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Introduction: Despite extensive research, comprehensive characterization of leukaemic stem cells (LSC) and information on their immunophenotypic differences from normal haematopoietic stem cells (HSC) is lacking. Herein, we attempted to unravel the immunophenotypic (IPT) characteristics and heterogeneity of LSC using multiparametric flow cytometry (MFC) and single-cell sequencing., Materials and Methods: Bone marrow aspirate samples from patients with acute myeloid leukaemia (AML) were evaluated using MFC at diagnostic and post induction time points using a single tube-10-colour-panel containing LSC-associated antibodies CD123, CD45RA, CD44, CD33 and COMPOSITE (CLL-1, TIM-3, CD25, CD11b, CD22, CD7, CD56) with backbone markers that is, CD45, CD34, CD38, CD117, sCD3. Single-cell sequencing of the whole transcriptome was also done in a bone marrow sample., Results: LSCs and HSCs were identified in 225/255 (88.2%) and 183/255 (71.6%) samples, respectively. Significantly higher expression was noted for COMPOSITE, CD45RA, CD123, CD33, and CD44 in LSCs than HSCs (p < 0.0001). On comparing the LSC specific antigen expressions between CD34+ (n = 184) and CD34- LSCs (n = 41), no difference was observed between the groups. More than one sub-population of LSC was demonstrated in 4.4% of cases, which further revealed high concordance between MFC and single cell transcriptomic analysis in one of the cases displaying three LSC subpopulations by both methods., Conclusion: A single tube-10-colour MFC panel is proposed as an easy and reproducible tool to identify and discriminate LSCs from HSCs. LSCs display both inter- and intra-sample heterogeneity in terms of antigen expressions, which opens the facets for single cell molecular analysis to elucidate the role of subpopulations of LSCs in AML progression., (© 2024 John Wiley & Sons Ltd.)

The aminotroponiminate (ATI) ligand stabilized germylene cation [(i-Bu) 2 ATIGe][B(C 6 F 5 ) 4 ] (2) is found to be an efficient low-valent main-group catalyst for the cyanosilylation of aldehydes and ketones (ATI=aminotroponiminate). It was synthesized by reacting [(i-Bu) 2 ATIGeCl] (1) with Na[B(C 6 F 5 ) 4 ]. The catalytic cyanosilylation of diverse aliphatic and aromatic carbonyl compounds (aldehydes and ketones) using 0.075-0.75 mol% of compound 2 was completed within 5-45 min. The catalytic efficiency seen with aliphatic aldehydes was around 15,800 h -1 , making compound 2 a capable low-valent main-group catalyst for the aldehyde and ketone cyanosilylation reactions. Further, DFT calculations reveal a pronounced charge localization at the germanium atom of compound 2, leading to its superior catalytic performance., (© 2024 Wiley-VCH GmbH.)

Detecting the Kirsten Rat Sarcoma Virus ( KRAS ) gene mutation is significant for colorectal cancer (CRC) patients. The KRAS gene encodes a protein involved in the epidermal growth factor receptor (EGFR) signaling pathway, and mutations in this gene can negatively impact the use of monoclonal antibodies in anti-EGFR therapy and affect treatment decisions. Currently, commonly used methods like next-generation sequencing (NGS) identify KRAS mutations but are expensive, time-consuming, and may not be suitable for every cancer patient sample. To address these challenges, we have developed KRASFormer , a novel framework that predicts KRAS gene mutations from Haematoxylin and Eosin (H & E) stained WSIs that are widely available for most CRC patients. KRASFormer consists of two stages: the first stage filters out non-tumor regions and selects only tumour cells using a quality screening mechanism, and the second stage predicts the KRAS gene either wildtype' or mutant' using a Vision Transformer-based XCiT method. The XCiT employs cross-covariance attention to capture clinically meaningful long-range representations of textural patterns in tumour tissue and KRAS mutant cells. We evaluated the performance of the first stage using an independent CRC-5000 dataset, and the second stage included both The Cancer Genome Atlas colon and rectal cancer (TCGA-CRC-DX) and in-house cohorts. The results of our experiments showed that the XCiT outperformed existing state-of-the-art methods, achieving AUCs for ROC curves of 0.691 and 0.653 on TCGA-CRC-DX and in-house datasets, respectively. Our findings emphasize three key consequences: the potential of using H & E-stained tissue slide images for predicting KRAS gene mutations as a cost-effective and time-efficient means for guiding treatment choice with CRC patients; the increase in performance metrics of a Transformer-based model; and the value of the collaboration between pathologists and data scientists in deriving a morphologically meaningful model., (Creative Commons Attribution license.)

To analyze and compare the intraoperative and post-operative outcomes of "on-clamp" laparoscopic partial nephrectomy (LPN) with "preoperative super-selective angioembolization" before LPN. This randomized clinical study was conducted at Gauhati Medical College Hospital, Guwahati, India, between November 2021 and November 2023. Adult patients of either gender diagnosed with T1 renal tumors were included in the study. All patients underwent diethylenetriamine pentaacetate scan preoperatively and at 1-month follow-up. The patients were randomized using a parallel group design with an allocation ratio of 1:1 to receive either preoperative angioembolization followed by LPN or conventional "on-clamp" LPN. Demographic and baseline parameters were recorded along with pre- and post-operative data. There was no significant difference between the two groups in terms of age (P = 0.11), gender distribution (P = 0.32), body mass index (P = 0.43), preoperative hemoglobin (P = 0.34), and preoperative estimated glomerular filtration rate (eGFR; P = 0.64). One patient in the embolization group required radical nephrectomy because of accidental backflow of glue into the renal artery during embolization whereas four patients required clamping due to inadequate embolization. Preoperative super-selective embolization yielded significantly less blood loss, compared to "on-clamp" LPN (145 [50.76 mL] vs. 261 [66.12 mL], P < 0.01). There was no significant difference between post-operative eGFR (at 1 month) between the two groups (P = 0.71). Preoperative embolization offers improved outcomes in the dissection plane, total operative time, and blood loss, compared to conventional "on-clamp" LPN but has no significant effect on change in eGFR., (Copyright: Singh VK., et al.)

Endoscopic ultrasound (EUS) is increasingly used as a therapeutic approach for gastrointestinal diseases, especially with the advent of lumen-apposing metal stents (LAMS). This has led to a rise in of EUS-guided gastrointestinal anastomosis procedures. Due to the reliability of intestinal conduits with LAMS, indications for EUS-guided gastrointestinal anastomosis are becoming more common and trend to potentially be standard care for gastric outlet obstruction, afferent loop syndrome, and EUS-directed transgastric interventions such as EUS-directed endoscopic retrograde cholangiopancreatography. Retrospective and prospective data indicate that the procedure is becoming widely adopted with promising outcomes. This article aims to review the existing literature on EUS-guided gastrointestinal anastomosis and predict its future developments., (© 2024 Japan Gastroenterological Endoscopy Society.)

The high concentration of antibiotics in aquatic environments is a serious environmental issue. In response, researchers have explored photocatalytic degradation as a potential solution. Through chemical vapor deposition (CVD), we synthesized copper selenide (β-Cu 2-x Se) and found it an effective catalyst for degrading tetracycline hydrochloride (TC-HCl). The catalyst demonstrated an impressive degradation efficiency of approximately 98% and a reaction rate constant of 3.14 × 10 -2 min -1 . Its layered structure, which exposes reactive sites, contributes to excellent stability, interfacial charge transfer efficiency, and visible light absorption capacity. Our investigations confirmed that the principal active species produced by the catalyst comprises O 2- radicals, which we verified through trapping experiments and electron paramagnetic resonance (EPR). We also verified the TC-HCl degradation mechanism using high-performance liquid chromatography-mass spectrometry (LC-MS). Our results provide valuable insights into developing the β-Cu 2-x Se catalyst using CVD and its potential applications in environmental remediation.

