Artificial intelligence-enabled rapid and symptom-based medication recommendation system (COV-MED) for the COVID-19 patients

In a general COVID-19 population in Cox’s Bazar, Bangladesh, we developed a medication recommendation system based on clinical information from the electronic medical record (EMR). Our goal was also to enable deep learning (DL) strategies to quickly assist physicians and COVID-19 patients by recommending necessary medications. The general demographic data, clinical symptoms, basic clinical tests, and drug information of 8953 patients were used to create a dataset. The learning model in this COVID-MED model was created using Keras (an open-source artificial neural network library) to solve regression problems. In this study, a sequential model was adopted. In order to improve the prediction capability and achieve global minima quickly and smoothly, the COVID-MED model incorporates an adaptive optimizer dubbed Adam. The model calculated a mean absolute error of 0.0037, a mean squared error of 0.000035, and a root mean squared error of 0.0059. The model predicts the output medications, such as injections or other oral medications, with around 99% accuracy. These findings show that medication can be predicted using information from the EMR. Similar models allow for patient-specific decision support to help prevent medication errors in diseases other than COVID-19

Polyamines confer salt tolerance in mung bean (Vigna radiata L.) by reducing sodium uptake, improving nutrient homeostasis, antioxidant defense and methylglyoxal detoxification systems

The physiological roles of PAs (putrescine, spermidine, and spermine) were investigated for their ability to confer salt tolerance (200 mM NaCl, 48 h) in mung bean seedlings (Vigna radiata L. cv. BARI Mung-2). Salt stress resulted in Na toxicity, decreased K, Ca, Mg, and Zn contents in roots and shoots, and disrupted antioxidant defense system which caused oxidative damage as indicated by increased lipid peroxidation, H2O2 content, O2•– generation rate, and lipoxygenase activity. Salinity-induced methylglyoxal (MG) toxicity was also clearly evident. Salinity decreased leaf chlorophyll (chl) and relative water content (RWC). Supplementation of salt affected seedlings with exogenous PAs enhanced the contents of glutathione and ascorbate, increased activities of antioxidant enzymes (dehydroascorbate reductase, glutathione reductase, catalase and glutathione peroxidase) and glyoxalase enzyme (glyoxalase II), which reduced salt-induced oxidative stress and MG toxicity, respectively. Exogenous PAs reduced cellular Na content and maintained nutrient homeostasis and modulated endogenous PAs levels in salt affected mung bean seedlings. The overall salt tolerance was reflected in improved tissue water and chl content, and better seedling growth

Exogenous Gallic Acid Confers Salt Tolerance in Rice Seedlings: Modulation of Ion Homeostasis, Osmoregulation, Antioxidant Defense, and Methylglyoxal Detoxification Systems

The worldwide saline-affected area is expanding day by day, and soil salinity restricts crop development and productivity, including rice. Considering this, the current study explored the response of gallic acid (GA) in conferring salinity tolerance in rice seedlings. Fourteen-day-old rice (Oryza sativa L. cv. BRRI dhan52) seedlings were treated with 200 mM NaCl alone or combined with 1 mM GA. Salt stress resulted in osmotic, ionic, and oxidative stress in rice seedlings. Osmotic stress increased proline accumulation and osmotic potential, which decreased the relative water content, chlorophyll contents, and dry weight. Ionic stress interrupted ion homeostasis by Na+ accumulation and K+ leakage. Osmotic and ionic stress, concomitantly, disrupted antioxidant defense and glyoxalase systems by higher production of reactive oxygen species (ROS) and methylglyoxal (MG), respectively. It resulted in oxidative damage indicated by the high amount of malondialdehyde (MDA). The supplementation of GA in salt-treated rice seedlings partially recovered salt-induced damages by improving osmotic and ionic homeostasis by increasing water balance and decreasing Na+ content and Na+/K+ ratio. Supplemental GA enhanced the antioxidant defense system in salt-treated rice seedlings by increasing ascorbate (AsA), glutathione (GSH), and phenolic compounds and the activities of AsA-GSH cycle enzymes, including monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), and glutathione reductase (GR) enzymes that accelerated ROS detoxification and decreased oxidative damage. Gallic acid also enhanced the detoxification of MG by triggering glyoxalase enzyme activities in salt-treated rice seedlings. The present findings elucidated that supplemental GA reversed salt-induced damage in rice seedlings through improving osmotic and ionic homeostasis and upregulating the ROS and MG detoxification system

Unique properties of TCR-activated p38 are necessary for NFAT-dependent T-cell activation.

