Whole-genome sequencing of three ciprofloxacin-resistant Salmonella Reading (ST93) strains, an emerging Salmonella serovar in the poultry sector of Pakistan.

In this study, we performed whole-genome sequencing of three ciprofloxacin-resistant Salmonella Reading strains isolated from poultry meat. Genomes of S. Reading strains contained an average of 4.81 Mbp size with 52.1% GC. The isolates exhibited blaOXA-10, aac [6']-Iaa, aadA1, cmlA1, qnrS1, and tetA resistance genes and IncX1 and IncX2 plasmids.

Effects of a High Trans Fatty Acid Diet on Kidney-, Liver-, and Heart-Associated Diseases in a Rabbit Model.

Trans fatty acids are specific unsaturated fats found in processed foods that undergo hydrogenation, leading to hepatic disorders such as metabolic-associated fatty liver disease (MAFLD) and conditions like CVD and CKD. The effects of different food samples containing trans fatty acids (elaidic and oleic acid) on the liver, heart, and kidney through antioxidant enzyme activity were investigated in animal models. Liver function tests (ALT, ALP, AST, and LDH), heart biomarker levels (CPK, TC, HDL, LDL, and triglycerides), and kidney biomarker levels (serum creatinine, blood urea nitrogen, and serum uric acid) were examined in serum of rabbits and the histopathology of liver tissues. Results showed that these biomarkers were more elevated in the Mujahid Ghee group than in the normal control, oleic acid, and Kausar Ghee groups. The concentration of antioxidant markers such as peroxidase, glutathione, catalase, thiobarbituric acid reactive substances, and superoxide dismutase were lower in the Mujahid Ghee group. HPLC showed that Mujahid Ghee had the highest quantified value of elaidic acid among all selected samples. Overall, this study demonstrated that elaidic acid in its purest form aggravated MAFLD in rabbit livers and provoked CVK and CVD.

Sulfonamide based pyrimidine derivatives combating Plasmodium parasite by inhibiting falcipains-2 and falcipains-3 as antimalarial agents.

In this report, we present the design and synthesis of a novel series of pyrimidine-tethered spirochromane-based sulfonamide derivatives aimed at combating drug resistance in malaria. The antimalarial effectiveness of these compounds was assessed in vitro. Structural validation of the synthesized compounds was conducted using mass spectrometry and NMR spectroscopy. Strong antimalarial activity against CQ-sensitive (3D7) and CQ-resistant (W2) strains of Plasmodium falciparum was demonstrated by the majority of the compounds. Notably, compounds SZ14 and SZ9 demonstrated particularly potent effects, with compound SZ14 showing IC50 values of 2.84 µM and SZ9 3.22 µM, indicating single-digit micromolar activity. The compounds exhibiting strong antimalarial activity were assessed through enzymatic tests against the cysteine protease enzymes of P. falciparum, falcipain-2 and falcipain-3. The results indicated that SZ14 and SZ9 inhibited PfFP-2 (IC50 values: 4.1 and 5.4 µM, respectively), and PfFP-3 (IC50 values: 4.9 and 6.3 µM, respectively). To confirm the compounds' specificity towards the parasite, we investigated their cytotoxicity against Vero cell lines, revealing strong selectivity indices and no significant cytotoxic effects. Additionally, in vitro hemolysis testing showed these compounds to be non-toxic to normal human blood cells. Moreover, predicted in silico ADME parameters and physiochemical characteristics demonstrated the drug-likeness of the synthetic compounds. These collective findings suggest that sulfonamide derivatives based on pyrimidine-tethered oxospirochromane could serve as templates for the future development of potential antimalarial drugs.

Understanding the Role of Polyunsaturated Fatty Acids in the Development and Prevention of Cancer.