The immune response associated with oncogenesis and potential oncological ther- apeutic interventions has dominated the field of cancer research over the last decade. T-cell lymphocytes in the tumor microenvironment are a crucial aspect of cancer's adaptive immunity, and the quantification of T-cells in specific can- cer types has been suggested as a potential diagnostic aid. However, this is cur- rently not part of routine diagnostics. To address this challenge, we present a new method called True-T , which employs artificial intelligence-based techniques to quantify T-cells in colorectal cancer (CRC) using immunohistochemistry (IHC) images. True-T analyses the chromogenic tissue hybridization signal of three widely recognized T-cell markers (CD3, CD4, and CD8). Our method employs a pipeline consisting of three stages: T-cell segmentation, density estimation from the segmented mask, and prediction of individual five-year survival rates. In the first stage, we utilize the U-Net method, where a pre-trained ResNet-34 is em- ployed as an encoder to extract clinically relevant T-cell features. The segmenta- tion model is trained and evaluated individually, demonstrating its generalization in detecting the CD3, CD4, and CD8 biomarkers in IHC images. In the second stage, the density of T-cells is estimated using the predicted mask, which serves as a crucial indicator for patient survival statistics in the third stage. This ap- proach was developed and tested in 1041 patients from four reference diagnostic institutions, ensuring broad applicability. The clinical effectiveness of True-T is demonstrated in stages II-IV CRC by offering valuable prognostic information that surpasses previous quantitative gold standards, opening possibilities for po- tential clinical applications. Finally, to evaluate the robustness and broader ap- plicability of our approach without additional training, we assessed the universal accuracy of the CD3 component of the True-T algorithm across 13 distinct solid tumors., Competing Interests: Manuel Salto-Tellez is a scientific advisor to Mindpeak and Sonrai Analytics, and has received honoraria recently from BMS, MSD, Roche, Sanofi and Incyte. He has received grant support from Phillips, Roche, MSD and Akoya. None of these disclosures are related to this work.., (© 2023 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.)

Monitoring the healthy development of a fetus requires accurate and timely identification of different maternal-fetal structures as they grow. To facilitate this objective in an automated fashion, we propose a deep-learning-based image classification architecture called the COMFormer to classify maternal-fetal and brain anatomical structures present in 2-D fetal ultrasound (US) images. The proposed architecture classifies the two subcategories separately: maternal-fetal (abdomen, brain, femur, thorax, mother's cervix (MC), and others) and brain anatomical structures [trans-thalamic (TT), trans-cerebellum (TC), trans-ventricular (TV), and non-brain (NB)]. Our proposed architecture relies on a transformer-based approach that leverages spatial and global features using a newly designed residual cross-variance attention block. This block introduces an advanced cross-covariance attention (XCA) mechanism to capture a long-range representation from the input using spatial (e.g., shape, texture, intensity) and global features. To build COMFormer, we used a large publicly available dataset (BCNatal) consisting of 12 400 images from 1792 subjects. Experimental results prove that COMFormer outperforms the recent CNN and transformer-based models by achieving 95.64% and 96.33% classification accuracy on maternal-fetal and brain anatomy, respectively.

The synthesis of secondary metabolites is a constantly functioning metabolic pathway in all living systems. Secondary metabolites can be broken down into numerous classes, including alkaloids, coumarins, flavonoids, lignans, saponins, terpenes, quinones, xanthones, and others. However, animals lack the routes of synthesis of these compounds, while plants, fungi, and bacteria all synthesize them. The primary function of bioactive metabolites (BM) synthesized from endophytic fungi (EF) is to make the host plants resistant to pathogens. EF is a group of fungal communities that colonize host tissues' intracellular or intercellular spaces. EF serves as a storehouse of the above-mentioned bioactive metabolites, providing beneficial effects to their hosts. BM of EF could be promising candidates for anti-cancer, anti-malarial, anti-tuberculosis, antiviral, anti-inflammatory, etc. because EF is regarded as an unexploited and untapped source of novel BM for effective drug candidates. Due to the emergence of drug resistance, there is an urgent need to search for new bioactive compounds that combat resistance. This article summarizes the production of BM from EF, high throughput methods for analysis, and their pharmaceutical application. The emphasis is on the diversity of metabolic products from EF, yield, method of purification/characterization, and various functions/activities of EF. Discussed information led to the development of new drugs and food additives that were more effective in the treatment of disease. This review shed light on the pharmacological potential of the fungal bioactive metabolites and emphasizes to exploit them in the future for therapeutic purposes., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature B.V. 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Linkages of urban and industrial cooling with sustainable development goals and climate change perspectives are well acknowledged, mainly for developing economies in tropical climates. Angul-Talcher region is one of the oldest industrial clusters of India, and the region experiences higher atmospheric heat island intensities with magnitudes of 7 to 9 °C attributed to the Industrial Heat Island (IHI) effect. In the present study, various measures for mitigating heat island effect in the region and assessed their impact using an Improved Weather Research and Forecasting model coupled with the Single-Layer Urban Canopy Model. The improved framework includes the release of industrial emissions at stack height and sector-wise diurnal profiles of anthropogenic heat (AH) released from vehicles, residential, and industry/power. The mitigation measures comprised strategies like alteration in building materials and conversion of landuse-landcover (LULC) of selected grid cells in the model domain to more vegetation or water bodies. It was noted that the cool roofs and walls together reduced IHIs by 0.5 °C, while green roofs and cool pavements achieved a reduction of 0.3 °C and 0.1 °C, respectively. The introduction of water bodies showed maximum reduction in IHIs by 3 to 5 °C during daytime and 1 to 2 °C over mining and industrial stations. During night-time, conversion to mixed forests was more effective (ΔT ≈ 1 °C) than conversion to water bodies. A combination of cool roofs with the introduction of water bodies in the mining areas and mixed forest patches in industry stations was found to be the most effective mitigation strategy for mitigating the industrial heat island effect over the Angul-Talcher region. These mitigation scenarios can/should serve as a theoretical reference for implementing actual mitigation measures, which would require consideration of economic, social, and policy aspects apart from scientific ones for practical application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Increasing land degradation by high level of metal wastes is of prime concern for the global research communities. In this respect, halophytes having specific features like salt glands, exclusion of excess ions, heavy metals (HMs) compartmentalization, large pool of antioxidants, and associations with metal-tolerant microbes are of great promise in the sustainable clean-up of contaminated sites. However, sustainable clean-up of HMs by a particular halophyte plant species is governed considerably by physico-chemical characteristics of soil and associated microbial communities. The present review has shed light on the superiority of halophytes over non-halophytes, mechanisms of metal-remediation, recent developments and future perspectives pertaining to the utilization of halophytes in management of HM-contaminated sites with the aid of bibliometric analysis. The results revealed that the research field is receiving considerable attention in the last 5-10 years by publishing ∼50-90% documents with an annual growth rate of 15.41% and citations per document of 29.72. Asian (viz., China, India, and Pakistan) and European (viz., Spain, Portugal, Belgium, Argentina) countries have been emerged as the major regions conducting and publishing extensive research on this topic. The investigations conducted both under in vitro and field conditions have reflected the inherent potential of halophyte as sustainable research tool for successfully restoring the HM-contaminated sites. The findings revealed that the microbial association with halophytes under different challenging conditions is a win-win approach for metal remediation. Therefore, exploration of new halophyte species and associated microorganisms (endophytic and rhizospheric) from different geographical locations, and identification of genes conferring tolerance and phytoremediation of metal contaminants would further advance the intervention of halophytes for sustainable ecological restoration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

