Stimulatory effects of smoke solution and biogas digestate slurry application on photosynthesis, growth, and methylation profiling of solanum tuberosum.

Biostimulants are obtained from various sources like plants, animals, microorganisms, and industrial by-products as well as waste material. Their utilization in agriculture practices is being increased that is giving positive results. The purpose of the current study was to use plant-derived smoke (SMK) solution and biogas digestate (BGD) slurry as biostimulant to elucidate their impact on potato (Solanum tuberosum) performance. The experiment was conducted in lab as well as field conditions, and SMK and BGD solutions were prepared in varying concentrations such as SMK 1:500, SMK 1:250, BGD 50:50, and BGD 75:25. Foliar applications were performed thrice during experiments and data were collected related to photosynthesis, growth, pigments, and genome-wide methylation profiling. Net photosynthesis rate (A) and water use efficiency (WUE) were found higher in SMK- and BGD-treated lab and field grown plants. Among pigments, BGD-treated plants depicted higher levels of Chl a and Chl b while SMK-treated plants showed higher carotenoid levels. Alongside, enhancement in growth-related parameters like leaf number and dry weight was also observed in both lab- and field-treated plants. Furthermore, DNA methylation profile of SMK- and BGD-treated plants depicted variation compared to control. DNA methylation events increased in all the treatments compared to control except for SMK 1:500. These results indicate that smoke and slurry both act as efficient biostimulants which result in better performance of plants. Biostimulants also affected the genome-wide DNA methylation profile that resultantly might have changed the plant gene expression profiling and played its role in plant responsiveness to these biostimulants. However, there is need to elucidate a possible synergistic effect of SMK and BGD on plant growth along with gene expression profiling.

Plant disease detection model for edge computing devices.

In this paper, we address the question of achieving high accuracy in deep learning models for agricultural applications through edge computing devices while considering the associated resource constraints. Traditional and state-of-the-art models have demonstrated good accuracy, but their practicality as end-user available solutions remains uncertain due to current resource limitations. One agricultural application for deep learning models is the detection and classification of plant diseases through image-based crop monitoring. We used the publicly available PlantVillage dataset containing images of healthy and diseased leaves for 14 crop species and 6 groups of diseases as example data. The MobileNetV3-small model succeeds in classifying the leaves with a test accuracy of around 99.50%. Post-training optimization using quantization reduced the number of model parameters from approximately 1.5 million to 0.93 million while maintaining the accuracy of 99.50%. The final model is in ONNX format, enabling deployment across various platforms, including mobile devices. These findings offer a cost-effective solution for deploying accurate deep-learning models in agricultural applications.

Determining epitope specificity of T-cell receptors with transformers.

SUMMARY: T-cell receptors (TCRs) on T cells recognize and bind to epitopes presented by the major histocompatibility complex in case of an infection or cancer. However, the high diversity of TCRs, as well as their unique and complex binding mechanisms underlying epitope recognition, make it difficult to predict the binding between TCRs and epitopes. Here, we present the utility of transformers, a deep learning strategy that incorporates an attention mechanism that learns the informative features, and show that these models pre-trained on a large set of protein sequences outperform current strategies. We compared three pre-trained auto-encoder transformer models (ProtBERT, ProtAlbert, and ProtElectra) and one pre-trained auto-regressive transformer model (ProtXLNet) to predict the binding specificity of TCRs to 25 epitopes from the VDJdb database (human and murine). Two additional modifications were performed to incorporate gene usage of the TCRs in the four transformer models. Of all 12 transformer implementations (four models with three different modifications), a modified version of the ProtXLNet model could predict TCR-epitope pairs with the highest accuracy (weighted F1 score 0.55 simultaneously considering all 25 epitopes). The modification included additional features representing the gene names for the TCRs. We also showed that the basic implementation of transformers outperformed the previously available methods, i.e. TCRGP, TCRdist, and DeepTCR, developed for the same biological problem, especially for the hard-to-classify labels. We show that the proficiency of transformers in attention learning can be made operational in a complex biological setting like TCR binding prediction. Further ingenuity in utilizing the full potential of transformers, either through attention head visualization or introducing additional features, can extend T-cell research avenues. AVAILABILITY AND IMPLEMENTATION: Data and code are available on https://github.com/InduKhatri/tcrformer.