Polyunsaturated fatty acids (PUFAs), notably omega-3 (n-3) and omega-6 (n-6), have received much attention owing to their multifaceted effects not only in the management of diverse pathological conditions but also in the maintenance of overall health of an individual. A disproportionately high n-6 to n-3 ratio contributes to the development of various disorders including cancer, which ranks as a leading cause of death worldwide with profound social and economic burden. Epidemiological studies and clinical trials combined with the animal and cell culture models have demonstrated the beneficial effects of n-3 PUFAs in reducing the risk of various cancer types including breast, prostate and colon cancer. The anti-cancer actions of n-3 PUFAs are mainly attributed to their role in the modulation of a wide array of cellular processes including membrane dynamics, apoptosis, inflammation, angiogenesis, oxidative stress, gene expression and signal transduction pathways. On the contrary, n-6 PUFAs have been shown to exert pro-tumor actions; however, the inconsistent findings and controversial data emphasize upon the need to further investigation. Nevertheless, one of the biggest challenges in future is to optimize the n-6 to n-3 ratio despite the genetic predisposition, age, gender and disease severity. Moreover, a better understanding of the potential risks and benefits as well as the cellular and molecular mechanisms of the basic actions of these PUFAs is required to explore their role as adjuvants in cancer therapy. All these aspects will be reviewed in this chapter.

Robust leishmanicidal upshot of some new diphenyl triazine-based molecules.

Amongst the neglected tropical diseases, leishmaniasis alone causes 30 000 deaths annually due to the protozoan parasite genus Leishmania. Existing therapies have serious drawbacks in safety, drug resistance, field-adapted application and cost. Therefore, new safer and shorter treatments are an urgent need of the time. Herein, we report the synthesis of fifteen novel diphenyl triazine and diphenyl triazine pyrimidine derivatives and their antileishmanial properties against Leishmania donovani, that causes fatal visceral leishmaniasis. Most of the synthesized analogues exhibited more than 90% inhibition against the promastigote stage of the parasite. Moreover, compounds T4 and T7 showed potent activity against extracellular promastigote (IC50 = 1.074 µM and IC50 = 1.158 µM) as compared to miltefosine (IC50 = 1.477 µM) and is nontoxic towards the host THP-1 macrophage cell line. Interestingly, compound T4 exhibited significant activity against amastigotes (7.186 µM) and induced the macrophages to prevent the survival of the parasite. Our results indicate that T4 represents a new structural lead for this serious and neglected disease.

Experience and side effects of COVID-19 vaccine uptake among university students: a cross-sectional survey study.

Introduction: Many people expressed concern over coronavirus vaccinations' reliability and side effects. This research aimed to assess university students' perceptions and experiences regarding the side effects of the COVID-19 vaccines in Bangladesh. Method: We conducted an online cross-sectional survey to collect responses from university students vaccinated with any vaccines administered in Bangladesh between November 2021 to April 2022. Bangladeshi university students over the age of 18 and having an internet connection was included in the study. A binary logistic regression analysis along with Pearson's Chi-square test were used to identify COVID-19 vaccine-related side effects predictors after receiving the first dose. Results: A total of 1,176 participants responded voluntarily to the online study, and most were vaccinated. More than half of the participants received the Sinopharm vaccine (56.5%), while others received Covishield (8.9%), Moderna (7.3%), and Pfizer (5.8%) vaccine. Around 32% of the participants reported side effects after receiving the first dose of the vaccine, including pain and edema (78.4%), body temperature (20.3%), and headache (14.5%), while a few experienced allergy, anxiety, and uneasy feelings. About 17% of the participants reported experiencing side effects after the second dose of the vaccine, including pain and edema (7.5%), body temperature (8.8%), and headache (7.3%). Most side effects were significantly associated with the Moderna vaccine (p < 0.001). Female students and those previously infected with COVID-19 were significantly associated with the side effects after taking the first dose of the vaccine. Conclusion: We found that side effects are mild and did not pose a significant challenge to Bangladesh's effort in managing and reducing the risk associated with the COVID-19 pandemic.

Giant Cell Tumor of the Temporal Bone with Direct Invasion into the Middle Ear and Skull Base: A Case Report.

Giant cell tumor (GCT) of bone is a rare, benign, osteolytic neoplasm that most commonly occurs in early adulthood and often involves the long bones of the body. Although GCT largely affects the epiphyses of long bones, several reports of GCT involvement of the cranial and facial bones exist in the literature. In addition to reviewing other reported cases of GCT of the lateral skull base in the literature, the authors report here on the clinical presentation, radiographic findings, and management of a patient found to have a GCT of the squamous part of temporal bone invading the middle ear and infratemporal fossae, which was treated by en bloc resection of the lateral skull base.

Comprehensive insights into Klebsiella pneumoniae: unravelling clinical impact, epidemiological trends and antibiotic-resistance challenges.