To gain insights into the idiosyncrasies of CD34 + enriched leukemic stem cells, we investigated the nature and extent of transcriptional heterogeneity by single-cell sequencing in pediatric AML. Whole transcriptome analysis of 28,029 AML single cells was performed using the nanowell cartridge-based barcoding technology. Integrated transcriptional analysis identified unique leukemic stem cell clusters of each patient and intra-patient heterogeneity was revealed by multiple LSC-enriched clusters differing in their cell cycle processes and BCL2 expression. All LSC-enriched clusters exhibited gene expression profile of dormancy and self-renewal. Upregulation of genes involved in non-coding RNA processing and ribonucleoprotein assembly were observed in LSC-enriched clusters relative to HSC. The genes involved in regulation of apoptotic processes, response to cytokine stimulus, and negative regulation of transcription were upregulated in LSC-enriched clusters as compared to the blasts. Validation of top altered genes in LSC-enriched clusters confirmed upregulation of TCF7L2, JUP, ARHGAP25, LPAR6, and PRDX1 genes, and serine/threonine kinases (STK24, STK26). Upregulation of LPAR6 showed trend towards MRD positive status (Odds ratio = 0.126; 95% CI = 0.0144-1.10; p = 0.067) and increased expression of STK26 significantly correlated with higher RFS (HR = 0.231; 95% CI = 0.0506-1.052; p = 0.04). Our findings addressed the inter- and intra-patient diversity within AML LSC and potential signaling and chemoresistance-associated targets that warrant investigation in larger cohort that may guide precision medicine in the near future., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Tyrosine kinase inhibitors (TKIs) are highly effective in treating chronic myelogenous leukemia (CML). However, primary and acquired drug resistance to TKIs have been reported. In this study, we used RNA sequencing followed by RQ-PCR to show that the proto-oncogene EVI1 targets the drug-metabolizing gene PTGS1 in CML. The PTGS1 promoter element had an EVI1 binding site, and CHIP assay confirmed its presence. Data from a publicly available CML microarray dataset and an independent set of CML samples showed a significant positive correlation between EVI1 and PTGS1 expression in CML. Downregulation of EVI1 in K562 cells and subsequent treatment with TKIs resulted in a lower IC 50 in the control cells. Furthermore, combined inhibition of BCR-ABL with imatinib and PTGS1 with FR122047 (PTGS1 inhibitor) synergistically reduced the viability of imatinib-resistant K562 cells. We conclude that elevated EVI1 expression contributes to TKIs resistance and that combined inhibition of PTGS1 and BCR-ABL may represent a novel therapeutic approach., (© 2022. Japanese Society of Hematology.)

Medical image analysis methods for mammograms, ultrasound, and magnetic resonance imaging (MRI) cannot provide the underline features on the cellular level to understand the cancer microenvironment which makes them unsuitable for breast cancer subtype classification study. In this paper, we propose a convolutional neural network (CNN)-based breast cancer classification method for hematoxylin and eosin (H&E) whole slide images (WSIs). The proposed method incorporates fused mobile inverted bottleneck convolutions (FMB-Conv) and mobile inverted bottleneck convolutions (MBConv) with a dual squeeze and excitation (DSE) network to accurately classify breast cancer tissue into binary (benign and malignant) and eight subtypes using histopathology images. For that, a pre-trained EfficientNetV2 network is used as a backbone with a modified DSE block that combines the spatial and channel-wise squeeze and excitation layers to highlight important low-level and high-level abstract features. Our method outperformed ResNet101, InceptionResNetV2, and EfficientNetV2 networks on the publicly available BreakHis dataset for the binary and multi-class breast cancer classification in terms of precision, recall, and F1-score on multiple magnification levels.

Antral follicle Count (AFC) is a non-invasive biomarker used to assess ovarian reserves through transvaginal ultrasound (TVUS) imaging. Antral follicles' diameter is usually in the range of 2-10 mm. The primary aim of ovarian reserve monitoring is to measure the size of ovarian follicles and the number of antral follicles. Manual follicle measurement is inhibited by operator time, expertise and the subjectivity of delineating the two axes of the follicles. This necessitates an automated framework capable of quantifying follicle size and count in a clinical setting. This paper proposes a novel Harmonic Attention-based U-Net network, HaTU-Net, to precisely segment the ovary and follicles in ultrasound images. We replace the standard convolution operation with a harmonic block that convolves the features with a window-based discrete cosine transform (DCT). Additionally, we proposed a harmonic attention mechanism that helps to promote the extraction of rich features. The suggested technique allows for capturing the most relevant features, such as boundaries, shape, and textural patterns, in the presence of various noise sources (i.e., shadows, poor contrast between tissues, and speckle noise). We evaluated the proposed model on our in-house private dataset of 197 patients undergoing TransVaginal UltraSound (TVUS) exam. The experimental results on an independent test set confirm that HaTU-Net achieved a Dice coefficient score of 90% for ovaries and 81% for antral follicles, an improvement of 2% and 10%, respectively, when compared to a standard U-Net. Further, we accurately measure the follicle size, yielding the recall, and precision rates of 91.01% and 76.49%, respectively.

Existing nuclei segmentation methods face challenges with hematoxylin and eosin (H&E) whole slide imaging (WSI) due to the variations in staining methods and nuclei shapes and sizes. Most existing approaches require a stain normalization step that may cause losing source information and fail to handle the inter-scanner feature instability problem. To mitigate these issues, this article proposes an efficient staining-invariant nuclei segmentation method based on self-supervised contrastive learning and an effective weighted hybrid dilated convolution (WHDC) block. In particular, we propose a staining-invariant encoder (SIE) that includes convolution and transformers blocks. We also propose the WHDC block allowing the network to learn multi-scale nuclei-relevant features to handle the variation in the sizes and shapes of nuclei. The SIE network is trained on five unlabeled WSIs datasets using self-supervised contrastive learning and then used as a backbone for the downstream nuclei segmentation network. Our method outperforms existing approaches in challenging multiple WSI datasets without stain color normalization.

Two routes can offer the first stannylene cyanide [(L)SnCN] (5); the substitution reaction of either stannylene amide [( i -Bu) 2 ATISnN(SiMe 3 ) 2 ] (3) or stannylene pyrrolide [( i -Bu) 2 ATISn(NC 4 H 4 )] (4) using an excess of trimethylsilyl cyanide (L = aminotroponiminate (ATI)). Using 0.1-2.0 mol% of compound 5, catalytic cyanosilylation of a variety of aliphatic and aromatic aldehydes was achieved at rt-50 °C in 0.33-2.0 h. The mechanism of this catalytic reaction is authenticated by the isolation of a structurally characterized intermediate.

The current study is the first worldwide to assess the genetic diversity of Kadaknath poultry using amplified fragment length polymorphism (AFLP) markers. Out of total 96 accessions, four were outliers and 92 were Kadaknath accessions of which 30 were males, 62 were females. Of these, 74 were jet black, 7 penciled and 11 were golden feather color type of Kadaknath. High level of polymorphism (23.94%) was observed in 387 loci amplified using six AFLP primer combinations. The Jaccard's similarity coefficient ranged from 0.211 to 0.754 with an average dissimilarity of 0.517. Based on the neighbor-joining method of clustering, all accessions were clustered into seven major clusters which were not consistent with their respective geographical locations. The mean values of effective multiplex ratio, polymorphic information content, resolving power and marker index were 15.16, 0.38, 9.87 and 5.85 respectively. Further, the high log-likelihood score was produced when the number of populations ( K ) was set at 7 while carrying out the population STRUCTURE analysis, which was also congruent with clustering analysis based on genetic diversity. The extent of genetic diversity detected in this study could be used for germplasm selection and developing conservation strategies of pure breed of Kadaknath.