Lymphocyte detection for cancer analysis using a novel fusion block based channel boosted CNN.

Tumor-infiltrating lymphocytes, specialized immune cells, are considered an important biomarker in cancer analysis. Automated lymphocyte detection is challenging due to its heterogeneous morphology, variable distribution, and presence of artifacts. In this work, we propose a novel Boosted Channels Fusion-based CNN "BCF-Lym-Detector" for lymphocyte detection in multiple cancer histology images. The proposed network initially selects candidate lymphocytic regions at the tissue level and then detects lymphocytes at the cellular level. The proposed "BCF-Lym-Detector" generates diverse boosted channels by utilizing the feature learning capability of different CNN architectures. In this connection, a new adaptive fusion block is developed to combine and select the most relevant lymphocyte-specific features from the generated enriched feature space. Multi-level feature learning is used to retain lymphocytic spatial information and detect lymphocytes with variable appearances. The assessment of the proposed "BCF-Lym-Detector" show substantial improvement in terms of F-score (0.93 and 0.84 on LYSTO and NuClick, respectively), which suggests that the diverse feature extraction and dynamic feature selection enhanced the feature learning capacity of the proposed network. Moreover, the proposed technique's generalization on unseen test sets with a good recall (0.75) and F-score (0.73) shows its potential use for pathologists' assistance.

Stratified Analysis of Survival Benefit for ABO-incompatible Deceased-donor Liver Transplantation: Multicenter Propensity Score-matched Study.

Background and Aims: Liver transplantation (LT) using ABO-incompatible (ABOi) grafts can extend the donor pool to a certain extent and hence reduce the waiting time for transplantation. However, concerns of the impending prognosis associated with this option, especially for patients with liver failure and higher model for end-stage liver disease (MELD) scores, who tend to be more fragile during the waiting period before LT. Methods: Recipients undergoing LT for acute-on-chronic liver failure or acute liver failure were retrospectively enrolled at four institutions. Overall survival was compared and a Cox regression analysis was performed. Propensity score matching was performed for further comparison. Patients were stratified by MELD score and cold ischemia time (CIT) to determine the subgroups with survival benefits. Results: Two hundred ten recipients who underwent ABOi LT and 1,829 who underwent ABO compatible (ABOc) LT were enrolled. The 5-year overall survival rate was significantly inferior in the ABOi group compared with the ABOc group after matching (50.6% vs. 75.7%, p<0.05). For patients with MELD scores ≤30, using ABOi grafts achieved a comparable overall survival rate as using ABOc grafts (p>0.05). Comparison of the survival rates revealed no statistically significant difference for patients with MELD scores ≥40 (p>0.05). For patients with MELD scores of 31-39, the overall survival rate was significantly inferior in the ABOi group compared with the ABOc group (p<0.001); however, the rate was increased when the liver graft CIT was<8 h. Conclusions: For recipients with MELD scores ≤30, ABOi LT had a prognosis comparable to that of ABOc LT and can be regarded as a feasible option. For recipients with MELD scores ≥40, ABOi should be adopted with caution in emergency cases. For recipients with MELD scores of 31-39, the ABOi LT prognosis was worse. However, those patients benefited from receiving ABOi grafts with a CIT of <8 h.

Evaluating the antioxidative defense response of selected indoor plants against benzene and formaldehyde.