Klebsiella pneumoniae, a challenging opportunistic bacterium, became a notable global health concern owing to its clinical impact, widespread epidemiology and escalating antibiotic resistance. This comprehensive review delves into the multifaceted dimensions of K. pneumoniae, with a focus on its clinical implications, epidemiological patterns and the critical issue of antibiotic resistance. The review also emphasizes the implications of K. pneumoniae in the context of antimicrobial stewardship and infection control. Epidemiological aspects are scrutinized, shedding light on the global distribution and prevalence of K. pneumoniae. Factors influencing its transmission and persistence in healthcare facilities and communities are examined, with patient demographics, healthcare practices and geographical variations. The review centres on antibiotic resistance, a critical issue in the era of bacteria displaying resistance to multiple drugs. The mechanisms of resistance used by K. pneumoniae against various classes of antibiotics are elucidated, along with the alarming rise of carbapenem-resistant strains. It also highlights ongoing research efforts and innovative strategies aimed at addressing this critical public health issue. This comprehensive review offers a holistic understanding of K. pneumoniae, emphasizing its clinical significance, global epidemiology and the immediate necessity for effective strategies to combat antibiotic resistance. It serves as a valuable resource for healthcare practitioners, researchers and policymakers seeking to manage better and mitigate the impact of this pathogen on public health.

Exploring the resistome, virulome, and mobilome of multidrug-resistant Klebsiella pneumoniae isolates: deciphering the molecular basis of carbapenem resistance.

BACKGROUND: Klebsiella pneumoniae, a notorious pathogen for causing nosocomial infections has become a major cause of neonatal septicemia, leading to high morbidity and mortality worldwide. This opportunistic bacterium has become highly resistant to antibiotics due to the widespread acquisition of genes encoding a variety of enzymes such as extended-spectrum beta-lactamases (ESBLs) and carbapenemases. We collected Klebsiella pneumoniae isolates from a local tertiary care hospital from February 2019-February 2021. To gain molecular insight into the resistome, virulome, and genetic environment of significant genes of multidrug-resistant K. pneumoniae isolates, we performed the short-read whole-genome sequencing of 10 K. pneumoniae isolates recovered from adult patients, neonates, and hospital tap water samples. RESULTS: The draft genomes of the isolates varied in size, ranging from 5.48 to 5.96 Mbp suggesting the genome plasticity of this pathogen. Various genes conferring resistance to different classes of antibiotics e.g., aminoglycosides, quinolones, sulfonamides, tetracycline, and trimethoprim were identified in all sequenced isolates. The highest resistance was observed towards carbapenems, which has been putatively linked to the presence of both class B and class D carbapenemases, blaNDM, and blaOXA, respectively. Moreover, the biocide resistance gene qacEdelta1 was found in 6/10 of the sequenced strains. The sequenced isolates exhibited a broad range of sequence types and capsular types. The significant antibiotic resistance genes (ARGs) were bracketed by a variety of mobile genetic elements (MGEs). Various spontaneous mutations in genes other than the acquired antibiotic-resistance genes were observed, which play an indirect role in making these bugs resistant to antibiotics. Loss or deficiency of outer membrane porins, combined with ESBL production, played a significant role in carbapenem resistance in our sequenced isolates. Phylogenetic analysis revealed that the study isolates exhibited evolutionary relationships with strains from China, India, and the USA suggesting a shared evolutionary history and potential dissemination of similar genes amongst the isolates of different origins. CONCLUSIONS: This study provides valuable insight into the presence of multiple mechanisms of carbapenem resistance in K. pneumoniae strains including the acquisition of multiple antibiotic-resistance genes through mobile genetic elements. Identification of rich mobilome yielded insightful information regarding the crucial role of insertion sequences, transposons, and integrons in shaping the genome of bacteria for the transmission of various resistance-associated genes. Multi-drug resistant isolates that had the fewest resistance genes exhibited a significant number of mutations. K. pneumoniae isolate from water source displayed comparable antibiotic resistance determinants to clinical isolates and the highest number of virulence-associated genes suggesting the possible interplay of ARGs amongst bacteria from different sources.

Chitosan/starch based unoxidized tannic acid modified microparticles for rapid hemostasis with broad spectrum antibacterial activity.