Deep learning has been widely utilized for medical image segmentation. The most commonly used U-Net and its variants often share two common characteristics but lack solid evidence for the effectiveness. First, each block (i.e., consecutive convolutions of feature maps of the same resolution) outputs feature maps from the last convolution, limiting the variety of the receptive fields. Second, the network has a symmetric structure where the encoder and the decoder paths have similar numbers of channels. We explored two novel revisions: a stacked dilated operation that outputs feature maps from multi-scale receptive fields to replace the consecutive convolutions; an asymmetric architecture with fewer channels in the decoder path. Two novel models were developed: U-Net using the stacked dilated operation (SDU-Net) and asymmetric SDU-Net (ASDU-Net). We used both publicly available and private datasets to assess the efficacy of the proposed models. Extensive experiments confirmed SDU-Net outperformed or achieved performance similar to the state-of-the-art while using fewer parameters (40% of U-Net). ASDU-Net further reduced the model parameters to 20% of U-Net with performance comparable to SDU-Net. In conclusion, the stacked dilated operation and the asymmetric structure are promising for improving the performance of U-Net and its variants., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In this article, we propose ICOSeg, a lightweight deep learning model that accurately segments the immune-checkpoint biomarker, Inducible T-cell COStimulator (ICOS) protein in colon cancer from immunohistochemistry (IHC) slide patches. The proposed model relies on the MobileViT network that includes two main components: convolutional neural network (CNN) layers for extracting spatial features; and a transformer block for capturing a global feature representation from IHC patch images. The ICOSeg uses an encoder and decoder sub-network. The encoder extracts the positive cell's salient features (i.e., shape, texture, intensity, and margin), and the decoder reconstructs important features into segmentation maps. To improve the model generalization capabilities, we adopted a channel attention mechanism that added to the bottleneck of the encoder layer. This approach highlighted the most relevant cell structures by discriminating between the targeted cell and background tissues. We performed extensive experiments on our in-house dataset. The experimental results confirm that the proposed model achieves more significant results against state-of-the-art methods, together with an 8× reduction in parameters.

Autophagy is a lysosomal degradation pathway that is constitutively active in almost every cell of our body at basal level. This self-eating process primarily serves to remove superfluous constituents of the cells and recycle the degraded products. Autophagy plays an essential role in cell homeostasis and can be enhanced in response to stressful conditions. Impairment in the regulation of the autophagic pathway is implicated in pathological conditions such as neurodegeneration, cardiac disorders, and cancer. However, the role of autophagy in cancer initiation and development is controversial and context-dependent. Evidence from various studies has shown that autophagy serves dual purpose and may assist in cancer progression or suppression. In the early stages of cancer initiation, autophagy acts as a quality control mechanism and prevents cancer development. When cancer is established and progresses to a later stage, autophagy helps in the survival of these cells through adaptation to stresses, including exposure to anti-cancer drugs. In this review, we highlight various studies on autophagic pathways and describe the role of autophagy in cancer, specifically acute myeloid leukemia (AML). We also discuss the prognostic significance of autophagy genes involved in AML leukemogenesis and implications in conferring resistance to chemotherapy., (© 2022. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

The visceral leishmaniasis (VL) elimination program in Nepal has largely completed the attack phase and is moving toward consolidation and maintenance phases. New VL foci are, however, appearing in Nepal, and therefore new innovative community-centered strategies need to be developed and tested. We conducted early case detection by an index case-based approach and assessed the feasibility, efficacy, and cost of an intervention for sandfly control through indoor residual spraying (IRS) or insecticidal wall painting (IWP) in new and low-endemic districts Palpa and Surkhet. IRS was performed in 236 households and IWP in 178 households. We screened 1,239 and 596 persons in Palpa and Surkhet, respectively, resulting in the detection of one VL case in Palpa. Both IWP and IRS were well accepted, and the percentage reductions in sandfly density after 1, 9, and 12 months of intervention were 90%, 81%, and 75%, respectively, for IWP and 81%, 59%, and 63% respectively for IRS. The cost per household protected per year was USD 10.3 for IRS and 32.8 for IWP, although over a 2-year period, IWP was more cost-effective than IRS. Active case detection combined with sandfly control through IWP or IRS can support to VL elimination in the consolidation and maintenance phase.

Evolving insect resistance to delta-endotoxins can be delayed by using a few strategies like high dosage, refugia, and gene stacking which require the expression of delta-endotoxins at sufficiently high levels to kill the resistant insects. In this study, we comparatively analyzed the efficacy of targeting truncated cry1Ac protein to the cytoplasm, endoplasmic reticulum (ER), and chloroplast to obtain high protein expression. mRNA and protein profiling of cry1Ac showed that both ER and chloroplast are efficient targets for expressing high levels of truncated cry1Ac. A maximum of 0.8, 1.6, and 2.0% cry1Ac of total soluble protein were obtained when the truncated cry1Ac was expressed in the cytoplasm, routed through ER, and targeted to the chloroplast. We further showed that not only the protein content but also the biological activity of truncated cry1Ac increases by sub-cellular targeting and the biological activity is slightly greater in the ER routed transgenic lines by conducting different bioassays on Helicoverpa armigera. Using native Western analysis, we demonstrated that the truncated cry1Ac protein could exist as oligomers in plant cells and this oligomerization capability is low in the cytoplasm. In conclusion, routing of delta endotoxins through ER is the first choice to obtain high protein expression and bioactivity., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Breast cancer needs to be detected early to reduce mortality rate. Ultrasound imaging (US) could significantly enhance diagnosing cases with dense breasts. Most of the existing computer-aided diagnosis (CAD) systems employ a single ultrasound image for the breast tumor to extract features to classify it as benign or malignant. However, the accuracy of such CAD system is limited due to the large tumor size and shape variation, irregular and ambiguous tumor boundaries, and low signal-to-noise ratio in ultrasound images due to their noisy nature and the significant similarity between normal and abnormal tissues. To handle these issues, we propose a deep-learning-based radiomics method based on breast US sequences in this paper. The proposed approach involves three main components: radiomic features extraction based on a deep learning network, so-called ConvNeXt, a malignancy score pooling mechanism, and visual interpretations. Specifically, we employ the ConvNeXt network, a deep convolutional neural network (CNN) trained using the vision transformer style. We also propose an efficient pooling mechanism to fuse the malignancy scores of each breast US sequence frame based on image-quality statistics. The ablation study and experimental results demonstrate that our method achieves competitive results compared to other CNN-based methods.