Volatile organic compounds (VOCs) such as formaldehyde and benzene are among the key contributors to indoor air pollution. The current situation of environmental pollution is alarming, especially indoor air pollution is becoming a challenge as affecting plants and humans. VOCs are known to adversely affect indoor plants by causing necrosis and chlorosis. In order to withstand these organic pollutants, plants are naturally equipped with an antioxidative defense system. The current research study aimed to evaluate the combined effect of formaldehyde and benzene on the antioxidative response of selected indoor C3 plants including Chlorophytum comosum, Dracaena mysore, and Ficus longifolia. After the combined application of different levels (0, 0; 2, 2; 2, 4; 4, 2; and 4, 4 ppm) of benzene and formaldehyde respectively, in an airtight glass chamber, the enzymatic and non-enzymatic antioxidants were analyzed. Analysis of total phenolics showed a significant increase (10.72 mg GAE/g) in F. longifolia; C. comosum (9.20 mg GAE/g); and D. mysore (8.74 mg GAE/g) compared to their respective controls as 3.76, 5.39, and 6.07 mg GAE/g. Total flavonoids (724 µg/g) were reported in control plants of F. longifolia which were increased to 1545.72 µg/g from 724 µg/g (in control) followed by 322.66 µg/g in D. mysore (control having 167.11 µg/g). Total carotenoid content also increased in D. mysore (0.67 mg/g) followed by C. comosum (0.63 mg/g) in response to increasing the combined dose compared to their control plants having 0.62 and 0.24 mg/g content. The highest proline content was exhibited by D. mysore (3.66 µg/g) as compared to its respective control plant (1.54 µg/g) under a 4 ppm dose of benzene and formaldehyde. A significant increase in enzymatic antioxidants including total antioxidants (87.89%), catalase (59.21 U/mg of protein), and guaiacol peroxidase (52.16 U/mg of protein) was observed in the D. mysore plant under a combined dose of benzene (2 ppm) and formaldehyde (4 ppm) with respect to their controls. Although experimental indoor plants have been reported to metabolize indoor pollutants, the current findings indicate that the combined application of benzene and formaldehyde is also affecting the physiology of indoor plants as well.

Systemic analysis identifying PVT1/DUSP13 axis for microvascular invasion in hepatocellular carcinoma.

BACKGROUND: Microvascular invasion (MVI) is an independent detrimental risk factor for tumor recurrence and poor survival in hepatocellular carcinoma (HCC). Competitive endogenous RNA (ceRNA) networks play a pivotal role in the modulation of carcinogenesis and progression among diverse tumor types. However, whether the ceRNA mechanisms are engaged in promoting the MVI process in patients with HCC remains unknown. METHODS: A ceRNA regulatory network was constructed based on RNA-seq data of patients with HCC from The Cancer Genome Atlas (TCGA) database. In total, 10 hub genes of the ceRNA network were identified using four algorithms: "MCC," "Degree," "Betweenness," and "Stress." Transcriptional expressions were verified by in situ hybridization using clinical samples. Interactions between ceRNA modules were validated by luciferase reporting assay. Logistic regression analysis, correlation analysis, enrichment analysis, promoter region analysis, methylation analysis, and immune infiltration analysis were performed to further investigate the molecular mechanisms and clinical transformation value. RESULTS: The ceRNA regulatory network featuring a tumor invasion phenotype consisting of 3 long noncoding RNAs, 3 microRNAs, and 93 mRNAs was constructed using transcriptional data from the TCGA database. Systemic analysis and experimentally validation identified a ceRNA network (PVT1/miR-1258/DUSP13 axis) characterized by lipid regulatory potential, immune properties, and abnormal methylation states in patients with HCC and MVI. Meanwhile, 28 transcriptional factors were identified as potential promotors of PVT1 with 3 transcriptional factors MXD3, ZNF580, and KDM1A promising as therapeutic targets in patients with HCC and MVI. Furthermore, miR-1258 was an independent predictor for MVI in patients with HCC. CONCLUSION: The PVT1/DUSP13 axis is significantly associated with MVI progression in HCC patients. This study provides new insight into mechanisms related to lipids, immune phenotypes, and abnormal epigenetics in oncology research.

Association of vitamin D receptor polymorphisms with cardiometabolic conditions in Pakistani population.

