of choice for active surveillance

Background The current COVID-19 pandemic has overloaded the diagnostic capacity of laboratories by the gold standard method rRT-PCR. This disease has a high spread rate and almost a quarter of infected individuals never develop symptoms. In this scenario, active surveillance is crucial to stop the virus propagation. Methods Between July 2020 and April 2021, 11580 oropharyngeal swab samples collected in closed and semi-closed institutions were processed for SARS-CoV-2 detection in pools, implementing this strategy for the first time in Cordoba, Argentina. Five-sample pools were constituted before nucleic acid extraction and amplification by rRT-PCR. Comparative analysis of cycle threshold (Ct) values from positive pools and individual samples along with a cost-benefit report of the whole performance of the results was performed. Results From 2314 5-sample pools tested, 158 were classified as positive (6.8%), 2024 as negative (87.5%), and 132 were categorized as indeterminate (5.7%). The Ct value shift due to sample dilution showed an increase in Ct of 2.6 {+/-}1.53 cycles for N gene and 2.6 {+/-}1.78 for ORF1ab gene. Overall, 290 pools were disassembled and 1450 swabs were analyzed individually. This strategy allowed correctly identifying 99.8% of the samples as positive (7.6%) or negative (92.2%), avoiding the execution of 7,806 rRT-PCR reactions which represents a cost saving of 67.5%. Conclusion This study demonstrates the feasibility of pooling samples to increase the number of tests performed, helping to maximize molecular diagnostic resources and reducing the work overload of specialized personnel during active surveillance of the COVID-19 pandemic.
Increased Long-Term Mortality in Patients Admitted to the Intensive Care Unit with Health-Care Associated Pneumonia

The American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) developed and periodically update guidelines for the diagnosis and management of community-acquired and nosocomial pneumonia based on the patient-care setting in which pneumonia evolved. ATS/IDSA provides guidelines for empiric antibiotic choices based on the category of pneumonia that is diagnosed. Pneumonia is a significant cause of mortality in the United States and when combined with influenza ranks as the eighth leading cause of death nationwide yet little is known about the mortality of critically ill patients with pneumonia that require admission to a medical intensive care unit (ICU). Our findings suggest that older age, higher severity of illness at ICU admission, and chronic comorbid illnesses are the main contributors to long-term mortality from pneumonia requiring ICU admission. In this cohort, we found an independent association between increased mortality and admission from the general hospital ward rather than directly from the emergency department. Our study did not demonstrate that initial guideline-based antibiotic therapy was associated with a reduction in short-term mortality; however, it did demonstrate a high prevalence of resistant pathogens in HCAP/HAP patients, which reflects ATS/IDSA guideline expectations
DESIGN OF MECHANICAL VISCOUS DAMPERS FOR STAY CABLES

External dampers have been utilized in a number of cable-stayed bridges to suppress transverse cable vibrations. However, simple and accurate damper design recommendations that concurrently consider all important cable parameters are lacking. Previous efforts have been based on the idealization of cables as taut strings. In this paper, the governing differential equation for vibration of cables containing a viscous damper is converted to a complex eigenvalue problem containing nondimensional cable parameters. Next, a parametric study is conducted involving repeated solutions of the eigenvalue problem for a wide range of nondimensional parameters. The effects of dampers on first mode vibration frequencies and first mode cable damping ratios are presented in nondimensional format. It is shown that, for the range of parameters involved in most stay cables, the influence of cable sag is insignificant, whereas the cable bending stiffness can have a significant influence on the resulting cable damping ratios. Simplified nondimensional relationships are proposed for calculating damper-induced changes in the first mode cable damping ratios. Results of lab tests on a scaled model cable are compared with estimated values using the formulation presented. Example problems are also presented for comparison and design purposes.
Vitamin D insufficiency as a risk factor for reproductive losses in miscarriage

Abstract Objective To study the relationship between vitamin D deficiency, VDR gene polymorphism rs10735810 (A > G), and a missed abortion in the first trimester of gestation; to determine the predictors of its risk. Research methods 178 women aged between 18 and 41 were surveyed. The main group consisted of patients with miscarriage (n = 101), verified at the hospital stage (O02.0; O02.1), which were stratified by I group (n = 58, patients with the first miscarriage) and II groups (n = 43, patients with repeated miscarriage). The control group (n = 77) consisted of women with a successful pregnancy (Z34.0), which subsequently ended in delivery at term with a live fetus. Patients were surveyed and data was extracted from primary medical records. The level of 25(OH)D in the blood serum was investigated by mass spectrometry (n = 99). Genotyping for the vitamin D receptor gene polymorphism rs10735810 (VDR A > G) was performed for 177 patients. Statistical data analysis was performed via Statistica 10 and SAS JMP 11 application packages, using single-factor prediction for quantitative and binary factors, ROC analysis, and CHAID decision tree construction. Results of the study WE found that patients with miscarriage in the first trimester of gestation (n = 60) more frequently than those in the control group (n = 39) had vitamin D insufficiency (93.3% versus 76.9%, p = .0183) including its deficiency, occurring at 25(OH)D of blood <20 ng/ml (71.7% versus 51.3%, p = .0392). This pattern was found in patients with the first miscarriage, where significant differences in the frequency of vitamin D deficiency were also detected in comparison with the control group (80.0% versus 51.3%, p = .0026). No direct correlation was found between the frequency of miscarriages in the first trimester and the variant of the polymorphism of the vitamin D receptor gene (VDR A > G [rs10735810]); the GG genotype in patients with repeated miscarriages was even less frequent compared to the control group (14.0% versus 23.7%, p = .3344). However, the decision tree has identified four risk classes and has determined that the highest risk of missed abortion in the cohort studied is formed by three predicates: smoking, serum level 25(OH)D < 6.5 ng/ml and VDR AA and GG genotypes. Conclusion The data obtained show that vitamin D insufficiency plays a pathogenetically significant role in early reproductive losses associated with miscarriages, both first and recurrent.
Using Team-Based Learning to Teach Data Science