Transgenic crops expressing Cry δ-endotoxins of Bacillus thuringiensis for insect resistance have been commercialized worldwide with increased crop productivity and spectacular socioeconomic gains. To attain the enhanced level of protein expression, the cry genes have to be extensively modified for RNA stability and translation efficiency in the plant systems. However, such modifications in nucleotide sequences make it difficult to express the cry genes in Escherichia coli because of the presence of E. coli rare codons. Induction of gene expression through the T7 promoter/lac operator system results in high levels of transcription but limits the availability of activated tRNA corresponding to rare codons that leads to translation stalling at ribosomes. In the present study, an Isopropyl ß-D-1-thiogalactopyranoside (IPTG)/rifampicin combination-based approach was adopted to induce transcription of cry genes through T7 promoter/lac operator while simultaneously inhibiting the transcription of host genes through rifampicin. The results show that the IPTG/rifampicin combination leads to high-level expression of four plant codon-optimized cry genes (cry2Aa, cry1F, cry1Ac, and cry1AcF). Northern blot analysis of the cry gene expressing E. coli samples showed that the RNA expression level in the IPTG-induced samples was higher as compared to that in the IPTG/rifampicin-induced samples. Diet overlay insect bioassay of IPTG/rifampicin-induced Cry toxins with Helicoverpa armigera larvae showed bioactivity (measured as LC 50 ) similar to the previous studies. The experiment has proved that recombinant synthetic gene (plant codon-optimized gene) with the combination of Rifampicin which inhibits DNA-dependent bacterial RNA polymerase and reduces the excessive baggage of translational machinery of the bacterial cell triggers the production of synthetic protein. Purification of protein using high pH buffer increases the solubility of the protein. Further, LC 50 analysis shows no reduction of protein activity leads to protein stability. Further, purified cry toxin protein can be used for crop protection against pests and a purified form of the synthetic protein can be used for antibody production and perform the immunoassay for the identification of the transgenic plant. The crystallographic structure of synthetic protein could be used for interaction study with another insect to see insecticidal activity., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ru II -Complexes of chelating heteroditopic N-heterocyclic carbene ligands featuring imidazol-2-ylidene (ImNHC) and 1,2,3-triazol-5-ylidene (tzNHC) donors connected via a CH 2 spacer, 1a-c, were found to be very effective catalysts for the cross-coupling of secondary and primary alcohols with the elimination of H 2 O. Diverse β-alkylated secondary alcohols were thus obtained by following this method in excellent yields of up to 95% by employing a very low catalyst (1a) loading of 0.01-0.001 mol% along with the inexpensive base KOH. Mechanistically, the present protocol follows the borrowing hydrogen strategy which was established by various control experiments including deuterium labelling experiments and importantly, 1 H NMR and ESI-MS analyses validated the participation of a Ru-H species in the catalytic cycle. Remarkably, the present system displayed the highest Ru-based TON of 396 000 for the β-benzylation of 1-phenylethanol with a catalyst loading of 1 ppm (0.0001 mol%). Additionally, diverse 2-alkylaminoquinoline derivatives were synthesized in a one-pot manner from 2-aminobenzyl alcohol, 2-arylacetonitrile, and various primary alcohols.

Increased urbanization and anthropogenic activities in tropical cities lead to the temperature gradient between the urban and rural environments, causing the urban heat island (UHI) phenomenon. This study is a pioneering attempt that examines the changes in the temporal evolution of the surface energy budget induced by urbanization known as the Anthropogenic Influence (AI) in modifying the urban climate of a tropical city using Weather Research and Forecasting (WRF) numerical modeling system. The AI from buildings, traffic and power plants is determined in five different scenarios and the model is validated with high temporal resolution in-situ data. These increased AIs provide improved WRF capability with root mean square error (RMSE) less than 2 °C and mean bias error (MBE) less than 0.5 °C between different performance indicators. Building envelopes (without indoor activity/equipment) are found to be a major contributor in exacerbating the island wide urban heat ∆T a AI, max to 3.7 °C compared to baseline all green scenario. This is followed by the air-conditioner (AC) systems that contribute up to 1.4 °C. The maximum local contribution of traffic and power plants to urban heat is 0.9 °C and 0.4 °C, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In this article, we present a new benchmark for the segmentation of the retinal external limiting membrane (ELM) using an image dataset of spectral domain optical coherence tomography (OCT) scans in a patient population with idiopathic full-thickness macular holes. Specifically, the dataset used contains OCT images from one eye of 107 patients with an idiopathic full-thickness macular hole. In total, the dataset contains 5243 individual 2-dimensional (2-D) OCT image slices, with each patient contributing 49 individual spectral-domain OCT tagged image slices. We display precise image-wise binary annotations to segment the ELM line. The OCT images present high variations in image contrast, motion, brightness, and speckle noise which can affect the robustness of applied algorithms, so we performed an extensive OCT imaging and annotation data quality analysis. Imaging data quality control included noise, blurriness and contrast scores, motion estimation, darkness and average pixel scores, and anomaly detection. Annotation quality was measured using gradient mapping of ELM line annotation confidence, and idiopathic full-thickness macular hole detection. Finally, we compared qualitative and quantitative results with seven state-of-the-art machine learning-based segmentation methods to identify the ELM line with an automated system., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Ecotropic viral integration site-1 (EVI1) is an oncogenic zinc finger transcription factor whose expression is frequently upregulated in a variety of cancers, including both myeloid malignancies and solid tumors. Previously, our group has shown that EVI1 knockdown minimizes the metastatic potential of colon cancer cells compared to that of control cells. In this study, to identify the potential targets that regulate cancer metastasis, control and EVI1 knockdown colon cancer cells were subjected to microarray. Differential gene expression analysis revealed significant downregulation of tissue inhibitor of matrix metalloproteinase-2 (TIMP2) in EVI1 expressing cells. EVI1 knockdown increased TIMP2 protein expression levels and reduced wound healing and migration capacity in metastatic cells. Mechanistically, the TIMP2 promoter harbors potential binding sites for EVI1; EVI1 binds to TIMP2 promoter and represses its expression, as observed using ChIP and luciferase assay, respectively. TIMP2 is an important metastasis suppressor gene; however, its function is suppressed in many cancers through hypermethylation. Thus, demethylation could prove to be a potential alternative to reactivate TIMP2 functional activity. Immunoprecipitation analysis showed that DNA-methyltransferase 1 (DNMT1), which plays a vital role in maintaining the genome methylation pattern during DNA replication and repair, interacts with EVI1 to promote TIMP2 silencing. Treating cancer cells in vitro with a known demethylation agent, 5-aza-2'-deoxycytidine (Aza-D), restored the optimal TIMP2 expression without altering EVI1 binding efficiency and reduced relative wound healing potential of cancer cells. Animal studies showed that Aza-D treated cells injected through the intravenous route exhibited reduced liver and skin metastasis when compared to non-treated cells. Furthermore, Aza-D treatment in mice delayed the metastasis progression compared to the vehicle treated group. Thus, the present study provides an insight into the therapeutic applications of demethylating agents to reduce cancer metastasis in models with EVI1 overexpressing tumors., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Iodine deficiency disorders are common endocrinopathies in Nepal. Children are at risk for iodine deficiency disorders. Irreversible mental retardation and brain damage in children are the devastating disorders lead by iodine deficiency. Therefore, the main objective of the study was to find out the prevalence of insufficient iodine level among the children of a secondary school. Methods: This descriptive cross-sectional study was conducted in urine from April 2019 to July 2019 after obtaining ethical approval from Nepal Health Research Council (Registration number: 802/2018). Forty-six urine samples were collected from school children for iodine estimation. Convenience sampling was done. Data were entered into Statistical Package for the Social Science version 21 and descriptive analyses were done. Point estimate at 95% confidence interval was calculated along with frequency and proportion for binary data. Results: Among the 46 students, majority 36 (78.30%) (95% Confidence Interval= 66.30-90.21) of the school children had insufficient urine iodine level. Among 36 salt samples collected from school children with low urine iodine level, 8 (22.2%) salt samples had iodine less than 15ppm. Conclusions: Iodine estimation revealed a very high percentage of urine samples containing insufficient levels of iodine is similar as compared to studies done in similar settings. Hence, the school children were at risk of iodine deficiency disorders. Iodine deficiency disorders prevention programs should be priority intervention based on available evidence.

The noncoding RNAs (ncRNA) comprise a substantial segment of the human transcriptome and have emerged as key elements of cellular homeostasis and disease pathogenesis. Dysregulation of these ncRNAs by alterations in the primary RNA motifs and/or aberrant expression levels is relevant in various diseases, especially cancer. The recent research advances indicate that ncRNAs regulate vital oncogenic processes, including hematopoietic cell differentiation, proliferation, apoptosis, migration, and angiogenesis. The ever-expanding role of ncRNAs in cancer progression and metastasis has sparked interest as potential diagnostic and prognostic biomarkers in acute myeloid leukemia. Moreover, advances in antisense oligonucleotide technologies and pharmacologic discoveries of small molecule inhibitors in targeting RNA structures and RNA-protein complexes have opened newer avenues that may help develop the next generation anti-cancer therapeutics. In this review, we have discussed the role of ncRNA in acute myeloid leukemia and their utility as potential biomarkers and therapeutic targets., Competing Interests: None., (AJBR Copyright © 2021.)