Apart from bone related effects, vitamin D has roles in immune modulation, hypertension, diabetes and cardiovascular diseases. Metabolic functions of vitamin D are mediated after binding with vitamin D receptor (VDR). VDR polymorphisms affect its physiological functions. Several VDR single nucleotide polymorphisms (SNPs) are reported previously. However, VDR polymorphisms causing influence on cardiovascular and metabolic disorders have not been investigated in Pakistani population so far. Therefore, present study was conducted to evaluate the role of VDR polymorphisms (rs2228570 and rs7975232) in the pathobiology of cardiometabolic disorders. In all, 400 cardiometabolic patients and 226 healthy control human adults were enrolled from Faisalabad, Pakistan. Biochemical parameters (serum glucose, liver function test, renal function test and lipid profile) were analyzed by standard kit methods. Genetic analysis was done by ARMS-PCR assay. Data was analyzed in SPSS v20. Regression analysis revealed that GG and AG genotypes of rs2228570 A>G polymorphism significantly increased the risk of hypertension in cardiovascular patients by 5.29 and 5.94 times respectively (GG: OR=5.29, 95% CI=1.63-17.2, p=0.005; AG: OR=5.94, 95% CI=1.70-20.7, p=0.005). However, rs7975232 C>A polymorphism was not correlated with cardiometabolic conditions. In conclusion, GG and AG genotypes of VDR SNP rs2228570 significantly contribute for hypertension in cardiovascular disease patients.

Prediction of tumor recurrence by distinct immunoprofiles in liver transplant patients based on mass cytometry.

Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is a marker of poor prognosis. However, the reliable biomarkers of post-LT HCC recurrence remain to be identified. In this study, serial peripheral blood samples from the LT recipients with and without HCC recurrence were collected at five time points. Single-cell mass cytomertry (CyTOF) was utilized for the in-depth analysis of peripheral blood monocellular cells (PBMCs). CyTOF analysis showed that at 3 weeks post-LT, the activated immune cell population was increased, while the fraction of immune cells with suppressive functions (myeloid-derived suppressive cells) was reduced. The post-LT immune composition in patients with LT for HCC was enormously different from that in patients with LT for causes other than HCC. Furthermore, at 3 weeks after LT, compared with patients without recurrence, the patients with HCC recurrences were high in two subsets of T cells: CD57+ HLA-DR+ CD8+ and CD28+γδ. The CD57+ HLA-DR+ CD8+ T cells presented high levels of perforin, granzyme B, and Ki-67 and displayed a highly cytotoxic and proliferative phenotype, while the CD28+γδ T cells had reduced levels of IFN-γ and, hence, were less activated compared to CD28- cells. Based on these findings, we concluded that analyzing the PBMCs of LT recipients by CyTOF can predict the post-LT HCC recurrence. The distinct immune features can stratify patients with the risk of HCC recurrence at 3 weeks after LT, which will help clinician in further management plan and improve the prognosis of patients.

Identification of QTLs for rice grain size and weight by high-throughput SNP markers in the IR64 x Sadri population.

Grain appearance is one of the most important attributes of rice. It is determined by grain size, shape, and weight, which in turn influences the rice yield and market value. In this study, QTLs for grain length, grain width, grain length/width ratio, and grain weight were mapped using the high-throughput indica/indica SNP platforms. The population of the mega indica variety IR64 and the high-quality aromatic variety Sadri from Iran was phenotyped. Based on this phenotypic data, plants of 94 F2:3 families including both parents were selected. A linkage map analysis of 210 SNP markers identified 14 QTLs controlling the grain length, grain width, length/width ratio, and 1,000 grain weight. Among these 14, one important region containing the QTLs for all the four studies' traits was mapped on chromosome 8. It was derived from Sadri for the decreased length/width ratio and increased grain weight. This study demonstrated the speed and efficiency in using multiplex SNP genotyping for QTL analysis. Moreover, this study identified four novel QTLs (qGL8, qTGW8, qLWR8, and qGW8) sharing the same position on chromosome 8 which were linked with grain quality characteristics between one indica and one aromatic variety. It will enable more precise marker-assisted selection for grain weight, shape, and size. Further in-depth studies are required to dissect this region of interest and identify the related gene(s).

CLIC1 Drives Angiogenesis in Hepatocellular Carcinoma by Modulating VEGFA.