The development of a rapid hemostat through a facile method with co-existing antibacterial activity and minimum erythrocyte lysis property stands as a major requirement in the field of hemostasis. Herein, a series of novel microparticle hemostats were synthesized using chitosan, different hydrothermally-treated starches, and cross-linked with tannic acid (TA) simultaneously in an unoxidized environment via ionotropic gelation method. Hemostats' comparative functional properties, such as adjustable antibacterial and erythrocyte compatibility upon various starch additions were evaluated. The in vivo hemostatic study revealed that the developed hemostats for mouse liver laceration and rat tail amputation had clotting times (13 s and 38 s, respectively) and blood loss (51 mg and 62 mg, respectively) similar to those of Celox™. The erythrocyte adhesion test suggested that erythrocyte distortion can be lowered by modifying the antibacterial hemostats with different starches. The broad-spectrum antibacterial efficacy of the hemostats remained intact against S. aureus (>90 %), E. coli (>80 %), and P. mirabilis bacteria upon starch modification. They also demonstrated high hemocompatibility (<3 % hemolysis ratio), moderate cell viability (>81 %), in vivo biodegradation, and angiogenesis indicating adequate biocompatibility and wound healing. The developed hemostats hold significant promise to be employed as rapid hemostatic agents for preventing major bleeding and bacterial infection in emergencies.

Anti-inflammatory and anti-diabetic properties of indanone derivative isolated from Fernandoa adenophylla in vitro and in silico studies.

Fernandoa adenophylla, due to the presence of phytochemicals, has various beneficial properties and is used in folk medicine to treat many conditions. This study aimed to isolate indanone derivative from F. adenophylla root heartwood and assess in-vitro anti-inflammatory and anti-diabetic characteristics at varying concentrations. Heat-induced hemolysis and glucose uptake by yeast cells assays were conducted to evaluate these properties. Besides, docking analyses were performed on four molecular targets. These studies were combined with molecular dynamics simulations to elucidate the time-evolving inhibitory effect of selected inhibitors within the active pockets of the target proteins (COX-1 and COX-2). Indanone derivative (10-100 µM) inhibited the lysis of human red blood cells from 9.12 ± 0.75 to 72.82 ± 4.36% and, at 5-100 µM concentrations, it significantly increased the yeast cells' glucose uptake (5.16 ± 1.28% to 76.59 ± 1.62%). Concluding, the isolated indanone might act as an anti-diabetic agent by interacting with critical amino acid residues of 5' adenosine monophosphate-activated protein kinase (AMPK), and it showed a binding affinity with anti-inflammatory targets COX-1, COX-2, and TNF-α. Besides, the obtained results may help to consider the indanone derivative isolated from F. adenophylla as a promising candidate for drug delivery, subject to outcomes of further in vivo and clinical studies.

An Unusual Presentation of Angiolymphoid Hyperplasia with Eosinophilia as Postauricular Mass: A case Report.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare, benign, reactive vaso-proliferative condition in the dermal and subcutaneous tissues of the head and neck. A 28-year-old female presented with slow-growing painless swelling behind her left ear. FNAC revealed benign soft tissue neoplasm and histopathological examination after surgical excision revealed angiolymphoid hyperplasia with eosinophilia. ALHE origin has been variously attributed to prior trauma, hyperestrogenemia, infectious agents, atopy, reactive hyperplasia, and benign neoplasia. Retroauricular ALHE has been rarely reported. However, on the basis of our case report, it should be a viable differential diagnosis when large subcutaneous tumors of the head and neck are encountered. When big subcutaneous tumors of the head and neck are present, especially in females, a valid differential diagnosis for angiolymphoid hyperplasia with eosinophilia, a rare condition marked by dermal or subcutaneous endothelial cell proliferation, should also be considered.

Effect of Myrtus communis L. Plant Extract as a Milk Supplement on the Performance, Selected Blood Parameters and Immune Response of Holstein Calves.