Herein, optimized headspace solid phase microextraction with gas chromatography-tandem mass spectrometry (HS-SPME-GC-MS/MS) was used to estimate the 2-acetyl-1-pyrroline (2-AP) in raw and cooked rice samples of ten different traditional and improved varieties. Furthermore, HS-SPME-GC-MS-based volatile profiling was subjected to untargeted analyses to identify major odorants in raw and cooked rice samples, and to understand chemical proximities among volatile profiles. Results showed that 2-AP content was remarkably increased in cooked rice compared to raw. Among the varieties studied, Pusa-1652 (Improved Kala Namak) and Kala Namak-2 were superior in the 2-AP content than Basmati varieties. Additionally, Govind Bhog, Kala Jeera and Jeera-32 had 2-AP content equivalent to or superior to Basmati rice varieties. Altogether, 18 and 22 volatiles were identified in the raw and cooked rice samples studied, respectively. Of these, ethyl butyrate, ethyl 3-methylbutanoate, 2-undecanone, ethyl benzoate, ethyl benzeneacetate, 2-methylnaphthalene, and 1-methylnaphthalene were characteristically detected in the cooked rice. The high amount of 2-ethyl-1-hexanol was uniquely found in raw rice samples, which can be a marker compound for freshly milled rice. Along with 2-AP, butanoic acid and benzoic acid derivatives, phenylethyl alcohol, ethyl 3-hydroxybutyrate, and indole may be responsible for the overall perceived characteristic Basmati-like aroma in cooked rice.

Purpose: To determine the effect of previous renal stone surgery on result and complications of percutaneous nephrolithotomy (PCNL)., Materials and Methods: Total 300 patients were enrolled in the study. We enrolled 100 surgery-naive cases (those with no history of any renal surgery) as control and labeled them as Group A. Group B comprised 100 cases who had PCNL in the past. Group C constituted 100 patients who had open renal stone surgery in the past. Stones were classified using Guy's stone score. PCNL was performed by standard technique in prone position and technical features encountered during operation and outcomes were compared between groups. Complications were graded using modified Clavien grading system., Results: There were no differences between the three groups in age, gender, body mass index, stone burden, and stone opacity. Multiple calyceal stones and distorted pelvicalyceal system anatomy were more in Group C, but stone score showed no statistically significant difference from other groups. The mean operative time (68.91 ± 21.27 min) and fluoroscopy time (264.40 ± 74.90 s) were longer in Group C, but there was no statistically significant difference between the groups. Multiple access was significantly more common in Group C compared to the other two groups ( P < 0.001). Access location too did not show any statistically significant difference between the groups. Postoperative complications were more in previous stone surgery patients, but did not show statistically significant difference., Conclusion: PCNL is a safe and effective treatment modality for patients with renal stones regardless of history of previous PCNL or open renal surgery., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Urology Annals.)

Background: Drug delivery system is a common practice in cancer treatment. RNA interference-mediated post-transcriptional gene silencing holds promise as an approach to knockdown in the expression of target genes responsible for cancer cell growth and metastasis. RNA interference (RNAi) can be achieved by delivering small interfering RNA (siRNA) and short hairpin RNA (shRNA) to target cells. Since neither interfering RNAs can be delivered in naked form due to poor stability, an efficient delivery system is required that protects, guides, and delivers the siRNA and shRNA to target cells as part of cancer therapy (chemotherapy)., Recent Findings: In this review, a discussion is presented about the different types of drug delivery system used to deliver siRNA and shRNA, together with an overview of the potential benefits associated with this sophisticated biomolecular therapy. Improved understanding of the different approaches used in nanoparticle (NP) fabrication, along with an enhanced appreciation of the biochemical properties of siRNA/shRNA, will assist in developing improved drug delivery strategies in basic and clinical research., Conclusion: These novel delivery techniques are able to solve the problems that form an inevitable part of delivering genes in more efficient manner and as part of more effective treatment protocols. The present review concludes that the nanoparticulate RNA delivery system has great possibility for cancer treatment along with several other proposed methods. Several NPs or nanocarriers are already in use, but the methods proposed here could fulfill the missing gap in cancer research. It is the future technology, which unravels the mystery of resolving genomic diseases that is, especially genomic instability and its signaling cascades., (© 2020 Wiley Periodicals LLC.)

Dialkylation of the 1,3-bis(1,2,4-triazol-1-yl)benzene with ethyl bromide results in the formation of [L-H2]Br2 which, upon salt metathesis with NH4PF6, readily yields the bis(triazolium) salt [L-H2](PF6)2 with non-coordinating counterions. [L-H2](PF6)2 and Ag2O react in a 1 : 1 ratio to yield a binuclear AgI-tetracarbene complex of the composition [(L)2Ag2](PF6)2 which undergoes a facile transmetalation reaction with [Cu(SMe2)Br] to deliver the corresponding CuI-NHC complex [(L)2Cu2](PF6)2. In contrast, the [L-H2]Br2 reacts with [Ir(Cp*)Cl2]2 to generate a doubly C-H activated IrIII-NHC complex 5. Similarly, the triazolinylidene donor supported diorthometalated RuII-complex 6 is also obtained. Complexes 5 and 6 represent the first examples of a stable diorthometalated binuclear IrIII/RuII-complex supported by 1,2,4-triazolin-5-ylidene donors. The synthesized IrIII-NHC complex 5 is found to be more effective than its RuII-analogue (6) for the reduction of a range of alkenes/alkynes via the transfer hydrogenation strategy. Conversely, RuII-complex 6 is identified as an efficient catalyst (0.01 mol% loading) for the β-alkylation of a wide range of secondary alcohols using primary alcohols as alkylating partners via a borrowing hydrogen strategy.

Visceral leishmaniasis (VL) in Nepal is found in 61 out of 75 districts including areas previously listed as non- endemic. This study focused on the role of housing conditions and its immediate environment in VL transmission, to limit future transmissions, ensure sustainable vector control and support the VL elimination program. The objective was to explore the risk factors in rural housing-and land lot typologies contributing to clinical VL occurrence and transmission. Housing structures and land lots were examined based on characteristics as risk factors of VL transmission in a case-control analysis. VL cases from 2013-2017 were identified based on the existing database from the Epidemiology and Disease Control Division and District Public Health Office from the plain Terai area (Morang, and Saptari districts) and hilly area (Palpa district) of Nepal. Two hundred and three built environments were analyzed (66 cases and 137 controls). Inferential statistics and logistic regression analysis were performed to determine the association of risk factors with VL. The risk factors with the highest odds of VL were: bamboo walls (adjusted odds ratio (AOR)- 8.1, 95% CI 2.40-27.63, p = 0.001), walls made of leaves/branches (AOR- 3.0, 95% CI 0.84-10.93, p = 0.090), cracks in bedroom walls (AOR- 2.9, 95% CI 0.93-9.19, p = 0.065), and placing sacks near sleeping areas (AOR- 19.2, 95% CI 4.06-90.46, p <0.001). Significant outdoor factors were: lots with Kadam trees (AOR- 12.7, 95% CI 3.28-49.09, p <0.001), open ground-outdoor toilets (AOR- 9.3, 95% CI 2.14-369.85, p = 0.003), moisture in outdoor toilet sheds (AOR- 18.09, 95% CI 7.25-451.01, p = 0.002), nearby- open land (AOR- 36.8, 95% CI 3.14-430.98, p = 0.004), moisture inside animal sheds (AOR- 6.9, 95% CI 1.82-26.66, p = 0.005), and surrounding animals/animals wastes particularly goats (AOR- 3.5, 95% CI 1.09-10.94, p = 0.036). Certain housing and surrounding environmental conditions and characteristics are risk factors for VL. Hence, elimination and educational programs should include the focus on housing improvement and avoidance of risk factors. Longitudinal interventional studies are required to document temporal relationships and whether interventions on these factors will have an impact on Leishmania transmission or burden., Competing Interests: The authors have declared that no competing interests exist.