Background: Chloride intracellular channel 1 (CLIC1) is upregulated in hepatocellular carcinoma (HCC). The present study aimed to investigate the role of CLIC1 in HCC angiogenesis. Materials and Methods: Immunohistochemistry (IHC) was used to test the expression of CLIC1 and CD34 in 67 pairs of HCC and paracarcinoma tissues. The prognosis data of the patients were used to analyze the clinical relevance of CLIC1. We built a coculture system of HCC cells and endothelial cells to explore the migration of endothelial cells. Conditioned media (CMs) from HCC cells was then collected to assess endothelial cell migration. Experiments were then conducted to confirm the relationship between CLIC1 and angiogenesis in a subcutaneous tumor model. Results: CLIC1 expression was higher in HCC tumor tissues than in paracarcinoma tissues. Patients with increased CLIC1 expression showed a higher microvascular density (MVD; P = .013). Kaplan-Meier curves indicated that patients with lower expression of CLIC1 had better overall survival (P < .001) and recurrence-free survival (P = .046). Vascular endothelial growth factor A (VEGFA) in CMs from CLIC1-knockdown cells was lower than in the control group, while VEGFA in CMs from CLIC1 overexpression cells was higher than in the control group. CMs from CLIC1 overexpression cell lines promote the in vitro migration of EA.hy926 cells. Meanwhile, adding Bevacizumab to CMs from CLIC1 overexpression cells significantly inhibited this migration. The growth of xenograft tumors derived from CLIC1-knockdown Huh7 cells was restrained compared with the control group (P < .001). IHC staining showed MVD was higher in tumors with CLIC1 overexpression. Conclusion: CLIC1 is a promising biomarker for predicting the prognosis of HCC patients, and expression of CLIC1 correlates with angiogenesis in HCC through regulating VEGFA.

Proteomics-based identification of the role of osteosarcoma amplified-9 in hepatocellular carcinoma recurrence.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies; its recurrence is associated with high mortality and poor recurrence-free survival and is affected by multisystem and multilevel pathological changes. To identify the key proteins associated with tumor recurrence and the underlying mechanisms, proteomic profiling of tumor specimens from early recurrence and nonrecurrence patients was performed in this study. Proteomics was applied to identify differentially expressed proteins during the early recurrence of HCC after surgery. Osteosarcoma amplified-9 (OS-9) was discovered, and the correlation between OS-9 expression and the clinicopathological characteristics of patients was analyzed. Invasion and migration were examined in SMMC-7721 cells with and without OS-9 overexpression. Proteomics was performed once again using SMMC-7721 cells with OS-9 overexpression to further analyze the proteins with altered expression. OS-9 was overexpressed in the early recurrence group, and OS-9 overexpression was associated with high serum alpha-fetoprotein levels and poor recurrence-free survival in 196 patients with HCC. The invasion and migration abilities of SMMC-7721 cells were enhanced in the OS-9 overexpression group. Bioinformatic functional enrichment methods, including Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis, revealed that the hypoxia-inducible factor 1 (HIF-1) and tumor necrosis factor (TNF) signaling pathways were activated in the OS-9 overexpression group. The migration and invasion capacities of OS-9 overexpressed HCC cell line were weakened while treated with HIF-1α or TNF-α inhibitors. Conclusion: Our results suggest that the overexpression of OS-9 is related to HCC recurrence, thereby contributing to the migration and invasion capacities of HCC cell line by regulating the HIF-1 and TNF pathways.

Development of a Novel Prognostic Nomogram for High Model for End-Stage Liver Disease Score Recipients Following Deceased Donor Liver Transplantation.

Background: A high model of end-stage liver disease (MELD) score (>30) adversely affects outcomes even if patients receive prompt liver transplantation (LT). Therefore, balanced allocation of donor grafts is indispensable to avoid random combinations of donor and recipient risk factors, which often lead to graft or recipient loss. Predictive models aimed at avoiding donor risk factors in high-MELD score recipients are urgently required to obtain satisfactory outcomes. Method: Data of patients with MELD score >30 who underwent LT at three transplantation institutes between 2015 and 2018 were retrospectively reviewed. Early allograft dysfunction (EAD), length of intensive care unit (ICU) stay, and graft loss were recorded. Corresponding independent risk factors were analyzed using stepwise multivariable regression analysis. A prediction model of graft loss was developed, and discrimination and calibration were measured. Results: After applying the exclusion criteria, 778 patients were enrolled. The incidence of EAD was 34.8% (271/778). Donor graft macrovesicular steatosis, graft-to-recipient weight ratio (GRWR), warm ischemia time (WIT), cold ischemia time (CIT), and ABO blood incompatibility, together with donor serum albumins, were independent predictors of EAD. The incidence of ICU stay over 10 days was 64.7% (503/778). Donor age, recipient's MELD score, Child score, and CIT were independent predictors of ICU stay. The 3-year graft survival rates (GSRs) in the training and validation cohorts were 64.2 and 59.3%, respectively. The independent predictors of graft loss were recipient's Child score, ABO blood type incompatibility, donor serum total bilirubin over 17.1 µmol/L, and cold CIT. A nomogram based on these variables was internally and externally validated and showed good performance (area under the receiver operating characteristic curve = 70.8 and 66.0%, respectively). For a recipient with a high MELD score, the avoidance of ABO blood type incompatibility and CIT ≥6 h would achieve a 3-year GSR of up to 78.4%, whereas the presence of the aforementioned risk factors would decrease the GSR to 35.4%. Conclusion: The long-term prognosis of recipients with MELD scores >30 could be greatly improved by avoiding ABO blood type incompatibility and CIT ≥6 h.