Nuclear factor of activated T cells (NFAT) transcription factors are required for induction of T-cell cytokine production and effector function. Although it is known that activation via the T-cell antigen receptor (TCR) results in 2 critical steps, calcineurin-mediated NFAT1 dephosphorylation and NFAT2 up-regulation, the molecular mechanisms underlying each are poorly understood. Here we find that T cell p38, which is activated by an alternative pathway independent of the mitogen-activated protein (MAP) kinase cascade and with different substrate specificities, directly controls these events. First, alternatively (but not classically) activated p38 was required to induce the expression of the AP-1 component c-Fos, which was necessary for NFAT2 expression and cytokine production. Second, alternatively (but not classically) activated p38 phosphorylated NFAT1 on a heretofore unidentified site, S79, and in its absence NFAT1 was unable to interact with calcineurin or migrate to the nucleus. These results demonstrate that the acquisition of unique specificities by TCR-activated p38 orchestrates NFAT-dependent T-cell functions

Experimental investigation on gas turbine engine performance using alternative fuel

The usage of fossil fuels is a significant contributor to carbon emissions in the aviation industry. Therefore, it is essential to identify alternative energy sources to power modern aircraft. This paper examines the application of biofuels as aviation fuel, which has a lower lifecycle emission compared to fossil fuels. The chosen biofuel was Palm methyl ester, which was blendedcwith Jet A1 at various volume ratios to determine the optimal blend ratio. ThecKingTech K180 micro gas turbine engine was used to evaluate the thrustcproduced for each fuel type at different engine speeds, and the engine pump pulse width was recorded for the corresponding thrust. The results were manually recorded and compared using Python. The study found that the performance remained satisfactory for a blend ratio as high as B50 (50% biodiesel mixed with Jet A1), with maximum thrust comparable to Jet A1. However, B70 and B100 produced significantly less thrust (around 11% and 15% less, respectively). The pump pulse width, which indicates fuel flow, was particularly good for B20, but increased linearly with additional biofuel content

The Effect of the COVID-19 Pandemic on Pulmonary Tuberculosis Control in the Selected Upazila Health Complexes of Dhaka Division, Bangladesh

Despite the enormous disruption of tuberculosis (TB) services reported globally, Bangladesh’s impact is not well documented. We aimed to assess the effect of the COVID-19 pandemic on the TB control program in Bangladesh from patients’ and service providers’ perspectives. We conducted a cross-sectional study from November–December 2021 at six conveniently selected Upazila Health Complexes (UHC) of the Dhaka division, Bangladesh. We conducted face-to-face interviews among 180 pulmonary TB service recipients and all TB service providers working in the selected UHC. We also reviewed TB registries from each UHC. All data were summarized using descriptive statistics tools. We found a 31% reduction in presumptive TB cases during 2021 compared to 2020. Other TB services, such as testing, were reduced by 16–36% during the same period. Service receivers reported a lack of transportation (95%), and a lack of adequate human resources (89%) as critical barriers to receiving and providing TB service, respectively. The findings of our study showed substantial interruption of TB service delivery during the COVID-19 pandemic, threatening the recent progress and pushback from achieving the 2035 End TB targets. Early mitigation of TB service delivery through adopting remote follow-ups using digital health technology and integrating COVID-19 and TB screening is essential for the continuity of essential TB services and achieving global TB targets

Antibiotic Prescribing Practices for Treating COVID-19 Patients in Bangladesh

Although national and international guidelines have strongly discouraged use of antibiotics to treat COVID-19 patients with mild or moderate symptoms, antibiotics are frequently being used. This study aimed to determine antibiotics-prescribing practices among Bangladeshi physicians in treating COVID-19 patients. We conducted a cross-sectional survey among physicians involved in treating COVID-19 patients. During September–November 2021, data were collected from 511 respondents through an online Google Form and hardcopies of self-administered questionnaires. We used descriptive statistics and a regression model to identify the prevalence of prescribing antibiotics among physicians and associated factors influencing their decision making. Out of 511 enrolled physicians, 94.13% prescribed antibiotics to COVID-19 patients irrespective of disease severity. All physicians working in COVID-19–dedicated hospitals and 87% for those working in outpatient wards used antibiotics to treat COVID-19 patients. The majority (90%) of physicians reported that antibiotics should be given to COVID-19 patients with underlying respiratory conditions. The most prescribed antibiotics were meropenem, moxifloxacin, and azithromycin. Our study demonstrated high use of antibiotics for treatment of COVID-19 patients irrespective of disease severity and the duty ward of study physicians. Evidence-based interventions to promote judicious use of antibiotics for treating COVID-19 patients in Bangladesh may help in reducing an overuse of antibiotics

Role of NFAT1 and NFAT1^S79 in NFAT2 and cytokine expression.