Background: As visceral leishmaniasis (VL) has recently expanded in previously non-endemic areas of Nepal, the health system is facing new challenges. Female community health volunteers(FCHVs) are playing an important role for VL elimination in Nepal. This study aimed to analyze the actual and potential role of FCHVs for VL elimination program as well as community awareness of the disease (VL) and protective measures. Methods: We used a concurrent embedded mixed methods design. Qualitative data were collected through in-depth interviews and focus group discussions with FCHVs of 22 VLendemic villages of 3 districts. Concurrently quantitative data were collected through formal interviews of 203 household heads of the same villages. Results: FCHVs are able to perform their duties in an efficient way with the support of their families and specific incentives. FCHVs in the VL-endemic region have a good ability to recognize the VL suspects and refer to health facilities. The feedback by the district health office on referred patients was weak thus missing the opportunity of involving FCHVs in the 6-months follow up. In houses with a previous VL case knowledge levels of prevention and treatment ofVL were significantly better than in houses without a previous VL case. More people in houses with a former VL patient were aware on VL transmission. Conclusion: FCHVs are playing an important role for VL elimination in Nepal through detection of suspected cases and referral and may play a role in vector surveillance., (© 2020 The Author(s).)

Notch signaling is a primitive signaling pathway having various roles in the normal origin and development of each multicellular organisms. Therefore, any aberration in the pathway will inevitably lead to deadly outcomes such as cancer. It has now been more than two decades since Notch was acknowledged as an oncogene in mouse mammary tumor virus-infected mice. Since that discovery, activated Notch signaling and consequent up-regulation of tumor-promoting Notch target genes have been observed in human breast cancer. Moreover, consistent over-expression of Notch ligands and receptors has been shown to correlate with poor prognosis in human breast cancer. Notch regulates a number of key processes during breast carcinogenesis, of which, one key phenomenon is epithelial-mesenchymal transition (EMT). EMT is a key process for large-scale cell movement during morphogenesis at the time of embryonic development. Cancer cells aided by transcription factors usurp this developmental program to execute the multi-step process of tumorigenesis and metastasis. In this review, we recapitulate recent progress in breast cancer research that has provided new perceptions into the molecular mechanisms behind Notch-mediated EMT regulation during breast tumorigenesis.

This manuscript reports the first examples of germylene stabilized cadmium complexes {[{(i-Bu)2ATIGe(i-Pr)}2(CdI2)] (3, monomeric), [{(i-Bu)2ATIGe(i-Pr)(CdCl2)}2] (6, dimeric), [{(i-Bu)2ATIGe(i-Pr)(CdI2)}2] (7, dimeric)} and novel germylene zinc complexes {[{(i-Bu)2ATIGe(i-Pr)}2(ZnCl2)] (2, monomeric), [{(i-Bu)2ATIGe(i-Pr)(ZnI2)}2] (5, dimeric)} (ATI = aminotroponiminate). The reactions of germylene zinc complex [{(i-Bu)2ATIGe(i-Pr)(ZnCl2)}2] (4) with elemental sulphur and selenium resulted in the first examples of germathione and germaselenone stabilized ZnCl2 complexes [{(i-Bu)2ATIGe(i-Pr)(S)(ZnCl2)}2] (8) and [{(i-Bu)2ATIGe(i-Pr)(Se)(ZnCl2)}2] (9), respectively. Compound 4 was obtained through the reaction of compound 2 with ZnCl2. Interconversions between the monomeric and dimeric zinc/cadmium complexes (2 ↔ 4/3 ↔ 7) are shown. Compounds 2-3 and 5-9 are characterized by multinuclear NMR spectroscopy and single crystal X-ray diffraction studies are performed on compounds 2-3, 5-7, and 9. To understand the nature of bonding in the first examples of germylene cadmium complexes, ab initio calculations are also carried out on compounds 3 and 7.

Objectives: The objective of this study is to compare postoperative morbidity of closure versus nonclosure of the lingual mucosa graft (LMG) harvest site in augmentation urethroplasty., Materials and Methods: From January 2015 to November 2016, a total of 42 patients who underwent LMG urethroplasty randomized in 2 groups. In Group 1, donor-harvesting site was left open while in Group 2, donor site was closed. Self-made questionnaires were to assess postoperative pain, difficulty in tongue protrusion, swelling and numbness in graft harvest site, speech impairment, and difficulty in tolerating liquid and regular diet., Results: Mean visual analog scales score was 7.1 in Group 1, and 7.9 in Group 2 on day 0, which was statistically significant. Nearly 90.47% of patients in closure group and 95.23% in nonclosure group were able to swallow liquid diet on day 0 ( P = 0.5604). On day 3, 95.71% of patients in Group 1 and 80% in Group 2 were able to swallow soft diet ( P = 0.1604). Numbness was present in 80.95% Group 1 and 71.42% in Group 2 on day 0, which improved to 28.57% pts in Group 1 and 33.33% in Group 2 on day 3. On day 3, slurring of speech was more frequent in closure group (80%). However, at the end of a week, there was no difference in both groups. Saliva production was significantly increased in Group 1 in the 1 st week., Conclusion: Long-term morbidities of closing or nonclosing the LMG donor site are similar, but in short term, there is less pain, less edema, early recovery of tongue movements in nonclosure groups., Competing Interests: There are no conflicts of interest.

Use of nanomaterials in the field of science and technology includes different fields in food industry, medicine, agriculture and cosmetics. Nanoparticle-based sensors have wide range of applications in food industry for identification and detection of chemical contaminants, pathogenic bacteria, toxins and fungal toxins from food materials with high specificity and sensitivity. Nanoparticle-microbe interactions play a significant role in disease treatment in the form of antimicrobial agents. The inhibitory mechanism of nanoparticles against different bacteria and fungi includes release of metal ions that interacts with cellular components through various pathways including reactive oxygen species (ROS) generation, pore formation in cell membranes, cell wall damage, DNA damage, and cell cycle arrest and ultimately inhibits the growth of cells. Nanoparticle-based therapies are growing to study the therapeutic treatments of plant diseases and to prevent the growth of phytopathogens leading to the growing utilization of engineered nanomaterials. Hence, with this background, the present review focuses thoroughly on detailed actions and responses of nanomaterials against different bacteria and fungi as well as food sensing and storage., Competing Interests: Compliance with ethical standardsAuthors declared that they do not have any conflict of interest.