Correlation between Salivary Levels of IGF-1, IGFBP-3, IGF-1/IGFBP3 Ratio with Skeletal Maturity Using Hand-Wrist Radiographs.

Objective: The relevance of growth determination in orthodontics is driving the search for the most precise and least invasive way of tracking the pubertal growth spurt. Our aim was to explore whether minimally invasive salivary estimation of biomarkers Insulin-like growth factor (IGF-1) and Insulin-like growth factor binding protein-3 (IGFBP-3) could be used to estimate skeletal maturity for clinical convenience, especially in children and adolescent age groups. Materials and Method: The cross-sectional study was conducted on 90 participants (56 girls and 34 males) with ages ranging from 6 to 25 years. Each subject's hand-wrist radiograph was categorized based on skeletal maturity, and saliva samples were estimated for IGF-1 and IGFBP-3 using the respective ELISA kits. Kruskal−Wallis nonparametric ANOVA was applied to compare different skeletal stages. Results: The study demonstrated low salivary IGF-1 levels at the prepubertal stage, with increase during pubertal onset and peak pubertal stage followed by a decline during pubertal deceleration to growth completion. Spearman's correlation coefficient demonstrated a strong positive association (r = 0.98 p < 0.01) between salivary IGF/IGFBP-3 ratio and different stages of skeletal maturity. Conclusion: Salivary IGF-1, IGFBP-3, and IGF/IGFBP-3 ratio could serve as a potential biochemical marker for predicting the completion of skeletal maturity.

Occupational Stress and Stress Busters Used Among Saudi Dental Practitioners During the COVID-19 Pandemic Outbreak.

OBJECTIVE: This study aims to assess the stress levels, stress busters (stress relievers), and coping mechanisms among Saudi dental practitioners (SDPs) during the coronavirus disease (COVID-19) pandemic outbreak. METHOD: A self-administered questionnaire was sent to SDPs via Google Forms. Cohen's stress score scale was used for stress evaluation, and the mean scores were compared based on age, gender, qualification, and occupation. In addition, comparisons of the utilization of stress coping mechanisms and stress busters based on gender, age, and occupation were evaluated. Descriptive statistics were carried out using SPSS Version 21.0 (IBM Corp, Armonk, NY). RESULTS: A total of 206 SDPs (69% males and 31% females) participated in the study. Male SDPs showed a higher score than females (P > 0.05). SDPs around age 50 years and above obtained high stress scores (25 ± 7.4) as compared with other age groups (P < 0.05). The occupational level showed higher stress scores (22.6 ± 4.6 than the other occupation groups (P < 0.05). The majority of the SDPs used watching TV/mobile/computer (80%) as a stress buster, followed by binge eating (64%), exercise (44%), smoking (32%), do-it-yourself (DIY; 23%), and meditation (17%). CONCLUSION: SDPs are experiencing stress levels during the COVID-19 pandemic. Male SDPs above age 50 years and private practitioners showed higher levels of stress scores. An overall commonly used stress buster was smoking in males and meditation in females.

Detection of tumour infiltrating lymphocytes in CD3 and CD8 stained histopathological images using a two-phase deep CNN.