This research aimed to understand the effects of adding myrtle plant extract obtained from its leaves (MPEL) and roots (MPER) to the milk fed to suckling female Holstein calves, focusing on performance, reproduction, selected blood parameters and immune response. The 50 Holstein female calves, one week of age, were divided into five groups: one group received no plant extract (Control), while the others were supplemented with myrtle plant extracts at doses of 25 mL/day leaf extract (MPEL-25), 25 mL/day root extract (MPER-25), 50 mL/day leaf extract (MPEL-50) and 50 mL/day root extract (MPER-50) for each calf in each treatment group. The extracts were given along with the milk to the experimental groups for 60 days, and for an additional 12 days post-weaning. The results reveal that the feed consumption and live weights increased significantly. Significantly higher leukocyte counts were observed in the 50 mL/head × day myrtle groups, and a higher IgG concentration was also noted in the MPER-50 group compared to the other groups. The serum non-esterified fatty acid (NEFA) concentration significantly decreased in the MPEL-50 and MPER-50 groups, whereas the betahyrdoxy butyric acid (BHBA) concentration increased and the serum glucose concentration significantly decreased with myrtle supplementation. In conclusion, it was determined that the performance, immune system and negative energy balance compensation of female Holstein calves were positively affected by administering extracts obtained from the leaves and roots of the Myrtus communis L. plant at dose levels of 25 and 50 mL/head × day for 72 days, without causing any side effects.

Reinvestigation of diphenylmethylpiperazine analogues of pyrazine as new class of Plasmodial cysteine protease inhibitors for the treatment of malaria.

Malaria eradication is still a global challenge due to the lack of a broadly effective vaccine and the emergence of drug resistance to most of the currently available drugs as part of the mainline artemisinin-based combination therapy. A variety of experimental approaches are quite successful in identifying and synthesizing new promising pharmacophore hybrids with distinct mechanisms of action. Based on our recent findings, the current study demonstrates the reinvestigation of a series of diphenylmethylpiperazine and pyrazine-derived molecular hybrids. Pyrazine-derived molecular hybrids were screened to investigate the antiplasmodial activity on drug-susceptible Pf3D7 and drug-resistant PfW2 strains. The selected compounds were shown to be potent dual inhibitors of cysteine protease PfFP2 and PfFP3. Time-course parasitic development study demonstrated that compounds were able to arrest the growth of the parasite at the early trophozoite stage. The compounds did not show hemolysis of red blood cells and showed selectivity to the parasite compared with the mammalian Vero and A5489 cell lines. The study underlined HR5 and HR15 as a new class of Plasmodial falcipain inhibitors with an IC50 of 6.2 µM and 5.9 µM for PfFP2 and 6.8 µM and 6.4 µM for PfFP3, respectively. Both compounds have antimalarial efficacy with IC50 values of 3.05 µM and 2.80 µM for the Pf3D7 strain, and 4.35 µM and 3.39 µM for the PfW2 strain, respectively. Further structural optimization may turn them into potential Plasmodial falcipain inhibitors for malaria therapeutics.

Distribution characteristics of reactive silicon in six water bodies in the Yangtze River Basin in China.

Terrestrial silicon (Si) from biogeochemically weathered rocks and soils into oceans must pass through several water bodies, resulting in some Si immobilized. Hence, the knowledge on Si distribution characteristics in different water bodies at a basin scale is helpful to understand Si immobilization. A total of 65 surface sediments and corresponding overlying water samples were sampled from six water bodies (Dianchi Lake, DL; Dadu River, DR; Tuojiang River, TR; Honghu Lake, HL; Donghu Lake, DhL; Taihu Lake, TL) in the Yangtze River Basin of China, total dissolved Si (TDSi) in overlying water and exchangeable Si (Ex-Si), active non-biogenic Si (NBSi), and total acid dissolved Si (TADSi) in sediments were analyzed. Water chemical parameters (pH, EC, and TDP) and sediment components (LOI, TN, TP, and TADFe) showed that the water environment characteristics of six water bodies differed. TDSi differed among regions and between lakes and rivers, significantly higher in water bodies in the upper reaches and rivers than the middle or lower reaches and lakes (p < 0.05), respectively. Ex-Si in sediments in the upper reaches was significantly higher than in the middle or lower reaches (p < 0.05), except for DhL, whose Ex-Si was the highest. Mean TADSi and active NBSi were significantly higher in lakes than rivers (p < 0.05). Oxidation of sediments significantly increased TDSi in overlying water and active NBSi in sediments (p < 0.01). Si forms in six water bodies significantly depended on components of the sediments (e.g. active Ca2+, Mg2+, Fe, and Al3+) and water chemical parameters (p < 0.05). Our results suggest that immobilization of Si in water bodies in the Yangtze River Basin depends on the types of water bodies and sediments, lakes and Fe-Al dominated sediments have a high potential to immobilize Si, but anthropogenic interference should not be ignored.