<p>(A) Interleukin (IL)-2 and tumor necrosis factor alpha (TNF-α) production in supernatants of wild-type (WT) or N1KO Jurkat clones stimulated with anti-CD3/CD28, phorbol myristate acetate (PMA)/ionomycin, or medium alone for 20 hours. The results represent the mean of 3 independent experiments ± SEM (<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004111#pbio.2004111.s004" target="_blank">S4 Data</a>). (B) WT or N1KO Jurkat clones were stimulated with anti-CD3/CD28, PMA/ionomycin, or medium alone for 48 hours, and NFAT2 expression was determined by immunoblotting. (C) The N1KO Jurkat clone was infected with retrovirus encoding HA-NFAT or HA-NFAT1^S79A, followed by single cell sorting of green fluorescent protein-positive (GFP⁺) cells. Quantitation of transduced gene product expression in 2 independent clones from each transduction was determined by immunoblotting with anti-HA. (D) Quantitation of IL-2 in the supernatants of HA-NFAT1 or HA-NFAT1^S79A Jurkat clones stimulated with anti-CD3/CD28, PMA/ionomycin, or medium alone. The results represent the mean of 3 independent experiments ± SEM (<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004111#pbio.2004111.s004" target="_blank">S4 Data</a>).</p

Phosphorylation of NFAT1^S79A is required for nuclear migration upon T-cell antigen receptor (TCR) stimulation.

<p>(A) Purified T cells from wild-type (WT) mice were infected with retrovirus encoding HA-NFAT1 or HA-NFAT1^S79A. The cells were stimulated with anti-CD3/CD28 for 1 hour and examined for NFAT1 (red) localization by confocal microscopy. DAPI was used to stain the nucleus. Scale bar = 10 μM. (B) Purified primary T cells from WT mice were stimulated and infected as in panel A, and NFAT1 levels in the cytosolic and nuclear fractions were assessed by immunoblotting. (C) Stable Jurkat cell lines expressing HA-NFAT1 or HA-NFAT1^S79A were stimulated with anti-CD3/CD28 for 1 hour, and the lysates were immunoprecipitated (IP) with anti-HA and immunoblotted (IB) for calcineurin A and HA. (D) Confocal images of in situ proximity ligation assay (PLA) of stable Jurkat cell clones expressing HA-NFAT or HA-NFAT1^S79A that had been stimulated with anti-CD3/CD28 for 15 minutes. Alexa Fluor 488 (green)-conjugated wheat germ agglutinin (WGA) was used to stain plasma membrane. Scale bar = 100 pixels (left panel). Quantification of the average dots and intensity per cell (WT-Uns [<i>n</i> = 166], anti-CD3/CD28 [<i>n</i> = 132]; S79A-Uns [<i>n</i> = 162], and anti-CD3/CD28 [<i>n</i> = 132]) (right panel) (<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004111#pbio.2004111.s005" target="_blank">S5 Data</a>). **<i>p</i> < 0.01, ****<i>p</i> < 0.0001. NS, not significant.</p

Optical Genome Mapping Identifies Novel Recurrent Structural Alterations in Childhood ETV6::RUNX1+ and High Hyperdiploid Acute Lymphoblastic Leukemia

The mutational landscape of B-cell precursor acute lymphoblastic leukemia (BCP-ALL), the most common pediatric cancer, is not fully described partially because commonly applied short-read next generation sequencing has a limited ability to identify structural variations. By combining comprehensive analysis of structural variants (SVs), single-nucleotide variants (SNVs), and small insertions-deletions, new subtype-defining and therapeutic targets may be detected. We analyzed the landscape of somatic alterations in 60 pediatric patients diagnosed with the most common BCP-ALL subtypes, ETV6::RUNX1+ and classical hyperdiploid (HD), using conventional cytogenetics, single nucleotide polymorphism (SNP) array, whole exome sequencing (WES), and the novel optical genome mapping (OGM) technique. Ninety-five percent of SVs detected by cytogenetics and SNP-array were verified by OGM. OGM detected an additional 677 SVs not identified using the conventional methods, including (subclonal) IKZF1 deletions. Based on OGM, ETV6::RUNX1+ BCP-ALL harbored 2.7 times more SVs than HD BCP-ALL, mainly focal deletions. Besides SVs in known leukemia development genes (ETV6, PAX5, BTG1, CDKN2A), we identified 19 novel recurrently altered regions (in n ≥ 3) including 9p21.3 (FOCAD/HACD4), 8p11.21 (IKBKB), 1p34.3 (ZMYM1), 4q24 (MANBA), 8p23.1 (MSRA), and 10p14 (SFMBT2), as well as ETV6::RUNX1+ subtype-specific SVs (12p13.1 (GPRC5A), 12q24.21 (MED13L), 18q11.2 (MIB1), 20q11.22 (NCOA6)). We detected 3 novel fusion genes (SFMBT2::DGKD, PDS5B::STAG2, and TDRD5::LPCAT2), for which the sequence and expression were validated by long-read and whole transcriptome sequencing, respectively. OGM and WES identified double hits of SVs and SNVs (ETV6, BTG1, STAG2, MANBA, TBL1XR1, NSD2) in the same patient demonstrating the power of the combined approach to define the landscape of genomic alterations in BCP-ALL