BACKGROUND: Immuno-score, a prognostic measure for cancer, employed in determining tumor grade and type, is generated by counting the number of Tumour-Infiltrating Lymphocytes (TILs) in CD3 and CD8 stained histopathological tissue samples. Significant stain variations and heterogeneity in lymphocytes' spatial distribution and density make automated counting of TILs' a challenging task. METHODS: This work addresses the aforementioned challenges by developing a pipeline "Two-Phase Deep Convolutional Neural Network based Lymphocyte Counter (TDC-LC)" to detect lymphocytes in CD3 and CD8 stained histology images. The proposed pipeline sequentially works by removing hard negative examples (artifacts) in the first phase using a custom CNN "LSATM-Net" that exploits the idea of a split, asymmetric transform, and merge. Whereas, in the second phase, instance segmentation is performed to detect and generate a lymphocyte count against the remaining samples. Furthermore, the effectiveness of the proposed pipeline is measured by comparing it with the state-of-the-art single- and two-stage detectors. The inference code is available at GitHub Repository https://github.com/m-mohsin-zafar/tdc-lc. RESULTS: The empirical evaluation on samples from LYSTO dataset shows that the proposed LSTAM-Net can learn variations in the images and precisely remove the hard negative stain artifacts with an F-score of 0.74. The detection analysis shows that the proposed TDC-LC outperforms the existing models in identifying and counting lymphocytes with high Recall (0.87) and F-score (0.89). Moreover, the commendable performance of the proposed TDC-LC in different organs suggests a good generalization. CONCLUSION: The promising performance of the proposed pipeline suggests that it can serve as an automated system for detecting and counting lymphocytes from patches of tissue samples thereby reducing the burden on pathologists.

Portal Vein Tumor Thrombosis and Hepatocellular Carcinoma - The Changing Tides.

Portal vein involvement is considered one of the most fearful complications of hepatocellular carcinoma (HCC). Portal vein tumor thrombosis (PVTT) is associated with aggressive tumor biology (high grade), high tumor burden (number and size of lesions), high levels of serum markers (AFP), poor liver function (deranged LFT), and poor performance status of patients. The Barcelona Clinic Liver Cancer staging system places HCC patients with PVTT in advanced stage (BCLC Stage-C). This group contains a fairly heterogeneous patient population, previously considered candidates for palliative systemic therapy with sorafenib. However, this provided modest overall survival (OS) benefit. The results of a recent Phase III (IMbrave150) trial favor the combination of atezolizumab and bevacizumab over sorafenib as a standard of care in advanced unresectable HCC. While only lenvatinib proved to be non-inferior against sorafenib in a phase III (REFLECT trial), regorafenib (RESORCE trial), ramucirumab (REACH-2), and cabozantinib (CELESTIAL) have been approved second-line therapy in phase III clinical trials. Recently, the data on the prospect of other modalities in the management of HCC with PVTT is mounting with favorable results. Targeting multiple pathways in the HCC cascade using a combination of drugs and other modalities such as RT, TACE, TARE, and HAIC appear effective for systemic and loco-regional control. The quest for the ideal combination therapy and the sequence set is still widely unanswered and prospective trials are lacking. With the armament of available therapeutic options and the advances and refinements in the delivery system, down-staging patients to make them eligible for curative resection has been reported. In a rapidly evolving treatment landscape, performing surgery when appropriate, in the form of LR and even LT to achieve cure does not seem farfetched. Likewise, adjuvant therapy and prompt management of the recurrences holds the key to prolong OS and DFS. This review discusses the management options of HCC patients with PVTT.

Arabian undergraduates perceptions regarding barriers among the geriatric patients for failing to keep dental appointments: A cross-sectional study.