Effect of a Dietary Essential Oil Blend in Dairy Cows during the Dry and Transition Period on Blood and Metabolic Parameters of Dams and Their Calves.

Cows face severe challenges of immunosuppression and negative energy balance during transition periods. The current study was designed to investigate the effects of essential oil blend supplementation in dairy cow's ration during dry periods on the health of the cow and calf. In the current study, 45 dry Holstein dairy cows were divided into three groups, each consisting of 15 animals. The control group was without any supplementation; the positive control group was only injected with 0.2 mg/kg levamisole (intramuscular) at 2 months before parturition and 1 month before parturition; and the treatment group was supplemented with 3 g/day for each cow essential oil blend mixed in total mixed ration (TMR). A mixed vaccine against E. coli, Rotavirus, and Coronavirus was administered to all cows before 42 days and after 21 days of calving. The day of the calving of the animal was accepted as day 0. Blood samples were collected from the coccygeal vein of all cows at -60, -45, -30, -15, -7, 0, 1 and 2 days, and the colostrum samples were taken on days 0, 1, and 2. Blood samples were also collected from the jugular vein (V. Jugularis) of the newborn calves on days 0, 1, and 2. The results of the hematological parameters revealed no difference in the total red blood cell count, hemoglobin amount, hematocrit, MCV, MCH, MCHC, RDW, PLT, MPV, and PCT values in both prenatal and postnatal blood of the cows (p > 0.05). In terms of immunological parameters, the total IgG level was significantly higher in the experimental group on the 7th day before birth compared to the other two groups, while the total leukocyte count, lymphocyte count, monocyte count and granulocyte counts were found to be lower after birth (p < 0005). Blood NEFA and BHBA levels were also lower in the experimental group compared to the other two groups (p < 0.005), and the blood glucose level was not different (p > 0.05). In calves, no difference was found between the groups in any of the parameters examined (p > 0.05). It is concluded that the dietary addition of an essential oil blend during the transition period enhanced the immune status and energy metabolism of cows without any effect on the health status of newborn calves.

Trends in Monkeypox transmission: Investigation into 30 most affected countries.

This research is based on the analysis of Monkeypox transmission, from may 7, 2022 to October 11, 2022, in 30 most affected countries around the globe. The most affected countries are selected through the cut point of at least 100 reported confirmed cases of infected persons over the aforementioned time span. We novely argue the exhibition of distributional similarities between the viral flow and well known power law in context of this neglected zoonotic disease. Moreover, model-based evidence suggesting the capability of pathogen to spread far and wide around its nucleus, are collected and presented. It is estimated that 70 % of the reported confirmed cases belonged to 20 % of the top most affected countries. Also, 70 % of the reported transmission was inflicted in 34 % of the days of reporting at least one case, on average.

A gradient mapping guided explainable deep neural network for extracapsular extension identification in 3D head and neck cancer computed tomography images.

BACKGROUND: Diagnosis and treatment management for head and neck squamous cell carcinoma (HNSCC) is guided by routine diagnostic head and neck computed tomography (CT) scans to identify tumor and lymph node features. The extracapsular extension (ECE) is a strong predictor of patients' survival outcomes with HNSCC. It is essential to detect the occurrence of ECE as it changes staging and treatment planning for patients. Current clinical ECE detection relies on visual identification and pathologic confirmation conducted by clinicians. However, manual annotation of the lymph node region is a required data preprocessing step in most of the current machine learning-based ECE diagnosis studies. PURPOSE: In this paper, we propose a Gradient Mapping Guided Explainable Network (GMGENet) framework to perform ECE identification automatically without requiring annotated lymph node region information. METHODS: The gradient-weighted class activation mapping (Grad-CAM) technique is applied to guide the deep learning algorithm to focus on the regions that are highly related to ECE. The proposed framework includes an extractor and a classifier. In a joint training process, informative volumes of interest (VOIs) are extracted by the extractor without labeled lymph node region information, and the classifier learns the pattern to classify the extracted VOIs into ECE positive and negative. RESULTS: In evaluation, the proposed methods are well-trained and tested using cross-validation. GMGENet achieved test accuracy and area under the curve (AUC) of 92.2% and 89.3%, respectively. GMGENetV2 achieved 90.3% accuracy and 91.7% AUC in the test. The results were compared with different existing models and further confirmed and explained by generating ECE probability heatmaps via a Grad-CAM technique. The presence or absence of ECE has been analyzed and correlated with ground truth histopathological findings. CONCLUSIONS: The proposed deep network can learn meaningful patterns to identify ECE without providing lymph node contours. The introduced ECE heatmaps will contribute to the clinical implementations of the proposed model and reveal unknown features to radiologists. The outcome of this study is expected to promote the implementation of explainable artificial intelligence-assiste ECE detection.