ABSTRACT Data science is collaborative and its students should learn teamwork and collaboration. Yet it can be a challenge to fit the teaching of such skills into the data science curriculum. Team-Based Learning (TBL) is a pedagogical strategy that can help educators teach data science better by flipping the classroom to employ small-group collaborative learning to actively engage students in doing data science. A consequence of this teaching method is helping students achieve the workforce-relevant data science learning goals of effective communication, teamwork, and collaboration. We describe the essential elements of TBL: accountability structures and feedback mechanisms to support students collaborating within permanent teams on well-designed application exercises to do data science. The results of our case study of using TBL to teach a modern, introductory data science course indicate that the course effectively taught reproducible data science workflows, beginning R programming, and communication and collaboration. Students also reported much room for improvement in their learning of statistical thinking and advanced R concepts. To help the data science education community adopt this appealing pedagogical strategy, we outline steps for deciding on using TBL, preparing and planning for it, and overcoming potential pitfalls when using TBL to teach data science.
Do Students Learn More from Erroneous Code? Exploring Student Performance and Satisfaction in an Error-Free Versus an Error-full SAS® Programming Environment

Abstract Teaching students statistical programming languages while simultaneously teaching them how to debug erroneous code is challenging. The traditional programming course focuses on error-free learning in class while students’ experiences outside of class typically involve error-full learning. While error-free teaching consists of focused lectures emphasizing correct coding, error-full teaching would follow such lectures with debugging sessions. We aimed to explore these two approaches by conducting a pilot study of 18 graduate students who voluntarily attended a SAS programming seminar held weekly from September 2018 through November 2018. Each seminar had a 10-min error-free lecture, 15-min programming assignment, 5-min break, 10-min error-full lecture, and 15-min programming assignment. We examined student performance and preference. While four students successfully completed both assignments and ten students did not successfully complete either assignment, one student successfully completed only the first assignment that directly followed the error-free lecture and three students successfully completed only the second assignment that directly followed the error-full lecture. Of the 15 students who responded, twelve (80%) preferred error-full to error-free learning. We will evaluate error-full learning on a larger scale in an introductory SAS course. Supplemental files are available online for this article.
Placental expression of endoglin, placental growth factor, leptin, and hypoxia-inducible factor-1 in diabetic pregnancy and pre-eclampsia

Abstract Objective To evaluate a level of expression of endoglin (Eng), leptin (Lep), placental growth factor (PlGF), and hypoxia-inducible factor-1alpha (HIF-1α) in placenta among women with pre-eclampsia and diabetes mellitus (DM), considering the method of glycemia correction and preconception care. Materials and methods A retrospective cohort study was conducted. A total of 124 women were divided into following groups: type 1 DM (n = 40), type 2DM (n = 31), gestational DM (n = 33), pre-eclampsia without DM (PE) (n = 10) and the control group (n = 10). The histochemical study was performed by using primary monoclonal antibodies to Eng, PlGF, Lep, and HIF-1α (Abcam, UK). Results The highest level of placental expression of Eng was observed in the PE group (20.34%). The same trend was also typical for T1DM (not planned) and insulin-treated groups: T2DM and GDM. An amount of cell with an PlGF expression was significantly higher in the control group (12.2%), while the lowest was observed in the pre-eclampsia group (1.18%) and T1DM (not planned) (1.26%). The placental leptin expression within each DM group was increased among the patients with unplanned pregnancy and those who received insulin therapy. We observed the lowest Lep expression in the PE group (6.3%). High level of HIF-1α expression was detected in T1DM (not planned) (30.44%) and PE (29.64%) as compared to the control group (11.62%). In T2DM and GDM insulin groups, the HIF-1α expression was significantly higher as compared to diet groups. Conclusion The obtained data show that DM and pre-eclampsia are associated with changes in angiogenic and metabolic placental factor expressions. The degree of changes depends on preconception care and the control of glycemia level during pregnancy.