BACKGROUND: Regular visits to the health care providers can develop a relationship that can extend beyond the physical health alone as the patient is transiting towards older age, adapting to changes in physical health, emotional health, and social connections. Apart from limiting access to health care services, the attitudes, beliefs, comfort level of the treating doctors towards the geriatric patients can motivate or demotivate them to access dental care. AIM: To explore the Saudi Arabian undergraduate students perception of geriatric patients and identify potential barriers that prevent the utilization of their dental appointment. METHODS: A close-ended questionnaire with one question and eight reasons was administered to the fifth year clinical students. The students were requested to specify their agreement with each question on a 5-point Likert scale. Among the barriers presented, each reason's approval was expressed as the percentage of the total number of responses. In addition, the gender comparison of mean scores was made, and an independent sample t-test was used to analyze the statements agreed by the students. All analyses were performed using Statistical Package of Social Sciences (SPSS) version 21.0 (IBM, USA) with the probability of statistical significance at 0.05 level. RESULTS: Fifty-one students recorded their perceptions on the questionnaire administered during their clinical posting in the fifth year of the geriatric dental education program. It was concluded that students believed that geriatric patients give overwhelming importance to other problems with minor importance to oral health care. In addition, gender comparison was more evident as the percentage expressed was more in females. CONCLUSIONS: There is a need for more clinical exposure of geriatric patients during their clinical postings. Student's acquaintance with didactic and clinical settings appears to be a critical element towards positive knowledge and attitude towards the geriatric population.

Anti-bacterial and wound healing-promoting effects of zinc ferrite nanoparticles.

BACKGROUND: Increasing antibiotic resistance continues to focus on research into the discovery of novel antimicrobial agents. Due to its antimicrobial and wound healing-promoting activity, metal nanoparticles have attracted attention for dermatological applications. This study is designed to investigate the scope and bactericidal potential of zinc ferrite nanoparticles (ZnFe2O4 NPs), and the mechanism of anti-bacterial action along with cytocompatibility, hemocompatibility, and wound healing properties. RESULTS: ZnFe2O4 NPs were synthesized via a modified co-precipitation method. Structure, size, morphology, and elemental compositions of ZnFe2O4 NPs were analyzed using X-ray diffraction pattern, Fourier transform infrared spectroscopy, and field emission scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy. In PrestoBlue and live/dead assays, ZnFe2O4 NPs exhibited dose-dependent cytotoxic effects on human dermal fibroblasts. In addition, the hemocompatibility assay revealed that the NPs do not significantly rupture red blood cells up to a dose of 1000 µg/mL. Bacterial live/dead imaging and zone of inhibition analysis demonstrated that ZnFe2O4 NPs showed dose-dependent bactericidal activities in various strains of Gram-negative and Gram-positive bacteria. Interestingly, NPs showed antimicrobial activity through multiple mechanisms, such as cell membrane damage, protein leakage, and reactive oxygen species generation, and were more effective against gram-positive bacteria. Furthermore, in vitro scratch assay revealed that ZnFe2O4 NPs improved cell migration and proliferation of cells, with noticeable shrinkage of the artificial wound model. CONCLUSIONS: This study indicated that ZnFe2O4 NPs have the potential to be used as a future antimicrobial and wound healing drug.

Antibiotic susceptibility and drug prescription pattern in uropathogenic Escherichia coli in district Muzaffarabad, Azad Jammu and Kashmir, Pakistan.

The present research study was done to determine the correlation between antibiotic susceptibility and drug prescription patterns in empirical treatment of uropathogenic Escherichia coli (E. coli) in two hospitals of district Muzaffarabad, Azad Kashmir, Pakistan. One hundred uropathogenic E. coli clinical isolates were collected from UTI patients who attended the Combined Military Hospital (CMH) and Abbas Institute of Medical Sciences (AIMS), district Muzaffarabad, AJK. All isolates were subjected to antibiotic susceptibility against seven commonly prescribed antibiotics by Kirby-Bauer disk diffusion method. However, all the E. coli isolates were susceptible to Imipenem. Eight percent and 10% of isolates from CMH and AIMS were found to be resistant against Nitrofurantoin drug respectively. Similarly, 94% and 74% isolates from CMH and 60% and 64% isolates from AIMS were found to be resistant against Co-trimoxazole and Coamoxiclave, respectively. Pipemedic acid resistance was also detected in 76% and 60% isolates from AIMS and CMH, respectively. Ciprofloxacin resistance was also observed in 54% and 36% isolates from AIMS and CMH, respectively. The finding of the study revealed that both hospitals have different drug susceptibility pattern against uropathogenic E. coli, which may be associated with patterns of drug prescription in empirical treatment of urinary tract infections. There is a vital need for appropriate development of hospital-specific antibiograms to determine appropriate empiric therapy of urinary tract infections.