Single nucleotide polymorphisms in vitamin D binding protein and 25-hydroxylase genes affect vitamin D levels in adolescents of Arab ethnicity in Kuwait.

Vitamin D deficiency (VDD) is widespread in the Arab world despite ample sunshine throughout the year. In our previous study, lifestyle and socio-demographic factors could explain only 45% of variability in vitamin D levels in Kuwaiti adolescents, suggesting that genetics might contribute to VDD in this region. Single nucleotide polymorphisms (SNP) in the 25-hydroxylase (CYP2R1) and the GC globulin (GC) genes have been reported to affect vitamin D levels in various ethnic groups in adults. In this study, we investigated the association of two SNPs from GC (rs4588 and rs7041) and three SNPs from CYP2R1 (rs10741657, rs11023374 and rs12794714) with vitamin D levels and VDD in a nationally representative sample of adolescents of Arab ethnicity from Kuwait. Multivariable linear regression, corrected for age, sex, parental education, governorate, body mass index, and exposure to sun, demonstrated that each of the 5 study variants showed significant associations with plasma 25(OH)D levels in one or more of the additive, recessive, and dominant genetic models - the rs10741657 under all the three models, rs12794714 under both the additive and recessive models, rs7041 under the recessive model; and rs4588 and rs11023374 under the dominant model. Minor alleles at rs4588 (T), rs7041 (A), rs11023374 (C), and rs12794714 (A) led to a decrease in plasma 25(OH)D levels - rs4588:[ß (95%CI) = -4.522 (-8.66,-0.38); p=0.033]; rs7041:[ß (95%CI) = -6.139 (-11.12,-1.15); p=0.016]; rs11023374:[ß (95%CI) = -4.296 (-8.18,-0.40); p=0.031]; and rs12794714:[ß (95%CI) = -3.498 (-6.27,-0.72); p=0.014]. Minor allele A at rs10741657 was associated with higher levels of plasma 25(OH)D levels [ß (95%CI) = 4.844 (1.62,8.06); p=0.003)] and lower odds of vitamin D deficiency (OR 0.40; p=0.002). These results suggest that the CYP2R1 and GC SNP variants are partly responsible for the high prevalence of VDD in Kuwait. Genotyping these variants may be considered for the prognosis of VDD in Kuwait.

Impact of graded levels of coated calcium butyrate on growth performance and serological indices during pre-weaning stage in Holstein calves.

The study aimed to analyze the impact of calcium butyrate supplementation in calf starter on growth performance indices associated with early rumen development to decrease the volume of milk or milk replacer feeding and enhance early starter intake in Holstein calves. For this purpose, twelve Holstein calves were randomly assigned into three treatments (n = 4/treatment); a control without coated calcium butyrate, T1, and T2 treatments supplemented with coated calcium butyrate 3 g and 6 g per day/head, respectively. Body weight was measured at days 7, 14, 21, 28, 35, 42, 49, and 56 of the trial, and the average daily weight gain and feed conversion ratio were determined. Blood samples were collected at 14, 28, 42, and 56 days of trial for serological parameters. Gut morphometry was performed at the end of trial at slaughtering by collecting duodenal samples. Furthermore, the meat was also evaluated for its quality parameters including pH and tenderness after slaughtering. The results indicated that the feed intake, average daily weight gain, feed conversion ratio, and gut morphometric parameters involving villus height and crypts depth of calves were improved in coated calcium butyrate-supplemented groups. Furthermore, the supplementation of calf starter with coated calcium butyrate significantly enhanced serum concentrations of glucose and total protein. Besides, Beta hydroxy butyrate (BHBA) levels of blood were also found to be elevated in both treatment groups. However, it was revealed that coated calcium butyrate supplementation had no significant effect on meat quality parameters. In conclusion, the supplementation of calf starter with coated calcium butyrate could improve calf performance.