Objectives: At the time when Nepal is on the verge of reaching the maintenance phase of the Visceral Leishmaniasis (VL) elimination program, the country is facing new challenges. The disease has expanded to 61 of the country's 75 districts including previously non-endemic areas where there is no control or patient management program in place. This study aimed to assess which elements of the surveillance and reporting systems need strengthening to identify cases at an early stage, prevent further transmission and ensure sustained VL elimination., Methods: In a cross-sectional mixed-method study, we collected data from two study populations in VL program and non-program districts. From February to May 2016, structured interviews were conducted with 40 VL patients, and 14 in-depth and semi-structured interviews were conducted with health managers., Results: The median total delay from onset of symptoms to successful reporting to the Ministry of Health was 68.5 days in the VL-program and 83 days in non-program districts. The difference in patient's delay from the onset of symptoms to seeking health care was 3 days in VL-program and 20 days in non-program districts. The diagnostic delay (38.5 days and 36 days, respectively), treatment delay (1 vs. 1 days) and reporting delay (45 vs. 36 days) were similar in program and non-program districts. The diagnostic delay increased three-fold from 2012, while treatment and reporting delay remained unchanged. The main barriers to surveillance were: (i) lack of access and awareness in non-program districts; (ii) growing private sector not included in and not participating to referral, treatment and reporting; (iii) lack of cooperation and coordination among stakeholders for training and deployment of interventions; (iv) insufficient validation, outreach and process optimisation of the reporting system., Conclusions: Corrective measures are needed to maintain the achievements of the VL elimination campaign and prevent resurgence of the disease in Nepal. A clear patient referral structure, reinforcement of report notification and validation and direct relay of data by local hospitals and the private sector to the district health offices are needed to ensure prompt treatment and timely and reliable information to facilitate a responsive system of interventions., (© 2018 John Wiley & Sons Ltd.)

Nepal has completed the attack phase of visceral leishmaniasis (VL) elimination and now needs active case detection (ACD) and vector control methods that are suitable to the consolidation and maintenance phases. We evaluated different ACD approaches and vector control methods in Saptari district. We assessed 1) mobile teams deployed in villages with VL cases in 2015 to conduct combined camps for fever and skin lesions to detect VL/PKDL (post-kala-azar dermal leishmaniasis) and other infections; 2) an incentive approach by trained female community health volunteers (FCHVs) in villages with no VL cases in 2015. Both were followed by house-to-house visits. For vector control, four villages were randomly allocated to insecticide impregnation of bednets, insecticide wall painting, indoor residual spraying (IRS), and control. Sandfly density (by CDC light traps, The John W. Hock Company, USA) and mortality (World Health Organization cone bioassay) were assessed in randomly selected households. One VL, three tuberculosis, one leprosy, and one malaria cases were identified among 395 febrile cases attending the camps. Post-camp house-to-house screening involving 7,211 households identified 679 chronic fever and 461 skin lesion cases but no additional VL/PKDL. No VL/PKDL case was found by FCHVs. The point prevalence of chronic fever in camp and FCHV villages was 242 and 2 per 10,000 populations, respectively. Indoor residual spraying and bednet impregnation were effective for 1 month versus 12 months with insecticidal wall paint. Twelve-month sandfly mortality was 23%, 26%, and 80%, respectively, on IRS, bednet impregnation, and insecticide wall painting. In Nepal, fever camps and insecticidal wall paint prove to be alternative, sustainable strategies in the VL post-elimination program.

Chronic myeloid leukemia (CML) is a myeloproliferative disease caused due to translocation between chromosome 9 and 22 leading to a chimeric gene product known as Bcr-Abl. Bcr-Abl fusion protein has constitutively activated Abl tyrosine kinase activity which is responsible for the uncontrolled proliferation in CML The tyrosine kinase inhibitors (TKIs) such as Imatinib, Dasatinib, and Nilotinib are the current first-line treatments approved by the United States Food and Drug Administration (US FDA) for the treatment of the disease. Despite the spectacular progress made over the decade with the TKIs, patients develop resistance to these TKIs. In such cases, stem cell transplant therapy, which is limited by donor availability, is the only proven cure for the patients. This highlights the need for the development of new strategies for CML treatment. The Bcr-Abl point mutations, including the gatekeeper T315I mutations, are the principal cause for the development of resistance to TKIs. However, other mechanisms are also involved in the failure of TKI therapy. This review outlines the Bcr-Abl dependent and independent mechanism of TKIs resistance development and the strategies used to overcome drug resistance, such as the development of ATP site and allosteric site inhibitors. Binding mode and structural elements of Bcr-Abl inhibition are discussed with emphasis on pathways involved in this complex disease to determine alternative strategies and combination therapies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Pepsin, a digestive enzyme, plays an important role in the metabolism of protein products in the stomach. The pH is regarded as the most pivotal criteria in appraising the pepsin's enzymatic activity. Pepsin is idle at the physiological pH (7.4) but dynamic in the acidic environments of the stomach (pH 2.0-4.0). Inspired by such pH regulatory actions, we have used pepsin as an enhancer, which is attached to silica nanoparticles for the doxorubicin release in the acidic tumor environment. Pepsin enzyme is transitional between the doxorubicin loaded silica nanoparticles and the biotin-avidin cap system, which intercedes the pores. The formed nanoplatform is poised at the physiological pH. However, when switched to low pH simulated conditions, the pepsin become vibrant and cleaves the avidin, rendering the clearance of the path for the diffusion of the drug. This design strategy augmented the drug bioavailability deep inside the solid tumor with enhanced uptake and apoptosis of the tumor cells in experimental lymphoma.

Objective: Develop an approach, One-class-at-a-time, for triaging psychiatric patients using machine learning on textual patient records. Our approach aims to automate the triaging process and reduce expert effort while providing high classification reliability., Materials and Methods: The One-class-at-a-time approach is a multistage cascading classification technique that achieves higher triage classification accuracy compared to traditional multiclass classifiers through 1) classifying one class at a time (or stage), and 2) identification and application of the highest accuracy classifier at each stage. The approach was evaluated using a unique dataset of 433 psychiatric patient records with a triage class label provided by "I2B2 challenge," a recent competition in the medical informatics community., Results: The One-class-at-a-time cascading classifier outperformed state-of-the-art classification techniques with overall classification accuracy of 77% among 4 classes, exceeding accuracies of existing multiclass classifiers. The approach also enabled highly accurate classification of individual classes-the severe and mild with 85% accuracy, moderate with 64% accuracy, and absent with 60% accuracy., Discussion: The triaging of psychiatric cases is a challenging problem due to the lack of clear guidelines and protocols. Our work presents a machine learning approach using psychiatric records for triaging patients based on their severity condition., Conclusion: The One-class-at-a-time cascading classifier can be used as a decision aid to reduce triaging effort of physicians and nurses, while providing a unique opportunity to involve experts at each stage to reduce false positive and further improve the system's accuracy.

Purpose: To report our initial experience with urethral reconstruction using a combined dorsal lingual mucosal graft (LMG) and ventral onlay preputial flap for long obliterative or near-obliterative strictures in circumcised patients., Materials and Methods: This was a retrospective study of 10 patients from January 2015 to June 2017 with long obliterative or near-obliterative anterior urethral strictures and circumcised prepuces. All patients underwent a combined approach using a dorsally LMG and a narrow preputial onlay flap ventrally to create a 26-30 Fr. neourethra over a 14-Fr Foley catheter. Success was defined as no requirement for additional urethral instrumentation. The follow-up period ranged from 6 to 32 months., Results: The patients ranged in age from 17 to 44 years (mean, 32.3±9.59 years) and stricture length ranged from 9 to 12.5 cm (mean, 10.77±1.15 cm). Four strictures were obliterative and six were near-obliterative. Two patients had a history of prior urethroplasty. The length of the LMGs harvested ranged from 11 to 14 cm (mean, 12.8±1.03 cm). The preputial flaps available were from 1 to 1.5 cm in width (1.29±0.16 cm) and the desired length. Maximum urinary flow rate (Qmax) achieved ranged from 12 to 26 mL/s (mean, 20.46±3.71 mL/s) after 3 months. One patient needed a single direct visualized internal urethrotomy and another patient develop temporary superficial penile necrosis. The success rate was 90%., Conclusions: Long obliterative and near-obliterative penile and penobulbar urethral strictures can still be treated in circumcised patients using available preputial skin along with lingual mucosa with good outcomes., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.